Science & Technology News 科學新聞

Mitochondrial mutation linked to blood pressure and cholesterol problems

2004-11-01T13:10:00.000+08:00

Mitochondrial mutation linked to blood pressure and cholesterol problems

New Haven, Conn. � Researchers at Yale and Syracuse Universities found the first direct evidence for a mutation in mitochondrial DNA that directly affects blood pressure and cholesterol levels.

It has long been known that several metabolic traits including high cholesterol and hypertension cluster in individuals more frequently than by chance, but the underlying causes were unknown. This study, published early in Science Express on line, suggests that altered mitochondria may account for the clustering as well as the disorders.

"Looking further, this finding raises the possibility that all features of the metabolic syndrome may be attributable to altered mitochondrial function," said Richard P. Lifton, Sterling Professor and Chair of Genetics at Yale and research team leader.

Metabolic syndrome is an emerging problem in industrial societies and. epidemic in the United States. The symptoms include high blood pressure, cholesterol and triglycerides, insulin resistance, obesity, and low HDL. There is independent evidence that altered mitochondrial function plays a role in insulin resistance and high triglyceride level, and the current finding indicates that these other components of metabolic syndrome may also linked to mitochondrial disfunction.

The clear correlation of mutation and disorder in this study was made possible by the evaluation of 142 people in four generations of an affected family. Although family members with each disorder � hypertension, hypercholesterolemia and hypermagnesemia � have the same mitochondrial mutation, the presence of the mutation does not produce all of the symptoms in each individual.

While this study focuses on a rare mutation in mitochondria that provides a clear link to specific disorders, mitochondrial function is known to decline with age in normal people and may be contributing to these common traits in the general population.

Other researchers included Frederick H. Wilson, Ali Hariri, Anita Farhi, Hongyu Zhao, Kitt Falk Petersen, Hakan R. Toka, Carlo Nelson-Williams, Michael Kashgarian, and Gerald I. Schulman at Yale, and Khalid M. Raja and Steven J. Scheinman at Syracuse University. Grants from the National Institutes of Health the Howard Hughes Medical Institute and the American Heart Association supported this research.

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Citation: Science Express (October 21, 2004).

都是粒腺體的錯！？

2004-11-01T13:09:00.000+08:00

都是粒腺體的錯！？
　　粒線體的突變似乎和代謝疾病息息相關，會導致如高血壓、高膽固醇等心血管疾病危險因子。

　　高血壓伴隨了其他心血管危險因子，如血液中高膽固醇和三酸甘油酯含量，以及糖尿病。雖然肥胖的人常會有這些代謝併發症狀，可是體重正常人也會有，所以過重並非主因。

　　耶魯大學醫學院的Richard Lifton等人發現了一位血液中鎂離子含量過低的女病人，接著他們發現粒線體中一連串的基因突變是主因。這位女病人的其他親人也有低鎂離子的症狀。追蹤了142個親人，他們大多有低鎂離子、高血壓和高膽固醇的問題。這些症狀都是遺傳自一位母親－－粒線體靠母系遺傳把突變傳給了一大票後代。

　　把整個粒線體定序了之後，他們發現一個鹼基的變化發生在tRNA的基因中，一個胸腺嘧啶變成了胞嘧啶，結果改變了tRNA的結構而影響了蛋白質合成。

　　舊金山加州大學的高血壓專家Theodore Kurtz指出，雖然還不知道為何這個粒腺體突變會造成多種症狀，不過這個發現是非常重要的。之前沒前個心臟病學家把粒腺體原來在高血壓以及其他心血管疾病危險因子上參了一腳，不過這個發現將改變一切。

原學術論文：
Science, Published online 21 October 2004. DOI: 10.1126/science.1102521 Link

The mystery of eye evolution

2004-11-01T13:07:00.000+08:00

Darwin's greatest challenge tackled: the mystery of eye evolution

Researchers provide concrete evidence about how the human eye evolved

When Darwin's skeptics attack his theory of evolution, they often focus on the eye. Darwin himself confessed that it was "absurd" to propose that the human eye evolved through spontaneous mutation and natural selection. Scientists at the European Molecular Biology Laboratory (EMBL) have now tackled Darwin's major challenge in an evolutionary study published this week in the journal Science. They have elucidated the evolutionary origin of the human eye.

Researchers in the laboratories of Detlev Arendt and Jochen Wittbrodt have discovered that the light-sensitive cells of our eyes, the rods and cones, are of unexpected evolutionary origin – they come from an ancient population of light-sensitive cells that were initially located in the brain.

"It is not surprising that cells of human eyes come from the brain. We still have light-sensitive cells in our brains today which detect light and influence our daily rhythms of activity," explains Wittbrodt. "Quite possibly, the human eye has originated from light-sensitive cells in the brain. Only later in evolution would such brain cells have relocated into an eye and gained the potential to confer vision."

The scientists discovered that two types of light-sensitive cells existed in our early animal ancestors: rhabdomeric and ciliary. In most animals, rhabdomeric cells became part of the eyes, and ciliary cells remained embedded in the brain. But the evolution of the human eye is peculiar – it is the ciliary cells that were recruited for vision which eventually gave rise to the rods and cones of the retina.

So how did EMBL researchers finally trace the evolution of the eye?

By studying a "living fossil," Platynereis dumerilii, a marine worm that still resembles early ancestors that lived up to 600 million years ago. Arendt had seen pictures of this worm's brain taken by researcher Adriaan Dorresteijn (University of Mainz, Germany). "When I saw these pictures, I noticed that the shape of the cells in the worm's brain resembled the rods and cones in the human eye. I was immediately intrigued by the idea that both of these light-sensitive cells may have the same evolutionary origin."

To test this hypothesis, Arendt and Wittbrodt used a new tool for today's evolutionary biologists – "molecular fingerprints". Such a fingerprint is a unique combination of molecules that is found in a specific cell. He explains that if cells between species have matching molecular fingerprints, then the cells are very likely to share a common ancestor cell.

Scientist Kristin Tessmar-Raible provided the crucial evidence to support Arendt's hypothesis. With the help of EMBL researcher Heidi Snyman, she determined the molecular fingerprint of the cells in the worm's brain. She found an opsin, a light-sensitive molecule, in the worm that strikingly resembled the opsin in the vertebrate rods and cones. "When I saw this vertebrate-type molecule active in the cells of the Playtnereis brain – it was clear that these cells and the vertebrate rods and cones shared a molecular fingerprint. This was concrete evidence of common evolutionary origin. We had finally solved one of the big mysteries in human eye evolution."

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眼睛的起源及演化

2004-11-01T13:04:00.000+08:00

眼睛的起源及演化

　各門類動物的眼睛結構大不相同，演化生物學家曾一度認為眼睛是多次起源的，可是一種海生小蟲子的眼睛和人類的相像程度讓生物學家要重新考慮眼睛的起源。

　　達爾文在提出天擇說時，就意識到眼睛的演化會是他理論的一大難題。他認為眼睛是經過簡單而不完美的漸進步驟演化而來的，而且幾乎所有科學家也相信複雜的眼睛起源自單細胞的感光受器。

　　儘管各種動物的眼睛大小和形狀大不相同，主要還是兩種形式。脊椎動物眼睛中的感光細胞主要是錐細胞和桿細胞，無脊椎動物的則為彈狀細胞（rhabdomeric photoreceptors）。雖然無脊椎動物和脊椎動物都用視蛋白來感光，不過它們的序列大不相同。有些科學家認為眼睛是單次起源的，可是有些卻認為眼睛在無脊椎動物和脊椎動物中至少各自起源一次。

　　德國海德堡歐洲分子生物學實驗室的發育生物學家Detlev Arendt和Joachim Wittbrodt等人發現一種海生小蟲子除了視蛋白之外，牠們還含有另外一些和人類極為相似的蛋白質。這個發現意味著脊椎動物和無脊椎動物的眼睛都來自一個共同的祖先，無脊椎動物的感光細胞經過多次變化才變成脊椎動物的。

　　他們之所以會漟眼睛起源這渾水，是因為Arendt發現一種五億年中幾乎不變的活化石海生環節動物－－岩蟲（Platynereis dumerilii）的眼睛裡有看似錐細胞和桿細胞的感光受器。這類感光細胞只有在少數無脊椎動物中有發現過，例如在扇貝。可是那些觀察主要是基於形態。

　　Arendt等人除了形態之外，他們還比較基因和蛋白質。德國Philipps Univ.的Kristin Tessmar-Raible首先試圖找尋岩蟲的無脊椎動物視蛋白基因，可是卻徒勞無功。可是經過徹底的搜尋後，她發現岩蟲的視蛋白和無脊椎動物的有所不同，和脊椎動物的視蛋白比較相像。他們也從岩蟲的基因組中找尋脊椎動物視網膜同源匣蛋白質（homeobox proteins），結果果然在岩蟲腦中找到同源匣蛋白質。

　　這個發現讓無脊椎動物和脊椎動物的眼睛萬本歸宗。他們還認為兩個感光竹系統是起源自兩側對稱動物的共同祖先。

　　不過美國國家眼睛研究所的Joram Piatigorsky表示，雖然這個發現和眼睛單次起源的想法相符，不過卻並不代表所有動物的眼睛必定演化自一個動物。這還是個尚待解答的演化學問題。

原學術論文：Arendt D., Tessmar-Raible K., Snyman H., Dorresteijn A. & Wittbrodt J. Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain. Science, 306. 869 - 871 (2004).

Iron-source preference of Staphylococcus aureus infections.

2004-10-11T16:15:00.000+08:00

Iron-source preference of Staphylococcus aureus infections.

Skaar EP, Humayun M, Bae T, DeBord KL, Schneewind O.
Science. 2004 Sep 10;305(5690):1626-8.
Committee on Microbiology, 920 East 58th Street, University of Chicago, Chicago, IL 60637, USA.

Although bacteria use different iron compounds in vitGro, the possibility that microbes distinguish between these iron sources during infection has hitherto not been examined. We applied stable isotope labeling to detect source-specific iron by mass spectrometry and show that Staphylococcus aureus preferentially imports heme iron over transferrin iron. By combining this approach with computational genome analysis, we identified hts (heme transport system), a gene cluster that promotes preferred heme iron import by S. aureus. Heme iron scavenging by means of hts is required for staphylococcal pathogenesis in animal hosts, indicating that heme iron is the preferred iron source during the initiation of infection.

PMID: 15361626 [PubMed - indexed for MEDLINE]

【挑嘴】的金黃葡萄球菌！

2004-10-11T16:14:00.000+08:00

【挑嘴】的金黃葡萄球菌！

惡名昭彰的金黃葡萄球菌(Staphylococcus aureus)會導致食物中毒(food poisoning)、腦膜炎(meningitis)、休克等病症。像一般細菌一樣，在葡萄球菌的繁殖過程中，鐵元素攝取也是必要的。

美國芝加哥大學微生物學家Olaf Schneewind與其研究團隊發現：金黃葡萄球菌其實是蠻挑嘴的，它們特別偏好特定來源的鐵元素，尤其血紅素(Hemoglobin)中的鐵元素，更是它們的最愛，此外，鐵元素得取的與否跟病菌的兇猛程度也是息息相關。

紅血球具攜帶血紅素的功能，血紅素內的亞鐵能與氧氣結合，形成氧合血紅素(oxyhemoglobin)，這種結合會受酸鹼值、溫度等因素所影響。此外，許多藥物也會使血紅素中的亞鐵轉換成三價的鐵離子，形成高鐵血紅素(methemoglobin)，如果血液中含有大量高鐵血紅素，皮膚就會變得藍黑。

在這份刊登於2004年九月份《科學》期刊的研究報告中，研究人員利用同位素標記化合物後，給予金黃葡萄球菌進行攝取，藉以追蹤金黃葡萄球菌的『飲食習慣』。文章中指出：相較於從運鐵蛋白質(transferring)獲得鐵元素，金黃葡萄球菌更偏好從血紅素中取得該項元素。

在得知金黃葡萄球菌選擇鐵元素的特殊喜好後，Olaf Schneewind與其研究團隊進一步分析金黃葡萄球菌的基因組，並辨識出一段與金黃葡萄球菌攝取血紅素內亞鐵離子有關的基因，hts(heme transport system)。接著，研究人員讓hts基因失活，並將這經過基因修飾的金黃葡萄球菌(htsB 和htsC)與正常的金黃葡萄球菌分別感染線蟲(C. elegans)與小鼠。實驗發現：正常金黃葡萄球菌在四十八小時內造成了近80%的線蟲死亡，在受感染的小鼠肝臟、腎臟組織也發現膿瘡出現。相反的，hts基因失活的金黃葡萄球菌則顯得溫和許多，即使四十八小時後，大多數的線蟲的存活狀況仍然相當良好，小鼠的器官也沒有顯著的傷害。

這項研究成果暗示著：透過影響金黃葡萄球菌對鐵元素的攝取能力，可以減弱病菌對宿主所造成的破壞；換句話說，釐清響金黃葡萄球菌的『用鐵』偏好，除了大大有助於藥物研發之外，也可望有益於病菌感染的症狀減緩。

原始論文：
Iron-source preference of Staphylococcus aureus infections. Science. 305：1626 (2004)

DNA barcodes tag species

2004-10-11T16:13:00.000+08:00

DNA barcodes tag species

Helen Pearson
Genetic sequence could give an instant biological identification.

Published online: 27 September 2004; doi:10.1038/news040927-2

Wouldn't it be great if every animal had an easy-to-read label, telling you to which species it belonged? Scientists are now one step closer to making this idea a reality, thanks to two studies showing that the DNA sequence of just one gene can tell very closely related species of birds and butterflies apart, and even flag up previously unrecognized ones.

The concept is called DNA barcoding. And if it works, it could find numerous uses. When a foreign ship docks, for example, inspection services could automatically scan ballast water for nasty species that they are keen to keep out. Or researchers in remote locations could use a handheld scanner to get an instant species identification.

At the moment, identifying species is a laborious process, based on characteristics such as the shape of a beak or the colour of a wing. But with DNA barcoding, scientists simply work out 650 letters in the genetic sequence of a single gene, called cytochrome c oxidase I.

This gene tends to vary a lot between species. Proponents of the method believe it is so variable that most different species will have a characteristic code, but many researchers are more sceptical.

Birds and butterflies

To show the system can work, Paul Hebert of the University of Guelph, Canada, and his colleagues read and compared the DNA barcodes from museum specimens of 260 species of North American birds.

They found that birds in different species had very different barcodes, whereas birds within the same species did not. They also support suspicions that some of the birds fall into four new species, they write in the Proceedings of the National Academy of Sciences1.

Working with a different team, Hebert focused on skipper butterflies in the forest of Costa Rica. The group analysed the DNA barcodes of over 480 specimens that had previously been grouped as one species (Astraptes fulgerator).

The barcodes fell into clear groups that suggested the butterflies belonged to ten distinct species. The researchers report in PloS Biology that the result matches known differences in their choice of foods and caterpillars2.

DNA database

Researchers have used the genetic sequences of animals to help work out their evolutionary relationships for over two decades. But they use a variety of different genes, whereas barcoding focuses on just one.

The idea gained credence last year, when Hebert showed that DNA barcodes could tell apart almost 2,000 species3. Now a series of projects around the world is showing that the system works in different animal groups. Supporters ultimately aim to catalogue the DNA barcode of each species, with its name, in a central database.

Daniel Janzen at the University of Pennsylvania, Philadelphia, who collected the butterflies used in the recent study, is enthusiastic about DNA barcodes. To identify a species of caterpillar, he currently has to rear it until it transforms into a butterfly and then send it to an expert taxonomist. A DNA barcode would allow him to classify caterpillars on the spot, he says, and work out the "gazillion species that give taxonomists nightmares".

The system has two other advantages over traditional taxonomy. It can be used to identify species from only a fragment of tissue or shell. And if barcode scanners become available, they could be used by amateurs.

But some researchers have reservations, seeing barcodes as a threat to traditional taxonomy. And even supporters acknowledge that the system will struggle to distinguish species whose genetic sequence is extremely similar, such as ones that have only recently diverged from one another. "We have to be a little bit cynical about where it works and where it doesn't," says ecologist Craig Moritz at the University of California, Berkeley.

Moritz says that, in some cases, it may be necessary to analyse more than one gene to properly identify a species. "There's strong debate about whether one gene fits all," he says.

生命的DNA數位條碼

2004-10-11T16:11:00.000+08:00

生命的DNA數位條碼

如果能夠都把動物打上如同貨品上的數位條碼，那麼我們豈不是可以隨時利用掃描器來分辨在野外遇到的動物是屬於哪一種。這個或許已經不是天方夜譚了。

這個構想稱為DNA數位條碼，除了好玩，它還有許多實際的用途。檢疫單位可以利用它來檢測外來生物的侵入。在外的科學家也可以隨時利用手提掃描器來鑑定物種。

迄今，鑑定物種仍是費時費力的，需要依靠許多外在特徵。可是有了DNA數位條碼，科學家只要搞定一個粒線體的基因(COI)的650個字元。這個基因的演化速率較快，因此序列隨著不同物種而異，每個物種都有可能有其獨特的序列。然而還是有科學家對此存疑。

為了排除疑慮，加拿大University of Guelph的動物學家Paul Hebert和洛特菲勒大學的分子生態學家Mark Stoeckle等人比較了博物館中，260種北美鳥類的DNA數位條碼。結果他們發現，不同種的鳥類帶有不同的DNA數位條碼，而且也顯示有些鳥的確是如有些分類學家懷疑般的分屬四個不同種。

和賓州大學的Daniel Janzen等人合作，Hebert等人分析了哥斯達黎加的480個弄蝶樣本，牠們之前被認為是同一種（Astraptes fulgerator）。可是他們的分析結果卻顯示，這些蝴蝶應該分屬十個不同種，而且和牠們選擇的食物息息相關。

科學家雖然早以利用DNA序列來為物種建立親緣關係樹，可是使用的是多種基因，而DNA數位條碼只利用一個。使用DNA數位條碼的想法在去年Hebert證實它可以區分出2千個不同物種時，開始獲得支持。在全世界也有好幾個不同計畫針對不同動物正在進行中，最終的目標是把各各物種的DNA數位條碼都鍵入中央資料庫中。

Janzen對此計畫充滿興趣。以往他只能把毛毛蟲養大成蝴蝶後，再能讓分類學家鑑定種類。DNA數位條碼卻能讓他輕易鑑定成千上萬個令分類學家不眠不休才看得完的物種。這個方法還有一個好處是只需要一小片組織就能做鑑定。如果掃描器面世，門外漢都可輕易使用。

可是還是有科學家對DNA數位條碼保持保留的態度，認為它不能區分出晚近才分化的物種。柏克萊加州大學的生態學家Craig Moritz認為，有些時候還是得使用超過一個基因。

原學術論文：Hebert P. D. N., Penton E. H., Burns J. M., Janze D. H. & Hallwachs W. PNAS (2004). DOI: 10.1073/pnas.0406166101Herbert P. D. N, Stoeckle M. Y., Zemlak T. S. & Francis C. M. PLoS Biol 2, e312 (2004). DOI: 10.1371/journal.pbio.0020312Herbert P. D. N, Ratsingham S. & Dewaard J. R. Proceedings of the Royal Society, B 270, S596-599 (2003).

Researchers devise potent new tools to curb ivory poaching

2004-10-11T16:07:00.000+08:00

Researchers devise potent new tools to curb ivory poaching

Despite a long-standing international ban on ivory trade, African elephants continue to be killed in large numbers for their prized tusks. But a team headed by a University of Washington biologist has devised a new means of determining the geographic origin of ivory that could prove a potent tool in slowing elephant poaching and the illegal ivory trade by identifying hot spots where enforcement should be increased.

It is relatively easy to monitor elephant populations with flights over the open savannas of eastern, central and southern Africa, but it is much harder to do the same in the dense forests of central and western Africa. Those forests are where elephants are currently being slaughtered wholesale, said Samuel Wasser, who holds the UW's endowed chair of conservation biology and is director of the Center for Conservation Biology.

"My colleagues working in the forests are saying, 'There are no elephants left here,'" he said. "That's the problem ?in the forest you don't notice the change in population until it's so dramatic that it's almost too late to do anything about it."

Wasser is lead author of a paper describing the new means of determining ivory origins, being published the week of Sept. 27 in the Proceedings of the National Academy of Sciences.

The African elephant population plummeted by 60 percent ?from 1.3 million to just 500,000 ?between 1979 and 1987, largely because of ivory poachers. An international agreement banning ivory trade was enacted in 1989, but still three of the largest ivory seizures have occurred since 2002.

In June 2002, authorities in Singapore seized a shipment of about 6.5 metric tons of ivory bound for the Far East. The shipment included 532 whole tusks, many more than 6 feet long, and 41,000 small carved ivory cylinders about the size of hanko stamps, used for document signatures. The cylinders alone were worth more than $6 million.

The new methods developed by Wasser's team can show generally where such ivory came from, alerting authorities to specific areas where added enforcement is needed to curb poaching.

Wasser and his colleagues extracted DNA from elephant droppings and skin biopsy samples collected from numerous locations in 16 African nations. They used that information to build a DNA-based reference map to assign tusk origin. They noted genetic differences in populations from one location to another, and used a statistical method to extrapolate genetic signatures to fill in gaps between sampled populations.

Matthew Stephens, a UW associate professor of statistics, developed a model allowing the researchers to build genetic profiles for elephant populations from which they do not have genetic samples. The model is weighted toward genetic information obtained from populations nearest those for which information is unavailable.

The method allows a DNA sample to be assigned to a fairly specific location, with a relatively high confidence that the assignment is correct. The study indicated that 50 percent of the samples tested were accurately located within 300 miles and 80 percent were accurate to within less than 600 miles. Accuracy was much greater among forest populations, which are more clearly defined because of terrain.

The new method allows for speedy determination of where a particular ivory sample came from, Wasser said. That is important because there is mounting pressure to lift the 1989 ivory trade ban enacted under the Convention on International Trade in Endangered Species. But many experts believe any legalization of ivory trade will only increase poaching. The new sampling method can help determine quickly whether that is true in time for exemptions to be altered before elephant populations suffer catastrophic damage, he said.

Two years ago, five African nations sought, and three received, an exemption from the ban so that they could conduct one-time ivory sales. Now numerous other countries are considering seeking exemptions, and some hope to obtain permanent exemptions.

"Once the door is cracked open, they try to force it open all the way," Wasser said.

He noted that a number of countries have kept ivory stockpiles since the 1989 ban, and the small central-African nation of Burundi has a stockpile of 80 tons ?despite the fact that it had only one elephant at the time of the ban. Some observers believe ivory has been sold from that stockpile and replenished from poached ivory.

"This method could detect such restocking in the future," Wasser said.

Tracking elephant ivory is just one example of the value of the sampling and statistical method, he said. The same methods can be used to establish the locations from which any endangered species' products originated, to help conservationists find ways to keep those species from extinction.

Wasser and his colleagues have trained narcotics-detection dogs to find the droppings from endangered species over large remote areas. The dogs can track up to 18 species at once at distances greater than a quarter-mile. Such non-invasive techniques can be used to quickly assemble genetic reference maps to apply this technology to other at-risk species.

Besides Wasser and Stephens, authors of the PNAS paper are Andrew Shedlock, formerly of the UW and now at Harvard University; Kenine Comstock and Elaine Ostrander of the Fred Hutchinson Cancer Research Center in Seattle; and Benezeth Mutayoba of Sokoine University of Agriculture in Tanzania.

###The research was supported by the U.S. Fish and Wildlife Service, the Gordon and Betty Moore Foundation, the Bosack Kruger Charitable Trust, the National Institutes of Health, the International Elephant Foundation and the Woodland Park Zoo in Seattle. The entire ivory seizure investigation is being funded by the International Fund for Animal Welfare.

For more information, contact Wasser at 206-543-1669 or wassers@u.washington.eduThe Center for Conservation Biology Web site is http://depts.washington.edu/conserv

A video news release will be available Sept. 27 from the International Fund for Animal Welfare. Contact Chris Cutter at 508-744-2066 or ccutter@ifaw.org

DNA追蹤非法象牙

2004-10-11T16:04:00.000+08:00

DNA追蹤非法象牙

保育人士和警方今後可以利用DNA來追蹤非法象牙的來源。

這個遺傳方法的準確度達到500至1000公里的範圍。這個新技術的產生是為了要應對通過網際網路源源不絕地流入美國的非法象牙。發展出此技術的西雅圖華盛頓大學的Samuel Wasser指出，這個方法可以很快地判斷出哪些象牙是非法的。象牙貿易在1989年被瀕臨絕種野生動植物國際貿易公約組織（CITES）禁止，不過現今充許南非的一些象群壯大的地區進行合法的象牙貿易。

他們從非洲16個國家的28個地點取得400頭大象的糞便或組織，粹取出DNA，然後分析各別地區特定基因的分佈頻率。Wesser指出，森林象群較孤立，和草原象群可能分屬不同物種，牠們的DNA也比較獨特。他們幾乎可以百分之百區分出西非和中非的草原和森林象群。在象群雜交的地區，雖然他們沒取樣，可是仍舊可以用原用的樣本外推出當地的基因頻率，準確度也達八成。於是他們可以製作出非洲大象的DNA圖譜。這有助於鑑定出瀕危的森林象群。

到了1989年，非洲象不到十年就從一百卅萬頭減少到只剩六十萬頭。至從象牙貿易在1989年被CITES禁止之後，盜獵者開始對森林象群開刀。CITES雖然利用地面部隊巡查空中看不到的森林大象屍體，不過進行起來不易。在剛果單單去年就有一萬隻象被幹掉，簡直就是大屠殺！根據保育組織TRAFFIC的報告，在美國每週有一千個象牙製品在eBay上拍賣。2002年6月，新加坡警方就起獲到6.5噸的非法象牙走私，包括了532箱滿載的貨櫃，總值超過六百萬美金。

這個方法有助於國際刑事警察組織偵查出非法象牙的來源。可是TRAFFIC的Tom Milliken指出，這個方法還不能解決非法獵殺象牙的問題。在動盪的剛果，有許多饑民獵殺大象是為充饑。如果象牙只是果腹的副產品，那麼餵飽饑民才能治本。

原學術論文：Wasser S. K., et al. Proc. Natl. Acad. Sci, (2004). DOI: 10.1073/pnas.0403170101

Firefly Compound Lights Up 'Protein Dance' In Living Animals

2004-09-09T10:25:00.000+08:00

Firefly Compound Lights Up 'Protein Dance' In Living Animals

St. Louis, July 29, 2004 -- Radiologists at Washington University School of Medicine in St. Louis have developed a first-of-its-kind noninvasive imaging technique that allows them to watch two proteins interacting in live animals.

The technique genetically fuses proteins of interest with carefully cleaved sections of luciferase, the protein fireflies use to create light. When the target proteins interact, the sections of luciferase come together and create light that can be detected outside the body by a highly sensitive camera.

"Instead of looking at a protein by itself, this technique lets us see when two proteins come together and dance," says David Piwnica-Worms, M.D., Ph.D., professor of molecular biology and pharmacology and of radiology. "Those kinds of interactions are very important for many different processes, and they're also key to developing and evaluating new drugs."

Piwnica-Worms and colleagues demonstrated the technique's feasibility on human proteins that interact in the presence of the antibiotic rapamycin. The research appears today in the online edition of the Proceedings of the National Academy of Sciences and will appear in print in the Aug. 17 issue of the journal.

According to Piwnica-Worms, understanding protein interactions has become much more important to biologists in recent years. "We've learned that the human genetic code only has a fraction of the genes we expected, and as a result it's become clear that the context of protein-to-protein interactions significantly affects what proteins can do," he explains. "That's what lets us get away with so few genes -- the same protein can do different things based on when or where it's used." Scientists have studied these interactions previously in cell cultures and in solutions obtained by carefully opening up cells. Luciferase has been used previously to identify the presence of molecules in the cell and in live animals, but this is the first time scientists have used it in the test tube or in live animals to detect the coupling of two proteins by a drug.

The biggest challenge of the project, according to Piwnica-Worms, was determining the best place to split luciferase.

"We were ideally looking for a split version of luciferase that had zero activity when separated but had very high light output when the partner proteins interacted," he explains.

Researchers led by Kathryn E. Luker, Ph.D., a postdoctoral fellow in Piwnica-Worms' lab, first divided luciferase into overlapping halves. They then produced many copies of the halves, and used an enzyme to chomp off varying lengths from the ends of the halves where the split was made. They packed the resulting library of luciferase fragments into phages, viruses that infect bacteria. Scientists allowed the phages to infect bacterial colonies, and then looked for bacteria that glowed.

Of 19,000 bacterial colonies, approximately 120 lit up. The three brightest were further tested to determine which pair of fragments worked best.

In a line of experimental mice, scientists genetically fused one member of the best pair of luciferase fragments onto the protein targeted by rapamycin, attaching the luciferase fragment to the specific portion of the protein where rapamycin establishes its bond. They attached the other luciferase fragment to a protein known through previous research to interact with rapamycin's target protein only in the presence of rapamycin. Using a commercially available instrument known as an in vivo bioluminescence camera, they found they could detect light from the luciferase fragments only when they injected the mice with rapamycin, causing the two proteins to interact. In mutations that disabled rapamycin's ability to bind to the target protein, scientists detected no light even after rapamycin injections.

According to Piwnica-Worms, the series of experiments proved the accuracy and selectivity of the new luciferase-based approach.

Scientists also successfully tested the new technique on two proteins linked to regulation of the cell life cycle. An anti-cancer drug is being developed to block the interaction of these proteins.

"We can now monitor the effects of that drug in live animals using the luciferase technique," says Piwnica-Worms. "It's been an exciting development ?we're already collaborating with several colleagues around campus to use this system to study interactions between seven or eight other important pairs of proteins."

Luker KE, Smith MCP, Luker GD, Gammon ST, Piwnica-Worms H, Piwnica-Worms D. Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proceedings of the National Academy of Sciences, Aug. 17, 2004.

親愛的，我看到你磷酸化了！

2004-09-09T10:08:00.000+08:00

親愛的，我看到你磷酸化了！

　　科學家利用螢火蟲的螢光酵素（luciferase）來顯示分子間運動的狀況。

　　生物體中的訊息傳遞路徑（signal pathway）管理著許多重要的功能，細胞週期的進行、新陳代謝等等作用都需要經由訊息傳遞路徑來調控。而在訊息傳遞路徑的調控當中，蛋白質之間的作用扮演了相當重要的角色，磷酸化（phosphorylation）就是一例。

　　不過訊息傳遞路徑的運作，會依細胞所處組織環境的不同而有所改變，這是不能在體外實驗中忠實呈現出來的一面。因此有人使用正子斷層攝影（PET）或是生物冷光（bioluminescence）的方式，嘗試以非侵入式的方法，來獲得生物體內蛋白質之間作用的過程。而目前偵測蛋白質之間作用的策略包括了活化或抑制轉譯的步驟、活化訊息傳遞路徑，或是還原被中斷的酵素活性。

　　在酵素活性方面，若將單一蛋白質切成兩半，這兩個片段並不會自行組合而產生作用。只有在這兩個片段能夠經由藥物等其他作用而再度團圓時，才會進行正常的酵素功能。但是螢火蟲的螢光酵素受限於其N端部分所發出的藍綠色光（藍綠色光穿透生物體的效果不佳）；水母的螢光酵素應用在生物體上的種種限制，所以現有的螢光酵素系統無法完全滿足非侵入式蛋白質作用造影的需求。

　　不過最近在美國華盛頓大學的博士後研究員Kathryn E. Luker所領導的研究中，則改進了現有的螢光酵素互補造影系統（luciferase complementation imaging, LCI）。

　　他們首先製造出不同重疊長度的螢光酵素N端及C端配對，然後使用細菌來觀察這些配對的作用狀況，選出發光度最強的三對，接著觀察這三對螢光酵素組合在生物體中的表現。

　　在老鼠方面的實驗，他們用選用了兩種因為免疫抑制劑rapamycin而作用的蛋白質，一種稱為mTOR（mammalian Target of Rapamycin）的蛋白質，另一個則是FKBP。他們將mTOR上一個跟FKBP-rapamycin複合物親和性很高的區域──FRB──與螢光酵素的N端部分結合；螢光酵素C端部分則與FKBP結合。結果顯示，只有在rapamycin注入老鼠體內時，螢光酵素片段才會結合而發出螢光，另外在細胞中觀察磷酸化相關的反應也得到很好的效果。

　　在他們的方法當中，螢光酵素片段在結合時所發出的螢光是背景的1200倍，超過目前現有系統的表現。這使得LCI這個檢測方法的靈敏度大大地提高，也讓偵測一些親和力沒那麼強的蛋白質作用成為可能。這個方法目前正用來進行更多不同蛋白質作用的檢測，不過可預見的是，這個方法將成為一個在藥物篩選上極為有力的工具。

原始論文：
Kathryn E. Luker, et al. Kinetics of regulated protein–protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. PNAS published July 29, 2004, 10.1073/pnas.0404041101.

Could heart drugs treat HIV?

2004-09-09T10:07:00.000+08:00

Could heart drugs treat HIV?

David Osumi-Sutherland
Cholesterol-lowering statins may provide an alternative to antiretrovirals.

A study of six AIDS patients has revealed that statins can reduce levels of HIV and boost immune cell numbers. If the results can be repeated in large-scale trials, it's hoped that statins could provide an alternative to standard HIV treatments.

Statins are taken by millions of people to lower cholesterol levels and help protect against heart disease. And studies have shown that cultured cells with low levels of cholesterol in their membranes are less likely to succumb to HIV infection.

So, Carlos Martínez from the Spanish Council for Scientific Research and colleagues decided to study the effects of cholesterol-lowering statin drugs on HIV patients. Their results are reported in the Journal of Experimental Medicine1.

A one-month course of statin treatment caused the virus levels of human patients to drop by up to 20-fold. Levels began to rise when patients stopped taking the drug.

When mice, injected with HIV-infected human cells, were given the drugs, their virus levels fell, in some cases to undetectable levels.

Together, these results suggest that statins may prove useful against HIV in human patients, says Martínez.

Killer virus

HIV suppresses the immune system by infecting and killing the cells of which it consists. Martínez believes that statins prevent the virus from entering healthy cells in the first place.

It is hoped that the drugs could offer an alternative to the standard AIDS treatment, highly active antiretroviral therapy (HAART). This therapy is becoming less effective as drug-resistant HIV strains continue to emerge.

Resistant strains have limited the options for many HIV-infected patients, explains HIV researcher Eric Freed of the HIV Drug Resistance Program at the National Cancer Institute in Frederick, Maryland. "This makes the development of alternative treatments especially urgent."

Statins could also prove safer than antiretrovirals. HAART can trigger serious side-effects, such as liver damage, but statins are relatively free of such problems.

Martínez hopes that statins could also be used preventatively. His study shows that white blood cells taken from patients on statins are less likely to succumb to HIV infection.

Larger clinical trials should be forthcoming, says Martínez. But he cautions that such studies are difficult to set up. It is hard to find HIV-positive patients who are not already taking anti-HIV medication, he points out. One solution may be to concentrate on patients who have already become resistant to the standard treatments.

心臟病藥物能夠治療愛滋病

2004-09-09T10:06:00.000+08:00

心臟病藥物能夠治療愛滋病

根據一項針對六位愛滋病患的研究報告，服用statins 類藥物(一種心臟病用藥)能夠降低愛滋病傷害的程度，及增加免疫細胞的數量。如果此結果能再經過大規模的實驗證實，則未來statins將可能會成為愛滋病的另一項替代療法。

世界上有數百萬人服用statins作為降膽固醇藥物，預防心臟病。組織培養顯示若細胞膜上的膽固醇含量低時，細胞較不易受到HIV的侵入感染。所以，西班牙科學研究協會的Carlos Martínez及其同事決定在愛滋病患的身上試驗statins所達到的效用，他們的結果發表在「實驗醫學」期刊(Journal of Experimental Medicine)上。

經過一個月的statins療程後，病患體內的病毒數量降低了20倍之多，一旦停止服藥，病毒量又會開始回升。以注射遭HIV感染之人類細胞的老鼠來進行試驗時，服藥同樣可以降低病毒的數量，某些案例中甚至到了無法偵測的程度。Martínez表示，這些結果共同顯示出statins似乎具有有效抵抗愛滋病的能力。

HIV藉由感染並摧毀免疫細胞的方式來抑制免疫系統，Martínez相信statins阻擋了病毒進入健康細胞的路徑。此藥物為愛滋病的標準療法--雞尾酒療法(Highly active antiretroviral therapy，HAART)提供了替代性的作法，隨著抗藥性HIV病毒株的出現，雞尾酒療法逐漸變得不如從前有效。

愛滋病研究者Eric Freed表示，抗藥性的病毒株已經使得病患沒有太多的治療選擇，這使得替代性療法的發展變得格外緊急。Statins除了具有抗愛滋病的療效，也比其他的抗反轉錄病毒藥物(antiretrovirals)要來的安全。雞尾酒療法會造成嚴重的副作用，例如肝臟受損，statins就沒有這種顧慮。

Martínez希望statins可以作為預防性用途之用，他的研究顯示服用statins的人，其白血球較不易受到愛滋病毒的入侵。Martínez也說大規模的臨床實驗是必須的，但此類的實驗並不易進行。要找到愛滋病檢驗呈陽性反應、又未曾服用任何抗HIV藥物的病患是相當困難，解決之道或許將從已對標準療法產生抗力的病患著手。

RNA Can Now Be Built Into 3-D Arrays

2004-09-09T10:04:00.000+08:00

No Longer Just For Biology, RNA Can Now Be Built Into 3-D Arrays

ARLINGTON, Va.?Researchers have coaxed RNA to self-assemble into 3-D arrays, a potential backbone for nanotech scaffolds. These RNA structures can form a wider variety of shapes than double-stranded DNA can and are easier to manipulate than many protein alternatives.

Peixuan Guo of Purdue University and his colleagues report the findings in the August 11, 2004, issue of the journal Nano Letters.

RNA (ribonucleic acid) molecules are best known for implementing the genetic information encoded in DNA (deoxyribonucleic acid). However, instead of using the long molecular strings to carry information, the researchers have achieved new control over RNA and created novel arrays.

By mixing the custom-made RNA strands with other substances, such as magnesium chloride, the researchers were able to get the strands to join into 3-D shapes.

In 1987, Guo discovered that a bacteria-infecting virus possesses a biomolecular nanomotor that requires RNA molecules to function. While determining how RNA works in that motor, he learned to manipulate and control RNA assembly.

Now, Guo and his colleagues have applied that knowledge to building artificial RNA nanostructures, including arge?3-D arrays formed from identical RNA building blocks. Because these arrays extend to several micrometers, far larger than individual RNA strands, they may potentially link nanofabrication with current microfabrication processes.

The researchers hope that the arrays, while still in the earliest stages of development, will one day serve as the scaffolding on which diagnostic chips, tiny sensors, gene delivery vehicles and other nanoscale devices will be mounted or constructed.

From the researchers:

iving systems contain a wide variety of nanomachines and ordered structures, including motors, pumps and valves. Our research is devoted to making these machines function outside their native environment.??Peixuan Guo, Purdue University

e have discovered a particular type of RNA molecule known as pRNA, or packaging RNA, that forms six-unit rings that can drive a tiny but powerful molecular motor.??Peixuan Guo

ur future research will focus on incorporating these nanomachines into nanodevices for such applications as drug or gene delivery, gears for nano-equipment, and intricate arrays and chips for diagnostic devices, sensors and electronics.??Peixuan Guo

his report demonstrates that RNA can be used to form a variety of artificial shapes and that we can assemble these shapes into arrays tens of microns in size. Using RNA tendency to self-assemble, we have built the arrays from many thousands of connected RNA building blocks. The arrays are stable and resistant to a wide range of environmental conditions, such as temperature, salt concentration, and pH.??Peixuan Guo

From experts at NSF:

he discovery of this viral RNA machine is quite remarkable and provides yet another example of the flexibility and versatility of RNA. Dr. Guo is exploiting the properties of RNA in a new and potentially important way.??Patrick Dennis, Program Director for Microbial Genetics at the National Science Foundation and the officer who oversees Dr. Guo award.

強勁的分子發動機─RNA奈米馬達 (nano-motor)

2004-09-09T10:02:00.000+08:00

強勁的分子發動機─RNA奈米馬達 (nano-motor)

美國普渡大學研究人員成功地把RNA組成3D陣列 (3D arrays)。

　　一般來說，具有遺傳訊息的去氧核糖核酸DNA可以轉譯成核糖核酸RNA，但是RNA分子結構比DNA分子結構具有多樣化的特性，也就是RNA可以形成多樣的結構（諸如：單體monomer、雙合體dimer、三合體trimer、六合體hexamer等等）。

　　普渡大學分子病毒學教授Peixuan Guo的研究團隊，早於1987年在phi29病毒裡發現一種特殊的RNA結構，它稱為pRNA(packaging RNA)，其pRNA單體(monomer)之間可以互相聯結組合成六合體（hexamer）環狀結構，而這種六合體環狀結構又稱做奈米馬達（nano-motor），它可以用來包裝DNA，把DNA分子送入病毒衣殼（procapsid）裡頭。

　　Peixuan Guo等人目前正把奈米馬達的概念應用在設計人工RNA奈米裝置中，他們已經成功地從RNA形成的模塊中建造出3D陣列，並且這些3D陣列更可以延伸至數個微米(micrometers)，進而搭起奈米製造（nanofabrication）與微米製造（microfabrication）之間的橋樑。而消息已刊登在2004年八月的《奈米通訊期刊》 (Nano Letters)。

　　Peixuan Guo指出，在生物體內具有各式各樣的奈米機器，例如細胞膜上的幫浦(pump)或馬達(motor)等，他們正致力在把這些生物體內的奈米裝置，拿到外界也就是活體外的環境下來表達，正如同上述的RNA六合體環狀結構，就可以用來當成精小但強又有利的奈米馬達。而目前這些RNA的3D陣列還是處於初期研發的階段，他們希望未來能夠把這些3D陣列應用在病理診斷晶片、微小感應器、基因治療使用的基因輸送載體以及電子儀器等研發。

原始論文：Shu D, Moll D, Deng Z, Mao C, and Guo P. 2004. Bottom-up assembly of RNA arrays and superstructures as potential parts in nanotechnology. Nano Letters 4: 1717-1724.

Lotus effect helps light move water

2004-09-09T09:57:00.000+08:00

Lotus effect helps light move water

5 August 2004

With the aid of a nanowire-coated surface, researchers at Arizona State University, US, have become the first to move water droplets simply by illuminating them with ultraviolet light. The technique could have applications in microfluidic devices.

Drop by drop
To achieve the result the team deposited silicon nanowires with diameters of 20-50 nm randomly on a silicon surface. Then they coated the wires with a monolayer of photochromic spiropyran molecules. These organic molecules are hydrophobic until illuminated with ultraviolet light. In fact, lotus leaves make use of a similar structure to repel water droplets - they have a very fine surface structure and are coated with hydrophobic wax crystals of around 1 nm in diameter (see Lotus effect shakes off dirt).

A water droplet will move across a surface if its advancing contact angle is lower than the receding contact angle. Shining ultraviolet light with a wavelength of 366 nm onto the spiropyran molecules converted them to their polar hydrophilic form and reduced the contact angle. So you might expect ultraviolet light to cause water droplets to move on any surface coated with spiropyran.

But there's a snag. On a smooth surface the transformation of the spiropyran molecules to their hydrophilic form reduced the contact angle by 12°. That wasn't enough to cause the water droplet to move, however, as the contact angle hysteresis (the difference between advancing and receding contact angles) for the smooth surface was 37° under visible radiation.

On a nanowire surface, in contrast, the contact angle hysteresis was only 17° and the illumination of the spiropyran molecules with UV light reduced the contact angle by 23°, nearly twice as much as for the smooth surface. As a result of both these factors the advancing contact angle became lower than the receding contact angle and the water droplets moved along the surface towards the source of the UV light.

"We have been working on the problem of using light to move microscopic amounts of water around for drug delivery and microanalysis applications," said Tom Picraux of Arizona State. "Our advance came when we realized that if the surface was roughened at the nanoscale, not only would we obtain the 'lotus-leaf effect', but we could also magnify the small change in water repelling controlled by light to a level that can overcome the hysteresis, or the attraction, that causes water to stick even when a drop is pushed along."

The process is also reversible since treating the spiropyran molecules with visible radiation with a wavelength of 450-550 nm caused them to return to their closed hydrophobic form.

Moving water droplets with light avoids the need to use potentially damaging electric fields, air bubbles, which can denature proteins, or microscopic mechanical pumps, which are expensive to make and difficult to repair.

The scientists, who reported their work in Journal of Physical Chemistry B, say their findings also point the way to enhanced fluidic motion and control in electrowetting and thermowetting microfluidic systems.

About the author
Liz Kalaugher is editor of nanotechweb.org.

蓮花效應有助於以光移動水滴

2004-09-09T09:56:00.000+08:00

蓮花效應有助於以光移動水滴

　美國亞歷桑那州立大學的科學家藉由將奈米線(nanowire)覆蓋在表面上，首度成功地僅憑紫外光照射就能移動水滴。這項技術未來可望應用在微流(microfluidic)元件上，或許將有助於藥物輸送等應用。

　　該研究小組先在矽表面上隨意沉積了直徑20-50奈米的矽奈米線，然後在奈米線上覆蓋單分子層光致色變(photochromic)的spiropyran分子，這種有機分子在照射紫外光之前是拒水性的。事實上，荷葉也是利用類似的效應來趕走水滴──葉面上覆蓋了直徑約1奈米的拒水性蠟質結晶行(參見奈米小辭典蓮花效應)。

　　位於表面的水珠如果往前的接觸角(contact angle)大於後退的接觸角，水珠就會向前移動。以波長366奈米的紫外光照射，能讓spiropyran分子轉變成親水性，接觸角因而降低。在平滑表面上，這個降幅為12°，尚不能使水珠移動，因為在光滑表面上，可見光的照射所引起的前後接觸角差值變化(contact angle hysteresis)可達37°。相形之下，在奈米線的表面，接觸角差值變化只有17°，而紫外光造成的降幅為23°，幾乎是光滑平面的兩倍。這兩個因素相加的結果，造成前進的接觸角變大而後退的接觸角變小，於是水珠會朝向紫外光源移動。

　　以波長450-550奈米的可見光照射，能使spiropyran分子恢復拒水性，因此上述過程是可逆的。以光來移動分子使科學家得以免除使用電場、氣泡或微機械幫浦，前兩者可能會使樣品變質，後者則既昂貴又不易修理。研究人員表示，這項發現為流體運動的強化及電濕潤(electrowetting)/熱濕潤(thermowetting)微流系統的控制，指出了一個條方向。詳見近期的Journal of Physical Chemistry B。

Discover Biological Basis For Autism

2004-08-21T13:17:00.000+08:00

Carnegie Mellon And University Of Pittsburgh Scientists Discover Biological Basis For Autism

PITTSBURGH -- A team of brain scientists at Carnegie Mellon University and the University of Pittsburgh have made a groundbreaking discovery into the biological basis for autism, a mysterious brain disorder that impairs verbal and non-verbal communications and social interactions.

Using functional magnetic resonance imaging (fMRI) scans, the researchers have found numerous abnormalities in the activity of brains of people with normal IQs who have autism. The new findings indicate a deficiency in the coordination among brain areas. The results converge with previous findings of white matter abnormalities in autism. (White matter consists of the "cables" that connect the various parts of the brain to each other). The new findings led the researchers to propose a new theory of the basis of autism, called underconnectivity theory, which holds that autism is a system-wide brain disorder that limits the coordination and integration among brain areas. This theory helps explain a paradox of autism: Some people with autism have normal or even superior skills in some areas, while many other types of thinking are disordered. The team's study will be published in the August edition of the British journal Brain and is available online at www.brain.oupjournals.org.

In explaining the theory, Marcel Just, one of the study's lead authors and director of Carnegie Mellon's Center for Cognitive Brain Imaging, compared the brain of a normal person to a sports team in which the members cooperate and coordinate their efforts. In an autistic person, though some "players" may be highly skilled, they do not work effectively as a team, thus impairing an autistic's ability to complete broad intellectual tasks. Because this type of coordination is critical to complex thinking and social interaction, a wide range of behaviors are affected in autism.

The research team believes these are the first findings in autism of differences in the brain activation patterns in a cognitive (non-social) task. The study produced two important new findings that help make sense of previous mysteries: The autistic participants had an opposite distribution of activation (compared to the control group) in the brain's two main language areas, known as Broca's and Wernicke's areas. There was also less synchronization of activation among key brain areas in the autistic participants compared to the control group.

To obtain technically acceptable fMRI data from high-functioning autistic participants, the researchers flew in people with autism from all over the eastern United States. High-functioning participants with autism (with IQ scores in the normal range) are rare, accounting for about 10 percent of all people with autism. Using non-invasive fMRIs, the team looked at the brains of 17 people with autism and 17 control subjects as they read and indicated their comprehension of English sentences. In both the healthy brains and in the brains with autism, language functions were carried out by a similar network of brain areas, but in the autism brains the network was less synchronized, and an integrating center in the network, Broca's area, was much less active. However, another center, Wernicke's area, which does the processing of individual words, was more active in the autism brains.

The brain likely adapts to the diminished inter-area communication in autism by developing more independent, free-standing abilities in each brain center. That is, abnormalities in the brain's white matter communication cables could lead to adaptations in the gray matter computing centers. This sometimes translates into enhanced free-standing abilities or superior ability in a localized skill.

These findings provide a new way for scientists and medical researchers to think about the neurological basis of autism, treating it as a distributed system-wide disorder rather than trying to find a localized region or particular place in the brain where autism lives. The theory suggests new research to determine the causes of the underconnectivity and ways to treat it. If underconnectivity is the problem, then a cognitive behavioral therapy might be developed to stimulate the development of connections in these higher order systems, focusing on the emergence of conceptual connections, interpretive language and so on. Eventually, pharmacological or genetic interventions will be developed to stimulate the growth of this circuitry once the developmental neurobiology and genetics of these brain connections are clearly defined by research studies such as these.

The research team is jointly headed by Just, the D.O. Hebb Professor of Psychology at Carnegie Mellon, and Dr. Nancy Minshew, professor of psychiatry and neurology at the University of Pittsburgh School of Medicine and director of its Center for Autism Research. Individuals with High Functioning Autism and Asperger's Syndrome between 10 and 55 years of age who are interested in participating in similar studies can send email to autismrecruiter@upmc.edu or call Nikole Jones at 412-246-5481.

自閉症研究的新視野

2004-08-21T13:16:00.000+08:00

自閉症研究的新視野

科學家提出新的理論來解釋自閉症(autism)的成因，認為自閉症可能是源於腦部整合性功能的不足所致。

提到自閉症，最令人印象深刻的莫過於達斯汀霍夫曼（Dustin Hoffman)在雨人（Rain man）一片中所飾演的角色。擁有出色的計算能力，日常生活一絲不苟，但無法與外界溝通，也很難找到一份可以賴以維生的工作。在這樣的狀況下，自閉症患者在某些方面優越的表現，反而為這種病症添上一抹神秘而令人感嘆的色彩。

自閉症的成因至今尚未有定論，父母的管教、染色體的異常、腦部損傷等等原因都有人提出過，但還沒有一個理論可以完整的解釋自閉症患者在某些情況表現優異，卻無法與他人溝通的現象。

美國卡內基梅隆大學（Carnegie Mellon University）與匹茲堡大學（University of Pittsburgh）合作發表了一個新理論：「溝通不良理論」（Underconnectivity theory），為自閉症的研究提供了一個新的視野。

在他們的實驗當中特別找來17位患有自閉症但智商正常的患者，以及17位正常人作為對照組。實驗的方式是測驗受試者對語句的理解力，同時並使用功能性磁振造影（fMRI）來觀察受試者腦部活動的情形。

他們的研究發現，自閉症患者在大腦維尼克區（Wernicke's area）的活動較布羅卡區（Broca's area）來得活躍。維尼克區負責處理的是一個句子當中，個別單字的意義，這可以解釋為何某些自閉症患者有優異的能力來處理個別單字。

而布羅卡區負責的是對句子的理解，由於自閉症患者布羅卡區的活動並不活躍，所以他們在瞭解一些結構複雜的句子時會遭遇到困難。

另一個發現是，自閉症患者腦部的皮質語言系統（cortical language system）中，各皮質區域之間的功能性連結較正常人來得不發達，可以佐證何以自閉症病人無法處理整合性的事件，這也與之前其他研究發現自閉症患者在腦部白質部分有缺陷的情況互相呼應。

同時也發現自閉症患者在腦部枕頂區域（occipitoparietal area）的活動較控制組來得低落，所以自閉症的患者較難想像出一段文字所描述的景象。能夠想像得出文字所描述的內容，就是一種腦部整合性的活動。

根據「溝通不良理論」的解釋，正是因為自閉症患者在腦部整合功能網路上有缺陷，使得他們對數字、文字、或是對某些事件的記憶力有極佳表現，但也使得他們無法順利的同時進行多樣工作，所以沒法與人正常的溝通，也限制了他們在其他整合性工作方面的表現。

藉由「溝通不良理論」就可以解釋自閉症患者一個最大的特徵──孤獨，無法與他人進行正常的社交行為。這是因為社交行為需要腦部極複雜的整合。一個人必須能夠同時解讀他人微妙的表情變化、用句遣詞，配合當下的情境，才能做出相當的應對。不管是對語句的理解或是一般的社交活動，這些複雜的整合性活動對於自閉症患者而言都是一件很困難的事。

可惜在現今這個社會架構當中，無法與人溝通無疑是個嚴重的缺陷，也限制了自閉症患者正常生活的能力。若能真正解開自閉症的成因，就可以設計更適合他們的訓練課程，使他們能融入正常的生活，而且也能發展出更有效治療自閉症的藥物。

原始論文：
Marcel Adam Just, et al. Cortical activation and synchronization during sentence comprehension in high-functioning autism：evidence of underconnectivity. Brain, 127, 1811-1821(2004).

Photon Marathon

2004-08-21T13:14:00.000+08:00

Photon Marathon

Somewhere between a light bulb and a laser is an unusual and sometimes puzzling type of light source called a random laser. It emits laser-like light, but in all directions. Now a research team believes they understand one of the mysteries of random lasers: why they can emit blasts of monochromatic light as pure as those of an ordinary laser. As the team reports in the 30 July PRL, their experiments and computer simulations show that each pure pulse begins as a single "lucky" photon that manages to bounce around hundreds of times before escaping.

In a typical laser, the light bounces back and forth inside a reflective cavity containing an amplifying material, such as a laser crystal. The ricocheting photons recruit more photons with each pass through the material and can escape through a partially transmitting mirror to make a beam.

Now imagine taking the crystal out of the cavity and grinding it into a powder, and you have a random laser. Hit it with brief pulses of excitation light, and the powder glows in response. The amplification happens when each photon scatters around many times inside the powder, continually eliciting more photons as it travels on a so-called random walk. When it finally escapes the powder, the light usually contains a spread of wavelengths that is broader than the nearly-single-wavelength output of a normal laser.

But if the amplification is strong enough, a random laser spits out extremely monochromatic light at several wavelengths, light that dominates its broader background emission. These "ultra-narrow" spikes in the spectrum appear at different wavelengths with each pulse and are unpredictable, unlike a normal laser, where the size of the reflecting cavity determines the beam's wavelength. Some researchers have proposed theories to explain this phenomenon, but others have remained unconvinced.

Now Diederik Wiersma of the European Laboratory for Nonlinear Spectroscopy in Florence and the Italian National Institute for the Physics of Matter and his colleagues have come up with an explanation, using results from experiments and computer simulations. The team's random laser consisted of a laser dye dissolved in alcohol along with particles of zinc oxide to scatter photons. When excited with green laser pulses, the mixture emitted the narrow peaks that others had seen.

Computer simulations reproduced the results and led to the explanation, which the researchers call the "lucky photon" effect. Although most photons emerge from their random walks through the liquid after about ten "ricochets," a very few photons walk the photon equivalent of a marathon--from 100 to 1,000 ricochets. In these rare cases, the original photon picks up an enormous number of companion photons of precisely its wavelength--perhaps 1012 of them in the case of a photon that ricochets 500 times.

"Why didn't we think of that before?" Wiersma recalls wondering after he and his colleagues ran the simulations. The random laser problem is deceptively similar to the more common scattering problems physicists look at, in which the medium doesn't amplify. Without amplification, a single photon traveling a marathon path length doesn't make a difference. "Once you understand that it happens, it is quite a natural explanation," says Wiersma.

"For sure, this model explains the random laser effect in some of the systems," agrees Mikhail Noginov of Norfolk State University in Virginia, noting the "good agreement" between the numerical calculations and experimental results. He hopes future experiments will test how broadly the model applies to other types of random lasers.

--Chelsea Wald

幸運光子造就隨機雷射

2004-08-21T13:13:00.000+08:00

幸運光子造就隨機雷射

義大利的研究人員相信他們已經找到隨機雷射(random laser)可以發出無方向性但卻具單色性的光源的原因了.

一般雷射的形成是讓光在具有增益介質的共振腔中來回振盪, 透過受激輻射使光強度不斷放大, 並具有同調性及單色性. 但如果把增益介質拿到共振腔外, 並將之磨成粉狀, 則變成一個隨機雷射. 此時若用短脈波光照射激發, 則這粉末將會發光. 如果光子在粉末中被散射很多次, 則會誘發出更多的光子. 最後當光子脫離粉末時, 其波長範圍會比一般的雷射光(幾近單色光)還要寬很多.

然而, 如果更進一步將激發光的強度增強, 隨機雷射所發出的光的波長則會只剩下幾個非常單色的波長. 這些波長的位置會隨著不同的激發脈波而改變, 而且是無法預測的. 不像一般的雷射, 光的波長的位置可由共振腔的寬度來決定. 在此之前也曾有一些研究人員提出理論來解釋這現象, 然而其他的人則尚抱持懷疑的態度.

在2004年7月30的Physical Review Letters中 European Laboratory for Nonlinear Spectroscopy in Florence and the Italian National Institute for the Physics of Matter的Diederik Wiersma及其同僚提出了一個模型, 他們認為, 雖然大部分的光子在增益介質中以隨機步行(random walk)的方式反彈大約十次則會離開物質, 然而有少數的光子卻可在物質中反彈100-1000次, 他們稱這些光子是"幸運的光子". 而這些少數的幸運光子在離開物質時則會伴隨著大量相同波長的同調光子. 估計500次的反彈, 一個光子將會被放大成1012個光子. 他們以實驗及電腦模擬來驗證這個模型, 並得到相當契合的結果.

Norfolk State University in Virginia的Mikhail Noginov表示, 沒錯, 這個模型在某些系統上可以解釋隨機雷射的效應. 然而他更希望能有更多的實驗來測試這個模型的適用範圍.

Hormone levels turn mouse mums fearless

2004-08-21T13:12:00.000+08:00

Hormone levels turn mouse mums fearless
05:00 01 August 04
NewScientist.com news service

Mouse mothers become fearless when levels of a particular hormone drop, reveals a new study. This gives mothers the courage to ferociously attack any would-be assailants to their offspring.

In response to scary or stressful situations, the brain secretes corticotropin-releasing hormone (CRH), which triggers a complex cascade of hormones that ready the body for action, such as raising blood sugar levels. It also feeds into the part of the brain which generates feelings of fear and anxiety. Elevated levels of CRH have been linked with symptoms of depression in both rodents and humans.

But lactating females have chronically low levels of CRH in the brain, which is thought to make them generally less anxious. For example, studies in humans show that nursing women are less perturbed, both physiologically and emotionally, by stressful situations.

Stephen Gammie and colleagues at the University of Wisconsin, Madison, US wondered if lowered CRH might also be responsible for a mother’s fearless bravery.

To test their theory, the team injected three different concentrations of CRH or a saline solution into the brains of nursing mothers and then placed a male her nesting cage. Compared to controls, who immediately assaulted the male, mice injected with the two higher doses of CRH showed almost no maternal aggression. Their response was delayed, their attacks less frequent and much shorter.

Stressful jobs

Mothers with the lowest levels of CRH attacked intruding males more than 20 times for the duration of about 45 seconds.

“Low levels of CRH seem to be necessary for maternal protective behaviour. It makes evolutionary sense for mothers to increase aggression because it’s critical for them just to keep the kids alive,” says Gammie. Unbalanced levels of CRH in humans may also be connected with post-partum depression, he says.

For the past few years, pharmaceutical companies have been working to develop CRH receptor blockers, like antalarmin, as a treatment for anxiety disorders, depression and post traumatic stress disorder. The drugs could have a performance-enhancing effect on people with extremely stressful jobs.

“In war, soldiers are under high stress constantly,” says Tracy Bale, who works on CRH and depression at University of Pennsylvania. “In those cases, a CRH blocker might help.”

However, results with animal studies suggest that responses could be highly sex-dependant. And, adds Bale, the dose would be critical because CRH is involved with many other bodily functions, including glucose metabolism. Blocking too much CRH might hinder performance more than it helps.

Journal reference: Behavioral Neuroscience (DOI: 10.1037/0735-7044.118.4.000)
Anna Gosline

賀爾蒙的濃度變化使母親無所畏懼

2004-08-21T13:11:00.000+08:00

賀爾蒙的濃度變化使母親無所畏懼

哺乳類雌性動物會不顧任何生命危險地保護自己的子女，研究發現，CRF（Corticotropin-Releasing Factor）的減少會降低母親的害怕與焦慮，來保護她們的子女。這項研究刊登於最新一期，八月號的Behavoiral Neuroscience。

在生物學上，這種母親不顧一切保護子女的行為，稱為母性侵略行為（maternal aggression）。不過之前很少有研究說明此母性侵略行為背後的生物機制究竟是什麼。美國威斯康辛大學麥迪遜校區的Stephen Gammie說：「我們已經知道，雌性動物在哺乳期時，害怕和焦慮的情緒會減少。也許就是如此，會讓母親們改變其正常行為，將原本只會引起恐懼情緒的刺激，轉變成攻擊的行為，並藉此保護自己的子女。」

為了證實此項假說，Gammie和他的同事便開始研究老鼠的母性侵略行為和腦中CRF的高低有何關聯。CRF是腦內的一種胜肽，可以控制行為。

在母鼠分娩後第六天，研究人員給母鼠注射三種不同劑量的CRF溶液和生理食鹽水（不含CRF）作為控制組。注射的情形是每天一次並連續打四天。然後把母鼠和小鼠放在一起並加入一個公鼠。由於公鼠有時候會去吃小鼠，在正常情形下母鼠會憤怒地去攻擊那些吃小鼠的公鼠。研究的結果發現，當沒有注射和只注射小劑量的CRF時，母鼠們會在45秒內超過20次攻擊公鼠。而中劑量的母鼠則會在八秒內攻擊六次；高劑量的母鼠卻什麼事也不做。

Gammie根據這個結果說明：「降低CRF濃度似乎是形成母性侵略行為的必要條件。」研究人員認為這個結果或許可以解釋為何產後憂鬱症（postpartum depression）的母親會忽略他們的子女甚至於虐待他們，因為產後憂鬱症可能和高CRF有關。或許將來可以設計阻斷或拮抗CRF接受器的藥物來進一步控制因壓力而引起的焦慮。

原始論文：S.C. Gammie, A. Negron, S. M. Newman, and J. S. Rhodes. Corticotropin-Releasing Factor Inhibits Maternal Aggression in Mice. Behavioral Neuroscience (DOI: 10.1037/0735-7044.118.4.000)

科學解析「盲者善聽」

2004-08-21T13:09:00.000+08:00

科學解析「盲者善聽」

盲人音樂家的才華洋溢是一再發生的巧合呢？還是由於專注的凝集呢？加拿大科學家們發現：年幼失明的盲者對於樂音變化的察覺能力確實遠遠強於後天失明者及普通人。

陰符經相傳為黃帝所作，文中曾提到：『盲者善聽，聾者善視；絕利一源，用師十倍；三反晝夜，用師萬倍』。這幾句話的主要意思為：喪失視力之便的盲人，聽力卻往往更為的敏感；屏除聽聞之利的聾者，視覺卻往往尖銳；所以，只要【全神貫注】地成就一件事情，便可以激發出十倍潛能；如果這份專注的功夫更能【持續】上一段時間，那更能產生萬倍的威力。

陰符經中舉了「盲者善聽」與「聾者善視」這兩個例子，但其中又以「盲者善聽」更為令人印象深刻，畢竟從古至今出現了太多才華洋溢的盲人音樂家，例如：Ray Charles 與 Stevie Wonder，他們的音樂作品都曾於二十世紀末風靡一時、專擅一方。

這些「盲者善聽」的偉大成就是純屬巧合呢？還是由於潛能的凝聚呢？加拿大科學家Pascal Belin與其研究團隊發表於2004年七月《自然》期刊(Nature 430：309)的研究成果指出：年幼失明的盲者對於樂音變化的察覺能力確實遠遠強於後天失明者及普通人。

在他們的研究中，將受試者區分為三大群體：第一群為七位年幼(二歲以前)失明盲者，第二群為七位年長(五歲到四十五歲間)後失明者，第三群則為十二位視力正常受試者。接著，研究人員要求這些受試者凝聽一系列由兩個連續且音高不同的樂音組成的音對，並對各音對中樂音的高低變化進行判斷。

實驗中，研究人員將音高差為1/8個八度音(相當於150音分值或1.5個半音)，音值(發聲體震動時延續時間的長短)為333毫秒的音對做為參照。通過對參照音對的兩個特徵變量分別進行四次對半遞減，64個實驗音對被分為8組，每組包含8個頻率不同抑揚相異的音對。實驗結果顯示：無論是對稍縱即逝的樂音變化(最短音值：20.8毫秒)，還是極其細微的音階波動(1/128個八度音)，相較於後天失明或視力正常的受試者，年幼失明的盲者都更能準確地辨析。

Pascal Belin推測：出生時的大腦中負責視覺、聽覺與其他感覺的神經系統都是相互聯繫的，只是在發育的過程中，大腦中各種感官間的聯繫會逐漸消失。然而，如果年幼失明，則這種感官間聯繫現象則會被保留下來，如此一來，大腦中的視覺皮質也可以協助處理聲音信息了。

本文感謝英國牛津大學經濟系劉一沛協助完成。

原始論文：Neuropsychology: pitch discrimination in the early blind. Nature. 2004 Jul 15;430(6997):309.

Nanoparticles target tumours

2004-08-12T13:56:00.001+08:00

Nanoparticles target tumours
29 July 2004

Researchers at Emory University, Georgia Institute of Technology and Cambridge Research & Instrumentation, all in the US, have used semiconductor nanocrystals (or quantum dots) to simultaneously target and image cancerous tumours in mice.

"Although other research groups have used quantum dots to either target or image cells, we believe this is the first time in vivo targeting and imaging has been achieved simultaneously," said Xiaohu Gao of Emory University and Georgia Institute of Technology.

Gao and colleagues used cadmium selenide-zinc sulphide (CdSe-ZnS) core-shell quantum dots with a diameter of 5 nm. They coated the nanoparticles with a protective layer of an ABC triblock copolymer and then a layer of poly (ethylene glycol). The triblock polymer protects the quantum dots from enzymes and other biomolecules and also acts to prevent leakage of toxic cadmium and selenium ions. Finally, they attached the quantum dots to a monoclonal antibody that targets prostate-specific membrane antigen on the prostate tumour cell surfaces.

When the team injected the quantum dots into the circulatory system of mice with solid prostate tumours the dots accumulated selectively at the site of the tumour. The scientists detected the dots by fluorescence imaging. They also tried "passive" targeting of the tumour by injecting quantum dots that weren't conjugated to antibodies. Although the quantum dots accumulated at the tumour sites as they leaked from the porous angiogenic blood vessels that grow in tumours, the process was slower and less efficient than for the quantum dots conjugated to antibodies.

"This is a new class of quantum dot conjugates designed specifically for complex in vivo applications," said Shuming Nie of Emory University and Georgia Institute of Technology. "They are stable over a broad range of pH and salt conditions and maintain their stability even after treatment with hydrochloric acid."

The researchers say they believe this is an important step in the quest to eventually use nanotechnology to target, image and treat cancer, cardiovascular plaques and neurodegenerative disease in humans.

"The larger surface area provided by quantum dots should allow the conjugation of multiple agents, and we envision the development of diagnostic and therapeutic dual-modality quantum dots," said Nie.

The scientists reported their work in Nature Biotechnology.

奈米微粒可標定腫瘤

2004-08-12T13:56:00.000+08:00

奈米微粒可標定腫瘤

　　美國的艾墨利(Emory)大學、喬治亞理工學院及劍橋儀器研發公司的科學家們，應用半導體奈米微晶(nanocrystals)或稱量子點(quantum dot)技術，已能在老鼠身上標定並觀察到腫瘤的影像。任職於艾墨利大學及喬治亞理工學院的Xiaohu Gao表示，雖然其他研究團隊也曾使用量子點來標定或觀察細胞，但該小組是最先能在活體內同時標定細胞並為其造影。

　　Gao和同事們使用硒化鎘(CdSe)為核、硫化鋅(ZnS)為殼、直徑約5奈米的量子點，並在外層包覆ABC三團聯共聚物(triblock copolymer)及聚乙二醇(pol(ethylene glycol))聚合物。這些聚合物保護層可將量子點與酵素及其他生化分子隔離，並可防止具有毒性的鎘(cadmium)及硒(selenium)金屬離子滲出。研究人員最後再將量子點連接上針對攝護腺癌的抗體，使量子點能標定攝護腺癌細胞的表面。

　　量子點經由注射進入老鼠體內，透過血液循環選擇性地累積在攝護腺腫瘤部位，科學家藉此偵測到老鼠腫瘤部位的螢光影像。他們也將未包裹抗體的量子點打入老鼠，這些量子點會由腫瘤新生的血管滲出而累積，但過程速度較慢效率也較低。該研究小組表示，這種新型量子點結合技術是特別針對複雜的體內應用而設計，在不同的酸鹼度及鹽類濃度都很穩定，甚至是以鹽酸處理後仍能維持其穩定度。

　　科學家相信，應用奈米科技發展運送藥物到腫瘤部位並為腫瘤造影的技術，能幫忙解決人類心血管斑塊阻塞及神經退化性疾病。量子點由於面積較大，可承載多種藥物，科學家期望能據此發展出具有診斷及治療雙效的量子點。詳見近期出刊的Nature Biotechnology。

2004-08-12T13:54:00.000+08:00

A nano-polymer a day keeps the microbes away
21 July 2004

Researchers at the University of Freiburg, Germany, have made a nanoparticle-containing polymer network that can act against microscopic organisms in several ways. The material repels bacteria and other microbes, releases a biocide and can also kill the organisms on contact.

"[Our work] demonstrates the potential of making template polymer networks for metal nanoparticles via readily available and relatively cheap starting materials, and might have applications in coatings for medical devices to keep them sterile," Joerg Tiller told nanotechweb.org. "There is also the potential for catalytic or optical applications."

The scientists based their material on the fact that it's possible to form silver nanoparticles within amphiphilically modified poly(ethylene imine) (PEI) derivatives in solution.

"As found in previous work, the approach of coating with silver nanoparticles instead of plain silver was very promising," said Tiller. "However, adhesion of bacteria dramatically changes the microbes' defence system, making them less vulnerable. So we decided to add an additional modification to the coatings: the microbe-repelling polymer poly(ethylene glycol) (PEG)."

To make the material the team copolymerized PEI, derivatized with double bonds, with 2-hydroxyethyl acrylate (HEA). The result was a polymer network containing nanoseparated PEI phases. The material can bind silver ions within these PEI phases as the silver links to the PEI's nitrogen groups. The HEA component, meanwhile, contained a hydroxyl group that can covalently attach to PEG.

"Most significant about our findings is that the silver nanoparticles can be formed within a coating simply by immersing it in aqueous silver nitrate solution, followed by treatment with aqueous ascorbic-acid solution," said Tiller. "Furthermore, the nanoparticle content can be perfectly controlled by the composition of the network."

The team tested the anti-microbial properties of the films by trying to grow Staphylococcus aureus bacteria on them. These bacteria are a major source of nosocomial infections - diseases acquired in hospital. After 12 hours of incubation at 37° C, the silver-loaded polymer networks did not support any bacterial colonies.

In contrast, colonies were visible after 12 hours on polymer networks that didn't contain silver nanoparticles, both on a PEG-modified and an unmodified version. The PEG-modified network supported four to five times fewer colonies than its sister material without PEG. The scientists say that this demonstrates the microbe-repelling properties of the "PEGylated" network.

Silver-loaded polymer networks did support bacterial colonies after longer periods, however. This indicates that the films only inhibited bacterial growth, i.e. that they were bacteriostatic.

The researchers reported their work in Advanced Materials.
About the author
Liz Kalaugher is editor of nanotechweb.org.

可抑菌的奈米織布

2004-08-12T13:51:00.000+08:00

可抑菌的奈米織布

　　德國科學家研究出一種含奈米微粒的聚合物織布，該材料除了可以驅除細菌或其他微生物，還能釋放殺菌成份，接觸時也能摧毀細菌或微生物的組織。這種材料可以做為維持醫療設備無菌狀態的包被物，同時也具有觸媒及光學上的應用潛力。

　　這種材料的製造主要是根據銀奈米微粒可以在聚乙烯亞胺(poly(ethylene imine), PEI)衍生物溶液中形成。弗萊堡(Freiburg)大學的Joerg Tiller指出，先前的研究發現包覆銀奈米微粒比包覆單純銀的織布更有效，然而細菌的吸附會大大強化微生物的防禦系統，因此他們在包覆物中又添加了抗菌的聚甘醇(poly(ethylene glycol), PEG)。

　　研究人員將二-羥乙基丙烯酸(2-hydroxyethyl acrylate, HEA)與具雙鍵的PEI衍生物共同聚合，製造出含有PEI相的聚合織布。這種材料能透過PEI的氮基與銀離子結合，HEA則藉由其氫氧基以共價鍵連接PEG。研究人員接著將織布浸入硝酸銀水溶液，再以菸鹼酸(ascorbic-acid)溶液處理，就可以在織布的網狀結構內形成銀奈米微粒。Tiller表示，這項工作證明了可以由便宜又容易取得的材料，製造出含金屬奈米微粒的聚合織布。

　　為了測試抗菌效果，研究小組在這種織布上培養金黃葡萄球菌(Staphylococcus aureus)，這是醫院內的一種主要感染源，結果發現在37℃下經12小時後，這種載有銀奈米微粒的織布並沒有任何菌落形成，相形之下，未含銀奈米微粒的織布，不論是否添加了PEG，都可觀察到菌落的形成，不過添加PEG的織布上的菌落數量要比未添加者少了四到五倍，顯示出這種聚甘醇烯化(PEGylated)的織布的抗菌特性。詳見近期的Advanced Materials.

Revised drug battles leukaemia

2004-08-03T14:21:00.000+08:00

Published online: 15 July 2004; doi:10.1038/news040712-13

Revised drug battles leukaemia
Helen Pilcher
Gleevec-resistant patients given fresh hope.

Cancer treatment's 'magic bullet' has had a makeover. Researchers have developed and tested a second-generation version of the leukaemia drug, Gleevec. It is hoped that the newcomer will offer relief to those who have developed resistance to the original drug.

Gleevec was the first cancer drug of its kind - designed specifically to target the molecules that cause chronic myeloid leukaemia (CML), a deadly form of cancer that affects 1 in 100,000 people. Since its approval by the US Food and Drug Administration in 2001, it has become the front-line therapy for CML. But around 20% of patients become resistant to the drug in the early stages of the disease, so other treatments are needed.

The new drug, called BMS-354825, shrinks tumours and prolongs life in mice with a Gleevec-resistant form of CML, researchers report in Science1. Around 80% of treated rodents were still alive one month after their cancer started to develop. Without treatment, all animals died within two weeks.

BMS-354825 also slows the proliferation of cultured bone marrow cells taken from CML patients, regardless of whether they have developed resistance to Gleevec or not.

In theory this means that the drug could work against both drug-resistant and Gleevec-treatable forms of human CML, says Neil Shah from the University of California, Los Angeles, who co-authored the study. But the best treatment regime may involve prescribing Gleevec and BMS-354825 together, he says.

Designer drugs

Gleevec, also known as imatinib, works by binding to and blocking an enzyme that drives the growth of leukaemia cells. Because it targets only the cancer cells, it leaves neighbouring healthy cells unharmed.

The problem is that sometimes genetic mutations occur that cause the enzyme to change shape and prevent the drug from latching on. BMS-354825 is less selective about how it binds to the enzyme, so it can attach even to mutated forms of the protein.

Up to now, 17 resistance-causing mutations have been spotted. The new drug works against 14 of the 15 tested so far. "We're optimistic that the other untested mutations will also be sensitive to the compound," says Shah.

At present, when Gleevec fails, patients hold out for a bone-marrow transplant. But less than a third of patients are eligible, discounted by their age and a lack of tissue-matched donors. Without treatment, the cancer is invariably fatal.

So BMS-354825 is a welcome addition to the CML armoury. Last November, the first human patient began taking the drug as part of a phase I clinical trial. Around 30 CML patients are taking the drug to help assess its safety.

"It's good news for the CML community," says Junia Melo who studies haematology at London's Hammersmith Hospital. But she says it is disappointing that one of the tested mutations is immune. The mutation, known as T315I, is responsible for around one fifth of all drug-resistant CML cases.

改造後的藥物大戰白血病

2004-08-03T14:20:00.000+08:00

改造後的藥物大戰白血病

癌症治療的神奇子彈有了新契機。科學家們發展出治療白血病藥物--Gleevec--的第二代，也對它進行了測試。人們希望這個新加入戰場的藥物能給那些對於原先藥物已有抗藥性的患者帶來希望。

慢性骨髓白血病(chronic myeloid leukaemia，CML)是一種致命的癌症，每十萬人中就有一人會罹患此病。Gleevec則是第一個特別針對慢性骨髓白血病所設計的藥物。自從美國食品與藥物管理局(Food and Drug Administration;FDA)在2001年核准後，Gleevec已經變成治療慢性骨髓白血病的前線藥物。但約有20%的病患在發病的早期即對此藥物有抗藥性，因此，其他的治療仍是需要的。

新的藥物被稱為BMS-354825，在罹患慢性骨髓白血病、且具有抗Gleevec藥性的實驗老鼠身上，此藥物能縮小腫瘤以及延長實驗老鼠的生命。在癌症開始發病後，80%接受治療的老鼠仍可以活上一個月以上，而未接受治療的老鼠則會在兩個星期內死去。

不管罹患慢性骨髓白血病的病患對Gleevec有沒有抗藥性，BMS-354825都能讓這些患者的骨髓細胞在培養基中延長生命。

參與這項研究，現任職於加州大學洛杉磯分校的Neil Shah表示，這樣的結果顯示BMS-354825對兩種藥物反應類型的患者都有一定的成效，但是最好的治療方式也許需要Gleevec和BMS-354825同時使用。

Gleevec又稱為imatinib，其機制為結合並阻礙一種會驅使白血病細胞生長的酵素產生作用。Gleevec只會攻擊癌細胞，因此不會使週邊的健康細胞受到傷害。但基因的突變會讓這個酵素改變形狀，使得Gleevec無法和其結合發揮藥效。而BMS-354825對酵素結合上的選擇性比較少，因此對已經改變形狀的酵素蛋白都仍具有結合的能力，所以可以改善病患對於Gleevec有抗藥性的問題。

迄今，17種會造成抗藥性的突變已經被標明了，經試驗其中的15種突變模式後，BMS-354825對之中的14種模式有作用。Shah表示，他們對其餘尚未和此藥物進行測試的突變模式抱持著樂觀的希望。

目前，當病患對Gleevec產生抗藥性後，他們只能寄望於骨髓的移植。但礙於年齡以及缺乏合適的捐贈者，只有少於三分之一的患者能夠進行骨髓移植的手術治療。沒有接受治療的病患勢必會走向死亡。

所以，BMS-354825在廣受歡迎之下，加入了對抗慢性骨髓白血病的生力軍。去年十一月，第一位人類病患在他第一期臨床治療上開始服用此藥物。約有30名病患正在使用BMS-354825，協助研究人員對此藥物的安全性進行評估。

在倫敦Hammersmith醫院進行血液學研究的Junia Melo說，這對慢性骨髓白血病的族群是件好消息，但她也失望地表示，突變模式測試中有一種對BMS-354825已具有免疫的能力了。這個對新藥物具有免疫能力的突變稱為T315I，在對藥物具有抗藥性的慢性骨髓白血病病例之中，大概有五分之一的比例和此種突變有關。

--References：Shah N. P., et al. Science, 305. 399 - 401 (2004).

聖杯化合物在酵素上的應用

2004-08-03T14:15:00.000+08:00

聖杯化合物在酵素上的應用

　生命體中，無時無刻都有很多的生理反應在進行著，這些生理反應大多需要酵素的參與才能夠進行，因此若某些酵素不足或是產生缺陷，嚴重地將足以致命，而為了更了解人體中的酵素，在研究上，我們常利用相似的配位子來模擬酵素活性中心周圍的環境，如異核含氮分子來代替組胺酸(histidine)，羰酸及酚鹽來代替天門冬胺酸(aspartic acid)，硫醇則用來代替半胱胺酸(cysteine)。

　　Reinaud 等人設計了聖杯化合物(calixarenes)以三個N-methyl imidazole聚集形成一個洞穴而將金屬鋅置於其中心，來模擬酵素周圍蛋白質的堆疊(圖一)因為蛋白質周圍是有相當多不同的分子以立體構型包圍。而作者合成此錯合物會形成穩定的四配位結構，其中一個配位基為水，但是其可以被很多中性分子所取代如醇類，胺類。
　　並很順利的得到配物基被乙醇取代的單晶，藉由其單晶結構發現氫鍵和CH---π作用力均對穩定結構有相當的功效。就其在圖二所示結構來看，鋅是一個四面體結構，和三個imidazole上的氮鍵結，平均距離1.98 Å，乙醇深埋在結構中心，鋅氧鍵長為1.984 Å，略短於Liver Alcohol Dehydrogenase 中鋅氧鍵長2.0 Å，但可歸因於人體酵素有較負的電荷(charge)，而其乙醇OH基利用很強的氫鍵(dO-N=2.86 Å)和一個OCH2Im單元鍵結，亞甲基則利用CH---π作用力和苯甲醚的環中心作用，碳至環中心距離為3.67 Å。作者認為可將此作用力視為酵素與基質穩定的要素。

　　在本文中另人注意的地方是聖杯化合物和鋅的關係，很類似人體中酵素和基質的關係，所以其鍵長的比較都相當的類似，可請各位到原論文看。而作者稱此化合物為Zn funnel complexes.

論文出處Seneque, O.; Giorgi, M.; Reinaud, O. J. Chem. Soc., Chem. Commum. 2001, 984-985.

為什麼癌症會轉移？

2004-07-28T15:38:00.000+08:00

為什麼癌症會轉移？

癌細胞的轉移可能是因為喚醒了身體中沈睡的胚胎發育相關轉錄因子所致。

一般來說，癌細胞進行轉移會分為幾個階段：第一個階段稱為侵犯（invasion），這個階段當中癌上皮細胞會鬆開癌細胞之間的連接，使得癌細胞「重獲自由」而能移動到其他地方去。第二個階段稱為內滲（intravasation），癌細胞穿過血管或淋巴管的內皮進入循環系統。第三個階段稱為外滲（extravasation），在這個階段當中，經過循環系統之旅洗禮的倖存者，會穿過微血管的內皮細胞到達新樂土－－其他的組織。最後的階段就是這些癌細胞的新大陸移民，在其他組織當中繁衍茁壯形成轉移的惡性腫瘤。

雖然目前已有研究披露出一些與轉移過程相關的基因，不過大部分的研究都是將癌細胞注射入循環系統中，如此便缺少了與侵犯和內滲作用相關的基因研究。而在麻省理工學院的懷德海研究所（Whitehead Institute）當中由Robert Weinberg所領導的研究團隊，則在最近發表與癌症轉移早期相關的研究結果。

首先他們使用當紅的微陣列（microarray）技術來分析會轉移的老鼠乳癌細胞的基因表現，從中他們找到一個重要的轉錄因子：Twist。這個轉錄因子在胚胎發育的某些過程中，肩負著引發細胞移動以及組織重組的任務。而類似的細胞移動以及組織重塑情形在腫瘤轉移的時候也會發生。
他們發現Twist會使由鈣黏附素E（E-cadherin）所調控的的細胞黏附作用失效，以及產生上皮細胞的上皮-間質轉化（Epithelial- Mesenchymal Transition, EMT）。而且被阻斷了Twist表現的癌細胞其轉移的程度會降低，並且在循環系統中的癌細胞數目也有減少的現象。另外在人類乳癌中的侵犯性小葉癌（invasive lobular carcinoma）當中也觀察到Twist抑制了鈣黏附素E的表現。
因此Weinberg等人推測，癌細胞之所以能進行轉移，可能是因為喚醒身體中沈睡已久，負責胚胎早期型態發育的基因，從而啟動相關的程序，因此獲得轉移的可怕能力。

未來在臨床上也許能開發藥物以抑制Twist這類基因的表現，避免腫瘤轉移；又或者可以藉由篩檢這些基因，早期發現腫瘤未來的走向，並給予適當的治療。也許以後癌症不再是那麼令人可怕的洪水猛獸，而會變成另一種慢性病也不一定。

原始論文：
Jing Yang, et al. Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis. Cell(117), 927-939,2004.

Could we defeat the menopause?

2004-07-28T15:37:00.000+08:00

News Published online: 01 July 2004; doi:10.1038/news040628-18

Could we defeat the menopause?

Helen R. Pilcher

Mouse ovaries offer up secret of new egg cells. From the 20th Annual Meeting of the European Society of Human Reproduction and Embryology, Berlin, Germany
Cells that are capable of making new eggs have been isolated from adult mouse ovaries. The finding supports an earlier suggestion that mammal ovaries could produce eggs throughout life, and shatters the dogma that women are born with a finite supply.

The researcher involved has even identified a molecule that boosts the activity of these cells and causes mice to develop twice as many egg follicles as normal. If it works in humans, such a chemical could provide a revolutionary treatment for women with a low egg-count, such as cancer survivors or those nearing menopause.

Jonathan Tilly from Harvard Medical School, Boston, who is behind the work, first hinted that adult mice might be able to grow new eggs earlier this year. In Nature, he reported seeing stem cells that were potentially able to develop into eggs within adult mouse ovaries1.

But he was unable to isolate the cells, so critics were not convinced. Now, Tilly has isolated the cells and shown that they display genetic markers that are characteristic of stem cells with the ability to develop into eggs. Although he will not disclose his method, he says he obtained 150 to 200 such cells from a single mouse ovary.

"It's an intriguing story," says Ursula Eichenlaub-Ritter from the University of Beilefeld, Germany, who studies ovarian development. But she cautions that the cells need to be characterized further before the case is proven.

Character building

Tilly has already started characterizing the cells. He has identified a gene in the mice that appears to regulate the stem cells' activity. When he knocked out this gene, the resulting mice had 40% more follicles in their ovaries than normal.

And he has even identified a molecule, which he calls GSA8, that has a similar effect. Tilly will not reveal the identity of GSA8. But he told this week's meeting of the European Society of Human Reproduction and Embryology in Berlin that when he injected it into female mice just before puberty, they ended up with almost double the normal number of follicles.

Tilly suspects that the same kind of mechanism could work in humans. "Why would Mother Nature put all her eggs in one basket when they would just sit there and accumulate DNA-related damage?" he asks. He points out that female flies, fish, birds and now mice all appear to make new eggs throughout life, so it is unlikely that humans would be any different.

原來還有新出廠的卵子？

2004-07-28T15:34:00.000+08:00

原來還有新出廠的卵子？

新的研究報告證實小鼠初生之後的卵巢環境仍具有製造新生卵子的能力。

哈佛大學醫學院 Tilly 博士的研究小組於今年初指出成年小鼠的卵巢仍能誘導幹細胞成為新生卵子的潛能（註1)，這表示小鼠初生之後 (postnatal) 的卵巢可能在某些條件存在下可以產生新的卵子，而不只是儲存M I卵子與週期催化成熟其中少數為M II卵子。本月 Tilly 等人在 ESHRE (European Society of Human Reproduction & Embryology) 年會發表的報告中表示，他們已進一步地篩選出這些細胞並找出一個遭抑制後能讓成年小鼠卵巢增生 40% 濾泡的基因。同時，他們也發現名為 GSA8 的具相似促濾泡增生效果的分子。

去年賓州大學(U Penn)的 Scholer 博士(現已應聘至德國 Max-Planck 研究院)等人發現利用體外培養小鼠胚幹細胞形成類似卵子的方法（註2,3）。波士頓兒童醫院 Daley 博士所主導的小組亦成功利用體外培養的方式以retinoic acid 等相關物質培養小鼠幹細胞，之後從 embryoid bodies 中生成精子細胞，並利用顯微注射成功使卵子受精（註4）。此次 Tilly 博士發表的結果雖不若上述兩者對不孕治療、複製、基因轉殖等技術以及相關倫理議題造成極大之震撼，但卻讓我們對哺乳動物生殖機轉的一個重要“典範”--初生之後的成熟卵巢“不”再製造新的卵子--有了重新思考的機會。雖然目前仍無證據支持其他哺乳類動物包括人類之成年卵巢亦有促濾泡增生暨產生新卵子的現象，我們期待此研究繼續的延伸及相關領域的突破，諸如卵巢移植/置換與冷凍技術（註5,6），在未來一方面可裨益相對高齡的計劃生育或接受過癌症療程之婦女受孕，另一方面可幫助瞭解更年期現象及開發新的療法幫助更年期前後的婦女。

後記：Tilly 等在 ESHRE 年會發表的報告已刊登於 Obstetrical & Gynecological Survey （註8）。

附註：
1. Johnson, J. et al (2004). Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428:145.

2. Hubner, K. et al (2003). Derivation of oocytes from mouse embryonic stem cells. Science 300:1251.

3. Dennis, C. (2003) Synthetic sex cells [Review]. Nature 424:364

4. Geijsen, N. et al. (2004) Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature 427:148

5. Oktay, K. et al. (2004) Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 363:837.

6. Oktay, K. and Buyuk, E. (2004) Fertility preservation in women undergoing cancer treatment. Lancet 363:1830.
New references updated (July 20, 2004)

7. Greenfeld, C. and Flaws, J.A. (2004) Renewed debate over postnatal oogenesis in the mammalian ovary. BioEssays 26:829

8. Johnson , J. et al (2004). Germline stem cells and follicular renewal in the postnatal mammalian ovary. Obstetrical & Gynecological Survey 59(7):518.

Avian flu grows more virulent

2004-07-26T15:32:00.001+08:00

Published online: 29 June 2004; doi:10.1038/news040628-13

Avian flu grows more virulent

Helen R. Pilcher

Virologists urge surveillance of possible outbreaks.

The bird flu virus is mutating and becoming more dangerous to mammals, say researchers. The discovery reinforces fears that a human pandemic of the disease could yet occur.

Avian flu hit the headlines in 1997 when a strain called H5N1 jumped from chickens to people, killing six people in Hong Kong. Within three days, the country's entire chicken population was slaughtered and the outbreak was controlled.

Since then new strains of virus have emerged, killing a further 14 people. As yet, no strain has been able to jump routinely from person to person. But if a more virulent strain evolves, the fear is that it could trigger widespread outbreaks, potentially affecting millions of people.

Now, genetic and animal studies show that the virus is becoming more menacing to mammals. Immediate action is needed to stem the virus's transmission, says Hualan Chen from Harbin Veterinary Research Institute, China, who was involved in the research.
'The disease could resurge at any time'
Marion KoopmansNational Institute of Public Health and the Environment

Sick chickens

Chen and colleagues studied 21 H5N1 flu virus samples taken from apparently healthy ducks, which act as a natural reservoir for the disease, in southern China between 1999 and 2002. The researchers inoculated groups of chickens, mice and ducks with virus samples taken from different years and waited to see which animals became ill. Their results are presented this week in the Proceedings of the National Academy of Sciences1.

As expected, ducks were immune to the virus's effects and the chickens fell sick. However, the mice also became ill, losing weight and the use of their limbs. Crucially, the severity of their illness was linked with the year from which the virus sample was taken. Viruses isolated in 2001 and 2002 made the animals more ill than those isolated earlier on.

The findings hint that some time around 2001, the virus became adept at infecting mammals. Genetic analysis of the same samples reveals that the virus's DNA changed over that time, suggesting that accumulated mutations may have contributed to the increased virulence.

Porcine hosts

Researchers are concerned that a virus that has acquired the ability to infect mice could also infect humans. "The disease could resurge [?] at any time," warns virologist Marion Koopmans from the National Institute of Public Health and the Environment in Bilthoven, the Netherlands.

The findings highlight the need for improved surveillance to ensure that any future outbreaks are curtailed, she says. Although domestic poultry are easily culled, wild animals are more difficult to contain. "It is impossible to eradicate the natural reservoir," says Koopmans, "so we need to learn to live with it."

Birds may not be the only villains in this story, however. Chen believes that pigs may also play a part. In Asia, chickens and pigs are often kept in close proximity, so the virus may have shuffled back and forth between the two species, picking up mutations and becoming better at infecting mammalian hosts. Humans may then have caught the disease from swine.

人禽共通的禽流感疫情隨時都可能再度爆發

2004-07-26T15:32:00.000+08:00

人禽共通的禽流感疫情隨時都可能再度爆發

1997年時，禽流感已因H5N1病毒突變為人禽共通種而在香港造成恐慌，今年又在東南亞如越南和泰國等國家捲土重來，造成24人染病死亡。所幸當時的病毒都還不能人傳人，若像SARS一樣可以在人群間彼此傳染，影響所及，恐怕會造成疫情的嚴重爆發，感染人數可能高達上百萬。

然而，最近卻有一份最新的研究結果顯示，這種情況似乎很有可能在不久的將來發生。中國大陸哈爾濱獸醫學院（Harbin Veterinary Research Institute, China）的研究小組在1999到2002年期間對中國南方健康鴨隻進行採樣，將取得的21份不同年份的H5N1病毒採樣培養於鴨隻、雞隻和老鼠體內，結果一如預期地，鴨隻還是健康，而雞隻則完全得病。但意外的是，他們發現老鼠也得病了，而且病情和病毒的年份有關，感染年份愈新的病毒，造成的病情愈嚴重。進一步分析，更發現到病毒的DNA隨著時間不斷在改變，這表示突變的累積的確可能會造成病毒威脅性的提升，如今病毒的威脅性既然已提高到這種程度，就有可能感染人類，引發比先前更為嚴重的疫情。

在中國南方，畜農通常是將豬隻和鴨隻集中混養，科學家因此推測，由於H5N1病毒對於鴨隻還不至於造成威脅，因此可以在鴨群間不斷增殖突變，甚至隨機性地演化為可以感染人類的種類，但因為是隨機性地，所以過去通常只有零星的病例發生，而且還無法造成人群間傳染；然而，同時由於還沒有充分證據顯示H5N1病毒能造成豬隻感染禽流感，因此，在鴨群間不斷傳播的病毒也可能傳染到豬隻這類哺乳類動物身上，繼續進行不受天擇淘汰影響的突變，等到產生可以感染其它哺乳類動物，甚至是人類的病毒，就有可能再度爆發疫情。如今H5N1病毒可以使老鼠感染禽流感，等於為這項假設提供了間接的證據。雖然科學家還不清楚禽流感病毒是如何突變為可以感染哺乳動物的種類，但顯然一些基因，如HA和PB2，必定涉及這項過程，如1997年時在豬群間流傳甚廣的H3N2病毒就包含有人、豬和禽流感病毒的重組基因片段，這些片段裡都具有如上所述的基因，故可以合理的推測這種情形必然與H5N1病毒感染老鼠的現象息息相關。

因此，科學家不斷呼籲相關單位加強戒備，以確保疫情不會爆發。然而持續突變當中的H5N1病毒是否真能夠在這之前就被人類控制住，似乎沒有人敢斷言。

這項研究結果已刊登於《美國國家科學院期刊》(Proceedings of the National Academy of Sciences, PNAS)上。
原學術論文：Chen, H. et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences 101, 10452–10457 (2004)

WHO urges action on bird flu outbreaks

2004-07-26T15:30:00.000+08:00

WHO urges action on bird flu outbreaks

Helen Pilcher

Sick poultry raise fears of human pandemic.

The World Health Organization has called for a prompt response to curb the spread of avian flu. The announcement follows reports that a potentially lethal virus has re-emerged in birds in Asia.

The last two weeks have seen a spate of outbreaks in Asian poultry, including at least one in China, two in Thailand and three in Vietnam. Tens of thousands of chickens and ducks have been slaughtered to halt the spread of the infection. No humans are thought to have been infected.

The WHO wants Asian countries to step up surveillance of poultry and humans. It is also asking authorities in newly hit countries to make samples of the virus strains that are responsible for the latest cases available to international research teams for study.

"If we can compare the viruses with each other and with those from the earlier outbreaks, we will have a much better picture of what is going on," says Shigeru Omi, head of the WHO's regional office for the Western Pacific. Such studies would confirm whether the virus has mutated into a new strain, and might guide the production of an effective vaccine.

The recent outbreaks show that the virus continues to circulate and that new cases could flare up in future, says Joseph Domenech, chief of the Animal Health Service at the UN Food and Agriculture Organization. "Eradication of the avian flu virus should be considered, at best, a long-term task," he says.

Strong hold

A study published in the Proceedings of the National Academy of Sciences1 says that the virus is becoming more of a threat to human health. And one in Nature2 suggests that it is gaining a stronger foothold among birds in Asia. Over the last six years, the disease has claimed just 23 human lives, although the fear is that a new, more virulent strain could emerge.

"There is no need for public anxiety, but it is vital that the countries affected share what they know with the international community," says Omi.

The affected Asian countries have responded promptly to the recent outbreaks. In China, more than 8,000 birds died or were slaughtered, including all chickens within a three-kilometre radius of the cases. Live poultry trade was suspended in all nearby animal markets.

And as scientists wait to see if the outbreaks have been successfully contained, human trials of a bird-flu vaccine are expected to begin. The biotechnology firms Aventis Pasteur, which has its headquarters in Lyon, France, and California-based Chiron have developed candidate vaccines. These are based on a strain known as H5N1, which was taken from a Vietnamese patient in February 2004.

提防禽流感再度來襲

2004-07-26T15:29:00.000+08:00

提防禽流感再度來襲

研究發現在亞洲引起數起恐慌的禽流感病毒在過去幾年內，一直和其他病毒進行基因交換，演化得對人更具威脅力。而且研究也預測禽流感在秋冬季再度來襲的機會很高。

H5N1病毒1997年在香港首度登場就幹掉了大批家禽，還殺死了六個人，逼迫衛生官員下令大量撲殺家禽。香港大學的病毒學家管軼等人自2000年在香港和中國南方的家禽中取樣，以監測H5N1病毒的再度來襲。研究顯示這個病毒起源自野鵝身上的良性病毒。可是當這種病毒到了雞鴨身上，一個輕微的改變就讓它們變得殺傷力極強。

管軼等人分析了各年份來自中國和香港的雞鴨身上的H5N1病毒，並且和來自印尼、泰國和越南在2003~04年疫情中的病毒相比。他們同時也分析了一些被禽流感幹掉的野鳥樣本。結果發現不同年份的H5N1病毒都有HA和NA這兩個來自野鵝病毒的基因，它們還有六個基因來自流感病毒。他們還發現有一株病毒在2002年前是未曾出現的，他們稱之為「基因型Z」，這株病毒之後還成了主流。而中國南方的家鴨似乎是這株病毒起源的溫床。

他們懷疑基因型Z病毒可能能夠在鳥類身上活得更愉快，所以很快地就在東亞的家禽中流行開來。他們也發現來自東南亞的基因型Z病毒，帶有一個特別突變在M2蛋白質上，造成對藥物的抗性。這個突變在其他諸如基因型B、Y和Z+病毒也可見。M2抗性在不同株病毒都可發現，顯然是病毒在感染的動物身上交換基因的結果。事實上人類的感冒病毒H3N2就在中國南方的豬身上發現過，如果H5N1帶原的豬也同時感染了H3N2，則它們就可以快樂地交換基因，而變得對人類更具威脅。

禽流感雖然在過去的六年內，只讓23人死亡，可是殺傷力更強的病毒可能會隨時出現。管軼相信這個病毒是極度危險的，它們的變化之快，可以再度成為全球性流行的死亡疾病。過去兩週內，就有幾起疫情傳出，至少有一起在中國、兩起在泰國、三起在越南。成千上萬隻雞鴨被撲殺以阻止疫情蔓延，所幸無人感染。世界衛生組織（WHO）警告亞洲國家要開始監控疫情。不過如果衛生官員能夠及時發出警訊和採取行動，其實並沒有必要引起恐慌。

原學術論文：Li K. S. et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature, 430, 209 - 213 doi:10.1038/nature02746 (2004).

Immune systems evolved more than once

2004-07-20T12:16:00.000+08:00

Immune systems evolved more than once

Laura Nelson

Primitive fish have advanced protective mechanism.

When discussing the attributes that make mammals special, a sophisticated immune response generally comes close to the top of the list. But now it seems that we're not so unique after all.
Researchers have found that fish-like creatures called lampreys have evolved their own system, using building blocks that are completely unrelated to the antibodies found in mammals. The discovery opens up a new world for immunologists, who had previously assumed there was only one way of doing things – ours.

"The result blew my mind," says Chris Amemiya, molecular geneticist at the Benaroya Research Institute in Seattle, and an author of the study. "Now we know there are at least two ways of making the adaptive immune system."
Shifting sequences

There are two types of immune response, innate and adaptive. Both spot and destroy pathogens such as viruses, bacteria and fungi. Innate immunity is inherited, and does not change over an animal's lifetime.

In contrast the adaptive system changes according to the antigens an animal encounters. Specialized genetic sequences shuffle together to generate an almost infinite variety of defence cells, which attack antigens using proteins called antibodies.

A particular antigen triggers the genetic sequence that recognises it to begin copying itself, producing antibodies to fight that antigen.

Scientists believe that the adaptive immune system evolved at around the same time as animals developed jaws, about 400 million years ago. They hoped to find signs of a primitive system in the lamprey. It doesn't have a jaw, but it does show some of the characteristics of an adaptive immune system, such as rejecting skin grafts.

But there was no hint that lampreys made antibodies.

Amemiya's group wondered whether the lamprey might be attacking foreign molecules in some other way. To test the idea, the team injected lamprey larvae with a cocktail of antigen molecules, then compared the genetic sequences of the inoculated animals with untouched ones.
They found that animals exposed to the pathogens produced 13 times more copies of a genetic sequence that generates a pathogen-binding protein that is unrelated to an antibody. "The lamprey has gone for a different basic building block to construct mechanisms to recognize antigens," says Hugh Reyburn, an immunologist at the University of Cambridge, UK.

脊椎動物另類的免疫－－八目鰻的適應性免疫

2004-07-20T12:15:00.000+08:00

脊椎動物另類的免疫－－八目鰻的適應性免疫

　　一般認為只有高等脊椎動物擁有複雜的適應性免疫系統，可是現在在低等脊椎動物八目鰻的身上也發現了一種前所未知的適應性免疫反應。

　　海生八目鰻（Petromyzon marinus）是四億年前直接從原始的脊椎動物演化而來的。牠們是一種活化石，讓我們能瞧見顎和對鰭在演化出來之前，脊椎動物可能長成怎麼個模樣。免疫有兩種，另別為先天免疫（innate immunity）和適應性免疫（adaptive immunity），前者終生不變，後者則會製造出變換無窮的抗體。科學家一般上相信適應性免疫是和顎差不多同時候演化出的，就在約四億年前。因此科學家希望在八目鰻身上瞭解原始的免疫系統。然而六○和七○年代的研究顯示八目鰻有一定程度的適應性免疫，例如牠們對皮膚的移植會排斥。可是八目鰻免疫系統的兵員顯然不是抗體和T細胞，這意味著八目鰻有完全不同於我們的適應性免疫，可是箇中奧妙是迄今仍是個謎。

　　為了瞭解八目鰻的免疫系統，美國阿拉巴馬大學的免疫學家Zeev Pancer等人把一個包含大腸桿菌（Escherichia coli）、細菌、線羊紅血球細胞等作成的雞尾酒注射入八目鰻幼體體內。大部分脊椎動物的淋巴球細胞會讓這些抗原給活化，並且協調適應性免疫反應，派出抗體和T細胞來摧毀這個外來入侵物。可是八目鰻的淋色球細胞並不從事協調工作，反而直接去對付這些抗原。八目鰻的淋色球細胞的一個細胞膜表面的多變淋巴球受器取代了抗體來對抗原雞尾酒起反應。這個受器有個高度多變的中段區域，可以重組以針對特定的抗原起免疫反應。

　　參與研究的Benaroya研究所的分子遺傳學家Chris Amemiya指出，如此一來已知的適應性免疫就有兩種。佛羅里達聖彼得堡All兒童醫院的遺傳學家Gary Litman指出，這個發現對瞭解脊椎動物的免疫系統演化是非常重要的。加拿大多倫多Sunnybrook and Women's學院衛生科學中心的細胞生物學家Jonathan Rast認為，類似的免疫反應搞不好也可以在其他脊椎動物身上找到，甚至還可能是個廣泛存在的免疫反應。

原學術論文：Pancer Z. et al. Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey. Nature, 430, 174 - 180, (2004). Article

X-ray evidence points to Japanese cult

2004-07-20T12:11:00.000+08:00

X-ray evidence points to Japanese cult
David Cyranoski

Forensic work leads to new arrests in 1995 shooting case.

Tokyo - Japanese police arrested three people on Wednesday in connection with the 1995 shooting of the country's top police official. The police identified the suspects using the massive SPring-8 synchrotron, a powerful X-ray beam that can reveal the chemical makeup of tiny samples.

The three are all former members of the Aum Shinrikyo cult, which on 20 March 1995 released sarin nerve gas on the Tokyo subway, killing 12 people. Ten days later Takaji Kunimatsu, then head of the National Police Agency and leader of the investigation into the attack, was shot and critically injured.

The key new evidence is reported to have come from analysis of metal traces found on one suspect's clothing. Impurities in this metal are believed to match those in the gun used to shoot Kunimatsu. The police have refused to make any statements, and the name of the scientist leading the new investigation is being withheld to protect his or her safety.

The police wouldn't have a case without SPring-8, says Akito Kakizaki, a physicist at the University of Tokyo. SPring-8, the world's most powerful synchrotron, can analyze samples weighing only trillionths of a gram - which, in criminal evidence, is often all that is available.
This is not SPring-8's first contribution to forensic science. In December 1998, evidence from the synchroton helped convict a woman suspected of killing four people at a festival by putting arsenic in a curry.

Ten milligrams of arsenic found at the suspect's home matched the chemical added to the curry. The synchrotron revealed matching bismuth and antimony impurities in the two samples.
"Conventional methods of analysis would need much more [arsenic]," says the scientist behind that analysis, Izumi Nakai, an analytic chemist at Tokyo University of Science and a member of the American Academy of Forensic Sciences, who is not involved in the current investigation. He thinks the police will use the method more in the future.

Also, synchrotron radiation leaves the sample intact. "We can repeat the experiment many times," says Nakai. "This is extremely important for investigating crimes."
Nakai became involved in the poisoning case through his study of arsenic in hair samples. He is now pushing for synchrotrons to become a staple of forensic science. For example, SPring-8 could identify the glass left behind at a hit-and-run accident or the source of confiscated marijuana, he says.

So far his efforts to get a dedicated synchrotron for forensic science have failed, but he is hopeful. "All countries will begin to use synchrotron energy for forensics," he says.
Only two other synchrotrons could handle samples as small as those in the shooting case: the US Advanced Photon Source at Argonne National Laboratory, Illinois, and the European Synchrotron Radiation Facility in Grenoble France. "With a machine any less powerful it would be difficult," says Kakizaki.

以同步輻射（synchrotron radiation）調查槍擊案！

2004-07-20T12:07:00.000+08:00

以同步輻射（synchrotron radiation）調查槍擊案！

　　同步輻射（synchrotron radiation）的一般應用是在醫學、生命科學、凝態物理、環保、生命科學、材料及冶金科學、及微機械技術研發等，此外可分析射擊殘跡（gunshot residue, GSR）來協助槍擊案調查。

　　日本警方近日藉由同步輻射的分析結果，逮捕了三名因涉嫌在１９９５年暗殺當時的警察廳長官國松孝次（Takaji Kunimatsu）的前奧姆真理教﹙現改名為阿萊夫教﹚的信徒。該名官員所幸最後逃過一劫。

　　１９９５年３月２０日，奧姆真理教在東京發動了造成１２人死亡，５５００多人受傷，１４人終身殘疾之駭人聽聞的地鐵沙林毒氣恐怖攻擊。時任日本警察廳長官的國松孝次正是對奧姆真理教調查的主要負責人。

　　能逮捕涉案嫌犯的關鍵證據是因為射擊國松孝次槍枝之射擊殘跡的金屬雜質與其中一名嫌犯衣服上採集到的殘跡相吻合。常見的殘餘金屬雜質為鉛（Pb）、鋇（Ba）、及銻（Sb）。這項結論是由可偵測約兆分之一克金屬（part per trillion, ppt）的同步輻射分析所獲得。為了避免報復行動，日本警方拒絕透露分析人員的身份。

　　同步輻射（synchrotron radiation）：近光速行進的帶電粒子，受到磁場作用而偏轉時，會沿著行進的切線方向發出輻射，即稱之。這種輻射脈波的強度與偏振程度很高，而且為連續光譜。此連續波段電磁波（一般而言所有的電磁波都可稱為光），涵蓋紅外線、可見光、紫外線及X 光，因此可應用於各領域需求。此分析所使用的日本高輝度光科學研究所的SPring-8是現今全球能量最高的同步輻射光源，高達80億電子伏特，可以產生硬Ｘ射線光束（台灣擁有的第三代同步輻射為13億電子伏特，但台灣在Spring-8有專屬光束線）。

　　金屬雜質為特異性較高的射擊殘跡，對嫌犯以及槍枝的連結，頗有助益。常用的GSR 分析有：極譜分析（Polaragraphy）、X光螢光分析（X-ray Fluorescence）、原子吸收光譜分析（Atomic Absorption Spectroscopy）、中子活化光譜分析（Neutron Activation Analysis, NAA）、誘導式耦合電漿原子放射光譜分析（Induced Couple Plasma-Atomic Emission Spectroscopy, ICP-AES）、放射光譜分析（Photoluminescence）、掃瞄式電子顯微鏡X光能譜分析（Scanning Electron Micriscope-Energy Disversive X-rays. SEM-EDX）以及X光繞射分析（X-rays Diffraction）。

　　目前只有美國能源部在伊利諾州（ Illinois）阿爾貢國家實驗室的先進光子源（US Advanced Photon Source at Argonne National Laboratory）以及在法國格勒諾布爾（Grenoble）的歐洲同步輻射裝置（European Synchrotron Radiation Facility,ESRF），能夠偵測到如此微量的金屬雜質。

　　同步輻射屬於非破壞性分析（non-destructive analysis）因此對於寶貴的刑案證物分析上，更具有保存證物的極大優點，可更廣泛應用於各種微物跡證分析。例如協助頗受國人關切的319槍擊案的調查。

US team breaks power density record

2004-07-19T14:22:00.000+08:00

US team breaks power density record
5 July 2004

Scientists from the Center for Ultrafast Optical Sciences at the University of Michigan in the US, claim to have generated a laser spot with a power density of 0.85x1022 watts per centimetre squared -- the highest intensity ever recorded. The intense focal spot, which measures 0.8 microns across, was made by optimizing the focusing of pulses from the Center's HERCULES laser system.

HERCULES is a custom-made titanium:sapphire laser that uses chirped pulse amplification (CPA) to generate ultrashort pulses with a power of 45 terawatts (27 femtosecond pulses containing 1.2 joules of energy). The Michigan team used adaptive optics, a well known technique for correcting wave-front distortion, to focus their pulses to the smallest spot possible. Pulses from HERCULES were reflected off a deformable mirror before being focused down by a paraboloid mirror.

The shape of the deformable mirror was adjusted to correct for any distortions in the beam and optimize the focusing. Using the technique the team managed to generate focused intensities of between 0.66 and 0.85x1022 watts per centimetre squared.

"It is the laser wave-front fluctuations that will ultimately limit the focused intensity and its spatial resolution," the team told delegates at the post-deadline session of CLEO 2004 in San Francisco in May. "In our case, HERCULES is remarkably stable. The shot-to-shot fluctuation of wave-front has an rms (root mean square) deviation from its average shape of about 1/20."

Gerard Mourou, the Center's director, invented CPA in the late 1980s as a way to amplify pulses to much higher powers. The technique involves stretching an ultrashort pulse to several nanoseconds so that it can amplified without its peak power damaging the gain medium. After amplification the pulse is recompressed to give a very powerful ultrashort pulse.

Author
Oliver Graydon is Editor of Optics.org and Opto & Laser Europe magazine

雷射光束﹕越小越有力

2004-07-19T14:19:00.000+08:00

雷射光束﹕越小越有力

　　美國密西根大學超快光學中心的科學家們﹐利用該中心的高能雷射系統(HERCULES (註): High Energy Repetitive CUos LasEr System)﹐製造出功率密度達8.5x1021 watts/cm2的雷射光束﹐宣稱是至今最高的記錄。

　　HERCULES雷射是該中心的科學家們自製的一套鈦: 藍寶石雷射系統, 透過chirped pulse amplification (CPA) 的技術﹐可以產生達45 terawatts (1 tera = 1012)的超短脈衝(在為時27 femtosecond的脈衝裡包含了1.2焦耳的能量)。他們是運用調適光學(adaptive optics) 的原理﹐將HERCULES射出的脈衝則先是經由一可變形的鏡子反射﹐來解決波前扭曲的問題﹐再將其通過一拋物面鏡進行聚焦中﹐以達成將雷射脈衝聚焦到最小尺寸的目的。藉著改變反射鏡的形狀﹐可以用來修正雷射光束中所有的扭曲﹐以使聚焦達到最佳化。而密西根大學的研究小組﹐利用這樣的技術﹐可以使所聚焦的雷射光達到6.6-8.5x1021 watts/cm2的功率密度。

　　根據研究小組在今年五月份在舊金山所舉行的的CLEO會議所發表的聲明﹐他們認為最終限制聚焦功率以及其空間的解像度的因素﹐就在於雷射光波前的變動。而他們所使用的雷射光源-HERCULES ﹐比較上來說十分地穩定: 其相鄰脈衝之間的波前﹐與平均波形的差別(rms ﹐根均方值)僅有1/20。

　　此外值得一提的是﹐在這項實驗中所運用的CPA技術﹐乃是由該中心的主任Gerard Mourou在1980年代末期所發明的。這項技術的特點在於將一個超短脈衝在域上延長成數奈秒長進行放大﹐然後再將其壓縮回原來的大小以得到功率密度增加的超短脈衝。

　　由於許多需要在高電磁場中進行的實驗(如粒子加速﹑短脈衝x-ray ﹑fast ignition fusion等)﹐都仰賴於高功率密度的(雷射)光源﹐這項實驗的成就﹐可望為從事相關領域的研究人員﹐提供一項有利的工具。

<註>"Hercules"是希臘神話中著名的大力士﹐用來為一高能雷射系統命名﹐可謂名符其實。

Quantum well energizes nanocrystals

2004-07-17T13:13:00.000+08:00

Quantum well energizes nanocrystals
7 July 2004

Semiconductor nanocrystals (or quantum dots) are attractive for use in a number of light-emitting technologies. But there's a snag: it's hard to pump nanocrystals electrically because of their insulating organic capping layers. Now scientists at Los Alamos National Laboratory and Sandia National Laboratories, both in the US, have transferred energy to nanocrystals from epitaxial quantum wells without the need for electrical contacts.

The non-radiative energy transfer process indirectly injects electron-hole pairs into the nanocrystals. These later recombine, emitting light as a result.
"The high efficiency of energy transfer in combination with the exceptional luminescent properties of nanocrystal quantum dots make hybrid quantum-well/nanocrystal devices feasible as efficient sources of any colour light - or even white light," said Victor Klimov of Los Alamos.
In this study the scientists chose to impart energy to the quantum well by optical pumping so that they could obtain additional information about how that energy then transferred to the nanocrystals. In real-life, however, they say they could also pump the quantum well electrically, in the same way that a common quantum-well light-emitting diode is pumped.
The researchers used a 3 nm InGaN quantum well underneath a monolayer of CdSe/ZnS core/shell nanocrystals. The nanocrystals, which had a core radius of 1.9 nm and a shell thickness of around 0.6 nm, were capped with organic molecules.
Klimov and colleagues pumped the quantum well by shining laser light with a wavelength of 266 nm on the device. The well transferred its energy to the nanocrystals with an efficiency of around 55%. And, according to the researchers, the nanocrystal capping layer did not significantly inhibit the process.
"The transfer of energy is fast enough to compete with exciton [bound electron/hole pair] recombination in the quantum well, and that allows us to 'move' more than 50% of the excitons to adjacent quantum dots," said Klimov. "The recombination of these transferred excitons leads to the emission of light with colour that can be controlled by quantum-dot size."
What's more, the researchers believe they may be able to achieve efficiencies of nearly 100% by improving the quality of the quantum wells to reduce non-radiative losses, and by optimizing the geometry of the nanocrystal/quantum-well structure.
The scientists, who reported their work in Nature, say that the technique could also find a use in nanocrystal-based optical amplifiers and lasers.
About the author
Liz Kalaugher is editor of nanotechweb.org.

量子井為量子點注入新能量

2004-07-17T13:11:00.000+08:00

量子井為量子點注入新能量

科學家成功地將能量由磊晶的量子井轉移至量子點之中

　　對於發光科技領域而言，由半導體奈米微晶形成的量子點(quantum dot)是一項吸引人的材料，但其外圍卻因包覆了絕緣的有機覆蓋層(organic capping)，因此不容易以外加電力的方式激發。最近美國Los Alamos及Sandia國家實驗室的科學家在不需電極接觸(electrical contacts)的情況下，成功地將能量由磊晶的量子井轉移至量子點之中。
　　量子井中的電子-電洞對透過非輻射性的能量轉移過程，以間接方式注入奈米微晶中，並在量子點中復合放出光子。Los Alamos的Victor Klimov表示，此種高效率能量轉移的方式，結合特殊量子點發射冷光的性質，使這種量子井/奈米微晶複合元件具有做為任一色光或甚至白光光源的潛力。
　　研究人員利用3nm的GaN當底層，上覆單層的量子點。這些量子點內核是半徑1.9nm的CdSe，外殼是厚度0.6nm的ZnS，外圍包覆了有機分子。研究人員以波長266nm的雷射激發該元件，由於能量轉移相當迅速，激子(exiton，即束縛的電子電洞對)在量子井中因復合而損失的能量少，使得約55%的能量可轉移至量子點內。由於量子點的發光波長取決於其尺寸，因此改變量子點的大小，即可調變發光的顏色。
　　研究人員相信，將量子井和量子點的結構加以優化，轉換效率將可接近100%，並預期此技術將可應用在以量子點為主的光放大器以及雷射上。

詳見近期的Nature雜誌。
Energy transfer from nano-thin layers of Sandia-grown quantum wells to the Los Alamos National Laboratory (LANL) nanocrystals above the nanolayers. Image courtesy of LANL.

Discover New Way to Identify Cell Growth

2004-07-15T16:10:00.000+08:00

UC Riverside Researchers Discover New Way to Identify Cell Growth

Finding in the Lab of Professor Frank Sauer has Relevance for Control of Cancer
(June 2, 2004)

RIVERSIDE, Calif. (www.ucr.edu) – In a discovery that has relevance in a variety of fields, including human health, UC Riverside Assistant Professor of Biochemistry Frank Sauer and colleagues at UC Riverside, in Germany, and in Wisconsin, have found a new way to identify when a living cell begins to grow.

“We have found a new marker, established by the cell, to detect the production of an essential protein that indicates cell growth,” said Sauer, about a research paper published last month in the prestigious journal, Science.

The paper, entitled, “TAF1 activates transcription by phosphorylation of serine 33 in histone H2B” is the result of four years of work. Co-authors include researchers from the University of Wisconsin-Madison and Heidelberg University.

Medical researchers could use the newly discovered marker as a diagnostic tool to monitor the emergence of cancer. The unwanted ‘awakening’ of cells from the dormant phase can result in uncontrolled cell growth that is loosely referred to as cancer. “We have developed a tool (antibody) that detects the novel marker and identifies growing cells,” Sauer said.

The research paper described the identification of the enzyme that controls cell growth by generating the novel “cell growth” marker. “You can activate the enzyme, or you can deactivate it,” Sauer said. “This may be used to create substances that can take a cell from the dormant stage to the active stage, or the other way around. This may help create substances that can stop cancerous cell growth.”

All higher organisms derive from a single cell, the fertilized egg that divides to generate different cell types, tissues and organs. Once the task has been completed, cells stop dividing and enter a dormant phase of the cell cycle. So any advance in recognizing the complex interplay of proteins that control and regulate the cell cycle has relevance for the diagnosis and treatment of cancer.

Sauer said that he and his colleagues have celebrated the result of a long research effort. “We had a very nice bottle of Champagne. Yes, this is a very important step towards our goal to understand the mechanisms that control cell growth.”

Sauer arrived at UC Riverside 18 months ago from Heidelberg (Germany). Between 1994 and 1997 he was a postdoctoral fellow at UC Berkeley.

鑑定細胞何時開始生長的新方法

2004-07-15T16:00:00.000+08:00

鑑定細胞何時開始生長的新方法

一種新的方法可用來鑑定活體細胞何時開始生長

　　加州大學河邊分校（UC Riverside）生化學系助理教授Frank Sauer等人發現一項新的方法可用來鑑定活體細胞何時開始生長。

　　Sauer等人在上個月的國際知名期刊—《科學》（Science）雜誌發表論文證實細胞核內組蛋白H2B可透過轉錄促進因子1（TAF1;Transcrptional activating factor 1）進而磷酸化其自身Serine 33的位置。此舉可啟動細胞核內的轉錄作用並促進細胞週期的進行以及細胞生長。

　　Sauer表示，他們發現一種新的由細胞所衍生出的標誌物（marker）可以用來偵測這種專門促進細胞生長的蛋白質，並同時研發出抗體來偵測這新的標誌物以及辨識出生長中的細胞。而未來醫學相關研究人員可應用這種新發現的標誌物作為監控癌細胞出現的診斷工具。

　　論文內容裡詳細描述如何辨識專門製造控制細胞生長標誌物的酵素，並且可以將此酵素活化或去活化，如此一來就可把細胞從休眠期帶進活化期，或是逆向而行，因此將可以使得不斷增生的癌細胞能夠停止生長。

　　由於所有高等生物均起源於一個單一細胞也就是受精卵，它可以分裂並分化成不同細胞、組織以及器官。當任務完成以後，細胞就會停止分裂並且進入細胞週期的休眠期中。因此在調控細胞週期方面的蛋白交互作用等研究如有進展，將可協助癌症的診斷與治療。

　　Sauer日前已經和他的同事慶祝這項長期以來得之不易的研究成果，他說這是探討控制細胞生長機制相當重要的階段，他們會繼續朝向自己的研究目標邁進！

原學術論文：
T. Maile, S. Kwoczynski, R. J. Katzenberger, D. A. Wassarman, and F. Sauer TAF1 Activates Transcription by Phosphorylation of Serine 33 in Histone H2B Science 14 May 2004 304: 1010-1014 [link]

輕輕一噴，SARS不敢近身！

2004-07-15T15:56:00.000+08:00

輕輕一噴，SARS不敢近身！

一種新的疫苗可以激起免疫反應來防止SARS病毒攻擊細胞.

嚴重急性呼吸道症候群（severe acute respiratory syndrome，SARS）的傳染途徑主要是患者的眼、口和鼻的黏膜（mucosal membranes）接觸到SARS病毒而傳染，再經由口、鼻腔進入呼吸道，藉著呼吸道黏膜細胞上的受體分子而進入細胞，因此，若能直接在呼吸道表面進行黏膜免疫（mucosal immunization），應會是相當有效的預防方法。最近，科學家就將SARS病毒（SARS-CoV）和人類呼吸道病毒（human respiratory virus）結合在一起，製出一種可預防SARS的鼻部噴霧疫苗（nasal-spray vaccine）。

之前已經知道，小牛副流行性感冒Ⅲ型病毒（bovine parainfluenza virus 3，BPIV3）可做成一種活性減毒疫苗（live attenuated vaccine）：BHPIV3，以鼻部噴霧的方式來預防人類副流行性感冒Ⅲ型病毒（human parainfluenza virus 3，HPIV3）引起的小兒肺炎。所以，研究人員便以BHPIV3為載體，把SARS-CoV的spike protein（S protein）基因接於其上，製成混種病毒（hybrid virus）。由於兩者主要都是感染呼吸道，以BHPIV3為載體來表現SARS的S protein（稱為BHPIV3/SARS-S vector），就可以直接引發呼吸道的免疫反應。

接著，研究人員以非洲綠猴（African green monkeys）為對象進行實驗，在接種混種病毒後一個月施以SARS病毒，結果發現有接種的綠猴都無感染的跡象，而對照組則出現SARS感染症狀，顯示混種病毒的確可抑制SARS病毒的感染能力。

因為副流感病毒疫苗早已應用於臨床，這個混種病毒製成的疫苗應該也是安全的。此外，它又同時具備預防HPIV3及SARS的功能。不過此法主要只能保護嬰兒或孩童；在成人體內，完善的免疫系統可能會辨識副流行性感冒病毒的表面蛋白質，而把BHPIV3/SARS-S vector中和掉，大大降低疫苗的效力。幸運的是，副流行性感冒病毒在表面蛋白質被換掉後仍具有感染能力，因此若換上不會引起免疫反應的蛋白質，改良後的混種病毒將成為最有效、且不分男女老少都適用的抗SARS利器。也許在不久的將來，人們防SARS只須一罐噴霧疫苗就夠了，如同使用防蚊液那樣：輕輕一噴，SARS不敢近身！

原始論文：
P. Collins et al. Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. The Lancet. (June 2004) doi:10.1016/S0140-6736(04)16501-X.

Noisy secret of Mona Lisa's smile

2004-07-14T17:06:00.000+08:00

Noisy secret of Mona Lisa's smile

19:00 23 June 04

Exclusive from New Scientist Print Edition. Subscribe and get 4 free issues.

For centuries, artists, historians and tourists have been fascinated by Mona Lisa's enigmatic smile. Now it seems that the power of Leonardo da Vinci's masterpiece comes in part from an unlikely source: random noise in our visual systems.

Christopher Tyler and Leonid Kontsevich at the Smith-Kettlewell Eye Research Institute in San Francisco manipulated a digital image of the painting by introducing random visual noise - the equivalent of the snow seen on a badly tuned TV set - and asked 12 observers how they rated the resulting expression on a four-point scale from sad to happy.

As would be expected, noise that lifted the edges of her mouth made Mona Lisa seem happier, and those that flattened her lips made her seem sadder. More surprising though, was how readily the visual noise changed people's perception of the Mona Lisa's expression.

Tyler says our visual system contains many sources of noise: fluctuations in the number of photons hitting light-receiving cells in the eye, spontaneous false activation of photon absorbing pigments, and randomness in the firing of neurons that carry the visual signals to the brain.

Tyler thinks this natural noise makes people observing the picture believe its expression is subtly changing, rather than thinking they are seeing a single ambiguous expression.

"That may be part of what makes the painting so powerful," he says, something Leonardo must have instinctively realised.

Journal reference: Vision Research (vol 44, p 1493)
Philip Cohen

讓蒙娜麗莎對你笑

2004-07-14T17:05:00.000+08:00

讓蒙娜麗莎對你笑

蒙娜麗莎的微笑嘴邊出現的隨機雜訊會影響看起來是快樂或不快樂.
© VISION RESEARCH

最近一項對於表情辨識的研究顯示，左右表情最深的可能不是眼睛。

這是由位於美國舊金山的史密斯凱特威爾眼科研究中心﹝Smith-Kettlewell Eye Research Institute﹞的兩位視覺神經學家Leonid L. Kontsevich及Christopher W. Tyler所進行的研究。這個實驗主要是研究人如何去辨認臉部表情的細微變化，所使用的是歷史上赫赫有名的代表作：蒙娜麗莎的微笑，這幅畫一直以蒙娜麗莎那介於憂愁與微笑之間，充滿魔力的曖昧表情而為人所知。

研究者將這幅畫以灰階的格式來顯示，並在畫上的不同部分加上隨機雜訊（random noise）而製成100多幅有些微不同的圖畫，這些加了雜訊的圖畫看起來就像電視畫面訊號不佳時的呈現。最後請12位受試者為這些經過影像處理的畫中人表情從悲傷到快樂分為4個等級來評分。結果發現，雜訊會改變蒙娜麗莎的表情，而且這些表情對於受試者來說是有意義的。

另外為了探索眼睛所帶來的訊息，他們將整張圖加上雜訊然後由受試者來為這些圖的高興或悲傷程度就21個等級評分。接著將12位受試者所選出來最快樂以及最悲傷的的圖畫影像加以平均，比較原畫以及這兩張經過影像處理的圖畫，結果顯示與原畫不同的是在嘴巴的形狀有了很大的改變！

接著他們再將原畫的上半部以及下半部加上屬於「快樂」及「悲傷」的雜訊。當圖畫下半部加上雜訊時，受試者會感覺到蒙娜麗莎的眼睛表情有所改變：但反之將圖畫上半部加上雜訊時，受試者卻不覺得蒙娜麗莎的眼睛有所改變。

這顯示決定一個人的表情並不是以往所想像的靈魂之窗，反而是嘴巴的部分。對於這樣的結果，科學家推測眼睛也許擔負著「增強」人的表情的功能，具有畫龍點睛的功效；又或者是眼睛的改變不是他們所採用的方法所能偵測得到的。

在我們的日常生活中，其實也是處處充滿著雜訊。像是我們眼睛接受到光子的波動時，會激發一些隨機的神經訊號，而這些在視覺系統的雜訊可能使我們能理解他人的表情含意。若能解開辨認他人表情變化的關鍵所在，也許將對一些患有臉部辨識喪失症（Prosopagnosia）的病人有所幫助。

原始論文：
Leonid L. Kontsevich, Christopher W. Tyler. What makes Mona Lisa smile？Vision Research(44),1493-1498,2004.

奈米蜘蛛抓得牢

2004-07-14T17:01:00.000+08:00

奈米蜘蛛抓得牢

　德國和瑞士科學家發現，蜘蛛利用一種叫凡得瓦力(van der Waals force)的靜電力，幾乎能再任何類型的表面上懸吊行走。根據計算，這些力量足以讓動物承載超過他們體重170倍的重量。這項結果有助於發展新型的黏劑。

　　不來梅市動物科學及仿生研究所的Antonia Kesel和他在蘇黎世大學的伙伴，以掃描式電子顯微鏡來觀察一種叫E．arcuata的蜘蛛足部。E．arcuata是一種跳躍型蜘蛛，牠不像一般蜘蛛需要架網來捕捉獵物。科學家發現，這些蜘蛛腳上都有一簇簇名為setule的毛髮，而每根setule都覆蓋著成上千萬更微小的毛髮，這些微細的毛髮大約只有幾百奈米寬，蜘蛛就是利用這樣的結構附著在物體表面。

　　Kesel等人透過原子力顯微鏡發現，每一根setule都可以產生超過40×10-9牛頓的力，對於一隻僅15毫克的蜘蛛來說，這是非常大的力量。研究人員表示，這些力的來源是作用於分子間的凡得瓦力，當它們結合起來，便在蜘蛛的腳上形成一股強大的力量。根據計算，如果有600000根setule接觸物體表面，蜘蛛便可產生0.025牛頓之力，這代表它們可承受比自己還重173倍的物體，而且這些力量不受環境影響，無論是光滑或潮濕的表面，蜘蛛都能任意行走。

　　蜘蛛的黏附能力優於其他利用黏液附著在物體表面的節肢動物(昆蟲和甲殼綱)，E．arcuata的行為與壁虎較為相似。Kesel表示，這項研究目的是要找出蜘蛛如何演化出黏著在物體表面的能力，結果發現這全都源自分子間的微小作用力。這項基礎研究或許有助於技術的創新，例如發展出利用凡得瓦力的便利貼，以應付潮濕或是油滑的表面。

"Smoking" Rain Clouds over the Amazon

2004-07-12T11:13:00.000+08:00

"Smoking" Rain Clouds over the Amazon

"Smoking" Rain Clouds over the Amazon

Forest fires in the Amazon rainforest intensify turbulence in the weather and could have global impact, report German Max Planck scientists

Several hundred thousand deforestation and agricultural fires burn during the dry season in the Amazon each year, peaking in September and October, and covering vast areas with dense smoke. The first results from SMOCC (Smoke, Clouds, and Climate), an international research project led by Prof. Dr. Meinrat O. Andreae of the Max Planck Institute for Chemistry in Mainz, show that smoke from these fires has a greater impact on weather and climate than was previously known. The smoke affects the formation of clouds, changes the behaviour of precipitation, and induces thunderstorms and hail. The changed cloud properties also lead to warming of layers higher up in the atmosphere and to transport of pollution to these layers, which can have more global impacts on climate (Science, 27 February 2004).

Small particles in the air, so-called aerosols, are important for the formation of clouds. Cloud droplets form by condensation of water vapour on these particles, and without aerosols in the atmosphere, clouds cannot form. Aerosols are formed both in natural and human processes. Since the industrial revolution, the number of human-produced particles in the atmosphere has increased drastically. The effect of these particles on the atmosphere and the climate has therefore been of great scientific interest for decades. One impact of the particles is that they reflect sunlight and prevent the sun from heating the Earth’s surface. This has a cooling effect on the climate. Another impact is that the particles can change the properties of clouds and precipitation, which is more difficult to understand, but ultimately also has a cooling effect on the climate. Together, these cooling effects may have cancelled a significant fraction of the greenhouse gas warming over the past century.

In the natural environment, the number of particles in the atmosphere is rather low. When clouds form, the number of cloud droplets will therefore also be low. On the other hand, in polluted air, the number of aerosol particles is much higher, and therefore the number of cloud droplets in clouds over polluted regions will be much higher. Clouds with a high number of droplets, but of smaller size, are more efficient in reflecting sunlight, and will thus, in the same way as the direct effect of aerosols, have a cooling effect on the Earth.

An increase in the number of the droplets is accompanied by a decrease of their size, since the amount of the condensable water vapour does not change. But smaller droplets do not easily collide with one another, which is necessary to form rain. Thousands of cloud droplets have to collide, in order to form a drop that is large and heavy enough to fall to Earth as a raindrop. The scientific project SMOCC (Smoke, Clouds, and Climate) has focused on this latter aspect. "We try to understand more about how the vast amount of aerosol particles, produced by deforestation in the Amazon, will affect clouds, weather and climate", says Meinrat O. Andreae.

The research team has found that the smoke from human induced fires indeed reduced the cloud droplet size dramatically. Due to this, precipitation was suppressed, and when it occurred, the onset of the precipitation was delayed from about 1500 meter above cloud base in unpolluted clouds to more than 7000 meter above cloud base in pyro-clouds (see Fig. 1). Also clouds that grew out of the polluted smoke haze, so-called smoky clouds, showed considerable suppression and delayed onset of precipitation.

The delayed onset of precipitation leads to the transport of heat to higher layers in the atmosphere. Heat is released to the air when water vapour condenses on the aerosol particles, and when liquid water freezes to ice. At the higher elevations the temperature is cold enough for water to freeze.The heat released at these higher elevations will reinforce the updraft of the air and lead to more intense turbulence, which will make the cloud more vigorous and can induce stormy weather, thunderstorms, lightning, heavy showers and hail. Hail stones as large as two centimeters in diameter has been reported from these cloud types.

Other effects of the suppressed and delayed onset of precipitation are that the heat released at high altitudes can induce substantial changes in the regional and global circulation of air. In addition, aerosol particles, water vapour, and gaseous pollutants can be transported through these clouds to high elevations in the atmosphere, where they can spread over much larger regions, possibly all over the entire globe. Thus, these effects can have more global impact, which will be studied in more detail in the future.

Original work:

Meinrat O. Andreae, Daniel Rosenfeld, Paulo Artaxo, Alexandre A. Costa, Göran P. Frank, Karla M. Longo and Maria A.F. Silva-Dias
Smoking rain clouds over the Amazon
Science, 303, 1337-1342 (27 February 2004)

煙‧雨‧雲

2004-07-12T11:12:00.000+08:00

煙‧雨‧雲

　發生森林大火之後，其破壞力從地表上焦黑的一片清楚可見，可是研究發現其所形成的煙霧對區域性，甚至全球性的氣候影響卻是意想不到的。在巴西的亞馬遜河流域進行的研究發現，森林大火形成的煙霧會降低降雨機率，可是卻增加了雨量。

　　大量的煙霧並不一定會形成會降雨的雲霧。科學家在亞馬遜河谷中發現，煙霧甚至還干擾了雲的形成。因此會減少或延緩降雨，因此形成更猛烈的暴雨。

　　雲朵要能夠形成，要有足夠的煙霧或塵埃使得水氣能附著凝結。為了要瞭解亞馬遜河流域上空大量濃煙的影響，兩個研究小組比較了森林大火的衛星圖像，測量了煙霧、雨量及雲層中的水滴。德國馬克斯普朗克化學研究所的Meinrat Andreae等人發現，過量的煙霧會降緩降雨，因為雲層中大部分的水滴雖然很多，可是都太小了。然後這些小水滴會一直上升到大氣層的更高處，至到冷卻到一定層度後再降落地面。當這些雨滴終於降落地面時，它們帶有的額外能量形成了更猛烈的暴雨，甚至還因在更高處冷卻而形成大冰雹，而暴雨又把更多煙霧和熱能吸入大氣層更高處，於是周而復使地形成循環的暴雨。

　　另外一個研究小組則描述了煙霧陰險的另一面：阻止雲層的形成。美國國家航空暨太空總署（NASA）的Ilan Koren等人則報告道，在森林上空籠罩著的煙霧會反射太陽光，在亞馬遜的旱季，有兩成的時間，煙霧厚到陽光無法穿透到地面。於是地面會冷卻，使得濕氣無法吸收到足夠的熱能而上升到大氣層以形成雲霧。可是少量的雲層反射掉的陽光較少，結果大氣層反而更熱了。讓地面冷卻的煙霧結果卻是讓地球溫度上升。這解釋了煙霧儘管預期有冷卻的效果，可是地球的溫度則不降反升。

　　麻省理工學院的Mario Molina指出，這兩個研究明確地顯示森林大火的確會影響雲霧。現在在赤道地區，森林大火還不時發生，好幾個世紀留下的傳統農耕方法並不會很快地消失。

原學術論文：
1) Andreae, M. O. et al. Smoking rain clouds over the Amazon. Science, 303, 1337-1342 (27 February 2004)
2) Koren, I. et al. Measurement of the effect of Amazon smoke on inhibition of cloud formation. Science, 303, 1342-1345 (27 February 2004)
3) Graf, H. The complex interaction of aerosols and clouds. Science, 303, 1309-1311 (27 February 2004)

Cocaine and the Brain: The Neurobiology of Addiction

2004-07-12T11:10:00.000+08:00

Cocaine and the Brain: The Neurobiology of Addiction
Christine Farrenkopf
In the eyes of the public, the word addict stirs up a negative image: a person of low moral character who willfully chooses to engage in questionable behavior. This image is perpetuated in the media; on a recent episode of E.R., the chief surgeon criticizes another doctor for allowing a heroin addict (who has been treated for an abscess) to exchange a dirty needle, explaining "we don漮 want these low-lives hanging around the hospital." The social stigma attached to addicts reflects the great gap that exists between scientific knowledge and public perception of addiction. Just as mental illness was viewed as a social problem instead of a medical issue until the last several decades, drug addiction continues to be seen as a character flaw instead of as the biological problem that it is.
As defined by the American Psychiatric Association, addiction is a "chronically relapsing disorder that is characterized by three major elements: (a) compulsion to seek and take the drug, (b) loss of control in limiting intake, and (c) emergence of a negative emotional state when access to the drug is prevented" (1). This disorder results from the repeated use of a drug over a prolonged period of time, causing physical changes in the brain.

Perhaps the most addictive of drugs is cocaine. Cocaine acts on the mesoaccumbens dopamine (DA) pathway of the midbrain, extending from the ventral tegumental area (VTA) to the nucleus accumbens (NAc). (2). This pathway is also known as the reward pathway as it is the area of the brain that is activated when someone has a pleasurable experience such as eating, sex, or receiving praise. (NOTE: The reward pathway was discovered through the technique of intracranial self-stimulation (ICSS) (3, p.53). An electrode was implanted in different areas of the brains of rats and was activated when the rats voluntarily pressed a lever. Stimulation in most sites in the brain was not reinforcing (ie, the rats did not regularly activate the electrode), but one site in particular was reinforcing: the reward pathway. Because of the positive effects felt when this pathway is stimulated, such behavior is reinforced.

In the DA pathway of a normal person, a transmitting neuron releases dopamine (a neurotransmitter), which then binds to dopamine receptors on the receiving neuron; an action potential is then propagated in the receiving neuron. (4). After this has occurred, the dopamine reuptake transporters (DATs) of the transmitting cell pump the dopamine back into the cell to be used again.

Cocaine binds to the dopamine reuptake transporters, thus blocking them from functioning. (See web reference (5). for an animation of this process.) As a result, dopamine levels increase in the synapse, and consequently, the receiving neuron is continuously stimulated. This constant firing of the neurons leads to a feeling of euphoria. In addicts, cocaine blocks between 60 and 77 percent of the DAT binding sites; in order to attain a "high," at least 47 percent of the binding sites must be blocked by cocaine. (6).

Cocaine also acts on the reuptake transporters of serotonin and norepinephrine, and therefore, the levels of these neurotransmitters are also increased. (2). Serotonin plays a role similar to dopamine in the DA pathway. Norepinephrine stimulates the "fight or flight" response of the sympathetic nervous system characterized by heightened heart rate, blood pressure, respiration rate, and body temperature as well as dilation of pupils and sweating; these phenomena produce an energizing feeling (7). p.103.

At a certain point, cocaine usage ceases to be a voluntary action: this is the onset of addiction. The positive reinforcement of the sensation of euphoria eventually alters the brain so that the use of cocaine is obligatory. Animal models have been used to demonstrate such positive reinforcement (8) p.1262-4. Lab rats were fitted with long-term intravenous catheters and were taught how to self-administer doses of cocaine by pressing a lever. The fact that the rats continued to self-administer cocaine demonstrates the desire of the rats to be under the influence of the drug. In addition, there is a correlation between the level of the dose of cocaine and the number of infusions a rat would give itself: the lower the dosage, the smaller the gap in-between self-administrations. This indicates that the rat is aware of the level of cocaine in its system and its desire to maintain that level through subsequent injections of the drug. These experiments demonstrate the "compulsion to seek and take the drug" aspect of the definition of addiction.

Another factor in the reinforcement of cocaine use lies in the fact that after cocaine administration, dopamine levels fall significantly below normal, pre-consumption levels (8) p.1272. The user therefore feels a "low," and the immediate response to alleviate this low is to take another hit of cocaine to again raise the level. Such behavior is referred to as a "binge," when a user continuously takes hits of cocaine to recover from ensuing lows (3) p.158. This demonstrates the "loss of control in limiting intake" aspect of the definition of addiction.

Recent research has shown that reinforcement is also linked to cocaine滻 ability to act on genetic material: it activates the gene that codes for the protein delta-FosB (whose levels are elevated in addicts) (9). This protein in turn activates the gene that produces a component of glutamate receptors (GluR2), which binds the neurotransmitter glutamate. An increase in GluR2 production has been shown to increase sensitivity to cocaine滻 rewarding effects.

Over a long period of usage, the brain responds to the above-normal levels of dopamine that are present during a hit. The main manifestation is a reduction in the number of dopamine receptors on the dendrites of neurons (10).; if there are fewer receptors, then there will be less stimulation of the nerves in the DA pathway. This demonstrates how the brain of an addict is physically different from that of a normal person.

Due to this physical change in the brain, an addict will respond differently to a particular dosage of cocaine. Tolerance develops in many addicts, wherein a larger dosage is needed to attain the same high that a user initially experienced (11, p.38). Sensitization may develop instead, wherein a user becomes more responsive to cocaine without increasing the dose (12). The biological mechanisms behind these two phenomena are not completely understood. There is evidence that whether tolerance or sensitization develops depends at least in part on the manner in which cocaine is delivered to the body: if cocaine is taken in spaced out intervals, sensitization results; if cocaine is taken continuously through an IV or through closely spaced injections, tolerance results (13). (14).

Because of the altered physiological state of the brain, events that previously caused stimulation of the DA pathway (pleasurable experiences other than cocaine use) no longer do; only cocaine can induce the feeling of happiness. When an addict ceases taking cocaine, he has no source of stimulation of the DA pathway and therefore experiences severe depression, irritability, and anxiety (symptoms that are opposite of the effects of the drug) (8) p.1271. (This is the "emergence of a negative emotional state when access to the drug is prevented" aspect of the definition of addiction.) Other factors also contribute to the negative behavior associated with withdrawal. For example, tests in lab animals have shown that levels of coricotropin releasing factor (CRF), which induces stress, rise while in withdrawal (8) p.1273.

With repeated drug use comes a phenomenon known as place conditioning, wherein particular places and cues become associated with cocaine use (15). Experiments using lab rats support such a conclusion (8) p.1267. Two distinct neutral environments are set up, one of which is paired with cocaine and the other with a placebo. When the rats are allowed to freely roam between the two environments after experiencing both the cocaine and placebo, we find that they choose to spend more time in the environment where they were given cocaine. This demonstrates that the drug comes to be associated with a certain place.

The road to recovery from cocaine addiction is a long one, particularly because a patient must struggle to overcome the odds of relapse: approximately half of recovering patients succumb to relapse within a year of detoxification (16).

The negative emotional state that results from cocaine withdrawal often causes patients to begin using the drug again. The challenge is to withstand the urge to use the drug during the time when the body "resets" the DA pathway (ie, more dopamine receptors will be activated due to the low levels of synaptic dopamine, which in turn will allow activities other than cocaine use to stimulate the reward pathway). Studies have shown that numbers of dopamine receptors will never return to pre-cocaine use levels.

Because addicts grow to associate certain places and cues with cocaine use, exposure to such stimuli may cause a relapse once an addict has "quit" (17). If reminded of an event linked with cocaine use (such as passing by a place where one formerly used the drug or watching people smoke crack), a recovering addict will very likely feel a strong craving (10). Such a reaction to these memory-based stimuli raises the question of how long memories are able to induce a response. Recent research has shown relapses in lab rats even after four months of abstinence (17).

There is no well-established treatment plan for cocaine addiction, but the most effective measures are to combine a medicine with drug counseling. Drugs such as vigabatrin are being developed that seek to reduce the pleasure of a cocaine hit (this drug stops cocaine from increasing dopamine levels in the DA pathway and prevents subjects from developing place/cue associations in baboons) (18). Anti-depressants are often prescribed to alleviate the negative behavior of withdrawal. New research is concentrating on neutralizing cocaine in the bloodstream so that it is unable to affect the DA pathway (18). While medications are an important part of the recovery process, counseling also plays a seminal role as the patient must learn to resist the urge to use cocaine. Group and individual therapy sessions aid patients in coming to terms with their problem and building up self-confidence (19). Cocaine-specific skills training (CST) teaches patients to identify the places and cues that cause them to feel cravings; they then seek to avoid or adjust their reactions to such stimuli (20).

Viewing cocaine addiction as a chronically relapsing disease of the brain is a new concept for much of the public. Such scientific evidence forces people to re-evaluate their views of addicts (in particular the stereotypes associated with them) as it demonstrates that an addict must be recognized as someone with an altered brain state, just as someone with a mental illness or Alzheimer滻 (15). Addicts cannot be cured through incarceration; instead, the process of recovery requires both counseling and medication. In fact, the lasting biological effects of cocaine addiction are so far-reaching that rehabilitators often comment that there is no way to "cure" someone of cocaine addiction - - one can only learn how to live with it.

Virus robs addicts of their high

2004-07-12T11:08:00.000+08:00

Published online: 22 June 2004; | doi:10.1038/news040621-2

Virus robs addicts of their high
Laura Nelson
Transgenic carrier inactivates cocaine in rat brains.

A cure for cocaine addiction is one step closer. A method has been developed of mopping up the drug in the brain so that it produces less euphoria. Scientists hope that addicts will be less inclined to keep taking the drug if they do not get their hit.

The idea of inactivating cocaine once it is in the body is not new. One approach is to inject addicts with antibodies that bind to the drug, in an attempt to counteract its powerful effect.

Previously, these antibodies were unable to get into the brain, so the effect of the treatment was limited. The new method uses a virus that invades the brain to deliver the antibodies.

"It's a neat idea," comments Arnold Ruoho, a pharmacologist at the University of Wisconsin–Madison. The virus is safe, he says, because any harmful gene sequences have been removed, but genes for the appropriate antibodies have been inserted into the virus's genome.

The treatment was developed by Kim Janda, a chemist at the Scripps Research Institute in La Jolla, California, and her colleagues. They gave eight rats nasal injections of the virus twice a day for three days and compared them to eight rats that did not receive the treatment. On the fourth day, they gave both groups a dose of cocaine.

The untreated rats behaved in a characteristic way after receiving the drug: sniffing, standing up on their hind legs and rocking backwards and forwards. But the rats that received the virus showed much less severe behaviour.

"If they are not demonstrating this activity, they are probably not feeling the high," says Janda.

Driving desire

Although human cocaine addicts do experience withdrawal symptoms, the main driving force that pushes recovering addicts into relapse is the psychological desire for a hit, Janda explains.

She hopes that addicts who want to quit could eventually be given the treatment. "It's for weak moments," she says. The virus lingers in the brain for around two weeks, so although they might relapse once, the absence of any euphoric feeling would then discourage them from taking it again.

If taking cocaine doesn't give you the 'high' it should be easier to quit.

科學家提出控制毒癮的新方法

2004-07-12T11:01:00.000+08:00

科學家提出控制毒癮的新方法

科學家發現，以基因轉殖後的病毒為載體將能產生古柯鹼抗體的基因送入老鼠免疫細胞中，透過免疫反應產生抗體與古柯鹼結合，以阻止古柯鹼分子通過血腦屏障進入腦中，可降低老鼠腦部對古柯鹼的亢奮反應。

「鐵欄杆後，是一名吸毒者因毒癮發作，四肢環抱身體而痛苦掙扎、冷汗直流的景象，他神志不清地向管理員不斷哭喊以尋求幫助，只因為毒癮的發作實在讓他痛苦難耐，感覺生不如死。」這可能是一般人對於勒戒所的印象，雖然並不是每個在這裡頭的人都是如此痛苦，但這的確突顯出毒犯戒毒的困難之處。本週才在台灣引起的禁藥解禁爭議裡，衛生署曾考慮解禁美沙酮（Methadone）這類歐美國家運用來進行「維持療法」（Maintenance Therapy）戒癮的人工合成鴉片類藥物，然而，俄專家在今年一月通過對比研究發現，一些吸毒者在接受美沙酮戒毒療法後產生的美沙酮戒斷症候群，比吸食真正毒品而產生的依賴性更加難以根除。隨著癮君子毒癮發作就控制不了犯罪的情形已然成為社會的隱憂之一，但除此之外，難道就沒有其它辦法了嗎？

其實，相關的研究已由美國斯克利普斯研究院（Scripps Research Institute）以科學家Kim Janda為首的研究小組在上個月發表於《國家科學院期刊》（Proceedings of the National Academy of Sciences, PNAS）上。她們以基因轉殖後的病毒為載體將能產生命名為GNC 92H2的古柯鹼抗體的基因送入老鼠免疫細胞中，企圖降低腦部對古柯鹼產生的欣快感。在她們的實驗中，連續三天，每天兩次，將病毒送入八隻老鼠體內，並再以八隻老鼠做對照組，四天後對實驗及對照兩組注射古柯鹼。結果發現，未受治療的老鼠在注射毒品後出現了呼吸急促、後腳站立和前後搖擺等典型的毒癮症狀，而受治療的老鼠情況則較輕微。她們認為，這項新方法運用在人類身上，就可能可以降低那種真正讓吸毒者近乎崩潰的強烈吸毒欲望，雖然不見得能夠立刻奏效，但欣快感的不再將使他們不再那麼想吸毒。

一般吸毒者在吸食古柯鹼後，古柯鹼分子會先由鼻腔進入，隨後通過血腦屏障（blood-brain barrier, BBB，這是在腦和脊髓內的毛細血管與神經組織之間存在的一個調節性界面，許多治療性的大分子都無法通過。）進入腦中，接著再由腦裡控制食慾、性慾等喜悅感的區域內的腦細胞膜上之多巴胺轉運體（即Dopamine transporter，基本功能是將多巴胺回收至細胞中，來控制神經突觸多巴胺的分泌量。）進入細胞內，並交換釋放出多巴胺（dopamine）。此神經傳導物質主要作用在一塊叫做「伏隔核」（nucleus accumbens）的區域，此區域充滿了製造和回應多巴胺的神經元，如果此區神經元長時期地被多巴胺所刺激，就會不斷地產生欣快的感覺，而這就是成癮的原因。Kim Janda為首的研究小組的目的就是希望能讓老鼠透過免疫反應產生抗體與古柯鹼結合，形成無法通過血腦屏障的大分子，避免進行接下來的細胞機制，以降低老鼠產生成癮的欣快感。

吸毒者的戒毒問題一直是國內關注的問題之一，因為與毒品相關的犯罪案件層出不窮，如先前形象清新的知名藝人蘇永康、安雅和安迪等就曾因此進入勒戒所，所幸他們的情況都還算輕微，雖一時引起社會關注，卻不至於造成嚴重的社會問題。然而，這只是冰山之一角，更有許多人因一時誤入歧途，染上毒癮，造成妻離子散、甚至鋌而走險而身陷囹圄，這無疑大大增加了社會的成本。科學家一直不斷想為這個問題提供一個解決之道，如今這項研究結果的出爐勢必能為許多想要洗新革面卻因毒癮難戒而一錯再錯的人提供另一個希望。

這項研究工作已經告一個段落，未來的工作將著眼於結合這項以病毒為載體的方法與其它主動和被動免疫的方法來決定這項方法是否能夠和其它方法配合得宜，為戒毒的科學研究再做更進一步的發展。

原學術論文：
M. R. A. Carrera, G. F. Kaufmann, J. M. Mee, M. M. Meijler, G. F. Koob, and K. D. Janda. Treating cocaine addiction with viruses. Proceedings of the National Academy of Sciences 101,10416-10421 (2004)

Multivitamins slow HIV

2004-07-12T10:57:00.000+08:00

Multivitamins slow HIV

Multivitamins slow HIV
Helen R. Pilcher
Onset of AIDS delayed by low-cost supplements.

A simple multivitamin pill may slow the advance of HIV, say US doctors. If so, patients in developing countries will be able to delay switching to more expensive drugs.

The suggestion emerged from a clinical trial involving nearly 1,080 pregnant women with HIV in Tanzania. Those who swallowed a daily dose of vitamins B, C and E for up to five years were around 50% less likely to progress to full-blown AIDS than those in a comparison group, the researchers report today in the New England Journal of Medicine1.

Lead author Wafaie Fawzi of Harvard School of Public Health, Boston, believes that multivitamins should be given to developing-world HIV patients in the early stages of the disease. Costing around $15 a person each year, this would be a relatively cheap way to improve their quality of life, he says.

The supplements could also postpone the point at which the disease worsens and patients need to be placed on antiretroviral therapy, which is more potent but costs around $300 to $400 for each patient annually. Patients are not usually placed on antiretroviral drugs until the disease worsens because of their side-effects.

The multivitamins "are definitely not a substitute" for antiretroviral therapy, says Lynne Mofenson who studies HIV in mothers and children at the National Institute of Child Health and Human Development in Rockville, Maryland. Efforts are also under way to expand access to retroviral drugs. But, because of the drugs' price and difficulties administering them in developing countries, less than 8% of the 6 million patients worldwide who need the therapy currently get it.

Better fare

Doctors have suspected for some time that patients who are undernourished or lacking particular nutrients may fare worse when infected with HIV, but Fawzi's clinical trial is the first to test this by randomly assigning patients to multivitamins or a placebo. Fawzi's supplements contained about six times the US recommended daily allowance of the vitamins.

Supplements are likely to have the biggest impact on HIV in the developing world, where poor nutrition is widespread. It is too early to say whether they will also benefit patients in the developed world, who probably already have good diets, says Mofenson, or whether they will have the same impact on men as women.

Experts do not yet know exactly how the vitamins help fight the disease, although the new study shows that they appear to cut the levels of the virus and boost the number of immune cells. The most likely explanation is that they make up for vitamin deficiencies and generally boost the workings of the immune system, says Simin Meydani who studies immunity and nutrition at Tufts University, Boston.

Whether multivitamins are important in fighting off other diseases is also a matter of debate. But there is no blanket prescription; in the latest HIV study, the researchers found that adding a vitamin A supplement to the multivitamin appeared to cut its beneficial effect. "You have to be careful - it could make things worse," Meydani says.

延緩愛滋惡化新利器

2004-07-12T10:56:00.000+08:00

延緩愛滋惡化新利器

一片綜合維生素（multivitamins）可能可以減緩人類免疫缺乏病毒（human immunodeficiency virus，HIV）感染後帶來的各種併發症。在開發中國家的患者將可延後接受昂貴藥物治療的時間。這個方法一年只需15塊美金，大大降低了患者在治療上的經濟負擔。

研究小組針對坦尚尼亞（Tanzania）1,080位女性HIV帶原者進行分組實驗，實驗組給予綜合維生素－含有維生素B群、維生素C及維生素E，對照組則給予安慰劑（placebo）。結果發現，實驗組病情惡化速率明顯減緩，抗反轉錄病毒藥物（antiretroviral therapy）開始使用的時間也就跟著延後。抗反轉錄病毒藥物雖然效用較強，卻相當昂貴（每位患者一年約需美金300~400元）；而且由於它會產生不少副作用，一般除非病情嚴重惡化，否則不會使用。

相較之下，綜合維他命片就顯得又便宜又安全了。不過，美國國家兒童健康與人類發展研究所﹙National Institute of Child Health and Human Development﹚的Lynne Mofenson直言：「綜合維生素還不足以成為抗反轉錄病毒藥物的代替品」。目前各國仍致力於推廣抗反轉錄病毒藥物的使用。可惜因它真的太貴了，在開發中國家又不易取得，全球約六百萬需要此藥物的患者，只有8％能真正得到治療。

過去，醫生已經發現營養不良的HIV患者病情會惡化得較快。這個實驗則顯示補充維生素攝取確實有助減緩病情。但實驗對象來自平日就缺乏維生素攝取的發展中國家，因此目前仍不能確定增加維生素攝取能否對本來營養就很充足的患者有同樣顯著的功效。此外，專家們也還不清楚維生素如何幫助患者打擊疾病，只知道綜合維生素還能減輕人類免疫缺乏病毒引起的併發症如口腔潰爛、吞嚥困難等，女性更可減輕噁心、嘔吐及腹瀉等症狀。這些身體上的不適會降低病患的食慾，使得他們無法攝取足夠的營養，免疫機能下降，最後便惡化成口腔念珠菌症（Candidiasis）、卡波西氏肉瘤（Kaposi's Sarcoma）、勃克氏淋巴瘤（Burkitt's lymphoma）等末期症狀。因此，補充微量維生素有助於增強系統免疫力。此外，綜合維生素還能抑制HIV複製，造成血液中病毒量明顯下降。氧化壓力（oxidative stress）會促使病毒增生，而維生素C及E正是有效的抗氧化劑，能避免氧化壓力的形成，也就讓HIV無法為所欲為地在患者體內複製。

不過值得注意的是，並非每一種維生素都有療效。實驗證實若只供給患者維生素A，結果與對照組無太大差異；如果將綜合維生素與維生素A一起供給，則本來綜合維生素的療效會降低，甚至有些併發症會更嚴重。美國波士頓塔夫茨大學（Tufts University）免疫與營養學家Simin Meydani就提出忠告：「使用這些維生素時你得小心點，它們有可能讓事情變得更糟糕。」

原始論文：
W. Fawzi et al. A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality. New England Journal of Medicine 351, 23 (July 2004).

Cactus extract offers hangover help

2004-07-09T10:14:00.000+08:00

Cactus extract offers hangover help

21:00 28 June 04

NewScientist.com news service

An extract of prickly pear cactus could herald help for hangovers, quelling some of the wretched symptoms that strike the morning after a night out.

Taking a capsule of the extract before a night of drinking and partying significantly reduced some of the symptoms of a hangover in young adults, compared with a placebo, showed a study by US scientists.

The extract produced statistically significant improvements in the nausea, lack of appetite and dry mouth afflicting the volunteers the morning after they had spent four hours swigging spirits. The overall assessment of hangover severity, based on nine symptoms, was reduced by nearly a fifth, but this result was not statistically significant.

Jeff Wiese, at Tulane University, New Orleans, stresses: "Our interest is not to eliminate the symptoms of the alcohol hangover so people could drink with impunity. The only known cure for the alcohol hangover is to not drink."

"Our interest is to discover what is causing the alcohol hangover, and to investigate what harms may be associated with the syndrome," he told New Scientist.

Vodka, gin and rum

Hangovers, or veisalgia as the condition is called medically, carry huge economic and health consequences, say Wiese's team. But despite this, little is known about its mechanism.

It has been associated with a heightened inflammatory response by the body to alcohol impurities called congeners and some preservatives. Extract from the skin of prickly pear fruit, called OFI, had previously been shown to dampen inflammatory response.

So Wiese's team gave 55 adults aged between 21 and 35 years old either OFI or placebo five hours before they staged a party. The subjects were given a fast-food dinner and then allowed to choose their tipple for the evening from vodka, gin or rum, which are relatively low in impurities, or bourbon, scotch or tequila, which are relatively high.

The team also tried to create a realistic situation for the alcohol consumption by throwing a party. This is because previous research suggested behaviour at parties could cause some hangover symptoms, e.g. sore muscles from over-enthusiastic dancing.

The inebriated party-goers were then driven home by limo. Two weeks later the party was repeated with those who had received a placebo getting OFI and vice versa.

Inflammation process

The morning after the parties, those given OFI were nursing less severe hangovers than those given placebo. In particular, it slashed the risk of a severe hangover by half.

The researchers also measured levels of a protein produced by the liver, called C-reactive protein, which is thought to be involved in the inflammation process.

The higher the levels, the worse the hangover, they found. This is the first study to show this, the team believes. Levels of this protein were also 40 per cent higher in the people who took placebo pills compared with those who took the OFI.

The researchers therefore believe that OFI eases hangovers by soothing the inflammatory response to alcohol.

Journal reference: Archives of Internal Medicine (vol 164, p 1334)

Shaoni Bhattacharya

避免宿醉，來點仙人掌吧！

2004-07-09T10:06:00.000+08:00

避免宿醉，來點仙人掌吧！

能夠大醉一場或許還蠻爽快的，不過卻要忍受第二天睡醒後難過得不得了的宿醉。在貪杯前先來點仙人掌精華可能能夠預防嚴重的宿醉。

在派對狂歡前先來顆仙人掌萃取物，能夠顯著地改善年輕人的宿醉，減輕第二天早上噁心想吐、食慾不振和口乾舌燥的症狀。Tulane Univ.的Jeff Wiese強調，他們的研究並非是要讓人可以毫無節制地狂飲。要改善宿醉的唯一方法是克制自己。他們更想瞭解的是，造成宿醉的原因為何，以及和這些症狀有關的傷害。

Wiese指出，宿醉造成了經濟上和健康上極大的代價。可是其機制還未明。宿醉可能是因為酒內的雜質等造成身體起發炎反應。而一種仙人掌果（Opuntia ficus indica）的萃取物OFI已知能夠抑制發炎反應。Wiese等人在派對開始前五個小時，發給55名年紀介於21歲至35歲的成人OFI或安慰劑。他們在吃飽了速食餐後，可以選擇痛飲伏特加、琴酒或萊姆酒等雜質成分低的烈酒，或波本威士忌、蘇格蘭威士忌及龍舌蘭酒等雜質成分較高的烈酒。

他們也試圖營造出派對的氣氛，因為有些研究認為派對上狂歡的行為，如熱舞造成的肌肉痠痛也會造成一些宿醉的症狀。兩週後，派對會再來一次，而上次服用了安慰劑的人則發到了OFI，反之亦然。第二天早晨，服用過OFI的人，宿醉狀況較服用過安慰劑的人還輕微。他們也發現肝中和發炎反應有關的C反應蛋白，在服用安慰劑的人中，其量比服過OFI的人還高四成。OFI顯然會抑制身體的發炎反應而減輕了宿醉症狀。

原學術論文：
Wiese J, McPherson S, Odden MC, Shlipak MG. Effect of Opuntia ficus indica on Symptoms of the Alcohol Hangover. Arch Intern Med. 2004 Jun 28;164(12):1334-40.

Rice yields plunging due to balmy nights

2004-07-09T10:04:00.000+08:00

Rice yields plunging due to balmy nights

10:23 29 June 04

NewScientist.com news service

Rice yields are crashing as a result of global warming at twice the rate predicted by climate modellers, according to the first “real world” experiment on the impact of rising temperatures.

The detailed study of crop yields and temperatures took place on long-standing research plots at the International Rice Research Institute at Los Banos in the Philippines. The results suggest that global rice yields could potentially fall by a catastrophic 50 per cent during this century.

The study found that on the Los Banos plots, “the 0.7°C increase in the mean daily temperature was associated with a rice yield decrease of 10 per cent – substantially greater than previous estimates”, says Kenneth Cassman from the University of Nebraska in Lincoln, and one of the research team.

Past predictions of future rice yields have forecast declines of five per cent for an increase of 0.7°C. But Cassman told New Scientist that those predictions are too low, because they missed the fact that global warming is most intense at night, when tropical plants need to cool off and respire.

Energy drain

In recent decades, global warming has generally been greater at night than during the day – a trend climatologists expect to continue.

At IRRI’s research site, the mean temperature rose by 0.7°C over the past 25 years. But while maximum temperatures rose by 0.35°C, night minima have risen by 1.1°C.

The research team, headed by the IRRI's Shaobing Peng, believe that the rice plants suffered from these higher night temperatures because it dramatically increases the amount of energy they expend on processes such as respiring during the hours of darkness. That leaves less energy for daytime photosynthesis, when their grain grows.

Cassman says the IRRI research site is unique because it has grown the same rice varieties and used the same growing techniques for many years, while also collecting detailed temperature records. That means sunlight and temperature are the only variables to explain changing yields.

Widely eaten

The UN Intergovernmental Panel on Climate Change (IPCC) currently predicts that without drastic action to halt emissions of greenhouse gases, there will be a rise of 3.6°C in average global temperatures in the coming century. The new findings suggest that could reduce yields of rice - the world’s most widely eaten food - by half.

However, some people believe that global warming should be good for crop yields. The veteran British TV botanist and environmentalist David Bellamy recently grabbed headlines by saying that plants should grow faster in a greenhouse world because the extra carbon dioxide in the atmosphere will make photosynthesis more efficient.

Cassman agrees that “the increased CO2 concentration should partly offset the negative effects of higher night-time temperatures.” But he points out that the Los Banos research plots have been subjected to both higher temperatures and higher CO2 levels, and the negative effects won.

The IPCC's Third Assessment Report in 2001 foresaw the Los Banos results, stating: "In the tropics, where some crops are near their maximum temperature tolerance, yields would decrease generally with even minimal changes in tremperature."

But the report also noted that the same might not apply at higher latitudes: "A few degrees of warming will lead to general increases in temperate crop yields."

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0403720101)

Fred Pearce

熱壞了稻米？！

2004-07-09T09:59:00.000+08:00

熱壞了稻米？！

研究顯示全球暖化對稻米的收成是個壞消息，炎夜的夜晚讓稻米產量下滑。

稻米養活了地球上一半的人口，稻米的產量每年得增加1%才能趕得上人口的增長。氣候變遷對稻米產量的影響，學界迄今仍無定論，美國內布拉斯加大學的Kenneth Cassman指出，這是因為我們對環境變遷如何影響農作物產量，瞭解還非常粗淺。

一般上的認知是，頂著大太陽的白天，加上大氣中二氧化碳的增加，應該能夠刺激植物的光合作用，因此產量上升。可是炎熱的夜晚，會增加植物的呼吸作用，因而降低植物的產量。Cassman和菲律賓馬尼拉國際稻米研究所的彭少兵等人分析了25年的氣候資料，以找出關鍵的因素。

他們的結果顯示，夜晚的最低溫每增加1°C，稻米的產量就降低了一成，可是產量和白天最高溫和產量卻沒有關聯。Cassman表示，現今的理論必須要修正了，因為它們把白天和夜晚的溫度都混在一起成為單一的平均溫，而事實上全球暖化讓夜晚的溫度上升得更多。

英國牛津大學的Chris West表示，全球暖化對食物的供給會有非常深遠的影響，如果這個關係對各地各種農作物都通用的話。現在的氣候模型預測到了2100年，全球溫度會升高1.5°C到4.5°C，夜晚將會更熱。West提議，要解決這個問題，可是要培育出能夠應付熱夜的新稻米品種。

原學術論文：
S. Peng et al. Rice yields decline with higher night temperature from global warming. PNAS published June 28, 2004, 10.1073/pnas.0403720101

Left brain damage may make people more vulnerable to infection

2004-07-05T13:35:00.000+08:00

Left brain damage may make people more vulnerable to infection

Epilepsy surgery on brain hemispheres produces different effects on immune system
A major immunological difference between the opposite halves of the human brain is now confirmed in a study published May 24, 2004 in the online edition of the Annals of Neurology. Researchers have found that damage or surgery to the left half of the brain may make a right-handed person more susceptible to being immunocompromised.
The results might help to explain intriguing earlier findings that suggested people who had strokes on the left side of their brains were more susceptible to infections.

"These findings raise the possibility that doctors need to be more aggressive in protecting patients from infection following strokes or surgery on the left side of the brain," said study director Kimford J. Meador, MD, of Georgetown University Hospital in Washington, D.C.

Are you a right-brain person--creative, emotional, big picture--or a left-brain person--logical, detail-oriented, practical?

The idea that the two halves of our brains are fundamentally different has settled comfortably in our imaginations, thanks equally to science fiction and self-help books. But beyond a predominant role in language for the left half, scientists have had a hard time pinning down what these differences mean for how our brain works.

Animal studies have shown distinct differences in how the two brain halves are linked to the immune system. Several years ago, Meador and his colleagues found preliminary evidence of similar differences in humans, which could be of great significance for medicine.

"The immune and nervous systems are interlinked, influencing each other in complex ways that we are just beginning to understand," said Meador.

In the present study, the researchers examined how the immune system responded to surgery on either side of the brain, following the progress of 22 epilepsy patients who had parts of their brain surgically removed in an attempt to control debilitating seizures.

Most patients who had surgery on the left side of their brains experienced significant decreases in immune function, with the immune system reducing the numbers of critical disease-fighting cells called lymphocytes and T-cells. By contrast, patients who had surgery on the right side of their brains saw the levels of their lymphocytes and T-cells significantly boosted.

It is important to note that this may be true only for right-handed patients, write the authors. Although they did not have enough left-handed and ambidextrous people in their study, the researchers note that non-right-handed people could have the opposite reaction. Or they might show equivalent immunologic responses to right and left brain injuries.

"Even with these results, we and others have examined only a small portion of possible immune responses in regards to left/right brain influences. Even more important, exactly how the brain alters immune response is unclear. Future studies will need to address these issues," said Meador.

左腦的損傷可能使人更容易受感染

2004-07-05T13:26:00.000+08:00

左腦的損傷可能使人更容易受感染

科學家發現左腦的損傷或手術可能會使右撇子的人更容易受到免疫性傷害。

最新的研究發現，實行腦部癲癇（Epilepsy）手術會引發不同的免疫反應，在最近一期的《神經學年鑒》（Annals of Neurology）所發表的一篇文章中已證實不同的免疫能力存在於人類另一半大腦中。

美國華盛頓喬治城大學（Georgetown University）附設醫院研究計畫主持人Kimford J. Meador說：「這項研究發現提醒醫生們要更積極保護左腦中風或是左腦手術的病人免於受到感染」。

一般來說，右半腦發達的人較具有創造力、善感及豐富想像力，而左半腦發達的人比較具有及邏輯性、方向性和行動力。然而，在兩邊腦室有都本質上的差異構築了我們有想像力。但是，我們左腦除了扮演主要的語言能力之外，科學家們還花費許多時間確定左腦在我們大腦運作中代表著其他不同的意義。

其實在實驗動物中，早就可看出左右兩大半腦與免疫系統的聯結有明顯的差異。數年前，Meador和他的同事發現到在人類也有相同差異性，這對於醫學而言帶來非凡的意義。Meador提到：「免疫系統與神經系統之間是互相聯結的，而我們才正開始瞭解它們是由複雜的路徑來影響彼此的」。

在這項研究裡，研究人員根據22位癲癇病患利用手術移除部份腦組織來控制減少癲癇發作情形，並且檢測在腦部手術中另一半腦室免疫反應。大部患者其左腦動過手術會顯著降低免疫系統的正常功能，伴隨著減少重要的「對抗疾病」(disease-fighting)細胞稱淋巴細胞（lymphocytes）包括殺手T細胞（T-cells）等。而相反的，右腦動過手術的患者其淋巴細胞及殺手T細胞卻是顯著的提升。

雖然在研究中沒有足夠左撇子以及左右手並用的實驗人數，但是作者提述到非右撇子的人可能會有與右撇子有不一樣的結果。或是非右撇子在左腦和右腦的損傷中其免疫反應是一樣。而更重要的是，確認腦部損傷是否會改變免疫能力目前還不是很清楚。Meador也說到：「需要更多的研究來修飾他們的論述」。

原學術論文：
Meador KJ, Loring DW, Ray PG, Helman SW, Vazquez BR, Neveu PJ. Role of cerebral lateralization in control of immune processes in humans. Ann Neurol. 2004 Jun;55(6):840-4.

Bad teeth not just from childhood

2004-07-03T12:35:00.000+08:00

Bad teeth not just from childhood

People with bad teeth can no longer just blame it on too many sweets or too few visits to the dentist as children, researchers say.

'Men aged 20 to 30 are the worst at looking after their oral health ' Professor Jimmy Steele, Newcastle University

A team from Newcastle University say it is an unhealthy adult lifestyle which causes poor oral health in later years.

The study, in the Journal of Dental Research, looked at data on over 300 people.

It found the link between family background and dental problems diminished with age.

The study, which used data from the Thousand Families Study, which has collected information on a cross-section of children born in Newcastle upon Tyne in 1947, found the link eventually became virtually insignificant.

The team studied childhood information taken from 337 volunteers, together with more recent data on adult health and lifestyle collected at age 50.

Researchers looked at the number of teeth people had lost over time, as tooth decay and gum disease are both cumulative and ultimately result in tooth loss.

It was found that the more cigarettes a person smoked, the more teeth he or she was likely to lose.

Previous research has shown that smoking restricts the blood flow in the gums, leading to disease and tooth loss.

Poor social circumstances in adult life are also associated with infrequent tooth brushing and irregular dental attendance, the researchers said.

Bad habits

The researchers are calling for more to be done to improve the dental health of adults as well as children, potentially including making smoking cessation advice part of dental care.

Dr Mark Pearce, the lead researcher and director of the Thousand Families Study, said: "Damage to teeth and gums happens over a long period of time and is irreversible.

"These findings demonstrate that it is just as important for adults to look after their teeth and gums as children, and that good oral healthcare habits shouldn't stop when people leave their family home."

He said: "Even if people aren't used to following a tooth-care regime, it's never too late for them to start .

"They can't turn the clock back but they can increase their chances of maintaining a good set of teeth into their old age - something which is very significant when you consider life expectancy is increasing all the time."

Professor Jimmy Steele, of Newcastle University's School of Dental Sciences, who also worked on the study, said: "Even people who look after their teeth when they are children may slip into bad habits when they leave home and indulge in an unhealthy lifestyle as young adults.

"It's common for chocolate bars to be substituted for meals, or for regular teeth brushing to stop.

"In fact, studies show that men aged 20 to 30 are the worst at looking after their oral health."

Smoking damage

A spokesperson for the British Dental Association said: "Looking after your teeth is important regardless of how old you are.

"A simple routine of brushing your teeth twice a day with a fluoride toothpaste can keep your mouth healthy, but you shouldn't ignore the other factors which can have an effect on your oral health.

"Some food and drink can stain your teeth, so try to avoid, or at least reduce, things like coffee, red wine and curries.

"Smoking not only affects how your teeth look, it can also cause gum disease and even mouth cancer. Giving up may be tough, but it's certainly worth it in the long run."

愛護牙齒永遠不嫌晚！

2004-07-03T12:29:00.000+08:00

愛護牙齒永遠不嫌晚！

有了一口爛牙不能再歸咎於小時候的習慣不好，最新的研究結果顯示人越老越要為自己的口腔健康負責。

這是由英國泰茵河畔新堡大學（University of Newcastle upon Tyne）的研究團隊所發表的研究結果。在英國有個稱為「Thousand Families Study」的研究計畫，這個研究始於1947年，記錄了1142位小朋友在15年間的健康、成長狀況、教育、社會經濟狀態和家庭環境。新堡團隊從該研究計畫當中挑了337個年紀介於49-51歲之間的自願者，針對他們口中殘存的牙齒進行研究。

由於蛀牙及各種牙齦疾病對口腔所造成的影響是日積月累的，而且最終都會使牙齒有所缺漏，所以研究殘存的牙齒就如同研究口腔的歲月記錄。

研究結果發現，個人家庭背景與其牙齒和牙齦健康狀況之間的相關性會隨著年紀增長而減低，同時個人成年之後的生活型態以及社經狀況與口腔健康之間的相關性卻逐漸提高。

同時並發現抽煙抽得越凶的人，其剩下的牙齒也就越少，這是因為抽煙會導致牙齦的血液循環不良並產生種種牙齦疾病，最後使得牙齒脫落。其他一些不良的生活起居習慣，像是不常刷牙或是沒有定期看牙醫都會有影響也會使得口腔健康狀況低落。研究結果並顯示，年紀介於20到30歲之間的男性對於口腔的照顧是最為疏忽的一群。

他們提出以下幾點方法幫助大家好好保養自己的口腔：
1. 每天使用含氟牙膏刷兩次牙
2. 盡量不吃甜食，尤其在正餐之間
3. 不抽煙
4. 應採納專家的意見來照顧自己的牙齒
5. 在餐後可嚼無糖口香糖以避免蛀牙

愛護牙齒永遠不嫌晚，尤其成年之後牙齒是一掉不復長的。而且成年人要比小朋友更好好照顧自己的口腔，就像人在30歲之後要為自己的長相負責一般，年紀越大越要為自己的口腔健康負責！

原始論文：
M.S. Pearce, et al. Do circumstances in early life contribute to tooth retention in middle age? Journal of Dental Research, 83(7) 562 – 566,2004.

Junk DNA yields new kind of gene

2004-06-30T11:40:00.000+08:00

Junk DNA yields new kind of gene
Regulates neighboring gene simply by being switched on

BOSTON-In a region of DNA long considered a genetic wasteland, Harvard Medical School researchers have discovered a new class of gene. Most genes carry out their tasks by making a product-a protein or enzyme. This is true of those that provide the body's raw materials, the structural genes, and those that control other genes' activities, the regulatory genes. The new one, found in yeast, does not produce a protein. It performs its function, in this case to regulate a nearby gene, simply by being turned on.
Joseph Martens, Lisa Laprade, and Fred Winston found that by switching on the new gene, they could stop the neighboring structural gene from being expressed. "It is the active transcription of another gene that is regulating the process," said Martens, HMS research fellow in genetics and lead author of the June 3 Nature study .

"I cannot think of another regulatory gene such as this one," said Winston, HMS professor of genetics. The researchers have evidence that the new gene, SRG1, works by physically blocking transcription of the adjacent gene, SER3. They found that transcription of SRG1 prevents the binding of a critical piece of SER3's transcriptional machinery.

The discovery raises tantalizing questions. How does this gene-blocking occur? Do other regulatory genes work in this fashion? Does the same mechanism occur in mammals, including humans?

At the same time, SRG1 provides clues to a recent puzzle. Researchers have lately begun to suspect that the long stretches of apparently useless, or junk, DNA might possess a hidden function. In the past year, evidence has been pouring in, not just from yeast but from mammals, that these apparently silent regions produce RNAs, which are associated with transcriptional activity (see Focus, March 5, 2004 http://focus.hms.harvard.edu/2004/
March5_2004/biological_chemistry.html). Yet no one has found associated protein products. "For us it is easy to look at those findings and say, 'Well maybe those are examples of what is going on here in yeast,'" said Martens.

If so, the findings would carry an important message for the post-human genome era-namely, that researchers' attempts to turn the masses of data churned out by the Human Genome Project into an understanding of what actually happens in the human body may be even more complex than they anticipated. One of the main challenges for that effort is to figure out how and when genes are turned on and off during normal development and disease. Rather than look only at how genes are regulated by proteins, they would have to turn their attention to a new, and possibly more-difficult-to-detect form of control. And given that junk DNA makes up 95 percent of chromosomes, the mechanism could be fairly common.

"I think if nothing else, this sends up an alert that this likely occurs in other cases," said Winston. "When people are looking to understand regulation of genes from whatever organism-humans, flies, mice, yeast-they cannot just look for proteins that are acting there. It might be that it is simply the act of transcribing that is causing regulation."

Like many researchers, Winston and his colleagues may have known in the back of their minds that someday they would have to contend with junk DNA, but it was not their intention to map a new gene in those wild and relatively uncharted regions of the chromosome. If anything, the yeast SER3 gene was their lodestar. What intrigued them about the gene, which is involved in the synthesis of the amino acid serine, was its unusual expression pattern. To be turned on, genes must first be bound by an activator molecule. A common activator in yeast is a molecule called Switch/Sniff. While most genes are turned on by Switch/Sniff, SER3 is turned off by the complex.

In the course of exploring how this repression happens, Martens came across an even more surprising result. "The usual story when a gene is transcriptionally repressed is that RNA polymerase, TATA binding protein and a host of other factors associated with active transcription, will not be there," he said. He, Laprade, a research associate, and Winston conducted a series of experiments and found that the factors were all present and active, and they were located just upstream of the SER3 promoter-as was a jot of DNA needed for the onset of transcription, the TATA element.

Thinking that the TATA element might signify the beginning of a new gene, one associated with both the active RNA polymerase and SER3 repression, Martens mutated it. "We no longer saw the RNA, and we found transcription of SER3 was de-repressed," he said. "That is when we thought, 'OK, we have got a new regulatory gene.'" After characterizing SRG1, which turned out to be 550 base pairs long, they tackled the question, How is it regulating SER3? They put the question on the table during a lab retreat atop a downtown skyscraper. "Everybody talks, and they are not allowed to show any data," said Winston. Out of that intellectual free-for-all, three models emerged.

The first held that RNA transcripts produced from SRG1 were being recruited to SER3 and were somehow repressing transcription. The researchers assumed that if this were true, it would not matter where the RNA came from. As it turned out, SER3 was repressed only when the RNA was produced by an adjacent SRG1. The second model, which proposed that the SRG1 promoter outcompeted the SER3 promoter for transcription factors, also did not hold up to experimental scrutiny.

There had been hints all along favoring the third model. In this one, transcription of the nearby SRG1 somehow prevents an activator from binding the SER3 promotor. Using chromatin immunoprecipitation, a powerful method for imaging the location of molecules in living cells, the researchers found that this was exactly what happened: a well-known activator fell off the SER3 promotor when SRG1 was turned on. In fact, when SER3 was replaced by a reporter gene, the same thing happened-the turning on of SRG1 prevented the activator from binding to that gene as well.

As for how this interference actually occurs, one possibility is that the machinery required to transcribe SRG1 -RNA polymerase, TATA-binding proteins and other factors-somehow spills over to the nearby SER3 promotor, physically preventing it from being approached by an activator. "It is also possible that active transcription alters chromatin structure and modifies things in other ways," said Winston. As for the molecule that got them started in the first place, Switch/Sniff, the researchers now think it may activate SRG1 and in that way bring about SER3's anomalous repression. "That is our current thinking," Winston said. It is a view he expects will be revised. "Every time we thought we understood everything going on here, we have been wrong. There are additional layers of complexity."

抑制基因表現的新方法

2004-06-30T11:35:00.000+08:00

抑制基因表現的新方法

　DNA轉錄的過程本身就是一種基因調控的方式。研究發現RNA聚合脢在轉錄的過程中，可以抑制鄰近基因的表現。

　　一般而言在基因表現時，是先由DNA轉錄產生RNA，再由RNA轉譯產生蛋白質。但仍然有許多的基因雖然不產生最終的蛋白質，其RNA卻仍然被轉譯出來。這些基因有的是為了產生具有功能性的RNA，例如：rRNA、tRNA、microRNA。但是其他無緣無故被轉錄的基因呢？過去科學界認為這是RNA聚合脢偶然發生的『失誤』。然而這些過去認為毫無意義的轉錄工作，目前似乎有了新的詮釋。

　　哈佛大學醫學院由Fred Winston所帶了的研究小組，觀察酵母菌中絲胺酸（serine）生合成酵素SER3的基因表現，發現在絲胺酸缺乏的環境中，轉錄因子可以進入SER3的啟動子（promoter），成功地轉錄出mRNA。但若是在絲胺酸不虞匱乏的環境下，轉錄工作就會由上游的SRG1基因開始，並且跨過SER3的啟動子。RNA聚合脢進行在進行轉譯工作時，由於佔據了SER3的啟動子，在空間上構成立體阻礙而妨礙了轉錄因子的進入，因而抑制了SER3基因。

　　以往這些不產生蛋白質的轉錄工作，大多是為了生產具有生物活性的RNA。但是Fred Winston等人發現的現象，其轉錄出來的RNA序列並不具重要性，反而是靠轉譯本身的過程來調控基因表現。

　　已知在高等動物的基因組裡面存在有大量的無用序列。傳統上認為是演化所留下的遺骸，隨著演化的過程累積而增加。但是這項研究顯示，部分『無用基因』的轉錄，可能是為了要調控其他基因的表現。這些看似無用的基因序列，或許反而是高等生物為了精密調控各種基因表現，而發展出來的超複雜基因調控法。

原始論文：
Marten J, et al. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429:571-574

Vaccines may increase virulence

2004-06-28T13:40:00.000+08:00

Pursue additional defences, urge malaria experts.
22 June 2004 HELEN PEARSON

Malaria kills 2-3 million people each year.
© WHO

Vaccines against malaria could cause the parasite to develop more vicious strains. But experts warn that the finding should not detract from the urgent hunt for a jab.

Malaria is caused by the parasite Plasmodium falciparum, which is injected into humans by mosquitoes. Over a dozen clinical trials are in progress for possible vaccines against the deadly disease. Most of these jabs create conditions in which, although the parasites can still infect people, the immune system slows their multiplication so they do not cause disease.

To investigate whether surviving parasites change with time, Margaret Mackinnon and Andrew Read at the University of Edinburgh, UK, infected a mouse with a type of Plasmodium and then passed blood carrying the parasite on to another animal seven days later. They repeated this process 20 times, to mimic the ailment passing from person to person.

Parasites that moved from one vaccinated animal to another evolved into nastier strains than those grown in non-vaccinated animals, the researchers show in PLoS Biology1. The vaccinated animals stayed healthy, but when the parasite they carried was transferred into other mice, it killed more red blood cells and made them lose more weight than the original malaria strain.

Mackinnon and Read believe that malaria vaccines could have the same effect in people. Perhaps over decades, P. falciparum might evolve into a more deadly form in vaccinated people, which would pose a greater threat than ever to those unprotected by a jab.

No magic bullet

Malaria vaccines are still vital, stresses Read, because people who are immunized will be protected from the disease. But he urges public health officials to pursue other methods to eliminate malaria, such as distributing nets and developing new drugs, even as jabs are developed. "You shouldn't think of vaccines as a magic bullet," he says.

Researchers might also avoid types of vaccine that allow the parasite to survive at low levels, he suggests. Instead, they could focus on classes of vaccine that hobble the parasite before it infects red blood cells or which cripple it in the mosquito and so stop it passing from one person to another.

Many of the vaccines under trial already take the latter approach. In fact experts predict that an effective malaria vaccine will probably trigger the immune system into attacking the parasite at several different stages of its life cycle.

But some experts are concerned that the new finding will undermine their efforts to stem a disease that kills 2 million to 3 million people each year. "It has no relevance to vaccine development," says Adrian Hill who is working on malaria jabs at the University of Oxford, UK.

Read disagrees: "The big question is, would the same thing happen with another virus?" If so, jabs against other diseases, such as measles, might also have promoted the emergence of more virulent strains. It is hard to tell whether this has happened, because improved medical practices make it difficult to compare death rates at a time before vaccination with those today.

竊取基因的小偷

2004-06-28T13:34:00.000+08:00

細菌能時常移動基因並彼此交換，在環境改變時，留下有用的、淘汰沒用的基因，所以它們是世上適應力最高的生物之一。雖然在一些親源相近卻不同寄主的菌種中，常擁有功能相同但序列迥異的基因，表示這些基因應該是來自於各自的寄主，不過對於基因是否能在不同生物界（kingdoms）之間的移轉，一直無法得到明確的證據。德國海德堡歐洲分子生物學實驗室的計算生物學家和瘧疾研究人員組成的研究小組，最近在發表於Genome Biology的文章中表示，一個專門在動物體內產生alpha 2-巨球蛋白（α2-macroglobulin, α2M）的基因，也在某些細菌中發現。

α2M是一種蛋白分解酵素的抑制物，當遭受外來細菌入侵，α2M便會把細菌的酵素抓起來，讓細菌無法再更深入體內擴散。這對動物來說是種十分便利的防禦機制，所以從大螃蟹到人，幾乎所有動物都保留了這個基因。不過一般認為除了動物，其他生物界都沒有此基因。所以，當研究小組在超過三十種細菌的體內發現這個基因時，著實嚇了一跳。深入研究發現，這些細菌雖然具有共同的特徵－－絕大多數是在動物體內寄生並造成疾病，但在演化樹上的關係卻是平行的。經過胺基酸序列比對發現，後生動物（metazoan）的α2M蛋白質與細菌該蛋白質是同源的（homologous）；而擁有α2M的數十種細菌，本身在系統發生學中呈現零散的分佈，並不符合垂直演化的模型。

因為在其他生物界都缺少α2M這個基因，研究人員認為對此現象最有可能的解釋是：早期的細菌祖先從原始動物寄主如後生動物身上「偷」到α2M基因之後，再藉著基因重組或交換，將此基因與其他細菌共享。雖然研究人員尚無法排除其他的可能性，譬如此基因可能只是在植物、真菌等生物界演化過程被弄丟罷了。不過就機率來說，在這「偷竊模式」中一次單純的基因轉換，總是比要在不同物種中不斷喪失同個基因容易得多。

α2M到了細菌體內後，真正的作用為何？根據在大腸桿菌（Escherichia coli）的研究大略得知，細菌型α2M可能具有阻礙寄主反微生物防禦機制的功能，可幫助細菌在寄主體內擴散，修補被寄主破壞的細胞壁，但與毒性強弱沒有關係。不過它真正的功能還需要更深入探討。而因細菌型α2M是一種細菌膜間質蛋白質（periplasmic proteins），容易受抗體影響，這項特性也將替未來疫苗研究提供新的方向。

原學術論文：
A. Budd et al. Bacterial α2-macroglobulins: colonization factors acquired by horizontal gene transfer from the metazoan genome? Genome Biology 5:R38 (May 2004) doi:10.1186/gb-2004-5-6-r38

基因讓花心大少變成痴情漢！？

2004-06-24T10:55:00.000+08:00

基因讓花心大少變成痴情漢！？

改變了一個基因的表現，就讓生性喜歡胡搞瞎搞的動物，變成只對另一半忠誠的好情鼠。

這個發現對演化生物學家認為複雜的社會行為是一小步一小步演化而來的假設是個大挑戰。許多物種間配偶之間長長久久的關係，似乎是抗利尿素（vasopressin）的受體V1aR有關。在前腦腹面有高V1aR表現的物種，比較可能是一夫一妻制的，反之則是對性放蕩的。對田鼠而言，就的確是如此，平原田鼠（Microtus ochrogaster）是一夫一妻的，牠們的表親草地田鼠（M. pennsylvanicus）則有多個性伴侶，是花心的傢伙。

美國亞特蘭大Emory Univ.的社會神經生物學家Lawrence Young等人，把平原田鼠的V1aR利用一種無害的病毒把它轉植入牠們的表親，好色的雄性草地田鼠腦中。基因移植幾天以後，原本喜歡亂交的嚙齒類動物長出了較高量的V1aR，並且失去了對多個雌性的強烈欲望，它們改變了左顧右盼的目光，對當前的配偶表現出格外的偏愛。當基因轉殖的雄草地田鼠和一隻雌田鼠獨處了24小時後，就算之後再放入另一隻新雌鼠，原本會喜新厭舊的雄草地田鼠再也不會去大搞外遇。

增加大腦這個區域的V1aR，當它形成親密的配偶關系時，動物大腦就會有一種受獎賞的感覺，所以這些好色的傢伙就會改變它們的花心行為。Young指出，這個研究顯示改變單一基因的活性就能改變動物的基本社會行為。

Young等人把這兩種鼠分別按雌雄關系配對，每一對允許有一天去相互認識，然後對雄性進行忠誠測試。每個田鼠都被允許在牠的伴侶和陌生鼠之間自由徘徊。結果發現平原田鼠和轉殖了基因的草地田鼠都愛和自己的侶伴擠在一塊。沒有接受基因轉植的草地田鼠則更喜歡獨處。之前的研究顯示增加V1aR的水平，可以加速平原田鼠形成配偶的速度。這項研究則進一步顯示轉殖基因能夠把花心的草地田鼠變成忠誠的好伴侶。

伊利諾大學香檳分校的神經科學家Gene Robinson表示，這個研究對瞭解社會行為的演化是非常重要的。大部分科學家認為社會行為的演化是許多基因發生了小變化的後果。可是這項研究卻表明了，複雜的社會行為像是配偶的親密結合也能只需要一個基因表現上的改變就能造成了。

不過同樣的機制是否可用於解釋人類的行為還是未知的人類。可是和田鼠相似，實行多妻制和一夫一妻的猴子有不同的V1aR表現量。所以對人類來說，那些花心的男人和忠心的男人可能也有相似的大腦化學機制。極度多情的男人，如唐璜或許就是V1aR基因發現了突變。但是人類的配偶機制要復雜得多，社會因素、經濟、歷史和個性差異都扮演著重要的角色。

雖然控制男人的花心行為不像控制老鼠這麼簡單，但是這類的研究或許可以幫助解釋浪漫愛情的神經生物學基礎。

原學術論文：
Lim, M. M. et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754 - 757 (17 June 2004); doi:10.1038/nature02539

Researchers make promiscuous animals monogamous by manipulating genes

2004-06-24T10:48:00.000+08:00

Researchers make promiscuous animals monogamous by manipulating genes

Finding could yield new insight into the Neurobiology of romantic love and the inability to form social bonds
ATLANTA -- Researchers at the Yerkes National Primate Research Center of Emory University and Atlanta's Center for Behavioral Neuroscience (CBN) have found transferring a single gene, the vasopressin receptor, into the brain's reward center makes a promiscuous male meadow vole monogamous. This finding, which appears in the June 17 issue of Nature, may help better explain the neurobiology of romantic love as well as disorders of the ability to form social bonds, such as autism. In addition, the finding supports previous research linking social bond formation with drug addiction, also associated with the reward center of the brain.
In their study, Yerkes and CBN post-doctoral fellow Miranda M. Lim, PhD, and Yerkes researcher Larry J. Young, PhD, of the Department of Psychiatry and Behavioral Sciences at Emory University's School of Medicine and the CBN, attempted to determine whether differences in vasopressin receptor levels between prairie and meadow voles could explain their opposite mating behaviors. Previous studies of monogamous male prairie voles, which form lifelong social or pair bonds with a single mate, determined the animals' brains contain high levels of vasopressin receptors in one of the brain's principal reward regions, the ventral pallidum. The comparative species of vole, the promiscuous meadow vole, which frequently mates with multiple partners, lacks vasopressin receptors in the ventral pallidum.

The scientists used a harmless virus to transfer the vasopressin receptor gene from prairie voles into the ventral pallidum of meadow voles, which increased vasopressin receptors in the meadow vole to prairie-like levels. The researchers discovered, just like prairie voles, the formerly promiscuous meadow voles then displayed a strong preference for their current partners rather than new females. Young acknowledges many genes are likely involved in regulating lifelong pair bonds between humans. "Our study, however, provides evidence, in a comparatively simple animal model, that changes in the activity of a single gene profoundly can change a fundamental social behavior of animals within a species."

According to previous research, vasopressin receptors also may play a role in disorders of the ability to form social bonds, such as in autism. "It is intriguing," says Young, "to consider that individual differences in vasopressin receptors in humans might play a role in how differently people form relationships."

And, Lim adds, past research in humans has shown the same neural pathways involved in the formation of romantic relationships are involved in drug addiction. "The brain process of bonding with one's partner may be similar to becoming addicted to drugs: both activate reward circuits in the brain."

The researchers' next step is to determine why there is extensive variability in behaviors among individuals within a species in order to better understand the evolution of social behavior.

Changes to insect-seeking calls of horseshoe bats may drive new species formation

2004-06-23T14:58:00.000+08:00

BU geographer Tigga Kingston links speciation potential to acoustic differences in calls
(Boston) -- It may not matter whether there is a mountain high enough or a river wide enough to keep members of a species apart. New species may diverge and form because of something as fundamental as a call to dine.
According to new research by Tigga Kingston, a research associate in the Department of Geography at Boston University, and Stephen Rossiter, a National Environment Research Council research fellow in the School of Biological Sciences at Queen Mary, University of London, geographical barriers may not be necessary for speciation. In their study of one species of bat in Southeast Asia, the scientists found that the bats were diverging into exclusive groups primarily because of acoustic differences in the calls they make to locate the insects they eat.

Their finding challenges long-standing theory that geographical barriers are the mechanism by which new species evolve. This new perspective on an old controversy appears in the June 10 issue of Nature.

For centuries, theorists have debated how new species form. Traditional thought holds that speciation occurs over long periods of time as a result of interbreeding among members of a group that are, for one reason or another, isolated from other members of the same population.

If, for example, geologic activity changed an area so that mountains rose and split a region populated by a species of bat, the bat populations on either side of a mountain would no longer be able to breed together. Their genetic information, including changes that lead to physical or behavioral adaptations to the demands of their environments, would no longer be pooled. Future generations of bats found on one side of the mountain would begin to diverge genetically from those on the opposite side. Eventually, the two populations of the bat species would become sufficiently different to qualify as separate species.

In their study, Kingston and Rossiter found that large-eared horseshoe bats (Rhinolophus philippinensis) are diverging to three sizes -- small, medium, and large -- despite their living next to one another. The researchers also discovered the animals' echolocation calls are harmonically distinct. This means the differently sized bats no longer hunt one another's food because they no longer can even "see" one another's food. According to the researchers, when food sources can be partitioned so precisely, it is a short hop to species divergence. They have, in fact, dubbed the divergence process, "harmonic hopping."

The researchers conducted their work in the rainforests of Sulawesi in Southeast Indonesia, a region known as "Wallacea" after Alfred Russell Wallace, a 19th century explorer who, together with Charles Darwin, posited some of the basic ideas that form current evolutionary theory. This region abounds in bat species. The researchers focused on the large-eared horseshoe bat, speculating that the different sizes might indicate a greater difference -- that of species divergence.

When they analyzed the recorded echolocation calls of the bats, Kingston and Rossiter found each size variant calls at a different acoustic variation of one fundamental frequency: 13.5 kHz. They found the large form calls at 27 kHz, the medium one at 40.5 kHz, and the small one at 54 kHz, each frequency a mathematically precise permutation of the basic 13.5-kHz frequency. These harmonic differences, according to the researchers, determine the type of insect any one size of large-eared horseshoe bat can hunt and feed upon. The low harmonic frequency used by large-sized horseshoe bats, for instance, is perfect for detecting large insects over long distances yet completely misses small insects, which are easily scoped out by small-sized horseshoe bats using the higher harmonic frequency.

The researchers speculate that the harmonic differences also can affect other communication among the bat groups, including calls that help them find one another for mating purposes. Harmonic hopping could, therefore, hinder mating between sizes, a key step in speciation. Taken together, the researchers say their findings indicate that sensory ecology may have an important function in speciation and may explain the rapid dissemination of horseshoe bat species in Southeast Asia, where some 30 species have originated in just the past five million years.

蝙蝠叫聲的種化契機

2004-06-23T14:51:00.000+08:00

牠們種化的契機。

演化生物學家把不能互相交配生下有生育力後代的生物，歸為不同的物種。從達爾文以降，演化生物學家就一直極力為新種產生的機制提出許許多多的理論。傳統上主流的理論認為新物種主要是因為有地理隔離阻止了不同族群的基因交流而產生的。然而近來的研究發現同域種化也是可能的，物種可能在同一地理區產生不會互相交配的族群。

美國波士頓大學的Tigga Kingston和英國倫敦大學的Stephen Rossiter在印尼蘇拉威西捕捉蝙蝠時，發現大耳蹄鼻蝠（Rhinolophus philippinensis）其實有三種不同的體型，牠們住在同一區域，不過卻從未雜交。

為何會如此呢？他們發現關鍵在於蝙蝠的回波定位的叫聲。蹄鼻蝠的叫聲通常只有一個頻率。體型最大的蝙蝠發出27.2 KHz低頻的叫聲，而體型中等和較小的蝙蝠則發出較尖的叫聲，分別是40.5 kHz和54 kHz，剛好各差了13.5 kHz。這些蝙蝠可能無法聽到那一群蝙蝠的叫聲，因為牠們的耳朵已經把其他叫聲過濾掉了，蹄鼻蝠的聽覺是調頻到剛好能聽到自己的聲音的，如此才能有效地利用昆蟲反射的聲波來定位。高頻的聲音比較適合掃描較小的獵物，因此不同體型的蝙蝠也各自追逐著不同大小的昆蟲。叫聲頻率的改變影響了食性和交配行為，因此可能形成了無形的屏障而創造出了新的物種。

無獨有偶，蘇拉威西的蝙蝠並不是孤單的，分子演化的趼究發現這樣的情況也可能發生在澳洲的蝙蝠。雖然科學家早提出叫聲的差異是是許多動物如鳴禽種化的動力，可是Kingston指出他們的研究是首次證實這個想法。

原學術論文：
Kingston, T. & Rossiter, S. J. Harmonic-hopping in Wallacea's bats. Nature 429, 654 - 657 (10 June 2004); doi:10.1038/nature02487

The skinny on fat: MIT researchers establish first link between eating and aging

2004-06-21T11:50:00.000+08:00

Denise Brehm, News Office
June 2, 2004

Forget the drastic reduction in carbs and calories called for by diet dictators. The day when people can eat their favorite foods, stay thin and live to be 120 without getting age-induced diabetes or cancer may be nearer than we think.

Scientists have known for decades that controlled famine can extend the lifespan of mammals by as much as 50 percent and that those long-lived, lean mammals don’t get the diseases of old age. But just how a vastly reduced caloric intake achieves that feat has been a mystery begging for a solution—until now.

Researchers at MIT believe they’ve found the key to a long, lean, healthy life in a single protein that controls whether a mammal stores fat or sheds it.

“For the first time, this study gives us a glimpse of how calorie restriction works at the molecular level. And it will ultimately lead to health benefits in people," said MIT Professor of Biology Leonard Guarente, who has been studying the aging process in yeast, roundworms and mice for more than a decade.

In the June 2 online issue of the journal Nature, scientists in Guarente’s lab, including Frédéric Picard, a research scientist in the Department of Biology who is an author of the paper, will publish their research results about how the Sirt1 mammalian gene promotes fat mobilization in mice.

A mammal generally burns the protein and carbohydrates in its food immediately; it stores fat in special cells called white adipose tissue (WAT). When it reduces its caloric intake, the WAT stops storing fat and begins releasing it for metabolism.

The paper’s authors learned that fat is released from or metabolized by the body, rather than stored, when the Sirt1 protein senses short-term famine and turns off the receptors that normally keep fat stored in fat cells. Thus fat cells shed their fat.

They write that this happens because the “Sirt1 protein activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal the Sirt1 protein binds to and represses the genes that are controlled by PPAR-gamma, the fat regulator," preventing fat from being stored in the body.

“The ability of fat cells to sense famine [or short-term hunger] and release the fat is regulated by this gene," said Guarente. “We like to think this applies to people as well as mice, but we don’t know for sure. If we could make this happen in people, it wouldn’t just make them live longer; it might also help prevent diseases of aging, like cancer, diabetes and heart disease."

Because WAT also makes hormones, especially leptin which controls satiety, Guarente speculates that by putting hormones into the bloodstream, fat cells also tell the body how fast to age.

“Conversely, fewer fat cells tell the body that it’s time to hunker down for survival. This means that evolutionarily speaking, fat plays a very important role," he said.

We know already fat or lack of it has vast implications in the lives of people, but putting them on an austere diet just isn’t feasible.

“It’s easy to put rodents on a spartan diet. With people it’s not so easy; they don’t want to diet," said Guarente.

In fact, the side effects in a human being whose diet was cut by about 50 percent—down to 1,000 to 1,200 calories a day, the reduction necessary to get the 50 percent extension in the lifespan—would create a very lean, cold, unhappy person with no sex drive. “It would be like eating every other day," says Guarente.

Unless, that is, you could find a way to mimic the molecular effect of famine without the actual dieting.

“If we could make a drug that would bind to Sirt1 and fool the body into thinking that it needed to release that fat, then maybe people could get the benefits of calorie restriction without the side effects," he said, describing a sort of fountain-of-youth drug that he hopes to create.

How would such a drug work? Would it require vigorous exercise? Might there be additional complications in humans, such as reduced resistance to disease?

“Evolutionarily, you would think it would make humans more resistant to infectious disease," Guarente said. “But you never know."

He suspects that vigorous exercise also will be required. The next step in the process, he added, is to determine if an increase in Sirt1 in the body leads to a higher rate of metabolism.

This research was funded by the National Institutes of Health.

A version of this article appeared in the June 9, 2004 issue of MIT Tech Talk (Volume 48, Number 30).

吃得少，活得久

2004-06-21T11:49:00.000+08:00

體脂肪較少的苗條老鼠比牠們的胖子同伴活得久，現在科學家鑑定出了一個生化分子路徑，可能可以解釋為何如此了。

　　一種稱為Sirt1的蛋白質能夠在挨餓時促進脂肪分解，因為它阻礙了其他蛋白質的活動，後者活化了促進脂肪儲存的基因。節食能讓許多動物延緩老化，科學家已鑑定出一些和這個現象有關的蛋白質。例如酵母菌利用Sir2p（和Sirt1同源的蛋白質）在食物短缺的情況下延長生命。麻省理工學院的Frederic Picard等人推測Sirt1在老鼠也會造成同樣的效果。

　　節食會造成白脂肪細胞分解脂肪，他們在培養的老鼠脂肪細胞中增加或減少Sirt1的產量，結果發現多量的Sirt1會讓細胞儲存較少的脂肪，而缺乏Sirt1的細胞則反之。經基因改造而製造出較少量Sirt1的老鼠，血液中的脂肪含量較少，顯示牠們的細胞吃進了更多的脂肪。Sirt1的作用顯然是抑制脂肪的儲存。

　　為何如此呢？他們的實驗顯示SIRT1會干擾PPARγ的作用，後者會促進好些和脂肪儲存的基因之表現。所以節了食，Sirt1就會抑制PPARγ，然後脂肪細胞就不會再保有脂肪，反而會釋放脂肪到血液中。白脂肪細胞也會製造一些激素，如纖瘦素（leptin），所以脂肪細胞也可能影響了老化的速度。

　　哈佛醫學院的分子生物學家David Sinclair指出，這項研究是一大步，它意味著Sirt1和苗條及長壽有關，就像在酵母菌中一樣。不過Sinclair和作者們也指出，節食不僅會減脂而已，這個研究只是代表了一小部分。

原學術論文：
Picard, F. et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature AOP, published online 2 June 2004; doi:10.1038/nature02583

Dog's verbal tricks probe origin of language

2004-06-18T15:40:00.000+08:00

17:58 10 June 04
NewScientist.com news service

A word-learning pet dog has given scientists clues that some animals may have the comprehension necessary for language, even though they cannot actually talk.

Rico, a smart border collie, was spotted on television by Julia Fischer and her colleagues at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. With a "vocabulary" of 200 words, Rico showed exceptional ability in retrieving specific toys when asked to fetch them.

The researchers decided to test whether Rico's ability was based on understanding and if he could learn and remember new words. They placed a new toy among his favourites and asked Rico to fetch it, using the unfamiliar name. The dog nearly always did. This suggests that Rico is using a system called "fast-mapping", which young children use to learn new words by matching new words to new objects. The study is the first to show fast-mapping in animals.

"It shows that fast-mapping is not specific to humans, that it probably has a more general purpose in figuring things out in your world," says Fischer.

"Dog owners often boast about the communicative and social abilities of their pets, and this study seems to vindicate them," writes Paul Bloom, a psychologist at Yale University, US, in a commentary accompanying the study in the journal Science.

Finely-tuned articulation

Fischer adds the results suggest there may be reasons other than comprehension which have stopped language evolving in dogs and chimps.

"With the evolution of language the constraints are not on the comprehension side - that had all been in place before humans uttered a word," she told New Scientist. "The constraints are more on the production side."

Making the jump from comprehension to talking may require a change in neural organisation to give voluntary control and fine-tune articulation, she says.

Another hypothesis suggests that gesturing is a pre-requisite to language developing. "Primates have fabulous control of their hands, but they don't gesture," Fischer explains. "So this shows there must be more going on, perhaps in terms of social cognition."

Retrieval rate

To be sure that Rico's language skills were not based on visual prompts, the researchers placed 10 known items in a room, while Rico and his owner waited in another room. The owner asked Rico to go in fetch two randomly chosen items 20 times. Rico correctly fetched 37 out of 40 toys.

When a new toy was placed in the adjacent room with seven other familiar objects, Rico correctly retrieved the unfamiliar item in seven out of 10 sessions.

He was then tested four weeks later to see if he remembered the link between the novel word and the novel item. The learned toy was placed among four completely new toys, and four familiar ones. In three out of six sessions, Rico picked the right one. "This retrieval rate is comparable to the performance of three-year-old toddlers," write the researchers.

Rico may be an exceptionally bright and studious dog, admits Fischer "If he were human, we would call him a workaholic. He's so motivated, it's mind-boggling."

She also points out that dogs may be a special case in responding to human language because they have co-evolved with humans. But other animals like apes have also shown comprehension.

Another factor could be that border collies are working dogs and have been selected to respond to a shepherd's calls. But despite their word skills, they do not make easy pets, she warns, as they require a lot of exercise and attention.

Journal reference: Science (vol 304, p 1682)
Shaoni Bhattacharya

懂得人類語言的狗狗

2004-06-18T15:29:00.000+08:00

科學家發現一隻邊界牧羊犬雖然不能說話，不過牠對人類語言的理解程度，甚至有如跚跚學步小孩。這意味著即使和人類關係疏遠的哺乳動物，都有語言學習能力的雛形。

　　字彙學習始於瞭解一個字和它背後所隱含的意義之關係。兒童的字彙學習有實物展示和消去法。例如在一個盤子中裝了他熟悉的香蕉和蘋果，再加上他不熟悉的水果來對應到一個新字，以建立一個新詞與一件陌生物體的關係，然後把這關係儲存在記憶中，這種能力在科學上稱為「快速繪圖」（fast mapping）。這種學習能力以往認為只有人類小孩會有，可是德國馬克斯普朗克演化人類學研究所的Julia Fisher等人發現一隻稱為Rico的邊界牧羊犬也有這樣的「快速繪圖」能力。

　　Rico在九○年代就在德國的電視上引起一陣騷動，這隻十歲大的狗可以記得200個玩具的名字，並按照順序把它們銜回。Fisher等人設計了一系列的實驗，在條件控制的環境下測試Rico的語言能力，要牠在一堆所熟悉的玩具中銜出一個牠從未聽過或看過的東西，以驗證牠的「快速繪圖」能力。結果Rico有七成的機會是對的，而且在未再受訓的情況下，一個月後還記得約一半的東西。Rico背下字彙的能力可和大猿、海豚、海象和鸚鵡相提共論。Fisher表示，Rico的表現顯示，人類語言能力的起始，也可見於其他動物，而且也符合聽比說更早演化出的理論。

　　耶魯大學的心理學家Paul Bloom表示，這個研究非常重要，因為它顯示狗也可以是研究比較認知心理學的好材料。不過他懷疑狗的能力可以相較於兒童，因為小孩學習一個字時，他學會的是把它關連到一個類別的東西，最終它可以形成一個句子來表達該字。Rico是否也是如此呢？還是只是學習一個字的指令，仍是未知的。

原學術論文：
Kaminski, J. Call, J. & Fisher, J. Word Learning in a Domestic Dog: Evidence for "Fast Mapping". Science, Vol 304, Issue 5677, 1682-1683 , 11 June 2004

Male susceptibility to disease may play role in evolution of insect societies

2004-06-17T14:53:00.001+08:00

A pair of scientists has proposed a new model for behavioral development among social insects, suggesting that a higher male susceptibility to disease has helped shape the evolution of the insects' behavior.
What might be called the "sick-male" theory has been proposed by animal behaviorists Sean O'Donnell of the University of Washington and Samuel Beshers of the University of Illinois at Urbana-Champaign, and appears in the current issue of Proceedings Biological Sciences, published by the Royal Society of London.

Among behaviors possibly affected are the division of labor between males and females and the relative social isolation experienced by males in many social insect colonies.

The researchers looked at Hymenoptera, an order of insects, including bees, ants and wasps, some of which have highly complicated societies and an unusual genetic makeup. These insects are called haplodiploids because males and females have a different number of sets of chromosomes. The females, like most animals, including humans, are diploid and have two sets of chromosomes, one from each parent. Hymenopteran males, however, hatch from unfertilized eggs and are haploids with just one set of chromosomes.

"Disease and infections are a very powerful and ongoing force in natural selection, and natural selection should favor individuals that possess forms of genes, or alleles, that make them more resistant to infection," said O'Donnell, a UW associate professor of psychology. "In some cases, an individual that has more than one form of a gene can ward off more parasites. In humans, for example, there are different forms of a blood gene that can help ward off malaria parasites. People with two different alleles for this gene are more resistant to malaria."

Because they are haploid, Hymenopteran males can't have alternate forms of any genes, or in other words, individual males have no genetic variability. This, O'Donnell and Beshers contend, puts males at a higher susceptibility to disease.

The researchers, who are trying to understand the basis of social behavior in these creatures, suggest that this male vulnerability has shaped certain behaviors in social insect colonies. These behaviors, they say, are designed to minimize the risk of disease transmission in a colony.

Division of labor is a prime example. While colonies vary widely in the total number of individuals, females vastly outnumber males and seem to do most of the work.

"Males typically do not do very much work for their colonies," said O'Donnell. "In some instances males do small amounts of labor inside the nest. But they rarely are allowed outside of the nest and they do not forage for food or building materials, activities that might expose them to disease pathogens.

"If males were exposed to disease we would expect females to avoid, and possibly to attack and kill those males to minimize disease being brought into the colony."

The sick-male theory proposes that female-biased societies, and differences in male and female behavior, may be responses to higher risks of infection to males, he said. The theory also predicts that in some cases males may be segregated or shunned inside the nest, again to reduce the colony's potential exposure to disease.

O'Donnell said much research still needs to be done to support the sick-male model and test whether males are less resistant to disease than females.

"We hope our study will inspire scientists to these ideas. Researchers need to challenge different species of social insects with disease pathogens to see whether males and females differ in disease resistance," he said. "Our understanding of the genetic basis of disease resistance is pretty weak, even medically. There actually is little evidence to show how genetic variability at the individual level is effective in fighting off disease, even though this is often assumed to be the case by biologists." The National Science Foundation funded the research.

為什麼公的可以遊手好閒？

2004-06-17T14:53:00.000+08:00

染色體的差異可能造成昆蟲雌雄之間對疾病耐受力不同，因此在演化的過程中影響了昆蟲社會結構的形成。

Sean O’Donnell以及Samuel Beshers提出病男理論（sick-male theory），試圖來解釋為何在一些高度組織化的昆蟲社會中有雌性當家的現象。

他們觀察的對象是膜翅類昆蟲（Hymenoptera），這類昆蟲包括了我們所熟知的蜜蜂、螞蟻以及大黃蜂，這些昆蟲都有著很複雜的社會結構。一般負責覓食、尋找修建巢穴的材料等工作都是由雌性負責。相較之下，雄性可以說是遊手好閒，不過平常雄性是不被允許外出的。

膜翅類昆蟲在雌雄之間的染色體數目很不相同，雌的染色體是二倍體（diploid）的，但雄的因為從未受精的卵中所孵出，所以它們的染色體數目比雌的少了一半，於是在基因上，雄性沒有對偶基因的組合。對偶基因（allele）的存在允許同一個基因可以有不同的組合，使得同種生物之間會有不同的表現型出現。

譬如鐮狀細胞性貧血（sickle cell anemia ），這是一種由於基因改變使得紅血球的形狀從甜甜圈變成鐮刀狀的疾病。這種貧血在非洲這種瘧疾極為猖獗的地方很常見，因為鐮刀狀紅血球使得鐮狀細胞性貧血病患不易感染瘧疾（malaria），比沒有罹患鐮狀細胞性貧血的人更有機會繁衍下一代。

病男理論認為，由於雄性無法有對偶基因的組合，這使得它們可能較雌性來得容易受到感染，因此雄性不被允許外出覓食，而且雌性的數目會較雄性來的多，這都是為了降低族群感染疾病的可能性。再者由於疾病在演化上扮演著強而有力的選擇力量，所以膜翅類昆蟲便演化出目前這種雌性當家的社會結構。

不過這個理論還需要進一步的證實，像是雄性是否真的比雌性容易受感染，不同的社會化昆蟲當中是否同樣存在這種情形。

原始論文：
Sean O’Donnell, Samuel Beshers. The role of male disease susceptibility in the evolution of haplodiploid insect societies. Proceedings of the Royal Society of London B, 271,979-983, (2004).

Undisturbed Amazonian forests are changing, say scientists

2004-06-16T13:25:00.000+08:00

A research team of U.S. and Brazilian scientists has shown that rainforests in central Amazonia are experiencing striking changes in dynamics and species composition. Although the cause of these changes-in what are believed to be completely undisturbed, old-growth forests-is uncertain, a leading explanation is that they are being driven by rising levels of carbon dioxide in the atmosphere.
Carbon dioxide levels have risen by 30% in the last 200 years as a result of industrial emissions, automobiles, and rapid forest burning, especially in the tropics. Much of this increase has occurred since 1960. Plants use carbon dioxide from the air for photosynthesis.

"The changes in Amazonian forests really jump out at you," said William Laurance, a U.S. scientist with the Smithsonian Tropical Research Institute in Panama. Laurance was the lead author of the paper, which appeared this week in the scientific journal Nature (Mar 11). "It's a little scary to realize that seemingly pristine forests can change so quickly and dramatically."

For the past two decades, the research team studied the fate of nearly 14,000 trees in the central Amazon, scattered across a landscape of 120 square miles in area. During the course of the study, most species of trees began growing faster. The forests also became more dynamic, with existing trees dying faster and being replaced by young new trees.

Even more important is that the species composition of the forest is changing. "There clearly are winners and losers," said Alexandre Oliveira of the University of S緌 Paulo, Brazil, another team member. "In general, large, fast-growing trees are winning at the expense of smaller trees that live in the forest understory."

"The decline of many small trees is intriguing because they tend to be so specialized," said Henrique Nascimento, a Brazilian researcher at the Smithsonian Tropical Research Institute. "They live in the dark interior of the forest, and are the only trees that can flower and reproduce in deep shade."

The most likely reason for these changes, say the researchers, is that rising carbon-dioxide levels are fertilizing the forests, leading to faster growth and more competition among trees for light, water, and soil nutrients. Under these conditions, big, fast-growing species of trees probably have an advantage over small, slower-growing trees.

"Sadly, this could be a signal that the forest's ecology is changing in fundamental ways," said team-leader Laurance. "Tropical rainforests are renowned for having lots of highly specialized species. If you change the tree communities then other species-especially the animals that feed on and pollinate the trees-will undoubtedly change as well."

"This appears to be yet another signal of effects on nature from increasing greenhouse gas concentrations and associated climate change," said Thomas Lovejoy of the Heinz Center for Science, Economics and Environment in Washington, D.C., who helped to establish the tree study in central Amazonian over two decades ago. "We really need more research to see if these remarkable changes are also happening in other tropical forests around the world. If they are, then it's likely that even the world's remotest forests are now being altered by human activities."

###
The Biological Dynamics of Forest Fragment Project, a joint effort of the National Institute for Amazonian Research (INPA) in Brazil and the Smithsonian Tropical Research Institute, seeks to answer questions about plant and animal relations, the biology of extinction, the process of forest regeneration, and the effects of forest edge and fragmentation on the genetic structure of tropical species.

The Smithsonian Tropical Research Institute is an international research center established in Panama by the Smithsonian Institution to increase knowledge of the past, present and future of tropical biodiversity and its importance to humanity. For more than 90 years, researchers, students and associates have conducted research in forest and marine habitats in Panama and at other sites throughout tropical regions of the world.

不再原始的原始森林

2004-06-16T13:24:00.000+08:00

人煙罕至的亞馬遜河流域的原始叢林理因不受到人類活動的影響，不過一項研究卻發現原始的雨林也受到了環境變遷的荼毒。

　　人類的活動，例如伐木、放火和開荒等當然會破壞雨林成千上萬種物種間的平衡。可是一項研究卻現，原本遠離人類活動範圍的生物群落，卻還會受到人類活動所導致的環境變遷所迫害。

　　史密森熱帶研究所的William Laurance指出，這樣的平衡之所以被破壞，是因為快速生長的樹種在CO2的滋養下生長得更旺盛了。如果這個趨勢持續下去，生長緩慢的樹種將飽受荼毒，這對生物多樣性的維持肯定是個糟透的消息。

　　Laurance等人在南美洲熱帶雨林裡的畫出69個各1公頃的區域，觀察樹木的生長情況長達廿年。他們原本是要把人煙罕至之18處的資料當成控制組，以對照人類活動較頻繁之處。可是後來他們卻發現，怎麼控制組卻不受控制。組成樹冠群的樹種長得更多了，而組成次樹冠群的樹種則減少了。Laurance指出，森林的動態顯然受到了改變。

　　Laurance懷疑CO2是罪魁禍首，因為在上個世紀開始大量燃燒化石燃料起，大氣中的CO2是有增無減。而CO2又是快速生長的樹種所不可或缺的營養，因此它們把握了先機，開始在森林裡稱霸。

　　英國University of Leeds的森林專家Oliver Phillips也同意CO2是主因。因為如果是其他原因如雨量的變化，那麼該有所改變的應該是耐潮或抗旱的樹種。這個趨勢令保育生物學家憂心忡忡，原來最荒無人跡之處仍脫離不了CO2的荼毒。

　　Laurance警告道，該擔心的還不止是生物多樣性的問題。生長緩慢的樹種，生產的木質和葉片密度較高，因此它們的淪陷代表熱帶雨林的固碳能力已大不如前。亞馬遜熱帶雨林每年清除掉6億噸CO2，大約是燃燒化石燃料所產成的8~10%。

　　Laurance主張，回歸到京都條約來限制CO2的排放是重要的。身為美國人，他對美國未能簽署京都條約而感到十分惱怒。我們已經有足夠的資訊知道我們該做些什麼了！

原學術論文：
Laurance, W.F. et al. Pervasive alteration of tree communities in undisturbed Amazonian forests. Nature, 428, 171 - 175, (2004).

Project: Errors, rewards, and the brain

2004-06-15T14:03:00.000+08:00

We and others have previously identified a component of the event-related brain potential, the Error-Related Negativity (ERN), that occurs when human subjects make errors in reaction time tasks or when they receive feedback indicating that they have made an error. Converging evidence from a variety of approaches, including fMRI and dipole analysis of EEG and MEG, suggests that the presence of an ERN in recordings at the scalp is associated with activity in the anterior cingulate cortex (for reviews, see Coles, Scheffers, & Holroyd, 1998, 2001: Falkenstein, Hohnsbein, & Hoormann, 1995: Falkenstein, Hoormann, Christ, & Hohnsbein, 2000: Gehring, Coles, Donchin, & Meyer, 1995).

We have proposed that the ERN is associated with an error-detection process involving a comparison between representations of the actual response activated and the correct or appropriate response (see Coles et al., 2001). When the comparison process detects a mismatch, an error signal is generated, and this signal is conveyed to a remedial action system, whose function is to correct or inhibit the error or to compensate for the error by making adjustments that assure that an error does not occur in the future. The error signal can also be generated by feedback that indicates that an error has been made.

Most recently, we have used neurophysiological data and computational modelling to argue that the ERN represents the activity of a more fundamental system, concerned with monitoring the value of environmental events (Holroyd & Coles, submitted). According to this view, when events are worse than expected (as for example, when an error is detected or when negative feedback is received), the basal ganglia generates an error signal which is conveyed by the dopamine system to the anterior cingulate. The anterior cingulate acts a motor controller to select the appropriate action based on the information conveyed by the error signal.

The proposed research projects are designed to address several questions that can be derived from our previous work. These questions concern (a) the generality of the monitoring system whose activity is reflected in the ERN, (b) the claim that the same neural system is involved in the processing of internally and externally generated error signals, and (c) whether activation of the monitoring system is dependent on the organism having control over the environment. This proposed research has no significant overlap with the research conducted by Prof. Dr. W. Hulstijn under the project entitled "Brain imaging of movement errors", which is supported by NICI.

That project is specifically concerned with movement errors, especially force errors, and their neural correlates. The present proposal is concerned with different issues, namely, the generality of the neural error processing system, and the extension of the error-processing model to situations involving the observation of errors.

People involved in this project
Drs. R.B. Mars (AiO)
Prof. dr. M.G.H. Coles (Promotor)
Prof. dr. W. Hulstijn (Co-Promotor)

生物：吃得少，活得久

2004-06-15T13:56:00.000+08:00

編輯：Gene
體脂肪較少的苗條老鼠比牠們的胖子同伴活得久，現在科學家鑑定出了一個生化分子路徑，可能可以解釋為何如此了。

一種稱為Sirt1的蛋白質能夠在挨餓時促進脂肪分解，因為它阻礙了其他蛋白質的活動，後者活化了促進脂肪儲存的基因。節食能讓許多動物延緩老化，科學家已鑑定出一些和這個現象有關的蛋白質。例如酵母菌利用Sir2p（和Sirt1同源的蛋白質）在食物短缺的情況下延長生命。麻省理工學院的Frederic Picard等人推測Sirt1在老鼠也會造成同樣的效果。

節食會造成白脂肪細胞分解脂肪，他們在培養的老鼠脂肪細胞中增加或減少Sirt1的產量，結果發現多量的Sirt1會讓細胞儲存較少的脂肪，而缺乏Sirt1的細胞則反之。經基因改造而製造出較少量Sirt1的老鼠，血液中的脂肪含量較少，顯示牠們的細胞吃進了更多的脂肪。Sirt1的作用顯然是抑制脂肪的儲存。

為何如此呢？他們的實驗顯示SIRT1會干擾PPARγ的作用，後者會促進好些和脂肪儲存的基因之表現。所以節了食，Sirt1就會抑制PPARγ，然後脂肪細胞就不會再保有脂肪，反而會釋放脂肪到血液中。白脂肪細胞也會製造一些激素，如纖瘦素（leptin），所以脂肪細胞也可能影響了老化的速度。

哈佛醫學院的分子生物學家David Sinclair指出，這項研究是一大步，它意味著Sirt1和苗條及長壽有關，就像在酵母菌中一樣。不過Sinclair和作者們也指出，節食不僅會減脂而已，這個研究只是代表了一小部分。

原學術論文：
Picard, F. et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature AOP, published online 2 June 2004; doi:10.1038/nature02583

這麼久以前的事怎麼記得起來？

2004-06-15T13:55:00.000+08:00

UCLA的科學家找到我們如何提取陳舊記憶的線索。

　　目前已知腦部海馬回（hippocampus）的部分負責處理並儲存短期記憶，但是長期記憶究竟如何提取與儲藏，還是個謎團，不過從UCLA在《Science》上所發表的研究結果可以看出一些端倪來。

　　他們使用了三種方法來確定這些陳舊的回憶如何被提取與儲存。

　　首先他們使用一種基因改造的老鼠，這種老鼠的CaMKII基因產生突變，所以失去可以回想起舊記憶的能力。接著刺激老鼠的足部使它們對籠子產生恐懼，並在3、18及36天之後測驗老鼠對籠子的恐懼回憶。結果發現老鼠在第三天(短期記憶)還記得籠子所帶來的恐懼，不過到18或36天（長期記憶）之後老鼠已經通通忘光光了。

　　在第二個實驗當中，他們將目標鎖定在一些已知與長期記憶有關的部位，像是前扣帶皮質（anterior cingulated cortex）、內側額葉皮質（medial prefrontal cortex）的prelimbic及infralimbic區域、顳葉（temporal cortex）、視覺皮質（visual cortex）等部位。當正常老鼠在足部刺激的36天之後看到籠子時，其前扣帶皮質區域會產生明顯的活動，而基因改造的老鼠則沒有這樣的現象。

　　第三個實驗當中，他們為正常的老鼠注射某種可以暫時抑制前扣帶皮質活動的藥物，結果顯示前扣帶皮質的不活動的確中斷老鼠回想起18及36天之前對籠子的記憶。

　　種種的證據都指出長期記憶的提取與儲存可能與前扣帶皮質有某種關連。UCLA研究團隊中的一員，Alcino Silva推測前扣帶皮質的功能若不能正常運作，就無法正確地提取出我們的舊回憶，這也許就是發生在癡呆症（dementia）病人身上的狀況。另外CaMKII的活動也被認為與長期記憶的形成有關。這些對長期記憶的研究，也許可以幫忙研發出能夠醫治像阿滋海默症或其他癡呆症等這些記憶相關疾病的藥物。

原始論文：
Paul W. Frankland, et al. The Involvement of the Anterior Cingulate Cortex in Remote Contextual Fear Memory. Science, 7 May 2004: 881-883 .

E. Coli Bacteria Make Alzheimer-Linked Fibers

2004-06-15T13:53:00.000+08:00

Fibers known to be important in Alzheimer disease also are produced by bacteria that cause ailments such as urinary tract infections, according to research at Washington University School of Medicine in St. Louis. The finding is described in the February 1 issue of the journal Science.

Scott J. Hultgren, Ph.D., the Helen Lehbrink Stoever Professor of Molecular Microbiology, led the study; Matthew R. Chapman, Ph.D., post-doctoral fellow in molecular microbiology was first author.

The scientists found that certain strains of the bacterium Escherichia coli (E. coli) produce amyloid fibers similar to those that can accumulate in the brain to form senile plaques, a hallmark of Alzheimer disease. The bacterial fibers, known as curli, form a meshwork around the bacteria, joining them together in clusters or communities known as biofilms. Bacteria in biofilms are more resistant to antibiotics and to the body immune defenses.

The discovery marks the first time that amyloid has been found in bacteria. Previously, amyloid was thought to be made only by cells of higher organisms. Even then, their presence was regarded as a mistake, a biological error.

his is the first example of a dedicated molecular machinery to produce amyloid and thus shows that amyloid production is not always a mistake,?says Hultgren. his finding gives us a powerful genetic system to study the molecular details of amyloid formation and may allow us to begin designing drugs that will block the formation of amyloid or treat or prevent human amyloid diseases.?

Salmonella bacteria also produce bacterial amyloid or curli, and the genes for curli production exist in other bacteria, as well, says Chapman. The process of curli production is similar to the formation of a snowflake on a dust particle. The particle is a nucleus that triggers the precipitation of ice crystals at its surface, setting off a chain reaction that leads to more ice crystals and growth of the snowflake.

Curli production in E. coli involves two main proteins, CsgA and CsgB. The A protein is released by the bacteria dissolved in the surrounding fluid. The B molecule is embedded in the wall of the bacterium and is exposed to the outside. Like dust particles in snowflake production, each B protein is a nucleus that triggers the precipitation of dissolved A-proteins. As the A proteins pop out of solution they join together and align into curli fibers, with each fiber attached to a B protein.

The finding also raises the important question of whether bacterial infections play some role in amyloid diseases, including Alzheimer disease.

Human amyloid diseases also are thought to involve dissolved amyloid proteins that undergo a change in shape and aggregate into fibers, says Hultgren. When those fibers develop in the brain, it leads to Alzheimer disease. According to Hultgren, he question is, what causes the soluble protein in human disease to convert into amyloid fibers? We can now study that mechanism in E. coli.?

Hultgren and Chapman speculate that bacterial infections could play a role in the development of amyloid plaques in Alzheimer disease and other amyloid diseases in at least two ways.

acteria might contribute directly to plaque formation through the amyloid they produce,?says Chapman, r they might contribute indirectly by triggering the precipitation of amyloid precursor proteins already present in the body.?Hultgren and his research team also are working to crystallize the combined A and B proteins to visualize how the two molecules interact.

earning that bacteria produce amyloid is a revelation,?says Paul Berg, Cahill Professor of Cancer Research and Biochemistry, Emeritus, at Stanford University School of Medicine and winner of the 1980 Nobel Prize in Chemistry.

hat discovery provides an additional vantage point from which to assess the role of amyloid production and accumulation in Alzheimer's disease and related neuro-pathologies. Hopefully, this model will reveal clues for preventing the devastating formation of amyloid plaques characteristic of those diseases."

類澱粉蛋白的剋星

2004-06-15T13:52:00.000+08:00

在酵母菌中找到可以對付類澱粉蛋白纖維（amyloid fiber）這個頑劣份子的剋星。

眾所皆知，阿滋海默症（Alzheimer's disease）的患者在其腦部會有類澱粉蛋白質所形成的斑塊。這種斑塊非常的頑強，可以耐高溫又耐寒，甚至在摧毀許多蛋白質的強力清潔劑的威脅之下都不為所動。不過現在這個令人束手無策的情況即將改觀，科學家在酵母菌的體內找到可以制服這個頑劣份子的剋星。

Susan Lindquist與James Shorter已將這個有趣現象所進行的初步研究刊登在《Science》上。

他們發現在酵母菌的體內有一種叫做Sup35的蛋白質，這種蛋白質可以幫助酵母菌將DNA上的密碼轉成氨基酸的序列。Sup35在某些條件之下會形成一種類澱粉蛋白纖維，而且這個類澱粉蛋白纖維與在阿滋海默症病人身上所找到的十分相似。與人類不同的是，這個類澱粉纖維並不會殺死酵母菌，而能與它和平共處。

同時他們也發現在酵母菌當中有另一種稱為Hsp104的蛋白質可以影響Sup35是否能形成類澱粉纖維。如果Hsp104的濃度很高或是根本沒有的時候，Sup35就不會形成類澱粉纖維；若是在Hsp104濃度很低的時候，就會催化這些纖維的產生。而且在Hsp104大量存在的狀況下，Hsp104可以將形成好的類澱粉蛋白纖維拆個粉碎。

另外嚴格來說，Sup35算是一種普恩蛋白（prion），可是Sup35並不像其他普恩蛋白一樣會傷害酵母菌，反而乖乖地在酵母菌體內待很久了，因此他們認為Sup35可能基於某種演化上的因素而保存了下來。再加上環境的變化會影響Hsp104在酵母菌當中的濃度，從而影響不同型態的Sup35形成，也改變了酵母菌體內的生理狀況；而且這個特色可以被一代接著一代的傳遞下去，所以Shorter等人認為這是一個環境引導演化的例子。

原始論文：
James Shorter, Susan Lindquist. Hsp104 Catalyzes Formation and Elimination of Self-Replicating Sup35 Prion Conformers. Science, Published online 25 May 2004.

粒線體突變是老化的元兇！？

2004-06-15T13:50:00.000+08:00

在老鼠進行的一項研究顯示，在粒線體的基因組內發生的突變是老化的元兇？

　　細胞一直都會受到活性氧分子（reactive oxygen species，簡稱ROS）的攻擊，尤其在粒線體把養分轉化成能量之時。躲在細胞核內的DNA可以免受池魚之殃，可是粒線體內的DNA也沒這麼走運，因此會飽受ROS的荼毒。在細胞核內，也有完備的DNA校對修復裝備，可是粒線體內卻缺乏檢查系統，所以任務就只交由一個蛋白質DNA聚合酵素-γ。因此粒線體內的DNA就比細胞核內的DNA來得容易損傷。

　　每個細胞都有成百上千個粒線體，因此科學家推測一個突變要能闖禍，則許多粒線體都有帶有它。在老年人的細胞中，同樣的突變常出現在大部分粒線體中。也有研究顯示一個粒線體內廣泛出現的突變會讓細胞萎縮。不過還是有人懷疑粒線體中隨機累積的突變會造成細胞的浩劫。

　　瑞典卡洛林斯卡學院的Aleksandra Trifunovic等人利用會大量累積粒線體突變的基因轉殖鼠來研究這個問題。他們把正常DNA聚合酵素-γ置換成一個校正效率極差的版本。結果結果這樣的老鼠就特別早死，沒有一隻活超過60週（正常鼠的平均壽命為100週），也在25週的青年期提早出現老化的症狀如體重下降、體質疏鬆、掉毛、貧血、生育力下降等。

　　美國國家環境衛生科學研究所的生化學家Matthew Longley指出，這個實驗提供了強力的證據顯示粒線體DNA突變和老化的密切關聯。西雅圖華盛頓大學的Lawrence A. Loeb和George M. Martin指出，DNA聚合酵素-γ只是其中一個和老化有關的分子而已。他們也表示，如果有辦法設計出一個校對能力超強的粒線體DNA聚合酵素，是否就能延長壽命呢？

原學術論文：
Trifunovic, A. et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417 - 423 (27 May 2004); doi:10.1038/nature02517

運動有助性生活(二)

2004-06-14T12:05:00.000+08:00

出處 : Exercise To Improve Your Sex Life
作者 : Core Holly, DN
譯者 : 雪林

運動在很多方面皆可以讓你的性生活更美滿。第一，使自己瘦一點，你會讓自己感覺更好。當你的身形和姿勢改進之後，你的強度，持久力和你的精力也會隨之改變。運動使你展現好身材。當然正常的性行為也是一種很好的運動。性可以增加呼吸作用，提高心跳頻率，同時改變肌肉的色調。運動再加上營養會比綜合荷爾蒙及處方藥產生更好的效果。
要改善多年以來因不良營養而造成的性功能失調，你必須改善你整體的健康，也就是說你需要運動。運動可以減少卡路里，血壓，增加骨質密度，除去過多的脂肪，保護及對抗所有疾病，幫助你延年益壽。

總括來說，性功能可以是一種感官刺激、記憶、接觸、化學、情緒和心理。性的運作與腦部的特殊部位、神經傳導、氮氣化物的製造、睪丸激素、攝護腺、循環系統、血糖穩定、細胞溝通等皆有關係，而這些種種變數都與營養及運動息息相關。

化學反應下的性(二)

2004-06-14T12:03:00.000+08:00

出處 : Better SEx Through Chemistry
作者 : John Morgenthaler
譯者 : 戴行

上期我們提及了精氨酸、膽素、維生素 B5 和菸鹼酸，這期我們再來看看另外三種營養素會對性產生何種化學作用：
4.Tyrosine 和 Phenylalanine（酥氨酸及苯氨基丙酸）。一些證據顯示，在腦部，神經傳導素度巴胺 (dopamine) 的活動與性行為有關。似乎愈高層級的度巴胺會產生越多的性興趣，反之亦然。 L-Dopa 是一種處方藥，但你可以藉由服用酥氨酸及苯氨基丙酸這兩種無需處方的氨基酸，來製造身體中的 L-Dopa ，增進你腦部度巴胺層級。

5.Yohimbe。 Corynanthe yohimbe 是一植物名，是一種生長在西非洲的樹木，數百年以來，這種民俗藥物一直為當地的部落和西印度群島的部落所應用著，以此樹的內皮蒸餾釀造成茶用以強化男性的精力和性能力。現在大部份的醫學文章著重在討論 yohimbe 與治療性無能間的關係，卻也有一些非科學的證據指出， yohimbe 的使用可以使性行為「好還要更好」。一本專為醫生使用的參考書「 The Physicians Desk Reference 」在描述某種藥物時，也對 yohimbe 有這樣的提及 ﹕「 Yohimbe 有可能會產生引起性慾的活動。」

對這些營養素有興趣的人，不妨請教醫生在不損害身體健康的情況下，始能服用並獲得最高的享受。

US says food from cloned animals is safe

2004-06-11T15:53:00.000+08:00

Meat and milk derived from animal clones is likely to be safe for human consumption, says a draft report by the US Food and Drug Administration. However, a decision on whether to allow the selling of food products from cloned animals will not be made for at least another year.

“Edible products from normal, healthy clones or their progeny do not appear to pose increased food consumption risks relative to comparable products from conventional animals, concludes the draft executive summary.

The FDA’s Center for Veterinary Medicine (CVM) is carrying out two reviews of cloning in cattle, pigs, sheep and goats. One is concentrating on the risk of consumption to humans, while the second focuses on the health risks of cloning to the animals themselves and their offspring.

In the first review, the FDA panel is trying to identify the “subtle hazards” to human health which might have arisen as a result of the nuclear transfer technology used to create clones. Deformed or diseased clones were excluded from their analysis, as these would not enter the human food chain.

Rare breed

Food from clones is unlikely for some time. One estimate puts the number of cloned cattle in the US at a couple of hundred, compared to 100 million normal cattle. And these clones are being used for breeding rather than for food.

"We do not want these products on the market until there has been a thoughtful, thorough and deliberate evaluation of the issues," said Stephen Sundlof, director of CVM, in the FDA Consumer magazine. "We want to make sure that the public is clearly informed and that they have had a chance to participate in the process."

A US National Academy of Sciences' report, commissioned by the FDA, reached a similar conclusion in August 2002: However, the NAS report did highlight adverse effects on animal welfare. For example, many cloned animals can have higher birthweights than normal which can cause difficulty at birth.

Also, consumer groups say the FDA has not considered society's reaction to eating foods derived from cloned animals. "They seem to be shockingly obtuse when it comes to the fact that this ... makes people very uncomfortable," Carol Tucker, of the Consumer Federation of America, told CNN.

大腦如何處理接收到的資訊？

2004-06-11T13:54:00.000+08:00

對於大腦如何處理由數百萬神經細胞傳遞的電子衝動來感知外界訊息一直是科學家極欲探索卻難以了解的問題。加州大學聖地牙哥分校（UCSD）的神經生物學家在5月30號<自然>（Nature)期刊線上版發表了他們的研究成果，對於解開這個謎題提供了一線希望。

　　由於目前普遍認為大腦是透過辨識電子衝動的時間長短和頻率大小來獲得訊息，因此了解大腦中可能參與掌控電路的組織或許能幫助我們對大腦如何處理訊息有進一步的認識。基於這樣的想法，科學家們鎖定大腦皮層中對於大腦電路分析最有直接關連的海馬迴（hippocampus)來作為研究的對象。結果顯示由海馬迴的角錐狀細胞(CA1 pyramidal cell)輸出的電子衝動會經由反覆、週期性的電路抑制來轉化成特殊形式的訊號然後傳遞到其他區域，而有些神經細胞只會對第一次傳達到的訊號做出回應的動作，有的神經細胞則是會對較頻率密集、連續性的訊號產生反應。

　　這樣的結果顯示大腦中的神經細胞在接受訊息上是採用一種分工合作的方式，因此雖然在任何時刻大腦中的任何神經細胞都可能接受到數以萬計的訊號，但是只有特定強弱、頻率的訊號才能對特定種類的神經細胞產生作用。

　　為什麼特定的時間、強弱和頻率這麼重要呢？假設我們現在正跟朋友碰面，然後寒暄、握手，想想看，如果大腦裡的神經細胞對訊號送達的時間沒有區別性的話，那麼可能會先感到和某人握手、寒暄然後才知道原來是和熟悉的朋友碰面的怪異感受。至於訊號強度、頻率則是會對大腦決定做出如何的反應有重要的影響：如果只是輕微的疼痛感那麼我們所產生的瞬間反應就不如巨大的疼痛來的明顯和強烈。這種區分訊號大小的功能能夠幫助我們對訊息的重要性做出判斷並選擇回應的順序。

　　當然，這項以海馬迴當作研究目標的研究成果只顯示了大腦如何處理訊息的一小部分。期待未來陸續會有相關的成果發表來幫助我們早日了解錯綜複雜的大腦！

原始論文：Nature, published online, 30 May 2004(doi:10.1038/nature02615)