國際科技信息

國際科技信息

英首次將人類胚胎干細(xì)胞用于三維打印

英國赫瑞瓦特大學(xué)和一家干細(xì)胞技術(shù)公司合作，開發(fā)出一種真空閥門式（valvebased）三維（3D）打印技術(shù)，首次將3D打印拓展到人類胚胎干細(xì)胞范圍。這一突破使得利用人類胚胎干細(xì)胞來“打造”移植用人體組織和器官成為可能，打印結(jié)構(gòu)還能用于藥物測試，加速改良測試過程。相關(guān)論文發(fā)表在2月5日出版的《生物制造》雜志上。

近幾年來，3D打印的方法已逐漸發(fā)展到生物制造領(lǐng)域。羅斯林 塞拉博干細(xì)胞技術(shù)公司商業(yè)開發(fā)經(jīng)理詹森 金說：“通常，實(shí)驗(yàn)室培養(yǎng)細(xì)胞是在二維平面生長，只有少數(shù)細(xì)胞能用三維打印方式。人類干細(xì)胞太敏感，難以用這種方式來控制。我們是世界上首次將人類胚胎干細(xì)胞打印出來并進(jìn)行培養(yǎng)的?！?/p>

打印過程中的關(guān)鍵問題是可控性和減少傷害，這樣才能保證細(xì)胞與組織的發(fā)育能力和正常功能。人類胚胎干細(xì)胞來自胚胎早期階段產(chǎn)生的“干細(xì)胞系”，沒有明確的發(fā)育方向，可以分化為人體內(nèi)任何類型的細(xì)胞。研究小組開發(fā)出了一種真空閥式細(xì)胞打印機(jī)，細(xì)胞被裝入打印機(jī)的兩個分離容器，然后按預(yù)先編好的程序，被統(tǒng)一打印到一個盤子上。該打印機(jī)充分考慮了人類胚胎干細(xì)胞的敏感性和脆弱性，能打印出具有高度活性的細(xì)胞。

當(dāng)人類胚胎干細(xì)胞被打印出來以后，還要經(jīng)過多項(xiàng)測試，如檢測它們的活性，看其是否還能分化為不同類型細(xì)胞；檢測細(xì)胞的打印密度、特征屬性和分布情況，以此評價(jià)這種打印方法的精確性。

“我們發(fā)現(xiàn)，這種真空閥門打印方式非常溫和，足以保持干細(xì)胞的發(fā)育能力，還能精確打出同樣大小的球體。更重要的是，打印出來的人類胚胎干細(xì)胞保持了它們的多能性，還能分化成其他類型的細(xì)胞?！闭撐暮现?、英國赫瑞瓦特大學(xué)的威爾·文妙·舒（音譯）說：“該方法是用氣壓驅(qū)動來打印細(xì)胞，通過開關(guān)微真空管能控制氣壓，通過改變噴頭直徑、入口氣壓或打開真空管的時(shí)間可以精確控制噴出細(xì)胞的數(shù)量?！?/p>

舒還指出，通過打印人類胚胎干細(xì)胞生成的3D結(jié)構(gòu)，我們能造出更精確的人體組織模型，這對藥物開發(fā)、毒性測試都非常有用，因?yàn)榇蟛糠炙幬镩_發(fā)都是以人類疾病為目標(biāo)，用人類組織來實(shí)驗(yàn)更有意義。

金表示：“這是一次科學(xué)的進(jìn)步。我們希望這一進(jìn)步能帶來長期的巨大價(jià)值，為人們提供可靠的藥物而不必用動物做藥物試驗(yàn)，提供用于移植的器官而無需捐獻(xiàn)，并能消除器官排斥和免疫抑制帶來的問題?！?/p>

3D printing breakthrough with human embryonic stem cells

A team of researchers from Scotland has used a novel 3D printing technique to arrange human embryonic stem cells(hESCs) for the very first time.

It is hoped that this breakthrough, which has been published on 5 February, in the journal Biofabrication, will allow three-dimensional tissues and structures to be created using hESCs, which could, amongst other things, speed up and improve the process of drug testing.

In the field of biofabrication,great advances have been made in recent years towards fabricating three-dimensional tissues and organs by combining artificial solid structures and cells; however, in the majority of these studies, animal cells have been used to test the different printing methods which are used to produce the structures.

Co-author of the study, Dr Will Wenmiao Shu, from Heriot-Watt University, said: "To the best of our knowledge, this is the first time that hESCs have been printed.The generation of 3D structures from hESCs will allow us to create more accurate human tissue models which are essential for in vitro drug development and toxicity-testing. Since the majority of drug discovery is targeting human disease, it makes sense to use human tissues."

In the longer term, this new method of printing may also pave the way for incorporating hESCs into artificially created organs and tissues ready for transplantation into patients suffering from a variety of diseases.

In the study, the researchers,from Heriot-Watt University in collaboration with Roslin Cellab,a stem cell technology company,used a valve-based printing technique, which was tailored to account for the sensitive and delicate properties of hESCs.

The hESCs were loaded into two separate reservoirs in the printer and were then deposited onto a plate in a pre-programmed,uniformed pattern.

Once the hESCs were printed,a number of tests were performed to discern how effective the method was.

For example, the researchers tested to see if the hESCs remained alive after printing and whether they maintained their ability to differentiate into different types of cells. They also examined the concentration, characterisation and distribution of the printed hESCs to assess the accuracy of the valvebased method.

Dr Shu said: "Using this valvebased method, the printed cells are driven by pneumatic pressure and controlled by the opening and closing of a microvalve. The amount of cells dispensed can be precisely controlled by changing the nozzle diameter, the inlet air pressure or the opening time of the valve.

"We found that the valvebased printing is gentle enough to maintain high stem cell viability,accurate enough to produce spheroids of uniform size, and,most importantly, the printed hESCs maintained their pluripotency – the ability to be differentiated into any other cell type."

Roslin Cellab has a track record of applying new technologies to human stem cell systems and will take the lead in developing 3D stem cell printing for commercial uses.

Jason King, business development manager of Roslin Cellab, said: "This world-first printing of human embryonic stem cell cultures is a continuation of our productive partnership with Heriot-Watt. Normally laboratory grown cells grow in 2D but some cell types have been printed in 3D. However,up to now, human stem cell cultures have been too sensitive to manipulate in this way.

英國科學(xué)家攻克磁共振成像新技術(shù)

磁共振成像（MRI）領(lǐng)域的一項(xiàng)新發(fā)現(xiàn)有望提高多發(fā)性硬化癥等腦部疾病的診斷率和監(jiān)測效果。研究人員指出，來自英國諾丁漢大學(xué)彼得 曼斯菲爾德爵士磁共振中心的這一研究成果，可能會為醫(yī)學(xué)界的磁共振成像提供一種新工具。

該項(xiàng)研究發(fā)表在日前出版的美國《國家科學(xué)院院刊》上，它揭示了利用新的磁共振成像技術(shù)生成的腦部圖像為何對神經(jīng)纖維走向如此敏感。

微神經(jīng)纖維以微電子信號的形式傳遞信息，腦白質(zhì)就是由數(shù)以十億計(jì)的微神經(jīng)纖維所構(gòu)成。研究人員指出，每個神經(jīng)纖維都由一種叫髓磷脂的脂肪物質(zhì)包裹著，從而能夠提高這些電子信號的行進(jìn)速度。

此前的研究已經(jīng)表明，磁共振圖像中的腦白質(zhì)外觀取決于神經(jīng)纖維與磁共振成像掃描儀所用極強(qiáng)磁場的方向之間的角度。

利用髓磷脂分子結(jié)構(gòu)方面的知識，諾丁漢大學(xué)的物理學(xué)家發(fā)明了一種新的模型，其中用又長又細(xì)且?guī)в刑厥猓ň哂懈飨虍愋缘模┐判缘目招墓艽砩窠?jīng)纖維。

此模型解釋了圖像對比取決于腦白質(zhì)中的纖維取向，并且也具有從磁共振圖像中推斷出神經(jīng)纖維的尺寸、方向等信息的潛力。

參與該項(xiàng)研究的Samuel Wharton說：“大多數(shù)基于磁共振成像的研究都集中在以毫米為長度單位而進(jìn)行的人體組織測量上，而我們對健康志愿者進(jìn)行的掃描實(shí)驗(yàn)以及由此制作的髓鞘模型都顯示，利用相當(dāng)簡單的成像技術(shù)即可生成尺寸、方向等更為具體的神經(jīng)纖維微觀信息?！彼a(bǔ)充說：“這些結(jié)果將為臨床醫(yī)生提供更多信息，用來識別并確定腦部損傷或異常狀況，也將有助于他們選擇適合某個特殊病人的掃描方法。”

諾丁漢大學(xué)物理學(xué)與天文學(xué)系系主任Richard Bowtell補(bǔ)充說：“對于生物醫(yī)學(xué)成像界而言，這些結(jié)果應(yīng)該能起到重要的推動作用?！?/p>

諾丁漢大學(xué)醫(yī)院信托中心專門研究多發(fā)性硬化癥的臨床副教授Nikolaos Evangelou認(rèn)為：“這項(xiàng)研究開辟了觀察大腦神經(jīng)纖維的多條新途徑。我們越是了解神經(jīng)及其周圍的髓磷脂，就越能在研究多發(fā)性硬化癥等腦部疾病方面取得成功?！?/p>

Evangelou說：“我們最近在了解和治療多發(fā)性硬化癥上取得的進(jìn)展都是基于可靠的基礎(chǔ)研究，其中有一項(xiàng)就是由Wharton博士和Bowtell教授所提供的?！?/p>

研究人員相信，這項(xiàng)研究將使世界各地的科學(xué)家和臨床醫(yī)生更加理解神經(jīng)纖維及其取向差異在磁共振成像中所造成的影響，并且在診斷和監(jiān)測多發(fā)性硬化癥（已知此病與髓磷脂流失有關(guān)）等腦部、神經(jīng)系統(tǒng)疾病方面也有潛在用途。

磁共振成像是利用核磁共振原理，依據(jù)所釋放的能量在物質(zhì)內(nèi)部不同結(jié)構(gòu)環(huán)境中不同的衰減，通過外加梯度磁場檢測所發(fā)射出的電磁波，即可得知構(gòu)成這一物體原子核的位置和種類，據(jù)此可以繪制成物體內(nèi)部的結(jié)構(gòu)圖像。將這種技術(shù)用于人體內(nèi)部結(jié)構(gòu)的成像，就產(chǎn)生出一種革命性的醫(yī)學(xué)診斷工具。快速變化的梯度磁場的應(yīng)用，大大加快了核磁共振成像的速度，使該技術(shù)在臨床診斷、科學(xué)研究的應(yīng)用成為現(xiàn)實(shí)，極大地推動了醫(yī)學(xué)、神經(jīng)生理學(xué)和認(rèn)知神經(jīng)科學(xué)的迅速發(fā)展。

MRI Research Sheds New Light On Nerve Fibers In The Brain

World-leading experts in magnetic resonance imaging(MRI) from The University of Nottingham’s Sir Peter Mansfield Magnetic Resonance Centre have made a key discovery which could give the medical world a new tool for the improved diagnosis and monitoring of neurodegenerative diseases like multiple sclerosis.

The new study, published in the Proceedings of the National Academy of Science, reveals why images of the brain produced using the latest MRI techniques are so sensitive to the direction in which nerve fibers run.

The white matter of the brain is made up of billions of microscopic nerve fibers that pass information in the form of tiny electrical signals. To increase the speed at which these signals travel,each nerve fiber is encased by a sheath of myelin. Previous studies have shown that the appearance of white matter in MRI depends on the angle between the nerve fibers and the direction of the very strong magnetic field used in an MRI scanner.

Based on knowledge of the molecular structure of myelin, the Nottingham physicists devised a new model in which the nerve fibers are represented as long thin hollow tubes with anisotropic magnetic properties. This model explains the dependence of image contrast on fiber orientation in white matter and potentially allows information about the nerve fibers(such as their size and direction)to be inferred from magnetic resonance images.

Research Fellow Dr Samuel Wharton said: “While most MRI-based research focuses on tissue measurements at the millimeter length scale, our experimental scans on healthy human volunteers and modeling of the myelin sheath shows that much more detailed microscopic information relating to the size and direction of nerve fibers can be generated using fairly simple imaging techniques. The results will give clinicians more context in which to recognize and identify lesions or abnormalities in the brain and will also help them to tailor different types of scan to a particular patient.”

Dr Nikolaos Evangelou,Clinical Associate Professor specializing in multiple sclerosis at the Nottingham University Hospitals Trust said: "This research opens new avenues of looking at the nerve fibers in the brain. The more we understand about the nerves and the myelin around them, the more successful we are in studying brain diseases, such as multiple sclerosis [MS]. The recent advances in our understanding and treatments of MS are based on basic, solid research such as the one presented by Dr Wharton and Bowtell.”

The research will give scientists and clinicians all over the world a better understanding of the effects of nerve fibers and their orientation in MRI and has potentially useful applications in the diagnosis and monitoring of brain and nervous system diseases like multiple sclerosis where there are known links to myelin loss.

美英開發(fā)出拉伸時(shí)可變色的新纖維

近日，美國哈佛大學(xué)和英國?？巳卮髮W(xué)材料科學(xué)家開發(fā)出一種結(jié)構(gòu)獨(dú)特的新纖維，能在拉伸時(shí)改變顏色，色彩可覆蓋整個可見光譜的范圍。纖維柔韌有彈性，本身還可作為一種智能材料感知熱和壓力。相關(guān)論文在線發(fā)表于最近的《先進(jìn)材料》雜志上。

這一靈感是模仿一種生長在南美洲熱帶的果實(shí)，俗稱奇異豬莓。該果營養(yǎng)價(jià)值很低，外表卻極漂亮，呈現(xiàn)明亮的幻彩藍(lán)。研究人員解釋說，許多生物能在地球上成功生存下來，就是靠著它們的光色搭配。對于種子和果實(shí)來說，進(jìn)化出明亮的顏色可以吸引播種媒介，尤其是鳥類。奇異豬莓的色彩極為誘人，是為了模仿另一種營養(yǎng)多肉的果實(shí)，欺騙鳥類來吃它們以把種子傳播到更遠(yuǎn)。

研究人員切開了奇異豬莓果實(shí)，從納米尺度詳細(xì)分析其結(jié)構(gòu)組成，發(fā)現(xiàn)種皮上層細(xì)胞是一種曲線形的多層重復(fù)排列，且每一層都是圓柱形的層狀結(jié)構(gòu)，這種結(jié)構(gòu)通過光波干涉產(chǎn)生了顏色，類似于肥皂泡的反光原理。首席研究員、埃克塞特大學(xué)自然光子學(xué)副教授彼得 武庫?？普f：“這種能控制光線的結(jié)構(gòu)性表層，是進(jìn)化為一種專門生理功能服務(wù)的表現(xiàn)，激發(fā)了我們的技術(shù)設(shè)計(jì)。”

“新纖維就是模仿這一自然結(jié)構(gòu)，我們對其進(jìn)一步設(shè)計(jì)后，使這種結(jié)構(gòu)特性進(jìn)一步發(fā)揮了出來?！闭撐念I(lǐng)導(dǎo)作者、哈佛工程與應(yīng)用科學(xué)學(xué)院博士后馬西亞斯·科勒說，“當(dāng)然植物不能改變顏色。但我們把這種結(jié)構(gòu)和一種彈性材料結(jié)合在一起，新的人造纖維就能在拉伸過程中展現(xiàn)出彩虹般變換的顏色。”

為了模仿這一關(guān)鍵結(jié)構(gòu)，他們創(chuàng)造了一種新的卷制方法，用多層高分子聚合物包裹玻璃芯，隨后再將玻璃芯腐蝕掉。

科勒說：“我們用了很細(xì)的纖維，用一種高分子聚合物雙分子層包裹它們，這就產(chǎn)生了折射率對比，在層數(shù)和彎曲程度恰當(dāng)?shù)那闆r下，圓柱截面就會產(chǎn)生鮮艷的色彩?！?/p>

這種工藝還可以擴(kuò)大規(guī)模，用于工業(yè)化生產(chǎn)。“我們的纖維卷制技術(shù)還可用于廣泛的材料，尤其是彈性材料，色彩調(diào)節(jié)范圍超過現(xiàn)有的任何熱延展纖維一個數(shù)量級?！闭撐暮现?、哈佛工程與應(yīng)用科學(xué)學(xué)院材料科學(xué)教授喬安娜 艾森伯格說。

研究人員還指出，這種纖維除了色彩亮麗可變以外，還有極佳的力學(xué)性質(zhì)，適用范圍極廣。

比如利用其延展性可以包覆各種復(fù)雜的形狀。由于纖維在不同張力下會呈現(xiàn)不同的色彩，其本身可作為一種智能型體育紡織品，在肌肉緊張程度不同的地方顯出不同顏色，或用于感知物體因受熱后的張力變化。

Color-tunable photonic fibers mimic the fruit of the 'bastard hogberry'plant

A team of materials scientists at Harvard University and the University of Exeter, UK, have invented a new fiber that changes color when stretched. Inspired by nature, the researchers identified and replicated the unique structural elements that create the bright iridescent blue color of a tropical plant's fruit.

The multilayered fiber,described today in the journal Advanced Materials, could lend itself to the creation of smart fabrics that visibly react to heat or pressure.

"Our new fiber is based on a structure we found in nature,and through clever engineering we've taken its capabilities a step further," says lead author Mathias Kolle, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences (SEAS). "The plant,of course, cannot change color. By combining its structure with an elastic material, however, we've created an artificial version that passes through a full rainbow of colors as it's stretched."

Since the evolution of the first eye on Earth more than 500 million years ago, the success of many organisms has relied upon the way they interact with light and color,making them useful models for the creation of new materials. For seeds and fruit in particular, bright color is thought to have evolved to attract the agents of seed dispersal,especially birds.

The fruit of the South American tropical plant,Margaritaria nobilis, commonly called "bastard hogberry," is an intriguing example of this adaptation. The ultra-bright blue fruit, which is low in nutritious content, mimics a more fleshy and nutritious competitor. Deceived birds eat the fruit and ultimately release its seeds over a wide geographic area.

"The fruit of this bastard hogberry plant was scientifically delightful to pick," says principal investigator Peter Vukusic, Associate Professor in Natural Photonics at the University of Exeter. "The light-manipulating architecture its surface layer presents, which has evolved to serve a specific biological function, has inspired an extremely useful and interesting technological design."

Vukusic and his collaborators at Harvard studied the structural origin of the seed's vibrant color.

They discovered that the upper cells in the seed's skin contain a curved, repeating pattern, which creates color through the interference of light waves. (A similar mechanism is responsible for the bright colors of soap bubbles.) The team's analysis revealed that multiple layers of cells in the seed coat are each made up of a cylindrically layered architecture with high regularity on the nano- scale.

The team replicated the key structural elements of the fruit to create flexible, stretchable and color-changing photonic fibers using an innovative rollup mechanism perfected in the Harvard laboratories.

復(fù)活滅絕酶揭示物種進(jìn)化創(chuàng)新功能

我們能生存下來，是因?yàn)槲覀兊淖嫦瘸晒Φ剡m應(yīng)了所處環(huán)境的變化。

但物種在進(jìn)化中是如何創(chuàng)新的？據(jù)物理學(xué)家組織網(wǎng)近日報(bào)道，一個由比利時(shí)弗蘭德斯生物技術(shù)研究所（VIB）、美國哈佛大學(xué)等多個單位的研究人員組成的國際小組，通過重建一種史前酵母菌細(xì)胞的DNA（脫氧核糖核酸）和蛋白質(zhì)，直接檢查了進(jìn)化的驅(qū)動力是如何通過一億年的作用，塑造了現(xiàn)代酶的。相關(guān)論文在線發(fā)表于《公共科學(xué)圖書館·生物學(xué)》上。

新基因的一個最大來源，就是已有基因在復(fù)制中的偶然變異。隨后，變異副本會不斷編碼合成最初的酶，執(zhí)行它們早期的功能。酶是一種生物催化劑，讓生物能操控分子按照自己的意愿行事。雖然也有其他一些酶不必經(jīng)過基因突變，也能執(zhí)行新功能，但相比之下，這兩種新酶可能在更細(xì)分的功能上有所不同。

在進(jìn)化過程中，這種創(chuàng)新模式已經(jīng)發(fā)生過千萬次，但人們對該模式是如何發(fā)生的還不太清楚。僅考察現(xiàn)有生物，會限制人們對實(shí)際進(jìn)化過程的理解，因?yàn)橐恍┻M(jìn)化的關(guān)鍵事件會被億萬年漫長的時(shí)間所覆蓋，我們需要的是一部“時(shí)間機(jī)器”。

研究人員“復(fù)活”了古代酵母菌的基因，并集中研究由這些基因編碼合成的酶的進(jìn)化，考察酶的進(jìn)化怎樣讓酵母菌在一億年里不斷擴(kuò)展它們的食物源。

最初的酶讓酵母菌細(xì)胞在進(jìn)化初期靠吃麥芽糖而生存，但基因復(fù)制的改變產(chǎn)生了新的酶，它們就有可能去吃環(huán)境中那些以前不能吃的糖。

“我們用測序重建算法預(yù)測了祖先遺留下來的古老基因的DNA序列，這些遺留基因從幾十個現(xiàn)在DNA序列中取得。由此我們能重建相應(yīng)的古老蛋白質(zhì)，將它們和現(xiàn)代蛋白質(zhì)進(jìn)行比較?！盫IB植物系統(tǒng)生物學(xué)系斯蒂芬·馬利說。

“復(fù)活”這些酶也意味著，研究人員能構(gòu)建出一幅有關(guān)該酶的詳細(xì)原子結(jié)構(gòu)圖，直接測定它們分解其他糖類的能力。利用這些信息，就能推導(dǎo)出該酶的特性是怎樣變化的，進(jìn)化怎樣使它們達(dá)到最優(yōu)化。

“我們的研究目標(biāo)非常具體，就是酵母菌怎樣進(jìn)化成能分解多種糖類的。我們發(fā)現(xiàn)，最初的基因，也就是為那些消化麥芽糖的蛋白質(zhì)編碼的基因，在進(jìn)化過程中被復(fù)制了許多次，某些副本DNA有了輕微改變，導(dǎo)致產(chǎn)生了新蛋白質(zhì)，能分解不同的糖類。通過模擬相應(yīng)蛋白質(zhì)中的這些改變，現(xiàn)在我們理解了DNA中一些很小的改變，也會導(dǎo)致全新功能的蛋白質(zhì)產(chǎn)生。”VIB系統(tǒng)生物學(xué)實(shí)驗(yàn)室的卡琳 沃戴科說。

研究人員認(rèn)為，酵母細(xì)胞開拓糖源的事件，也反映了物種在進(jìn)化創(chuàng)新中廣泛采用的一種策略。沃戴科說：“具有新功能的DNA不會憑空出現(xiàn)，但卻能在已有的DNA功能片斷的復(fù)制中，逐漸得到加強(qiáng)。通過重建史前的、曾在進(jìn)化過程中被多次復(fù)制過的DNA片斷，我們能詳細(xì)考察每個副本所發(fā)生的改變，它們怎樣逐漸發(fā)展出了新功能。我們的研究提供了獨(dú)特的視角，讓人們能看到達(dá)爾文進(jìn)化論的詳細(xì)分子細(xì)節(jié)。”

Resurrection of extinct enzymes reveals evolutionary strategy for the invention of new functions

How does evolution innovate? We exist because our ancestors have had the ability to adapt successfully to changes in their environment; however, merely examining present-day organisms can limit our understanding of the actual evolutionary processes because the crucial events have been masked by the passage of aeons – what we need is a time machine. Scientists from VIB, KU Leuven, University of Ghent and Harvard have done the next-best thing; by reconstructing DNA and proteins from prehistoric yeast cells, they were able to directly examine the evolutionary forces that have acted over the last 100 million years to shape modern-day enzymes – biological catalysts that enable organisms to manipulate molecules to their will.

The scientists set out to explore how new genes emerge,how they contribute to the survival of the evolving organism, and how,after a humble start, evolution then refines the function of new genes and hones the efficiency of the enzymes that they encode. One of the richest sources of such new genes is the chance duplication of existing genes. One copy of the gene can then continue to encode the original enzyme, allowing it to perform its original task, while the other is free to change and to perhaps take on a new function;alternatively, the two new enzymes might sub-divide the original task.

Although this pattern of innovation is known to have happened many thousands of times during evolution, the way in which it occurs hasn't been clear.In a paper published December 11 in the online Open Access journal PLOS Biology, Karin Voordeckers,Chris Brown and Kevin Verstrepen from VIB in Leuven, together with Steven Maere from VIB and the University of Ghent, tackled this problem, focusing their attention on the evolution of enzymes that have allowed yeast to exploit changing food sources over the last 100 million years of evolution.

The scientists 'resuscitated'ancestral yeast genes, allowing them to examine the properties of enzymes that existed tens of millions of years ago. The original enzyme originally enabled the yeast cells to survive on a diet of maltose, a common sugar, but duplications of their genes gave rise to new enzymes which opened up the possibility of feeding off other types of sugar in the environment.The resurrection of these enzymes meant that the scientist could build up a detailed picture of their atomic structure and directly determine their ability to break down different types of sugars. Armed with this information, they could work out exactly how the enzymes had changed their specificity and how evolution drove their optimisation.

科學(xué)家實(shí)現(xiàn)近室溫條件下單分子存儲

近日，一個由美國麻省理工大學(xué)、印度科學(xué)教育研究院等單位科學(xué)家組成的國際小組，對以往的“分子存儲”實(shí)驗(yàn)技術(shù)進(jìn)行了改良，使其能在攝氏零度左右運(yùn)行，并使制造工藝大大簡化。相關(guān)論文發(fā)表在《自然》雜志網(wǎng)站上。

上世紀(jì)80年代時(shí)，硬盤每平方英寸只能存半兆字節(jié)，現(xiàn)在已接近百萬兆。

如果能實(shí)現(xiàn)單分子存儲，有望使存儲密度再提高1000倍。但以往的技術(shù)要求物理系統(tǒng)在接近絕對零度下工作，而且存儲設(shè)備是一種“三明治”式夾層結(jié)構(gòu)，由兩層鐵磁電極夾一層存儲分子構(gòu)成，制造工藝復(fù)雜而耗時(shí)。

改良后的存儲設(shè)備制造工藝大大簡化。其存儲分子由印度研究人員開發(fā)，用的是“石墨烯片”，即一層平面碳分子層附著鋅原子構(gòu)成，互相之間天然具有整齊排列在一起的性質(zhì)。該設(shè)備只有一個鐵磁電極，相當(dāng)于半個“三明治”，通過沉積法就能形成非常薄且排列整齊的原子層。

電極設(shè)備由麻省理工大學(xué)雅格戴斯·穆德拉小組開發(fā)。

最初，他們是在鐵磁電極上沉積了一層薄膜材料，然后在上面再加一層鐵磁電極，做成磁性存儲器的標(biāo)準(zhǔn)結(jié)構(gòu)。按照設(shè)想，通過相對改變電極的磁性方向，會使設(shè)備的導(dǎo)電性產(chǎn)生跳變，而這兩種導(dǎo)電狀態(tài)就分別代表了二進(jìn)制中的0和1。但令人吃驚的是，他們檢測到導(dǎo)電性發(fā)生了兩個跳變而不是一個，這表明兩個電極各自獨(dú)立改變了設(shè)備的導(dǎo)電性。他們又用一個鐵磁電極和一個普通金屬電極進(jìn)行了實(shí)驗(yàn)，普通金屬電極只是為了讀取通過分子的電流，結(jié)果發(fā)現(xiàn)導(dǎo)電性跳變依然存在。

為此他們改變了設(shè)計(jì)。制造一個存儲單元時(shí)，其底層電極用沉積法，形成幾乎完美的一層，然后鋪上存儲分子，頂層電極設(shè)計(jì)成一個微小針尖，就像原子力顯微鏡尖端的探針那樣，在存儲分子上占不到1納米。穆德拉解釋說，如果上面再沉積一層鐵磁電極，電極分子就傾向于和存儲分子混合，會削弱其性能。而且為防止存儲單元之間靠得太近而彼此影響，他們用堆疊式存儲克服了壓縮密度的限制。

“在近室溫下表現(xiàn)出導(dǎo)電性的轉(zhuǎn)變，這一效果來自分子與磁性表面之間的強(qiáng)相互作用，能讓分子有磁性并保持穩(wěn)定?！蹦碌吕牟┦可?、麻省理工大學(xué)材料科學(xué)與工程系的卡西克·拉曼說。

目前，他們造出的實(shí)驗(yàn)性存儲設(shè)備導(dǎo)電性雖然只改變了20%，還不足以用作商業(yè)設(shè)備，但穆德拉表示，這還只是概念性論證。

他們提出的理論解釋了人們未曾預(yù)料的單電極轉(zhuǎn)換現(xiàn)象，經(jīng)過進(jìn)一步研究有望設(shè)計(jì)出新的有機(jī)分子，使導(dǎo)電性變化率更高。

Storing data in individual molecules: Molecular memory near room temperature

Moore's law—the wellknown doubling of computer chips'computational power every 18 months or so—has been paced by a similarly steady increase in the storage capacity of disk drives.In 1980, a hard drive could store about a half-megabyte of data in a square inch of disk space; now,manufacturers are closing in on a million megabytes of data per square inch.

An experimental technology called molecular memory, which would store data in individual molecules, promises another 1,000-fold increase in storage density. But previous schemes for molecular memory have relied on physical systems cooled to near absolute zero. In the Jan. 23 online edition of Nature, an international team of researchers led by Jagadeesh Moodera, a senior research scientist in the MIT Department of Physics and at MIT's Francis Bitter Magnet Laboratory, describes a new molecular-memory scheme that works at around the freezing point of water—which in physics parlance counts as "room temperature."

Moreover, where previous schemes required sandwiching the storage molecules between two ferromagnetic electrodes, the new scheme would require only one ferromagnetic electrode. That could greatly simplify manufacture,as could the shape of the storage molecules themselves: because they consist of flat sheets of carbon atoms attached to zinc atoms, they can be deposited in very thin layers with very precise arrangements.

The storage molecules were developed by chemists at the Indian Institute of Science Education and Research in Kolkata, who are co-authors on the Nature paper.The Indian chemists believed that the molecules could be useful for the type of experimental devices studied by Moodera's group,which use "spin," a property of tiny particles of matter, to represent data.

Half a sandwich

Under Moodera's supervision, Karthik Raman, then a PhD student in MIT's Department of Materials Science and Engineering and now a scientist at IBM's Research Lab in India, and Alexander Kamerbeek, a visiting student from the University of Groningen, deposited a thin film of the material on a ferromagnetic electrode and added a second ferromagnetic electrode on top—the standard structure for magnetic memories. The idea is that a relative change in the electrodes'magnetic orientations causes a sudden jump in the device's conductivity. The two states of conductivity represent the 1s and 0s of binary logic.

To their surprise, however, the MIT researchers measured not one but two jumps in conductivity. That implied that the electrodes were changing the device's conductivity independently. "According to the common knowledge, this shouldn't happen," Moodera says.

美首次實(shí)現(xiàn)兩相斥離子環(huán)永久互連

近日，美國西北大學(xué)的科研人員開發(fā)出一種方式，能夠制成新型的自由基化合物：他們第一次將通常情況下會相互排斥的兩個相同的陽離子環(huán)永久地連接起來，而這被許多科學(xué)家稱之為不可能完成的任務(wù)。

從表面來看，這些環(huán)應(yīng)該“憎恨”彼此，因?yàn)樗鼈兠總€都攜帶了4個正電荷。

但通過引入自由基，即化合物分子在光熱等外界條件下，共價(jià)鍵發(fā)生均裂而形成的具有不成對電子的原子或基團(tuán)，科學(xué)家能夠營造出“愛恨交織”的關(guān)系，并最終以陽離子環(huán)的“愛戀”互連作為結(jié)果。

不成對的電子需要進(jìn)行配對以呈現(xiàn)出穩(wěn)定狀態(tài)，同時(shí)研究人員也證明，一個環(huán)的單電子對另一環(huán)單電子的吸引力要比它們之間的排斥力更強(qiáng)。這個過程能利用機(jī)械鍵合而不是化學(xué)鍵合把陽離子環(huán)連接起來，因而能夠一次到位，不易被撕扯開來。

有關(guān)這類新型穩(wěn)定的有機(jī)自由基的研究報(bào)告已發(fā)表在1月25日出版的《科學(xué)》雜志上。

該?；瘜W(xué)系教授弗雷澤斯圖達(dá)特說：“人們并非在兩個環(huán)的連接嘗試中以失敗告終，而是他們從不認(rèn)為那可能實(shí)現(xiàn)。但現(xiàn)在，我們做到了。”事實(shí)上，斯圖達(dá)特正是上世紀(jì)80年代將機(jī)械鍵合引入化合物的早期先驅(qū)者之一。

作為論文的第一作者，喬納森 巴恩斯嘗試的第一種策略是臨時(shí)增加電子以減少電荷，并使兩個環(huán)連接起來，而其在首次嘗試時(shí)就奏效了。當(dāng)化合物被氧化并失去電子時(shí)，強(qiáng)大的正向力將卷土重來。雖然“憎恨”一直都在，但兩個環(huán)卻自此難以分開。

誠然，大多數(shù)有機(jī)自由基都只能存活很短時(shí)間，但這種新型自由基化合物卻能在空氣和水中穩(wěn)定存在?；衔锪铍娮釉诮Y(jié)構(gòu)內(nèi)隱藏起來，因此它們無法與外界環(huán)境發(fā)生任何反應(yīng)。機(jī)械鍵合亦十分耐受，盡管存在著不利的靜電反應(yīng)。

科學(xué)家稱，新型化合物不僅具有引人注目的電子特性，還能夠?qū)崿F(xiàn)快速的低成本制造。兩個互鎖環(huán)也能在數(shù)納米的空間內(nèi)容納巨大的電荷量，或能擴(kuò)展成長鏈狀的聚合物?；衔飫t能從6種氧化態(tài)中擇一，總共接受多達(dá)8個電子。因此，這也將有助于電池、半導(dǎo)體和電子存儲設(shè)備制造的技術(shù)改進(jìn)。

Exotic new chemical compound could be useful in batteries,semiconductors, electronic memory devices

Northwestern University graduate student Jonathan Barnes had a hunch for creating an exotic new chemical compound, and his idea that the force of love is stronger than hate proved correct.He and his colleagues are the first to permanently interlock two identical tetracationic rings that normally are repelled by each other. Many experts had said it couldn't be done.

On the surface, the rings hate each other because each carries four positive charges (making them tetracationic). But Barnes discovered by introducing radicals(unpaired electrons) onto the scene, the researchers could create a love-hate relationship in which love triumphs.

Unpaired electrons want to pair up and be stable, and it turns out the attraction of one ring's single electrons to the other ring's single electrons is stronger than the repelling forces.

The process links the rings not by a chemical bond but by a mechanical bond, which, once in place, cannot easily be torn asunder.

The study detailing this new class of stable organic radicals will be published Jan. 25 by the journal Science.

"It's not that people have tried and failed to put these two rings together—they just didn't think it was possible," said Sir Fraser Stoddart, a senior author of the paper. "Now this molecule has been made. I cannot overemphasize Jonathan's achievement—it is really outside the box. Now we are excited to see where this new chemistry leads us."

Sir Fraser is the Board of Trustees Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. In the late 1980s, he was one of the early pioneers to introduce an additional type of bond, the mechanical bond,into chemical compounds.

The new Northwestern compound has attractive electronic characteristics and can be made quickly and inexpensively. Down the road, it may be possible to expand this first linked pair into a longer chain-like polymer where this methodology could be useful in new technologies for batteries,semiconductors and electronic memory devices.

Driven by curiosity, Barnes only began to look at the radical chemistry of the ring cyclobis(paraquat-p-phenylene) two years ago, nearly 25 years after the ring was first made.

"I wondered what would happen if we took it all the way to the max," said Barnes, the paper's first author and a member of Stoddart's group. "Can we take two of these rings, each with four positive charges, and make them live together?"

The rings repel each other like the positive poles of two magnets.Barnes saw an opportunity where he thought he could tweak the chemistry by using radicals to overcome the hate between the two rings.

"We made these rings communicate and love each other under certain conditions,and once they were mechanically interlocked, the bond could not be broken," Barnes said.

Barnes' first strategy—adding electrons to temporarily reduce the charge and bring the two rings together—worked the first time he tried it. He, Stoddart and their colleagues started with a full ring and a half ring that they then closed up around the first ring (using some simple chemistry), creating the mechanical bond.

When the compound is oxidized and electrons lost, the strong positive forces come roaring back—"It's hate on all the time,"Barnes said—but then it is too late for the rings to be parted. "That's the beauty of this system," he added.

高分子薄膜緩釋技術(shù)或成為疫苗接種新方法

據(jù)麻省理工學(xué)院新聞網(wǎng)1月28日報(bào)道，該校研究人員日前開發(fā)出一種類似于膏藥的疫苗，這種疫苗通過高分子薄膜的方式輸送藥物，可提高DNA疫苗的有效性。相關(guān)論文1月27日發(fā)表在《自然·材料學(xué)》雜志網(wǎng)絡(luò)版上。

疫苗通常由滅活病毒制成，通過刺激人體免疫系統(tǒng)的方式，幫助免疫系統(tǒng)建立屏障阻止病毒感染。然而，這種方法對于艾滋病等病毒而言過于危險(xiǎn)。近年來，為開發(fā)出更加有效和安全的疫苗，許多科學(xué)家在探索制造DNA疫苗。

大約20年前，科學(xué)家發(fā)現(xiàn)，一種DNA編碼的病毒蛋白能夠在嚙齒動物中引起強(qiáng)烈的免疫反應(yīng)，但在人體上一直無法復(fù)制。直到不久前，一種被稱為電穿孔的方法在DNA疫苗的接種上獲得了一些突破。這種方法首先需要在皮下注射DNA，然后再用電極產(chǎn)生電場，促使皮膚細(xì)胞膜打開小空隙，允許DNA進(jìn)入。然而，這個過程較為痛苦，接種結(jié)果也存在不確定性。

新研究采用了不同的方法將DNA傳遞到皮膚當(dāng)中，這種疫苗由多層被植入DNA的高分子材料組成。高分子薄膜上有若干個微型針頭，貼在皮膚上時(shí)能夠滲入皮膚中大約半毫米，這種深度足以使藥物進(jìn)入表皮細(xì)胞，又不會接觸到真皮層的神經(jīng)末梢，因此不會引發(fā)疼痛。一旦被貼在皮膚上后，薄膜就會逐漸降解，疫苗的釋放過程從數(shù)天到數(shù)周不等。

研究人員可通過控制高分子薄膜層數(shù)的方法控制DNA的投遞量，還能夠通過控制高分子薄膜遇水分解的速度來控制用藥時(shí)間。由于這種方法增加了DNA與免疫系統(tǒng)之間的交互時(shí)間，因此也提高了疫苗的有效性。在小鼠實(shí)驗(yàn)中，研究人員發(fā)現(xiàn)新方法接種效果優(yōu)于電穿孔法。下一步，他們還將在類靈長動物上開展進(jìn)一步的實(shí)驗(yàn)。

研究人員稱，這種疫苗貼用于多種疾病的免疫，因?yàn)镈NA序列可以很容易按照不同疾病的需要進(jìn)行轉(zhuǎn)化。與蛋白質(zhì)疫苗相比，其優(yōu)勢在于，每個蛋白質(zhì)都有其特殊性，在生產(chǎn)和接種效果上都存在不確定性，但DNA的行為始終是相同的，不管它采用怎樣的抗原編碼。

負(fù)責(zé)該項(xiàng)研究的麻省理工學(xué)院生物工程和材料學(xué)教授達(dá)雷爾 歐文說，如果這種疫苗能夠在人體試驗(yàn)中獲得成功，將會讓接種疫苗的方式發(fā)生巨大改變。由于不再需要注射器并能夠在室溫下儲存，疫苗的使用和運(yùn)輸將更加安全。此外，針對皮膚中豐富的免疫細(xì)胞、可生物降解的緩釋材料的使用、無痛接種也是這種疫苗接種方式的優(yōu)勢?！斑@是一種有趣的方法，不但適用于接種基于DNA的病毒抗原，也適用于其他小分子的傳輸。”歐文說。

A safer way to vaccinate

Vaccines usually consist of inactivated viruses that prompt the immune system to remember the invader and launch a strong defense if it later encounters the real thing. However, this approach can be too risky with certain viruses, including HIV.

In recent years, many scientists have been exploring DNA as a potential alternative vaccine.About 20 years ago, DNA coding for viral proteins was found to induce strong immune responses in rodents, but so far, tests in humans have failed to duplicate that success.

In a paper appearing in the Jan. 27 online issue of Nature Materials, MIT researchers describe a new type of vaccine-delivery film that holds promise for improving the effectiveness of DNA vaccines. If such vaccines could be successfully delivered to humans, they could overcome not only the safety risks of using viruses to vaccinate against diseases such as HIV, but they would also be more stable, making it possible to ship and store them at room temperature.

This type of vaccine delivery would also eliminate the need to inject vaccines by syringe, says Darrell Irvine, an MIT professor of biological engineering and materials science and engineering.“You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin,” he says.

Irvine and Paula Hammond,the David H. Koch Professor in Engineering, are the senior authors of the Nature Materials paper. Both are members of MIT’s David H.Koch Institute for Integrative Cancer Research. The lead author of the paper is Peter DeMuth, a graduate student in biological engineering.

Gradual vaccine delivery

Scientists have had some recent success delivering DNA vaccines to human patients using a technique called electroporation.This method requires first injecting the DNA under the skin, then using electrodes to create an electric field that opens small pores in the membranes of cells in the skin, allowing DNA to get inside.However, the process can be painful and give varying results,Irvine says.

“It's showing some promise but it's certainly not ideal and it's not something you could imagine in a global prophylactic vaccine setting, especially in resource-poor countries,” he says.

Irvine and Hammond took a different approach to delivering DNA to the skin, creating a patch made of many layers of polymers embedded with the DNA vaccine.These polymer films are implanted under the skin using microneedles that penetrate about half a millimeter into the skin — deep enough to deliver the DNA to immune cells in the epidermis, but not deep enough to cause pain in the nerve endings of the dermis.

Once under the skin, the films degrade as they come in contact with water, releasing the vaccine over days or weeks. As the film breaks apart, the DNA strands become tangled up with pieces of the polymer, which protect the DNA and help it get inside cells.

The researchers can control how much DNA gets delivered by tuning the number of polymer layers. They can also control the rate of delivery by altering how hydrophobic (water-fearing) the film is. DNA injected on its own is usually broken down very quickly,before the immune system can generate a memory response.When the DNA is released over time, the immune system has more time to interact with it, boosting the vaccine’s effectiveness.

The polymer film also includes an adjuvant — a molecule that helps to boost the immune response. In this case, the adjuvant consists of strands of RNA that resemble viral RNA, which provokes inflammation and recruits immune cells to the area.