Centrosome misorientation reduces stem cell division during ageing

Jun Cheng1,5, Nezaket Türkel2,5,6, Nahid Hemati2,5, Margaret T. Fuller4, Alan J. Hunt1 & Yukiko M. Yamashita2,3

1. Department of Biomedical Engineering, Center for Ultrafast Optical Science
2. Life Sciences Institute, Center for Stem Cell Biology,
3. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
4. Departments of Developmental Biology and Genetics, Stanford University, School of Medicine, Stanford, California 94305, USA
5. These authors contributed equally to this work.
6. Present address: Peter MacCallum Cancer Centre, Anatomy and Cell Biology Department, University of Melbourne, Melbourne, Victoria 3002, Australia.

Correspondence to: Yukiko M. Yamashita2,3 Correspondence and requests for materials should be addressed to Y.M.Y. (Email: yukikomy@umich.edu).

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Abstract

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.

No more third time lucky

NIH clamps down on proposal resubmissions.

Heidi Ledford

The US National Institutes of Health (NIH) announced last week that biomedical researchers will be able to amend and resubmit a failed funding application only once. Applicants whose grants are unfunded after the second submission may reapply only after designing a new proposal.

New law threatens Italian research jobs

Scientists protest over government's cost cutting.

Emiliano Feresin & Alison Abbott

Nearly 2,000 Italian researchers will lose promised permanent positions under a law that is expected to come into force by the end of the year. They may have to leave public research altogether.

Computer circuit builds itself

Organic molecules organize themselves to form a bridge between electrodes.

Geoff Brumfiel
Flexible circuitsComputer circuits made from organic molecules could be used to build lightweight, flexible displays.ASSOCIATED PRESS

A team of European physicists has developed an integrated circuit that can build itself. The work, appearing in this week's Nature1, is an important step towards its ultimate goal — a self-assembling computer.

Today's computer chips are made by etching patterns onto semiconducting wafers using a combination of light and photosensitive chemicals. But the technique is being pushed to the limit as ever more processing power is being packed onto chips, requiring engineers to etch details just a few tens of nanometres across. So scientists are hunting for alternative ways to assemble even tinier chips.

“We dump it in a beaker with a solution of the molecules, we take it out, we wash it, and it works.”

Dago de Leeuw
Philips Research Laboratories, the Netherlands

Letting them build themselves is, in many ways, the most obvious solution, says Dago de Leeuw, a researcher at Philips Research Laboratories in Eindhoven, the Netherlands. "The nicest example is DNA," he says. Our genetic code provides a set of instructions that can be used to marshal molecules into an entire person, and researchers would like to come up with a similar set of compounds able to organize each other into circuits.

That's no small task. To make a circuit that is truly self-assembling, physicists would need to get insulators, conducting electrodes and semiconductor transistors to all link to each other automatically — something that is still a long way away, says de Leeuw.
Chip 'n dip

But his team has made an important step. They took a long organic molecule with mobile electrons, called quinquethiophene, that behaves like a semiconductor and attached it to a long carbon chain with a silicon group at the end, which acts an an anchor.

“Self-assembly and nanotechnology is certainly cool, but the one thing missing is higher performance.”

Hagen Klauk
Max Planck Institute for Solid State Research, Germany

The researchers then dunked a circuit board with preprinted electrodes into a solution of their new molecules. The molecules hooked on to an insulating layer between the electrodes, forming bridges from one electrode to the next. It took billions to make the connection, but they were tightly packed enough that a current could flow across them. "The different molecules are like little bricks," says Edsger Smits, another researcher at Philips. "Frankly it worked much better than we expected."

The team used the technique to construct a simple circuit that generates a code based on an input voltage. Although the system depends on the preprinted electrodes to act as a template, the circuit is truly self-assembling, says de Leeuw: "We dump it in a beaker with a solution of the molecules, we take it out, we wash it, and it works."

The new technique is impressive but still needs improvement, says Hagen Klauk, an electrical engineer at the Max Planck Institute for Solid State Research in Stuttgart, Germany. "Self-assembly and nanotechnology is certainly cool, but the one thing missing is higher performance," he says. The mobility of electrons through the circuit, he explains, means that the transistors would make for a very slow computer.

Klauk hopes that improving the characteristics of the molecules and tweaking the technique will eventually lead to self-assembling circuits that out-perform existing technologies, which use thick films of organic molecules.

For his part, de Leeuw says the next step will be figuring out a way to develop self-assembling electrodes. In the meantime, however, he says the group's circuits may already have a use. Because the bridge of molecules is very thin, it is extraordinarily sensitive to passing particles. The team believes that it could be used to develop sensors for different kinds of airborne material, such as pathogens or dangerous chemicals.

Flying The Anti-Porn Skies

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Web Video Marketing TV™ Opening Local Marketing Offices Nationwide

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Business web video marketing has quickly become the advertising and marketing medium of choice for all businesses, and business video directories are where all businesses and professionals need to post their videos for maximum web exposure. The viral nature of web video produces tremendous marketing results at a price far below any other advertising or marketing.

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The Web Video Marketing TV offices will be owned and operated by local entrepreneurs who will also be the exclusive local sales agents for the many business video websites that make up Channels Video Network. The owners of the local Web Video Marketing TV will receive comprehensive training to prepare to provide the highest level of video marketing services. The local agency offices will operate in conjunction with Channels Video Network through an exclusive joint venture agreement where the local agent provides sales and customer service and Channels Video Network provides the web infrastructure, technical services, and all other aspects of web operations.

McCain caught in DMCA flap

YouTube denies special treatment to candidate

Written by Shaun Nichols in San Francisco

Video-sharing site YouTube has declined to give special treatment to Republican presidential candidate John McCain over digital millenium copyright act (DMCA) claims.

In an exchange of letters, the site and McCain's campaign staff engaged in a debate over the controversial law, which requires web sites to take down content which contains copyrighted material at the request of the copyright holder in order. McCain voted to approve the DMCA in 1998.

The issue surrounds campaign videos produced by McCain which contained clips from broadcasts by Fox News. The network contended that McCain was illegally using is copyrighted broadcasts in the advertisements and filed a DMCA claim to have the video clips removed from the internet.

McCain's campaign sent a letter to YouTube asking the site to allow the clips to remain online while it was determined whether the videos constituted fair use, a series of protections which allows individuals to use copyrighted clips under certain circumstances. Earlier this year, US courts decided that copyright holders had the responsibility to consider fair use before filing a DMCA takedown claim.

The campaign contended that because the clips were brief and non-commercial in nature, they fell under the protections of fair use and as such should not be removed. The letter also suggested that the site extend special protections to political campaigns which would allow for a more thorough review before clips could be removed due to a DMCA claim.



YouTube countered in a letter contending that if the site complied with the campaign's request, it could lose the DMCA protections which shield sites from lawsuits. The site also said that, given the amount of video uploads it receives on a regular basis, it could not make special concessions to isolate and protect campaign videos.

"The fact remains that we do not know who uploaded what content in user vid eos, who uploaded the videos or what authorization the uploader may or may not have to use that content," read the letter.

"Moreover, while we agree with you that the US presidential election-related content is invaluable and worthy of the highest level of protection, there is a lot of other content on our global site that our users find to be equally important, including political campaigns from around the world at all levels of government, human rights movements, and other important voices."