Alzheimer's disease protein controls movement in mice

June 21, 2013 ? Researchers in Berlin and Munich, Germany and Oxford, United Kingdom, have revealed that a protein well known for its role in Alzheimer's disease controls spindle development in muscle and leads to impaired movement in mice when the protein is absent or treated with inhibitors. The results, which are published in The EMBO Journal, suggest that drugs under development to target the beta-secretase-1 protein, which may be potential treatments for Alzheimer's disease, might produce unwanted side effects related to defective movement.

Alzheimer's disease is the most common form of dementia found in older adults. The World Health Organization estimates that approximately 18 million people worldwide have Alzheimer's disease. The number of people affected by the disease may increase to 34 million by 2025. Scientists know that the protein beta-secretase-1 or Bace1, a protease enzyme that breaks down proteins into smaller molecules, is involved in Alzheimer's disease. Bace1 cleaves the amyloid precursor protein and generates the damaging Abeta peptides that accumulate as plaques in the brain leading to disease. Now scientists have revealed in more detail how Bace1 works.

"Our results show that mice that lack Bace1 proteins or are treated with inhibitors of the enzyme have difficulties in coordination and walking and also show reduced muscle strength," remarked Carmen Birchmeier, one of the authors of the paper, Professor at the Max-Delbr?ck-Center for Molecular Medicine in Berlin, Germany, and an EMBO Member. "In addition, we were able to show that the combined activities of Bace1 and another protein, neuregulin-1 or Nrg1, are needed to sustain the muscle spindles in mice and to maintain motor coordination."

Muscle spindles are sensory organs that are found throughout the muscles of vertebrates. They are able to detect how muscles stretch and convey the perception of body position to the brain. The researchers used genetic analyses, biochemical studies and interference with pharmacological inhibitors to investigate how Bace1 works in mice. "If the signal strength of a specific form of neuregulin-1 known as IgNrg1 is gradually reduced, increasingly severe defects in the formation and maturation of muscle spindles are observed in mice. Furthermore, it appears that Bace1 is required for full IgNrg1 activity. The graded loss of IgNrg1 activity results in the animals having increasing difficulties with movement and coordination," says Cyril Cheret, the first author of the work.

Drug developers are interested in stopping the Bace1 protein in its tracks because it represents a promising route to treat Alzheimer's disease. If the protein were inhibited, it would interfere with the generation of the smaller damaging proteins that accumulate in the brain as amyloid plaques and would therefore provide some level of protection from the effects of the disease. "Our data indicate that one unwanted side effect of the long-term inhibition of Bace1 might be the disruption of muscle spindle formation and impairment of movement. This finding is relevant to scientists looking for ways to develop drugs that target the Bace1 protein and should be considered," says Birchmeier. Several Bace1 inhibitors are currently being tested in phase II and phase III clinical trials for the treatment of Alzheimer's disease.

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The above story is reprinted from materials provided by European Molecular Biology Organization, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Cyril Cheret, Michael Willem, Florence R Fricker, Hagen Wende, Annika Wulf-Goldenberg, Sabina Tahirovic, Klaus-Armin Nave, Paul Saftig, Christian Haass, Alistair N Garratt, David L Bennett, Carmen Birchmeier. Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles. The EMBO Journal, 2013; DOI: 10.1038/emboj.2013.146

Note: If no author is given, the source is cited instead.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/sHLWL8aBr_0/130621132645.htm

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Research confirms: people who wear glasses are perceived as ...

GREEN BAY, WI ? Most people today who have worn glasses know the stereotype that comes with donning a pair of specs. Green Bay psychology major Miranda Demars embarked on a research study to see if that stereotype holds true.

?We wanted to know just purely on a first-impression basis whether these people thought in a stereotypical way, based on whether or not they wore glasses,? she said.

Demars and her team showed 49 participants different pictures of the exact same models with or without glasses. The participants then gave every picture a rating based on intelligence, trustworthiness, employability, friendliness and attractiveness.

The study shows individuals who were wearing glasses in the photos were perceived as more intelligent and trustworthy. But those identical individuals pictured without glasses were perceived as more attractive. The study showed glasses did not have a significant impact on someone?s employability or friendliness.

Demars says her findings have useful applications for college students keen to make the best first impression. ?It really depends on what look you?re going for,? she said. ?If you?re going on a date, maybe you want to take the glasses off. If you?re going to class or have a job interview, or you are going to court, you might want to wear the glasses.?

Students around campus were questioned what they see when they look at someone with glasses.

?I don?t think it?s that big of a deal. I think because I wear them, I think, if you need them, you need them,? a sophomore said. ?I think people see individuals without glasses as more appealing. Sometimes I do feel like I feel differently when I do not wear glasses,? Elena, a sophomore, said. Demars says while first impressions might hold true, it?s a excellent idea to look beyond someone?s glasses.

Demars was one of several UW ? Green Bay psychology students who presented their research at the Midwest Psychological Association convention in Chicago last week. She says she would like to broaden her research to show whether the participants also wore glasses and whether that created a bias.

Source: http://referenceandeducation.4ove.com/2013/06/22/research-confirms-people-who-wear-glasses-are-perceived-as-being-more-intelligent/

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What farm bill's failure says about immigration reform in the House (CNN)

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Particle accelerator that can fit on a tabletop opens new chapter for science research

June 20, 2013 ? Physicists at The University of Texas at Austin have built a tabletop particle accelerator that can generate energies and speeds previously reached only by major facilities that are hundreds of meters long and cost hundreds of millions of dollars to build.

"We have accelerated about half a billion electrons to 2 gigaelectronvolts over a distance of about 1 inch," said Mike Downer, professor of physics in the College of Natural Sciences. "Until now that degree of energy and focus has required a conventional accelerator that stretches more than the length of two football fields. It's a downsizing of a factor of approximately 10,000."

The results, which were published this week in Nature Communications, mark a major milestone in the advance toward the day when multi-gigaelectronvolt (GeV) laser plasma accelerators are standard equipment in research laboratories around the world.

Downer said he expects 10 GeV accelerators of a few inches in length to be developed within the next few years, and he believes 20 GeV accelerators of similar size could be developed within a decade.

Downer said that the electrons from the current 2 GeV accelerator can be converted into "hard" X-rays as bright as those from large-scale facilities. He believes that with further refinement they could even drive an X-ray free electron laser, the brightest X-ray source currently available to science.

A tabletop X-ray laser would be transformative for chemists and biologists, who could use the bright X-rays to study the molecular basis of matter and life with atomic precision, and femtosecond time resolution, without traveling to a large national facility.

"The X-rays we'll be able to produce are of femtosecond duration, which is the time scale on which molecules vibrate and the fastest chemical reactions take place," said Downer. "They will have the energy and brightness to enable us to see, for example, the atomic structure of single protein molecules in a living sample."

To generate the energetic electrons capable of producing these X-rays, Downer and his colleagues employed an acceleration method known as laser-plasma acceleration. It involves firing a brief but intensely powerful laser pulse into a puff of gas.

"To a layman it looks like low technology," said Downer. "All you do is make a little puff of gas with the right density and profile. The laser pulse comes in. It ionizes that gas and makes the plasma, but it also imprints structure in it. It separates electrons from the ion background and creates these enormous internal space-charge fields. Then the charged particles emerge right out of the plasma, get trapped in those fields, which are racing along at nearly the speed of light with that laser pulse, and accelerate in them."

Downer compared it to what would happen if you threw a motorboat into a lake with its engines churning. The boat (the laser) makes a splash, then creates a wave as it moves through the lake at high speed. During that initial splash some droplets (charged particles) break off, get caught up in the wave and accelerate by surfing on it.

"At the other end of the lake they get thrown off into the environment at incredibly high speeds," said Downer. "That's our 2 GeV electron beam."

Former UT Austin physicist Toshiki Tajima and the late UCLA physicist John Dawson conceived the idea of laser-plasma acceleration in the late 1970s. Scientists have been experimenting with this concept since the early 1990s, but they've been limited by the power of their lasers. As a result the field had been stuck at a maximum energy of about 1 GeV for years.

Downer and his colleagues were able to use the Texas Petawatt Laser, one of the most powerful lasers in the world, to push past this barrier. In particular the petawatt laser enabled them to use gases that are much less dense than those used in previous experiments.

"At a lower density, that laser pulse can travel faster through the gas," said Downer. "But with the earlier generations of lasers, when the density got too low, there wasn't enough of a splash to inject electrons into the accelerator, so you got nothing out. This is where the petawatt laser comes in. When it enters low density plasma, it can make a bigger splash."

Downer said that now that he and his team have demonstrated the workability of the 2 GeV accelerator, it should be only a matter of time until 10 GeV accelerators are built. That threshold is significant because 10 GeV devices would be able to do the X-ray analyses that biologists and chemists want.

"I don't think a major breakthrough is required to get there," he said. "If we can just keep the funding in place for the next few years, all of this is going to happen. Companies are now selling petawatt lasers commercially, and as we get better at doing this, companies will come into being to make 10 GeV accelerator modules. Then the end users, the chemists and biologists, will come in, and that will lead to more innovations and discoveries."

Source: http://feeds.sciencedaily.com/~r/sciencedaily/matter_energy/physics/~3/9LhwOQQGWK8/130620132412.htm

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Plants 'seen doing quantum physics'

21 June 2013 Last updated at 05:26 ET By Jason Palmer Science and technology reporter, BBC News

The idea that plants make use of quantum physics to harvest light more efficiently has received a boost.

Plants gather packets of light called photons, shuttling them deep into their cells where their energy is converted with extraordinary efficiency.

A report in Science journal adds weight to the idea that an effect called a "coherence" helps determine the most efficient path for the photons.

Experts have called the work "a nice proof" of some contentious ideas.

Prior work has shown weaker evidence that these coherences existed in relatively large samples from plants.

But the new study has been done painstakingly, aiming lasers at single molecules of the light-harvesting machinery to show how light is funnelled to the so-called reaction centres within plants where light energy is converted into chemical energy.

What has surprised even the researchers behind the research is not only that these coherences do indeed exist, but that they also seem to change character, always permitting photons to take the most efficient path into the reaction centres.

Until very recently, quantum mechanics - a frequently arcane branch of physics most often probed in laboratory settings at the coldest temperatures and lowest pressures - would not have been expected in biological settings.

The fact that plants and animals are extremely warm and soft by comparison would suggest that delicate quantum states should disappear in living things, leaving behaviour explicable by the more familiar "classical physics" that is taught in school.

But the new results join the ranks of a field that seems finally to be gaining ground: quantum biology.

'Something shocking'

Niek van Hulst of the Institute of Photonic Sciences in Castelldefels, Spain, and colleagues studied the light-harvesting complexes of purple bacteria to address the question.

Continue reading the main story

The weird world of quantum mechanics

Quantum mechanics starts with the simple idea that energy does not come in just any amount; it comes in discrete chunks, called quanta. But deeper into the theory, some truly surprising - and useful - effects crop up

• Superposition: A particle exists in a number of possible states or locations simultaneously - strictly, an electron might be in the tip of your finger and in the furthest corner of the Universe at the same time. It is only when we observe the particle that it 'chooses' one particular state
• Entanglement: Two particles can become entangled so that their properties depend on each other - no matter how far apart they get. A measurement of one seems to affect the measurement of the other instantaneously - an idea even Einstein called "spooky"
• Tunnelling: A particle can break through an energy barrier, seeming to disappear on one side of it and reappear on the other. Lots of modern electronics and imaging depends on this effect

These are literally like antennas that gather up light, and are arranged like adjacent rings.

When laser light is shone on just one isolated ring, some of it is re-released in the form of what is called fluorescence.

But what the team saw is that over time, that amount of fluorescence rose and fell - a sign that the energy was coming and going elsewhere: a coherence.

This is linked to the quantum mechanical notion of a "superposition": that a particle can effectively be in multiple places at once - or try multiple paths simultaneously.

"What you see here is this photon comes in, and it sees many energy pathways," explained Prof van Hulst.

"Where does it go? It goes to the one that's most efficient, the one where this quantum effect tells you it has the highest probability (of being put to use)," he told BBC News.

But the soft, flexible, warm conditions at room temperature mean that, as things move and jiggle - as life tends to do - that most efficient path can change. Remarkably, so did the evident path along the rings.

"Nature is very robust at keeping this up no matter what happens - this for me is something shocking," Prof van Hulst continued.

"The result is that this fluffy stuff at room temperature where everything is variable, it just works - with an efficiency of 90%: way, way better than any solar cell we can make ourselves."

'Several questions'

Rienk van Grondelle of the Free University Amsterdam called the work "a very nice proof that the ideas that existed about these coherences are actually correct".

"The system is able to overcome this problem by sampling two or three of those pathways at the same time and simply use the one that is best - I think it's very, very beautiful," he told BBC News.

Other researchers are less convinced. Daniel Turner of the University of Toronto has been working on similar problems and says that the study's primary proof - the comings and goings of the fluorescence - are "not necessarily directly relevant to how photosynthesis works in natural conditions".

"There are still several questions regarding how the results of this and other? measurements of highly purified protein extracts relate to the natural sunlight conditions experienced by photosynthetic organisms," he told BBC News.

Even the notion of what is meant by "quantum effects" in relation to biology, he said, was still up for debate.

But for Prof van Grondelle, the paper is another impressive addition to this debate.

"Of course (the acceptance of quantum effects in biology) is not going to come from one single paper," he said.

"It will take more evidence, and maybe more elaborate evidence that this is really happening. But this is how science goes."

Source: http://www.bbc.co.uk/news/science-environment-22996054#sa-ns_mchannel=rss&ns_source=PublicRSS20-sa

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Senators closing in on border security compromise

WASHINGTON (AP) ? White House-backed immigration legislation is gaining momentum in the Senate, where key lawmakers say they are closing in on a bipartisan compromise to spend tens of billions of dollars stiffening the bill's border security requirements without delaying legalization for millions living in the country unlawfully.

"This is a key moment in the effort to pass this bill. This is sort of the defining 24 to 36 hours," Sen. Lindsey Graham, R-S.C., said Wednesday night after a day of private talks.

Under the emerging compromise, the government would grant legal status to immigrants living in the United States unlawfully at the same time the additional security was being put into place. Green cards, which signify permanent residency status, would be withheld until the security steps were complete.

Officials described a so-called border surge that envisions doubling the size of the Border Patrol with 20,000 new agents, constructing hundreds of miles of additional fencing along the border with Mexico and purchasing new surveillance drones to track would-be illegal border crossers. The cost of the additional agents alone was put at $30 billion over a decade.

Other details were not immediately available, although it was expected that modifications to the bill would range far beyond border security provisions. The changes under consideration were the result of negotiations involving the bipartisan Gang of Eight who drafted the bill and Republicans seeking alterations before they would commit to voting for it.

The officials spoke on the condition of anonymity because the talks were private.

If agreed to, the changes could clear the way for a strong bipartisan vote within a few days to pass the measure that sits atop President Barack Obama's second-term domestic agenda.

The developments came as Democrats who met with House Speaker John Boehner on Wednesday quoted him as saying he expected the House to pass its own version of an immigration bill this summer and Congress to have a final compromise by year's end.

Boehner, R-Ohio, already has said the legislation that goes to the House in the next month or two will not include a pathway to citizenship for immigrants in the United States illegally.

Precise details of the pending agreement in the Senate were unavailable, but Sen. John Hoeven, R-N.D., said it involved a major increase of resources to the border, including more manpower, fencing and technology. The underlying legislation already envisions more border agents; additional fencing along the U.S-Mexico border; surveillance drones; a requirement for employers to verify the legal status of potential workers; and a biometric system to track foreigners who enter and leave the United States at air and seaports and by land.

It was unclear what other portions of the legislation might be changed. There is pressure from some Republicans to make sure no federal benefits go to immigrants who are in the country illegally, at least until they become citizens.

"Our whole effort has been to build a bipartisan group that will support the bill," said Hoeven, who has not yet stated a position on the legislation. "That's what this is all about, and it's focused on border security."

Sen. Chuck Schumer, D-N.Y., one of the bill's most prominent supporters, said discussions with Republicans "have been really productive. We've made a lot of progress in the last 24 hours. Now we have some vetting to do with our respective allies."

The potential compromise came into focus one day after the Congressional Budget Office jolted lawmakers with an estimate saying that as drafted, the legislation would fail to prevent a steady increase in the future in the number of residents living in the United States illegally.

The estimate appeared to give added credibility to Republicans who have been pressing Democrats to toughen the border security provisions already written into the bill. Schumer and Sen. Bob Menendez, D-N.J., met at midday with Graham, Hoeven and Sen. Bob Corker, R-Tenn. The Democrats and Graham are part of Gang of Eight.

If ratified, the compromise would mark concessions on both sides.

Some Republicans have been unwilling to support a bill that grants legal status to immigrants in the country illegally until the government certifies that the border security steps have achieved 90 percent effectiveness in stopping would-be border crossers.

On the other hand, Democrats have opposed Republican proposals to make legalization contingent on success in closing the border to illegal crossings. Under the legislation as drafted, legalization could begin as soon as a security plan was drafted, but a 10-year wait is required for a green card.

One plan to change that was sidetracked on a vote of 61-37.

Sen. Rand Paul, R-Ky., said his proposal would require Congress to vote annually for five years on whether the border is secure. If lawmakers decide it is not, "then the processing of undocumented workers stops until" it is, he said. The decision would be made based on numerous factors, including progress toward completion of a double-layered fence along the U.S.-Mexico border and toward a goal of 95 percent capture of illegal entrants. A system to track the border comings and goings of foreigners is also required.

While the public debate was taking place, lawmakers involved in the private talks expressed optimism.

Across the Capitol, House Republican leaders sought to present a friendlier face to Hispanics ? a group that gave Obama more than 70 percent support in last year's presidential election.

Boehner met with the Democratic-dominated Congressional Hispanic Caucus, while rank-and-file members of his party reviewed areas of agreement with Latino religious leaders.

"It's a conversation Republicans want to have," Rep. Cathy McMorris Rodgers, R-Wash., said later at a news conference outside the Capitol.

Separately, the House Judiciary Committee approved legislation creating a program allowing farm workers to come to the United States to take temporary jobs in the United States.

The measure is one of several that the panel is considering in the final weeks of June as part of a piece-by-piece approach to immigration rather than the all-in-one bill that Senate is considering.

___

Associated Press writer Laurie Kellman contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/89ae8247abe8493fae24405546e9a1aa/Article_2013-06-20-US-Immigration/id-557a29f2f5ca48ff8c1af2b96935fc6a

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Video: DreamWorks CEO's 'Really Good Arrangement' With Netflix

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