Finding a family for a pair of orphan receptors in the brain

Wednesday, May 22, 2013

Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological diseases.

The results are published in the Proceedings of the National Academy of Sciences, Early Edition.

The human genome is littered with orphans: proteins that look like they will bind and respond to a hormone or a brain chemical, based on the similarity of their sequences to other proteins. However, scientists haven't figured out what each orphan's partner chemical is yet.

Orphans that look like GPCRs (G protein-coupled receptors) currently number about 100. GPCRs are the targets of many drugs and are involved in vision, smell and brain cells' responses to a host of hormones and neurotransmitters. One orphan GPCR, called GPR37, has attracted interest from researchers because it is connected with an inherited form of Parkinson's disease. It is abundant in the dopamine-producing neurons that degenerate in Parkinson's. But its partner chemical, or "ligand," has not been found.

"We reasoned that GPR37 had to be doing something important, besides becoming misfolded in some forms of Parkinson's," says senior author Randy Hall, PhD, professor of pharmacology at Emory University School of Medicine.

Working with Hall, graduate student Rebecca Meyer devised a way to detect when cells producing GPR37 were reacting with GPR37's ligand.

"Usually, cells remove GPCRs from their surfaces when they encounter their ligand," Meyer says. "So we set things up so that GPR37 would be labeled red on the surface of the cell, but would appear green once internalized."

They discovered that cells producing GPR37 ? and also a close relative, GPR37L1 -- respond to a protein known as prosaposin, which was discovered by John O'Brien of University of California San Diego in the 1990s.

Prosaposin is a growth factor for brain cells and protects them from stress. Scientists studying it had worked out that it stimulates cells via a GPCR ? but which one was unclear until now. In animal models, prosaposin has shown potential for treating conditions such as stroke, Parkinson's and neuropathic pain. An artificial fragment of prosaposin called prosaptide has been tested in clinical studies, but it quickly breaks down in the body.

"That's the reason why it was so important to find the receptor," Hall says. "Then we can actually do some pharmacology."

Now, Hall's laboratory is planning to look for other compounds that can activate GPR37 as well. These could be more stable in the body than the previously studied protein fragment and thus better potential drugs.

Doctors have reported a few cases of genetic deficiency in prosaposin, leading to severe neurodegeneration. Mice engineered to lack GPR37 have more subtle brain perturbations, so Hall also plans to test the hypothesis that prosaposin acts by both GPR37 and GPR37L1, by "knocking out" both in mice, potentially duplicating the same severe effects seen in the human cases of prosaposin deficiency.

###

Emory Health Sciences: http://whsc.emory.edu/home/news/index.html

Thanks to Emory Health Sciences for this article.

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Source: http://www.labspaces.net/128351/Finding_a_family_for_a_pair_of_orphan_receptors_in_the_brain

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Baby's life saved with groundbreaking 3-D printed device that restored his breathing

May 22, 2013 ? Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions weren't true.

"Quite a few doctors said he had a good chance of not leaving the hospital alive," says April Gionfriddo, about her now 20-month-old son, Kaiba. "At that point, we were desperate. Anything that would work, we would take it and run with it."

They found hope at the University of Michigan, where a new, bioresorbable device that could help Kaiba was under development. Kaiba's doctors contacted Glenn Green, M.D., associate professor of pediatric otolaryngology at the University of Michigan.

Green and his colleague, Scott Hollister, Ph.D., professor of biomedical engineering and mechanical engineering and associate professor of surgery at U-M, went right into action, obtaining emergency clearance from the Food and Drug Administration to create and implant a tracheal splint for Kaiba made from a biopolymer called polycaprolactone.

On February 9, 2012, the specially-designed splint was placed in Kaiba at C.S. Mott Children's Hospital. The splint was sewn around Kaiba's airway to expand the bronchus and give it a skeleton to aid proper growth. Over about three years, the splint will be reabsorbed by the body. The case is featured today in the New England Journal of Medicine.

"It was amazing. As soon as the splint was put in, the lungs started going up and down for the first time and we knew he was going to be OK," says Green.

Green and Hollister were able to make the custom-designed, custom-fabricated device using high-resolution imaging and computer-aided design. The device was created directly from a CT scan of Kaiba's trachea/bronchus, integrating an image-based computer model with laser-based 3D printing to produce the splint.

"Our vision at the University of Michigan Health System is to create the future of health care through discovery. This collaboration between faculty in our Medical School and College of Engineering is an incredible demonstration of how we achieve that vision, translating research into treatments for our patients," says Ora Hirsch Pescovitz, M.D., U-M executive vice president for medical affairs and CEO of the U-M Health System.

"Groundbreaking discoveries that save lives of individuals across the nation and world are happening right here in Ann Arbor. I continue to be inspired and proud of the extraordinary people and the amazing work happening across the Health System."

Kaiba was off ventilator support 21 days after the procedure, and has not had breathing trouble since then.

"The material we used is a nice choice for this. It takes about two to three years for the trachea to remodel and grow into a healthy state, and that's about how long this material will take to dissolve into the body," says Hollister.

"Kaiba's case is definitely the highlight of my career so far. To actually build something that a surgeon can use to save a person's life? It's a tremendous feeling."

The image-based design and 3D biomaterial printing process can be adapted to build and reconstruct a number of tissue structures. Green and Hollister have already utilized the process to build and test patient specific ear and nose structures in pre-clinical models. In addition, the method has been used by Hollister with collaborators to rebuild bone structures (spine, craniofacial and long bone) in pre-clinical models.

Severe tracheobronchomalacia is rare. About 1 in 2,200 babies are born with tracheomalacia and most children grow out of it by age 2 or 3, although it often is misdiagnosed as asthma that doesn't respond to treatment.

Severe cases, like Kaiba's, are about 10 percent of that number. And they are frightening, says Green. A normal cold can cause a baby to stop breathing. In Kaiba's case, the family was out at a restaurant when he was six weeks old and he turned blue.

"Severe tracheobronchomalacia has been a condition that has bothered me for years," says Green. "I've seen children die from it. To see this device work, it's a major accomplishment and offers hope for these children."

Before the device was placed, Kaiba continued to stop breathing on a regular basis and required resuscitation daily.

"Even with the best treatments available, he continued to have these episodes. He was imminently going to die. The physician treating him in Ohio knew there was no other option, other than our device in development here," Green says.

Kaiba is doing well and he and his family, including an older brother and sister, live in Ohio.

"He has not had another episode of turning blue," says April. "We are so thankful that something could be done for him. It means the world to us."

Source: http://feeds.sciencedaily.com/~r/sciencedaily/strange_science/~3/Ez9mfi50NQA/130522180102.htm

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Senate panel approves immigration bill

Senate Judiciary Committee Chairman Sen. Patrick Leahy, D-Vt., right, confers with the committee's ranking Republican, Sen. Chuck Grassley, R-Iowa, on Capitol Hill in Washington, Monday, May 20, 2013, as the committee assembles to work on a landmark immigration bill to secure the border and offer citizenship to millions. The panel is aiming to pass the legislation out of committee this week, setting up a high-stakes debate on the Senate floor. (AP Photo/J. Scott Applewhite)

Senate Judiciary Committee Chairman Sen. Patrick Leahy, D-Vt., right, confers with the committee's ranking Republican, Sen. Chuck Grassley, R-Iowa, on Capitol Hill in Washington, Monday, May 20, 2013, as the committee assembles to work on a landmark immigration bill to secure the border and offer citizenship to millions. The panel is aiming to pass the legislation out of committee this week, setting up a high-stakes debate on the Senate floor. (AP Photo/J. Scott Applewhite)

Senate Judiciary Committee members Sen. Chuck Schumer, D-N.Y., left, and Sen. Richard Durbin, D-Ill. confer on Capitol Hill in Washington, Monday, May 20, 2013, as the committee assembled to work on a landmark immigration bill to secure the border and offer citizenship to millions. The panel is aiming to pass the legislation out of committee this week, setting up a high-stakes debate on the Senate floor. (AP Photo/J. Scott Applewhite)

WASHINGTON (AP) ? Far-reaching legislation to grant a chance at citizenship to millions of immigrants living illegally in the United States cleared the Senate Judiciary Committee on a solid bipartisan vote Tuesday night after supporters somberly sidestepped a controversy over the rights of gay spouses.

The 13-5 vote cleared the way for an epic showdown on the Senate floor on the measure, which is one of President Barack Obama's top domestic priorities yet also gives the Republican Party a chance to recast itself as more appealing to minorities.

The committee's action sparked rejoicing from immigration activists who crowded into a Senate committee room to witness the proceedings. "Yes, we can!" they shouted as they clapped rhythmically to show their pleasure.

In addition to creating a pathway to citizenship for 11.5 million immigrants, the legislation creates a new program for low-skilled foreign labor and would permit highly skilled workers into the country at far higher levels than is currently the case.

At the same time, it requires the government to take costly new steps to guard against future illegal immigration.

There was suspense to the end of the committee's deliberations, when Sen. Patrick Leahy, the Vermont Democrat who serves as chairman, sparked a debate over his proposal to give same-sex and heterosexual spouses equal rights under immigration law.

"I don't want to be the senator who asks people to choose between the love of their life and the love of their country," he said, adding he wanted to hear from others on the committee.

In response, he heard a chorus of pleas from the bill's supporters, seconding private appeals from the White House, not to force a vote that they warned would lead to the bill's demise.

"I believe in my heart of hearts that what you're doing is the right and just thing," said one of them, Sen. Richard Durbin, D-Ill. "But I believe this is the wrong moment, that this is the wrong bill."

In the hours leading to a final vote, the panel also agreed to a last-minute compromise covering an increase in the visa program for high-tech workers, a deal that brought Sen. Orrin Hatch, R-Utah over to the ranks of supporters.

Under the compromise, the number of highly skilled workers admitted to the country would rise from 65,000 annually to 110,000, with the possibility of a further rise to 180,000, depending in part on unemployment levels.

Firms where foreign labor accounts for at least 15 percent of the skilled work force would be subjected to tighter conditions than companies less dependent on H-IB visa holders.

The compromise was negotiated by Hatch, whose state is home to a growing high tech industry, and Sen. Chuck Schumer, D-N.Y. It is designed to balance the interests of industry, which relies increasingly on skilled foreign labor, and organized labor, which represents American workers.

AFL-CIO President Rich Trumka attacked the deal sharply as "anti-worker," although he also made clear organized labor would continue to support the overall legislation.

Robert Hoffman, senior vice president for government affairs at the Information Technology Industry Council, welcomed the deal. "We obviously want to keep moving the bill forward and building support for the legislation, and this agreement allows us to do so," he said.

The issue of same-sex spouses hovered in the background from the start, and as the committee neared the end of its work, officials said Leahy had been informed that both the White House and Senate Democrats hoped he would not risk the destruction of months of painstaking work by putting the issue to a vote.

"There have been 300 amendments. Why shouldn't we have one more?" he told reporters at one point, hours before called the committee into session for a final time to debate the legislation.

A few hours later, Republicans and Democrats both answered his question bluntly.

"This would fracture the coalition. I could not support the bill," said Sen. Lindsey Graham, R-S.C., who was a member of the bipartisan so-called Gang of Eight that drafted the core elements of the bill.

Republicans and Democrats alike also noted that the Supreme Court may soon issue a ruling that renders the controversy moot.

Despite the concern that bipartisan support for the legislation was fragile, there was no doubting the command over committee proceedings that backers held.

In a final reminder, an attempt by Sen. Ted Cruz., R-Texas, to delete the pathway to citizenship failed on a 13-5 vote.

In defeat, he and others said they, too, wanted to overhaul immigration law, but not the way that drafters of the legislation had done.

Sen. Charles Grassley, R-Iowa, recalled that he had voted to give "amnesty" to those in the country illegally in 1986, the last time Congress took a major look at immigration. He said that bill, like the current one, promised to crack down on illegal immigration, but said it had failed to do so.

The centerpiece provision of the legislation allows an estimated 11 million people living in the U.S. illegally to obtain "registered provisional immigrant status" six months after enactment if certain conditions are also met.

Applicants must have arrived in the United States before Dec. 31, 2011, and maintained continuous physical presence, must not have a felony conviction of more than two misdemeanors on their record, and pay a $500 fine.

The registered provisional immigrant status lasts six years and is renewable for another $500. After a decade, though, individuals could seek a green card and lawful permanent resident status if they are up to date on their taxes and pay a $1,000 fine and meet other conditions.

Individuals brought to the country as youths would be able to apply for green cards in five years.

___

AP White House Correspondent Julie Pace contributed to this report.

Associated Press

Source: http://hosted2.ap.org/apdefault/495d344a0d10421e9baa8ee77029cfbd/Article_2013-05-21-Immigration/id-34ebee79b5af4fc1a13749fc0f8e63f1

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Flickr Shows Signs of Life With Slick Web Redesign, Killer Android App

Flickr wants to remind you that it’s a photo site. “Everything that we’ve done in this new redesign has been about putting the photo front and center,” says Flickr VP Brett Wayn. For a photo site, Flickr looks like it ...

Source: http://www.wired.com/gadgetlab/2013/05/flickr-update-android/

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Myanmar leader making landmark White House visit

FILE - In this Nov. 19, 2011 file photo, President Barack Obama, left, stands next to Myanmar President Thein Sein during a group photo session at the East Asia Summit in Nusa Dua, on the island of Bali, Indonesia. Thein Sein?s historic White House visit next week is the culmination of U.S. outreach to a former pariah regime. That?s been based on a principle of taking ?action for action? by deepening ties in response to democratic reforms. (AP Photo/Charles Dharapak, File)

FILE - In this Nov. 19, 2011 file photo, President Barack Obama, left, stands next to Myanmar President Thein Sein during a group photo session at the East Asia Summit in Nusa Dua, on the island of Bali, Indonesia. Thein Sein?s historic White House visit next week is the culmination of U.S. outreach to a former pariah regime. That?s been based on a principle of taking ?action for action? by deepening ties in response to democratic reforms. (AP Photo/Charles Dharapak, File)

WASHINGTON (AP) ? Former general Thein Sein on Monday becomes the first Myanmar president to be welcomed to the White House in almost 47 years, crowning a dramatic diplomatic rehabilitation for his nation after years of international isolation.

But activists are angry about President Barack Obama hosting Thein Sein, and lawmakers are wary. The Myanmar leader has led the shift from decades of direct military rule, but has stalled on some reform commitments and failed to stop bloody outbursts of ethnic violence.

Thein Sein previously served in a repressive junta, and his meetings at the White House and Congress would have been all-but-impossible before he took the helm of a nominally civilian government in 2011. His name was only deleted from a blacklist barring travel to the U.S. last September.

He arrived in Washington Saturday, six months after Obama made history with an unprecedented U.S. presidential visit to the country also known as Burma. The administration's outreach to Myanmar's generals has provided an important incentive for the military to loosen controls on citizens and reduce dependence on China.

Myanmar has been rewarded by relaxation of tough economic sanctions, and Thein Sein will be addressing U.S. businessmen keen to capitalize on the opening of one of Asia's few untapped markets.

"President Thein Sein's visit underscores President Obama's commitment to supporting and assisting those governments that make the important decision to embrace reform," the White House said in its announcement of Monday's visit.

It will be the first by a Myanmar leader since a September 1966 visit by Ne Win, an independence hero-turned dictator, who began the nation's descent from regional rice bowl to economic basket case. Thein Sein visited New York last September for the U.N. General Assembly but did not come to Washington.

The U.S. last month announced it is considering duty-free access for Myanmar to U.S. markets, and there could be progress Monday toward a bilateral trade and investment framework agreement.

The most significant outcome of Thein Sein's trip could be a symbolic one. Obama is expected to use "Myanmar" ? the country name adopted by the junta in 1989 ? when he meets Thein Sein. However, the U.S. will keep using "Burma" in official documents.

Thein Sein will be accorded the protocol due to a foreign president, yet his Washington welcome will pale next to that granted last September to Nobel laureate Aung San Suu Kyi, the opposition leader who met Obama and was presented by Congress with the highest civilian award it can bestow.

Human rights activists and Myanmar campaigners have sharply criticized the administration for inviting Thein Sein, arguing it sends the wrong message and wastes leverage to press for further democratic change. The administration says it is important to signal U.S. support for his reform agenda, likely still opposed by military hardliners.

Ahead of the trip, Myanmar released at least 19 political prisoners in what has become a pattern for amnesties that coincide with high-profile international meetings as a way of highlighting the government's benevolent policies. Right groups say at least 160 political detainees are still held.

The government has permitted the International Committee of the Red Cross access to its notorious prisons for the first time in seven years. But hasn't allowed adequate humanitarian access to conflict zones where tens of thousands have been displaced. Authorities have failed to stop, and may have abetted in some cases, an explosion in communal violence that has killed hundreds and led to segregation of Muslim communities.

The U.S. Campaign for Burma said Thein Sein's trip follows a troubling downward trend in Myanmar, and that "instead of honoring an abusive leader" the U.S. should tie its concessions to conditions.

____

Associated Press writer Aye Aye Win in Yangon, Myanmar, contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-05-20-US-Myanmar/id-d98c16df76f4493b9bf1727e67e02e7a

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Nanoantennas improve infrared sensing

May 20, 2013 ? A team of University of Pennsylvania engineers has used a pattern of nanoantennas to develop a new way of turning infrared light into mechanical action, opening the door to more sensitive infrared cameras and more compact chemical-analysis techniques.

The research was conducted by assistant professor Ertugrul Cubukcu and postdoctoral researcher Fei Yi, along with graduate students Hai Zhu and Jason C. Reed, all of the Department of Material Science and Engineering in Penn's School of Engineering and Applied Science.

It was published in the journal Nano Letters.

Detecting light in the mid-infrared range is important for applications like night-vision cameras, but it can also be used to do spectroscopy, a technique that involves scattering light over a substance to infer its chemical composition. Existing infrared detectors use cryogenically cooled semiconductors, or thermal detectors known as microbolometers, in which changes in electrical resistance can be correlated to temperatures. These techniques have their own advantages, but both need expensive, bulky equipment to be sensitive enough for spectroscopy applications.

"We set out to make an optomechanical thermal infrared detector," Cubukcu said. "Rather than changes in resistance, our detector works by connecting mechanical motion to changes in temperature."

The advantage to this approach is that it could reduce the footprint of an infrared sensing device to something that would fit on a disposable silicon chip. The researchers fabricated such a device in their study.

At the core of the device is a nanoscale structure -- about a tenth of a millimeter wide and five times as long -- made of a layer of gold bonded to a layer of silicon nitride. The researchers chose these materials because of their different thermal expansion coefficients, a parameter that determines how much a material will expand when heated. Because metals will naturally convert some energy from infrared light into heat, researchers can connect the amount the material expands to the amount of infrared light hitting it.

"A single layer would expand laterally, but our two layers are constrained because they're attached to one another," Cubukcu said. "The only way they can expand is in the third dimension. In this case, that means bending toward the gold side, since gold has the higher thermal expansion coefficient and will expand more."

To measure this movement, the researchers used a fiber interferometer. A fiber optic cable pointed upward at this system bounces light off the underside of the silicon nitride layer, enabling the researchers to determine how far the structure has bent upwards.

"We can tell how far the bottom layer has moved based on this reflected light," Cubukcu said. "We can even see displacements that are thousands of times smaller than a hydrogen atom."

Other researchers have developed optomechanical infrared sensors based on this principle, but their sensitivities have been comparatively low. The Penn team's device is an improvement in this regard due to the inclusion of "slot" nanoantennas, cavities that are etched into the gold layer at intervals that correspond to wavelengths of mid-infrared light.

"The infrared radiation is concentrated into the slots, so you don't need any additional material to make these antennas," Cubukcu said. "We take the same exact platform and, by patterning it with these nanoscale antennas, the conversion efficiency of the detector improves 10 times."

The inclusion of nanoantennas provides the device with an additional advantage: the ability to tailor which type of light it is sensitive to by etching a different pattern of slots on the surface.

"Other techniques can only work at the maximum absorption determined by the material itself," Yi said. "Our antennas can be engineered to absorb at any wavelength."

While only a proof-of-concept at this stage, future research will demonstrate the device's capabilities as a low-cost way of analyzing individual proteins and gas molecules.

The research was supported by the National Science Foundation, Penn's Materials Research Science and Engineering Center, Penn's Nano/Bio Interface Center and the Penn Regional Nanotechnology Facility.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/matter_energy/physics/~3/Jgspaa9juWA/130520142912.htm

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Finnish MeeGo Startup Jolla Reveals First Phone: 4.5? Display, Customisable Shells, $513 Price-Tag, Shipping At Year's End

Jolla, the Finnish MeeGo startup composed of ex-Nokians?building their own mobile hardware and?Sailfish OS, has finally taken the wraps off its first handset, revealing what the hardware will look like on its website. The design is a clean-looking, elegant slab, with the most stand-out feature being the coloured shell on the back that wraps around half the sides of the phone to create a dual-tone sandwich effect. The shell colours, which appear to be user-customisable, can also influence the theme colours of the Sailfish UI. This is a feature Jolla is calling “the Other Half”. “Attach the Other Half and your Jolla becomes alive and unique,” the text notes. “Magically, the software changes to match your selected colour and design. Your Ambience. Your Jolla.” It’s unclear exactly what technology is linking hardware and software but it sounds like it could be NFC. The removable, customisable shells bring to mind Nokia’s Lumia 820 — a device for which Nokia has released the 3D print files so owners of 3D printers can ?design and print their own custom shell. The Lumia 820 shells, however, do not have any link to the Windows Phone software. Jolla’s handset will cost??399 ($513) and is slated to ship at the end of the year. Jolla notes: Expected availability by end of 2013 subject to demand in your local market. Sales will start in European countries with more countries to follow. If you join the Movement and get the pre-order number to buy the phone when available, you?ll pay no more than 399?; including applicable VAT in Europe, but excluding shipping costs, duties and any local taxes. Specs wise, the device has a 4.5″ Estrade display, a dual-core chip, 4G, 16GB internal memory plus a microSD card slot, an 8MP auto focus camera, a user-replaceable battery. The device is powered by Jolla’s Sailfish OS but can also run Android apps, giving it something of a leg up. Jolla is also encouraging developers to build native Sailfish apps too. The hardware reveal is also the start of Jolla’s pre-order sales campaign, announced last month. Jolla confirmed it is taking pre-orders from today, with the first shipments due at the start of Q4 2013. It is accepting pre-orders of either ?100 or??40 for a limited edition Jolla (plus exclusive Other Half for those making the higher payment). It is also accepting pre-orders without any down payment to be among

Source: http://feedproxy.google.com/~r/Techcrunch/~3/t0xDTBxX_oo/

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