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Thursday, April 18, 2013
Monday, April 15, 2013
Ordinary skin cells morphed into functional brain cells
Apr. 14, 2013 ? Researchers at Case Western Reserve School of Medicine have discovered a technique that directly converts skin cells to the type of brain cells destroyed in patients with multiple sclerosis, cerebral palsy and other so-called myelin disorders.
This discovery appears today in the journal Nature Biotechnology.
This breakthrough now enables "on demand" production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body. In patients with multiple sclerosis (MS), cerebral palsy (CP), and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced.
The new technique involves directly converting fibroblasts -- an abundant structural cell present in the skin and most organs -- into oligodendrocytes, the type of cell responsible for myelinating the neurons of the brain.
"Its 'cellular alchemy,'" explained Paul Tesar, PhD, assistant professor of genetics and genome sciences at Case Western Reserve School of Medicine and senior author of the study. "We are taking a readily accessible and abundant cell and completely switching its identity to become a highly valuable cell for therapy."
In a process termed "cellular reprogramming," researchers manipulated the levels of three naturally occurring proteins to induce fibroblast cells to become precursors to oligodendrocytes (called oligodendrocyte progenitor cells, or OPCs).
Tesar's team, led by Case Western Reserve researchers and co-first authors Fadi Najm and Angela Lager, rapidly generated billions of these induced OPCs (called iOPCs). Even more important, they showed that iOPCs could regenerate new myelin coatings around nerves after being transplanted to mice -- a result that offers hope the technique might be used to treat human myelin disorders.
When oligodendrocytes are damaged or become dysfunctional in myelinating diseases, the insulating myelin coating that normally coats nerves is lost. A cure requires the myelin coating to be regenerated by replacement oligodendrocytes.
Until now, OPCs and oligodendrocytes could only be obtained from fetal tissue or pluripotent stem cells. These techniques have been valuable, but with limitations. "The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes," explained co-author and myelin expert Robert Miller, PhD, professor of neurosciences at the Case Western Reserve School of Medicine and the university's vice president for research. "The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells."
This initial study used mouse cells. The critical next step is to demonstrate feasibility and safety using human cells in a lab setting. If successful, the technique could have widespread therapeutic application to human myelin disorders. "The progression of stem cell biology is providing opportunities for clinical translation that a decade ago would not have been possible," said Stanton Gerson, MD, professor of Medicine-Hematology/Oncology at the School of Medicine and director of the National Center for Regenerative Medicine and the UH Case Medical Center Seidman Cancer Center. "It is a real breakthrough."
Additional co-authors of the publication include Case Western Reserve School of Medicine researchers Anita Zaremba, Krysta Wyatt, Andrew Caprariello, Daniel Factor, Robert Karl, and Tadao Maeda.
The research was supported by funding from the National Institutes of Health, the New York Stem Cell Foundation, the Mt. Sinai Health Care Foundation and Case Western Reserve University School of Medicine.
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The above story is reprinted from materials provided by Case Western Reserve University, via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- Fadi J Najm, Angela M Lager, Anita Zaremba, Krysta Wyatt, Andrew V Caprariello, Daniel C Factor, Robert T Karl, Tadao Maeda, Robert H Miller, Paul J Tesar. Transcription factor?mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nature Biotechnology, 2013; DOI: 10.1038/nbt.2561
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/aD-E-BbZdCA/130414193143.htm
Immigration reform: What to do about those who arrive legally but never leave?
An estimated 40 percent of the more than 10 million undocumented people in the US today came legally but stayed on after their visa expired. It's a major issue in the immigration debate.
Motorists wait in lanes of traffic heading into the United States from Mexico at the border crossing in San Ysidro, California, the busiest land border crossing in the U.S. An estimated 40 percent of the more than 10 million undocumented people in the US today came legally but stayed on after their visa expired.
Mike Blake/REUTERS
EnlargeAs the Senate?s ?Gang of 8? immigration reformers puts the final touches on legislation expected to be introduced this coming week, there?s a simple-sounding problem with a long-elusive solution that the group will have to finally nail down: how to figure out when and if the 150 million foreigners who come into the United States every year actually leave.
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The policy of following who comes and who goes from America?s massive borders and hundreds of air and seaports, known in immigration wonk talk as ?entry-exit? and formally as the US-VISIT program at the Department of Homeland Security, is one of the many issues the bipartisan group of senators vowed to tackle in their bill and is a particular priority for Sen. Marco Rubio (R) of Florida.
It?s not an academic issue: somewhere in the neighborhood of 40 percent of the more than 10 million undocumented people in the US today came legally but stayed on after their visa expired.
Although often overlooked next to the more emotionally-charged issue of securing America?s Southern border, the long-standing problem of figuring out how to make sure the nation?s legal immigration system is enforced is likewise vitally important ? and going to be politically contentious.
?Without a real entry-exit tracking system, the rest of immigration law is irrelevant,? says Mark Krikorian, executive director for the Center for Immigration Studies, a group that advocates for lower immigration levels. ?You can have Herman Cain?s electrified fences and any kind of other ridiculous border control measure but if we?re letting people in legally and then not paying any attention to whether they leave, what difference does the border control make??
Why is this so hard?
Beginning in the mid-1990s, Congress has asked for a system for tracking entry and exit from the US by non-US citizens a half-dozen times, upgrading its request from a ?biographic? system of personal details to a ?biometric? system of personal identifiers (chiefly fingerprints) after the 9/11 terror attacks.
While the US has achieved a nearly-universal level of biographic intake when foreigners come into the country, there?s little exit monitoring at the nation?s land borders and some monitoring at air and seaports. And biometric screening is years away.
Today, all entering foreigners are subject to biographic and biometric screening. To determine when foreigners exit the country, that data is checked against airline flight manifests and, soon, Canadian data showing non-US citizens who cross the US-Canada border.
But getting to the biometric standard Department of Homeland Security Secretary Janet Napolitano believes would be ideal could take another half-decade or longer and cost as much as $10 billion, according to Republican aides on Capitol Hill who have studied the system.
In nearly two decades, then, Congress has asked for a viable entry-exit system on multiple occasions and gotten a half-loaf in return. (By the end of this year, Napolitano told a Senate hearing recently, DHS is aiming to provide country-by-country overstay rates.)
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Monday, April 8, 2013
Deep rifts exposed in latest round of Iran nuclear talks
Two days of Iran nuclear talks in Kazakhstan have exposed the depth of division and scale of mismatched expectations between Iran and six world powers, as they spar over ways to limit Iran?s most sensitive nuclear work.
The talks were unprecedented in both their intensity and depth, say officials from both sides, and even included a direct 30- to 40-minute exchange between the top American and top Iranian diplomats across the negotiating table.
Yet instead of narrowing a chasm that has bedeviled five rounds of talks in a year between Iran and the P5+1 group (the US, Russia, China, Britain, France, and Germany), this round appeared to illustrate like never before the magnitude of the diplomatic challenge ahead.
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The P5+1 demands that Iran give up enriching uranium to 20 percent ? a few technical steps away from bomb-grade ? and disable one deeply buried facility, in exchange for a partial lifting of crippling sanctions. That proposal would be a first step toward a broader deal to ensure Iran will never make a nuclear bomb.
Iran says it needs to know that final deal will guarantee its ?right? to enrich uranium for peaceful purposes and an end to sanctions; Iranian officials indicated that they counter-proposed exchanging 20 percent enrichment for a lifting of all unilateral sanctions.
MUTUAL MISPERCEPTIONS
That disconnect and ?mutual misperceptions? now risk damaging the diplomatic process, says Ali Vaez, the senior Iran analyst for the International Crisis Group, who spoke to delegates on both sides at the talks in the Kazakh city of Almaty.
?The P5+1 expected instant gratification of its meaningful ? but modest ? offer of sanctions relief, while Iran saw an opportunity to devise a road map toward recognition of its rights to enrichment,? says Mr. Vaez.
Differences now remain ?as wide as the distance between the first step and the end game,? says Vaez. ?Still, there is a real cost in declaring failure and as prospects of a deal narrow, the temptation of more coercive alternatives grows. The ironic end result of years of mutual escalation is that both parties are now loathe to use the leverage they have sacrificed so much to acquire.?
Stern words were exchanged by diplomats in public, as each side sought to portray the other as needing to go home and recalibrate their thinking. No date was set for the next round of talks, but decisions on how to proceed could come within days.
?There may not have been a breakthrough, but there was also not a breakdown,? said a senior US official, who spoke on condition of anonymity.
"It is fair to say that Iran is only prepared to take very minimal steps with respect to constraints on its nuclear program while expecting very significant rewards in return [which is] not a realistic basis for progress," said the US official. ?This was such a detailed, such an intense, and such a complex 48 hours, we ourselves are just absorbing all that we heard and all that was discussed ? we all really need to absorb and digest what we?ve heard.?
During the first day of talks, Iranian diplomats announced their need for an agreed framework on the ?dimensions? and ?final outcome? of the process before they could take initial steps, concerned that P5+1 demands could mount ? including a requirement to stop all enrichment ? with only marginal sanctions relief.
The current P5+1 offer, which has been seen by the Monitor, envisions Iran to eventually take unspecified ?additional significant steps? before key sanctions could be lifted.
A Western diplomat said the P5+1 had been ?somewhat puzzled? by the Iranian response.
IRAN'S NEGOTIATOR
Iran?s chief negotiator Saeed Jalili, told the Monitor in an interview after the Almaty talks that Iran had ?always? told the P5+1 that such a framework agreement was necessary to ?foster cooperation.?
?I like to think that we tried our very best to take as many questions as was possible to us,? Mr. Jalili told the Monitor. ?We took a lot of time, taking those questions, providing responses, explaining our positions, our ideas, in great detail. This was so thorough that finally the members of [the P5+1] were asked, ?Do you have any remaining questions?? and nobody had any questions.?
Iran?s concluding statement used several positive phrases. Iran had put forward a ?plan of action? that incorporated the P5+1 proposal, Jalili said, and he mentioned ?forward movement? and that the ?new conditions? of Iran?s initiative were meant to propel talks in a ?constructive fashion.?
It was ?now up to the P5+1 to demonstrate its willingness and sincerity to take proportionate confidence building steps,? said Jalili. ?Creating confidence is a two-way street, and today after many measures taken by the Islamic Republic of Iran to provide additional confidence, now [the P5+1] must work to gain the confidence of the Iranian people.?
He said that enriching uranium up to 20 percent was the ?right of the Iranian people,? but added ? without being specific ? that ?this can be an issue to help create further confidence.?
P5+1 PERSPECTIVE
The P5+1 saw Iran?s diplomatic moves in a very different and dimmer light.
?[Iran] responded to our proposal with some ideas that were a minimal response [that] not only had very, very tiny steps, in our view, but wanted a lot of return for those tiny steps,? said the senior US official. ?The gulf between their current position and ours is quite great.?
Those differences were made clear in the long direct conversation (through interpreters) between Jalili and the head of the American delegation, US Undersecretary of State for Political Affairs Wendy Sherman. That was one of several, diplomats said, between Jalili and individual P5+1 negotiators.
Still, such unprecedented exchanges do not replace making progress on substantive issues, said the senior US official.
?We do see the world differently,? said the US official. ?We come from different cultures, different backgrounds, and different ways of solving problems. And so it takes a lot of time to understand each other and to understand what each other is saying ? the devil is truly in the details.?
DETAILS OF DISPUTE
Among those details are how to handle Iran?s growing stockpile of 20 percent enriched uranium. Iran says it needs it to fuel a research reactor in Tehran, and has converted some 40 percent of that stockpile into oxide for fuel use ? rendering that portion virtually unusable for further enrichment to bomb-grade levels of 90 percent.
Past fuel swap deals have failed; the current P5+1 proposal would enable Iran to purchase that fuel and medical isotopes.
?What we are insisting on is our right to enrich,? Jalili told the Monitor. ?This is equally true for 5 percent or 20 percent. You know well that 20 percent enriched uranium is used for medical purposes. One million Iranian patients are using these isotopes.?
Jalili added: ?Today the fuel is exclusively used for humanitarian matters, medical purposes, exclusively peaceful purposes.?
Another hurdle was not overcome in Almaty. Several UN Security Council resolutions require Iran to halt all enrichment, at all levels, until it has resolved remaining questions about possible past weapons-related work with the UN?s International Atomic Energy Agency (IAEA).
Iranian officials say they reject nuclear weapons as un-Islamic, but also that they will never halt enrichment, which they consider an ?inalienable right,? as a signatory to the Nuclear Non-Proliferation Treaty (NPT). That is why Iran says it wants to know now that it will still be able to enrich when the process is over, before any initial steps.
P5+1 officials themselves have variable interpretations, with Russia in the past stating that Iran should have that ?right? to enrich recognized. Moscow called this round of talks in Almaty a ?step forward.?
?What we are talking about is full compliance with the Security Council resolutions and [Iran?s] responsibilities under the NPT,? said the senior US official. ?And we have always said that when they meet [those], then they can see their way to a truly peaceful, civil, nuclear program under the NPT, and all sanctions can be lifted. So there is no mystery here about what the end of the story is.?
That point in some ways returns the current diplomatic process full circle, to the earlier, maximalist proposals laid down by both sides last spring.
?The irony is that the more the two sides understand their respective positions, the more they realize how far apart and entrenched they are,? says Vaez, the ICG Iran analyst.
Still, P5+1 diplomats said they had never seen such an open exchange with Iran.
Catherine Ashton, the European Union foreign policy chief who leads negotiations on behalf of the P5+1, stated that the two sides remained ?far apart on the substance? of the talks, but added: ?For the first time that I?ve seen, [there was] a real back and forth between us, where we are able to discuss details, to pose questions, and to get answers directly.?
* Follow Scott Peterson on Twitter at @peterson__scott
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Source: http://news.yahoo.com/deep-rifts-exposed-latest-round-iran-nuclear-talks-134300957.html
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