Botox finds new wrinkle in brain communication

Friday, May 3, 2013

National Institutes of Health researchers used the popular anti-wrinkle agent Botox to discover a new and important role for a group of molecules that nerve cells use to quickly send messages. This novel role for the molecules, called SNARES, may be a missing piece that scientists have been searching for to fully understand how brain cells communicate under normal and disease conditions.

"The results were very surprising," said Ling-Gang Wu, Ph.D., a scientist at NIH's National Institute of Neurological Disorders and Stroke. "Like many scientists we thought SNAREs were only involved in fusion."

Every day almost 100 billion nerve cells throughout the body send thousands of messages through nearly 100 trillion communication points called synapses. Cell-to-cell communication at synapses controls thoughts, movements, and senses and could provide therapeutic targets for a number of neurological disorders, including epilepsy.

Nerve cells use chemicals, called neurotransmitters, to rapidly send messages at synapses. Like pellets inside shotgun shells, neurotransmitters are stored inside spherical membranes, called synaptic vesicles. Messages are sent when a carrier shell fuses with the nerve cell's own shell, called the plasma membrane, and releases the neurotransmitter "pellets" into the synapse.

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) are three proteins known to be critical for fusion between carrier shells and nerve cell membranes during neurotransmitter release.

"Without SNAREs there is no synaptic transmission," said Dr. Wu.

Botulinum toxin, or Botox, disrupts SNAREs. In a study published in Cell Reports, Dr. Wu and his colleagues describe how they used Botox and similar toxins as tools to show that SNAREs may also be involved in retrieving message carrier shells from nerve cell membranes immediately after release.

To study this, the researchers used advanced electrical recording techniques to directly monitor in real time carrier shells being fused with and retrieved from nerve cell membranes while the cells sent messages at synapses. The experiments were performed on a unique synapse involved with hearing called the calyx of Held. As expected, treating the synapses with toxins reduced fusion. However Dr. Wu and his colleagues also noticed that the toxins reduced retrieval.

For at least a decade scientists have known that carrier shells have to be retrieved before more messages can be sent. Retrieval occurs in two modes: fast and slow. A different group of molecules are known to control the slow mode.

"Until now most scientists thought fusion and retrieval were two separate processes controlled by different sets of molecules", said Dr. Wu.

Nevertheless several studies suggested that one of the SNARE molecules could be involved with both modes.

In this study, Dr. Wu and his colleagues systematically tested this idea to fully understand retrieval. The results showed that all three SNARE proteins may be involved in both fast and slow retrieval.

"Our results suggest that SNAREs link fusion and retrieval," said Dr. Wu.

The results may have broad implications. SNAREs are commonly used by other cells throughout the body to release chemicals. For example, SNAREs help control the release of insulin from pancreas cells, making them a potential target for diabetes treatments. Recent studies suggest that SNAREs may be involved in neurological and psychiatric disorders, such as schizophrenia and spastic ataxia.

"We think SNARES work like this in most nerve cell synapses. This new role could change the way scientists think about how SNAREs are involved in neuronal communication and diseases," said Dr. Wu.

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Xu J et al. "SNARE proteins synaptobrevin, SNAP-25 and syntaxin are involved in rapid and slow endocytosis at synapses." Cell Reports, May 2, 2013. DOI: 10.1016/j.cellrep.2013.03.010

NIH/National Institute of Neurological Disorders and Stroke: http://www.ninds.nih.gov

Thanks to NIH/National Institute of Neurological Disorders and Stroke for this article.

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Source: http://www.labspaces.net/128118/Botox_finds_new_wrinkle_in_brain_communication

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Kim Kardashian and Kanye West: Actually Getting Married This Year?!

Source: http://www.thehollywoodgossip.com/2013/05/kim-kardashian-and-kanye-west-actually-getting-married-this-year/

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States fear loss of health care aid

WASHINGTON (AP) ? Thousands of people with serious medical problems are in danger of losing coverage under President Barack Obama's health care overhaul because of cost overruns, state officials say.

At risk is the Pre-Existing Condition Insurance Plan, a transition program that's become a lifeline for the so-called "uninsurables" ? people with serious medical conditions who can't get coverage elsewhere. The program helps bridge the gap for those patients until next year, when under the new law insurance companies will be required to accept people regardless of their medical problems.

In a letter this week to Health and Human Services Secretary Kathleen Sebelius, state officials said they were "blindsided" and "very disappointed" by a federal proposal they contend would shift the risk for cost overruns to states in the waning days of the program. About 100,000 people are currently covered.

"We are concerned about what will become of our high risk members' access to this decent and affordable coverage," wrote Michael Keough, chairman of the National Association of State Comprehensive Health Insurance Plans. States and local nonprofits administer the program in 27 states, and the federal government runs the remaining plans.

"We fear...catastrophic disruption of coverage for these vulnerable individuals," added Keough, who runs North Carolina's program. He warned of "large-scale enrollee terminations at this critical transition time."

The crisis is surfacing at a politically awkward time for the Obama administration, which is trying to persuade states to embrace a major expansion of Medicaid under the health care law. One of the main arguments proponents of the expansion are making is that Washington is a reliable financial partner.

The root of the problem is that the federal health care law capped spending on the program at $5 billion, and the money is running out because the beneficiaries turned out to be costlier to care for than expected. Advanced heart disease and cancer are common diagnoses for the group.

Obama did not ask for any additional funding for the program in his latest budget, and a Republican bid to keep the program going by tapping other funds in the health care law failed to win support in the House last week.

Brian Cook, a spokesman for the HHS agency overseeing the health care law, took issue with idea that thousands of people could lose coverage, though he did not elaborate.

"These actions are part of our careful management of the program to ensure that there is a seamless transition ... for enrollees, and that funding is spent appropriately," he said in a written statement.

The administration has given the state-based plans until next Wednesday to respond to proposed contract terms for the program's remaining seven months.

Delivered last Friday, the new contract stipulated that states will be reimbursed "up to a ceiling."

"The 'ceiling' part is the issue for us," Keough said in an interview. "They are shifting the risk from the federal government, for a program that has experienced huge cost overruns on a per-member basis, to states. And that's a tall order."

State officials say one likely consequence of the money crunch will be a cost shift to people in the program, resulting in sudden increases in premiums and copayments. Many might just drop out, said Keough.

If a state and HHS can't come to an agreement, the federal government will take over that state's program for the rest of this year. Amie Goldman, director of the Wisconsin program, said that would be an unneeded and possibly risky disruption for patients who'll have to change insurance next year anyway, when the pre-existing conditions plan formally ends.

Goldman said in her state, for example, the University of Wisconsin hospital isn't part of the federal government's provider network. "My colleagues in other states have similar concerns about holes in the network," she said. "I think it puts people at medical risk."

At his news conference this week, Obama acknowledged the rollout of his health care law wouldn't be perfect. There will be "glitches and bumps" he said, and his team is committed to working through them. However, it's unclear how the pre-existing conditions plan could get more money without the cooperation of Republicans in Congress.

The program got off to a slow start, partly because insurance isn't cheap. It offers policies at market rates, and that can mean premiums of $500 a month for someone in their 50s. The first inkling of financial problems came in February, when HHS announced a freeze on new applications.

The plan was intended only as a stopgap until the law's main push to cover the uninsured starts next year. Subsidized private insurance will be available through new state-based markets, as well as an expanded version of Medicaid for low-income people. At the same time, virtually all Americans will be required to carry a policy, or pay a fine.

States are free to accept or reject the Medicaid expansion, and the new problems with the stopgap insurance plan could well have a bearing on their decisions.

Source: http://news.yahoo.com/states-fear-loss-health-care-aid-064805309.html

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Ebola's secret weapon revealed

May 2, 2013 ? Researchers have discovered the mechanism behind one of the Ebola virus' most dangerous attributes: its ability to disarm the adaptive immune system.

University of Texas Medical Branch at Galveston scientists determined that Ebola short-circuits the immune system using proteins that work together to shut down cellular signaling related to interferon. Disruption of this activity, the researchers found, allows Ebola to prevent the full development of dendritic cells that would otherwise trigger an immune response to the virus.

"Dendritic cells typically undergo a process called 'maturation' when they're infected by a virus -- they change shape and present antigens on their surface that tell T-cells to attack that particular virus, thus generating an adaptive immune response," said UTMB professor Alexander Bukreyev, senior author of a paper on the discovery now online in the Journal of Virology. "But Ebola prevents dendritic-cell maturation and produces a severe infection without an effective adaptive immune response. We found that its ability to do this depends on several specific regions of two different proteins."

Bukreyev's research group made the discovery after a series of procedures that started with a clone of the Ebola Zaire virus strain. Working under maximum-containment conditions in a biosafety level 4 facility in UTMB's Galveston National Laboratory, the team introduced mutations into the virus' genetic code at four locations thought to generate proteins that affected immune response.

They then infected human dendritic cells with each of the resulting new strains and compared the results with those produced by unmutated Ebola Zaire. Each of the four new viruses, they found, was unable to suppress dendritic-cell maturation.

"We saw two very interesting things," Bukreyev said. "First, that these mutations restore maturation of dendritic cells very effectively, and second, that a mutation in even one of these genetic domains makes the virus unable to suppress maturation. That means that the virus needs multiple combined effects in order to undermine the immune system in this way."

Ebola's ability to evade the human immune response is one of the factors that accounts for its high mortality rate -- up to 90 percent in humans -- and the notoriety that it gained after its first appearance in Zaire in 1976, in an outbreak that killed 280 people. Zaire -- now the Democratic Republic of the Congo -- is the home country of Ndongala Lubaki, lead author on the paper and a postdoctoral fellow at UTMB.

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Story Source:

The above story is reprinted from materials provided by University of Texas Medical Branch at Galveston.

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. N. M. Lubaki, P. Ilinykh, C. Pietzsch, B. Tigabu, A. N. Freiberg, R. A. Koup, A. Bukreyev. The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results from the Cooperative Effect of at Least Two Viral Domains. Journal of Virology, 2013; DOI: 10.1128/JVI.03316-12

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/top_news/top_environment/~3/c6CT4d4pdj0/130502192226.htm

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Take note! Google just announced a new Chrome app for Google Keep, so now you can easily jot down yo

Take note! Google just announced a new Chrome app for Google Keep, so now you can easily jot down your thoughts while you're surfing the web.

Read more...

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/7u8Ir0EoYP8/take-note-google-just-announced-a-new-chrome-app-for-g-487358224

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Diplo And Skrillex Reveal Their Surprising New Group: Jack U

Duo to debut project at Diplo's Mad Decent Block Parties this summer.
By Elizabeth Lancaster

Skrillex and Diplo
Photo: Getty Images

Source: http://www.mtv.com/news/articles/1706634/diplo-skrillex-mad-decent-block-party.jhtml

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'DWTS' final four? The finale could see a shakeup

TV

Michael Maloney TODAY contributor

8 hours ago

There are seven remaining pairs on "Dancing With the Stars" and only three more elimination nights before the finals. So, barring any surprise double eliminations, there will be four couples -- not the traditional three -- competing in the finale on May 20.

ABC

?It?s good for that fourth couple who?ll get paid an extra couple of bucks,? pro Val Chmerkovskiy shrugged to reporters in Monday night?s post-show press line.

Derek Hough thinks it?s a good idea too.

"Honestly, it means more dances for the finals," the three-time mirror-ball champion said. ?It?s more entertainment for the viewers at home, and that?s what it?s all about.?

Hough has said in the past that it?s best to come in either fourth or first, since exiting right after the semifinals means a dancer doesn?t have to come up with two more routines for a finale that he or she may or may not win.

?I think differently about that now,? he said. ?When I said that, I might have been thinking I didn?t want to do all that hard work. But I?m of the frame of mind that it?s an absolute pleasure and joy to be able to do any dance number on the show -- every time, even for results shows.?

Recap: 'Dancing With the Stars' judges take the ballroom to the bathroom

While anything can happen between now and the finals, it seems likely that three of the four finalists will be the competition's consistently high-scoring duos: Kellie Pickler and Hough, Zendaya and Chmerkovskiy, and Jacoby Jones and Karina Smirnoff. The fourth slot is up for grabs.

But the only sure thing right now is that Hough and Pickler won?t be going home on Tuesday night. They scored enough points on Monday to earn immunity.

Related:? Andy on how he's ranked on 'Dancing': 'It's not fair'

But while Hough and Pickler are safe for now, the pro feels that writing off low-scorer Andy Dick before the end just might be a mistake, given the show?s passionate fan base.

?I hope the judges did Andy a favor with their (strong) comments,? Hough offered. ?If you feel that (your favorite) is being picked on, then you?re going to say to yourself, ?I?m going to vote for him!??

Source: http://www.today.com/entertainment/dancing-stars-final-four-finale-could-see-shakeup-6C9676198

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