Category: Science

Nerve cells warn brain of damage to inner earNerve cells warn brain of damage to inner ear

Some nerve cells in the inner ear can signal tissue damage in a way similar to pain-sensing nerve cells in the body, according to new research from Johns Hopkins. If the finding, discovered in rats, is confirmed in humans, it may lead to new insights into hyperacusis, an increased sensitivity to loud noises that can lead to severe and long-lasting ear pain.

“We are still a long way from being able to treat hyperacusis,” says Paul Fuchs, Ph.D., professor of otolaryngology-head and neck surgery, neuroscience and biomedical engineering at the Johns Hopkins University School of Medicine, “but our results suggest that cells called type II afferent neurons are similar to pain-sensing neurons in the rest of the body, so lessons about interventions elsewhere could apply to the ear, too.”

A summary of the research will be published online in the journalProceedings of the National Academy of Sciences during the week of Nov. 9.

The new discovery came as a result of interest in why this small subset of afferent nerve cells — nerves that take information from the inner ear to the brain — are quite insensitive to sound. “If they aren’t very good at relaying sounds, what are they doing?” says Fuchs.

Fuchs and his team knew that these type II afferents connect to specialized sensory cells in the ear of mammals. These so-called outer hair cells amplify the sound waves that enter the inner ear, giving mammals very sensitive hearing over a wide range of frequencies. But, according to Fuchs, this specialization comes at a cost.

“Outer hair cells are the canaries in the coal mine for the inner ear, in that they’re the first cells to die due to loud noise, age or other factors,” says Fuchs. “Since they can’t regenerate, their death leads to permanent hearing loss.” So one possible role for type II afferents, he adds, would be to warn the brain of impending damage to outer hair cells.

It was known that nearby supporting cells respond to outer hair cell damage by increasing their inner calcium levels and releasing the chemical messenger ATP. Fuchs’ team knew that type II afferent neurons can respond to ATP, so they damaged outer hair cells while monitoring type II neurons in surgically removed inner ear tissue. Indeed, outer hair cell rupture caused robust excitation of type II neurons.

Fuchs says that the ATP released by the supporting cells is probably what gets the neurons to fire, and the supporting cells might release ATP in response to ATP that leaks out of the ruptured outer hair cells. But he noted that “outer hair cells don’t have to rupture to release ATP. Progressive damage caused by loud noises or other stress is enough to increase ATP levels in the fluid of the inner ear.”

Over evolutionary time, such a mechanism could have evolved to help mammals avoid further damage to their hearing. Such effects might depend on heightened sensitivity of the type II neurons after trauma, akin to the heightened sensitivity of pain-sensing nerves in damaged skin. Hypersensitivity to loud sound (hyperacusis) is a paradoxical consequence of hearing loss in many people. Everyday noises such as slamming doors, clanking dishes and barking dogs can become irritating and even painful.

The good news, Fuchs says, is that the analogies with pain elsewhere in the body provide guidance for future studies. For example, a compound that suppresses pain-sensing nerve cells elsewhere, also prevented type II afferent neurons from firing in response to outer hair cell death. At present, Fuchs cautions, this is a restricted experimental result. But, it provides a “proof of concept” for treating pain associated with inner ear damage. And the Fuchs laboratory plans to explore this question in their ongoing research.

This medical research study,”Nerve cells warn brain of damage to inner ear” was recently published on Johns Hopkins Medicine

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Obama nemesis Hobby Lobby probed for allegedly buying black market biblical itemsObama nemesis Hobby Lobby probed for allegedly buying black market biblical items

As the world’s foremost collector of rare biblical artifacts, Steven Green may have made a deal with the devil – helping to preserve Iraq’s disappearing Christian heritage by allegedly buying black market items plundered by the Islamic State.

Green, whose family-owned Hobby Lobby company clashed bitterly with the Obama administration over federal health care laws that required it to cover reproductive services, is being investigated by Customs & Border Protection reportedly for attempting to smuggle as many as 300 age-old cuneiform tablets from Iraq into the U.S. via Israel, labeling them “tiles.” It was not clear if the probe centers on Green, the company, or both, but the shipment was reportedly addressed to Hobby Lobby headquarters in Oklahoma City.

The tablets, which The Daily Beast reported are thousands of years old and inscribed with text used in ancient Assyria and Babylonia, were seized by Customs agents in Memphis, Tenn., in 2011, but were on their way into Green’s collection of the “rarest and most significant biblical texts and artifacts ever assembled” including “cuneiform tablets dating from the time of Abraham, Dead Sea Scroll fragments, biblical papyri and manuscripts, Torah scrolls, and rare printed Bibles.”

“We understand that Hobby Lobby is cooperating with the investigation related to certain biblical artifacts.”

– Steven Bickley, Museum of the Bible

Some 40,000 historical Christian artifacts and objects are being prepped for display in Green’s $400 million, 430,000-square-foot, 8-story “Museum of the Bible,” set to open in late 2017 just three blocks from the U.S. Capitol in Washington.

“We understand that Hobby Lobby is cooperating with the investigation related to certain biblical artifacts,” said Museum of the Bible Vice President Steven Bickley in a statement to “The Museum of the Bible is a separate not-for-profit entity made possible by the generous charitable contributions of the Green family and others.”

Little is known publicly about this case, and U.S. Customs did not comment on’s inquiry. But one U.S. archaeologist who has worked with the Greens said the family is very meticulous and ethical about acquisitions.

“In my opinion the Greens would not have knowingly purchased antiquities from an unknown or suspected source,” said the archaeologist, a prominent professor at a respected university who asked not to be identified. “However, the authorities are extremely sensitive about any antiquities coming into the market at this time and are critical of almost any trade or sale between the Middle East and other countries, especially with regard to well-funded private collectors such as the Greens. Therefore, they would be a prime target of investigation.”

Others called Hobby Lobby’s reported claim that the tablets were hand-crafted “tiles” worth just $300 a piece “ludicrous.”

The tablets could be worth anywhere from $2,000 to $30,000 each, according to Amr Al-Azm, an associate professor Middle East History and Anthropology in the Department of Social Sciences at Shawnee State University.

And calling the tablets “tiles” is comparable to labeling ancient books as tiles, because they are both square shaped, said Eric Meyers, an archaeologist and director of the graduate program in religion at Duke University. He estimated that ISIS reaps up to $100 million a year by selling plundered artifacts on the black market.

Under Iraqi law, cultural heritage is the property of the state, with antiquities recognized as “national treasures” and anyone who removes them from the country is a thief. This can in turn trigger a legal claim in the United States, as well as the United Kingdom, that would allow Iraq to recover them. And it could likewise expose any sellers, dealers, or purchasers to criminal penalties.

American law also criminalizes the receipt, possession, and transport of stolen property. Penalties for violating the National Stolen Property Act can be up to 10 years in prison and fines.

In August, the FBI issued an alert that Islamic State’s looted antiquities were being sold in the American market, and warned collectors and dealers who purchase these objects may be funding terror activities and would be subject to sanctions and prosecution under federal law.

If the smuggling allegations are true, the Greens could argue they saved important historical and cultural religious artifacts from sure destruction at the hands of terrorists in an unstable, war-torn country, Al-Azm said.

However, both Al-Azm and Meyers said buying artifacts from terrorists is both unethical and illegal. Besides funding the terror operations, dealing with the looters also encourages continued pillaging and destruction of sacred sites.

As the Islamic State wages waves of terror in Iraq and Syria, how to best handle the organized and systematic pillaging and destruction of irreplaceable historical objects and artifacts and religious sites is a hot topic among academics, archeologists, bureaucrats and historians.

The Islamic State has become so well organized in its looting of antiquities, the terror group has its own black market network that has become one of its leading sources of revenue.

The Islamic State demands a 20 percent cut of any looted objects sold by locals, regulates access to historical sites, in part by issuing permits and licenses and in addition to performing their own looting, also hires contractors to raid sites, Al-Azm said.

The Islamic State formed the its own Archaeological Administration in the city of Manbij to organize the sale and transfer of artifacts, which it distributes through a highly organized network of approved dealers, Al-Azm said.

“This evidence indicates that the control and sale of looted antiquities is extremely lucrative, well worth the time and financial investment by ISIS,” Al-Azm said. “ISIS is clearly involved and profiting at every level from the illicit trade of antiquities—from their initial extraction from the ground to their final sale and exit from ISIS-controlled territory.”

Over the past few months, pillaging and destruction by the Islamic State has only become “darker and more sinister”, Al-Azm said.

“In what can only be described as cultural atrocities, ISIS very publicly set out to destroy the contents of the Mosul Museum and the archaeological sites of Nineveh and Hatra most likely extensively looting them as well,” Al-Azm said. “These atrocities shocked the world, allowing ISIS to demonstrate its ability to act with impunity and illustrating the impotence of the international community to prevent the atrocities.”

While looting is an extremely old phenomenon, “as old as the pyramids,” Al-Azm pointed out, and has continued over the centuries largely in countries involved in war, Meyers said items stolen in Iraq have flooded the market since the first Gulf War, turning up largely in the hands of dealers throughout the middle east and Europe.

Many other irreplaceable items have been destroyed and thrown away, which is tragic, said Meyers who is involved with American Schools of Oriental Research, which works on behalf of U.S. Department of State to document, protect, and preserve the cultural heritage of war-torn Syria and northern Iraq.

Sept. 30, The State Department announced a $5 million reward for anyone who could provide information that disrupts the Islamic State’s plundering activities.

“ISIL’s damage and looting of historic sites in Syria and Iraq have not only destroyed irreplaceable evidence of ancient life and society but have also helped fund its reign of terror inside those countries,” the State Department announced from the New York Metropolitan Museum. “ISIL’s damage and looting of historic sites in Syria and Iraq have not only destroyed irreplaceable evidence of ancient life and society but have also helped fund its reign of terror inside those countries.”

The investigation has reportedly extended over four years, and in the end, Green and his $3.7-billion company could face civil fines or criminal charges. The Greens took on the Obama administration previously in the U.S. Supreme Court case Burwell v. Hobby Lobby. In a June, 2014 decision, the high court allowed the company an exemption to the Obamacare healthcare mandate on religious grounds from providing certain kinds of contraception.

Source:- Foxnews


Structure of an enzyme complex that plays a vital role in cancer development determinedStructure of an enzyme complex that plays a vital role in cancer development determined

Researchers at UT Southwestern Medical Center have deciphered the long-sought atomic structure of PRC2, an enzyme complex that plays a key role in the development of several types of cancer, in particular blood cancer.

PRC2, or polycomb repressive complex 2, is a key regulator of human development and controls gene expression patterns by altering the structure of chromatin, a complex formed by protein and DNA. As an enzyme complex, PRC2 modifies a protein in chromatin, resulting in key changes in chromatin structure that silence certain genes. Abnormal regulation of PRC2 function, often caused by mutations in the PRC2 gene, has been linked to cancers such as lymphoma, leukemia, brain tumors, and other diseases, including Weaver syndrome, a rare congenital disorder associated with rapid growth, skeletal abnormalities, and delayed development.

“Our findings bring us one step closer to understanding the chemistry of how PRC2 functions in normal cells and how mutations in the gene cause disease,” said senior author Dr. Xin Liu, Assistant Professor of Obstetrics and Gynecology, and of Biophysics at UT Southwestern.

The findings were published online Oct. 16 by the journal Science.

“Producing either too much or too little PRC2 enzyme can unexpectedly silence or activate genes, which is not good for the cell. This study revealed how a ‘normal’ level of PRC2 enzyme activity is kept and regulated in cells,” explained Dr. Liu, also a member of the Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Harold C. Simmons Comprehensive Cancer Center, and a W.W. Caruth, Jr. Scholar in Biomedical Research.

Dr. Liu said the findings identify the various ways that PRC2 acts, which in turn is helpful in understanding the chemical basis of related diseases and should aid in the development of new treatments for those diseases.

“Indeed, several clinical trials are currently ongoing to target PRC2, and we believe our work will shed light on these and other studies in drug development by offering insights into how PRC2 works at the atomic level,” he said.

In particular, Dr. Liu indicated that small-molecule drugs are being developed to inhibit PRC2 enzyme activity for treatment of some types of lymphoma. These drugs may prove beneficial, he said, since PRC2 has been found to be overly active in promoting further development of these cancer types.

The findings lay the groundwork for further investigation of PRC2 function and regulation in both normal and diseased cells. Among next steps, the research team led by Dr. Liu is now elucidating how PRC2 is regulated during interactions with chromatin and how the complex interacts with other cellular proteins on and off chromatin. This work may offer a deeper and more thorough understanding of PRC2 function and its dysregulation in human disease.

From a science perspective, this finding is groundbreaking. The 4-year-long investigation — for the first time — revealed the 3-D atomic structure of PRC2, in this case from a fungus and at high resolution. Some molecules known to regulate the enzyme activity of PRC2 in both normal and cancer cells were captured in action in the structure as well. This work not only solved some long-standing mysteries about the molecular mechanisms of PRC2 enzyme catalysis and regulation, but also provided a structural framework for the development of future cancer therapies.

“The widely used analytic technique of X-ray crystallography was utilized to deduce the protein structures based on X-ray diffraction patterns of PRC2 crystals generated at synchrotron particle accelerators,” said Dr. Lianying Jiao, a postdoctoral researcher in the Liu lab and first author of the study.

The research was supported by grants from the Cancer Prevention and Research Institute of Texas, the Welch Foundation, the Rita Allen Foundation, and the National Institutes of Health. Dr. Liu also received support as a W.W. Caruth, Jr. Scholar in Biomedical Research at UT Southwestern, and from the Cecil H. and Ida Green Center Training Program in Reproductive Biology Sciences.

The study used resources of the Advanced Photon Source at Argonne National Laboratory and of the Advanced Light Source at Lawrence Berkeley National Laboratory, both supported by the U.S. Department of Energy Office of Science.


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