Epigenetic changes shed light on biological mechanism of autism

Apr. 23, 2013 ? Scientists from King's College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits.

The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits.

ASD affects approximately 1 in 100 people in the UK and involves a spectrum of disorders which manifest themselves differently in different people. People with ASD have varying levels of impairment across three common areas: deficits in social interactions and understanding, repetitive behaviour and interests, and impairments in language and communication development.

Evidence from twin studies shows there is a strong genetic component to ASD and previous studies suggest that genes that direct brain development may be involved in the disorder. In approximately 70% of cases, when one identical twin has ASD, so does the other. However, in 30% of cases, identical twins differ for ASD. Because identical twins share the same genetic code, this suggests non-genetic, or epigenetic, factors may be involved.

Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence -- they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies.

The researchers studied an epigenetic mechanism called DNA methylation. DNA methylation acts to block the genetic sequences that drive gene expression, silencing gene activity. They examined DNA methylation at over 27,000 sites across the genome using samples taken from 50 identical twin pairs (100 individuals) from the UK Medical Research Council (MRC) funded Twins Early Development Study (TEDS): 34 pairs who differed for ASD or autism related behaviour traits, 5 pairs where both twins have ASD, and 11 healthy twin pairs.

Dr Chloe Wong, first author of the study from King's College London's Institute of Psychiatry, says: "We've identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder."

DNA methylation at some genetic sites was consistently altered for all individuals with ASD, and differences at other sites were specific to certain symptom groups. The number of DNA methylation sites across the genome was also linked to the severity of autism symptoms suggesting a quantitative relationship between the two. Additionally, some of the differences in DNA methylation markers were located in genetic regions that previous research has associated with early brain development and ASD.

Professor Jonathan Mill, lead author of the paper from King's College London's Institute of Psychiatry and the University of Exeter, says: "Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions."

Dr Alycia Halladay, Senior Director of Environmental and Clinical Sciences from Autism Speaks who funded the research, says: "This is the first large-scale study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical but have different symptoms. These findings open the door to future discoveries in the role of epigenetics -- in addition to genetics -- in the development of autism symptoms."

The study was funded by Autism Speaks, Medical Research Council UK (MRC) and the Brain and Behavior Research Foundation (NARSAD). The twins were selected from the Twins Early Development Study (TEDS) which is funded by the MRC with additional support from the US National Institutes of Health.

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The above story is reprinted from materials provided by King's College London.

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Journal Reference:

1. C C Y Wong, E L Meaburn, A Ronald, T S Price, A R Jeffries, L C Schalkwyk, R Plomin, J Mill. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Molecular Psychiatry, 2013; DOI: 10.1038/mp.2013.41

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/health_medicine/genes/~3/5SSPuYtQGZA/130423091113.htm

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Scientists provide 'new spin' on emerging quantum technologies

Apr. 23, 2013 ? An international team of scientists has shed new light on a fundamental area of physics which could have important implications for future electronic devices and the transfer of information at the quantum level.

The electrical currents currently used to power electronic devices are generated by a flow of charges. However, emerging quantum technologies such as spin-electronics, make use of both charge and another intrinsic property of electrons ? their spin ? to transfer and process signals and information.??

The experimental and theoretical work, carried out by researchers from York?s Department of Physics, the Institute of Nanoscience in Paris and the University of Missouri-Columbia, USA, could have important implications for spintronics and quantum information technologies.

The team looked at semiconductors? structures ? the base of current electronic devices and of many spintronic device proposals - and the problems created by internal fields known as spin-orbit fields. In general, these tend to act differently on each electronic spin, causing a phenomenon referred to as ?spin-decoherence?. This means that the electronic spins will behave in a way which cannot be completely controlled or predicted, which has important implications for device functionalities.

To address this problem, the scientists looked at semiconductor structures called ?quantum wells? where the spins can be excited in a collective, coherent way by using lasers and light scattering. ?????

They demonstrated that these collective spin excitations possess a macroscopic spin of quantum nature. In other words, the electrons and their spins act as a single entity making them less susceptible to spin orbit fields, so decoherence is highly suppressed.

The theoretical work was led by Dr Irene D?Amico from York?s Department of Physics, and Carsten Ullrich, an Associate Professor from Missouri-Columbia?s Department of Physics. The project began with their prediction about the effect of spin Coulomb drag on collective spin excitations, and developed into a much larger international project spanning over three years, which was funded in the UK by a Royal Society grant, with additional funding from the Engineering and Physical Sciences Research Council (EPSRC).

Dr D?Amico said: ?This work has developed into a strong international collaboration which has greatly improved our understanding at fundamental level of the role of many-body interactions on the behaviour of electron spins.

?By combining experimental and theoretical work, we were able to demonstrate that through many-body interactions, a macroscopic collection of spins can behave as a single entity with a single macroscopic quantum spin, making this much less susceptible to decoherence. In the future, it may be possible to use these excitations as signals to transport or elaborate information at the quantum level.?

After reporting their results in the journal Physical Review Letters last year, the team of scientists confirmed and extended the results by considering different materials and type of excitation. The second set of experiments, were recently reported in Physical Review B (Rapid Communication) and highlighted by the Journal as an ?Editor?s Suggestion?.

Dr Florent Perez, who led the experimental work with Florent Baboux, at the CNRS/Universit? Paris VI, says the results strongly suggest that the quantum nature of the macroscopic spin is universal to collective spin excitations in conductive systems.

He said: ?The collaboration with Irene D?Amico and Carsten Ullrich has been particularly powerful to disentangle the puzzle of our data. In our first joint work we constructed an interpretation of the phenomenon which was confirmed in a second investigation carried out on a different system. This paved the way for a universality of the effect.?

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Journal References:

1. F. Baboux, F. Perez, C. A. Ullrich, I. D?Amico, J. G?mez, M. Bernard. Giant Collective Spin-Orbit Field in a Quantum Well: Fine Structure of Spin Plasmons. Physical Review Letters, 2012; 109 (16) DOI: 10.1103/PhysRevLett.109.166401
2. F. Baboux, F. Perez, C. A. Ullrich, I. D'Amico, G. Karczewski, T. Wojtowicz. Coulomb-driven organization and enhancement of spin-orbit fields in collective spin excitations. Physical Review B, 2013; 87 (12) DOI: 10.1103/PhysRevB.87.121303

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_technology/~3/FO4fPwHMdsc/130423091030.htm

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Boston bomb suspect charged; religious motive seen

FILE - This file photo provided Friday, April 19, 2013 by the Federal Bureau of Investigation shows Boston Marathon bombing suspect Dzhokhar Tsarnaev. A court official says Dzhokhar Tsarnaev, the surviving suspect in the bombings, is facing federal charges and has made an initial court appearance in his hospital room, Monday, April 22, 2013. (AP Photo/Federal Bureau of Investigation, File)

FILE - This file photo provided Friday, April 19, 2013 by the Federal Bureau of Investigation shows Boston Marathon bombing suspect Dzhokhar Tsarnaev. A court official says Dzhokhar Tsarnaev, the surviving suspect in the bombings, is facing federal charges and has made an initial court appearance in his hospital room, Monday, April 22, 2013. (AP Photo/Federal Bureau of Investigation, File)

A moment of silence in honor of the victims of the Boston Marathon bombing is observed on Boylston Street near the race finish line, exactly one week after the tragedy, Monday, April 22, 2013, in Boston, Mass. (AP Photo/Robert F. Bukaty)

People pause for a moment of silence near the Statehouse in Boston at 2:50pm, Monday, April 22, 2013, exactly one week after the first bomb went off at the finish area of the Boston Marathon. (AP Photo/Elise Amendola)

People link hands to form a human chain from a makeshift memorial for fallen MIT police officer Sean Collier to a campus police station at the Massachusetts Institute of Technology in Cambridge, Mass., Monday, April 22, 2013. A moment of silence for victims of the marathon bombings was also observed during the event. Collier was fatally shot on the MIT campus Thursday, April 18, 2013. Authorities allege that Boston Marathon bombing suspects Tamerlan and Dzhokhar Tsarnaev were responsible. (AP Photo/Steven Senne)

A moment of silence in honor of the victims of the bombing at the Boston Marathon is observed at the corner of Boylston and Berkeley Streets near the race finish line, Monday, April 22, 2013, in Boston, Mass. At 2:50 p.m., exactly one week after the bombings, many bowed their heads and cried at the makeshift memorial on Boylston Street, three blocks from the site of the explosions, where bouquets of flowers, handwritten messages, and used running shoes were piled on the sidewalk. (AP Photo/Robert F. Bukaty)

BOSTON (AP) ? The two brothers suspected of bombing the Boston Marathon appear to have been motivated by a radical brand of Islam but do not seem connected to any Muslim terrorist groups, U.S. officials said Monday after interrogating and charging Dzhokhar Tsarnaev with crimes that could bring the death penalty.

Tsarnaev, 19, was charged in his hospital room, where he was in serious condition with a gunshot wound to the throat and other injuries suffered during his attempted getaway. His older brother, Tamerlan, 26, died Friday after a fierce gunbattle with police.

The Massachusetts college student was charged with using and conspiring to use a weapon of mass destruction. He was accused of joining with his brother in setting off the shrapnel-packed pressure-cooker bombs that killed three people and wounded more than 200 a week ago.

The brothers, ethnic Chechens from Russia who had been living in the U.S. for about a decade, practiced Islam.

Two U.S. officials said preliminary evidence from the younger man's interrogation suggests the brothers were motivated by religious extremism but were apparently not involved with Islamic terrorist organizations.

Dzhokhar communicated with his interrogators in writing, precluding the type of back-and-forth exchanges often crucial to establishing key facts, said the officials, who spoke on condition of anonymity because they were not authorized to discuss the investigation publicly.

They cautioned that they were still trying to verify what they were told by Tsarnaev and were looking at such things as his telephone and online communications and his associations with others.

In the criminal complaint outlining the allegations, investigators said Tsarnaev and his brother each placed a knapsack containing a bomb in the crowd near the finish line of the 26.2-mile race.

The FBI said surveillance-camera footage showed Dzhokhar manipulating his cellphone and lifting it to his ear just instants before the two blasts.

After the first blast, a block away from Dzhokhar, "virtually every head turns to the east ... and stares in that direction in apparent bewilderment and alarm," the complaint says. Dzhokhar Tsarnaev, "virtually alone of the individuals in front of the restaurant, appears calm."

He then quickly walked away, leaving a knapsack on the ground; about 10 seconds later, a bomb blew up at the spot where he had been standing, the FBI said.

The FBI did not say whether he was using his cellphone to detonate one or both of the bombs or whether he was talking to someone.

The criminal complaint shed no light on the motive for the attack.

The Obama administration said it had no choice but to prosecute Dzhokhar Tsarnaev in the federal court system. Some politicians had suggested he be tried as an enemy combatant in front of a military tribunal, where defendants are denied some of the usual constitutional protections.

But Tsarnaev is a naturalized U.S. citizen, and under U.S. law, American citizens cannot be tried by military tribunals, White House spokesman Jay Carney said. Carney said that since 9/11, the federal court system has been used to convict and imprison hundreds of terrorists.

Shortly after the charges were unveiled, Boston-area residents and many of their well-wishers ? including President Barack Obama at the White House ? observed a moment of silence at 2:49 p.m. ? the moment a week earlier when the bombs exploded.

Across Massachusetts, the silence was broken by the tolling of church bells.

"God bless the people of Massachusetts," said Gov. Deval Patrick at a ceremony outside the Statehouse. "Boston Strong."

Also Monday, the governor and Roman Catholic Cardinal Sean O'Malley were among the mourners at St. Joseph Church at the first funeral for one of the victims, Krystle Campbell. The 29-year-old restaurant manager had gone to watch a friend finish the race.

"She was always there for people. As long as Krystle was around, you were OK," said Marishi Charles, who attended the Mass. "These were the words her family wanted you to remember."

Amid a swirl of emotions in Boston, there was cause for some celebration: Doctors announced that everyone injured in the blasts who made it to a hospital alive now seems likely to survive.

That includes several people who arrived with legs attached by just a little skin, a 3-year-old boy with a head wound and bleeding on the brain, and a little girl riddled with nails.

"All I feel is joy," said Dr. George Velmahos, chief of trauma surgery at Massachusetts General Hospital, referring to his hospital's 31 blast patients. "Whoever came in alive stayed alive."

As of Monday, 51 people remained hospitalized, three of them in critical condition. At least 14 people lost all or part of a limb; three of them lost more than one.

Dzhokhar Tsarnaev had gunshot wounds to the head, neck, legs and hands when he was captured hiding out in a boat in a backyard in the Boston suburb of Watertown, authorities said.

A probable cause hearing ? at which prosecutors will spell out the basics of their case ? was set for May 30. According to a clerk's notes of Monday's proceedings in the hospital, U.S. Magistrate Judge Marianne Bowler indicated she was satisfied that Tsarnaev was "alert and able to respond to the charges."

Tsarnaev did not speak during the proceeding, except to answer "no" when he was asked if he could afford his own lawyer, according to the notes. He nodded when asked if he was able to answer some questions and whether he understood his rights as explained to him by the judge.

Federal Public Defender Miriam Conrad, whose office has been assigned to represent Tsarnaev, declined to comment.

Tsarnaev could also face state charges in the slaying of a Massachusetts Institute of Technology police officer, who was shot in his cruiser Thursday night on the MIT campus in Cambridge.

News of the criminal charges pleased some of the people gathered at a makeshift memorial along the police barricades on Boylston Street, where the attack took place.

Amy McPate a Massachusetts native now living in Maine, said she usually opposes the death penalty, but thinks it should apply in this case.

"They were more than murderers. They're terrorists. They terrorized the city," she said. "The nation has been terrorized."

Kaitlynn Cates of Everett, who suffered a leg injury in the bombing, said from her hospital room: "He has what's coming to him."

Among the details in the FBI affidavit:

? One of the brothers ? it wasn't clear which one ? told a carjacking victim during their getaway attempt, "Did you hear about the Boston explosion? I did that."

?The FBI said it searched Tsarnaev's dorm room at the University of Massachusetts-Dartmouth on Sunday and found BBs as well as a white hat and dark jacket that look like those worn by one of the suspected bombers in the surveillance photos the FBI released a few days after the attack.

___

Associated Press writers Steve Peoples, Allen Breed, Bridget Murphy, Jay Lindsay and Bob Salsberg in Boston contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/3d281c11a96b4ad082fe88aa0db04305/Article_2013-04-22-Boston%20Marathon-Explosions/id-91bca5c5b15f4ac0970214ebeee6ef9d

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Most EU bank union work can be done without law change: Eurogroup head

By Jan Strupczewski

WASHINGTON (Reuters) - The euro zone's top project to boost economic growth - banking union - will not be delayed for now by a row over whether it needs EU law changed because most of the work can be done before this is settled, a senior euro zone official said on Saturday.

Jeroen Dijsselbloem, the Dutch finance minister who chairs the monthly meetings of his euro zone colleagues, said the dispute on the legal requirements of the banking union can go in parallel with more technical work on how it would function.

"I am, in a sense, relaxed about it, because I know that we can push forward at least 80-90 pct of the project," Dijsselbloem told a news conference on the sidelines of the spring meeting of the International Monetary Fund.

The EU has already made the first step - it agreed the European Central Bank would take over the supervision of all banks in the euro zone from July 2014 in what is called the Single Supervisory Mechanism.

Dijsselbloem said the 17 countries using the euro can also move ahead with further harmonizing deposit guarantee programs, and creating rules on when the euro zone bailout fund, the European Stability Mechanism, or ESM, can buy a stake in a euro zone bank to boost its capital when no-one else can or wants to.

The euro zone will also create a network of national authorities responsible for closing down failing banks that will operate under the same rules.

It is the next step that becomes difficult.

The euro zone wants to transform the network of national resolution authorities into a single European institution that would decide which euro zone banks will be closed.

It would also have the ESM fund to pay for the process, until enough fees from banks accrue to cover any potential expense. The ambitious plan was for such a single resolution mechanism to be in place in 2014.

However, Germany, the euro zone's biggest economy, faces elections in September. It believes that to create such an authority, which could order the closure of a German bank, or use German taxpayers' money to pay for the closure of a bank elsewhere in the euro zone, EU laws have to be changed.

The European Commission, the executive arm of the European Union, says existing law provides sufficient basis.

"The crucial point is: can we have a single resolution authority - this is where the Germans feel a treaty change is needed to have a stronger legal basis," Dijsselbloem said.

A change of European Union treaties would substantially delay the launch of the banking union because apart from the time needed to negotiate the amendments it would also require time for parliaments of the 27 EU countries to ratify it.

There would also be a risk that the ratification fails in one or more countries and that some EU governments would use the opportunity to trade their support for concessions in other areas, opening the door to long and difficult negotiations.

But Dijsselbloem said the problem could be solved later.

"90 percent of the project can be pushed forward and there is a lot of work to be done there, so as far as I am concerned there is not going to be any delay," he said.

"We are going to work on these elements and in parallel have this debate if we need treaty change, what do we need to fix in this treaty change. We can do that in parallel while putting all the building blocks in place. So we might not lose any time."

(Reporting By Jan Strupczewski; Editing by Neil Stempleman)

Source: http://news.yahoo.com/most-eu-bank-union-done-without-law-change-182351061--business.html

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Author Dennis Lehane Praises Heroic Reaction to Boston Bombings (ABC News)

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The Tech That Helped Take Down Marathon Bombing Suspect Dzhokar Tsarnaev

The second suspect in the brutal Boston Marathon bombings has been apprehended, after five days of uncertainty and fear. And while all credit for Dzhokar Tsarnaev's capture goes to the men and women of the many, many agencies that spent the last week tracking him down, technology played as prominent a role as it ever has in a time of national crisis. More »

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Muscle repair after injury helped by fat-forming cells

Apr. 19, 2013 ? UC San Francisco scientists have discovered that muscle repair requires the action of two types of cells better known for causing inflammation and forming fat.

The finding in mice, published in the April 11 issue of Cell, showed that a well-known immune cell called the eosinophil [ee-oh-SIN-oh-fil] carries out the beneficial role in two ways -- by clearing out cellular debris from damaged tissue and teaming up with a type of cell that can make fat to instead trigger muscle regrowth.

The study, led by Ajay Chawla, MD, PhD, an associate professor of medicine at the UCSF Cardiovascular Research Institute, showed that after eosinophils move to the site of injury, they collaborate with a kind of progenitor cell -- immature cells similar to stem cells -- to drive the formation of new muscle fibers. The progenitors, called the fibro/adipogenic cells (FAP), do not spin off muscle cells directly.

"Without eosinophils you cannot regenerate muscle," Chawla said.

FAP cells have been known for their role in making fat, which occurs as the body ages or experiences prolonged immobility. They also have been known to make cells that form connective tissue. But the UCSF study showed that FAP cells also team up with eosinophils to make injured muscles get stronger rather than fatter, at least in mice.

In a kind of cellular chain reaction, Chawla's team found that when eosinophils at the site of muscle injury secrete a molecule called IL-4, FAP cells respond by expanding their numbers. And instead of becoming fat cells, they act on the true muscle stem cells to trigger the regrowth of muscle fibers.

"They wake up the cells in muscle that divide and form muscle fibers," he said.

Eosinophils help fight bacteria and parasites, as do other immune cells, but eosinophils are more often thought of for their maladaptive roles in allergies and other inflammatory reactions. Eosinophils comprise only a few percent of immune cells.

Chawla's team found that, even before active muscle repair, the chain reaction initiated by eosinophils performs another necessary task -- taking out the garbage.

"Eosinophils, acting via FAPs, are needed for the rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues," Chawla said.

Bigger and more abundant immune cells called macrophages -- with large appetites and a propensity to gobble up debris in other destructive scenarios -- had often, but erroneously, been credited with cleaning up messes within distressed muscle tissue.

"Bites from venomous animals, many toxicants, and parasitic worms all trigger somewhat similar immune responses that cause injury," Chawla said. "We want to know if eosinophils and FAPs are universally employed in these situations as a way to get rid of debris without triggering severe reactions such as anaphylactic shock."

Additional UCSF co-authors include postdoctoral fellow Jose E. Heredia, PhD; specialist Lata Mukundan, PhD; technician Francis Chen; Rahul Deo, MD, PhD, an assistant professor of medicine in residence; and Richard M. Locksley, MD, an immunologist and professor of medicine. Stanford researchers Thomas Rando, MD, PhD, and graduate student Alisa Mueller also were members of the study team.

The National Institutes for Health and the California Institute for Regenerative Medicine funded the research.

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The above story is reprinted from materials provided by University of California - San Francisco. The original article was written by Jeffrey Norris.

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Journal Reference:

1. Jose?E. Heredia, Lata Mukundan, Francis?M. Chen, Alisa?A. Mueller, Rahul?C. Deo, Richard?M. Locksley, Thomas?A. Rando, Ajay Chawla. Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration. Cell, 2013; 153 (2): 376 DOI: 10.1016/j.cell.2013.02.053

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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/~3/dLKOFclSb0E/130419171649.htm

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