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Institute to Focus on Exploring Genome Function

   (NIH) - 4/25/2012 - The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, has awarded 10 grants, totaling $10.5 million, to develop revolutionary technologies that will help researchers identify millions of genomic elements that play a role in determining what genes are expressed and at what levels in different cells. These multi-year grants are part of the Encyclopedia of DNA Elements (ENCODE) project, whose aim is to provide the scientific community with a comprehensive catalog of functional genomic elements that will ultimately help explain the role that the genome plays in health and disease.
   "The ENCODE project is providing a Rosetta Stone to understand how the sequence of the human genome forms the words that tell our bodies how to work at the molecular level," said Eric D. Green, M.D., Ph.D., director of NHGRI, which directs and funds the ENCODE project. "By developing more revolutionary technologies for probing genome function, we expect to accelerate these efforts."
   Sequencing the human genome and identifying the small fraction of its bases that directly code for proteins were among the first steps in understanding how the genome functions. But the remaining larger fraction of functional genomic elements continues to be a mystery. In response, NHGRI launched the ENCODE project to identify all the functional elements in the human genome, along with the modENCODE project to identify the functional elements in the fly and worm genomes and a smaller effort examining the mouse genome. These projects have been rapidly releasing data to the research community.
   These ENCODE efforts have collected large amounts of data with a wide variety of cell types, in many cases identifying key functional landmarks. By studying these landmarks, researchers can establish the locations of DNA sequences that perform a variety of essential functions.
   "In an exciting development, researchers are beginning to use the ENCODE catalogs to understand how variation in the DNA sequence might influence diseases such as cancer and autoimmune disorders," said Mike Pazin, Ph.D., a program director for ENCODE in NHGRI's Division of Extramural Research.
   Each person has one genome sequence that is basically the same in all cell types. In contrast, many genomic elements function in only some cell types. As a result, researchers must test many cell types using many different experimental approaches to develop a detailed inventory of the functional elements in the genome. Revolutionary technological improvements are required to discover and test the millions of functional elements and to learn more precisely what they do. Significant advances are also needed to establish whether information about these functional elements can be used in the diagnosis and treatment of disease.
   "The current ENCODE efforts owe a good part of their success to technology development that has occurred over the last decade," said Elise A. Feingold, Ph.D., a program director for ENCODE in NHGRI's Division of Extramural Research. "In addition to the technologies developed through this program, ENCODE has benefitted enormously from advances fostered by NHGRI’s DNA sequencing technology initiative, the $1000 Genome Program."
   The new technology development grants are focused on these areas:
Discovery of functional genomic elements will be addressed by funding projects for a new assay to identify RNA splicing elements, new assays to identify promoters and enhancers, as well as a project to improve assays for identifying functional elements by allowing these assays to work reliably using smaller samples. Splicing is the process that joins RNA copies of gene segments together to form mRNA, the blueprint for the production of proteins.
   Errors in splicing sometimes lead to human disease. Promoters specify the sites in the genome where genes begin and much gene regulation occurs. Enhancers are genomic elements that can turn on expression of nearby and distant genes. Mutations in promoters and enhancers can cause human disease.
   Validation of biological elements will be addressed by funding projects for new methods with improved throughput, and a smaller project to improve accuracy by testing elements in their natural genomic context.
Computational analysis will be addressed by funding projects to predict regulatory protein binding and gene expression based on sequence alone, and to predict chromosomal interactions and link functional elements to their target genes.
   Recipients of the technology development awards are:
  1.  Discovery of Functional Elements
   Christopher Burge, Ph.D.; Massachusetts Institute of Technology, Cambridge, Mass.; $800,000 (over three years); Researchers will develop a new technology to catalog all of the RNA branch points that form in mRNA during splicing.
   Mats Ljungman, Ph.D.; University of Michigan, Ann Arbor; $1,200,000 (over three years); Using bromouridine labeling of RNA, these researchers will develop new assays (BruChase-Seq and BrUV-Seq) to identity promoters and enhancers and to measure mRNA degradation and splicing kinetics.
  Raymond David Hawkins, Ph.D.; University of Washington School of Medicine, Seattle; $460,000 (over two years); These researchers will improve the power of ChIP-seq assays to identify functional elements. ChIP-seq is one of the fundamental assays used in ENCODE to identify the locations in the genome that are attached to a particular protein.
   2. Validating the Biological Role of Functional Elements
   Barak Cohen, Ph.D.; Washington University in St. Louis; $1.1 million (over three years); These investigators will develop a method to test tens of thousands of promoters in primary cells.
  Peggy Farnham, Ph.D.; University of California Davis; $540,000 (over two years); These investigators will test the function of genomic regions that bind large numbers of regulatory proteins. They will precisely remove parts of the genome, and ask how neighboring genes are affected.
   Jason Lieb, Ph.D.; University of North Carolina at Chapel Hill; $1.3 million (over three years); Researchers will develop a method to test tens of thousands of regions of open chromatin for enhancer, promoter, insulator and silencer activity. In cells, the DNA of the genome is associated with proteins to form chromatin. Active regulatory elements in the genome are thought to reside in open chromatin, where the DNA is more exposed.
  Tarjei Sigurd Mikkelsen, Ph.D.; The Broad Institute of MIT and Harvard, Cambridge, Mass.; $1.1 million (over three years); Researchers will test tens of thousands of elements in integrated reporters, for enhancer activity, insulator function and RNA processing regulation. Insulators are elements that form boundaries in the genome, dividing the genome into functionally separated neighborhoods.
  Jay Shendure, M.D., Ph.D.; University of Washington, Seattle; $1.9 million(over three years); These investigators will develop methods to capture or synthesize tens of thousands of regulatory elements, and test them in cell lines and mice. Capture is a technique used to purify particular DNA sequences from a complex mix.
3. Computational Analysis
   Christina Leslie, Ph.D.; Memorial Sloan-Kettering Cancer Center, New York City; $1.6 million (over three years); Investigators will develop new computational approaches to understand cell-specific gene expression programs, modeling cell-specific transcription as a function of chromatin state and transcription factor binding. Though the genome is essentially the same in all cell types, different genes are active in different cell types because different cell types have different regulatory proteins.
   Guo-cheng Yuan, Ph.D.; Dana-Farber Cancer Institute, Boston; $530,000 (over two years); Researchers will develop novel computational methods to characterize chromatin states and predict chromatin interactions from these states. Functional elements that work together are thought to physically interact with each other by looping out parts of the genome that are in between.
   For more information about the ENCODE and modENCODE projects, please visit http://www.genome.gov/10005107.

Charges Filed in Massive Internet Fraud Scheme

   (RPC) - 4/22/2012 - Preet Bharara, the United States Attorney for the Southern District of New York, announced on April 20 the extradition of Anton Ivanov from Estonia to face charges of conspiracy to commit wire fraud and computer intrusion, among other offenses. The charges relate to the alleged operation of a massive and sophisticated Internet fraud scheme that infected with malware more than four million computers located in over 100 countries. The malware secretly altered the settings on infected computers enabling Ivanov and the six other charged defendants – Vladimir Tsastsin, Timur Gerassimenko, Dmitri Jegorov, Valeri Aleksejev, Konstantin Poltev, and Andrey Taame – to digitally hijack Internet searches and re-route computers to certain websites and advertisements.
   The defendants subsequently received millions of dollars in fees as a result of unintended visits to these websites and ads by users of infected computers. The malware also prevented the installation of anti-virus software and operating system updates on infected computers, leaving those computers and their users unable to detect or stop the defendants’ malware, and exposing them to attacks by other viruses.
   Ivanov, an Estonian citizen, was arrested in Estonia on November 8, 2011, when the Indictment against him was unsealed. He arrived in the Southern District of New York on April 20 and was presented and arraigned before U.S. Magistrate Judge Debra Freeman.
   Bharara stated: “ Operating from thousands of miles away, this defendant and his co-conspirators allegedly concocted a diabolical scheme that infected millions of computers and victimized legitimate advertisers and websites alike. Cyber crime is a grave and constant threat that is international in its scope and requires international solutions. The arrests in this case and today’s extradition of this defendant are emblematic of the kind of international cooperation that is required to fight this threat. We are committed to fighting and winning this battle .”
   The following allegations are based on the Indictment and other court documents previously filed in Manhattan federal court:
   From 2007 until October 2011, Ivanov, Tsastsin, Gerassimenko, Jegorov, Aleksejev, Poltev, and Taame controlled and operated various companies that masqueraded as legitimate publisher networks (the “Publisher Networks”) in the Internet advertising industry. The Publisher Networks entered into agreements with ad brokers under which they were paid based on the number of times that Internet users clicked on the links for certain websites or advertisements, or based on the number of times that certain advertisements were displayed on certain websites. Thus, the more traffic that went to the advertisers’ websites and display ads, the more money the defendants earned under their agreements with the ad brokers. The defendants fraudulently increased the traffic to the websites and advertisements that would earn them money and made it appear to advertisers that the Internet traffic came from legitimate clicks and ad displays on the defendants’ Publisher Networks when, in actuality, it had not.
   To carry out the scheme, the defendants and their co-conspirators used what are known as “rogue” Domain Name System (“DNS”) servers, and malware (“the Malware”) that was designed to alter the DNS server settings on infected computers. Victims’ computers became infected with the Malware when they visited certain websites or downloaded certain software to view videos online. The Malware altered the DNS server settings on victims’ computers to route the infected computers to rogue DNS servers controlled and operated by the defendants and their co-conspirators. The re-routing took two forms that are described in detail below: “click hijacking” and “advertising replacement fraud.” The Malware also prevented the infected computers from receiving anti-virus software updates or operating system updates that otherwise might have detected the Malware and stopped it. In addition, the infected computers were also left vulnerable to infections by other viruses.
   When the user of an infected computer clicked on a search result link displayed through a search engine query, the Malware caused the computer to be re-routed to a different website. Instead of being brought to the website to which the user asked to go, the user was brought to a website designated by the defendants. Each “click” triggered payment to the defendants under their advertising agreements. This click hijacking occurred for clicks on unpaid links that appeared in response to a user’s query as well as clicks on “sponsored” links or advertisements that appeared in response to a user’s query – often at the top of, or to the right of, the search results – thus causing the search engines to lose money. For example:
  •  When the user of an infected computer clicked on the domain name link for the official website of Apple-iTunes, the user was instead taken to a website for a business unaffiliated with Apple Inc. that purported to sell Apple software.
  • When the user of an infected computer clicked on the domain name link for the official government website of the Internal Revenue Service, the user was instead taken to the website for H&R Block, a major tax preparation business.
   Using the DNS Changer Malware and rogue DNS servers, the defendants also replaced legitimate advertisements on websites with substituted advertisements that triggered payments to the defendants. For example:
  • When the user of an infected computer visited the home page of the Wall Street Journal, a featured advertisement for the American Express “Plum Card” had been fraudulently replaced with an ad for “Fashion Girl LA.”
  • When the user of an infected computer visited the Amazon.com website, a prominent advertisement for Windows Internet Explorer 8 had been fraudulently replaced with an ad for an email marketing business.
   In conjunction with the arrests in Estonia on November 8, 2011, authorities in the United States obtained a court order to implement a remediation plan to minimize any disruption of Internet service to the users of computers infected with the Malware. This remediation was necessary because the dismantling of the defendants’ rogue DNS servers – to which millions of computers worldwide had been redirected – would potentially have caused all of those computers, for all practical purposes, to lose access to websites. As part of that order, the defendant’s rogue DNS servers have been replaced with legitimate ones administered by the Internet Systems Consortium (“ISC”), a not-for-profit entity, for a limited period of 120 days. A subsequent order extended the period of operation for another 120 days, ending on July 9, 2012.
   Ivanov, 27, of Tartu, Estonia, faces a maximum sentence of 85 years in prison in connection with the charges in the Indictment.
   Estonian nationals Tsastsin, Gerassimenko, Jegorov, Aleksejev, and Poltev were also arrested in November 2011, and are in custody in Estonia. The last defendant, Taame, who is a Russian national, remains at large.
   The case against all seven defendants was scheduled to be heard before U.S. District Judge Lewis A. Kaplan.
   Bharara praised the outstanding investigative work of the Federal Bureau of Investigation, National Aeronautics and Space Administration-Office of the Inspector General, and the Estonian National Police and Border Guard Board. He also thanked the Office of International Affairs in the U.S. Department of Justice’s Criminal Division for its assistance with the extradition.
   This case is being handled by the Office’s Complex Frauds Unit. Assistant U.S. Attorneys Sarah Lai, James Pastore, and Alexander Wilson are in charge of the prosecution.
   The charges and allegations contained in the Indictment are merely accusations, and the defendants are presumed innocent unless and until proven guilty.
   Source: Financial Fraud Enforcement Task Force

EPA Publishes U.S. Greenhouse Gas Inventory

   WASHINGTON - (EPA) - 4/16/2012 - The U.S. Environmental Protection Agency (EPA) has released the 17th annual U.S. greenhouse gas inventory. The final report shows overall emissions in 2010 increased by 3.2 percent from the previous year. The trend is attributed to an increase in energy consumption across all economic sectors, due to increasing energy demand associated with an expanding economy, and increased demand for electricity for air conditioning due to warmer summer weather during 2010.
    Total emissions of the six main greenhouse gases in 2010 were equivalent to 6,822 million metric tons of carbon dioxide. These gases include carbon dioxide, methane, nitrous oxide, hydrofluorocarbons, perfluorocarbons and sulfur hexafluoride. The report indicates that overall emissions have grown by over 10 percent from 1990 to 2010.
    The Inventory of U.S. Greenhouse Gas Emissions and Sinks: 1990-2010 is the latest annual report that the United States has submitted to the Secretariat of the United Nations Framework Convention on Climate Change, which sets an overall framework for intergovernmental efforts to tackle the challenge posed by climate change.
   EPA prepares the annual report in collaboration with experts from multiple federal agencies and after gathering comments from stakeholders across the country.
    The inventory tracks annual greenhouse gas emissions at the national level and presents historical emissions from 1990 to 2010. The inventory also calculates carbon dioxide emissions that are removed from the atmosphere by “sinks,” e.g., through the uptake of carbon by forests, vegetation and soils.
   Source: EPA

Holding Company CEO Charged with Bank Fraud

   BROOKLYN, N.Y. – 4/13/2012 - The former chief executive officer of a publicly held food products company that traded on the NASDAQ and manufactured and distributed a line of baking mixes and spices was indicted on April 13 on conspiracy, bank fraud and false statement charges arising out his scheme to inflate Synergy’s sales through a $26 million bank fraud scheme. Mair Faibish, the former chief executive officer of Synergy Brands Inc., was arrested earlier in the day and was due to appear in court before U.S. Magistrate Judge Viktor V. Pohorelsky in Brooklyn.
   The charges were announced by Loretta E. Lynch, U.S. Attorney for the Eastern District of New York; James T. Hayes Jr., Special Agent-in-Charge, Department of Homeland Security (DHS), Homeland Security Investigations (HSI), New York Field Office; and Nassau County, N.Y., Police Commissioner Thomas V. Dale.
    As alleged in the indictment, the defendant and his co-conspirators fraudulently inflated Synergy’s sales by approximately 20 percent for the quarter ending June 30, 2008, through an international check kiting scheme in which they kited approximately $750 million worth of checks not backed by sufficient funds through various banks in the United States and Canada.
   The defendant caused those checks to be deposited into bank accounts of associated food manufacturers and distributors in Canada. The Canadian companies then sent checks in corresponding amounts, but also not backed by sufficient funds, back to Synergy. Because the banks made deposited funds immediately available for withdrawal, the scheme artificially inflated the companies’ bank account balances while the scheme was ongoing. The defendant and his co-conspirators used Synergy’s fraudulently inflated bank account balance to book millions of dollars in fictitious accounts receivable and revenue. By the end of the scheme, Signature Bank had lost approximately $26 million that the defendant and his co-conspirators had withdrawn before the bank discovered the scheme.
   In addition to the bank fraud and conspiracy charges, the indictment charges that the defendant made false statements to the U.S. Securities and Exchange Commission (SEC) about Synergy’s financial condition in a public filing, specifically: (1) that Synergy had approximately $44.5 million in sales, when approximately 20 percent of those sales were fictitious; (2) that Synergy had approximately $40 million in cost of goods sold, when approximately 20 percent of the cost of goods sold was fictitious; and (3) that Synergy recognized approximately $1.5 million in “prepaid expenses,” when at least 25 percent of those prepaid expenses were fictitious.
    According to the company’s filings with the SEC, Synergy was a holding company with subsidiaries that distributed nationally known food and beauty products to retailers and wholesalers and manufactured baking products through its Loretta Baking Mix Products subsidiary. Synergy also sold premium cigars to restaurants, hotels, casinos and country clubs as well as directly to consumers over the Internet and through its retail store in Miami.
   “The defendant allegedly defrauded an FDIC-insured bank out of millions of dollars through a massive check-kiting scheme, as well as fraudulently inflated Synergy’s financial statements in order to make the struggling company appear prosperous. These false representations were then provided to the SEC and the investing public,” Lynch said. “Corporate executives who abuse their positions of trust can expect to be investigated and prosecuted to the full extent of the law.”
   If convicted, the defendant faces a maximum sentence of 30 years in prison on the most serious charge in the indictment.
   The government’s case is being prosecuted by Assistant U.S. Attorneys Ilene Jaroslaw and Sylvia Shweder.
   Source: Financial Fraud Enforcement Task Force

Pesticides Associated With Lower Birth Weight

   Oakland, Calif. – (EWG) - 4/9/2012 - A new study is reinforcing obstetricians’ standard warning that pregnant women should avoid exposure to pesticides in foods and weed killers because the chemicals can harm the developing fetus.
   In the study, Cincinnati-area women had levels of organophosphate insecticides that significantly affected birth weight and gestation period.
   “This latest report is further evidence that babies in the womb are exquisitely sensitive to pesticide exposure,” said Ken Cook, president and co-founder of Environmental Working Group. “While much has been done to reduce people’s exposure to organophosphates, this important study shows that even remaining exposures are harmful.”
   Lead researcher Bruce Lanphear MD MPH, and his colleagues tracked an ethnically and economically diverse group of more than 300 expectant mothers from the Cincinnati area. They found that newborns of women with the highest levels of organophosphates in their urine were delivered, on average, about half a week earlier and weighed one-third of a pound less than those of women with the lowest exposures.
   The abstract of the new study can be found in the journal Environmental Health Perspectives.
   For years, EWG has urged the US Environmental Protection Agency to reduce the use of these highly toxic pesticides in agriculture and advised consumers to avoid fruits and vegetables with the highest levels of pesticides. Last year, three studies found that prenatal exposure to organophosphates was associated with diminished IQ in children. Other research has linked organophosphate exposure in children to increased risk of attention deficit hyperactivity disorder (ADHD).
   Source: EWG release

NIH Study: Arsenic Turns Stem Cells Cancerous

   (NIH) - 4/7/2011 - Researchers at the National Institutes of Health have discovered how exposure to arsenic can turn normal stem cells into cancer stem cells and spur tumor growth. Inorganic arsenic, which affects the drinking water of millions of people worldwide, has been previously shown to be a human carcinogen. A growing body of evidence suggests that cancer is a stem-cell based disease. Normal stem cells are essential to normal tissue regeneration, and to the stability of organisms and processes. But cancer stem cells are thought to be the driving force for the formation, growth, and spread of tumors.
   Michael Waalkes, Ph.D., and his team at the National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, part of NIH, had shown previously that normal cells become cancerous when they are treated with inorganic arsenic. This new study shows that when these cancer cells are placed near, but not in contact with normal stem cells, the normal stem cells very rapidly acquire the characteristics of cancer stem cells. It demonstrates that malignant cells are able to send molecular signals through a semi-permeable membrane, where cells can't normally pass, and turn the normal stem cells into cancer stem cells.
   “This paper shows a different and unique way that cancers can expand by recruiting nearby normal stem cells and creating an overabundance of cancer stem cells,” Waalkes said. “The recruitment of normal stem cells into cancer stem cells could have broad implications for the carcinogenic process in general, including tumor growth and metastases.”
   This reveals a potentially important aspect of arsenic carcinogenesis and may help explain observances by researchers working with arsenic that arsenic often causes multiple tumors of many types to form on the skin or inside the body. The paper is online in Environmental Health Perspectives.Waalkes' lab started working with stem cells about five years ago. The researchers used a prostate stem cell line, not embryonic stem cells.
   “Using stem cells to answer questions about disease is an important new growing area of research. Stem cells help to explain a lot about carcinogenesis, and it is highly likely that stem cells are contributing factors to other chronic diseases,” Waalkes said.
   Stem cells are unique in the body. They stay around for a long time and are capable of dividing and renewing themselves. “Most cancers take 30 or 40 years to develop,” said Linda Birnbaum, Ph.D., director of NIEHS and NTP. “It makes sense that stem cells may play a role in the developmental basis of adult disease. We know that exposures to toxicants during development and growth can lead to diseases later in life.”
   Next, the laboratory team will look to see if this finding is unique to arsenic or if it is applicable to other organic and inorganic carcinogens.
   Source:  http://www.nih.gov/

Photo by Steve Rensberry (c) 2014