Articles from groundbreaking new Violence and Gender journal published

PUBLIC RELEASE DATE:

5-Feb-2014

Contact: Kathryn Ruehle kruehle@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, February 5, 2014Mary Ann Liebert, Inc., publishers has announced the publication of six articles from Violence and Gender, a new peer-reviewed journal dedicated to the understanding, prediction, and prevention of violence and spearheaded by Mary Ellen O'Toole, PhD, Forensic Behavioral Consultant and Senior FBI Profiler/Criminal Investigative Analyst (ret.). The Journal is the international forum for the critical examination of biological, genetic, behavioral, psychological, racial, ethnic, and cultural factors as they relate to the gender of perpetrators of violence, and explores the difficult issues that are vital to threat assessment and violence prevention. The articles are available free on the Violence and Gender website at http://www.liebertpub.com/vio.

Among the published articles is "Why Do Young Males Attack Schools? Seven Discipline Leaders Share Their Perspectives," which offers an unprecedented look into the reasons for the high incidence of school shootings in the U.S., and addresses the reasons we see mostly young males (15-29) committing these types of crimes. The article delves into what motivates these perpetrators, including the potential role of the copycat phenomenon in behavior. Sharing their perspectives are world-renowned experts Jorge Folino, MD, PhD, National University of La Plata (Buenos Aires Province, Argentina); James Garbarino, PhD, Loyola University Chicago (IL); Steven Gorelick, PhD, Hunter College, City University of New York (New York, NY); Helin Hkknen-Nyholm, PhD, PsyJuridica Ltd. (Espoo, Finland); J. Reid Meloy, PhD, University of California, San Diego (La Jolla, CA); Stanton Samenow, PhD, Alexandria, VA; and Yuki S. Nishimura, MD, PhD, Keio University (Yokohama City, Japan).

"Violence is complicated, and too often misunderstood, myth-based, and stereotyped; we are shocked when we see the 'nice guy' next door arrested for serial murder, or the quiet loner go on a shooting rampage," says Dr. O'Toole. "Many of us even default to using terms like 'monster' and 'evil' to explain such behavior and the people responsible. These archaic terms don't educate us or explain the violence but rather catapult us back in time. It's time for change in how we view violence."

Other published articles include an insightful roundtable discussion with Christopher Kilmartin, PhD, University of Mary Washington (Fredericksburg, VA), and Col. Jeffery M. Peterson, USMC (ret.) and Center for Naval Analyses (Alexandria, VA), entitled "Sexual Assault in the Military: A Discussion of the Current Status and Future Prevention;" the Review article "The Mission-Oriented Shooter: A New Type of Mass Killer," by Editor-in-Chief Mary Ellen O'Toole, PhD; and a Perspective entitled "Understanding Brain Health Can Prevent Another Sandy Hook Shooting," by Jeremy Richman, PhD, Founder and CEO of The Avielle Foundation (Sandy Hook, CT).

"The imperative for this journal is urgent," said publisher Mary Ann Liebert, "we must stem the tide, and the papers in Violence and Gender have a most important mandate."

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The full inaugural issue of Violence and Gender will be published in Spring 2014.

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Articles from groundbreaking new Violence and Gender journal published

Can Genetic Engineering Mitigate California’s Drought?

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STANFORD, CA Water is in increasingly short supply in many parts of the United States. Here in California, where most of the state is experiencing extreme drought, 2013 was the driest year on record, and we have had no relief during what should be the height of the rainy season. Moreover, theres no end in sight: The Climate Prediction Center of the National Weather Serviceforecaststhat the drought will persist or intensify at least through April.

Reservoir levels are dropping, the snow pack is almost nonexistent, and many communities have already imposed restrictions on water usage. In the city of Santa Cruz, for example, restaurants can no longer serve drinking water unless diners specifically request it; Marin County residents have been asked not to clean their cars or to do so only at eco-friendly car washes; and there are limitations on watering lawns in towns in Mendocino County.

But it is the states premier industry farming that will feel the pinch most. In an average year, farmers use 80 percent of the water used by people and businesses, according to the Department of Water Resources.

During a January 19 press conference at which he declared a water emergency, Governor Jerry Brown said of the drought, This is not a partisan adversary. This is Mother Nature. We have to get on natures side and not abuse the resources that we have.

Drought may not be partisan, but it does raise critical issues of governance, public policyand how best to use the states natural resources. It also offers an example of the Law of Unintended Consequences: Ironically, Santa Cruz, Mendocino and Marin counties all of which boast politically correct, far-left politics are among the local jurisdictions that have banned a key technology that could conserve huge amounts of water.

The technology is genetic engineering performed with modern molecular techniques, sometimes referred to as genetic modification (GM) or gene-splicing, which enables plant breeders to make old crop plants do spectacular new things, including conserve water. In the United States and about 30 other countries, farmers are using genetically engineered crop varieties to produce higher yields, with lower inputs and reduced impact on the environment.

Even with R&D being hampered by resistance from activists and discouraged by governmental over-regulation, genetically engineered crop varieties are slowly but surely trickling out of the development pipeline in many parts of the world. Cumulatively, over 3.7 billion acres of them have been cultivated by more than 17 million farmers in 30 countries during the past 15 years without disrupting a single ecosystem or causing so much as a tummy ache in a consumer.

Most of these new varieties are designed to be resistant to herbicides, so that farmers can adopt more environment-friendly no-till farming practices and more benign herbicides; or to be resistant to pests and diseases that ravage crops. Others possess improved nutritional quality. But the greatest boon of all both to food security and to the environment in the long term will likely be the ability of new crop varieties to tolerate periods of drought and other water-related stresses. Where water is unavailable for irrigation, the development of crop varieties able to grow under conditions of low moisture or temporary drought could both boost yields and lengthen the time that farmland is productive.

Even where irrigation is feasible, plants that use water more efficiently are needed. Because irrigation for agriculture accounts for roughly 70 percent of the worlds fresh water consumption, the introduction of plants that grow with less water would allow much of it to be freed up for other uses. Especially during drought conditions, even a small percentage reduction in the use of water for irrigation could result in huge benefits.

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Can Genetic Engineering Mitigate California's Drought?

Is the male or female brain more vulnerable to triggers of violent behavior?

PUBLIC RELEASE DATE:

5-Feb-2014

Contact: Kathryn Ruehle kruehle@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, February 5, 2014Human behaviors such as violence depend on interactions in the brain between genetic and environmental factors. An individual may be more vulnerable to developing violent behaviors if they have predisposing factors and are then exposed to stress, abuse, or other triggers, especially early in life. The latest research on how differences between the male and female brain contribute to sex differences in violence is explored in Violence and Gender, a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Violence and Gender website at http://www.liebertpub.com/vio.

The article "Not Hardwired: The Complex Neurobiology of Sex Differences in Violence" describes the complex and flexible biological mechanisms in the brain that lead to the development of behaviors. These include interconnected neural networks, multiple genes, and chemical signals such as hormones and neurotransmitters, which can be modified by environmental factors. Brain structure, function, and connectivity can all differ between men and women, affecting how they may change on exposure to stressful or abusive triggers.

"Neurobiologist Dr. Debra Niehoff explains the amazing interaction of how our brains, genetics, and environmental influences can interact and serve as the genesis for violent behavior," says Editor-in-Chief of Violence and Gender Mary Ellen O'Toole, PhD, Forensic Behavioral Consultant, and Senior FBI Profiler/Criminal Investigator Analyst (ret.). "This holistic view of the origin of violence means that reducing violence will not be a simple fix because it does not have a single origin or cause. The temptation to delineate a male and female brain must be resisted because there is overlap between the two. With more research will come greater insight and knowledge about the biological and environmental causes of violence. With more knowledge will come answers; answers will lead to solutions, and with solutions will come prevention."

###

About the Journal

Violence and Gender is the only peer-reviewed journal focusing on the understanding, prediction, and prevention of acts of violence. Through research papers, roundtable discussions, case studies, and other original content, the Journal critically examines biological, genetic, behavioral, psychological, racial, ethnic, and cultural factors as they relate to the gender of perpetrators of violence. Led by Editor-in-Chief Mary Ellen O'Toole, PhD, Forensic Behavioral Consultant and Senior FBI Profiler/Criminal Investigative Analyst (ret.), Violence and Gender explores the difficult issues that are vital to threat assessment and prevention of the epidemic of violence. Violence and Gender is published quarterly online with Open Access options and in print, and is the official journal of The Avielle Foundation.

About the Publisher

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Is the male or female brain more vulnerable to triggers of violent behavior?

Can Genetic Engineering Mitigate California's Drought?

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STANFORD, CA Water is in increasingly short supply in many parts of the United States. Here in California, where most of the state is experiencing extreme drought, 2013 was the driest year on record, and we have had no relief during what should be the height of the rainy season. Moreover, theres no end in sight: The Climate Prediction Center of the National Weather Serviceforecaststhat the drought will persist or intensify at least through April.

Reservoir levels are dropping, the snow pack is almost nonexistent, and many communities have already imposed restrictions on water usage. In the city of Santa Cruz, for example, restaurants can no longer serve drinking water unless diners specifically request it; Marin County residents have been asked not to clean their cars or to do so only at eco-friendly car washes; and there are limitations on watering lawns in towns in Mendocino County.

But it is the states premier industry farming that will feel the pinch most. In an average year, farmers use 80 percent of the water used by people and businesses, according to the Department of Water Resources.

During a January 19 press conference at which he declared a water emergency, Governor Jerry Brown said of the drought, This is not a partisan adversary. This is Mother Nature. We have to get on natures side and not abuse the resources that we have.

Drought may not be partisan, but it does raise critical issues of governance, public policyand how best to use the states natural resources. It also offers an example of the Law of Unintended Consequences: Ironically, Santa Cruz, Mendocino and Marin counties all of which boast politically correct, far-left politics are among the local jurisdictions that have banned a key technology that could conserve huge amounts of water.

The technology is genetic engineering performed with modern molecular techniques, sometimes referred to as genetic modification (GM) or gene-splicing, which enables plant breeders to make old crop plants do spectacular new things, including conserve water. In the United States and about 30 other countries, farmers are using genetically engineered crop varieties to produce higher yields, with lower inputs and reduced impact on the environment.

Even with R&D being hampered by resistance from activists and discouraged by governmental over-regulation, genetically engineered crop varieties are slowly but surely trickling out of the development pipeline in many parts of the world. Cumulatively, over 3.7 billion acres of them have been cultivated by more than 17 million farmers in 30 countries during the past 15 years without disrupting a single ecosystem or causing so much as a tummy ache in a consumer.

Most of these new varieties are designed to be resistant to herbicides, so that farmers can adopt more environment-friendly no-till farming practices and more benign herbicides; or to be resistant to pests and diseases that ravage crops. Others possess improved nutritional quality. But the greatest boon of all both to food security and to the environment in the long term will likely be the ability of new crop varieties to tolerate periods of drought and other water-related stresses. Where water is unavailable for irrigation, the development of crop varieties able to grow under conditions of low moisture or temporary drought could both boost yields and lengthen the time that farmland is productive.

Even where irrigation is feasible, plants that use water more efficiently are needed. Because irrigation for agriculture accounts for roughly 70 percent of the worlds fresh water consumption, the introduction of plants that grow with less water would allow much of it to be freed up for other uses. Especially during drought conditions, even a small percentage reduction in the use of water for irrigation could result in huge benefits.

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Can Genetic Engineering Mitigate California's Drought?

Running with genetic scissors: how a breakthrough technology works

News Release

Short DNA sequences known as PAM (shown in yellow) enable the bacterial enzyme Cas9 to identify and degrade foreign DNA, as well as induce site-specific genetic changes in animal and plant cells. The presence of PAM is also required to activate the Cas9 enzyme. (Illustration by KC Roeyer.)

A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have determined how the bacterial enzyme known as Cas9, guided by RNA, is able to identify and degrade foreign DNA during viral infections, as well as induce site-specific genetic changes in animal and plant cells. Through a combination of single-molecule imaging and bulk biochemical experiments, the research team has shown that the genome-editing ability of Cas9 is made possible by the presence of short DNA sequences known as PAM, for protospacer adjacent motif.

Our results reveal two major functions of the PAM that explain why it is so critical to the ability of Cas9 to target and cleave DNA sequences matching the guide RNA, says Jennifer Doudna, the biochemist who led this study. The presence of the PAM adjacent to target sites in foreign DNA and its absence from those targets in the host genome enables Cas9 to precisely discriminate between non-self DNA that must be degraded and self DNA that may be almost identical. The presence of the PAM is also required to activate the Cas9 enzyme.

With genetically engineered microorganisms, such as bacteria and fungi, playing an increasing role in the green chemistry production of valuable chemical products including therapeutic drugs, advanced biofuels and biodegradable plastics from renewables, Cas9 is emerging as an important genome-editing tool for practitioners of synthetic biology.

Understanding how Cas9 is able to locate specific 20-base-pair target sequences within genomes that are millions to billions of base pairs long may enable improvements to gene targeting and genome editing efforts in bacteria and other types of cells, says Doudna who holds joint appointments with Berkeley Labs Physical Biosciences Division and UC Berkeleys Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI).

Jennifer Doudna and Samuel Sternberg used a combination of single-molecule imaging and bulk biochemical experiments to show how the RNA-guided Cas9 enzyme is able to locate specific 20-base-pair target sequences within genomes that are millions to billions of base pairs long. (Photo by Roy Kaltschmdit)

Doudna is one of two corresponding authors of a paper describing this research in the journal Nature. The paper is titled DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. The other corresponding author is Eric Greene of Columbia University. Co-authoring this paper were Samuel Sternberg, Sy Redding and Martin Jinek.

Bacterial microbes face a never-ending onslaught from viruses and invasive snippets of nucleic acid known as plasmids. To survive, the microbes deploy an adaptive nucleic acid-based immune system that revolves around a genetic element known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. Through the combination of CRISPRs and RNA-guided endonucleases, such as Cas9, (Cas stands for CRISPR-associated), bacteria are able to utilize small customized crRNA molecules (for CRISPR RNA) to guide the targeting and degradation of matching DNA sequences in invading viruses and plasmids to prevent them from replicating. There are three distinct types of CRISPRCas immunity systems. Doudna and her research group have focused on the Type II system which relies exclusively upon RNA-programmed Cas9 to cleave double-stranded DNA at target sites.

What has been a major puzzle in the CRISPRCas field is how Cas9 and similar RNA-guided complexes locate and recognize matching DNA targets in the context of an entire genome, the classic needle in a haystack problem, says Samuel Sternberg, lead author of the Nature paper and a member of Doudnas research group. All of the scientists who are developing RNA-programmable Cas9 for genome engineering are relying on its ability to target unique 20-base-pair long sequences inside the cell. However, if Cas9 were to just blindly bind DNA at random sites across a genome until colliding with its target, the process would be incredibly time-consuming and probably too inefficient to be effective for bacterial immunity, or as a tool for genome engineers. Our study shows that Cas9 confines its search by first looking for PAM sequences. This accelerates the rate at which the target can be located, and minimizes the time spent interrogating non-target DNA sites.

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Running with genetic scissors: how a breakthrough technology works

New Biotech Makes It Much Easier to Genetically Modify Monkeys

A new gene-editing technique could lead to more useful animal models of disease, and perhaps one day more effective gene therapy for humans

Genetically modified long-tailed macaques. Credit: Cell, Niu et al.

Like many babies, the wide-eyed twins are cute. The fact that they are macaque monkeys is almost beside the point. What is not beside the point, however, is their genetic heritage. These baby macaques are, as reported inCell, the first primates to have been genetically modified using an extremely precise gene-editing tool based on the so-called CRISPR/Cas system.

Conducted by researchers in China, the new study is significant because it paves the way for the custom development of laboratory monkeys with genetic profiles that are similar to those found in humans with certain medical disorders. Although mice and rats have long been the animals of choice when creating living models of human disease, they have not been very helpful for studying neurological conditions such as autism and Alzheimers disease; the differences between rodent and human brains are just too great.

To be sure, a few other genetically modified monkeys have been born over the past decade and a half, but the methods used to alter their DNA were not as efficient or as easy to use as the CRISPR/Cas technology. The amount of genome engineering in monkeys is pretty small, says George Church, a professor of genetics at Harvard Medical School.So yes, this [paper] is a pretty big deal.

CRISPR stands for clustered regularly interspaced short palindromic repeats and refers to what at first glance appear to be meaningless variations and repeats in the sequence of molecular letters (A, T, C and G) that make up DNA. These CRISPR patterns are found in many bacteria and most archaea (an ancient group of bacteria that is now considered to be different enough from other one-celled organisms to merit is own taxonomic kingdom, along with bacteria, protists, fungi, plants and animals).

First identified in bacteria in 1987, CRISPR elements started being widely used to create genetic engineering tools only in 2013. It took that long to figure out that the patterns actually served a purpose, determine out what that purpose washelping archaea and bacteria to recognize and defend themselves against virusesand then adapt that original function to a new goal.

Basically, biologists learned that certain proteins associated with the CRISPR system (dubbed, straightforwardly enough, CRISPR-associated, or Cas, proteins) act like scissors that cut any strands of DNA they come across. These cutting proteins, in turn, are guided to specific strands of DNA by complementary pieces of RNA (a sister molecule to DNA). The bacteria generate specific guide strands of RNA whenever they encounter a virus that is starting to hijack their cellular machinery. The guide-RNA complements the viral DNA, which is how the Cas proteins know where to cut. The bacteria then keep a copy of the viral DNA in their own genetic sequence between two CRISPR elements for future reference in case a similar virus tries to cause trouble later on.

In the past couple of years researchers have learned how to trick the Cas proteins into targeting and slicing through a sequence of DNA of their own choosing. By developing strands of RNA that precisely complement the part of the DNA molecule that they want to change, investigators can steer the Cas proteins to a predesignated spot and cut out enough genetic material to permanently disrupt the usual expression of the DNA molecule at that location.

In essence, scientists have turned a bacterial self-defense mechanism into an incredibly precise gene-editing tool. By some accounts CRISPR technology has been successfully tried out on 20 different kinds of higher organisms (meaning higher than bacteria) in just the past year or so.

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New Biotech Makes It Much Easier to Genetically Modify Monkeys

Ronald Crystal, M.D., receives Pioneer Award

PUBLIC RELEASE DATE:

31-Jan-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, January 31, 2014In recognition of his seminal work on adenoviral vectors, which accelerated the translation of gene therapy from the research laboratory to the clinic, Ronald G. Crystal, MD (Weill Cornell Medical College, Cornell University, New York City), has received a Pioneer Award from Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Human Gene Therapy is commemorating its 25th anniversary by bestowing this honor on the leading 12 Pioneers in the field of cell and gene therapy selected by a blue ribbon committee* and publishing a Pioneer Perspective by each of the award recipients. The article by Dr. Crystal is available on the Human Gene Therapy website.

Currently it is standard practice to use a modified virus as a transport vehicle to deliver therapeutic genes to patients. But this concept was new, innovative, and technically challenging when Dr. Crystal began developing the molecular tools and methods in the late 1980s. In the Pioneer Perspective "Adenovirus: The First Effective In Vivo Gene Delivery Vector," Dr. Crystal provides historical insights on the many years of research and testing needed to design, optimize, manufacture, and evaluate the performance of adenoviral vectors. He describes the first in vivo studies, the first human studies, and the many current applications of this useful gene delivery system.

"Ron led the way in the clinical translation of adenoviral vectors in the very early days of gene therapy," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

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*The blue ribbon panel of leaders in cell and gene therapy, led by Chair Mary Collins, PhD, MRC Centre for Medical Molecular Virology, University College London, selected the Pioneer Award recipients. The Award Selection Committee selected scientists that had devoted much of their careers to cell and gene therapy research and had made a seminal contribution to the field--defined as a basic science or clinical advance that greatly influenced progress in translational research.

About the Journal

Human Gene Therapy, the official journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its sister journals, Human Gene Therapy Methods, published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of content for all three publications and a free sample issue may be viewed on the Human Gene Therapy website.

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Ronald Crystal, M.D., receives Pioneer Award

Puzzling question in bacterial immune system answered

A central question has been answered regarding a protein that plays an essential role in the bacterial immune system and is fast becoming a valuable tool for genetic engineering. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have determined how the bacterial enzyme known as Cas9, guided by RNA, is able to identify and degrade foreign DNA during viral infections, as well as induce site-specific genetic changes in animal and plant cells. Through a combination of single-molecule imaging and bulk biochemical experiments, the research team has shown that the genome-editing ability of Cas9 is made possible by the presence of short DNA sequences known as "PAM," for protospacer adjacent motif.

"Our results reveal two major functions of the PAM that explain why it is so critical to the ability of Cas9 to target and cleave DNA sequences matching the guide RNA," says Jennifer Doudna, the biochemist who led this study. "The presence of the PAM adjacent to target sites in foreign DNA and its absence from those targets in the host genome enables Cas9 to precisely discriminate between non-self DNA that must be degraded and self DNA that may be almost identical. The presence of the PAM is also required to activate the Cas9 enzyme."

With genetically engineered microorganisms, such as bacteria and fungi, playing an increasing role in the green chemistry production of valuable chemical products including therapeutic drugs, advanced biofuels and biodegradable plastics from renewables, Cas9 is emerging as an important genome-editing tool for practitioners of synthetic biology.

"Understanding how Cas9 is able to locate specific 20-base-pair target sequences within genomes that are millions to billions of base pairs long may enable improvements to gene targeting and genome editing efforts in bacteria and other types of cells," says Doudna who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI).

Doudna is one of two corresponding authors of a paper describing this research in the journal Nature. The paper is titled "DNA interrogation by the CRISPR RNA-guided endonuclease Cas9." The other corresponding author is Eric Greene of Columbia University. Co-authoring this paper were Samuel Sternberg, Sy Redding and Martin Jinek.

Bacterial microbes face a never-ending onslaught from viruses and invasive snippets of nucleic acid known as plasmids. To survive, the microbes deploy an adaptive nucleic acid-based immune system that revolves around a genetic element known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. Through the combination of CRISPRs and RNA-guided endonucleases, such as Cas9, ("Cas" stands for CRISPR-associated), bacteria are able to utilize small customized crRNA molecules (for CRISPR RNA) to guide the targeting and degradation of matching DNA sequences in invading viruses and plasmids to prevent them from replicating. There are three distinct types of CRISPR-Cas immunity systems. Doudna and her research group have focused on the Type II system which relies exclusively upon RNA-programmed Cas9 to cleave double-stranded DNA at target sites.

"What has been a major puzzle in the CRISPR-Cas field is how Cas9 and similar RNA-guided complexes locate and recognize matching DNA targets in the context of an entire genome, the classic needle in a haystack problem," says Samuel Sternberg, lead author of the Nature paper and a member of Doudna's research group. "All of the scientists who are developing RNA-programmable Cas9 for genome engineering are relying on its ability to target unique 20-base-pair long sequences inside the cell. However, if Cas9 were to just blindly bind DNA at random sites across a genome until colliding with its target, the process would be incredibly time-consuming and probably too inefficient to be effective for bacterial immunity, or as a tool for genome engineers. Our study shows that Cas9 confines its search by first looking for PAM sequences. This accelerates the rate at which the target can be located, and minimizes the time spent interrogating non-target DNA sites."

Doudna, Sternberg and their colleagues used a unique DNA curtains assay and total internal reflection fluorescence microscopy (TIRFM) to image single molecules of Cas9 in real time as they bound to and interrogated DNA. The DNA curtains technology provided unprecedented insights into the mechanism of the Cas9 target search process. Imaging results were verified using traditional bulk biochemical assays.

"We found that Cas9 interrogates DNA for a matching sequence using RNA-DNA base-pairing only after recognition of the PAM, which avoids accidentally targeting matching sites within the bacterium's own genome," Sternberg says. "However, even if Cas9 somehow mistakenly binds to a matching sequence on its own genome, the catalytic nuclease activity is not triggered without a PAM being present. With this mechanism of DNA interrogation, the PAM provides two redundant checkpoints that ensure that Cas9 can't mistakenly destroy its own genomic DNA."

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Puzzling question in bacterial immune system answered

Impact of battlefield-related genitourinary injuries described in Journal of Men’s Health

PUBLIC RELEASE DATE:

28-Jan-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, January 28, 2014Modern combat and the global war on terror, with increased use of improvised explosive devices, have led to a nearly 350% increased rate of genitourinary injuries. The often debilitating long-term sexual, psychological, fertility, and hormonal effects of these traumatic wounds and the need for new coordinated approaches to care are the focus of a Review article and Guest Editorial in Journal of Men's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The articles are available free on the Journal of Men's Health website at http://www.liebertpub.com/jmh.

The Review "Genitourinary Trauma in the Modern Era of Warfare" discusses why battlefield genitourinary injuries have increased so dramatically in recent years and how they have changed. The article is coauthored by Justin Han, MD and Chris Gonzalez, MD, MBA, Northwestern University Feinberg School of Medicine and Jesse Brown Veterans Affairs Medical Center (Chicago, IL), and Mark Edney, MD, Peninsula Urology Associates (Salisbury, MD) and Lieutenant Colonel, U.S. Army Reserve, 48th Combat Support Hospital (Ft. Meade, MD).

Janice Bray, MD, MBA, Chief, Central Texas Veterans Health Care System (Temple, TX), describes the potentially devastating physical, psychological, and social impact of these combat woundsand in particular their effects on future relationships, intimacy, parenting, self-worth, and suicide riskin the guest editorial "Genitourinary Trauma: A Battle Cry for Integrated Collaborative Veteran-Centric Care."

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About the Journal

Journal of Men's Health is the premier peer-reviewed journal published quarterly in print and online that covers all aspects of men's health across the lifespan. The Journal publishes cutting-edge advances in a wide range of diseases and conditions, including diagnostic procedures, therapeutic management strategies, and innovative clinical research in gender-based biology to ensure optimal patient care. The Journal addresses disparities in health and life expectancy between men and women; increased risk factors such as smoking, alcohol abuse, and obesity; higher prevalence of diseases such as heart disease and cancer; and health care in underserved and minority populations. Journal of Men's Health meets the critical imperative for improving the health of men around the globe and ensuring better patient outcomes. Tables of content and a sample issue can be viewed on the Journal of Men's Health website at http://www.liebertpub.com/jmh.

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Impact of battlefield-related genitourinary injuries described in Journal of Men's Health

Right on target: New era of fast genetic engineering

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(Image: Kotryna Zukauskaite)

A simple, very powerful method is making genome editing much easier and faster prepare for a revolution in biology and medicine

SEQUENCING genomes has become easy. Understanding them remains incredibly hard. While the trickle of sequence information has turned into a raging torrent, our knowledge isn't keeping up. We still have very little understanding of what, if anything, all our DNA does.

This is not a problem that can be solved by computers. Ultimately, there is only one way to be sure what a particular bit of DNA does you have to alter it in real, living cells to see what happens. But genetic engineering is very difficult and expensive.

At least, it used to be. Last month, two groups announced that they had performed a mind-boggling feat. They targeted and disabled nearly every one of our genes in cells growing in a dish. They didn't knock out all the genes in each cell at once, of course, but one gene at a time. That is, they individually modified a staggering 20,000 genes. "It's truly remarkable," says Eric Lander, director of the Broad Institute of MIT and Harvard, who led one of the studies. "This is transformative."

To put it into perspective, in 2007 an international project was launched to target and "knock out" each of the 20,000 genes a mouse possesses. It took the collective effort of numerous labs around the world more than five years to complete, and it cost $100 million. Now two small teams have each done something similar in a fraction of the time and cost. The secret: a simple and powerful new way of editing genomes. The term breakthrough is overused, but this undoubtedly is one. "It's a game-changer," says Feng Zhang, also at the Broad Institute, who led the other study.

The technique, unveiled just a year ago, is generating tremendous excitement as its potential becomes clear. It is already starting to accelerate the pace of research Lander and Zhang used it to find out which genes help cancer cells resist a drug, for instance. In years to come, it is likely to be used in gene therapy, and to create a new generation of genetically engineered organisms with extensive but precise changes to their genomes. And if we ever do decide to genetically modify people, this is the tool to do it with.

While genetic engineers have done some amazing things, their first tools were very crude. They bombarded cells with extra DNA sometimes literally in the hope that it might occasionally get added to a cell's genome. But there was no way to control where in the genome it went, and if added DNA ends up in the wrong place it can cause havoc. Also, this approach does not allow for any tinkering with existing genes, which is the key to finding out what they and their variants do.

So in the past couple of decades the focus has switched to genome editing. To visualise how it works, imagine the genome as a collection of cookbooks written on long scrolls of paper and cared for by blind librarians. The librarians try to repair any damage but because they can't read they are easily tricked.

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Right on target: New era of fast genetic engineering

A natural sugar delivers DNA aptamer drug inside tumor cells

PUBLIC RELEASE DATE:

27-Jan-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, January 27, 2014Drugs comprised of single strands of DNA, called aptamers, can bind to targets inside tumor cells causing cell death. But these DNA drugs cannot readily get inside tumor cells on their own. Effective delivery of DNA aptamers using a natural polysaccharide as a carrier is described in an article in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. The article is available on the Nucleic Acid Therapeutics website.

Tatyana Zamay and coauthors, Krasnoyarsk State Medical University, Siberian Branch Russian Academy of Sciences, and Center for Reproductive Medicine (Krasnoyarsk, Russia), and University of Ottawa, Canada, combined the polysaccharide arabinogalactan, obtained from the larch tree, with a DNA drug that binds to and disrupts the activity of vimentin, a structural protein required for cell division. Vimentin is often over-produced by tumor cells compared to normal cells.

In the article "DNA-Aptamer Targeting Vimentin for Tumor Therapy in Vivo" the authors show that an aptamer targeting vimentin inhibits tumor growth more effectively when it is administered as a mixture with arabinogalactan than alone.

"This work demonstrates the advancement of aptamer therapeutic application through increased bioavailability using a nontoxic polysaccharide based therapy," says Executive Editor Graham C. Parker, PhD.

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Nucleic Acid Therapeutics is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC, and C.A. Stein, MD, PhD, City of Hope National Medical Center, Duarte, CA; and Executive Editor Graham C. Parker, PhD.

About the Journal

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A natural sugar delivers DNA aptamer drug inside tumor cells

Do brain connections help shape religious beliefs?

PUBLIC RELEASE DATE:

27-Jan-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, January 27, 2014Building on previous evidence showing that religious belief involves cognitive activity that can be mapped to specific brain regions, a new study has found that causal, directional connections between these brain networks can be linked to differences in religious thought. The article "Brain Networks Shaping Religious Belief" is published in Brain Connectivity, a bimonthly peer-reviewed journal from Mary Ann Liebert, Inc., publishers, and is available free on the Brain Connectivity website at http://www.liebertpub.com/brain.

Dimitrios Kapogiannis and colleagues from the National Institute on Aging (National Institutes of Health, Baltimore, MD) and Rehabilitation Institute of Chicago, IL, analyzed data collected from functional magnetic resonance imaging (fMRI) studies to evaluate the flow of brain activity when religious and non-religious individuals discussed their religious beliefs. The authors determined causal pathways linking brain networks related to "supernatural agents," fear regulation, imagery, and affect, all of which may be involved in cognitive processing of religious beliefs.

"When the brain contemplates a religious belief," says Dr. Kapogiannis, "it is activating three distinct networks that are trying to answer three distinct questions: 1) is there a supernatural agent involved (such as God) and, if so, what are his or her intentions; 2) is the supernatural agent to be feared; and 3) how does this belief relate to prior life experiences and to doctrines?"

"Are there brain networks uniquely devoted to religious belief? Prior research has indicated the answer is a resolute no," continues study co-author Jordan Grafman, Director, Brain Injury Research and Chief, Cognitive Neuroscience Laboratory, Rehabilitation Institute of Chicago. "But this study demonstrates that important brain networks devoted to various kinds of reasoning about others, emotional processing, knowledge representation, and memory are called into action when thinking about religious beliefs. The use of these basic networks for religious practice indicates how basic networks evolved to mediate much more complex beliefs like those contained in religious practice."

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About the Journal

Brain Connectivity is the journal of record for researchers and clinicians interested in all aspects of brain connectivity. The Journal is under the leadership of Founding and Co-Editors-in-Chief Christopher Pawela, PhD, Assistant Professor, Medical College of Wisconsin, and Bharat Biswal, PhD, Chair of Biomedical Engineering, New Jersey Institute of Technology. It includes original peer-reviewed papers, review articles, point-counterpoint discussions on controversies in the field, and a product/technology review section. To ensure that scientific findings are rapidly disseminated, articles are published Instant Online within 72 hours of acceptance, with fully typeset, fast-track publication within 4 weeks. Tables of content and a sample issue may be viewed on the Brain Connectivity website at http://www.liebertpub.com/brain.

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Do brain connections help shape religious beliefs?

Audi Bets on Bio Gasoline Startup

Startup Global Bioenergies uses genetic engineering to avoid one of the costliest steps in biofuel production.

Test plant: Global Bioenergies is adapting this test facility, owned by the European research organization Fraunhofer, to produce biofuels using a new process that avoids a costly distillation step.

Audi is investing in a startup, Paris-based Global Bioenergies, that says it can make cheap gasoline from sugar and other renewable sources. The strategic partnership includes stock options and an unspecified amount of funding.

As with conventional biofuel production, Global Bioenergies technology uses microrganisms to ferment sugars to produce fuel. But its process eliminates the second most costly part of producing biofuelsthe energy-intensive distillation step. And by making gasoline instead of making ethanol, the startup skirts a major problem hampering growth in biofuelsthe fact that the market for ethanol is saturated.

Global Bioenergies has demonstrated its technology in the lab and is building two pilot facilities to produce isobutene, a hydrocarbon that a partner will convert into gasoline through an existing chemical process. The larger of the two pilot facilities will be big enough to support the production of over 100,000 liters of gasoline a year.

The process addresses one of the key challenges with conventional biofuels productionthe fuel can kill the microrganisms that make it. In a conventional fermentation process, once the concentration of ethanol gets to about 12 percent, it starts to poison the yeast so that it cant make any more ethanol.

Global Bioenergies has genetically engineered E. coli bacteria to produce a gas (isobutene) that bubbles out of solution, so its concentration in the fermentation tank never reaches toxic levels. As a result the bacteria can go on producing fuel longer than in the conventional process, increasing the output of a plant and reducing capital costs.

The isobutene still needs to be separated from other gases such as carbon dioxide, but Global Energies says this is much cheaper than distillation.

The new process doesnt address the biggest cost of biofuels todaythe cost of the raw materials. Its designed to run on glucose, the type of sugar produced from corn or sugarcane. But the company is adapting it to work with sugars from non-food sources such as wood chips, which include glucose but also other sugars such as xylose.

Audis partnership with Global Bioenergies is part of push by the automaker to reduce greenhouse gas emissions in the face of tightening regulations. Audi recently announced two other investments in cleaner fuels. It funded a project to make methane using renewable energythe methane can be used to run Audis natural-gas fueled cars (see Audi to Make Fuel Using Solar Power). And it funded Joule Unlimited, which is using photosynthetic microrganisms to make ethanol and diesel (see Audi Backs a Biofuels Startup).

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Audi Bets on Bio Gasoline Startup

Debate rages over labeling genetically modified food

Inject a gene from a certain cold-water fish into a strawberry, and the strawberry can withstand colder temperatures. But would you still want to eat it?

Such advances in genetic engineering have implications for helping feed a growing, hungry world but a lot of people aren't too keen on eating those advances just yet.

Others wouldn't hesitate.

The difference reflects the "wild, messy debate" surrounding genetically modified food, with one of the more recent skirmishes centering on whether food labels should contain information about such ingredients, according to Nick George, president of the Midwest Food Processors Association, based in Madison.

Wisconsin's agriculture and food production industries find themselves smack in the middle of the debate.

"This is a big issue," George said. "It's not going away."

Neither, it seems, are genetically engineered crops in the American food chain.

The U.S. Department of Agriculture estimates that 93% of soybean acres and 85% of corn acres in 2013 were planted with genetically modified, herbicide-tolerant crop varieties.

The percentage of insect-resistant corn planted in 2013 stood at 76%, according to the USDA. The insect-resistant corn contains a gene from the soil bacterium Bt Bacillus thuringiensis. The bacteria produce a protein that is toxic to specific insects.

Consider that there are nearly 1.3 million dairy cows in Wisconsin, and some of them are no doubt eating corn with genetically modified ingredients.

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Debate rages over labeling genetically modified food

Man who developed first vaccine for hepatitis B leaves £30million to charity

25 Jan 2014 00:01

PROFESSOR Sir Ken Murray, one of the first researchers in genetic engineering, saved many lives worldwide.

PRESSTEAM

A SCIENTIST who developed the first vaccine for hepatitis B has left 30million to the charity he founded in Edinburgh.

Professor Sir Ken Murrays groundbreaking work was credited with saving lives worldwide.

The 82-year-old, who worked at Edinburgh University for more than 30 years and was one of the first researchers in genetic engineering, died at home in the city last April.

His will reveals his estate was worth 45million with his fortune built on royalties from the vaccine.

The main beneficiaries are the Darwin Trust of Edinburgh, founded by Sir Ken in 1983.

They will receive 30million to support the education of young scientists and fund research and facilities at Edinburgh University.

Trust chairman Dr John Tooze, 75, said: Ken was an extraordinary man who remained very modest despite the huge royalties that his hepatitis B vaccine brought him.

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Man who developed first vaccine for hepatitis B leaves £30million to charity