February 9, 2009, 6:19 AM CT
Silence is golden
A team of scientists led by Rutgers' Samuel Gunderson has developed a novel gene silencing platform with very significant improvements over existing RNAi approaches. This may enable the development and discovery of a new class of drugs to treat a wide array of diseases. Critical to the technology is the approach this team took to specifically target RNA biosynthesis.
The research findings are published in the journal Nature Biotechnology
, published online in the February 8th issue.
Gunderson, an associate professor in the Department of Molecular Biology and Biochemistry at Rutgers, The State University of New Jersey, has created highly efficient gene silencing agents that function via a novel mechanism of action. The agents are single-stranded oligonucleotides, called U1 Adaptors, that have dual, and independent, functions. First is a target-gene binding domain that can be tailored to any gene. The second domain inhibits mRNA maturation by binding U1 snRNP, a component of the cellular splicing apparatus.
By combining both capabilities in the same molecule, the U1 Adaptor can inhibit the pre-mRNA maturation step of polyA tail addition in a gene specific manner. Further, the domains of the oligonucleotide are independent so transcript binding and U1 snRNP binding can be independently optimized and adapted to a wide array of genes linked to disease.........
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February 6, 2009, 6:20 AM CT
Exploring genetic causes of schizophrenia
A newly released study shows that schizophrenia is caused, at least in part, by large, rare structural changes in DNA referred to as copy number variants (CNVs) not the tiny, single letter alterations (single nucleotide polymorphisms (SNPs) that researchers have pursued for years. The findings are published February 6 in the open-access journal PLoS Genetics
Schizophrenia is one of the most common psychiatric disorders, but researchers have yet to determine significant genetic links. Over the past two decades, dozens of genes and SNPs have been identified as possible candidates, but the current study dismisses them.
"The literature is replete with dozens of genes and SNPs identified as linked to schizophrenia," says first author Anna Need, PhD, a postdoctoral associate in the Center for Human Genome Variation at the Duke Institute for Genome and Sciences Policy. "But we systematically retested all the leading candidates and concluded that most, if not all of them, are false positives." Need says she believes the prior studies were too small to properly assess the role of SNPs.
Need worked with senior author David Goldstein, of the Center for Human Genome variation, and a team of geneticists to scan the genome of schizophrenia patients and healthy controls for SNPs and copy number variants (CNVs). While none of the previously heralded SNPs appeared significant in schizophrenia, several CNVs emerged as potentially causative.........
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February 6, 2009, 6:16 AM CT
Selling of personalized medicine prematurely?
We appears to be a long way off from using genetics to reliably gauge our risks for specific diseases, say scientists at the University of Pittsburgh Graduate School of Public Health as per a research findings published on Feb. 5 in the online journal PLoS Genetics.
Yet, a number of companies currently offer personalized genetic testing for diseases like cancer, heart disease and diabetes, and tout the ability of DNA testing to predict future health risks.
"The rapid discovery of new genetic risk factors is giving us vitally important insights into human health, but a strong association between these factors and disease risk may not reliably predict which health issues a specific individual will face in the future," said Daniel E. Weeks, Ph.D., senior author and professor of human genetics and biostatistics at the University of Pittsburgh Graduate School of Public Health. "Our study indicates that even though we can paint a picture of our genetic makeup with current tests, this may not be enough to help us understand our individual risk for disease".
The study focused on single nucleotide polymorphisms, or SNPs variations in short DNA sequences that have been associated with the presence of particular diseases, and that exist in the millions in the human genome. Many companies currently offer individualized estimates for disease risks based on genome-wide SNP genotyping. These tests typically scan 500,000 to 1 million SNPs, searching for only a handful linked to a specific disease.........
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February 6, 2009, 6:14 AM CT
Converting adult stem cells to embryonic-like stem cells
The simple recipe researchers earlier discovered for making adult stem cells behave like embryonic-like stem cells just got even simpler. A new report in the February 6th issue of the journal Cell
, a Cell Press publication, shows for the first time that neural stem cells taken from adult mice can take on the characteristics of embryonic stem cells with the addition of a single transcription factor. Transcription factors are genes that control the activity of other genes.
The discovery follows a 2006 report also in the journal Cell
that showed that the introduction of four ingredients could transform differentiated cells taken from adult mice into "induced pluripotent stem cells" (iPS) with the physical, growth, and genetic characteristics typical of embryonic stem cells (http://www.eurekalert.org/pub_releases/2006-08/cp-wff080906.php). Pluripotent refers to the ability to differentiate into most other cell types. The same recipe was later shown to work with human skin cells as well (http://www.eurekalert.org/pub_releases/2007-11/cp-srt111307.php).
Subsequent studies observed that the four-ingredient recipe could in some cases be pared down to just two or three essential ingredients, said Hans Schler of the Max Planck Institute for Molecular Biomedicine in Gera number of. "Now we've come down to just one that is sufficient. In terms of the biology, it's really quite amazing".........
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February 5, 2009, 6:24 AM CT
How influenza virus hijacks human cells
High resolution image of the key domain of the influenza virus polymerase. The active site responsible for RNA cleavage is shown in red. Its activity is crucial for the virus to multiply in human cells.
Credit: Stephen Cusack, EMBL
Influenza is and remains a disease to reckon with. Seasonal epidemics around the world kill several hundred thousand people every year. In the light of looming pandemics if bird flu strains develop the ability to infect humans easily, new drugs and vaccines are desperately sought. Scientists at the European Molecular Biology Laboratory (EMBL) and the joint Unit of Virus Host-Cell Interaction (UVHCI) of EMBL, the University Joseph Fourier (UJF) and the National Centre for Scientific Research (CNRS), in Grenoble, France, have now precisely defined an important drug target in influenza. In this week's Nature
they publish a high-resolution image of a crucial protein domain that allows the virus to hijack human cells and multiply in them.
When the influenza virus infects a host cell its goal is to produce a number of copies of itself that go on to attack even more cells. A viral enzyme, called polymerase, is key to this process. It both copies the genetic material of the virus and steers the host cell machinery towards the synthesis of viral proteins. It does this by stealing a small tag, called a cap, from host cell RNA molecules and adding it onto its own. The cap is a short extra piece of RNA, which must be present at the beginning of all messenger RNAs (mRNAs) to direct the cell's protein-synthesis machinery to the starting point. The viral polymerase binds to host cell mRNA via its cap, cuts the cap off and adds it to the beginning of its own mRNA a process known as 'cap snatching'. But exactly how the polymerase achieves this and which of the three subunits of the enzyme does what, has remained controversial.........
Posted by: Mark Read more Source
February 4, 2009, 5:59 AM CT
Disproving a 15-year-old Theory
A delay in traffic may cause a headache, but a delay in the nervous system can cause much more. University of Missouri scientists have uncovered clues identifying which proteins are involved in the development of the nervous system and observed that the proteins previously thought to play a significant role, in fact, do not. Understanding how the nervous system develops will give scientists a better understanding of neurological diseases, such as multiple sclerosis and Charcot-Marie-Tooth disorders.
"Speed is the key to the nervous system," said Michael Garcia, investigator in the Christopher S. Bond Life Sciences Center and assistant professor of biological sciences in the MU College of Arts and Science. "The peripheral nervous system 'talks' to muscles through nerve impulses in response to external stimuli. When babies are born, they do not have fully developed nervous systems, and their systems run slower. Eventually, the nervous system matures. Our study tried to understand that maturation process".
The process of nerve cells maturation is called myelination. During myelination, a layer of myelin (electrically insulating material) wraps or forms around the axons (part of the nerve cell that conducts electrical impulses). Nerve impulses travel faster in myelinated nerve cells.........
Posted by: Daniel Read more Source
February 4, 2009, 5:53 AM CT
How a deadly fungus evades the human immune system
This is a polysaccharide capsule of C. neoformans by Scanning Electron microscopy.
Credit: Albert Einstein College of Medicine
Scientists at Albert Einstein College of Medicine of Yeshiva University have discovered how a deadly microbe evades the human immune system and causes disease.
The study, reported in the journal Proceedings of the National Academy of Sciences
), may help researchers develop new therapies or vaccines against infections caused by Cryptococcus neoformans
These fungal infections occur most usually in those with compromised immune systems ─ particularly AIDS patients and transplant patients who must take lifelong immunosuppressive treatment. The fungus causes an estimated one million deaths each year worldwide, including some 600,000 in sub-Saharan Africa. The main author of the study was Susana Frases-Carvajal, Ph.D., a postdoctoral fellow in microbiology & immunology at Einstein.C. neoformans
typically enters the body through the lungs and can spread throughout the body, including the brain. The resulting infection, called cryptococcosis, can cause chest pain, dry cough, abdominal swelling, headache, blurred vision, or confusion. The infection can be fatal, particularly if not treated with antifungal medications.
"It's a horrendous disease, and even with treatment, you often can't get rid of it," says the paper's senior author, Arturo Casadevall, M.D., Ph.D., professor and chair of microbiology & immunology.........
Posted by: Mark Read more Source
February 2, 2009, 6:10 AM CT
Drug improves learning and memory
WASHINGTON A team of Arizona psychology experts, geneticists and neuroresearchers has reported that a safe and effective drug used to treat vascular problems in the brain has improved spatial learning and working memory in middle-aged rats. Eventhough far from proving anything about human use of the drug, the finding supports the scientific quest for a substance that could treat progressive cognitive impairment, cushion the cognitive impact of normal aging, or even enhance learning and memory throughout the life span.
The finding appears in the recent issue of Behavioral Neuroscience
, which is published by the American Psychological Association. The drug in question, Fasudil, has been used for more than 10 years to treat vascular problems in the brain, often helping with recovery from stroke.
In this study, the scientists injected hydroxyfasudil, the active form of Fasudil, into middle-aged (17-18 months old) male rats daily starting four days before behavioral testing and continuing throughout testing. Injection made it easy to give the drug to rats, but people take it in pill form.
Rats were tested on the water radial-arm maze, which assessed how well they remembered which of the radiating arms had a reward, a sign of accurate spatial learning and working memory. Rats given a high dose (0.3750 mg per kg of weight) of hydroxyfasudil successfully remembered more items of information than those given a low dose (0.1875 mg per kg). Both dosed groups performed significantly better than control-group rats given saline solution. On this same test, the high-dose group showed the best learning (fewest total errors) and best working memory (measured two different ways).........
Posted by: Daniel Read more Source
January 30, 2009, 6:09 AM CT
New class of allergy drugs
If you've ever wondered why some allergic reactions progress quickly and may even become fatal, a new research report reported in the February 2009 issue of the Journal of Leukocyte Biology
(http://www.jleukbio.org) provides an important part of the answer. In the report, researchers from Queen's University of Belfast, University of Oxford and Trinity College Dublin show for the first time that eotaxin, a chemical that helps immune cells locate the site of infection, blocks basic "fighter" cells from transforming into "seeker" dendritic cells, resulting in a heightened allergic response.
"Our study reveals a new role for the chemokine eotaxin in controlling immune cell types at the site of allergic reaction," said Nigel Stevenson, a researcher involved in the study. "These findings are crucial for our understanding of allergic responses and appears to be instrumental for the design of new allergy drugs".
Stevenson and his colleagues made this discovery by using immune cells grown in the lab and from healthy volunteers. Then the scientists mimicked what occurs during an allergic reaction by treating the cells with eotaxin, which was previously believed to only attract immune cells during an allergic reaction. Through a series of laboratory procedures, they tracked changes in immune cell type and observed that eotaxin inhibits monocytes becoming dendritic cells (that find foreign invaders so other immune cells can neutralize them), resulting in more "fighter" cells being present during an allergic response. This discovery shows how and why eotaxin plays an important role in the severity of allergic reactions and appears to be a target for an entirely new class of allergy medications.........
Posted by: JoAnn Read more Source
January 30, 2009, 6:02 AM CT
How vision sends its message to the brain
Researchers have known for more than 200 years that vision begins with a series of chemical reactions when light strikes the retina, but the specific chemical processes have largely been a mystery. A team of scientists from the United States and Switzerland, have she new light on this process by "capturing" this chemical communication for future study. This research, reported in the February 2009 issue of The FASEB Journal
(http://www.fasebj.org), may lead to the development of new therapys for some forms of blindness and vision disorders.
At the center of the discovery is the signaling of rhodopsin to transducin. Rhodopsin is a pigment in the eye that helps detect light. Transducin is a protein (sometimes called "GPCR") which ultimately signals the brain that light is present. The scientists were able to "freeze frame" the chemical communication between rhodopsin and transducin to study how this takes place and what goes wrong at the molecular level in certain disorders.
As per Krzysztof Palczewski, a senior scientist involved in the research, "The results may have important implications for discovery and development of more specific medicines to treat GPCR-linked dysfunction and disease." Examples of health problems involving GPCR dysfunction include blindness, diabetes, allergies, depression, cardiovascular defects and some forms of cancer.........
Posted by: Mike Read more Source