December 13, 2007, 9:43 PM CT

Biocapture Surfaces for Studying Brain Chemistry

A research team at Penn State has developed a novel method for attaching small molecules, such as neurotransmitters, to surfaces, which then are used to capture large biomolecules. By varying the identity and spacing of the tethered molecules, scientists can make the technique applicable to a wide range of bait molecules including drugs, chemical warfare agents, and environmental pollutants. Ultimately, the scientists also hope to identify synthetic biomolecules that recognize neurotransmitters so that they can fabricate extremely small biosensors to study neurotransmission in the living brain.

In the brain, dozens of different small signaling molecules interact with thousands of large receptive proteins as part of the fundamental communication process between nerve cells. This cacophony of specific interactions is highly dependent on nanoscale molecular structure. One key to advancing our understanding of how the brain works is to identify the nature of the association between neurotransmitters and their binding partners. The technique of producing these high-affinity materials will be published in January 2008 in the journal Advanced Materials by a research team headed by Anne Milasincic Andrews, associate professor of veterinary and biomedical sciences, and including Paul S. Weiss, distinguished professor of chemistry and physics......... Posted by: Emily      Read more         Source

December 12, 2007, 9:54 PM CT

Dramatically lowering costs of DNA sequencing

Using computer simulations, scientists at the University of Illinois have demonstrated a strategy for sequencing DNA by driving the molecule back and forth through a nanopore capacitor in a semiconductor chip. The technique could lead to a device that would read human genomes quickly and affordably.

Being able to sequence a human genome for $1,000 or less (which is the price most insurance companies are willing to pay) could open a new era in personal medicine, making it possible to precisely diagnose the cause of a number of diseases and tailor drugs and therapy procedures to the genetic make-up of an individual.

Despite the tremendous interest in using nanopores for sequencing DNA, it was unclear how, exactly, nanopores could be used to read the DNA sequence, said U. of I. physics professor Aleksei Aksimentiev. We now describe one such method.

Aksimentiev and collaborators describe the method in a paper accepted for publication in the journal Nano Letters, and posted on the journals Web site.

Through molecular dynamics simulations, we demonstrate that back-and-forth motion of a DNA molecule in a nanopore capacitor 1 nanometer in diameter produces an electrostatic fingerprint that can be used to read the genetic sequence, said Aksimentiev, who also is a researcher at the Beckman Institute......... Posted by: Emily      Read more         Source

December 11, 2007, 10:30 PM CT

Natural human hormone as the next antidepressant?

Philadelphia, PA, December 11, 2007 Novel therapy strategies for major depression with broader therapy success or a more rapid onset of action would have immense impact on public health, a new study reported in the December 1st issue of Biological Psychiatry explains. This new study reports findings that support the evaluation of a potential new antidepressant agent.

As per the lead author on this study, Kamilla Miskowiak, MSc: Eventhough depression is often correlation to problems in the chemistry of the brain, recent evidence also suggests that there may be structural problems as well with nerve cells not being regenerated as fast as normal or suffering from toxic effects of stress and stress hormones. This led the scientists to evaluate the effects of erythropoietin (Epo), a hormone naturally produced by the kidneys that stimulates the formation of red blood cells and is known as a therapy for anemia. The authors explain that new evidence shows that Epo also has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans, suggesting that it may be a candidate in the therapy of depression.

In this study, Miskowiak and his colleagues reviewed the effects of Epo on the neural and cognitive processing of emotional information in healthy volunteers using functional magnetic resonance imaging (fMRI). They observed that Epo regulated the emotional responses of those volunteers that received it, similar to the effects of current antidepressants. Ms. Miskowiak explains that this finding provides support to the idea that Epo affects neural function and may be a candidate agent for future therapy strategies for depression. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, confirms its potential: Epo appears to have neurotrophic effects in the brain in animals. The current data suggest that Epo may modulate human brain activity linked to the processing of emotion. Together, there may now be sufficient evidence to justify evaluating the antidepressant effects of Epo and related compounds in humans......... Posted by: Emily      Read more         Source

December 11, 2007, 10:08 PM CT

Neurotransmitters in biopolymers

Research reported December 11 in the journal Advanced Materials describes a potentially promising strategy for encouraging the regeneration of damaged central nervous system cells known as neurons.

The technique would use a biodegradable polymer containing a chemical group that mimics the neurotransmitter acetylcholine to spur the growth of neurites, which are projections that form the connections among neurons and between neurons and other cells. The biomimetic polymers would then guide the growth of the regenerating nerve.

There is currently no therapy for recovering human nerve function after injury to the brain or spinal cord because central nervous system neurons have a very limited capability of self-repair and regeneration.

Regeneration in the central nervous system requires neural activity, not just neuronal growth factors alone, so we thought a neurotransmitter might send the necessary signals, said Yadong Wang, assistant professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and principal investigator of the study. The research was supported by Georgia Tech, the National Science Foundation and the National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Chemical neurotransmitters relay, amplify and modulate signals between a neuron and another cell. This new study shows that integrating neurotransmitters into biodegradable polymers results in a biomaterial that successfully promotes neurite growth, which is necessary for victims of central nervous system injury, stroke or certain neurodegenerative diseases to recover sensory, motor, cognitive or autonomic functions......... Posted by: Emily      Read more         Source

December 11, 2007, 8:26 PM CT

New computational technique can predict drug side effects

Early identification of adverse effects of drugs before they are tested in humans is crucial in developing new therapeutics, as unexpected effects account for a third of all drug failures during the development process. Now scientists at the University of California, San Diego (UCSD) have developed a novel technique using computer modeling to identify potential side effects of pharmaceuticals, and have used the technique to study a class of drugs that includes tamoxifen, the most prescribed drug in the therapy of breast cancer. Their study is currently available on line at PLoS Computational Biology.

Conventional test methods screen compounds in animal studies in advance of human trials in the hope of identifying the side effects of promising therapeutics. The UCSD team led by Philip Bourne, Ph.D., professor of pharmacology at UCSDs Skaggs School of Pharmacy and Pharmaceutical Sciences and Lei Xie, Ph.D., of the San Diego Supercomputer Center at UCSD instead uses the power of computational modeling to screen specific drug molecules using a worldwide repository, the Protein Data Bank (PDB), containing tens of thousands of three-dimensional protein structures.

Drug molecules are designed to bind to targeted proteins in order to achieve a therapeutic affect, but if the small drug molecule that functions as a key attaches to an off-target protein that has a similar binding site, or lock, side effects can result......... Posted by: Emily      Read more         Source

December 10, 2007, 10:51 PM CT

Vaccine shows promise in preventing mono

A new study suggests that a vaccine targeting Epstein-Barr virus (EBV) may prevent infectious mononucleosis, usually known as mono or glandular fever. The study is reported in the December 15 issue of The Journal of Infectious Diseases, now available online.

EBV is a member of the herpes virus family and one of the most common viruses in humans, with nearly all adults in developed countries such as the United States having been infected. EBV is often asymptomatic but usually causes infectious mononucleosis, with 30 to 40 percent of adolescents who contract the virus developing the disease. EBV is also linked to many other diseases, some of the most serious being lymphomas and other lymphoproliferative diseases in people with compromised immune systems, such as transplant patients. Despite the frequency of EBV infections and infectious mononucleosis, the new study is the first to suggest the efficacy of a vaccine in preventing infectious mononucleosis.

The study was conducted by Etienne M. Sokal, MD, PhD, and his colleagues at several Belgian institutions and pharmaceutical companies. The vaccine targets glycoprotein 350, a protein that facilitates the entry of EBV into immune system cells. In this preliminary, Phase II clinical trial, 181 young adults who had not previously been infected by EBV received three doses of either a placebo or the vaccine......... Posted by: Emily      Read more         Source

December 10, 2007, 10:32 PM CT

MIT corrects sickle-cell anemia in mice

MIT scientists have successfully treated mice with sickle-cell anemia in a process that begins by directly reprogramming the mice's own cells to an embryonic-stem-cell-like state, without the use of eggs.

This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed induced pluripotent stem (IPS) cells, which recently have been derived in mice as well as humans.

"This demonstrates that IPS cells have the same potential for treatment as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells," said MIT biology professor Rudolf Jaenisch, a member of the Whitehead Institute for Biomedical Research.

The research, reported Dec. 6 in Science online, was carried out in Jaenisch's laboratory. The IPS cells were derived using modifications of the approach originally discovered in 2006 by the Shinya Yamanaka laboratory at Kyoto University.

A disease of the blood marrow caused by a defect in a single gene, sickle-cell anemia is the most common inherited blood disorder in the United States, affecting more than 70,000 Americans and one in 500 African-Americans, as per the National Institutes of Health.

The researchers in Jaenisch's lab studied a therapeutic application of IPS cells with the sickle-cell anemia model mouse developed by the laboratory of Tim Townes of the University of Alabama at Birmingham. The mouse model had been designed to include relevant human genes involved in blood production, including the defective version of that gene......... Posted by: Emily      Read more         Source

Mon, 10 Dec 2007 04:22:30 GMT

The Hidden Workings of Our Minds

How do great artists create? How do brilliant scientists solve the hardest problems in their field? Listen to them try to explain and you''ll probably be disappointed. Artists say mysterious things like: "The picture just formed in my mind." Writers tell us that: "I don''t know where the words come from." Scientists say they: "Just had a hunch."

Of course, not all scientists, artists and writers give such mysterious answers. Some talk about the processes they went through or what inspired their conceptual jump. But their explanations are almost invariable unsatisfying. They usually can''t really explain how they made that vital leap of the imagination. This is strange. Why is it that otherwise brilliant and articulate people seem unable to adequately explain their thought processes? Don''t they know how they did it?

What is true of great scientific and artistic leaps of imagination is also true in everyday life. When people are asked why they chose one career over another, one partner over another or one flavour of ice-cream over another, the same problems emerge. Often, people''s answers are unconvincing or they just don''t know.

Psychologists no longer find this inability to explain our internal mental processes strange. Like Freud all those years ago, modern cognitive psychologists have come to accept that a lot of the time we don''t have much of a clue what''s going on in our own minds, and there''s evidence to prove it.

Mysterious thoughts
In a classic review of the literature, Nisbett and Wilson (1977) looked at many, many cognitive and social psychology studies conducted in the 1960s, 70s and earlier. These studies involved manipulating participants'' behaviour. For an example, have a look at my report of this classic study of cognitive dissonance.

After reviewing all these studies where experimenters are messing with participants'' minds, Nisbett and Wilson came to the following conclusions:

People are mostly unaware that their behaviour or thought processes have been changed by the experimenter.

Even if they are aware of the manipulation, they can''t identify the process of change that occurred.

Most people cannot connect their changed thought or behaviour with the experimenter''s manipulation.

Frustratingly, it seems that the most powerful workings of the mind are hidden away from view, even when we go rummaging around. If this is true, what about the explanations that people actually give for their behaviour? Where do these come from and are they ever right?

Nisbett and Wilson reach two further disturbing conclusions:

When coming up with their explanations, people don''t seem to access the correct thought process(es). If they do then it only happens when the explanation is plausible.

Sometimes people do report the correct reason for what they''ve done, but it''s probably only a coincidence.

If Nisbett and Wilson are right it has profound implications for what we can know about our own thoughts and whether we can believe what other people say about theirs.

The evidence
In the next few posts I''ll explain some of the evidence for these claims. But in the meantime think about a relatively common experience like driving. Most drivers have had the experience of having driven for a length of time without noticing any traffic signals, yet they still stop at every red light.

Some part of our minds has clearly been paying attention and it''s these automatic unconscious processes that are keeping us alive. But there''s a major difference between being on automatic pilot because it suits us, and being unable to get off automatic pilot even if we want to.

It''s this idea of not having access to the vast majority of our own thoughts, even when we try, that has been such a major psychological insight for modern cognitive psychologists.

This post is part of a series on the hidden workings of our unconscious:

» The Hidden Workings of Our Minds

Our Secret Attitude Changes

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References

Nisbett, R. E., & Wilson, T. D. (1977). Telling more than we can know: Verbal reports on mental processes. Psychological Review, 84(3), 231-259.Labels: Cognitive Psychology Posted by: Jerry      Read more     Source

December 9, 2007, 5:26 PM CT

Research finds link between depression

Depression nearly triples the risk of death following a heart attack, even when accounting for other heart attack risk factors, as per research presented today at the American College of Neuropsychopharmacology (ACNP) annual meeting, which showed that among 360 depressed, post myocardial infarction patients followed for more than six years, those who did not recover from their depression in the first six months were more than twice as likely to die.

This study was one of several presented at a panel which examined the links between depression and vascular disease. There is an unequivocal link between depression and heart disease, but it is not clear what causes this link, said Alexander Glassman, M.D., Professor of Psychiatry at Columbia University, College of Physicians and Surgeons and ACNP member. There is a whole series of factors that link depression and heart disease and we are just beginning to understand how antidepressants act in people who have these conditions together. Additional risk factors that tend to be major medical predictors of death from a heart attack include the severity of the heart attack and variability in various measures of heart function during recovery.

Depression has increasingly been recognized to increase the risk for cardiovascular disease. Possible reasons for this association include sticky platelets, a condition depressed patients are likely to have, or autonomic nervous activity, which increases heart irritability......... Posted by: Emily      Read more         Source

December 7, 2007, 9:20 PM CT

Secrets of Alcohol's Effect on Brain Cells

Alcohol triggers the activation of a variety of genes that can influence the health and activity of brain cells, and new research from Weill Cornell Medical College in New York City sheds light on how that process occurs.

The findings, reported in the Nov. 21 issue of The Journal of Neuroscience, may also edge researchers closer to understanding alcohol-linked disorders such as the brain damage linked to chronic alcoholism, and the abnormal brain development seen in the fetal alcohol syndrome (FAS).

"If you are going to understand the biological effects of alcohol on genes within cells, you have to understand the molecular machinery driving the transcription, or activation, of the genes in question. That's what we believe we have done here," says the study's senior author Dr. Neil L. Harrison, professor of pharmacology and pharmacology in anesthesiology at Weill Cornell.

In research conducted in cell cultures and in mouse neurons in vivo, his team observed that alcohol stimulates a ubiquitous, stress-linked biochemical cascade-called the heat shock pathway-to send a molecule called heat shock factor 1 (HSF1) into the neuron's nucleus. HSF1 then stimulates the transcription of a number of of the genes known to be activated by alcohol.

The fact that alcohol triggers the activation of genes in the brain is not new and has long been the subject of intense research......... Posted by: Emily      Read more         Source