Posts tagged science

August 8, 2012

Researchers capture evolutionary dynamics in a new theoretical framework that could help explain some of the mysteries of how and why species change over time.

Although the qualitative description of evolution – its observed behavior and characteristics – is well-established, a comprehensive quantitative theory that captures general evolution dynamics is still lacking. There are also many lingering mysteries surrounding the story of life on Earth, including the question of why sex is such a prevalent reproductive strategy. A team of scientists from the Chinese Academy of Sciences; Jilin University in Jilin, China; and the State University of New York at Stony Brook, led by Prof. Jin Wang, has examined some of these puzzles from a physical science prospective. They propose a new theory of evolution with two ingredients: the underlying emergent “fitness” landscape and an associated evolutionary force called “curl flux,” which causes species to move through the emergent fitness landscape in a spiraling manner.

The researchers captured evolutionary relationships in a system of equations. They then created quantitative pictures that visualized evolutionary pathways as journeys through a mountainous terrain of peaks and valleys of biological fitness. The key breakthrough beyond the conventional quantitative theory of evolution is the emergent curl flux, which is generated by interactions between individuals within or across species. The underlying emergent landscape gradient and the curl flux act together as a “Yin and Yang” duality pair to determine the dynamics of general evolution, says Wang. An example of similar behavior is the particle and wave duality that determines the dynamics of the quantum world, he notes. The researchers also note that this combined effect is analogous to the way electric and magnetic forces both act on electrons.

The new theory provides a physical foundation for general evolution dynamics. The researchers found that interactions between individuals of different species can give rise to the curl flux. This can sustain an endless evolution that does not lead to areas of higher relative fitness, even if the physical environment is unchanged.

This finding offers a theoretical framework to explain the Red Queen Hypothesis, which states that species continually evolve in order to fend off parasites that are themselves continually evolving. The hypothesis, first proposed by evolutionary biologist Leigh Van Valen in 1973, gets its name from the character of the Red Queen in Lewis Carroll’s book Through the Looking-Glass, who observed that in her world it was necessary to keep running just to stay in one place. The idea of endless co-evolution through the maintenance of the genetic variation due to the curl flux could help explain the benefits of sexual reproduction, since the mixing and matching of genes preserves a greater diversity of traits. When a species’ arms race with a co-evolving parasite takes an unexpected twist, a previously unnecessary trait could suddenly turn into the key to surviving. In the co-evolving world, there is no guarantee for “survival of the fittest” and it is often necessary to keep running for survival.

Source: PHYS.ORG

August 8, 2012 By Lia Samson

(Phys.org) — In a recent paper, Aleksander Ellis of the University of Arizona Eller College of Management and a colleague demonstrate that lack of sleep can cause deviant behavior at work.

Early 2011 saw a spate of reports in the media about air traffic controllers sleeping on the job as a result of sleep deprivation. The potential harm from this behavior is obvious, but what about the average office job? Can sleep deprivation cause counterproductive, or even unethical, behavior in organizations?

“Over the past decade, Americans have been getting less and less sleep, and estimates are that this trend will continue,” said Professor of Management and Organizations Aleksander Ellis, the Charles and Candice Nelson Fellow. “In fact, in certain industries, lack of sleep is worn as a badge of honor.”

In a recent paper published in the Academy of Management Journal, Ellis and co-author Michael Christian of Kenan-Flagler Business School at the University of North Carolina-Chapel Hill demonstrate that lack of sleep can cause deviant behavior.

In one part of the study, for instance, the researchers asked a group of subjects to respond to an email that contained colloquial language and misspellings. One of the sleep-deprived subjects responded with an unprofessional, personal attack. This is just one example Ellis and Christian cite to demonstrate how sleep deprivation reduces self-control and increases hostility.

Ellis and Christian are currently working on a parallel project that examines how sleep deprivation affects the tendency of individuals to behave unethically by conforming to the behavior of unethical authority figures.

Source: PHYS.ORG

August 8th, 2012

The brain has billions of neurons, arranged in complex circuits that allow us to perceive the world, control our movements and make decisions. Deciphering those circuits is critical to understanding how the brain works and what goes wrong in neurological disorders.

MIT neuroscientists have now taken a major step toward that goal. In a new paper appearing in the Aug. 9 issue of Nature, they report that two major classes of brain cells repress neural activity in specific mathematical ways: One type subtracts from overall activation, while the other divides it.

“These are very simple but profound computations,” says Mriganka Sur, the Paul E. Newton Professor of Neuroscience and senior author of the Nature paper. “The major challenge for neuroscience is to conceptualize massive amounts of data into a framework that can be put into the language of computation. It had been a mystery how these different cell types achieve that.”

Neuroscientists report that two major classes of brain cells repress neural activity in specific mathematical ways: One type subtracts from overall activation, while the other divides it.

The findings could help scientists learn more about diseases thought to be caused by imbalances in brain inhibition and excitation, including autism, schizophrenia and bipolar disorder.

Lead authors of the paper are grad student Caroline Runyan and postdoc Nathan Wilson. Forea Wang ’11, who contributed to the work as an MIT undergraduate, is also an author of the paper.

A fine balance

There are hundreds of different types of neuron in the brain; most are excitatory, while a smaller fraction are inhibitory. All sensory processing and cognitive function arises from the delicate balance between these two influences. Imbalances in excitation and inhibition have been associated with schizophrenia and autism.

“There is growing evidence that alterations in excitation and inhibition are at the core of many subsets of neuropsychiatric disorders,” says Sur, who is also the director of the Simons Center for the Social Brain at MIT. “It makes sense, because these are not disorders in the fundamental way in which the brain is built. They’re subtle disorders in brain circuitry and they affect very specific brain systems, such as the social brain.”

In the new Nature study, the researchers investigated the two major classes of inhibitory neurons. One, known as parvalbumin-expressing (PV) interneurons, targets neurons’ cell bodies. The other, known as somatostatin-expressing (SOM) interneurons, targets dendrites — small, branching projections of other neurons. Both PV and SOM cells inhibit a type of neuron known as pyramidal cells.

To study how these neurons exert their influence, the researchers had to develop a way to specifically activate PV or SOM neurons, then observe the reactions of the target pyramidal cells, all in the living brain.

First, the researchers genetically programmed either PV or SOM cells in mice to produce a light-sensitive protein called channelrhodopsin. When embedded in neurons’ cell membranes, channelrhodopsin controls the flow of ions in and out of the neurons, altering their electrical activity. This allows the researchers to stimulate the neurons by shining light on them.

The team combined this with calcium imaging inside the target pyramidal cells. Calcium levels reflect a cell’s electrical activity, allowing the researchers to determine how much activity was repressed by the inhibitory cells.

“Up until maybe three years ago, you could only just blindly record from whatever cell you ran into in the brain, but now we can actually target our recording and our manipulation to well-defined cell classes,” Runyan says.

Taking a circuit apart

In this study, the researchers wanted to see how activation of these inhibitory neurons would influence how the brain processes visual input — in this case, horizontal, vertical or tilted bars. When such a stimulus is presented, individual cells in the eye respond to points of light, then convey that information to the thalamus, which relays it to the visual cortex. The information stays spatially encoded as it travels through the brain, so a horizontal bar will activate corresponding rows of cells in the brain.

Those cells also receive inhibitory signals, which help to fine-tune their response and prevent overstimulation. The MIT team found that these inhibitory signals have two distinct effects: Inhibition by SOM neurons subtracts from the total amount of activity in the target cells, while inhibition by PV neurons divides the total amount of activity in the target cells.

“Now that we finally have the technology to take the circuit apart, we can see what each of the components do, and we found that there may be a profound logic to how these networks are naturally designed,” Wilson says.

These two types of inhibition also have different effects on the range of cell responses. Every sensory neuron responds only to a particular subset of stimuli, such as a range of brightness or a location. When activity is divided by PV inhibition, the target cell still responds to the same range of inputs. However, with subtraction by SOM inhibition, the range of inputs to which cells will respond becomes narrower, making the cell more selective.

Increased inhibition by PV neurons also changes a trait known as the response gain — a measurement of how much cells respond to changes in contrast. Inhibition by SOM neurons does not alter the response gain.

The researchers believe this type of circuit is likely repeated throughout the brain and is involved in other types of sensory perception, as well as higher cognitive functions.

Sur’s lab now plans to study the role of PV and SOM inhibitory neurons in a mouse model of autism. These mice lack a gene called MeCP2, giving rise to Rett Syndrome, a rare disease that produces autism-like symptoms as well as other neurological and physical impairments. Using their new technology, the researchers plan to test the hypothesis that a lack of neuronal inhibition underlies the disease.

Source: Neuroscience News

ScienceDaily (Aug. 8, 2012) — Stressed and non-stressed people use different brain regions and different strategies when learning. This has been reported by the cognitive psychologists PD Dr. Lars Schwabe and Professor Oliver Wolf from the Ruhr-Universität Bochum in the Journal of Neuroscience. Non-stressed individuals applied a deliberate learning strategy, while stressed subjects relied more on their gut feeling. “These results demonstrate for the first time that stress has an influence on which of the different memory systems the brain turns on,” said Lars Schwabe.

The experiment: Stress due to ice-water

The data from 59 subjects were included in the study. Half of the participants had to immerse one hand into ice-cold water for three minutes under video surveillance. This stressed the subjects, as hormone assays showed. The other participants had to immerse one of their hands just in warm water. Then both the stressed and non-stressed individuals completed the so-called weather prediction task. The subjects looked at playing cards with different symbols and learned to predict which combinations of cards announced rain and which sunshine. Each combination of cards was associated with a certain probability of good or bad weather. People apply differently complex strategies in order to master the task. During the weather prediction task, the researchers recorded the brain activity with MRI.

Two routes to success

Both stressed and non-stressed subjects learned to predict the weather according to the symbols. Non-stressed participants focused on individual symbols and not on combinations of symbols. They consciously pursued a simple strategy. The MRI data showed that they activated a brain region in the medial temporal lobe — the hippocampus, which is important for long-term memory. Stressed subjects, on the other hand, applied a more complex strategy. They made their decisions based on the combination of symbols. They did this, however, subconsciously, i.e. they were not able to formulate their strategy in words. The result of the brain scans was also accordingly: In the case of the stressed volunteers the so-called striatum in the mid-brain was activated — a brain region that is responsible for more unconscious learning. “Stress interferes with conscious, purposeful learning, which is dependent upon the hippocampus,” concluded Lars Schwabe. “So that makes the brain use other resources. In the case of stress, the striatum controls behaviour — which saves the learning achievement.”

Source: Science Daily

8-Aug-2012

The molecular missteps that disrupt brain function in the most common form of adult-onset muscular dystrophy have been revealed in a new study published by Cell Press. Myotonic dystrophy is marked by progressive muscle wasting and weakness, as well as excessive daytime sleepiness, memory problems, and mental retardation. A new mouse model reported in the August 9 issue of the journal Neuron reproduces key cognitive and behavioral symptoms of this disease and could be used to develop drug treatments, which are currently lacking.

The red dots are the toxic RNAs accumulating in the nucleus (blue) of a myotonic dystrophy cell (these are induced pluripotent stem, or iPS, cells) and the green is a neuronal marker. Credit: Charizanis et al., Neuron.

"The new animal model reproduces important aspects of myotonic dystrophy brain disease, so this model may be useful to develop biomarkers and test future drug therapies," says senior study author Maurice Swanson of the University of Florida.

Previous studies had shown that mutated genes underlying the disease produce toxic ribonucleic acids (RNAs) during transcription, and these RNAs cause the production of incorrect forms of proteins in muscle tissue by blocking the actions of a protein called MBNL1. As a result, proteins typically found in fetal muscles increase in abundance, while the normal suite of proteins found in adult muscles decrease in number. However, until now, it was not clear whether molecular abnormalities similar to those in muscle tissue of individuals with mytonic dystrophy also occur in the brain, resulting in the cognitive neurological problems.

In the new study, Swanson and his team focused on a related protein called MBNL2, which is found in the brain. They developed a new mouse model that lacked a functional Mbnl2 gene. These animals experienced an increase in the amount of rapid eye movement sleep as well as learning and memory deficits, similar to human patients.

The researchers also found extensive evidence of toxic RNAs in the hippocampus, as well as signs that fetal proteins were being produced in the brains of adult mutants. This pattern was also evident in the autopsied brain tissue of humans who had myotonic dystrophy. “This study should accelerate our understanding of how myotonic dystrophy mutations impact brain development and function,” Swanson says.

Source: EurekAlert!

By Lisa Cosgrove | August 7, 2012

It is part of the human condition to have implicit biases—and remain blissfully ignorant of them. Academic researchers, scientists, and clinicians are no exception; they are as marvelously flawed as everyone else. But it is not the cognitive bias that’s the problem. Rather, the denial that there is a problem is where the issues arise. Indeed, our capacity for self-deception was beautifully captured in the title of a recent book addressing researchers’ self-justificatory strategies, Mistakes Were Made (But Not by Me).

Illustration by Dusan Petricic

Decades of research have demonstrated that cognitive biases are commonplace and very difficult to eradicate, and more recent studies suggest that disclosure of financial conflicts of interest may actually worsen bias. This is because bias is most often manifested in subtle ways unbeknownst to the researcher or clinician, and thus is usually implicit and unintentional.  For example, although there was no research misconduct or fraud, re-evaluations of liver tissue of rats exposed to the drug dioxin resulted in different conclusions about the liver cancer in those rats: compared to the original investigation, an industry-sponsored re-evaluation identified fewer tissue slides as cancerous and this finding affected policy recommendations (water quality standards were weakened). (See also Brown, Cold Spring Harbor Laboratory Press, 13–28, 1991.) This example is just one of many that points to a genericrisk that a financial conflict of interest may compromise research or undermine public trust.

Indeed, recent neuroscience investigations demonstrate that effective decision-making involves not just cognitive centers but also emotional areas such as the hippocampus and amygdala. This interplay of cognitive-emotional processing allows conflicts of interest to affect decision-making in a way that is hidden from the person making the decision.

Despite these findings, many individuals are dismissive of the idea that researchers’ financial ties to industry are problematic. For example, in a recent essay in The Scientist, Thomas Stossel of Brigham & Women’s Hospital and Harvard Medical School asked, “How could unrestricted grants, ideal for research that follows up serendipitous findings, possibly be problematic? The money leads to better research that can benefit patients.” Many argue that subjectivity in the research process and the potential for bias can be eradicated by strict adherence to the scientific method and transparency about industry relationships. Together, scientists believe, these practices can guarantee evidence-based research that leads to the discovery and dissemination of “objective” scientific truths. The assumption is that the reporting of biased results is a “bad apple” problem—a few corrupt individuals engaging in research fraud. But what we have today is a bad barrel.

Some have begun to use the analytic framework of “institutional corruption” to bring attention to the fact that the trouble is not with a few corrupt individuals hurting an organization whose integrity is basically intact. Institutional corruption refers to the systemic and usually legal—and often accepted and widely defended—practices that bring an organization or institution off course, undermine its mission and effectiveness, and weaken public trust. Although the entire field of biomedicine has come under scrutiny because of concerns about an improper dependence on industry and all medical specialties have struggled with financial conflicts of interest, psychiatry has been particularly troubled, being described by some as having a crisis of credibility.

This credibility crisis has been played out most noticeably in the public controversy surrounding the latest revision to the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM is often referred to as the “Bible” of mental disorders, and is produced by the American Psychiatric Association (APA), a professional organization with a long history of industry ties. DSM-5, the revised edition scheduled for publication in May, 2013, has already been criticized for “disease mongering,” or pathologizing normal behavior. Concerns have been raised that because the individuals responsible for making changes and adding new disorders have strong and long-standing financial associations to pharmaceutical companies that manufacture the drugs used to treat these disorders, the revision process may be compromised by undue industry influence.

Researchers, clinicians, and psychiatrists who served on the DSM-IV have pointed out that adding new disorders or lowering the diagnostic threshold of previously included disorders may create “false positives,” individuals incorrectly identified as having a mental disorder and prescribed psychotropic medication.  For example, there was a heated debate about pathologizing the normal grieving process if DSM-5 eliminated the bereavement exclusion for major depressive disorder (MDD).  The concern was that widening the diagnostic boundaries of depression to include grief as a “qualifying event,” thereby allowing for a diagnosis of MDD just 2 weeks after the loss of a loved one, would falsely identify individuals as depressed. Although it is not the APA’s intent to play handmaiden to industry, the reality is that such a change would result in more people being prescribed antidepressants following the loss of a loved one. In fact, psychiatrist Allen Frances, who chaired the DSM-IV task force, has noted that DSM-5 would be a “bonanza” for drug companies.

After receiving criticism about potential bias in the development of the DSM-IV, the APA required that DSM-5 panel members file financial disclosures. Additionally, during their tenure on the panels they were not allowed to receive more than $10,000 from pharmaceutical companies or have more than $50,000 in stock holdings in pharmaceutical companies (unrestricted research grants were excluded from this policy). The majority of diagnostic panels, however, continue to have the majority of their members with financial ties to the pharmaceutical industry. Specifically, 67 percent of the 12-person panel for mood disorders, 83 percent of the 12-person panel for psychotic disorders, and all 7 members of the sleep/wake disorders panel (which now includes ‘‘Restless Leg Syndrome’’) have ties to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.

Clearly, the new disclosure policy has not been accompanied by any reduction in the financial conflicts of interest of DSM panel members. Moreover, Darrel Regier, speaking on behalf of the APA and in defense of DSM panel members with industry ties, told USA Today. “There’s this assumption that a tie with a company is evidence of bias. But these people can be objective.”  However, as science has repeatedly shown, transparency alone cannot mitigate bias and is an insufficient solution for protecting the integrity of the revision process. Objectivity is not a product that can be easily secured by adherence to the scientific method. Rather, there is a generic risk that a conflict of interest may result in implicit, unintentional bias. Similarly, as Sinclair Lewis said, “It is difficult to get a man to understand something when his salary depends upon his not understanding it.”

Source: TheScientist