Science News & Reviews

Mice show empathy

2006-07-21T09:09:00.000-07:00

Science 312, 1967–1970 (2006)
A mouse watching a cage-mate writhe in pain will writhe more itself, an observation that Jeffrey Mogil and his team at McGill University in Montreal conclude is evidence of rodent empathy.
The researchers tested mice in twos, giving one or both mildly painful shots of acetic acid. If the two were strangers, they behaved as if they were on their own. But if they had lived together for a few weeks, and both got a shot, they both showed more abdominal constrictions, termed writhing, than when given a shot alone. The effect vanished if the roomies could not see one another.
Empathy has previously been considered an attribute of primates alone. Of course, the empathetic response does not indicate that the mice consciously felt sorry for one another — only that they respond to each other's pain.

It's All in the Mind

2006-04-28T07:38:00.000-07:00

How do physiological and molecular variation combine to create a range of motivational drives that becomes manifest as a range of behaviors? Champagne et al. report measurements of dopamine in the nucleus accumbens of female rats caring for (licking and grooming) their pups. This region of the brain is known to contribute to motivating behaviors, particularly those that are followed by reward, such as the consumption of food. The increase in dopamine preceded the initiation of licking and grooming acts by the mothers, and the size and duration of the dopamine signal correlated with the duration of the act. Furthermore, mothers previously scored as high or low in licking/grooming (greater than 1 standard deviation from the mean of a normally distributed group) exhibited consistently high or low scores in the dopamine signal and in the density of dopamine receptors in the shell of the nucleus accumbens. Taken together with earlier studies in this series, these results begin to establish a neurochemical basis for individual differences in maternal behavior.
J. Neurosci. 24, 4113 (2004).

Neurons in the orbitofrontal cortex encode economic value

2006-04-26T20:40:00.000-07:00

Economic choice is the behaviour observed when individuals select one among many available options. There is no intrinsically 'correct' answer: economic choice depends on subjective preferences. This behaviour is traditionally the object of economic analysis1 and is also of primary interest in psychology2. However, the underlying mental processes and neuronal mechanisms are not well understood. Theories of human and animal choice1 have a cornerstone in the concept of 'value'. Consider, for example, a monkey offered one raisin versus one piece of apple: behavioural evidence suggests that the animal chooses by assigning values to the two options4. But where and how values are represented in the brain is unclear. Here we show that, during economic choice, neurons in the orbitofrontal cortex (OFC) encode the value of offered and chosen goods. Notably, OFC neurons encode value independently of visuospatial factors and motor responses. If a monkey chooses between A and B, neurons in the OFC encode the value of the two goods independently of whether A is presented on the right and B on the left, or vice versa. This trait distinguishes the OFC from other brain areas in which value modulates activity related to sensory or motor processes. Our results have broad implications for possible psychological models, suggesting that economic choice is essentially choice between goods rather than choice between actions. In this framework, neurons in the OFC seem to be a good candidate network for value assignment underlying economic choice.

Younger Moms' Kids Get Longevity Edge

2006-04-17T13:18:00.000-07:00

MONDAY, April 17 (HealthDay News) -- Society's oldest members are most likely to be born to its youngest mothers, new research suggests.
The odds of living to 100 and beyond double when a person is born to a woman under 25 years of age, compared to those people born to older mothers, according to one of the most rigorous studies on the subject yet conducted.
The finding may also help clear up a statistical mystery -- three years ago, the same husband-and-wife team of researchers found that being the first-born child in a family also boosted longevity, although no one knew why.
"It turns out that the whole phenomenon of first-born order and longevity is driven by young maternal age," said study co-author Leonid Gavrilov, a research associate at the Center on Aging at the University of Chicago.
In other words, he said, first-born children are simply more likely than their siblings to have been born when mom was in her teens or early 20s.
The study, which was funded by the U.S. National Institute on Aging (NIA) and the Society of Actuaries, was presented recently at the Population Association of America annual meeting, in Los Angeles.
As nutrition and health care continue to improve, so too does the number of Americans whose years extend into the triple-digits.
"Certainly there were more [centenarians] in the 2000 census than there were in 1990, and most people think this population will grow," said Georgeanne Patmios, acting chief of the Population and Social Processes Branch of the NIA's Behavioral and Social Research Program.
According to the Census Bureau, there were 37,000 Americans aged 100 years or older in 1990, and by 2000 that population had risen to 55,000. According to experts, women are three to five times more likely to live beyond 100 than men.
But what other factors encourage "extreme" old age? Previous research by Gavrilov and his wife/co-researcher, Natalia Gavrilova, has uncovered some clues. For example, in research published over the past few years, they found that U.S. centenarians were more likely to come from farming families in the Midwest than from any other demographic.
They also discovered that being the first-born in a family meant a lot, boosting the odds of making it to 100 by nearly 80 percent.
"But nobody knew why that was -- sometimes in research you get answers, but you also get new questions," Gavrilov said.
So, he and his wife set out to solve that puzzle. They selected 198 centenarians from across the United States, checking and double-checking their ages using every form of documentation available. Comparing the centenarians' histories to those of their siblings, the researchers then analyzed the data to help explain the "first-born effect."
One theory -- that first-born children might have been relatively protected from pediatric illness because they weren't surrounded by disease-bearing siblings in infancy -- didn't pan out. "We found that even at age 75 it still matters that one is first-born," Gavrilov said. "It's a late-life phenomenon."
A second theory -- that first-born kids reaped the benefit of a relatively young, strong and productive father -- also fell flat. "We got the very clear result that the father's age wasn't important," the Chicago researcher said.
That wasn't the case for mothers. In fact, statistical analysis revealed that young maternal age at birth completely accounted for the first-born effect.
"It is very rare in science that you have such clear-cut results. But here, when we saw the results, we went 'Wow,'" Gavrilov said. Overall, children born to an under-25 mother had double the odds of living to 100 and beyond, compared to offspring of women who delivered at a later age.
So, why do young moms tend to bear more long-lived children? "At this point all we have is hypotheses," Gavrilov said. "One is biological -- that maybe the eggs are different in their quality, and the best ones, the most vigorous eggs, go first to fertilization."
He said his wife Natalia came up with a competing theory: That young moms haven't had time to pick up the latent, chronic infections that might in some way impede the long-term health of their offspring. "This might interfere with normal development," Gavrilov said. "So, when the children are born they are superficially healthy but maybe they are not really strong enough to survive to 100."
Patmios said the question of why younger mothers might bear more resilient offspring remains "open, but it's worthy of additional research." She stressed that it has proven extremely tough to get in-depth, reliable data for events that happened over a century ago. "There are a lot of other factors that probably contribute to exceptional longevity which, given the dataset that Dr. Gavrilov has to use, he can't assess," she said.
And what about the longevity of children born to today's moms, who are often postponing first pregnancy to their 30s or even 40s? According to Gavrilov, advances in diet and health care mean American newborns still have a better chance of living out a century than their great-grandparents did.
"The data shows that there is a steady increase in living to age 100, despite the fact that women are tending to postpone their childbearing years," he said.

Cooperation, Punishment, and the Evolution of Human Institutions

2006-04-10T15:42:00.000-07:00

Explaining the scale, diversity, and historical dynamics of human cooperation is increasingly bringing together diverse empirical and theoretical approaches. For decades, this challenge has energized evolutionary and economic researchers to ask: Under what conditions will decision-makers sacrifice their own narrow self-interest to help others? Although classic evolutionary models based on relatedness and reciprocity have explained substantial swaths of the cooperation observed in many species, including our own, theoretical work in the 1980s demonstrated that the puzzle of cooperation in large groups, or in situations without much repeated interaction, remained unsolved and would likely require alterative theoretical formulations.

Such cooperative dilemmas, or "public goods" problems, involve situations in which individuals incur a cost to create a benefit for the group. In our society, think of recycling, buying a hybrid car, valor in combat, voting, and donating blood. The dilemma arises from free-riders who enjoy the group benefits created by the contributions of others without paying the costs. Even if nearly everyone is initially cooperative and contributes, free-riders can profit and proliferate, leading to the eventual collapse of cooperation. So, understanding how public goods problems can be solved has provoked great interest, both because human societies have somehow managed to solve many such problems to varying degrees, and because some of the world's most pressing issues, such as global climate change, are essentially public goods dilemmas. On page 108 of this issue, Gürerk et al. take an important step in understanding how self-sustaining cooperative institutions may have emerged over the course of human history.

Recent models have demonstrated how evolutionary processes (genetic or cultural) can maintain cooperation in large groups or without repeated interaction. Costly signaling models have shown how cooperation by "high-quality individuals" (those who are potentially desirable as allies or mates) can be sustained if such individuals can accurately signal their quality by making substantial cooperative contributions to public goods. For example, great hunters might supply all the meat for a public feast, or millionaires might donate a recreational center to their community. Similarly, reputation-based models have shown how cooperation can be sustained if individuals' reputations for not contributing to public goods reduce their payoffs (or fitness) by altering how others treat them in certain dyadic social interactions. Finally, models that allow individuals to both contribute to the public good and to sanction noncontributors have revealed stable cooperative solutions, especially when the strategies for cooperation and punishment are influenced by social learning. Thus, a number of possible stable solutions to the puzzle of cooperation in large groups, or cooperation without repeated interaction, have now emerged.
It turns out, however, that finding a stable solution is only the first step in confronting the dilemma of cooperation. Each of the above approaches can actually stabilize any behavior or practice, independent of whether it delivers any benefit to anyone. This includes behaviors that reduce the payoff or fitness of the group. For example, instead of public goods contributions, costly signaling could maintain behaviors involving dangerous physical feats (like scaling icy mountain peaks), aggressive displays (like beating up your neighbor), or extravagantly wasteful feasts. Similarly, the same reputational and sanctioning mechanisms that can stabilize cooperation can also sustain maladaptive practices such as consuming the brains of dead relatives, flattening the foreheads of infants, or binding the feet of young girls. Thus, there are actually a multitude of stable equilibria, only some of which are cooperative. What determines which equilibria emerge and/or spread?
Three broad theoretical approaches confront the problem of equilibrium selection. The first, and perhaps the most intuitive, is that rational, forward-looking individuals recognize the long-term payoffs available at stable cooperative equilibria, assume others are similarly sensible, and choose the cooperative state. The second approach is based on the stochasticity inherent in any interaction. Different stable equilibria are more or less susceptible to this stochasticity, meaning that in the long-run, some equilibria will be substantially more common than others. The third mechanism, cultural group selection, gives priority to the competition among social groups who have arrived at different culturally evolved equilibria. This intergroup competition favors the spread of individuals and practices from groups stabilized at more cooperative equilibria. In humans, competition between groups can take the form of warfare, demographic production (some social groups reproduce faster than others), or more subtle forms in which individuals learn decisions and strategies by preferentially observing more successful individuals, many of whom are more successful because they live in groups at stable cooperative equilibria. This can lead to a flow of decisions, strategies, and even preferences from more cooperative groups to less cooperative ones, or to a migration of individuals among groups that favors the spread of the more cooperative equilibria.
Gürerk et al. address the issue of equilibrium selection with an elegant addition to the existing experimental work on public goods. In their experiment, individuals (the "players") choose between two different "institutions." In one institution, players can contribute money to a group project. The sum of all contributions to the project is augmented by a fixed percentage and then is divided equally among all players, regardless of their contributions. Previous experiments established that when this interaction is repeated, mean contributions to the public good drop to near zero (a noncooperative equilibrium). The other "sanctioning" institution is very similar, except that after players have contributed, they can pay to punish (reduce the payoff of) other players. When this interaction is played repeatedly a substantial fraction of players punish low contributors, causing mean contributions to rise and stabilize near full cooperation (a cooperative equilibrium). Both institutions were run concurrently for 30 interactions and players could, initially and after each subsequent interaction (after seeing others' payoffs), choose their institution for the next interaction.
The principal findings of Gürerk et al. can be summarized simply. Initially, most players picked the institution without sanctioning possibilities. But, as usual, free-riders in the nonsanctioning institution started driving mean contributions downward, so cooperators, who hate being exploited by free-riders, started reducing their contributions. Meanwhile, in the sanctioning institution, punishers started driving contributions up by inflicting costs on noncontributors, despite the personal cost of punishing. After a few interactions, players from the nonsanctioning institution--presumably seeing the higher payoffs of those choosing the sanctioning institution--increasingly switched institutions. Notably, despite the incoming flow of migrants from the nonsanctioning institution, the mean contributions in the sanctioning institution consistently increased or held stable near full cooperation. In fact, most incoming migrants, consistent with local norms in their new setting, increased their contributions during their first interaction in the sanctioning institution, and a majority administered some punishment.
What does this tell us about equilibrium selection? First, the players' degree of rationality did not permit them to foresee the final outcome and select the higher payoff institution on the first interaction. Second, despite the stochasticity of human decisions, neither institution drifted to another equilibrium. What did happen is that once players from the lower payoff institution observed the higher payoffs of the other institution, they wanted to adopt either the practices of the higher payoff institution, or the decisions and strategies of those other players. Consistent with ethnographic and historical case studies, the present work provides an important experimental demonstration of cultural group selection in action, as the two alternative equilibria compete for shares of the total population.
The course charted by Gürerk et al. should spur more empirical work on how processes of equilibrium selection influence the evolution of institutional forms. Many questions remain to be tackled: for example, what happens if switching institutions is costly, or if information about the payoffs in the other institution is poor? Or, what happens if individuals cannot migrate between institutions, but instead can vote on adopting alternative institutional modifications? Such work can both help us understand how humans became such a cooperative species, and teach us how to build durable cooperative institutions that solve public goods problems and are readily spread.

A male gene for a male brain

2006-03-21T06:53:00.000-08:00

Male and female brains are different in important ways — not just in generating distinct sexual behaviours, but also in terms of cognition and other key functions. Until recently, these differences were thought to arise from the effects of sex hormones during brain development, but there have been several hints lately that genes in the adult brain have a role in maintaining this male–female divide. Work from Eric Vilain and colleagues now shows that the Y-chromosome gene Sry directly influences the function of the brain in adult males.
Sry is a transcriptional regulator and is best known as the master controller of male sexual development. However, previous studies have shown that, intriguingly, this gene is also expressed in the adult male brain. Vilain and colleagues confirmed this, showing that Sry mRNA is present at a low level throughout the brain cortex in male mice, and at higher levels in two regions: the mammillary bodies and the substantia nigra (SN). Focusing on the SN, which controls voluntary movement, the authors showed that the SRY protein colocalizes with tyrosine hydroxylase (TH), an enzyme that is involved in the synthesis of the neurotransmitter dopamine, which is essential for the functioning of this region.
To investigate the functions of SRY in TH-expressing cells, male rat SNs were microinfused with antisense oligonucleotides targeted against Sry. This led to reduced TH expression in the SN and in regions that are usually innervated by TH-expressing neurons, showing that SRY directly regulates the expression of this enzyme. The authors were also able to show that SRY expression in the SN has a functional consequence. Microinfusion of Sry antisense oligonucleotides into the SN on one side of the brain reduced the stepping activity of rats using the forelimb on the corresponding side of the body.
The fact that SRY functions in the adult male brain in a way that doesn't rely on hormones indicates that we should think differently about sexual dimorphisms in the brain, taking direct genetic effects into account. This will be important for many reasons, not least for understanding the differing susceptibilities of men and women to psychiatric disorders and other neurological diseases.
Nature Reviews Genetics 7, 244-245 (April 2006)

New genetic discovery explains 74 percent cases of age-related macular degeneration

2006-03-06T12:37:00.000-08:00

A new study, led by researchers at Columbia University Medical Center, pinpoints the role that two genes – Factor H and Factor B – play in the development of nearly three out of four cases of age-related macular degeneration (AMD), a devastating eye disease that affects more than 10 million people in the United States.
Findings indicate that 74 percent of AMD patients carry certain variants in one or both genes that significantly increase their risk of this disease.
Published in Nature Genetics, the research is a continuation of work published last year by the same team in the Proceedings of the National Academy of Sciences (PNAS, April 30, 2005 issue, see Columbia press release: http://www.cumc.columbia.edu/news/press_releases/AMD-Allikmets.html). Led by Rando Allikmets, Ph.D., the Acquavella Associate Professor in Ophthalmology, Pathology and Cell Biology at Columbia University Medical Center, the research team included collaborating groups headed respectively by Gregory Hageman, Ph.D., professor of ophthalmology and visual sciences at the University of Iowa Roy J. and Lucille A. Carver College of Medicine, and by Michael Dean, Ph.D., at the National Cancer Institute of the National Institutes of Health.
The PNAS study showed that several variants in the Factor H gene significantly increase the risk of developing AMD. Factor H encodes a protein that helps shut down an immune response against bacterial or viral infection, once the infection is eliminated. People with these inherited risk-increasing variations of Factor H are less able to control inflammation caused by infectious triggers, which may spark AMD later in life.
Though the effect of Factor H on AMD is large, variation in this gene alone does not fully explain who gets AMD and who doesn't. As described in the PNAS paper, about one-third (29 percent) of people with a Factor H risk variant had not been diagnosed with AMD.
The investigators decided to look for additional culprits and focused on genes in the same immune response pathway that contains Factor H.
Their genetic analysis of 1,300 people quickly identified Factor B as the major modifier of the disease. The discovery makes good biological sense: while Factor H is an inhibitor of the immune response to infection, Factor B is an activator. Because of the complementary roles of the these two genes, a protective Factor B variation can protect against AMD, even if one carries a risk-increasing variant of Factor H, and vice versa.
As described in Nature Genetics, the two genes explained nearly three out of four AMD cases: 74 percent of the subjects with AMD had either the Factor H or Factor B risk variant (or both), but no protective variants of either gene.
"I am not aware of any other complex disorder where nearly 75 percent of genetic causality has been identified," said Dr. Rando Allikmets, who is senior author of the paper.
"These findings are significant because they absolutely confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD. We confirmed this association not just statistically and genetically but, most importantly, pinpointed the biological origin of the disease," added Dr. Allikmets. "In just a few short years, we've gone from knowing very little about what causes AMD to knowing quite a lot. We now have clear targets for early therapeutic intervention."
Though the new paper explains much of the genetic risk, the specific triggers that set off the immune response and subsequent inflammation are still unknown. Researchers at Columbia University Medical Center and the University of Iowa are now searching for specific viral and bacterial culprits.
Published online: 5 March 2006; doi:10.1038/ng1750

FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains

2006-02-28T16:13:00.000-08:00

Nature Neuroscience 9, 443 - 452 (2006) Published online: 19 February 2006; doi:10.1038/nn1654
A major challenge in systems neuroscience is to perform precise molecular genetic analyses of a single neuronal population in the context of the complex mammalian brain. Existing technologies for profiling cell type–specific gene expression are largely limited to immature or morphologically identifiable neurons. In this study, we developed a simple method using fluorescent activated cell sorting (FACS) to purify genetically labeled neurons from juvenile and adult mouse brains for gene expression profiling. We identify and verify a new set of differentially expressed genes in the striatonigral and striatopallidal neurons, two functionally and clinically important projection neuron subtypes in the basal ganglia. We further demonstrate that Ebf1 is a lineage-specific transcription factor essential to the differentiation of striatonigral neurons. Our study provides a general approach for profiling cell type–specific gene expression in the mature mammalian brain and identifies a set of genes critical to the function and dysfunction of the striatal projection neuron circuit.

Depression model leaves mice with molecular scar

2006-02-28T15:57:00.000-08:00

In addition to triggering a depression-like social withdrawal syndrome, repeated defeat by dominant animals leaves a mouse with an enduring "molecular scar" in its brain that could help to explain why depression is so difficult to cure, suggest researchers funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH).
In mice exposed to this animal model of depression, silencer molecules turned off a gene for a key protein in the brain's hippocampus. By activating a compensatory mechanism, an antidepressant temporarily restored the animals' sociability and the protein's expression, but it failed to remove the silencers. A true cure for depression would likely have to target this persistent stress-induced scar, say the researchers, led by Eric Nestler, M.D., The University of Texas Southwestern Medical Center, who report on their findings online in Nature Neuroscience during the week of February 26, 2005.
"Our study provides insight into how chronic stress triggers changes in the brain that are much more long-lived than the effects of existing antidepressants," explained Nestler.
Mice exposed to aggression by a different dominant mouse daily for 10 days became socially defeated; they vigorously avoided other mice, even weeks later. Expression of a representative gene in the hippocampus, a memory hub implicated in depression, plummeted three-fold and remained suppressed for weeks. However, chronic treatment with an antidepressant (the tricyclic imipramine) restored expression of the gene for brain derived neurotrophic factor (BDNF) to normal levels and reversed the social withdrawal behavior. BDNF in the hippocampus has been linked to memory, learning and depression, but Nestler said social defeat stress probably similarly affects other genes there as well.
The researchers pinpointed how social defeat changes the BDNF gene's internal machinery. They traced the gene expression changes to long-lasting modifications in histones, proteins that regulate the turning on-and-off of genes via a process called methylation. Methyl groups, the silencer molecules, attach themselves to the histones, turning off the gene. Notably, imipramine was unable to remove these silencer molecules, suggesting that they remained a latent source of vulnerability to future depression-like responses to stress.
Imipramine reversed the suppressed BDNF gene expression by triggering a compensatory mechanism, acetylation, in which molecular activators attach themselves to the gene and overcome the silencer molecules. Imipramine turned off an enzyme (Hdac5) that degrades the activators, allowing them to accumulate.
"The molecular scar induced by chronic stress in the hippocampus, and perhaps elsewhere in the brain, can't be easily reversed," said Nestler. "To really cure depression, we probably need to find new treatments that can remove the silencer molecules."

Tsankova NM, Berton O, Renthal W, Kumar A, Neve R, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature Neuroscience. Published online, 2/26/2006
To better understand the molecular mechanisms of depression and antidepressant action, we administered chronic social defeat stress followed by chronic imipramine (a tricyclic antidepressant) to mice and studied adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters in the hippocampus. Defeat stress induced lasting downregulation of Bdnf transcripts III and IV and robustly increased repressive histone methylation at their corresponding promoters. Chronic imipramine reversed this downregulation and increased histone acetylation at these promoters. This hyperacetylation by chronic imipramine was associated with a selective downregulation of histone deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the hippocampus blocked imipramine's ability to reverse depression-like behavior. These experiments underscore an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression.

PSYCHOLOGY: Unintentional Music Sharing

2006-02-23T21:30:00.000-08:00

Might our selves be revealed by our choices in music? Rentfrow and Gosling explored this question by asking 74 college students to provide individual top-10 lists of their favorite songs, which were then recorded onto CDs. The students were also asked to provide self-report ratings on personality measures, such as extraversion and conscientiousness; terminal and instrumental values, such as a comfortable life and ambition; and affect and self-esteem. Eight listeners were then asked to rate the students on the same criteria, solely on the basis of hearing their music selections. The measures for which listener judgments correlated most strongly with the self-report data were the personality trait of openness to experience and the instrumental value of imagination. Furthermore, three other listeners had previously coded the songs for 25 experimentally tested musical attributes (for instance, the amount of singing), and these characteristics also displayed correlations with openness and imagination (along with several other traits and values). The results show a differentiating and consistent linkage between our musical tastes and the impressions of us that strangers form purely from learning which songs we like.
Psychol. Sci. 17, 236 (2006).

Rats Are Smarter Than We Think

2006-02-23T21:23:00.000-08:00

Although both human and nonhuman animals may use basic associative mechanisms to learn about causal relations, humans have a deeper understanding of causal relations that cannot be reduced to associative learning. In contrast, there is no definite proof that animals, including nonhuman primates, possess deep causal understanding. Blaisdell et al. (p. 1020) present evidence that rats can reason about the effects of their causal interventions. Rats correctly predicted that interventions on one effect of a common-cause model would not affect the other effect. Thus, rats can engage in more sophisticated causal reasoning than predicted by associative models.

Science 17 February 2006:Vol. 311. no. 5763, pp. 1020 - 1022DOI: 10.1126/science.1121872
Causal Reasoning in Rats
Empirical research with nonhuman primates appears to support the view that causal reasoning is a key cognitive faculty that divides humans from animals. The claim is that animals approximate causal learning using associative processes. The present results cast doubt on that conclusion. Rats made causal inferences in a basic task that taps into core features of causal reasoning without requiring complex physical knowledge. They derived predictions of the outcomes of interventions after passive observational learning of different kinds of causal models. These competencies cannot be explained by current associative theories but are consistent with causal Bayes net theories.

Don't Think Too Much

2006-02-23T21:17:00.000-08:00

Science 17 February 2006:Vol. 311. no. 5763, p. 935DOI: 10.1126/science.311.5763.935
Buying oven mitts and buying a car demand completely different types of decision-making. Most people would scarcely think about the mitts and agonize over the car. That's exactly the wrong way to go about it, according to a provocative new study.
On page 1005, Ap Dijksterhuis and colleagues at the University of Amsterdam in the Netherlands report a series of experiments with student volunteers and real-life shoppers that suggests that too much contemplation gets in the way of good decision-making--especially when the choice is complicated. Conscious deliberation is best suited for simple decisions such as choosing oven mitts, the researchers argue, whereas complex decisions like picking a car are best handled by the unconscious mind.
"They're elegant experiments with a simple design and eye-popping result," says Timothy Wilson, a psychologist at the University of Virginia in Charlottesville. The research should "stimulate some useful new thinking" among decision researchers, says Daniel Kahneman of Princeton University.
The problem with conscious thought, Dijksterhuis contends, is that you can only think about so many things at the same time. He hypothesized that decisions that require evaluating many factors may be better handled by unconscious thought processes.
To test the idea, Dijksterhuis and colleagues asked volunteers to read brief descriptions of four hypothetical cars and pick the one they'd like to buy after mulling it over for 4 minutes. The researchers made the decision far simpler than it is in real life by limiting the descriptions to just four attributes such as good gas mileage or poor legroom. One of the cars had more plusses than the others, and most participants chose this car. But when the researchers made the decision more complex by listing 12 attributes for each car, people identified the best car only about 25% of the time--no better than chance. The real surprise came when the researchers distracted the participants with anagram puzzles for 4 minutes before asking for their choices. More than half picked the best car. The counterintuitive conclusion, Dijksterhuis says, is that complex decisions are best made without conscious attention to the problem at hand.
To test the idea in a more natural setting, the researchers visited two stores: the international furniture store IKEA and a department store called Bijenkorf. A pilot study with volunteer subjects had suggested that shoppers weigh more attributes when buying furniture than when buying kitchen accessories and other simple products commonly purchased at Bijenkorf. The researchers quizzed shoppers at the two stores about how much time they'd spent thinking about their purchases and then called them a few weeks later to gauge their satisfaction. Bijenkorf shoppers who spent more time consciously deliberating their choices were more pleased with their purchases--evidence that conscious thought is good for simple decisions, Dijksterhuis says. But at IKEA, the reverse was true: Those who reported spending less time deliberating turned out to be the happiest.
Jonathan Schooler, a psychologist at the University of British Columbia in Vancouver, says the study builds on evidence that too much reflection is detrimental in some situations. But "it adds an important insight" by identifying complexity as a key factor in determining which kind of thought process leads to the best decision. Schooler isn't ready, however, to dispense with conscious thought when it comes to complex decisions. "What I think may be really critical is to engage in [conscious] reflection but not make a decision right away," says Schooler.
Dijksterhuis agrees. When an important decision arises, he gathers the relevant facts and gives it his full attention at first. Then, he says, "I sit on things and rely on my gut."

Why Sex?

2006-02-23T21:07:00.000-08:00

Science 17 February 2006:Vol. 311. no. 5763, pp. 960 - 961DOI: 10.1126/science.1124663
Why sex? This has been one of the most fundamental questions in evolutionary biology. In many species, males do not provide parental care to the offspring. Clearly, the rate of reproduction could be increased if all individuals were born as females and reproduced asexually without the need to mate with a male (parthenogenetic reproduction). Parthenogenetically reproducing females arising in a sexual population should have a twofold fitness advantage because they, on average, leave twice as many gene copies in the next generation. Nonetheless, sexual reproduction is ubiquitous in higher organisms. Why do all these species bother to have males, if males are associated with a reduction in fitness? The main solution that population geneticists have proposed to this conundrum is that sexual reproduction allows genetic recombination, and that genetic recombination is advantageous because it allows natural Darwinian selection to work more efficiently. New empirical evidence supporting this theory now comes from a study by Paland and Lynch on page 990 in this issue (1).
One reason why selection works more efficiently in the presence of recombination--that is, the exchange of genetic material between chromosomes--is that selected mutations tend to interfere with each other in the absence of recombination (2, 3). Imagine, for example, a beneficial mutation (A) arising in one individual and another beneficial mutation (B) arising in another gene in an individual that does not carry mutation A. In the absence of recombination, mutation B would be eliminated when mutation A reaches a frequency of 100% in the population, and vice versa. No individual carrying both beneficial mutations could be created, and only one of the mutations could eventually reach a frequency of one in the population. Recombination speeds up the rate of adaptive evolution because it allows several beneficial mutations to be combined in the same individual. Likewise, when multiple deleterious mutations are present in the population, recombination has the potential for creating new offspring chromosomes with fewer deleterious mutations than either of the parental chromosomes. The famous population geneticist John Maynard- Smith compared this situation to having two cars: one with a broken engine and one with a broken transmission. Neither of them can run, but if you can replace the broken part in one car with a part from the other car you can produce a new functional car. Recombination allows broken parts to be shuffled among chromosomes, allowing new combinations to arise for selection to act on. Under suitable assumptions regarding the way deleterious mutations affect organismal fitness, the advantage of recombination in eliminating deleterious mutations can outweigh the twofold cost of sex (3).
However, the selection theories are not free of contradictions and problems. Some of them rely on so-called group-selection arguments, where adaptive properties are properties of a whole population and not of individuals. If sexually reproducing individuals and their offspring do not have an immediate selective advantage in otherwise asexual populations, it is hard to see how populations can ever evolve from asexual to sexual reproduction. Additionally, the best explanations regarding deleterious mutations rely on strong assumptions regarding the distribution of selective effects (3), and there may be other factors favoring sex, such as increased resistance to pathogens (4). An observed genomic correlation between the rate of recombination and variability within species (5) suggests that there is an interaction between selection and recombination, but a direct difference between sexual and asexual populations has been hard to establish.
However, the new study by Paland and Lynch (1) provides direct empirical support for an excess accumulation of mutations in asexually reproducing populations compared to sexual populations. They examined different populations of the small crustacean Daphnia pulex, a type of water flea. Daphnia are excellent organisms to study in this regard because parthenogenetic Daphnia populations have arisen multiple times from sexual populations. Comparing asexual and sexual populations of Daphnia is, therefore, the perfect tool for examining the population genetic consequences of sexual reproduction (see the figure).
Paland and Lynch (1) compared the number of mutations with possible functional effects (nonsynonymous mutations) to the number of mutations with no functional effects (synonymous mutations) in 14 asexual and 14 sexual Daphnia populations. They observed a clear excess of nonsynonymous mutations in the asexual populations. They also estimated that close to 90% of the nonsynonymous mutations were subject to selection. These results suggest that the asexually reproducing species carry a higher load of deleterious mutations and that selection is not as efficient in the asexual as in the sexual populations. It does not directly demonstrate that selection against deleterious mutations is what maintains sexual reproduction, but the results do confirm the most important component of the selection theory: Asexual reproduction leads to an accumulation of deleterious mutations. It seems that males are allowed to exist after all, because they help females get rid of deleterious mutations.
The study is also interesting from another point of view. The estimate of the proportion of new mutations in Daphnia that are under selection is fairly high (>90%). Over the past 30 years, the paradigmatic theory in molecular evolution has been the Neutral Theory (6), which assumes that the vast majority of genetic polymorphisms have little or no selection acting upon them. However, the study by Paland and Lynch (1), and other recent studies (7, 8), suggest instead that many or most polymorphisms may be under selection. Slowly, our weltanschauung in evolutionary biology is changing from a static view of a largely optimized genome to a dynamic view of organisms constantly challenged by selection and struggling with the large genetic load imposed by deleterious and new advantageous mutations segregating in the population.

Reproductive Social Behavior: Cooperative Games to Replace Sexual Selection

2006-02-23T20:48:00.000-08:00

Science 17 February 2006:Vol. 311. no. 5763, pp. 965 - 969DOI: 10.1126/science.1110105

A recent review of diversity in animal reproductive social behavior (1) raises questions about Darwin's 1871 theory of sexual selection (2). Unlike the theories of evolution through common descent and of evolutionary change by natural selection, Darwin's theory of sexual selection has continually drawn criticism from evolutionists, notably Huxley in 1938 (3). Darwin wrote "Males of almost all animals have stronger passions than females" and "the female... with the rarest of exceptions is less eager than the male... she is coy." Darwin explained these templates as resulting from females choosing mates who are "vigorous and well-armed... just as man can improve the breed of his game-cocks by the selection of those birds which are victorious in the cock-pit." He continues, "Many female progenitors of the peacock must... have... by the continued preference of the most beautiful males, rendered the peacock the most splendid of living birds."
Since 1871, sexual selection theory has often been restated (4), yet contemporary definitions share Darwin's central narrative: "We now understand... Males, who can produce many offspring with only minimal investment, spread their genes most effectively by mating promiscuously... Female reproductive output is far more constrained by the metabolic costs of producing eggs or offspring, and thus a female's interests are served more by mate quality than by mate quantity" (5). This narrative is taught in biology textbooks (6), is axiomatic to evolutionary psychology (7), and is broadcast in popular media (8).
The reproductive social behavior of most species has not been studied, but a great many of those that have been do not conform to Darwinian sexual-selection templates. We suggest that sexual selection is always mistaken, even where gender roles superficially match the Darwinian templates.
There are fundamental problems that universally undercut all applications of sexual selection theory to any species, including the contradiction between sexual selection's rationale and the reason for sexual versus asexual reproduction, the difficulty of sustaining a stable hierarchy of genetic quality within a gene pool in the face of continued directional selection for high-ranked genotypes, and the use of different fitness definitions for males and females. These and other fatal problems are detailed in the references accompanying table S1.
We think that the notion of females choosing the genetically best males is mistaken. Studies repeatedly show that females exert choice to increase number, not genetic quality, of offspring and not to express an arbitrary feminine aesthetic. Instead, we suggest that animals cooperate to rear the largest number of offspring possible, because offspring are investments held in common. We therefore propose replacing sexual selection theory with an approach to explaining reproductive social behavior that has its basis in cooperative game theory. We introduce a notion of allocating time into various relationships to maximize cooperative, or "team," fitness. In this theory, we can observe that diverse social organizations emerge from how individuals accrue direct benefits from the relationships they develop with one another within diverse ecological contexts.
Cooperative Games in Reproductive Social Behavior
Here, we explain reproductive social behavior in developmental time, not evolutionary time. A social system develops from the interaction of individuals just as body parts develop from the interaction of tissues. In our model, each animal acts continually as an individual or as a team member, and the value of an action is scored by how it contributes to that animal's average fitness accumulation rate (9). An individual's actions involve obtaining and exchanging direct benefits to increase the number of offspring successfully reared (10–14). We further envision a future two-tier theory that will embed this phenotypic treatment within an overarching evolutionary-genetic model.
Maynard Smith introduced game theory to biology in the 1980s, including the evolutionary stable strategy (ESS), a population-genetic counterpart to the Nash competitive equilibrium (NCE) of game theory (15). A competitive game ends when an NCE is attained, i.e., the state where each player cannot better its position, given the positions of the other players. In competitive games, the players do not communicate.
In cooperative games, players make threats, promises, and side payments to each other; play together as teams; and form and dissolve coalitions. Cooperative games usually end up at different solutions to an NCE. Nash also investigated cooperative games and introduced the concept of a Nash bargaining solution (NBS) as an outcome of these games (16).
Logic of bargaining and side payments. To illustrate, consider a "payoff matrix" that indicates the direct benefit each player receives in every scenario (17)
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Molecule that may hold key to learning and memory

2006-02-22T12:50:00.000-08:00

Independent research teams from Harvard Medical School and Children's Hospital Boston have identified a master protein that sheds light on one of neurobiology's biggest mysteries--how neurons change as a result of individual experiences. The research, which appears in two papers in the latest issue of Science (Feb 17), identifies a central protein that regulates the growth and pruning of neurons throughout life in response to environmental stimuli. This protein, and the molecular pathway it guides, could help investigators understand the process of learning and memory, as well as lead to new therapies for diseases in which synapses either fail to form or run rampant, such as autism, neurodegenerative diseases, and psychiatric disorders.
Though axons and dendrites can be easily spotted waxing and waning under the microscope, the molecular middlemen working inside the cell to shape the neuron's sinewy processes have been much more elusive. The teams found a protein that works in the nucleus of neurons that either pares down or promotes synapses depending on whether or not the neuron is being activated. The protein, myocyte enhancer factor 2 (MEF2), turns on and off genes that control dendritic remodeling. In addition, one of the teams has identified how MEF2 switches from one program to the other, that is, from dendrite-promoting to dendrite-pruning, and the researchers have identified some of MEF2's targets.
The uncovering of the MEF2 pathway and its genetic switch helps fill in a theoretical blank in neurobiology, but what excites the researchers are the potential implications for the clinic. "Changes in the morphology of synapses could turn out to be very important in a whole host of diseases including neurodegenerative as well as psychiatric disorders," said Azad Bonni, MD, PhD, HMS Associate Professor of Pathology who, with colleagues, authored one of the papers. Michael Greenberg, PhD, HMS Professor of Neurology at Children's Hospital Boston, who led the other team, believes that the MEF2 pathway could play a role in autism and other neurodevelopmental diseases.
The protein works by either activating or actively repressing target genes. In working on a group of neurons in the developing rat cerebellum, HMS research fellow in pathology Aryaman Shalizi, and HST medical student Brice Gaudilliere along with Bonni and their colleagues, found the MEF2 repressor promoted synaptic differentiation. In a separate study, Steven Flavell, a graduate student in neurology, Greenberg, and their colleagues found the MEF2 activator inhibited the growth of dendritic spines in the rat hippocampus, an area of the brain associated with memory and learning. Flavell, and also the Bonni team, found the activated, or dendrite-whittling, form of MEF2 comes on in response to increased neuronal activity.
That MEF2 activation leads to the inhibition of synapse formation, makes sense in light of what is known about the nervous system. In memory and learning, as well as development, activity leads to a sculpting, or cutting away, of synapses. What may be more surprising is the way activity causes MEF2 to switch from repressor to activator.
What Bonni and his colleagues found is that molecules modify a particular spot on MEF2, and transform it into a repressor. By removing the modification, known as sumoylation, MEF2 becomes an activator.
MEF2 was first identified in neurons in the 1990s. In 1999, Zixu Mao, then an HMS research fellow, working with Bonni, Greenberg, and colleagues showed that MEF2 promotes neuronal survival but little else was known about the protein. Though they knew that MEF2 comes in activated and repressor forms, neither team knew how exactly the protein works. They suspected it might play a role in regulating activity-dependent synaptic remodeling and set out to find out if that was the case.
Taken together, the findings of the two groups might appear puzzling for they seem to say that MEF2 promotes synapse formation by repressing genes and suppresses synapse formation by activating genes. The puzzle resolves itself when one considers the possibility that the genes being turned on and off act to discourage synapse formation. In fact, Flavell and his colleagues have identified two of MEF2's targets, arc and SynGAP. The arc protein appears to play a role in internalizing glutamate receptors, which occurs when dendrites are being disassembled. SynGAP works to turn off the synapse-promoting ras gene. Bonni and his colleagues have identified yet a third target, Nur77. There are bound to be others.
The identification of these targets, and more generally the opening up of the MEF2 pathway, could lead to new therapies for a host of diseases in which synapses either fail to form or run rampant. In fact, Greenberg is currently a member of a consortium that is trying to get at the molecular underpinnings of autism. "We think the MEF2 pathway may be central," he said.

Learning and memory stimulated by gut hormone

2006-02-22T11:58:00.000-08:00

Researchers at Yale School of Medicine have found evidence that a hormone produced in the stomach directly stimulates the higher brain functions of spatial learning and memory development, and further suggests that we may learn best on an empty stomach.
Published in the February 19 online issue of Nature Neuroscience by investigators at Yale and other institutes, the study showed that the hormone ghrelin, produced in the stomach and previously associated with growth hormone release and appetite, has a direct, rapid and powerful influence on the hippocampus, a higher brain region critical for learning and memory.
The team, led by Tamas L. Horvath, chair and associate professor of the Section of Comparative Medicine at Yale School of Medicine, and associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, and Neurobiology, first observed that peripheral ghrelin can enter the hippocampus and bind to local neurons promoting alterations in connections between nerve cells in mice and rats. Further study of behavior in the animals showed that these changes in brain circuitry are linked to enhanced learning and memory performance.
Because ghrelin is highest in the circulation during the day and when the stomach is empty, these results also indicate that learning may be most effective before meal-time.
"Based on our observations in animal models, a practical recommendation could be that children may benefit from not overeating at breakfast in order to make the most out of their morning hours at school," said Horvath. "The current obesity epidemic among American school children, which to some degree has been attributed to bad eating habits in the school environment, has been paralleled by a decline of learning performance. It is however too early to speculate if hormonal links between eating and learning are involved in that phenomenon."
Horvath said that high ghrelin levels or administration of ghrelin-like drugs could also protect against certain forms of dementia, because aging and obesity are associated with a decline in ghrelin levels and an increased incidence of conditions of memory loss like Alzheimer's disease.

Across China's frontier

2006-02-21T21:27:00.000-08:00

China has become the preferred place for international firms to open research labs — and Japan is leading the way.
Electronics engineer Min-Yu Hsueh wasn't planning to swap California for Beijing, but when the invite came he found it very hard to refuse. A Chinese-American entrepreneur based in San Jose, Hsueh was three years ago working on setting up his next company. Then, out of the blue, Japanese electronics giant NEC offered him the chance to run its first research lab in China."They said: 'China is expanding its market, so we want to play there more efficiently, and we need to invent new technologies'," Hsueh recalls. He was impressed by the plans, and now runs NEC Laboratories China in Beijing, leading a team of 40 researchers, most of them computer scientists.NEC is just one of a host of Japanese companies to have set up research facilities in China in recent years. These firms hope to hire China's well-trained and relatively inexpensive young scientists, and to adapt existing products to the burgeoning Chinese market. The companies are encouraged by generous tax relief for investing in research and development, and hopes that they will be able to secure intellectual property in China (see Nature 438, 420–421; 2005).But for research managers brought up in Japan's system of teamwork and corporate loyalty, the fast-moving, Mandarin-speaking environment takes some getting used to. "It's challenging for them," says Hironori Uchibori, senior economist at Mizuho Research Institute in Tokyo. "But the importance of China is rising, so they are trying to make it work."In 2005, Mizuho surveyed almost 1,400 medium and large industrial firms in Japan and found that more than 250 had already established research labs in China. Only 116 had done so in the United States.Japanese firms are not the only ones heading for China. US electronics company Motorola was the first foreign firm to set up a research lab there, back in 1993. Since then there's been a veritable gold rush, and there are now some 700 labs operated by multinational companies, according to a 2005 United Nations report. That report found that firms favoured China more than any other nation as the location for expanding research and development over the next five years (see graph). In the survey, 60% of European companies said that they had plans to expand their research abroad, but fully 90% of Japanese ones said so.Competition to hire top graduates is stiff in China, and many Japanese companies are strengthening their ties with universities in a bid to snag students after they graduate. For example, Osaka-based Matsushita Electric Industrial Company has researchers that teach classes at Dalian University of Technology in the northeastern province of Liaoning. The company, best known for its Panasonic brand, has several labs in China and opened a software development facility in Dalian in 2004.
"It's tough to recruit good students there, so we want them to get interested in us," says Atsushi Ando of Matsushita's research strategy group. Matsushita says that over the next few years it will triple or quadruple the number of researchers and engineers at its Dalian lab from the current 100.But recruitment isn't the only issue: many Japanese firms are keen to train the Chinese students in their corporate ethos so that their recruits stay put. Hitachi and Fujitsu both say that they are trying to imbue young researchers with Japanese virtues, such as teamwork and corporate loyalty. Since Hitachi established a Chinese lab in 2000, it has invited many of its 60 Chinese researchers to Japan for six months to learn these virtues. "We started from scratch, so educating researchers was the toughest thing for our first five years," says Michiharu Nakamura, a Hitachi vice-president in charge of the Beijing laboratory.Lab managers may laud the quality of Chinese graduates, but the monthly salaries paid the recruits are only about a quarter of the US$2,000 or so that similar graduates get in Japan. And managers are aware that US companies such as Microsoft and IBM have a more positive image among students. Many Japanese employers also acknowledge that the research 'culture' in China, with its strong emphasis on individualism and competition, has more in common with that of the United States than with the Japanese model.This might explain why NEC has let Hsueh take a Western approach to running his lab. His management practices are more Californian than Japanese: English is the working language, and researchers get financial bonuses for filing patents, publishing papers and producing ideas that become incorporated into prototypes. "This approach is a first for NEC," Hsueh says.Other companies are also shifting responsibility from Japanese managers to Chinese nationals. Many group leaders at Hitachi, for example, are now Chinese. The main challenge over the next few years, Nakamura says, is to develop products there not just for China, but for global markets as well.

Why you should go with your gut

2006-02-21T20:59:00.000-08:00

Study says unconscious consideration yields most satisfying decisions. http://www.nature.com/news/2006/060213/full/060213-9.html
The best way to make a tough decision is to put your feet up and think about something else. So says an investigation of people shopping for cars, clothes and furniture.Many people assume that the best way to tackle a difficult choice is to list the pros and cons and ponder them deeply. Others believe we do better to sleep on it, leaving the decision-making to our unconscious, or intuition.A team of researchers at the University of Amsterdam, The Netherlands, carried out a series of studies to distinguish between these ideas. In one experiment, university students read a list of features about four different cars, such as facts on their mileage and legroom, before deciding which car to pick.The experiment was set so that some students were presented with a short list of features, making for a simple decision, while others faced a bafflingly long list of 12 competing characteristics. Some students were left to think about their decisions for a few minutes, whereas others were distracted by being asked to solve anagrams.Don't think about itFor the simple decisions, students made better choices when they thought consciously about the problem. But for the more complex choice, they did better after not thinking about it, Ap Dijksterhuis and his colleagues report in Science1. To carry this idea into the real world, the team also studied people who were shopping: either in an Amsterdam department store, where they bought straightforward clothes or kitchenware, or in IKEA, where they bought furniture, which one might expect to be a more complicated decision-making process. The team asked the shoppers whether they had thought hard about their purchase beforehand, and a few weeks later asked them whether they were happy with it.These results confirmed the earlier ones. Department-store shoppers who made simple purchases were happier if they had thought consciously about their choice in advance. IKEA shoppers, on the other hand, were happier with their choice if they hadn't mulled them over.At least when making some complicated decisions, such as choosing a car or house, the results suggest that we would actually do better to go with our gut.The big pictureResearchers do not know exactly why this unconscious deliberation should be so successful. But it is well accepted that our conscious brain can only process a limited amount of information at one time. This could mean that we simply lose the big picture with complex decisions.Dijksterhuis and his team also propose that, although we are unaware of it, our brains are churning through the mass of information involved in a complex decision and sifting out the best option.The study ties in with a growing trend in psychology research over the past 15 years, suggesting that our unconscious mind is more important than we once thought. "A lot of complicated processes occur without our being aware of it," says Daniel Kahneman, an authority on decision making at Princeton University, New Jersey.Snap decisionsThe results might help to explain why experts, such as doctors or firemen, can sometimes make seemingly intuitive snap decisions that turn out to be correct. These people have a wealth of knowledge, but they don't need to consciously work through it to make an accurate judgement.
But the theory doesn't mean that going purely on impulse is a good idea: you still need some information to mull over before making your decision. Particularly when making potentially life-changing judgments such as whom to marry or which career to choose, experts say, study and deliberation are vital to reveal all the options open to us."I would not advise people to buy a car or house without making a list," Kahneman says. "You will probably improve your intuitions by making a list and then sleeping on it."

Possible 'universal strategy' to combat addiction

2006-02-14T14:02:00.000-08:00

An international research team led by the University of Saskatchewan has discovered a signaling pathway in the brain involved in drug addiction, together with a method for blocking its action, that may point to a single treatment strategy for most addictions.
Their findings appear in the March issue of the prestigious journal Nature Medicine.
The team, led by Xia Zhang, associate professor in the U of S department of psychiatry, found that a naturally occurring enzyme known as PTEN acts on the part of the brain where many drugs of abuse exert their rewarding effects - the ventral tegmental area (VTA).
"Our results suggest a potential universal strategy for treating drug addiction," Zhang says. "Most drugs of abuse act on the neurons in this area."
He cautions that much work remains to be done before a treatment based on the discovery could be developed to help drug addicts. This includes several years of further testing, including animal and, finally, human trials.
"We have our peptide, but there's a long way to go before a clinical application," he says.
"Dr. Zhang's research is important to our understanding of drug addiction. His work epitomizes how health research holds the key to improved health and quality of life for Canadians and people throughout the world," said Dr. Rémi Quirion, Scientific Director of the Canadian Institutes of Health Research Institute of Neurosciences, Mental Health and Addiction.
Zhang, who worked with colleagues at the U of S, University of Toronto, and Vanderbilt University in Tennessee on the project, explains that VTA brain cells are sensitive to serotonin, a hormone associated with learning, sleep and mood. The team discovered that PTEN acts on these serotonin receptors, increasing brain cell activity. This is the same "reward" process sparked by drugs of abuse.
Armed with this knowledge, the team designed a molecule called a peptide, tailored to fit the serotonin receptors and block PTEN. When rats were treated with this PTEN-blocker, it shut down the drug reward process – including the process that induces craving and withdrawal.
The study, funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council, looked at nicotine and THC (the active ingredient in marijuana). However, Zhang says the results could also hold true for other drugs such as cocaine, heroin, and even methamphetamine.
Zhang's U of S research team is part of the Neural Systems and Plasticity Research Group, one of several interdisciplinary health sciences research groups at the University.
The group, dedicated to the study of brain systems and how they change with experience, draws expertise from numerous departments across six colleges on campus.

Apocalypse now: fears of gene doping are realised

2006-02-03T11:19:00.000-08:00

by Owen Slot
A new substance has emerged that suggests the next stage in the drugs battle has started
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THE grim new world of gene doping, for so long viewed as the apocalyptic future of illegal performance-enhancement in sport, has dawned in Germany. Experts had been concerned that advances in gene therapy would start to impact on sport by the time of the Beijing Olympics in 2008. However, evidence from a court case in Magdeburg, Germany, suggests that a new brand of cheats could be injecting in time for the Turin Winter Games, which start next week.
Gene doping is the big fear among those fighting for clean sport. It involves manipulation of the human genetic code and thus evades standard detection methods. And a German court has identified the distribution among coaches of a substance called Repoxygen, which works in this way to produce erythropoietin (EPO) indigenously.
“You would have to be blind not to see that the next generation of doping will be genetic,” Dick Pound, the chairman of the World Anti-Doping Agency, told scientists only two months ago. It seems that this next generation has arrived.
Evidence of gene doping has been stumbled upon at the trial of Thomas Springstein, the coach and partner of Grit Breuer, twice the European 400 metres champion, who was banned for taking the stimulant Clenbuterol. Springstein is accused of supplying steroids to female athletes that he has been coaching in Germany; the body of evidence against him was fortified by a police raid on the home he shares with Breuer, during which 20 chemical substances were said to have been found, 12 of which are yet to be identified.
Also removed from their house was Springstein’s laptop. At the start of his trial, Springstein’s lawyer failed in his plea to keep private the contents of his e-mail inbox. Certain e-mails were read out in court and it was in one exchange with the doctor of a Dutch speed-skating club that the incriminating evidence was allegedly discovered. Among a large number of doping products discussed, the prosecution claims, was the use of the aforementioned ground-breaker, Repoxygen.
The e-mails were passed on to Professor Werner Franke, a German cell biologist largely responsible for exposing those behind the drugs regimes of the former East German sports system. Franke told The Times that he was “devastated” by what he read. “We have been expecting gene doping, but not so soon,” he said. “I don’t know how they have it, but they do. This is the crossing of the Rubicon. This is a real advance in criminality.”
His reaction was matched by Michele Verroken, the director of the consultancy Sporting Integrity and former head of anti-doping at UK Sport. “When I first read about it, I thought, ‘Wow, someone’s cracked it,’” she said. “This is a really significant development.”
Repoxygen was pioneered in 2002 by Oxford Biomedica, an Oxford-based pharmaceutical company. It is a hugely significant breakthrough for the healthcare market for which it had been intended, primarily to treat serious anaemia.
The human body already produces EPO indigenously. EPO, in turn, is the agent that produces the red blood cells that carry oxygen to the muscles. When an athlete’s body is tiring, it is because it craves oxygen. This is why athletes can enhance performance by injecting synthetic EPO, the illegal part of the process. The brilliance of Repoxygen is that it gives the body the gene with which it can stimulate further EPO production on its own.
In announcing its breakthrough product on June 6, 2002, Oxford Biomedica explained that use of Repoxyen allows the body to “switch a gene on in response” to a low oxygen level and then, when that level has been raised, to “switch the gene off, providing an exquisite control mechanism for the production of EPO in situ”.
Within three months, the anti-doping movement had registered its concern over misuse. “We see Repoxygen as a significant threat,” Larry Bowers, the managing director of the US Anti-Doping Agency, said after a meeting in Atlanta in October 2002. “You can turn it on and off. It acts more or less like the body.”
While Bowers et al attempt to pioneer a test for gene doping, the immediate question is how Repoxygen got on to the black market. While Oxford Biomedica made the Repoxygen prototype, it never went into production because the company believed that it could not compete in the pharmaceutical market where EPO was already so readily available.
“We didn’t develop it any further,” Professor Alan Kingsman, Oxford Biomedica’s chief executive, said. “So it simply remains in the fridge. And we maintain very close controls, so I’d be extremely surprised if anything we made got on to the black market.”
One conclusion is that other laboratories had reproduced Repoxygen from information gleaned from Oxford Biomedica’s launch. “It would take a fairly advanced lab to make it,” Kingsman said. “But it would be very irresponsible for a number of reasons. For a start, we only went as far as testing it on mice. To use it in the human body would be playing with fire.”

Dry earwax? It's genetic

2006-01-30T19:42:00.000-08:00

Genetics researchers have uncovered the key gene behind the mystery of human earwax.
Finally.
The report in Monday's Nature Genetics journal solves a long-running anthropologist's riddle - why many people in China and Korea, as well as elsewhere in Asia, have dry earwax while the rest of humanity enjoys the sticky variety.
The finding could represent the leading edge of some new reports about non-disease-related genes that are responsible for visible changes in human anatomy, population researchers say.
Geneticists had known the neighborhood of the earwax gene from previous work and decided to pin it down. The earwax riddle surprisingly comes down to a single gene, dubbed ABCC11, reports a Japanese team led by Koh-ichiro Yoshiura of the Nagasaki University Graduate School of Biomedical Sciences. The gene comes in two types, or alleles, corresponding to wet or dry earwax.
By examining 126 Japanese volunteers, the team determined that the dry-earwax gene is recessive, meaning both parents must pass a copy to their children for it to work. To chart a global earwax gene map, the team next looked at volunteers from 33 populations worldwide, from Native Americans to Ashkenazi Jews to Polynesian islanders. The dry-earwax allele probably arose "in northeast Asia and thereafter spread throughout the world," the team concludes.
"These results are amazing," says biological anthropologist Mark Shriver of the Pennsylvania State University in University Park by e-mail. Shriver says the Japanese team's success points the way to future finds of disease-related genes specific to certain populations worldwide, as well as glimpses of how evolution changes genes in people over time.
"We should recognize that we really know very little right now and embrace any chance to learn about how the forces of evolution have shaped human biology," he says.
In December, Shriver and colleagues, led by geneticist Keith Cheng of the Pennsylvania State University College of Medicine in Hershey, identified a gene responsible for much of the difference in human skin color between Europeans and Africans. Other genes probably govern skin hues elsewhere.
Taken with the earwax find, the trend is toward genetic research finding more of the non-disease genes responsible for physical differences in people worldwide, says anthropologist Joanna Mountain of Stanford University in Palo Alto.
"We're all curious what makes people different," she says.
Mountain suggests the dry-earwax allele probably originated within the past 30,000 years, "or even much more recently."
Intriguingly, the dry-earwax gene turns up fairly often in Native Americans, in about 30% of a sample of that population.
That suggests the emigrants from Asia who first populated North and South America brought the gene with them, the Japanese team says.
Dry earwax may have given people in northeast Asia some advantage during past periods of cold climate, not freezing as readily, the researchers suspect,
But "this is still pretty speculative," Mountain says.

幽默风趣的女人令男人却步

2006-01-30T15:19:00.000-08:00

（中央社记者黄贞贞伦敦三十日讯）幽默风趣的男人令女人心动，但是谈笑风生的女性，却很难成为男性心仪的对象。最新研究发现，有幽默感的女人，容易让男人「相形见绌」，备感威胁，因此男人不会选择和这样的女性结为连理。这份由西安大略大学University of WesternOntario、麻州大学University of Massachusetts等进行的研究，预定本周在「人类行为演化」期刊公布。英国「独立报」引述研究指出，男性在寻找人生伴侣时，对那些很会谈笑的女性，丝毫没有兴趣，但是如果只是「一夜情」或短暂的男女关係，有幽默感的女性仍会让男性心动进而追求。
负责这项研究的心理医师马汀Dr. Rod Martin分析指出，男性认为风趣幽默是男人的专利，加上有幽默感的女性，通常都是反应灵敏的聪明人，这让男性备感威胁，因此不敢「一亲芳泽」。马汀和研究人员对数千名二十多岁的男女进行调查，询问男性「有幽默感的女人是不是很迷人时」，他们大多肯定表示「是」，但是再继续询问，他们是否愿意娶一个能让自己开怀大笑的女人时，答案几乎都是「不愿意」。马汀说，男人在择偶时，宁可选择「知道如何欣赏幽默感」的女人，也不要「讲笑话让人开怀大笑」的女人。
(博讯2006年1月31日; boxun.com)

The nervous system mobilize hematopoietic stem cells

2006-01-30T12:45:00.000-08:00

Study led by Mount Sinai School of Medicine may provide new hope for cancer patients and others with compromised immune systemsNew
study by Mount Sinai researchers may lead to improved stem cell therapies for patients with compromised immune systems due to intensive cancer therapy or autoimmune disease. The study is published in this week's issue of Cell.
A group, led by Paul Frenette, Associate Professor of Medicine at Mount Sinai School of Medicine, found that the sympathetic--or "fight or flight" branch--of the nervous system plays a critical role in coaxing bone marrow stem cells into the bloodstream. Bone marrow cells known as hematopoietic stem cells are the source for blood and immune cells.
Hematopoietic stem cell transplants are now routinely used to restore the immune systems of patients after intensive cancer therapy and for treatment of other disorders of the blood and immune system, according to the National Institutes of Health. While physicians once retrieved the stem cells directly from bone marrow, doctors now prefer to harvest donor cells that have been mobilized into circulating blood.
In normal individuals, the continuous trafficking of the stem cells between the bone marrow and blood fills empty or damaged niches and contributes to the maintenance of normal blood cell formation, according to the researchers. Although it has been known for many years that the mobilization of hematopoietic stem cells can be enhanced by multiple chemicals, the mechanisms that regulate this critical process are largely unknown, they said.
One factor in particular, known as hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF), is widely used clinically to elicit hematopoietic stem cell mobilization for life-saving bone marrow transplantation, said Dr. Frenette.
Several years ago, Dr. Frenette's group reported that a second compound, fucoidan, which is synthesized by certain seaweeds, could also spur the stem cells into action. The group speculated that the seaweed derivative might work by imitating a similar compound, called sulfatide, naturally present in mammalian tissues.
To test the idea, the researchers examined mice lacking the enzyme responsible for making sulfatide.
"Lo and behold, mice lacking the enzyme Cgt did not mobilize hematopoietic stem cells at all when treated with the stimulating factor G-CSF or fucoidan," Dr. Frenette said. "You don't get such dramatic results that often in science. We knew we had stumbled onto something important."
To their surprise, further study failed to connect the stalled stem cell movement to sulfatide. Rather, they found, the deficiency stemmed from a defect in the transmission of signals sent via the sympathetic nervous system. The products of Cgt contribute to the myelin sheath that coats and protects nerve cells, they explained.
Mice with other nervous system defects also exhibited a failure to mobilize bone marrow stem cells, they found. Moreover, drugs that stimulate the sympathetic nervous system restored stem cell movement into the blood stream in mice with an impaired ability to respond to norepinephrine, the signature chemical messenger of the sympathetic system.
"The nervous system plays an important role in producing signals that maintain the stem cell niche and retention in bone marrow," Dr. Frenette said.
"The new findings add another dimension of complexity to the processes involved in stem cell maintenance and mobilization and emphasize the interrelationships among the nervous, skeletal and hematopoietic systems," he added. "They all have to work together – to talk to each other – to produce blood and maintain stem cells."
The results suggest that differences in the sympathetic nervous systems of stem cell donors may explain "conspicuous variability" in the efficiency with which they mobilize hematopoietic cells into the bloodstream, the researchers said. Furthermore, drugs that alter the signals transmitted by the sympathetic nervous system to the stem cells in bone may offer a novel strategy to improve stem cell harvests for stem cell-based therapeutics, they added.
The unexpected findings by Frenette and his colleagues further "suggest that the pharmacological manipulation of the sympathetic nervous system may be a means of therapeutically targeting the stem cells in their niche for the purpose of either mobilization or, conversely, attracting stem cells to the niche following transplantation," they added. For more information.

Master Genetic Switch Found For Chronic Pain

2006-01-26T16:25:00.000-08:00

In experiments with mice, researchers have found that eliminating what appears to be a master genetic switch for the development of pain-sensing neurons knocks out the animals' response to "neuropathic pain." Such pain is abnormal pain that outlasts the injury and is associated with nerve and/or central nervous system changes. The animals rendered deficient in the gene, called Runx1, also showed lack of response to discomfort caused by heat and cold and inflammation. The researchers said that their findings, reported in the February 2, 2006, issue of Neuron, could have implications for the design of improved pain therapies. In their experiments, Qiufu Ma and colleagues studied the Runx1 gene because past research had shown it to code for a protein "transcription factor," which is a master regulator of multiple genes. Runx1 is one of a group of proteins that are key players involved in transmitting external sensory information, like pain and the perception of movement, to the spinal cord. In two other related papers in the same issue, Silvia Arber and colleagues and Tom Jessell and colleagues examine related aspects of the biological importance underlying the Runx transcription factors. For more information.

Gene Could Hold Key to Schizophrenia

2006-01-20T17:23:00.000-08:00

Deleting a single gene in the brains of mice caused their memories to be affected in way that resembled schizophrenia in humans, U.S. scientists report. Before the gene was removed, the mice were trained to use external clues to look for chocolate treats buried in sand. But after being injected with a genetically engineered virus that deleted the NR1 gene, the mice were unable to learn a similar task. The study, by a team from UT Southwestern Medical Center in Dallas, appears in the current issue of The Journal of Neuroscience. For information.

Monogamy: dopamine ties the knot

2006-01-18T20:01:00.000-08:00

Prairie voles form lasting pair bonds with their mating partners after a single experience of sexual activity, and this reward-related learning depends on dopamine. A new paper reports that two dopamine receptor subtypes contribute differently to the initial formation of pair bonds and to their maintenance by the promotion of selective aggression toward alternative mates.
Monogamy is rare among mammalian species, with only 3–5% forming lifelong pair bonds. The prairie vole Microtus ochrogaster forms such enduring bonds after a single initial mating encounter, but why are these prairie-dwelling critters 'addicted to love' when their mountain- and meadow-dwelling cousins indulge in lifelong promiscuity? The answer may lie in the same neurobiological culprit already implicated in drug addiction, the neurotransmitter dopamine. A group of scientists report a role for particular dopamine receptor subtypes both in establishing pair bonds in sexually naive male prairie voles and also in maintaining the integrity of the bond after it has formed. For more information, see Nature Neuroscience 9, 7 - 8 (2006).

South Korean Team's Remaining Human Stem Cell Claim Demolished

2006-01-12T15:49:00.000-08:00

In an announcement that researchers worldwide both expected and feared, Woo Suk Hwang's last remaining claim to have advanced the promising field of human embryonic stem (ES) cells has been declared fraudulent. In a report released on 10 January, a committee at Seoul National University (SNU) found that Hwang and his colleagues fabricated data in their breakthrough 2004 Science paper reporting the first creation of a stem cell line from a cloned human blastocyst. In an interim report in late December, the committee had already determined that a second paper by the team, published in 2005, was fraudulent (Science, 6 January, p. 22).
The final report concludes that Hwang and his colleagues did successfully clone a dog, which the scientists reported in Nature in August 2005. It also said that the Hwang team made some progress toward cloning early-stage human embryos. But the 2004 publication amounts to "none other than deceiving the scientific community and the public at large," the report says. (An English summary of the report is available on the SNU Web site at www.snu.ac.kr/engsnu.)
In the two papers published in Science, Hwang and his co-workers had claimed to have accomplished three firsts. The 2004 paper reported the cloning of a human blastocyst, through a process known as somatic cell nuclear transfer, and the derivation of ES cells from that cloned blastocyst; the 2005 paper reported the derivation of 11 human ES cell lines genetically matched to patients.
With both papers now thoroughly discredited, "we're back to the time prior to [Hwang's 2004] publication; there is no evidence at all that we can make [stem cells] from human embryos created through nuclear transfer," says Alan Trounson, a stem cell researcher at Monash University in Clayton, Australia. Hwang's team had also claimed phenomenal advances in efficiency in its 2005 paper, reporting that it needed fewer than 20 eggs to produce each stem cell line. Work in most other mammals suggests that it usually takes 100 to 200 eggs for one stem cell line, and many researchers say the unraveling of Hwang's work resurrects the question of whether the technique will ever be efficient enough for routine clinical application.
For more information: Science Magazine, 13 January 2006 , pp. 156 - 157.

Animal Eggs "To Grow Stem Cells"

2006-01-12T15:28:00.000-08:00

Stem cell researchers are looking to use animal eggs as 'hosts' to grow human cells. A Chinese team has already claimed to have created human embryonic stem cells using rabbit eggs which had had their genetic material removed. UK experts said the option had to be considered because there were too few human eggs for research. Scientists say cells created using animal eggs would only be used in the lab, but critics condemned the plan. The recent controversy over South Korean researcher, Hwang Woo-suk, has added impetus to the need to find new sources of eggs, scientists say. For more information.

Brain Protein May Be Linked to Depression

2006-01-06T15:13:00.000-08:00

Scientists have discovered a protein that seems to play a crucial role in developing depression, a finding that may lead to new treatments for the often debilitating illness — and fundamental understanding of why it strikes. Although problems with the mood-regulating brain chemical serotonin have long been linked to depression, scientists don't know what causes the disease that afflicts some 18 million Americans — or exactly what serotonin's role is. The newly found protein, named p11, appears to regulate how brain cells respond to serotonin, researchers from Rockefeller University and Sweden's Karolinska Institute report Friday in the journal Science. For more information.

Why hard work makes people happy

2006-01-06T14:50:00.000-08:00

Researchers from Gothenburg University in Sweden have been studying published data on what makes people happy. They believe working to achieve a goal, rather than attaining it, makes people more satisfied - although they said good relationships were important.
UK experts agreed, but said the work had to match an individual's strengths. The Gothenburg team have been studying hundreds of interviews carried out with people across the world to find out what makes them feel fulfilled. They said winning the lottery or achieving a goal at work gave a temporary high, but it did not last. Instead, they found that working hard to reach a target was more fulfilling.
Lead researcher Dr Bengt Bruelde, from the university's philosophy department, said: "The important thing is to remain active. "From our research the people who were most active got the most joy. It may sound tempting to relax on a beach, but if you do it for too long it stops being satisfying." He said the full research would be published in the summer.
Averil Leimon, of the British Psychological Society, said: "Hard work is satisfying, but only if it suits you. "The work has to use a person's strengths otherwise it can be demoralising. " If it does, research has shown that the happiness is not even linked to the rewards that are on offer. But she added: "Relationships can also have a significant impact. Strong relationships whether through family, the church, friends or work can inoculate you against feeling low."

Timeline of A Controversy

2006-01-03T13:19:00.000-08:00

A chronology of Woo Suk Hwang's stem-cell research
29 December 2005
The Seoul National University (SNU) team that has been investigating the South Korean researcher reports that there is no evidence that Woo Suk Hwang's stem cells came from patient-specific clones. Last week the investigators said that at least nine of eleven stem-cell lines in Hwang's 2005 Science paper were not what the paper claimed them to be (see 23 December entry below). Now they add that the remaining two lines also do not match the DNA of patients, as they were meant to. Instead they match cells from other, normal embryos created by in vitro fertilization. "Currently, we cannot find stem cells that have identical DNA fingerprint traces with patients and Hwang's team does not have scientific data to prove they did harvest patient-specific stem cells," says Jung-Hye Roe, director of research at SNU, in a press conference.
Science issues a statement saying: "There is no question in our minds that the stem-cell paper published 19 May 2005 by the journal Science needs to be retracted, and we are proceeding swiftly but appropriately in that direction." Science adds that they have not yet received official notification of the SNU investigation results, nor do they have all of the co-authors' signatures on a retraction agreement. They give the authors a deadline of 30 December, after which they say they will move towards an editorial retraction.
23 December 2005
A rapid investigation of Hwang's work at Seoul National University delivers a damning initial verdict: large amounts of the data in his 2005 landmark paper on patient-specific stem cells were fabricated. The university's investigating team announces in a televised press conference that the data in the 2005 Science paper came from just two cell lines, not 11 as claimed. This "cannot be some error from a simple mistake, but can only be seen as a deliberate fabrication", the panel says. Hwang says that these two stem cell lines, which are frozen in his lab, were derived from cloned embryos from specific patients. The university is doing tests to validate this. Investigation says Hwang lied Korean scandal will have global fallout.
16 December 2005
Science announces that Hwang and Schatten have written to request a retraction of their 2005 paper. Science editor Donald Kennedy says the journal received the letter hours before Hwang's press conference in South Korea (see entry below). Kennedy quoted from the letter during a press conference with reporters: "After analyzing the data, our team concludes the results...could not be trusted... Therefore we are requesting to withdraw the paper." Science says it must wait for the entire research team to consent to the retraction - a process that Kennedy says should take "days or weeks - not months."
Apology and defense - Hwang tells a press briefing that he and his team did create stem cells matched to individual patients, but that there were "mistakes made, human errors, in taking photographs and in the preservation of the stem cells''. Hwang says he will seek agreement from his co-authors to retract the Science paper, and will investigate how the mistakes were made. He adds that his team is thawing some frozen stem-cell lines from the study to authenticate them.
15 December 2005
Accusation of fake data: News stations across Korea report allegations from one of Hwang's collaborators that the work from May 2005 was based on fabricated data. Roh tells the MBC and two other television stations that Hwang had told him "there are no cloned embryonic stem cells".
13 December 2005
Schatten asks Hwang to retract their May 2005 Science paper. Schatten claims he has news of allegations from someone involved with the experiment that make him want his name removed from the paper. According to a release from the University of Pittsburgh, Schatten writes to Science and his co-authors: "My careful re-evaluations of published figures and tables, along with new problematic information, now casts substantial doubts about the paper's accuracy."
A letter from eight scientists, including Ian Wilmut, the cloner of Dolly the sheep, is published in Science calling for validation of Hwang's results: "We encourage Hwang's laboratory to cooperate with us to perform an independent test of his cell lines."
11 December 2005
Investigation opened - Seoul National University announces an investigation of Hwang's research, as requested by Hwang himself. The university hospital treats Hwang for stress and exhaustion.
05 December 2005
Investigation opened - University of Pittsburgh officials say they have opened a preliminary inquiry into the 2005 paper.
04 December 2005
Media outlets report that the MBC has apologized for the reporting tactics used in their 22 November programme on Hwang.
Mistake in the 2005 paper: According to Science editors, Hwang contacts them to alert them to erroneous duplications in some images published as part of the Supporting Online Material for the 2005 paper. "We made some unintentional error by using about 4 pictures redundantly," he says. Science determines that the redundant images did not appear in the PDF version of the accepted paper, but were inserted later, and says the mistake does not affect the paper's scientific conclusions.
01 December 2005
Accusation of mis-matched DNA - The MBC challenges the credibility of Hwang's data. Pursuing a tip-off, MBC gets five samples of patient-specific cell lines from Hwang and sends them, together with corresponding tissue samples, to an independent lab for DNA analysis. The programme reports that the DNA in one cell line does not match the tissue sample as it should. There are many possible explanations for MBC's findings, such as contamination. But the mismatch also raises the possibility that the embryonic stem-cell lines were not cloned from the stated patients. Hwang stands by his science.
According to Science, Moon Il Park, Director and Chair of the Institutional Review Board (IRB) on Human Subjects Research and Ethics Committees at Hanyang University Hospital, reveals to them the results of an investigation by the hospital IRB and Seoul National University IRB. It finds that: "1) two researchers under Dr. Woo Suk Hwang's supervision donated oocytes voluntarily without any coercion and 2) approximately US$1,445 was paid for direct expenses." This was not illegal or in violation of the Helsinki Guidelines of 1964, which prohibit coercion of research subjects. Park also told Science: "We strongly believe that the identified concerns have no impact on the validity of the scientific conclusions."
24 November 2005
Admission of payments for eggs: Hwang admits that his stem-cell research used eggs from paid donors and junior members of his team. He resigns from his official positions, saying he will continue his research.
22 November 2005
Seoul-based Munhwa Broadcasting Corporation (MBC) aired an investigative news programme showing further evidence that Hwang used eggs from junior members of his lab - the PD Diary program was called "The Myth of Hwang Woo-suk and Suspicions over Eggs."
21 November 2005
Sun Il Roh, a fertility expert at MizMedi Hospital in Seoul and a co-author of the landmark paper, admits that 20 eggs he procured and gave to Hwang for his 2004 study were paid for. Roh, a co-author on the 2005 paper, insists that Hwang did not know this.
12 November 2005
Schatten publicly cuts all ties to Hwang and his team at Seoul National University.
Mistake in the 2005 paper: The 2005 paper's authors provide Science with corrections to data in the paper's table 2, which are not thought to significantly alter the work's conclusions. The corrected table is published.
11 November 2005
According to Science, Schatten tells them he has stopped working with Hwang, because he believes Hwang misrepresented facts about consent issues related to the 2004 paper. Science asks Hwang to inform them of any concerns regarding his research. Hwang says he is looking into the matter.
10 November 2005
According to Science, Gerald Schatten, a biologist at the University of Pittsburgh and co-author of the May 2005 Science paper, alerts them to Korean press reports alleging that researcher Sun Il Roh has illegally traded ova. Schatten reassures Science that "none of the oocytes used in Professor Hwang's '04 or '05 Science papers were obtained from reimbursed women donors."
-- October 2005
Hwang resumes research, ending his voluntary suspension of activities.
19 October 2005
South Korea's government launches the World Stem Cell Hub, an international network for exchanging embryonic stem-cell lines and cloning technology. Hwang is to be its head.
03 August 2005
Cloned dogHwang and colleagues announce the first cloned dog - Snuppy, an Afghan hound (Lee B. C. et al. Nature436, 641; 2005). Some scientists hail his birth as a feat of ingenuity and perseverance, others question its value.
19 May 2005
Landmark paperHwang's team at the Seoul National University in South Korea reports it has established 11 embryonic stem-cell lines derived from the skin cells of individual patients (W. S. Hwang et al. Science 308, 1777-1783; 2005). The experiment is hailed as a huge step towards the medical use of person-specific cell lines. It also backs up the embryo-cloning claims in the team's February 2004 paper.
13 January 2005
The South Korean government approves Hwang's embryonic stem cell research. It is the first approval issued under the nation's new bioethics law.
01 January 2005
South Korean bioethics law comes into effect.
22 May 2004
The annual meeting of the Korean Bioethics Association calls on Hwang and a review board to answer questions about funding sources and the recruitment of egg donors. The association wants the National Human Rights Commission, an independent investigative body funded by the government, to pursue the case. But the commission's bioethics task force was not intended to investigate specific research projects.
-- May 2004
Ethical questions: Questions are raised about ethical practices in Hwang's work after investigations by Nature. It appears that some of the eggs may have come from junior members of the research team. This is potentially problematic because obtaining human eggs is painful and risky. Hwang denies any wrongdoing, but says that he will suspend his research until a new national bioethics law comes into effect in the new year.
-- February 2004
Biologists say that the South Korean breakthrough has alerted Western researchers to the pace of scientific and technological progress in East Asia. Hwang and colleagues attribute their success to a supportive cultural environment, well-funded laboratories, and legislation permitting human embryos to be cloned for research. Also critical to the researchers' success was their collection of 242 human eggs from 16 female volunteers.
12 February 2004
Landmark paper: Woo Suk Hwang from Seoul National University in South Korea and colleagues announced that they have cloned 30 human embryos and harvested stem cells from one of them (W. S. Hwang et al. Science 303, 1669-1674; 2004). The work makes headlines worldwide, as a step towards stem-cell therapies for diseases such as Parkinson's. Other groups have claimed to clone human embryos, but the supporting evidence has been sketchy. This success will also need further supporting evidence.

Gene Discovered Linking High-Fat Diet To Diabetes

2006-01-03T12:27:00.000-08:00

A team at the University of California at San Diego has identified a gene that produces an enzyme that enables cells in the pancreas to recognize glucose and secrete insulin. Furthermore, a high fat diet suppresses the enzyme. In a study published in the research journal Cell, Dr. Jamey D. Marth and colleagues describe the gene that encodes GnT-4a, a glucose transporter enzyme. Without GnT-4a, beta cells in the pancreas fail to produce insulin when exposed to glucose and fat. Marth's team studied mice that did not carry the GnT-4a gene and found that the animals initially had high blood glucose levels, which progressed to beta cell failure followed by the development of type 2 diabetes. Normal mice that carried the GnT-4a enzyme but were fed a high-fat diet had reduced GnT-4a expression, followed by the chain of events leading to type 2 diabetes. "Our findings suggest that the current human epidemic in type 2 diabetes may be a result of GnT-4a enzyme deficiency," Marth commented in a university release. If further research confirms the findings, one possible clinical application would be the development of therapeutic agents that boost GnT-4a levels, and Marth is currently working on this. Agents that inhibit GnT-4a may also be useful in preventing a number of diseases inked to too much insulin production, such as cancer and cardiovascular disease. SOURCE: Cell, December 29, 2005. For more information.

Top science journal to print stem cell retraction

2005-12-30T11:40:00.000-08:00

Science is to publish the most prominent retraction in its long and distinguished history. The Washington-based journal said on Friday it had obtained signed agreement from all 23 South Korean co-authors to withdraw the landmark paper on therapeutic cloning published in May under the leadership of Hwang Woo-suk. For more information.

Trend Of Earlier Puberty Continues Among US Girls

2005-12-23T10:08:00.000-08:00

The age at which girls in the U.S.A. reach puberty is continuing to dip, with heavier weights and changing national demographics playing important roles, according to a new study. Research over the years has documented a gradual decline in the average age at which U.S. girls have their first menstrual period - from the age of 12.75 in the 1960s to about 12.5 in the early 1990s. The new findings, published in the Journal of Pediatrics, show that the trend has continued. National data for the years 1999 through 2002 put the average age at menarche - the first menstrual period - at just over 12.3 years, researchers at Tufts University in Boston found. For more information.

South Korean Stem-Cell Researcher Resigns

2005-12-23T08:58:00.000-08:00

South Korean researcher Hwang Woo-suk resigned from his university on Friday after the school said he fabricated stem-cell research that had raised hopes of new cures for hard-to-treat diseases. A university panel, releasing initial findings of a probe, accused Hwang of damaging the scientific community with his deception, while South Korea's government rued the scandal surrounding the country's star scientist and said it may pull its funding for his research. For more information.

Scientists Discover New Skin Color Gene

2005-12-19T12:40:00.000-08:00

A team at Penn State University has found just one tiny change in a key gene plays a major role in determining skin pigmentation. The finding, published in Science, may help explain why people of European descent have lighter skin than those from Africa. Potentially, it may also lead to the development of new ways to modify skin colour without damaging it by tanning or using harsh chemical lighteners. For more information.

Mona Lisa's Smile 83 Percent Happy

2005-12-15T14:11:00.000-08:00

A computer has been used to decipher the enigmatic smile of Leonardo da Vinci's Mona Lisa, concluding that she was mainly happy. The painting was analysed by a University of Amsterdam computer using "emotion recognition" software. It concluded that the subject was 83% happy, 9% disgusted, 6% fearful and 2% angry. For more information at BBC or AP.

South Korea Stem Cell Success 'Faked'

2005-12-15T12:56:00.000-08:00

A doctor who provided human eggs for research by cloning pioneer Hwang Woo-suk said in a broadcast Thursday that the South Korean scientist agreed to withdraw a key research paper because most of the stem cells produced for the article were faked. Roh Sung-il, chairman of the board at Mizmedi Hospital, told KBS television that Hwang had agreed to ask the journal Science to withdraw the paper, published in June to international acclaim. For more information.

Engineered Stem Cells Help Deliver Drugs Into The Brain

2005-12-15T12:49:00.000-08:00

One of the great challenges for treating Parkinson's diseases and other neurodegenerative disorders is getting medicine to the right place in the brain. The brain is a complex organ with many different types of cells and structures, and it is fortified with a protective barrier erected by blood vessels and glial cells -- the brain's structural building blocks -- that effectively blocks the delivery of most drugs from the bloodstream. But now scientists have found a new way to sneak drugs past the blood-brain barrier by engineering and implanting progenitor brain cells derived from stem cells to produce and deliver a critical growth factor that has already shown clinical promise for treating Parkinson's disease. For more information.

NIH Launches Cancer Genome Project

2005-12-14T11:44:00.000-08:00

Genetic Mapping Could Revolutionize Treatment and Prevention, Health Officials Say. Federal health officials yesterday launched the biggest genetic research endeavor since the landmark human genome project: an ambitious effort to categorize all of the hundreds of molecular glitches that turn normal healthy cells into cancers. The Cancer Genome Atlas, whose total cost could reach $1 billion or more, will for the first time direct the full force of today's sophisticated genetic technologies to the thorough understanding of a single disease -- one that will eventually strike nearly half of all Americans alive. For more information.

Mice Created With Human Brain Cells

2005-12-13T19:46:00.000-08:00

Add another creation to the strange scientific menagerie where animal species are being mixed together in ever more exotic combinations. Scientists announced Monday that they had created mice with small amounts of human brain cells in an effort to make realistic models of neurological disorders such as Parkinson's disease. Led by Fred Gage of the Salk Institute in San Diego, the researchers created the mice by injecting about 100,000 human embryonic stem cells per mouse into the brains of 14-day-old rodent fetuses. Those mice were each born with about 0.1 percent of human cells in each of their heads, a trace amount that doesn't remotely come close to "humanizing" the rodents. For more information.

2005-12-08T11:14:00.000-08:00

Scientists Discover New Cellular Structures
Researchers say they've identified tiny structures that may prepare the groundwork for how new cells form and function. These cellular structures, called GW bodies, play an important role in gene regulation (RNA interference), according to a team from the University of Florida, Gainesville. The discovery marks a major shift in the understanding of cell biology, and could aid the development of treatments for cancer and autoimmune diseases. It might also improve gene therapy, the researchers say. GW bodies are located in the jelly-like cytoplasm that surrounds the nucleus, and appear to help regulate genetic material called microRNA. MicroRNA typically switch genes off to control cell reproduction and development, but the Florida team found this process functioned poorly when GW bodies were absent. The study appears in the online issue of Nature Cell Biology. For more information.

Baby, you make my "love molecule" soar

2005-12-07T15:25:00.000-08:00

ROME (Reuters) - Your heartbeat accelerates, you have butterflies in the stomach, you feel euphoric and a bit silly. It's all part of falling passionately in love -- and scientists now tell us the feeling won't last more than a year. The powerful emotions that bowl over new lovers are triggered by a molecule known as nerve growth factor (NGF), according to Pavia University researchers. The Italian scientists found far higher levels of NGF in the blood of 58 people who had recently fallen madly in love than in that of a group of singles and people in long-term relationships. But after a year with the same lover, the quantity of the 'love molecule' in their blood had fallen to the same level as that of the other groups. The Italian researchers, publishing their study in the journal Psychoneuroendocrinology, said it was not clear how falling in love triggers higher levels of NGF, but the molecule clearly has an important role in the "social chemistry" between people at the start of a relationship. For more discussion.

Big brain means small testes

2005-12-07T14:25:00.000-08:00

The brainier male bats are, the smaller their testicles, according to a new study. Researchers suggest the correlation exists because both organs require a lot of energy to grow and maintain, leading individual species to find the optimum balance. The analysis of 334 species of bat found that in species where the females were promiscuous, the males had evolved larger testes but had relatively small brains. In species, where the females were monogamous, the situation was reversed. Male fidelity appeared to have no influence over testes or brain size. Both brain tissue and sperm cells require a lot of metabolic energy to produce and maintain. The different species appear to have evolved a preference for developing one organ more than the other, presumably determined by which will help them produce more offspring. “An extraordinary range of testes mass was documented across bat species - from 0.12% to 8.4% of body mass. That exceeds the range of any other mammalian order,” says Scott Pitnick, from Syracuse University in New York, US, one of the research team. Primate testes vary between species from 0.02% and 0.75% of body mass. For more information.