Fertility hormones and Creutzfeldt-Jakob disease

Certain fertility hormones could theoretically put women at risk of developing brain-wasting Creutzfeldt-Jakob disease.The fatal disease is spread by prions, infectious and misfolded proteins that also cause BSE, commonly known as mad cow disease in cattle. In Thursday's issue of the journal Public Library of Science One, researchers from Canada, France and the U.S. show for the first time that prions can exist in fertility hormones derived from urine.
The risk is theoretical and no single case has been documented of a woman contracting CJD from the hormone products, stressed Dr. Daniel Krewski, an author of the study and director of the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa."The risk is likely to be small but it is a risk that could be a real risk and what we're trying to do is perhaps be a little bit more proactive than we've been in the past when we identify a new potential pathway of disease transmission," Krewski said.
Fertility doctors said there is a widely-used alternative to urine-based fertility products. But those synthetic hormones don't work for every woman and some still opt for urine-based treatments."I don't use them [urine-derived hormones] very often but the next time the opportunity comes up to, I'll have to have a very careful discussion with my patients so they're fully aware of our now limited understanding of the safety," said Dr. Tom Hannam, who runs a fertility centre in Toronto.
No screening test

About one in 10,000 Canadians is affected by CJD, and could theoretically pass on prion proteins in their urine or blood. Krewski's research used highly sensitive, state-of-the-art testing to detect the proteins in samples of the fertility drugs. The researchers said they are flagging the potential danger to look for proactive ways of preventing risks to the population in the future rather than reacting to risks.For Misty Busch of Cloverdale, B.C., who injected fertility hormones derived from human urine when she was trying to get pregnant with her three-year-old twins, learning of the tiny possibility of prion disease infection was worrying.

There is no commercially available test to screen donors for CJD or to help women like Busch determine if they've been exposed to prions."I guess I'm going to have to sit and wait til we've got more technology," Busch said.Human prion diseases like CJD can also be transmitted through medical or surgical procedures.

Urine donors are screened for symptoms of neurological disease but prion diseases can have a long incubation period during which the urine may be infectious, said study co-author Dr. Neil Cashman, scientific director of PrioNet Canada, and Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases at the University of British Columbia.

Toward an understanding of human will

Nature Reviews Neuroscience 9, 934-946 (December 2008)

doi:10.1038/nrn2497

Abstract
The capacity for voluntary action is seen as essential to human nature. Yet neuroscience and behaviourist psychology have traditionally dismissed the topic as unscientific, perhaps because the mechanisms that cause actions have long been unclear. However, new research has identified networks of brain areas, including the pre-supplementary motor area, the anterior prefrontal cortex and the parietal cortex, that underlie voluntary action. These areas generate information for forthcoming actions, and also cause the distinctive conscious experience of intending to act and then controlling one's own actions. Volition consists of a series of decisions regarding whether to act, what action to perform and when to perform it. Neuroscientific accounts of voluntary action may inform debates about the nature of individual responsibility.

Seizures and neuronal activity

The first study to examine the activity of hundreds of individual human brain cells during seizures has found that seizures begin with extremely diverse neuronal activity, contrary to the classic view that they are characterized by massively synchronized activity. The investigation by Massachusetts General Hospital (MGH) and Brown University researchers also observed pre-seizure changes in neuronal activity both in the cells where seizures originate and in nearby cells. The report will appear in Nature Neuroscience and is receiving advance online publication.


"Our findings suggest that different groups of neurons play distinct roles at different stages of seizures," says Sydney Cash, MD, PhD, of the MGH Department of Neurology, the paper's senior author. "They also indicate that it may be possible to predict impending seizures, and that clinical interventions to prevent or stop them probably should target those specific groups of neurons."

Epileptic seizures have been reported since ancient times, and today 50 million individuals worldwide are affected; but much remains unknown about how seizures begin, spread and end. Current knowledge about what happens in the brain during seizures largely comes from EEG readings, which reflect the average activity of millions of neurons at a time. This study used a neurotechnology that records the activity of individual brain cells via an implanted sensor the size of a baby aspirin.

The researchers analyzed data gathered from four patients with focal epilepsy – seizures that originate in abnormal brain tissues – that could not be controlled by medication. The participants had the sensors implanted in the outer layer of brain tissue to localize the abnormal areas prior to surgical removal. The sensors recorded the activity of from dozens to more than a hundred individual neurons over periods of from five to ten days, during which each patient experienced multiple seizures. In some participants, the recordings detected changes in neuronal activity as much as three minutes before a seizure begins and revealed highly diverse neuronal activity as a seizure starts and spreads. The activity becomes more synchronized toward the end of the seizure and almost completely stops when a seizure ends.

"Even though individual patients had different patterns of neural activity leading up to a seizure, in most of them it was possible to detect changes in that activity before the upcoming seizure," says co-lead and corresponding author Wilson Truccolo, PhD, Brown University Department of Neuroscience and an MGH research fellow. "We're still a long way from being able to predict a seizure – which could be a crucial advance in treating epilepsy – but this paper points a direction forward. For most patients, it is the unpredictable nature of epilepsy that is so debilitating, so just knowing when a seizure is going to happen would improve their quality of life and could someday allow clinicians to stop it before it starts."

Cash adds, "We are using ever more sophisticated methods to handle the large amounts of data we are collecting from patients. Now we are assessing how well we actually can predict seizures using ensembles of single neurons and are continuing to use these advanced recording techniques to unravel the mechanisms that cause human seizures and leveraging this knowledge to make the most of animal models." Cash is an assistant professor of Neurology at Harvard Medical School, and Truccolo an assistant professor of Neuroscience (Research) at Brown.

Provided by Massachusetts General Hospital

Genes linked to Leukemia- 3 different mutations

Three groups of mutations which cause acute myeloid leukaemia, a cancer of the white blood cells, have been identified by scientists.The researchers suggest their work on mice, published in Nature Genetics, could lead to new treatments.

Immature

During the illness, the bone marrow, which produces blood cells, starts to churn out immature white blood cells.
This changes the balance of the blood.The white blood cells are not properly developed so they cannot fight infection and there are too few red blood cells to carry oxygen around the body.
The disease can be fatal within weeks if left untreated.
The research group at the Wellcome Trust Sanger Institute investigated how this form of leukaemia arises because they say there had been little progress in developing new drugs.
Three groups
The most common mutation implicated in the cancer is to the Npm1 gene.
By switching this gene on in blood cells in mice, the researchers were able to show that it boosted the ability of cells to renew themselves, which is a sign of cancer. Yet only a third of mice went on to develop leukaemia.
The researchers concluded other mutations must also play a part.

They randomly mutated genes in mice, with a technique known as insertional mutagenesis. By looking at mice which developed cancer, they could then trace which mutations were involved.

They found two additional types of mutation. One affects cell division and growth, while the other modifies the cell's environment.
Dr George Vassiliou, consultant haematologist from the Wellcome Trust Sanger Institute, said they had "found critical steps that take place when the cancer develops. Identifying the biological steps in turn means we can look for new drugs to reverse the process."
He told the BBC: "Getting new drugs to patients could take decades, but what can happen sooner is using drugs which are already on the shelf, but in a more targeted way."
Dr David Grant, scientific director at Leukaemia & Lymphoma Research, said: "New designer drugs which target specific genetic mutations are proving increasingly effective in the treatment of blood cancers.
"This is a very important study as it offers an invaluable insight into the role of the most common form of mutation found in acute myeloid leukaemia. It explains how it develops and the other genetic factors that drive the leukaemia's growth.

"It offers a potential model for the development of new drugs for this terrible disease in the future."

Gene linked to loss of abilty to feel pain and to smell

The gene responsible for the loss of our ability to feel pain is also involved in the loss of our sense of smell, an international team of researchers have found.Prof essor Frank Zufall, of the University of Saarland School of Medicine, in Germany, and colleagues, report their findings online this week in the journal Nature.

The researchers tested three people in their 30s with a rare genetic inability to feel pain (congenital analgesia) and found they were unable to smell at all (a condition known as anosmia).Interestingly, none of the subjects had been aware that they could not smell.Being unable to feel pain sounds enticing, but people with congenital analgesia frequently bite their tongues, break bones or burn themselves without being aware of it, sometimes leading to severe damage.

On the plus side, two of the individuals in the study had given birth with completely pain-free labour.
It is known that the inability to feel pain is due to a particular defective gene (SCN9A), which codes for a particular type of sodium channel protein. These sodium channels are essential for pain nerves to be able to send messages.The researchers wondered if the sodium channels could be important in smell detection too.

Knocking out smell

The team first showed that the olfactory sensory nerves that relay smell information in both humans and mice did indeed contain the sodium channels.Then they produced a genetically-altered strain of mice that lacked the sodium channels and were unable to smell.They compared these mice with normal mice, carefully recording the electrical activity of single nerve cells as the animals were exposed to smells.

Surprisingly, the nerve cells responded normally to smell, but the signals were not reaching further into the brain.The sodium channels appear to be essential for triggering the release of neurotransmitter, which is essential for transmission of information from one nerve cell to the next.Zufall sees this work as being of fundamental importance in understanding how the brain processes smell, but there could be other advantages."You can imagine a spray which you use to temporarily knock out your sense of smell", he suggests, "which may be useful for people working in situations with awful smells". Smell (or lack of it) may be a side-effect we have to consider when we take a drug for severe pain in years to come, as several pharmaceutical companies are racing to develop pain relief drugs targeting these particular sodium channels.

Do we control our neurons or do they control us?

Do we control our neurons or do they control us? If everything we do starts in the brain, what kind of neural activity would reflect free choice? And how would you feel about your free will if we were to tell you that neuroscientists can look at your brain activity, and tell that you are about to make a decision to move – and that they could do this a whole second and a half before you yourself became aware of your own choice?


Scientists from UCLA and Harvard -- Itzhak Fried, Roy Mukamel and Gabriel Kreiman -- have taken an audacious step in the search for free will, reported in a new article in the journal Neuron. They used a powerful tool – intracranial recording – to find neurons in the human brain whose activity predicts decisions to make a movement, challenging conventional notions of free will.

Fried is one of a handful of neurosurgeons in the world who perform the delicate procedure of inserting electrodes into a living human brain, and using them to record activity from individual neurons. He does this to pin down the source of debilitating seizures in the brains of epileptic patients. Once he locates the part of the patients’ brains that sparks off the seizures, he can remove it, pulling the plug on their neuronal electrical storms.

Such epileptic seizures are random. No one knows when to expect them, so after the electrodes are implanted everybody sits around and waits. This gives researchers a unique opportunity to observe human neurons in action: During the wait, patients may volunteer to participate in experiments, allowing scientists to discover what functions the recorded neurons carry out. The invasive surgery required to implant electrodes (performed routinely in animals like rats and monkeys for research) cannot be done in humans unless a medical condition (such as epilepsy that does not respond to drugs) calls for it. Such investigations are, therefore, rare.

Fried and his colleagues implanted electrodes in twelve patients, recording from a total of 1019 neurons. They adopted an experimental procedure that Benjamin Libet, a pioneer of research on free will at the University of California, San Francisco, developed almost thirty years ago: They had their patients look at a hand sweeping around a clock-face, asked them to press a button whenever they wanted to, and then had them indicate where the hand had been pointing when they decided to press the button. This provides a precise time for an action (the push) as well as the decision to act. With these data the experimenters can then look for neurons whose activity correlated with the will to act.

Such neurons, they found, abound in a region of the frontal lobe called the supplementary motor area, which is involved in the planning of movements. But here is the interesting thing: about a quarter of these neurons began to change their activity before the time patients declared as the moment they felt the urge to press the button. The change began as long as a second and a half before the decision, and as early as seven tenths of a second before it, this activity was robust enough that the researchers could predict with over 80 percent accuracy not only whether a movement had occurred, but when the decision to make it happened.

Foods for the brains

Eating a healthful diet has always been wise. But can certain foods, drinks, and supplements actually make you smarter? In other words, is the concept of "brain food" factual or just hype? Recent studies have shown that nutrients may have significantly positive effects on the brain. In fact, some foods can maximize your brain's potential and remove obstacles to optimal functioning and disease.

How the brain uses nutrients

The brain uses carbohydrates for energy and omega-3 fatty acids for forming its cell structure. B vitamins play an essential role in brain function. In combination with folic acid, vitamins B6 and vitamin B12 help manufacture and release chemicals in the brain known as neurotransmitters. The nervous system relies on neurotransmitters to communicate messages within the brain, such as those that regulate mood, hunger, and sleep. In addition, foods rich in antioxidant nutrients, such as vitamin C and vitamin E and beta-carotene, help protect brain cells from free-radical damage caused by environmental pollution. Protection against free radicals is important to protecting the brain well into the golden years.

1. Egg yolks for your brain function

A healthy benefit of egg yolks is that they contribute choline to the diet. Choline is a component of two fat-like molecules in the brain that are responsible for brain function and health. A choline deficiency may contribute to age-related mental decline and Alzheimer's disease.

2. Spinach protects the brain from age-related problems

Spinach helps protect the brain from oxidative stress while reducing the risk of suffering from an age-related decline in function. Researchers found that feeding aging rats spinach-rich diets significantly improved their learning capacity and motor skills. Including spinach in your diet may lessen brain damage from strokes and neurological disorders.

3. Yellowfin Tuna protects against Alzheimer's

A cold-water fish, yellowfin tuna is a rich source of omega-3 fatty acids. This is important if we remember that structurally, the brain is made up of 60% fat. Consuming foods rich in omega-3 fatty acids keeps cells' membranes flexible and maximizes their ability to allow important nutrients in. Yellowfin tuna is rich in the B vitamin niacin, which also protects the brain against Alzheimer's disease.

4. Cranberries for improvements in memory, balance and coordination

Animal studies suggest that cranberries protect brain cells from free-radical damage. Moreover, consumption of this tart fruit is associated with improvements in memory, balance and coordination.

5. Sweet potatoes provide nourishment for the brain

Sweet potatoes are especially brain-nourishing. They are rich in vitamin B6 (necessary for manufacturing a certain kind of neurotransmitters), as well as carbohydrates (the only fuel source the brain uses) and antioxidant nutrients (vitamin C and beta-carotene).

6. Strawberries reduce the risk of age-related brain decline

Strawberries help protect the brain while reducing the risk of developing age-related brain function decline. Just half a cup provides 70% of the Recommended Daily Value (RDV) for vitamin C. Research studies have shown that strawberry eaters may have a higher learning capacity and better motor skills than non-strawberry eaters.

7. Kidney beans to improve your cognitive function

One cup of cooked kidney beans contains almost 19% of the RDV for the B-vitamin thiamin. Thiamin is critical for cognitive function because it is needed to synthesize choline. Kidney beans are rich in inositol (part of the B-complex vitamin family). Inositol may improve symptoms of depression and mood disorders.

8. Raisin bran to prevent migraines and headaches

Raisin bran provides carbohydrates, iron, B vitamins, folic acid, calcium and magnesium. These are all important nutrients for brain fuel, as well as health and vitality. In addition, magnesium is a mineral that helps relax blood vessels, preventing the constriction and dilation characteristic of migraine and tension headaches. Increased intake of magnesium has been shown to reduce episodes of these types of headaches.

9. Lamb Loin aids concentration and mental performance

Lamb loin is eaten less in the United States than almost any other country in the world. This is unfortunate because it is rich in vitamin B12 and iron. Iron is important for brain health because a deficiency can impair concentration and mental performance.

10. Wheat germ is good for the brain

Wheat germ is a powerful brain food because it is rich in vitamin E and selenium (both very potent antioxidant nutrients), as well as choline and magnesium.

Another good source of choline is peanuts.

Other good sources are flaxseeds and olive oil.

More About Cognitive Biases

Memory errors


Further information: Memory bias

• Consistency bias – incorrectly remembering one's past attitudes and behavior as resembling present attitudes and behavior.

• Cryptomnesia – a form of misattribution where a memory is mistaken for imagination.

• Egocentric bias – recalling the past in a self-serving manner, e.g. remembering one's exam grades as being better than they were, or remembering a caught fish as being bigger than it was.

• False memory – confusion of imagination with memory, or the confusion of true memories with false memories.

• Hindsight bias – filtering memory of past events through present knowledge, so that those events look more predictable than they actually were; also known as the "I-knew-it-all-along effect."[30]

• Reminiscence bump – the effect that people tend to recall more personal events from adolescence and early adulthood than from other lifetime periods.

• Rosy retrospection – the tendency to rate past events more positively than they had actually rated them when the event occurred.

• Self-serving bias – perceiving oneself responsible for desirable outcomes but not responsible for undesirable ones.

• Suggestibility – a form of misattribution where ideas suggested by a questioner are mistaken for memory.

• Telescoping effect – the effect that recent events appear to have occurred more remotely and remote events appear to have occurred more recently.

• Von Restorff effect – the tendency for an item that "stands out like a sore thumb" to be more likely to be remembered than other items.

Common theoretical causes of some cognitive biases

• Bounded rationality – limits on optimization and rationality

• Attribute substitution – making a complex, difficult judgement by unconsciously substituting an easier judgement

• Attribution theory, especially:

o Salience

• Cognitive dissonance, and related:

o Impression management

o Self-perception theory

• Heuristics, including:

o Availability heuristic – estimating what is more likely by what is more available in memory, which is biased toward vivid, unusual, or emotionally charged examples

o Representativeness heuristic – judging probabilities on the basis of resemblance

o Affect heuristic – basing a decision on an emotional reaction rather than a calculation of risks and benefits
• Introspection illusion

• Adaptive bias

• Misinterpretations or misuse of statistics.

Drugs to Brain Breakthrough

A new way of delivering drugs to the brain has been developed by scientists at the University of Oxford.
They used the body's own transporters - exosomes - to deliver drugs in an experiment on mice.The authors say the study, in Nature Biotechnology, could be vital for treating diseases such as Alzheimer's, Parkinson's and Muscular Dystrophy.

The Alzheimer's Society said the study was "exciting" and could lead to more effective treatments.
Research barrier
One of the medical challenges with diseases of the brain is getting any treatment to cross the blood-brain barrier.

The barrier exists to protect the brain, preventing bacteria from crossing over from the blood, while letting oxygen through.However, this has also produced problems for medicine, as drugs can also be blocked.
In this study the researchers used exosomes to cross that barrier. Exosomes are like the body's own fleet of incredibly small vans, transporting materials between cells.

"Many potential drugs have not been properly tested because you couldn't get enough of them into the brain”
Dr Susanne Sorensen

Alzheimer's Society

The team at Oxford harvested exosomes from mouse dentritic cells, part of the immune system, which naturally produce large numbers of exosomes.They then fused the exosomes with targeting proteins from the rabies virus, which binds to acetylcholine receptors in brain cells, so the exosome would target the brain.They filled the exosomes with a piece of genetic code, siRNA, and injected them back into the mice.
The siRNA was delivered to the brain cells and turned off a gene, BACE1, which is involved in Alzheimer's disease.

The authors reported a 60% reduction in the gene's activity.
"These are dramatic and exciting results" said the lead researcher Dr Matthew Wood.
"This is the first time this natural system has been exploited for drug delivery."

Customised
The research group believes that the method could modified to treat other conditions and other parts of the body.
Dr Wood said: "We are working on sending exosomes to muscle, but you can envisage targeting any tissue.
"It can also be made specific by changing the drug used."

The researchers are now going to test the treatment on mice with Alzheimer's disease to see if their condition changes.The team expect to begin trials in human patients within five years. Dr Susanne Sorensen, head of research at the Alzheimer's Society, said: "In this exciting study, researchers may have overcome a major barrier to the delivery of potential new drugs for many neurological diseases including Alzheimer's.
She said the blood-brain barrier had been an "enormous issue as many potential drugs have not been properly tested because you couldn't get enough of them into the brain." She added: "If this delivery method proves safe in humans, then we may see more effective drugs being made available for people with Alzheimer's in the future."

Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "This is innovative research, but at such an early stage it's still a long way from becoming a treatment for patients. "Designing drugs that cross the blood brain barrier is a key goal of research that holds the promise of improving the effectiveness of Alzheimer's treatments in the future."
Exosomes may have other medical applications.

Alexander Seifalian, a professor of nanotechnology and regenerative medicine at University College London, told the BBC: "Experimental evidence indicates that exosomes can prime the immune system to recognize and destroy cancer cells, making them a potential tool as cancer vaccines."
He also said exosomes "could well form the cornerstone of nanoscale drug delivery systems of the future."
He added: "The apparent versatility and established biosafety of exosomes underscores the potential of these biological membrane vesicles to be of tremendous potential in the realm of nanotechnology and regenerative medicine."

Evening lights can damage Melatonin Production

Having the lights on in the evening may be damaging to health


Having the lights on before bedtime could result in a worse night's sleep, according to a study to be published in the Journal of Endocrinology and Metabolism.

The research shows that the body produces less of the sleep hormone melatonin when exposed to light.

Sleep patterns have been linked to some types of cancer, blood pressure and diabetes. The US researchers also found lower melatonin levels in shift workers. Lifestyles may have moved on from a day/night rhythm, but it seems the human body has not.The pineal gland produces melatonin through the night and starts when darkness falls. Researchers have shown that switching on lights in the home switches off the hormone's production.

Less melatonin
In the study, 116 people spent five days in room where the amount of light and sleep was controlled. They were awake for 16 hours and asleep for eight hours each day.Initially the patients were exposed to 16 hours of room light during their waking hours. They were then moved onto eight hours of room light in the morning and eight hours of dim light in the evening.The researchers found that electrical light between dusk and bedtime strongly suppressed melatonin levels. With dim light, melatonin was produced for 90 minutes more a day.
Dr Joshua Gooley, lead author from Brigham and Women's Hospital and Harvard Medical School, said: "Our study shows that this exposure to indoor light has a strong suppressive effect on the hormone melatonin. "This could, in turn, have effects on sleep quality and the body's ability to regulate body temperature, blood pressure and glucose levels."

Keeping the lights on through the night also reduced the amount of melatonin produced.Dr Gooley said: "Given that chronic light suppression of melatonin has been hypothesised to increase relative risk for some types of cancer and that melatonin receptor genes have been linked to type 2 diabetes, our findings could have important health implications for shift workers."

Sherwin Nuland - World Class surgeon from deep depression

Nfac 186: Brain disorder 'messaging clue'

Nerve fibres are 'message highways'. Scientists say they have discovered a "maintenance" protein that helps keep nerve fibres that transmit messages in the brain operating smoothly.The University of Edinburgh team says the finding could improve understanding of disorders such as epilepsy, dementia, MS and stroke.In such neurodegenerative disorders, electrical impulses from the brain are disrupted.This leads to an inability to control movement, and muscles wasting away.

The brain works like an electrical circuit, sending impulses along nerve fibres in the same way that current is sent through wires.These fibres can measure up to a metre, but the area covered by the segment of nerve that controls transmission of messages is no bigger than the width of a human hair.

Signal failure

The scientists discovered that the protein Nfasc186 is crucial for maintaining the health and function of the segment of nerve fibres - called the axon initial segment (AIS) - that controls transmission of messages within the brain.They found that the AIS and the protein within it are important in ensuring the nerve impulse has the right properties to convey the message as it should.Professor Peter Brophy, director of the University of Edinburgh's Centre for Neuroregeneration, said: "Knowing more about how signals in the brain work will help us better understand neurodegenerative disorders and why, when these illnesses strike, the brain can no longer send signals to parts of the body."

Dr Matthew Nolan, of the university's Centre for Integrative Physiology, said: "At any moment tens of thousands of electrical impulses are transmitting messages between nerve cells in our brains. "Identifying proteins that are critical for the precise initiation of these impulses will help unravel the complexities of how brains work and may lead to new insights into how brains evolved."

The work was funded by the Wellcome Trust and the Medical Research Council.

Enzyme that enhances memory

There are drugs that help you remember what you learn, and ones that erase your memory. But until now, there have no substances with the power to enhance and strengthen old memories hovering on the brink of being forgotten. Now a group of neuroscientsts say they've isolated a single enzyme in the brain that can help long-term memories remain crisp in your mind.


Reut Shema and his colleagues knew that the enzyme PKMzeta helped maintain the long-term storage of memories in the brain. But recently they discovered that boosting levels of PKMzeta helped rats recall, in great detail, events they'd experienced many days beforehand. Lowering levels of the enzyme caused the rats to forget old memories more quickly. What's remarkable about this discovery is that the enzyme can help the animals recall these old memories even if they weren't boosting their levels of PKMzeta at the time the memories were formed.

A release about the study, published today in Science, explains:

Shema and colleagues now show that overexpressing the enzyme in the insular cortex region of the rat brain can strengthen more than one memory at a time and improve memories that were established months before the enzyme experiment.If the same treatment works for humans, we could be looking at a way to deal with age-related memory loss. And a way to help us recall information we once knew intimately, but which has grown cloudy as the years have passed.

You can read the authors' full account of their experiments and how the enzyme works, in Science.

Attributional Biases

Social biases (from wikipedia)


Most of these biases are labeled as attributional biases.

• Actor–observer bias – the tendency for explanations of other individuals' behaviors to overemphasize the influence of their personality and underemphasize the influence of their situation (see also Fundamental attribution error). However, this is coupled with the opposite tendency for the self in that explanations for our own behaviors overemphasize the influence of our situation and underemphasize the influence of our own personality.

• Dunning–Kruger effect – a twofold bias. On one hand the lack of metacognitive ability deludes people, who overrate their capabilities. On the other hand, skilled people underrate their abilities, as they assume the others have a similar understanding.[36]

• Egocentric bias – occurs when people claim more responsibility for themselves for the results of a joint action than an outside observer would.

• Forer effect (aka Barnum effect) – the tendency to give high accuracy ratings to descriptions of their personality that supposedly are tailored specifically for them, but are in fact vague and general enough to apply to a wide range of people. For example, horoscopes.

• False consensus effect – the tendency for people to overestimate the degree to which others agree with them.[37]

• Fundamental attribution error – the tendency for people to over-emphasize personality-based explanations for behaviors observed in others while under-emphasizing the role and power of situational influences on the same behavior (see also actor-observer bias, group attribution error, positivity effect, and negativity effect).[38]

• Halo effect – the tendency for a person's positive or negative traits to "spill over" from one area of their personality to another in others' perceptions of them (see also physical attractiveness stereotype).[39]

• Herd instinct – common tendency to adopt the opinions and follow the behaviors of the majority to feel safer and to avoid conflict.

• Illusion of asymmetric insight – people perceive their knowledge of their peers to surpass their peers' knowledge of them.[40]

• Illusion of transparency – people overestimate others' ability to know them, and they also overestimate their ability to know others.

• Illusory superiority – overestimating one's desirable qualities, and underestimating undesirable qualities, relative to other people. (Also known as "Lake Wobegon effect," "better-than-average effect," or "superiority bias").[41]

• Ingroup bias – the tendency for people to give preferential treatment to others they perceive to be members of their own groups.

• Just-world phenomenon – the tendency for people to believe that the world is just and therefore people "get what they deserve."

• Moral luck – the tendency for people to ascribe greater or lesser moral standing based on the outcome of an event rather than the intention

• Outgroup homogeneity bias – individuals see members of their own group as being relatively more varied than members of other groups.[42]

• Projection bias – the tendency to unconsciously assume that others (or one's future selves) share one's current emotional states, thoughts and values.[43]

• Self-serving bias – the tendency to claim more responsibility for successes than failures. It may also manifest itself as a tendency for people to evaluate ambiguous information in a way beneficial to their interests (see also group-serving bias).[44]

• System justification – the tendency to defend and bolster the status quo. Existing social, economic, and political arrangements tend to be preferred, and alternatives disparaged sometimes even at the expense of individual and collective self-interest. (See also status quo bias.)

• Trait ascription bias – the tendency for people to view themselves as relatively variable in terms of personality, behavior and mood while viewing others as much more predictable.

• Ultimate attribution error – similar to the fundamental attribution error, in this error a person is likely to make an internal attribution to an entire group instead of the individuals within the group.

What shapes our language

Via: Voxy Blog

Biases in Probability and Belief

Biases in probability and belief

From Wikipedia


Many of these biases are often studied for how they affect business and economic decisions and how they affect experimental research.

• Ambiguity effect – the tendency to avoid options for which missing information makes the probability seem "unknown."[26]

• Anchoring effect – the tendency to rely too heavily, or "anchor," on a past reference or on one trait or piece of information when making decisions (also called "insufficient adjustment").

• Attentional bias – the tendency to neglect relevant data when making judgments of a correlation or association.

• Authority bias – the tendency to value an ambiguous stimulus (e.g., an art performance) according to the opinion of someone who is seen as an authority on the topic.

• Availability heuristic – estimating what is more likely by what is more available in memory, which is biased toward vivid, unusual, or emotionally charged examples.

• Availability cascade – a self-reinforcing process in which a collective belief gains more and more plausibility through its increasing repetition in public discourse (or "repeat something long enough and it will become true").

• Base rate neglect' or Base rate fallacy – the tendency to base judgments on specifics, ignoring general statistical information.[27]

• Belief bias – an effect where someone's evaluation of the logical strength of an argument is biased by the believability of the conclusion.[28]

• Clustering illusion – the tendency to see patterns where actually none exist.

• Capability bias – the tendency to believe that the closer average performance is to a target, the tighter the distribution of the data set.

• Conjunction fallacy – the tendency to assume that specific conditions are more probable than general ones.[29]

• Forward Bias - the tendency to create models based on past data which are validated only against that past data.

• Gambler's fallacy – the tendency to think that future probabilities are altered by past events, when in reality they are unchanged. Results from an erroneous conceptualization of the Law of large numbers. For example, "I've flipped heads with this coin five times consecutively, so the chance of tails coming out on the sixth flip is much greater than heads."

• Hindsight bias – sometimes called the "I-knew-it-all-along" effect, the tendency to see past events as being predictable.[30]

• Illusory correlation – inaccurately perceiving a relationship between two events, either because of prejudice or selective processing of information.[31]

• Observer-expectancy effect – when a researcher expects a given result and therefore unconsciously manipulates an experiment or misinterprets data in order to find it (see also subject-expectancy effect).

• Optimism bias – the tendency to be over-optimistic about the outcome of planned actions.[32]

• Ostrich effect – ignoring an obvious (negative) situation.

• Overconfidence effect – excessive confidence in one's own answers to questions. For example, for certain types of questions, answers that people rate as "99% certain" turn out to be wrong 40% of the time.[33][34]

• Positive outcome bias – the tendency of one to overestimate the probability of a favorable outcome coming to pass in a given situation (see also wishful thinking, optimism bias, and valence effect).

• Pareidolia – a vague and random stimulus (often an image or sound) is perceived as significant, e.g., seeing images of animals or faces in clouds, the man in the moon, and hearing hidden messages on records played in reverse.

• Pessimism bias – the tendency for some people, especially those suffering from depression, to overestimate the likelihood of negative things happening to them.

• Primacy effect – the tendency to weigh initial events more than subsequent events.[35]

• Recency effect – the tendency to weigh recent events more than earlier events (see also peak-end rule).

• Disregard of regression toward the mean – the tendency to expect extreme performance to continue.

• Stereotyping – expecting a member of a group to have certain characteristics without having actual information about that individual.

• Subadditivity effect – the tendency to judge probability of the whole to be less than the probabilities of the parts.

• Subjective validation – perception that something is true if a subject's belief demands it to be true. Also assigns perceived connections between coincidences.

• Well travelled road effect – underestimation of the duration taken to traverse oft-traveled routes and over-estimate the duration taken to traverse less familiar routes.

List of Cognitive biases

From Wikipedia

Decision-making and behavioral biases

Many of these biases are studied for how they affect belief formation, business decisions, and scientific research.

• Anchoring – the common human tendency to rely too heavily, or "anchor," on one trait or piece of information when making decisions.

• Attentional Bias – implicit cognitive bias defined as the tendency of emotionally salient stimuli in one's environment to preferentially draw and hold attention.

• Bandwagon effect – the tendency to do (or believe) things because many other people do (or believe) the same. Related to groupthink and herd behavior.

• Bias blind spot – the tendency to see oneself as less biased than other people.[2]

• Choice-supportive bias – the tendency to remember one's choices as better than they actually were.

• Confirmation bias – the tendency to search for or interpret information in a way that confirms one's preconceptions.[3]

• Congruence bias – the tendency to test hypotheses exclusively through direct testing, in contrast to tests of possible alternative hypotheses.

• Contrast effect – the enhancement or diminishing of a weight or other measurement when compared with a recently observed contrasting object.[4]

• Denomination effect – the tendency to spend more money when it is denominated in small amounts (e.g. coins) rather than large amounts (e.g. bills).[5]

• Distinction bias – the tendency to view two options as more dissimilar when evaluating them simultaneously than when evaluating them separately.[6]

• Endowment effect – "the fact that people often demand much more to give up an object than they would be willing to pay to acquire it".[7]

• Experimenter's or Expectation bias – the tendency for experimenters to believe, certify, and publish data that agree with their expectations for the outcome of an experiment, and to disbelieve, discard, or downgrade the corresponding weightings for data that appear to conflict with those expectations.[8]

• Extraordinarity bias – the tendency to value an object more than others in the same category as a result of an extraordinarity of that object that does not, in itself, change the value.[citation needed]

• Focusing effect – the tendency to place too much importance on one aspect of an event; causes error in accurately predicting the utility of a future outcome.[9]

• Framing effect – drawing different conclusions from the same information, depending on how that information is presented.

• Hostile media effect - the tendency to see a media report as being biased due to one's own strong partisan views.

• Hyperbolic discounting – the tendency for people to have a stronger preference for more immediate payoffs relative to later payoffs, where the tendency increases the closer to the present both payoffs are.[10]

• Illusion of control – the tendency to overestimate one's degree of influence over other external events.[11]

• Impact bias – the tendency to overestimate the length or the intensity of the impact of future feeling states.[12]

• Information bias – the tendency to seek information even when it cannot affect action.[13]

• Interloper effect – the tendency to value third party consultation as objective, confirming, and without motive. Also consultation paradox, the conclusion that solutions proposed by existing personnel within an organization are less likely to receive support than from those recruited for that purpose.

• Irrational escalation – the phenomenon where people justify increased investment in a decision, based on the cumulative prior investment, despite new evidence suggesting that the decision was probably wrong.

• Loss aversion – "the disutility of giving up an object is greater than the utility associated with acquiring it".[14] (see also Sunk cost effects and Endowment effect).

• Mere exposure effect – the tendency to express undue liking for things merely because of familiarity with them.[15]

• Money illusion – the tendency to concentrate on the nominal (face value) of money rather than its value in terms of purchasing power.[16]

• Moral credential effect – the tendency of a track record of non-prejudice to increase subsequent prejudice.

• Negativity bias – the tendency to pay more attention and give more weight to negative than positive experiences or other kinds of information.

• Neglect of probability – the tendency to completely disregard probability when making a decision under uncertainty.[17]

• Normalcy bias – the refusal to plan for, or react to, a disaster which has never happened before.

• Omission bias – the tendency to judge harmful actions as worse, or less moral, than equally harmful omissions (inactions).[18]

• Outcome bias – the tendency to judge a decision by its eventual outcome instead of based on the quality of the decision at the time it was made.

• Planning fallacy – the tendency to underestimate task-completion times.[12]

• Post-purchase rationalization – the tendency to persuade oneself through rational argument that a purchase was a good value.

• Pseudocertainty effect – the tendency to make risk-averse choices if the expected outcome is positive, but make risk-seeking choices to avoid negative outcomes.[19]

• Reactance – the urge to do the opposite of what someone wants you to do out of a need to resist a perceived attempt to constrain your freedom of choice.

• Restraint bias – the tendency to overestimate one's ability to show restraint in the face of temptation.

• Selective perception – the tendency for expectations to affect perception.

• Semmelweis reflex – the tendency to reject new evidence that contradicts an established paradigm.[20]

• Social comparison bias – the tendency, when making hiring decisions, to favour potential candidates who don't compete with one's own particular strengths.[21]

• Status quo bias – the tendency to like things to stay relatively the same (see also loss aversion, endowment effect, and system justification).[22][23]

• Unit bias — the tendency to want to finish a given unit of a task or an item. Strong effects on the consumption of food in particular.[24]

• Wishful thinking – the formation of beliefs and the making of decisions according to what is pleasing to imagine instead of by appeal to evidence or rationality.[25]

• Zero-risk bias – preference for reducing a small risk to zero over a greater reduction in a larger risk.

Inhibition of cravings in men and in women

World wide more women than men suffer from eating disorders and obesity. The following study sheds some light on why that might be the case. A study was done at Brookhaven National Laboratory by Gene-Jack Wang on inhibition of cravings for food in hungry people. A PET scan was used to see the brain activation in people who had been fasting when they were exposed to the sight, smell and taste of their favourite foods. Some subjects were also asked to try to ignore their cravings for food.


The brain scans indicated that men were more successful in inhibiting their cravings. By choosing to ignore the food craving, they could actually suppress their cravings and alter their brain metabolism reducing the activation in their para-limbic and limbic regions of the brain. These areas control awareness of hunger and desire for food. The men reported that they felt less desire for food when they tried to ignore their hunger. The women in the study did not show such a decrease in activation and reported no decrease in hunger no matter how they tried to control the urge. Women’s brains also showed a much greater response to their favourite foods when their brains were imaged. These findings may shed light on the reasons that women struggle to maintain their weight.

Why is it so hard to know what someone else wants or needs?

10 Foods That Help To Increase Dopamine And Norepinephrine Naturally!

10 Foods That Help To Increase Dopamine And Norepinephrine Naturally!


Apples: A compound found in apples called "quercetin' is an antioxidant that studies have shown may not only help in the prevention of cancer but may also play an important role in the prevention of neurodegenerative disorders. There may be something to that old saying, "An apple a day keeps the doctor away . . ."

Banana: A banana is a good source of tyrosine. Tyrosine is the amino acid neurons turn into norepinephrine and dopamine. Norepinephrine and dopamine are excitatory neurotransmitters that are important in motivation, alertness, concentration and memory.

Beets: Betaine, an amino acid naturally present in certain vegetables, particularly beetroot (beets), is an antidepressant of the first order. Betaine acts as a stimulant for the production of SAM-e (S-adenoslmethionine). The body cannot do without SAM-e, which it produces. SAM-e is directly related to the production of certain hormones, such as dopamine and serotonin. Dopamine is responsible for feelings of well-being and pleasure.

Chicken: Chicken, like eggs, contains complete protein that increases levels of the excitatory neurotransmitters norepinephrine and dopamine. Chicken is also a good source of coenzyme Q10 (Co Q10), which increases the energy generating potential of neurons.

Cheese: Cheese is a well known protein food . . . Protein provides amino acids, which help produce dopamine and norepinephrine. Cottage Cheese: One of the “must eat” foods on every expert’s list, cottage cheese is recommended as a substitute for other soft cheeses and dairy products. Cottage cheese provides the protein that can help boost mood and energy levels, without some of the fat of hard cheeses.

Eggs: Research from the University of California, Berkeley suggests that people who suffer from depression have low amount of serotonin, norepinephrine and dopamine in their brains. One natural antidepressant is to increase dopamine by eating protein-rich foods. such as eggs for this purpose, because they are versatile and appeal to some people who choose not to eat meat.

Fish: Omega-3 fatty acids are found in seafood, especially mackerel, salmon, striped bass, rainbow trout, halibut, tuna, and sardines. These fatty acids may have many jobs in the body, including a possible role in the production of neurotransmitters. Fish have easily digestible protein, many trace nutrients, high quality essential fatty acids, low cholesterol levels and low saturated fat levels.
French scientists have shown that rats deficient in omega-3 fatty acids had more receptors for the neurotransmitter serotonin and a corresponding decrease in dopamine in the frontal cortex.

Watermelon: Watermelon juice is fat free and loaded with vitamins A, B6, and C! Vitamin B6 is used by the body to manufacture neurotransmitters such as serotonin, melatonin, and dopamine. Vitamin C also enhances the immune system while protecting the body from free radicals.

Wheat Germ: Wheat Germ is a good source of Phenylalanine. Phenylalanine is an essential amino acid found in the brain and blood plasma that can convert in the body to tyrosine, which in turn is used to synthesize dopamine.

A healthly, balanced diet is rich in whole “natural” and unprocessed foods. It is especially high in plant foods, such as fruits, vegetables, grains, beans, seeds and nuts. Fruits are vegetables are rich in fiber, vitamins, minerals, antioxidants that protect the body cells from damaging. They also help raise serotonin levels in the brain.

Beans and legumes are rich in protein and are healthful boosters of both dopamine and norepinephrine. Also, Protein Meat, Milk, Eggs, Cheese, fish and other seafood are very healthy, high-protein, dopamine-and-norepinephrine-booster food.

Coma brain image techniques being developed in Aberdeen

People in general may not be aware that the coma scales that doctors around the world use to rate the type of coma actually came from previous work in Aberdeen. Now, Brain imaging techniques to find out more about patients in a coma are being developed by University of Aberdeen scientists.The new Aberdeen Coma Science Group - believed to be the first of its kind in Scotland - hopes to provide greater insights into coma patient awareness.This would be used to help guide treatment and provide information for relatives and clinicians.North east of Scotland patients will initially assist the research.The scanning technique is called functional MRI - fMRI.

Prof Christian Schwarzbauer is leading the work, which will involve patients being given fMRI scans while exposed to stimuli such as pictures, sounds, smell and touch.He said: "Thanks to advances in medical care our chances of surviving a severe accident are much higher than they used to be.
"Doctors can save the lives of many patients who suffer brain injury, but, if the injury is severe, the patient may not regain consciousness and slip into a coma."Knowing to what extent a patient is aware will not only be of great importance to doctors, carers and therapists but also to the patient's relatives”Prof Christian Schwarzbauer, University of Aberdeen.

"Some will regain consciousness but others will remain in a so-called vegetative state. With their eyes open and possibly even wandering, these patients appear to be awake but show no signs of awareness of themselves or their environment." Prof Schwarzbauer said: "The accurate diagnosis of disorders of consciousness such as coma and persistent vegetative state is a major challenge for clinicians.

"Can we really be sure that some of these patients are completely unaware? It's possible that some of these patients are fully aware but are simply unable to move or control their movements."There is a possibility that patients who do not show any brain activation may not be giving a response because their hearing has been impaired because of the accident."Therefore it is important to extend the range of tests to include other senses such as vision or touch."He added: "Our aim is to develop new diagnostic methods for these patients because knowing to what extent a patient is aware will not only be of great importance to doctors, carers and therapists but also to the patient's relatives."

Atrial Fibrilation treatment could reduce dementia

A heart trace or ECG can show up the problem. Treating stroke survivors for a heartbeat problem called atrial fibrillation (AF) might prevent many patients from going on to develop dementia, UK experts believe.

Research into nearly 50,000 patients' records found that AF after a stroke more than doubles the risk of dementia.Doctors say we should now investigate whether more vigorous treatment with drugs to control AF might delay or even prevent dementia.

The work appears in Neurology journal.

Atrial fibrillation is the most common heart rhythm disturbance and affects up to 500,000 people in the UK. Although not usually life-threatening in itself, it does increase the risk of stroke. "These results may help us identify potential treatments that could help delay or even prevent the onset of dementia”

Lead researcher Dr Phyo Kyaw

Blood-thinning drugs and medication to slow the irregular heartbeat are often prescribed to reduce stroke risk.Now experts at the University of East Anglia in the UK believe tighter management of AF might also offer some protection against dementia.They looked at research where people with and without AF were followed up to see how many went on to develop dementia.By analysing 15 separate studies they found that stroke survivors with AF were 2.4 times more likely to develop dementia than stroke survivors who did not have the heart condition. About a quarter of patients with stroke and atrial fibrillation were found to have developed dementia during follow-up. Lead researcher Dr Phyo Kyaw said: "These results may help us identify potential treatments that could help delay or even prevent the onset of dementia. Options could include more rigorous management of cardiovascular risk factors or of AF, particularly in stroke patients."

Rebecca Wood of Alzheimer's Research UK said: "While this paper shows there is a link between atrial fibrillation and dementia, we don't yet know if treating atrial fibrillation will prevent or delay the onset of dementia.

"More research will give us the answers we urgently need."

What makes us human

What makes us human

Cognitive Dissonance explained by a TEDster

Cognitive dissonance

Robert Sapolsky

Brain Plasticity

Ed Boyen Shining a Light on Consciousness

The brain engineer: Shining a light on consciousness
Profile

Ed Boyden leads the Synthetic Neurobiology Group at the Media Lab at the Massachusetts Institute of Technology. His group develops software and technologies for controlling neural circuits in order to understand how cognition and emotion arise, and to try and treat intractable brain disorders.

by Rowan Hooper

 Neuroengineer Ed Boyden is best known for his pioneering work on optogenetics, which allows brain cells to be controlled using light. A speaker at the TED2011 conference this week, his vision, he tells Rowan Hooper, is nothing less than to understand the brain, treat neural conditions and figure out the basis of human existence.

Give us your elevator pitch.

I run the synthetic neurobiology group. We develop software, electrical and optical tools to allow people to analyse brain dynamics. Unlike a computer, the brain is made of thousands of different types of cell, and we don't know how they work. We need to be able to turn the cells on and off to see how they cooperate to implement brain computations, and how they go awry in brain disorders. What we're doing is making genetically encoded neurons that we can turn on and off with light. By shining light on these cells we can activate them and see what they do.

What brain functions will this allow you to study?

Scientists now have unprecedented abilities to perturb and record from the brain, and that's allowing us to go after complex ideas like thought and memory. Our tools will help us parse out emotion, memory, attention and consciousness. Put psychology and neuroscience together with neuroengineering, and some of the biggest questions in neuroscience become tractable.

Tell us about your tools.

The core idea is to take molecules that sense light and convert it into electrical energy, and put them in neurons. We can take a given class of brain cells and develop a virus to deliver genes to these cells. Then we can shine light on these cells and activate them and see what they do.

Where do you get the light-sensitive molecules?

We mine the genomes of the world – fungi, plants, archaea, bacteria – looking for molecules that convert light into different kinds of energy. We're finding stuff already that you could never have dreamed up. We've found several classes of molecules that can pump negative charge in or positive charge out of cells. That's really powerful in terms of what it allows us to do.

Can this approach treat disease?

Imagine we have an epileptic brain and we want to quiet it down. We can put these cells in, shine light on them and turn them off, using a technique called neural silencing. Turning off seizures is a "killer app" for this sort of thing because there's no other way to turn off brain circuits transiently.

We can also, potentially, install light sensors onto the spare neurons in blind people, converting the spare neurons into a camera so they can send info to the brain. We've done this in mice.
Another condition we're working on in mice is post-traumatic stress disorder. We use implants to stimulate brain regions with light and causally assess which cells are associated with which emotions and memories. This way we can find true clinical targets to treat the condition.

It sounds quite invasive.

If we want to drive light very precisely in the central nervous system then we need some kind of implant. We are working on an array of optical devices that can beam light into the brain itself in three dimensions. The width of one of these devices is something like one-eighth that of the deep brain stimulation electrodes used to treat Parkinson's. We're also working hard to try and do this wirelessly.

What other problems do you need to overcome?

We're using molecules from other species – from algae, from archaebacteria and fungi – and we need to put these into human cells. One thing that could happen is that the cells could die if the immune system detects them as foreign. So we've done the first preclinical study, working with primates (Neuron, DOI: 10.1016/j.neuron.2009.03.011). There doesn't seem to be cell death or an active immune response, there don't seem to be immune cells infiltrating the brain. All the classical responses we looked for, we couldn't find.

I would be the first to admit this is early days, but given the potential power of ultra-precise activation and silencing of neurons in the very complex neural circuits of the brain, we're very eager to pursue the science.

You majored in physics. What drew you to neuroscience?

We've got all these rules from physics about how the universe works, but how do we perceive? How do we think? How do we feel? We haven't exactly got a lot of insight into that from knowing about quarks and leptons. We know about the building blocks of the universe, but knowing a lot about physics doesn't help us understand the brain as a complex physical system – and that's one of the outstanding problems of the 21st century.

You work a lot with mouse models. How are you going to get at problems like consciousness by working on animals?

Consciousness and free will are always going to be tricky to analyse in anything but a human, and it's even tricky to analyse in humans. But there are people who are doing very clever things.We can record neurons in the motor regions of the human brain, and it turns out that there are neurons that fire almost a second before people are aware they want to make a decision. So maybe we can't analyse free will and consciousness in the animal brain per se, but if people find neural signatures of free will or consciousness then we can go into the animal brain and perturb them and see what happens. Then we can start to get at causality.

Where do you see this going, long term?

There are two ways of looking at this. One, in the medium term, is the kind of synthetic neurobiology we work on now, in the sense of taking an intact human brain and fixing it. The other would be building brains from scratch, and that's something we haven't even really thought about. We don't know enough about the brain to build one completely from scratch. But it's good to reevaluate every five or 10 years.

Alzheimers

Chemical Switch of Programmed cell death

FLIP Switch of Programmed Cell DeathResearch involving programmed cell death has lead to new information about the involvement of a protein named FLIP in cell survival and cell death.Researchers identified the protein FLIP and the silencing of the enzyme RIPK3 as important clues to the confusing nature of caspase-8. Caspase-8 has been linked to programmed cell death but also has been noted as an essential enzyme during embryonic development. It had been reported previously that mice missing genes to produce caspase-8 exhibited numerous problems during embyronic development leading to lethal outcomes. Previous reports also showed RIPK3 as responsible in cell death via programmed necrosis.
By creating and studying mice lacking genes to produce caspase-8 and RIPK3, the scientists discovered an important role of FLIP. In the new study, mice missing genes for both caspase-8 and RIPK3 production did not experience the severe embryonic developmental problems seen previously with mice lacking caspase-8, were born at normal rates and appeared normal in early life.

After analyzing these new findings, the researchers found that FLIP combines with caspase-8 to form a new enzyme complex. This enzyme complex disrupts RIPK3, resulting in a prevention of cell death via programmed necrosis.The researchers also showed that FLIP prevented caspase-8 from triggering cell death via apoptosis, though the exact mechanisms are not understood. Understanding the interactions of FLIP, caspase-8 and RIPK3 better could greatly improve research into treating neuroblastomas, brain cancer and infected cells.



Further details are provided in the release below, though this is research that will probably be much better understood by studying the original research paper at Nature.



Protein identified that serves as a switch in a key pathway of programmed cell death

Work led by St. Jude Children’s Research Hospital investigators provides fresh insight into mechanisms controlling programmed cell death pathways and offers new targets in the fight against cancer and virus-infected cells.Work led by St. Jude Children’s Research Hospital scientists identified how cells flip a switch between cell survival and cell death that involves a protein called FLIP.

The findings solve a riddle that has puzzled scientists for more than a decade regarding the dual nature of caspase-8, an enzyme intimately linked to the cell’s suicide pathway but also essential for cell survival during embryonic development and the immune response. Researchers identified FLIP and the silencing of another enzyme, named RIPK3, as playing pivotal roles. The study was published in the March 2 advance online edition of Nature.

Douglas Green, Ph.D., the paper’s senior author and chair of the St. Jude Department of Immunology, said work is already underway to use the findings to generate new cancer treatment targets and fresh insight into the missteps that give rise to certain tumors as well as evidence of how some virus-infected cells escape the pathways designed to dispatch such threats.“It is a pretty rare thing to ‘cure’ a lethal mutation in an animal by removing another gene. When that happens, the biology shouts out to us that this is important. We just have to listen,” Green said.

FLIP’s role was identified after investigators bred mice that lacked genes for both caspase-8 and RIPK3. Previous research identified RIPK3 as responsible for orchestrating cell death via programmed necrosis. Once viewed as an uncontrolled form of cell death, programmed necrosis is now recognized as a distinct form of cell suicide. The body relies on both programmed necrosis and apoptosis, the more common process, to rid itself of damaged, dangerous or unneeded cells.
While loss of caspase-8 was known to be lethal during embryonic development, in this study investigators showed mice that lacked both caspase-8 and RIPK3 were born at normal rates and appeared developmentally normal early in life.
Investigators went on to show that caspase-8 prevents programmed necrosis by combining with FLIP to form an enzyme complex that disrupts RIPK3 functioning and so prevents death via programmed necrosis. The work also demonstrated that FLIP expression prevents caspase-8 from triggering cell death via apoptosis, although the exact mechanism must still be determined. Apoptosis relies on caspase enzymes and other molecules to ensure the cell self destructs.

Green said the findings provide insight into the mechanisms at work in neuroblastoma and other tumors that suffer a loss of caspase-8. “We are beginning collaborative experiments to examine these tumors to see if RIPK3 is deleted or blocked,” he said. Neuroblastoma arises in cells of the sympathetic nervous system. It is the most common solid tumor in children, accounting for up to 10 percent of all childhood cancers.

Notes about the research article
Andrew Oberst, a St. Jude postdoctoral fellow, is the study’s first author. The other authors are Christopher Dillon, Ricardo Weinlich, Laura McCormick and Patrick Fitzgerald, all of St. Jude; Cristina Pop and Guy Salvesen, of Sanford-Burnham Medical Research Institute, La Jolla; and Razq Hakem, of the University of Toronto.

The research was supported in part by the National Institutes of Health, the Canadian Institutes of Health Research, the Sass Foundation for Medical Research and ALSAC.

Contact: Summer Freeman – St. Jude Children’s Research Hospital

Source: Press release from St. Jude Children’s Research Hospital

Proteomics explained by Danny Hillis

Anxiety inhibits Decision Making

Decreased Neural Inhibition Makes Decision Making Harder For The AnxiousNew psychology research from CU-Boulder suggests that “neural inhibition” is a critical component in our ability to make choices. Psychologists have proposed people who suffer from anxiety could have decreased neuronal inhibition, which makes it more difficult to make important decisions.
CU-Boulder study sheds light on how our brains get tripped up when we’re anxious
A new University of Colorado at Boulder study sheds light on the brain mechanisms that allow us to make choices and ultimately could be helpful in improving treatments for the millions of people who suffer from the effects of anxiety disorders.

In the study, CU-Boulder psychology Professor Yuko Munakata and her research colleagues found that “neural inhibition,” a process that occurs when one nerve cell suppresses activity in another, is a critical aspect in our ability to make choices.“The breakthrough here is that this helps us clarify the question of what is happening in the brain when we make choices, like when we choose our words,” Munakata said. “Understanding more about how we make choices, how the brain is doing this and what the mechanisms are, could allow scientists to develop new treatments for things such as anxiety disorders.”

Researchers have long struggled to determine why people with anxiety can be paralyzed when it comes to decision-making involving many potential options. Munakata believes the reason is that people with anxiety have decreased neural inhibition in their brain, which leads to difficulty making choices.

“A lot of the pieces have been there,” she said. “What’s new in this work is bringing all of this together to say here’s how we can fit all of these pieces of information together in a coherent framework explaining why it’s especially hard for people with anxiety to make decisions and why it links to neural inhibitors.”

A paper on the findings titled “Neural inhibition enables selection during language processing” appeared in the Aug. 30Proceedings of the National Academy of Sciences. CU-Boulder professors Tim Curran, Marie Banich and Randall O’Reilly, graduate students Hannah Snyder and Erika Nyhus and undergraduate honors thesis student Natalie Hutchison co-authored the paper.In the study, they tested the idea that neural inhibition in the brain plays a big role in decision-making by creating a computer model of the brain called a neural network simulation.“We found that if we increased the amount of inhibition in this simulated brain then our system got much better at making hard choices,” said Hannah Snyder, a psychology graduate student who worked with Munakata on the study. “If we decreased inhibition in the brain, then the simulation had much more trouble making choices.”

Through their model they looked at the brain mechanisms involved when we choose words. They then tested the model’s predictions on people by asking them to think of the first verb that comes to mind when they are presented with a noun.

“We know that making decisions, in this case choosing our words, taps into this left-front region of the brain, called the left ventrolateral prefrontal cortex,” Munakata said. “We wanted to figure out what is happening in that part of the brain that lets us make these choices. Our idea here, which we have shown through the word-choosing model, is that there’s a fight between neurons in this area of the brain that lets us choose our words.”

They then tested the model’s predictions that more neural inhibition in the brain makes it easier to make choices by examining the effects of increased and decreased inhibition in people’s brains. They increased inhibition by using a drug called midazolam and found that people got much better at making hard choices. It didn’t affect other aspects of their thinking, but rather only the area of making choices. They investigated the effects of decreased inhibition by looking at people with anxiety.

“We found that the worse their anxiety was, the worse they were at making decisions, and the activity in their left ventrolateral prefrontal cortex was less typical,” Munakata said.There are two ways in which the research could be helpful in improving treatments for anxiety, according to Snyder. While specific medications that increase neural inhibition are currently used to treat the emotional symptoms of anxiety disorders, the findings suggest that they might also be helpful in treating the difficulty those suffering from anxiety have in selecting one option when there are too many choices.
“Secondly, a more precise understanding of what aspects of cognition patients are struggling with could be extremely valuable in designing effective approaches to therapy for each patient,” she said. “For example, if someone with an anxiety disorder has difficulty selecting among multiple options, he or she might benefit from learning how to structure their environment to avoid choice overload.”
The work was done in CU-Boulder’s Center for Determinants of Executive Function and Dysfunction, which brings together researchers from different areas of expertise on campus and beyond including experts on drug studies, neuroimaging and anxiety. The center is funded by the National Institute of Mental Health.

Contact: Yuko Munakata

Source: University of Colorado at Boulder

Quit Smoking with Neuroscience

Quit Smoking Messages in the BrainQuit smoking messages were more effective when tailored toward an individual and when that individual showed greater activity in self-related brain regions such as the dorsomedial prefrontal cortex.Using MRI, researchers compared subjects’ brain images taken during self-appraisal tasks, neutral messages, tailored quit smoking messages and generalized quit smoking messages.
The subjects that showed more brain activity during self-appraisal tasks were more likely to quit smoking four months after hearing tailored quit smoking messages than the other groups. More than 50% of these subjects had quit smoking four months later.These results suggest that more tailored public health messages may improve response rates. This research also suggests that brain imaging could be extremely useful in improving behavioral modification messages such as quit smoking commercials.

Readers interested in ways to improve quit smoking messages, neuromarketing and public health campaigns can find more details in the release below.Certain parts of the brain activated in people who heard tailored health messages and quit smoking

People who demonstrated a stronger brain response to certain brain regions when receiving individually tailored smoking cessation messages were more likely to quit smoking four months after, a new study found.

The new University of Michigan study underscores the importance of delivering individually tailored public health messages to curb unhealthy behaviors, said principal investigator Hannah Faye Chua, who led the study as a research assistant professor at the U-M School of Public Health. It also begins to uncover the underlying neural reasons why these individually tailored messages are so much more effective than a one-size-fits-all approach, said Chua, who now works in the private sector. The study is in the journal Nature Neuroscience.Researchers have known for 15 years that tailored public health messages that account for a person’s individuality work better at curbing unhealthy behaviors but until now, they haven’t known why.Chua and the research team hypothesized that portions of the brain activated during self-related processing were also engaged when people received individually tailored health messages, and that this brain activity accounted for the increased effectiveness of tailored messages.

For the study, the research group assessed 91 people who wanted to stop smoking, and based on those answers they designed an individual smoking cessation program for each subject.Next, researchers imaged subjects’ brains with MRI to see which portions responded to tailored and untailored messages about smoking cessation, and also to neutral messages. They then compared the brain response to the brain response during a self-appraisal task in which participants, still in MRI, made yes-no judgments to self-related statements such as “I am shy” or “I am athletic.”
Several brain regions activated during the self-related task also appeared to activate during the tailored messages in the same group of smokers. After the scan, participants completed the full smoking intervention program that was designed for each subject.
“The bottom line is that people who are more likely to activate self-related regions of the brain during tailored message processing, particularly dorsomedial prefrontal cortex, are more likely to quit 4 months after,” Chua said.

The findings have broad public health implications. “The bigger picture of this is advertisers are increasing using functional MRI to test advertising,” said Vic Strecher, professor in the U-M SPH who worked on the project. “If you can imagine that people who create fast food or who sell cigarettes are doing this in an effort to convey a stronger message, we really need to better understand the ways our health messages can be more effective.”Chua stressed that researchers don’t want to use functional MRI as a predictor for success of public health messages; it’s simply not economically feasible. They do, however, want to better understand and eventually map the portions of the brain responsible for making decisions that will improve their health.

Some people had a stronger brain response than others to the tailored messages, Chua said, but it’s not clear why. It may be that their brains are hardwired to process information differently, or that those people had a stronger desire or commitment to quitting.“However, the desire is not just motivation, because there was no difference in motivation between quitters and non-quitters,” Chua said. More than 50 percent of people quit after the four month follow-up; most smoking cessation programs range from 15 to 30 percent success. “Over 50 percent is really a successful measure,” Chua said.

Notes about this research:

The University of Michigan School of Public Health has been promoting health and preventing disease since 1941, and is ranked among the top public health schools in the nation. Whether making new discoveries in the lab or researching and educating in the field, our faculty, students, and alumni are deployed around the globe to promote and protect our health.

Contact: Laura Bailey - University of Michigan

Source: University of Michigan press release