Body”s own molecular protection against arthritis discovered

Washington, May 19 (ANI): An international team of scientists has discovered that a natural molecule in the body counters the progression of osteoarthritis.

The findings from The Scripps Research Institute in California and the National Research Institute for Child Health and Development in Japan could one day lead to new therapies for some common diseases of aging.

The molecule the team studied, microRNA 140 (miR-140), is part of a recently discovered category of genetic molecules—”microRNAs” or “non-coding RNAs” which do not code for proteins, yet often play a vital role in gene expression.

“This is the first report showing the critical role of a specific non-coding RNA in bone development. Moreover, surprisingly, we observed that microRNA 140 acts against arthritis progression. This is among the first evidence that non-coding RNA plays a key role in age-dependent diseases,” said Hiroshi Asahara, associate professor of molecular and experimental medicine at Scripps Research.

The study was published in an advanced, online issue of the journal Genes & Development. (ANI)

Why a whiff of cats scares the hell out of a mouse

Washington, May 14 (ANI): If you were a mouse, a mere whiff of a cat, rat or snake would be enough to scare you away.

Your stress hormone levels would go up and you”d begin to take extra precautions, hugging the ground as you carefully investigated your surroundings.

Now, researchers have discovered what it is that upsets the mice so much.

It turns out that the triggers for fear are related but species-specific urinary proteins known as Mups, which are secreted by almost every land-dwelling vertebrate.

Those chemicals are picked up by sensory neurons found in the mouse vomeronasal organ.

Importantly, Mups sensed by this organ were already known to act as chemical pheromones, which serve to communicate within a species.

For examples, pheromones emitted by male mice motivate aggressive behaviour in other males.

The new findings show that Mups also act as kairomones, a word used to describe chemicals used in communication between two species – and specifically those that offer a benefit to the recipient without benefiting the animals that produced them.

Kairomones had mainly been identified in insect communication and, until now, their identity and detection was mostly unknown in mammals, according to the researchers.

“At first, I was sceptical,” said Lisa Stowers of The Scripps Research Institute in reference to the new results that led them to Mups.

Earlier studies by her team had identified Mups as the active ingredient in pheromones.

“Here, we looked for the cues [for fear] and ended in the same family of proteins,’ she added.

In hindsight, Stowers says, the discovery makes perfect sense—Mups are incredibly stable molecules in the environment and once animals had a receptor for one of them, any duplication of the underlying genes would have opened the door for the evolution of related receptors capable of detecting related molecules.

“Our findings suggest that the stabilization and expansion of Mup chemosensation resulted in the co-option of function to include both inter- and intraspecies communications,” wrote the researchers.

In fact, Stowers said they now suspect kairomone communication might have come first.

That kind of co-option of existing sensory mechanisms offer a ready molecular solution to what would otherwise be a difficult problem— the evolution of a variety of species-specific molecular detectors.

The researchers say it”s not yet clear whether mice can tell the difference between a cat, rat, or any other species based on a whiff of them alone.

“There”s a difference in the pattern of activation in neurons for cats versus rats, which may mean they can tell,” said Stowers.

But there”s overlap in the neural patterns too and it could be that part that matters.

What is clear is that this fear behaviour in the mice is completely hardwired.

The study has been published in the latest issue of the journal Cell, a Cell Press publication. (ANI)

Potential target for drugs to combat alcohol addiction identified

Washington, May 13 (ANI): A new research has helped researchers identify potential target for drugs to combat alcohol addiction.

A team at The Scripps Research Institute has found decisive evidence that a specific neurotransmitter system—the endocannabinoid system—is active in a brain region known to play a key role in the processing of memory, emotional reactions, and addiction formation.

Their study also shows that this system can dampen the effects of alcohol, suggesting an avenue for the development of drugs to combat alcohol addiction.

“This study will change a lot in the field. I”m confident it will have a big impact,” said Scripps Research Associate Professor Marisa Roberto, who was first author of the paper.

Paul Schweitzer, associate professor of the neurobiology of addiction at Scripps Research and corresponding author of the paper, said: “This is very new. It is the first time a study has shown a direct cellular interaction between endocannabinoids and alcohol in the brain.”

The new research overturns the conclusions of a paper published by a European group in the Journal of Neuroscience in 2001. This paper claimed that endocannabinoid receptors, in particular the most common type called CB1, did not exist in the brain region called the central amygdala.

Schweitzer said: “Yet CB1 receptors are very abundant. They are almost everywhere in the brain and there are lots of them. The endocannabinoid system acts on appetite, mood, memory—and addiction. Addiction is why we started to study it in the central amygdala.”

The research was published in the journal Neuropsychopharmacology on May 12. (ANI)

New study sheds light on potential treatment for Gaucher”s disease

London, May 10 (ANI): Scientists at The Scripps Research Institute have shed light on a mechanism that enables a potential treatment for Gaucher”s disease and other lysosomal storage diseases.

In the new study, the researchers revealed how the widely available prescription drugs diltiazem, verapamil, and in some cases dantrolene, acted on cells from patients with Gaucher”s disease.

The drugs increased calcium levels in a subcellular compartment called the endoplasmic reticulum—a convoluted membranous sac within the cell where the folding of many proteins takes place.

“This study is likely to motivate clinical trials for the treatment of neuropathic lysosomal storage diseases, including Gaucher”s disease, where the current standard of care, enzyme replacement therapy, is ineffective,” Nature quoted team leader Dr. Jeffery Kelly, as saying.

“The research is especially promising because we enhanced the cellular folding and function of mutated lysosomal enzymes, whose deficient function is linked to lysosomal storage diseases, using two distinct categories of FDA-approved drugs that have been shown to be safe and effective for the treatment of high blood pressure and muscle spasms,” he added.

“We wanted to uncover general principles that could be applied to a variety of loss-of-function protein misfolding diseases. This study reveals how we can enhance the capacity of the cellular machinery to fold and traffic a mutant enzyme, so that the protein can function better,” said Derrick Sek Tong Ong, first author of the paper.

Gaucher”s disease is the most common genetic disease among the Ashkenazi Jewish population of Eastern European ancestry.

Symptoms include bruising easily due to low blood platelets, enlargement of the liver and spleen, and fatigue due to anaemia.

In the new paper, the lab found that the prescription drugs diltiazem and verapamil were effective in restoring partial cellular folding, trafficking, and function to mutant enzymes responsible for three lysosomal storage disorders, including Gaucher”s disease.

The findings were published in an advance, online edition of the journal Nature Chemical Biology. (ANI)

Groundbreaking new understanding of stem cells

London, May 3 (ANI): Researchers from The Scripps Research Institute have detailed some striking differences between the biochemistry of stem cells versus mature cells—a feat that could one day lead to new therapies.

Led by Gary Siuzdak, the researchers used a unique approach to better understand stem cells, which have the ability to change or “differentiate” into adult cell types (such as hair cells, skin cells, nerve cells).

Understanding how stem cells mature opens the door for scientists and physicians to manipulate the process to meet the needs of patients, potentially treating such intractable conditions as Parkinson”s disease and spinal injury.

“In the past, scientists trying to understand stem cell biology focused on genes and proteins. In our study, we looked at stem cell regulation in a different way—on the biochemical level, on a functional level. With metabolomics profiling, we were able to look at naturally occurring small molecules and how they control cell fate on a completely different level,” Nature quoted Ding as saying.

The new paper describes parts of the stem cell “metabolome”— the complete set of substances (“metabolites”) formed in metabolism, including all naturally occurring small molecules, biofluids, and tissues.

The scientists then compared this profile to those of more mature cells, specifically of nerve cells and heart cells.

After tallying the results, the scientists had found about 60 previously unidentified metabolites associated with the progression of stem cells to mature cells, as well as an unexpected pattern in the chemistry that mirrored the cells” increasing biological maturity.

The study of metabolomics is relatively new, having emerged only over the past decade or so.

“One of the most interesting aspects of metabolomics is how little we know. We don”t know what the vast majority of metabolites are, or what they do. It is an area ripe for discovery,” commented Siuzdak.

In the current study, the team used liquid chromatography-mass spectrometry (LCMS), which draws on two more traditional techniques to provide scientists with the ability to chemically analyse virtually any molecular species.

The group then analysed the resulting data using an open-access bioinformatics platform XCMS.

The XCMS software allows researchers to identify and assess metabolite and peptide features that show significant change between sample groups—in this case mouse stem cells versus mature cells.

The most difficult part of untargeted metabolomics studies is analysing the results and characterizing metabolites, said Oscar Yanes, the new paper”s first author.

Still, Yanes shifted though the data on stem cells and identified an unexpected pattern— stem cell metabolites had highly unsaturated structures compared with mature cells, and levels of highly unsaturated molecules decreased as the stem cells matured.

Highly unsaturated molecules, which contain little hydrogen, can easily react and change into many other different types of molecules.

“The study reveals an astounding cellular strategy. The capacity of embryonic stem cells to generate a whole spectrum of cell types characteristic of different tissues (a phenomenon referred to as plasticity) is mirrored at the metabolic level,” said Yanes.

“We were not expecting these results. Although in retrospect it makes sense that stem cells (which can form almost any cell) have metabolites that are chemically flexible,” said Siuzdak.

The study was published in an advance, online edition of the prestigious journal Nature Chemical Biology. (ANI)

How we can sense temperatures

London, Apr 24 (ANI): A group of experts has shed new light on the molecular mechanism that enables us to sense temperature, such as the heat from a sizzling stove.

The finding by scientists at The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF) could one day lead to new therapies for conditions such as acute or chronic inflammatory pain.

The study, which was led by Scripps Research and GNF Professor Ardem Patapoutian, was published in the journal Nature Neuroscience.

To understand temperature sensation, the researchers focused on a protein called TRPV1, which is a member of a small family of proteins known to enable temperature sensation, and is involved in inflammation and the communication of pain to the brain. After producing thousands of mutants of this protein, the scientists were able to identify a region of the protein that enabled temperature sensitivity and to detail some of the molecular mechanisms at work in the molecule.

“Ever since the discovery of these proteins, it has been an outstanding question how they can be activated by temperatures,” said Research Associate Jörg Grandl, a member of the Patapoutian lab and first author of the paper. “The new study addresses this question.”

“Because our ability to sense temperature is closely linked to our ability to sense pain, some of these ion channels are considered targets to treat chronic inflammatory and neuropathic pain indications,” said Patapoutian. “Understanding these proteins could be crucial in designing future drugs that can either activate or block them.” (ANI)

How genetic mutations lead to diabetes

Washington, April 20 (ANI): Scientists at The Scripps Research Institute have finally cracked the 40-year-old mystery of how certain genetic mutations lead to Type 1 diabetes.

According to researchers, their findings could lead to novel therapies for Type 1 diabetes and other autoimmune diseases.

“People have been looking for the mechanism linking HLA and autoimmunity for 40 years. This study provides a big leap forward in understanding and suggests a critical new target to intervene in type 1 diabetes,” said Scripps Research Professor Luc Teyton, who led the study with Scripps Research Professor Ian Wilson.

While genes predispose people to many different types of diseases in many different ways, specific genetic variations are especially strong predictor of the development of type 1 diabetes.

Three genetic variations in particular (HLA-DQ2, HLA-DQ8, and HLA-DR0405)-all located in the region of the genome called HLA for “human leukocyte antigen”-are known to dramatically increase risk of coming down with the condition.

These three genes encode molecules that present peptides (protein fragments) to the body”s T cells. T cells then determine whether the peptide being presented is dangerous and needs to be eliminated from the body-as in the case of foreign invaders such as bacteria or viruses-or whether the peptide is “self,” part of the host and something the immune system needs to leave alone. However, in the context of type 1 diabetes, T cells aggressively attack the body”s own cells.

The scientists wanted to know on a molecular level how mutations in the immune surveillance machinery could lead to type 1 diabetes.

Research Associate Adam Corper of the Wilson lab, who was first author of the paper with Kenji Yoshida of the Teyton lab, said: “We were interested in trying to understand why certain MHC molecules (which are molecules in mice analogous to HLA molecules in humans) are linked to autoimmune disease, particularly type 1 diabetes. In particular, we wanted to know why a single residue at position 57 on the ß chain of HLA molecules seems to be linked to the disease.”

In the new research, the team used a series of structural and biophysical studies to answer that question.

The study was published in an advanced, online issue of the Journal of Clinical Investigation on April 19, 2010, and will appear in the May print edition of the journal. (ANI)

How genetic mutations lead to diabetes

Washington, April 20 (ANI): Scientists at The Scripps Research Institute have finally cracked the 40-year-old mystery of how certain genetic mutations lead to Type 1 diabetes.

According to researchers, their findings could lead to novel therapies for Type 1 diabetes and other autoimmune diseases.

“People have been looking for the mechanism linking HLA and autoimmunity for 40 years. This study provides a big leap forward in understanding and suggests a critical new target to intervene in type 1 diabetes,” said Scripps Research Professor Luc Teyton, who led the study with Scripps Research Professor Ian Wilson.

While genes predispose people to many different types of diseases in many different ways, specific genetic variations are especially strong predictor of the development of type 1 diabetes.

Three genetic variations in particular (HLA-DQ2, HLA-DQ8, and HLA-DR0405)-all located in the region of the genome called HLA for “human leukocyte antigen”-are known to dramatically increase risk of coming down with the condition.

These three genes encode molecules that present peptides (protein fragments) to the body”s T cells. T cells then determine whether the peptide being presented is dangerous and needs to be eliminated from the body-as in the case of foreign invaders such as bacteria or viruses-or whether the peptide is “self,” part of the host and something the immune system needs to leave alone. However, in the context of type 1 diabetes, T cells aggressively attack the body”s own cells.

The scientists wanted to know on a molecular level how mutations in the immune surveillance machinery could lead to type 1 diabetes.

Research Associate Adam Corper of the Wilson lab, who was first author of the paper with Kenji Yoshida of the Teyton lab, said: “We were interested in trying to understand why certain MHC molecules (which are molecules in mice analogous to HLA molecules in humans) are linked to autoimmune disease, particularly type 1 diabetes. In particular, we wanted to know why a single residue at position 57 on the ß chain of HLA molecules seems to be linked to the disease.”

In the new research, the team used a series of structural and biophysical studies to answer that question.

The study was published in an advanced, online issue of the Journal of Clinical Investigation on April 19, 2010, and will appear in the May print edition of the journal. (ANI)

Junk food addiction may be clue to obesity – study

Bingeing on high-calorie foods may be as addictive as cocaine or nicotine, and could cause compulsive eating and obesity, according to a study published on Sunday.

The findings in a study of animals cannot be directly applied to human obesity, but may help in understanding the condition and in developing therapies to treat it, researchers wrote in the journal “Nature Neuroscience.”

The study, involving rats, found that overconsumption of high-calorie food can trigger addiction-like responses in the brain and that high-calorie food can turn rats into compulsive eaters in a laboratory setting, the article said.

The scientists also found decreased levels of a specific dopamine receptor — a brain chemical that allows a feeling of reward — in overweight rats, as has been reported in humans addicted to drugs, the article said.

“Obesity may be a form of compulsive eating. Other treatments in development for other forms of compulsion, for example drug addiction, may be very useful for the treatment of obesity,” researcher Paul Kenny of The Scripps Research Institute in Florida said in a telephone interview.

Obesity-related diseases cost the United States an estimated $150 billion each year, according to U.S. federal agencies. An estimated two-thirds of American adults and one-third of children are obese or overweight.

For the study, Kenny and colleagues headed to the grocery store.

“We basically bought all of the stuff that people really like — Ding-Dongs, cheesecake, bacon, sausage, the stuff that you enjoy, but you really shouldn’t eat too often,” he said.

They also bought healthy foods and devised a diet plan for three groups of rats.

One group ate a balanced healthy diet. Another group received healthy food, but had access to high-calorie food for one hour a day. Rats in the third group were fed healthy meals and given unlimited access to high-calorie foods.

The rats in the third group developed a preference for the high-calorie food, munched on it all day and quickly became obese, Kenny said.

The rats in the experiment had also been trained to expect a minor shock when exposed to a light. But when the rats that had unlimited access to high-calorie food were shown the light, they did not respond to the potential danger, Kenny said. Instead, they continued to eat their snacks.

“What we’re seeing in our animals is very similar to what you’d see in humans who overindulge,” he said. “It seemed that it was okay, from what we could tell, to enjoy snack foods, but if you repeatedly overindulge, that’s where the problem comes in.”

JoAnne Allen

Junk food addiction may be clue to obesity: Study

Mon, Mar 29 10:30 AM

Bingeing on high-calorie foods may be as addictive as cocaine or nicotine, and could cause compulsive eating and obesity, according to a study published on Sunday.

The findings in a study of animals cannot be directly applied to human obesity, but may help in understanding the condition and in developing therapies to treat it, researchers wrote in the journal “Nature Neuroscience.”

The study, involving rats, found that over consumption of high-calorie food can trigger addiction-like responses in the brain and that high-calorie food can turn rats into compulsive eaters in a laboratory setting, the article said.

The scientists also found decreased levels of a specific dopamine receptor — a brain chemical that allows a feeling of reward — in overweight rats, as has been reported in humans addicted to drugs, the article said.

“Obesity may be a form of compulsive eating. Other treatments in development for other forms of compulsion, for example drug addiction, may be very useful for the treatment of obesity,” researcher Paul Kenny of The Scripps Research Institute in Florida said in a telephone interview.

Obesity-related diseases cost the United States an estimated $150 billion each year, according to U.S. federal agencies. An estimated two-thirds of American adults and one-third of children are obese or overweight.

For the study, Kenny and colleagues headed to the grocery store.

“We basically bought all of the stuff that people really like — Ding-Dongs, cheesecake, bacon, sausage, the stuff that you enjoy, but you really shouldn’t eat too often,” he said.

They also bought healthy foods and devised a diet plan for three groups of rats.

One group ate a balanced healthy diet. Another group received healthy food, but had access to high-calorie food for one hour a day. Rats in the third group were fed healthy meals and given unlimited access to high-calorie foods.

The rats in the third group developed a preference for the high-calorie food, munched on it all day and quickly became obese, Kenny said.

The rats in the experiment had also been trained to expect a minor shock when exposed to a light. But when the rats that had unlimited access to high-calorie food were shown the light, they did not respond to the potential danger, Kenny said. Instead, they continued to eat their snacks.

“What we’re seeing in our animals is very similar to what you’d see in humans who overindulge,” he said. “It seemed that it was okay, from what we could tell, to enjoy snack foods, but if you repeatedly overindulge, that’s where the problem comes in.”
Reuters

Junk food as addictive as cocaine fix

London, March 29 (ANI): Pigging out on junk food is as addictive as taking heroin and cocaine, according to a new research.

In the new study, scientists from The Scripps Research Institute have shown for the first time that the same molecular mechanisms that drive people into drug addiction are behind the compulsion to overeat, pushing people into obesity.

The study has demonstrated clearly that in rat models the development of obesity coincides with a progressively deteriorating chemical balance in reward brain circuitries.

As these pleasure centers in the brain became less and less responsive, rats quickly developed compulsive overeating habits, consuming larger quantities of high-calorie, high-fat foods until they become obese.

The very same changes occurred in the brains of rats that over-consumed cocaine or heroin, and are thought to play an important role in the development of compulsive drug use.

Scripps Research Associate Professor Paul J. Kenny said that the study, which took nearly three years to complete, confirms the ‘addictive’ properties of junk food.

“It presents the most thorough and compelling evidence that drug addiction and obesity are based on the same underlying neurobiological mechanisms. In the study, the animals completely lost control over their eating behavior, the primary hallmark of addiction. They continued to overeat even when they anticipated receiving electric shocks, highlighting just how motivated they were to consume the palatable food,” Kenny said.

The new research was published March 28, 2010 in an advance online edition of the journal Nature Neuroscience. (ANI)

Junk food addiction may be clue to obesity – study

Bingeing on high-calorie foods may be as addictive as cocaine or nicotine, and could cause compulsive eating and obesity, according to a study published on Sunday.

The findings in a study of animals cannot be directly applied to human obesity, but may help in understanding the condition and in developing therapies to treat it, researchers wrote in the journal “Nature Neuroscience.”

The study, involving rats, found that overconsumption of high-calorie food can trigger addiction-like responses in the brain and that high-calorie food can turn rats into compulsive eaters in a laboratory setting, the article said.

The scientists also found decreased levels of a specific dopamine receptor — a brain chemical that allows a feeling of reward — in overweight rats, as has been reported in humans addicted to drugs, the article said.

“Obesity may be a form of compulsive eating. Other treatments in development for other forms of compulsion, for example drug addiction, may be very useful for the treatment of obesity,” researcher Paul Kenny of The Scripps Research Institute in Florida said in a telephone interview.

Obesity-related diseases cost the United States an estimated $150 billion each year, according to U.S. federal agencies. An estimated two-thirds of American adults and one-third of children are obese or overweight.

For the study, Kenny and colleagues headed to the grocery store.

“We basically bought all of the stuff that people really like — Ding-Dongs, cheesecake, bacon, sausage, the stuff that you enjoy, but you really shouldn’t eat too often,” he said.

They also bought healthy foods and devised a diet plan for three groups of rats.

One group ate a balanced healthy diet. Another group received healthy food, but had access to high-calorie food for one hour a day. Rats in the third group were fed healthy meals and given unlimited access to high-calorie foods.

The rats in the third group developed a preference for the high-calorie food, munched on it all day and quickly became obese, Kenny said.

The rats in the experiment had also been trained to expect a minor shock when exposed to a light. But when the rats that had unlimited access to high-calorie food were shown the light, they did not respond to the potential danger, Kenny said. Instead, they continued to eat their snacks.

“What we’re seeing in our animals is very similar to what you’d see in humans who overindulge,” he said. “It seemed that it was okay, from what we could tell, to enjoy snack foods, but if you repeatedly overindulge, that’s where the problem comes in.”

JoAnne Allen

Junk food addiction may be clue to obesity – study

*Overindulgence may alter brain responses

Stocks | Healthcare

By JoAnne Allen

WASHINGTON, March 28 (Reuters) – Bingeing on high-calorie foods may be as addictive as cocaine or nicotine, and could cause compulsive eating and obesity, according to a study published on Sunday.

The findings in a study of animals cannot be directly applied to human obesity, but may help in understanding the condition and in developing therapies to treat it, researchers wrote in the journal “Nature Neuroscience.”

The study, involving rats, found that overconsumption of high-calorie food can trigger addiction-like responses in the brain and that high-calorie food can turn rats into compulsive eaters in a laboratory setting, the article said.

The scientists also found decreased levels of a specific dopamine receptor — a brain chemical that allows a feeling of reward — in overweight rats, as has been reported in humans addicted to drugs, the article said.

“Obesity may be a form of compulsive eating. Other treatments in development for other forms of compulsion, for example drug addiction, may be very useful for the treatment of obesity,” researcher Paul Kenny of The Scripps Research Institute in Florida said in a telephone interview.

Obesity-related diseases cost the United States an estimated $150 billion each year, according to U.S. federal agencies. An estimated two-thirds of American adults and one-third of children are obese or overweight.

For the study, Kenny and colleagues headed to the grocery store.

“We basically bought all of the stuff that people really like — Ding-Dongs, cheesecake, bacon, sausage, the stuff that you enjoy, but you really shouldn’t eat too often,” he said.

They also bought healthy foods and devised a diet plan for three groups of rats.

One group ate a balanced healthy diet. Another group received healthy food, but had access to high-calorie food for one hour a day. Rats in the third group were fed healthy meals and given unlimited access to high-calorie foods.

The rats in the third group developed a preference for the high-calorie food, munched on it all day and quickly became obese, Kenny said.

The rats in the experiment had also been trained to expect a minor shock when exposed to a light. But when the rats that had unlimited access to high-calorie food were shown the light, they did not respond to the potential danger, Kenny said. Instead, they continued to eat their snacks.

“What we’re seeing in our animals is very similar to what you’d see in humans who overindulge,” he said. “It seemed that it was okay, from what we could tell, to enjoy snack foods, but if you repeatedly overindulge, that’s where the problem comes in.”

Structure of ”swine flu” virus found

Washington, Mar 25 (ANI): The structure of a key protein from the virus that caused last year”s “swine flu” influenza epidemic has been solved by a team of scientists from The Scripps Research Institute and other institutions.

The development explain why young people have been more vulnerable than older individuals in recent pandemic.

The structure reveals that the virus shares many features with influenza viruses common in the early 20th century.

The team”s findings were published in the March 25, 2010, issue of Science Express, an advance, online publication of selected research papers from the prestigious journal Science.

In the study, the team describes the structure of the hemagglutinin (the influenza virus envelope protein) from the H1N1 swine flu virus that triggered the pandemic in 2009 and is still circulating in the human population. The team then compared the swine flu hemagglutinin protein with a range of different human H1N1 flu viruses in the past century.

“Parts of the 2009 virus are remarkably similar to human H1N1 viruses circulating in the early 20th century,” said Scripps Research Professor Ian Wilson, who was the senior author of the study. “Our findings provide strong evidence that exposure to earlier viruses has helped to provide some people with immunity to the recent influenza pandemic.”

The information should be useful for scientists and public health officials as they respond to current and future pandemics. (ANI)

Stem cell transplantation may correct rare genetic disorder in kids

Washington, Sep 18 (ANI): Scripps Research Institute scientists have offered new hope for parents whose children suffer from the rare genetic disorder ‘cystinosis’ by showing through an experiment on mice that stem cell transplantation can successfully correct the defect.

“After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder. This study is an important step toward that goal,” said principal investigator Stephanie Cherqui.

In the study, the researchers used bone marrow stem cell transplantation to address symptoms of cystinosis in a mouse model.

The procedure virtually halted the cystine accumulation responsible for the disease, and the cascade of cell death that follows.

Cystine is a by-product of the break down of cellular components the body no longer needs in the cell’s “housekeeping” organelles, called lysosomes.

Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes it to build up, forming crystals that are especially damaging to the kidneys and eyes.

Cystinosis is a rare but devastating disease affecting children as young as six months, who begin to suffer renal dysfunction, which grows progressively worse with time. Other symptoms include diabetes, muscular disease, neurological dysfunction, and retinopathy.

The only available drug to treat cystinosis, cysteamine, while slowing the progression of kidney degradation, does not prevent it, and end-stage kidney failure is inevitable.

In the new study, the researchers found that transplanted bone marrow stem cells carrying the normal lysosomal cystine transporter gene abundantly engrafted into every tissue of the experimental mice.

This led to an average drop in cystine levels of about 80 percent in every organ.

Not only it prevented kidney dysfunction, there was less deposition of cystine crystals in the cornea, less bone demineralization, and an improvement in motor function.

“The results really surprised and encouraged us. Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective,” says Cherqui.

Cherqui said that adult bone marrow stem cell therapy is particularly well suited as a potential treatment for cystinosis because these cells target all types of tissues.

In addition, stem cells reside in the bone marrow for the duration of a patient’s life, becoming active as needed, a particular benefit for a progressive disease like cystinosis.

The study has been published in the journal Blood. (ANI)

New gene linked to progressive hearing loss identified

Washington, Sept 4(ANI): Scientists from The Scripps Research Institute have discovered a gene responsible for progressive hearing loss.

The has team found a gene, called Loxhd1, which is necessary for maintaining proper functioning hair cells in the inner ear.

However, mutations in this gene can lead to degradation of the hair cells and a disruption of the process that enables hearing.

“It is thought that mutations in several hundred genes can lead to deafness,” said team leader Ulrich Mueller, a professor in the Department of Cell Biology and member of the Skaggs Institute for Chemical Biology at Scripps Research.

“However, for many forms of deafness, we don’t know what effects the genes have. In this new research, we have linked a previously uncharacterized gene to deafness, first in mice and then in humans,” said Mueller.

During the study, researchers used a technique called forward genetics in their quest to better understand the genetic basis of hearing and hearing loss.

In forward genetics, scientists make mutations at random in germ cells, screen the resulting models for physical characteristics of interest (in this case hearing impairment), then amplify these traits through the breeding of several generations.

The gene responsible for the trait is then identified through positional cloning.

In this case, the scientists were able to generate a new mouse line with hearing impairment that they called samba and then clone the gene responsible, Loxhd1, which had never before been associated with deficits in hearing.

When the mice inherited two copies of the mutated gene, they were profoundly deaf shortly after birth.

This is the third hearing-related gene that the Mueller lab has discovered.

“In humans, the prevailing difficulty is progressive hearing loss,” he said.

“As you age, you lose your hearing slowly. Since this mutation can lead to progressive hearing loss, it provides us with more information on the genetic underpinnings of this condition and gives us clues as to how it might be corrected,” he added.

The study appears in American Journal of Human Genetics, a publication of Cell Press. (ANI)

2 new antibodies may pave way for powerful AIDS vaccine

Washington, Sep 4 (ANI): In what may be called the discovery of an Achilles heel on the AIDS virus, researchers have found two powerful new antibodies to HIV, called PG9 and PG16, that could ultimately lead to a powerful vaccine for the deadly disease.

Researchers associated with the International AIDS Vaccine Initiative (IAVI), at The Scripps Research Institute, and at the biotechnology companies Theraclone Sciences and Monogram Biosciences, made the breakthrough discovery, which they will use to craft novel approaches to designing an AIDS vaccine.

Moreover, the global collaboration and process that led to the discovery of the two new broadly neutralizing antibodies (bNAbs) are likely to produce more such antibodies, which may in turn reveal additional vulnerabilities of HIV, adding still more vitality to the effort to develop a vaccine against AIDS.

“The findings themselves are an exciting advance toward the goal of an effective AIDS vaccine because now we’ve got a new, potentially better target on HIV to focus our efforts for vaccine design. And having identified this one, we’re set up to find more, which should further accelerate global efforts in AIDS vaccine development,” said Wayne Koff, senior vice president of research and development at IAVI.

Broadly neutralizing antibodies to HIV are produced by a minority of HIV-infected individuals and are distinct from other antibodies to HIV because they neutralize a high percentage of the many types of HIV in circulation worldwide.

It is widely believed that to prevent HIV infection an AIDS vaccine would need to teach the body to produce these powerful antibodies before exposure to the virus.

Animal experiments have suggested that conceptually such a vaccine would work.

Before the discovery, only four antibodies to HIV had been discovered that were widely agreed to be broadly neutralizing.

The two newly discovered bNAbs-PG9 and PG16-are the first to have been identified in more than a decade and are the first to have been isolated from donors in developing countries, where the majority of new HIV infections occur.

Besides, previously identified bNAbs against HIV have functioned by binding to places on HIV that have proven difficult to exploit by means of vaccine design.

“These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design. So now we may have a better chance of designing a vaccine that will elicit such broadly neutralizing antibodies, which we think are key to successful vaccine development,” said Dennis Burton at Scripps.

The two new antibodies target a region of the viral spike used by HIV to infect cells.

The viral spike glycoproteins, termed gp120 and gp41, are highly variable and have evolved to thwart immune attack.

But biochemical studies suggest that PG9 and PG16 target regions of gp120 that do not change, which probably accounts for their breadth of neutralization.

Now researchers are planning to focus on studying the molecular structure of PG9 and PG16 and that of the region they target on the HIV spike.

They will use this information to try to devise immunogens-the active ingredients of vaccines-that elicit similar antibodies.

The study has been published in the journal Science. (ANI)

Genetic variations lined to brain size

Washington, August 19 (ANI): In what may help improve the scientific understanding of autism and other neurological disorders, an international team of researchers have for the first time shown that natural variations in a specific gene influence brain structure.

Co-led by Scripps Research Institute scientists, the research grew out of a larger project called the Thematic Organized Psychosis (TOP) study, which was led by Ole Andreassen at Ullelval University Hospital and Institute of Psychiatry at the University of Oslo in Norway.

TOP called for using extensive magnetic resonance imaging (MRI) scanning of hundreds of patients, including many with severe mental disorders, in collaboration with Anders Dale of the University of California, San Diego (UCSD), School of Medicine.

In the current study, the researchers focused on a gene called MECP2 because it plays major roles in controlling brain development.

Past studies with mice have shown that MECP2 regulates the activity of a wide range of other genes important in brain development. Substantial mutations in the gene also cause the rare disease Retts syndrome, in which brain growth slows, leading to a range of debilitating neurological problems and mental retardation.

Previous studies have also linked MECP2 to autism.

Given its obvious import, Schork says: “This was a logical gene to target.”

During the study, the researchers explored whether common variations likely to have small effects individually in the MECP2 and surrounding region in the DNA of patients could be tied directly to the way a patient’s brain develops.

They found that indeed some of these variations, known as single-nucleotide polymorphisms (SNPs), did correlate well with various measures of a patient’s brain, though there was no identifiable tie between the variations and the mental disorders.

The closest connection they found was between two specific SNPs and lower surface area folds of the outer layer, or cortex, of the brain-the “grey matter,” which plays critical roles in thinking, language, memory, and other functions.

“So, those sorts of common variations actually do have some functional consequences that are dictating variations in brain size,” says Schork.

Interestingly, the pattern was only seen in males.

Schork and his colleagues say that because MECP2 has been linked to autism, there is a very real possibility that studying SNPs in autistic patients might reveal one or more that link to brain development problems. This could even illuminate possible paths for autism treatments, they say.

The researchers are also looking at possible connections between variations in other key genes and various brain regions.

Besides overall brain size, researchers believe that some neurological conditions might be tied to increases in the size of certain brain components, perhaps due to unidentified genetic mutations. This could prevent other components from growing to their full size due to the limited space inside a skull, preventing proper functioning.

“Who knows? This opens things up considerably. Now we can cast a much wider net and maybe rope in genes nobody had a clue about and discover something that otherwise wouldn’t have been known,” says Schork.

The study has been reported in an advance, online Early Edition of the Proceedings of the National Academy of Sciences (PNAS). (ANI)

First technique to produce effective anti-leukaemia agent developed

Washington, Apr 18 (ANI): More than a decade after discovering kapakahines- marine-derived natural products with anti-leukaemia potential-scientists have found the first technique to synthesise them in laboratory in large quantities, by using only acetylene gas, a handful of amino acids, and a dozen inventive steps.

Kapakahines were isolated from a South Pacific sponge in trace quantities, but its lack of availability stalled any future studies.

But, thanks to the efforts of researchers at Scripps Research Institute that unlimited production of kapakahine is now possible.

Thus, research on the compound can proceed and may eventually lead to new drug treatments.

Cripbrochalina olemda, a common tube-type sponge like organism, produces a compound called kapakahine B, among other molecules of interest, which has shown potential for fighting leukaemia.

The researchers have said that kapakahine B, which has an unusual structure, uses some never-before-seen mechanism to fight cancer cells.

For a long time, researchers around the world have unsuccessfully tried to devise a method for synthesizing the kapakahines.

Scripps researchers, led by Phil Baran, started on with more basic research, in which they successfully synthesized a simpler related compound, psychotrimine, with no known pharmaceutical potential.

Inspired by this, the researchers created a highly reactive and selective chemical component referred to as a quaternary centre that, because of structural similarities, also drives the essential first step in the kapakahines synthesis.

Later, they set out on a somewhat riskier venture to develop a second stage needed to synthesize kapakahines.

Then, the researchers predicted that using the quaternary centre, they could produce two intermediate isomers, or molecules with the same chemical formula but different structures.

One of the isomers was predicted to be an ideal stepping stone toward the kapakahines, but more difficult to make.

They predicted that the second isomer would be much more reactive, and in theory its concentration would grow sufficiently as it moved toward equilibrium with the first isomer.

And finally, they synthesized two kapakahines for the first time and in gram quantities.

One of the compounds, kapakahine B, has shown potential in fighting leukaemia cells, which could further help in developing potential drug treatment.

The research has been published online by the Journal of the American Chemical Society. (ANI)