Genes controlling insulin ‘alter’ body clock

Washington, Sept 18 (ANI): Scientists at University of California, San Diego have identified certain insulin-regulating genes that can also alter the timing of the body clock.

They said that the findings can lead to new approaches to treating disorders such as metabolic syndrome that can result, at least in part, from chronic disruption of the sleep-wake cycle.

“People knew that the clock regulates many different processes, but what they didn’t realize what that when you tweak those processes, it feeds back and alters the clock,” said Steve Kay, Dean of the Division of Biological Sciences at the University of California, San Diego, who led the study along with John Hogenesch of the University of Pennsylvania.

A molecular clock controls daily physiological rhythms in many types of cells, even cells grown in culture.

By engineering cultured cells to glow yellow when a particular clock gene switched on, the team made the cycle visible. They then interfered with every human gene to see which would shift the clock. They found that hundreds altered the timing.

“We just suddenly discovered 350 new genes that affect the clock that weren’t known before,” Kay said.

However, subsequent screening to confirm the genes’ effect on a second clock gene narrowed the list to 200.

Seven genes involved in insulin control also influenced the rhythms of the clock.

“What came out very strongly was this close relationship between circadian regulation and insulin signalling. There’s a reciprocal relationship between circadian dysfunction and metabolic dysfunction,” said Kay.

The researchers suggest that genetically altered mice with malfunctioning clocks become obese and develop diet-induced diabetes.Understanding this close relationship between circadian regulation and metabolic homeostasis should provide novel ways of identifying new therapies for metabolic disease,” Kay added.

The study appears in journal Cell. (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)

Gene linked to male infertility identified

Washington, Sept 16 (ANI): Scientists from Virginia Commonwealth University have identified a gene that may contribute to male infertility.

The research team hopes that the new findings would lead to new approaches to male contraception.

Sperm are produced in the testicles through a three-step process called spermatogenesis.

During the final stage, known as spermiogenesis, a lot of changes take place, including the packaging of DNA into the sperm head and the formation of the sperm tail, which propels the sperm cell toward the egg.

The study conducted using mouse model showed that mice lacking a protein called meiosis expressed gene 1, or MEIG1, were sterile as a result of impaired spermiogenesis – the process that encompasses changes in the sperm head and the formation of the tail.

The team also found that MEIG1 associates with the Parkin co-regulated gene protein, or PACRG protein, and that testicular PACRG protein is reduced in MEIG1-deficient mice.

PACRG is thought to play a key role in assembly of the sperm tail, and the reproductive phenotype of PACRG -deficient mice mirrors that of the MEIG1-mutant mice.

“We discovered that MEIG1 is essential for male fertility. Moreover, our findings reveal a critical role for the MEIG1/PACRG partnership in the function of a structure that is unique to sperm, the manchette. The absence of a normal manchette in mice lacking MEIG1 totally disrupts the maturation process of sperm,” said Dr Jerome F. Strauss III, dean in the VCU School of Medicine.

“In addition to having an impact on fertility, the discovery identifies a new target for drug discovery for a much needed reversible male method of contraception,” he added.

The study is published in the Early Edition of the Proceedings of the National Academy of Sciences. (ANI)

Master gene that switches on disease-fighting cells identified

London, Sep 14 (ANI): British scientists have identified the master gene, called E4bp4, that causes blood stem cells to turn into disease-fighting ‘Natural Killer’ (NK) immune cells.

The discovery, by researchers at Imperial College London, UCL and the Medical Research Council’s National Institute for Medical Research, could one day help scientists boost the body’s production of these frontline tumour-killing cells, creating new ways to treat cancer.

By ‘knocking out’ E4bp4 in a mouse model, the researchers created the world’s first animal model entirely lacking NK cells, but with all other blood cells and immune cells intact.

The breakthrough model should help solve the mystery of the role that Natural Killer cells play in autoimmune diseases, such as diabetes and multiple sclerosis.

According to many scientists, these diseases are a result of malfunctioning NK cells that turn on the body and attack healthy cells, which cause disease instead of fighting it.

They believe that clarifying NK cells’ role could lead to new ways of treating these conditions.

Natural Killer cells – a type of white blood cell – are a major component of the human body’s innate, quick-response immune system, providing a fast frontline defence against tumours, viruses and bacterial infections.

The gene E4bp4 is the ‘master gene’ for NK cell production, which means it is the primary driver that causes blood stem cells in the bone marrow to differentiate into NK cells.

Led by Dr Hugh Brady, the researchers are hoping to progress with a drug treatment for cancer patients which reacts with the protein expressed by their E4bp4 gene, causing their bodies to produce a higher number of NK cells than normal, to increase the chances of successfully destroying tumours.

“If increased numbers of the patient’s own blood stem cells could be coerced into differentiating into NK cells, via drug treatment, we would be able to bolster the body’s cancer-fighting force, without having to deal with the problems of donor incompatibility,” Nature quoted Brady as saying.

The researchers proved the pivotal role E4bp4 plays in NK production when they knocked the gene out in a mouse model.

Without E4bp4 the mouse produced no NK cells whatsoever but other types of blood cell were unaffected.

“Now finally, with our discovery of the NK cell master gene and subsequent creation of our mouse model, we will be able to find out if the progression of these diseases is impeded or aided by the removal of NK cells from the equation. This will solve the often-debated question of whether NK cells are always the ‘good guys’, or if in certain circumstances they cause more harm than good,” said Brady.

The study has been published in Nature Immunology. (ANI)

Vitamin C can help protect DNA damage of skin cells

Washington, Sept 10 (ANI): Researchers at the University of Leicester and Institute for Molecular and Cellular Biology in Portugal have found that vitamin C can help protect DNA damage of skin cells and lead to better skin regeneration.

Previous research has shown that DNA repair is upregulated in people consuming vitamin C supplements.

In the new study, the researchers have provided some mechanistic evidence.

The researchers used affymetrix microarray, for looking at gene expression, and the ‘Comet’ assay to study DNA damage

“The exposure to solar ultraviolet radiation increases in summer, often resulting in a higher incidence of skin lesions. Ultraviolet radiation is also a genotoxic agent responsible for skin cancer, through the formation of free radicals and DNA damage,” said lead researcher Tiago Duarte, formerly of the University of Leicester, and now at the Institute for Molecular and Cellular Biology in Portugal.

“Our study analysed the effect of sustained exposure to a vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in human dermal fibroblasts.

“We investigated which genes are activated by vitamin C in these cells, which are responsible for skin regeneration.

“The results demonstrated that vitamin C may improve wound healing by stimulating quiescent fibroblasts to divide and by promoting their migration into the wounded area. Vitamin C could also protect the skin by increasing the capacity of fibroblasts to repair potentially mutagenic DNA lesions,” Duarte added.

The researchers hope that the results will be of great relevance to the cosmetics industry.

“The study indicates a mechanism by which vitamin C could contribute to the maintenance of a healthy skin by promoting wound healing and by protecting cellular DNA against damage caused by oxidation,” said Dr Marcus S. Cooke from the Department of Cancer Studies and Molecular Medicine and Department of Genetics, at the University of Leicester.

“These findings are particular importance to our photobiology interests, and we will certainly be looking into this further,” Cooke added.

The findings have been published in the journal Free Radical Biology and Medicine. (ANI)

Kelly Osbourne blames her DNA for drug addiction

Washington, Sept 10 (ANI): ‘Dancing with the Stars’ contestant Kelly Osbourne has blamed her genes for her drug addiction.

Kelly’s father, rockstar Ozzy Osbourne, has had a long struggle with drugs, which makes her believe her DNA was pre-programmed to make her an addict.

Contactmusic quoted Kelly as telling BBC Radio 5 Live: “I don’t have any shadow of a doubt that addiction is a disease. It is in your genes.

“The only people in my family who don’t have that gene are my mother and my sister Amy.

“I consider myself lucky that I saw both sides of it. Drugs stop you from screaming on the outside, but you are still screaming on the inside.

“I was addicted by 16. Drugs stopped me from feeling a certain way. Some people experience euphoria but I never felt that. They numbed me and gave me confidence.

It was like a magic medicine.”

The 24-year-old Kelly has been in rehab four times and is presently drug free. (ANI)

Engineered human fusion protein stops HIV-1 replication in mice

Washington, September 9 (ANI): Inspired by New World owl monkeys’ ability to make a fusion protein that potently blocks HIV-1 infection, scientists at the University of Geneva in Switzerland have engineered a human HIV-1 inhibitor.

Lead researcher Jeremy Luban points out that owl monkeys make AoT5Cyp, and that the human genome encodes the equivalent of the two components of this fusion protein, namely TRIM5 and cyclophilin A.

However, adds the researcher, humans do not make the T5Cyp fusion protein.

In their new study, Luban and colleagues have engineered a human HIV-1 inhibitor modeled after AoT5Cyp, by fusing human cyclophilin A to human TRIM5 (hT5Cyp).

The researchers said that the human fusion protein blocked HIV-1 infection of human macrophage and T cell lines, without disrupting normal cell function.

During the study, the researchers engineered some mice to lack B, T, and NK immune cells, so that the animals would not reject grafts of human material.

The team then engrafted with human CD4+ T cells engineered to contain hT5Cyp.

HIV-1 replication was potently inhibited in these animals.

Based on their findings, the researchers came to the conclusion that hT5Cyp is a robust inhibitor of HIV-1 replication, and a promising anti-HIV-1 gene therapy candidate.

The study has been published in the Journal of Clinical Investigation. (ANI)

New gene may provide better immune defense against anthrax

Washington, Sept 9 (ANI): Scientists from University of California have identified a gene in anthrax-causing bacteria that could be used as a potential therapeutic target for the deadly disease.

The ClpX gene in bacterium Bacillus anthracis not only contributes to the severity of the anthrax disease but also makes it more difficult for a patient’s immune system to fight the infection.

Inhibiting this gene can prompt body’s natural defence mechanism to better fight the disease.

Mattias Collin, of Lund University, and Marc A. Williams, of the University of Rochester, praised the study and said that this might provide a new way to treat anthrax poisoning.

“This study has indeed identified a potential treasure trove in ClpX”, Colin and Williams wrote. (ANI)

Turning off oncogene may inhibit lung cancer stem cells’ growth

Washington, Sep 9 (ANI): A lung cancer oncogene, called PKCiota, is necessary for the proliferation of lung cancer stem cells, and turning it off could act as a key for the treatment of this deadly disease, according to scientists at the Mayo Clinic campus in Florida.

These stem cells are rare and powerful master cells that manufacture the other cells that make up lung tumours, and are resistant to chemotherapy treatment.

The study also shows that an agent, aurothiomalate, being tested at Mayo Clinic in a phase I clinical trial substantially inhibits growth of these cancer stem cells.

“Our data indicate that PKCiota is required for the earliest steps in the development of lung cancer, which is the expansion of tumor-initiating cells or cancer stem cells,” said the study’s senior author, Dr. Alan Fields.

“Lung cancer stem cells appear to be the major drivers in many common lung cancers, and in order for a therapeutic treatment to be effective, it has to disrupt these cancer stem cells. We show that aurothiomalate, the agent now being tested in lung cancer patients, can, in fact, target these cells,” he added.

While aurothiomalate was once used to treat rheumatoid arthritis, the researchers have now discovered that it can also target PKCiota.

Currently, the agent is being tested in patients at Mayo Clinic’s sites in Minnesota and Arizona and, based on this phase I trial, a phase II human clinical trial is planned to combine aurothiomalate with agents targeted at other molecules involved in cancer growth.

“We had previously shown that PKCiota is required to maintain tumor growth, but what this study sought to determine is whether PKCiota is involved in the initial steps of lung cancer development,” said Fields.

Fields said that, in mice, an oncogene known as Kras is thought to transform normal lung stem cells into cancer stem cells, thereby initiating lung cancer.

In the present study, the researchers established a strain of mice in which Kras can be activated at the same time that the PKCiota gene is inactivated.

They found that when the PKCiota gene is inactivated, Kras was unable to cause errant growth and expansion of lung stem cells in mice, the process that initiates tumour formation.

“What this told us is that Kras requires PKCiota to transform the lung stem cells and make them proliferate. In other words, PKCiota is downstream from Kras, and is necessary for Kras to initiate lung tumor formation,” said Fields.

After discovering that aurothiomalate disables PKCiota, the researchers tested whether this agent is effective against lung cancer that develops due to Kras mutation.

“The drug showed potent inhibitory effects on the Kras-dependent proliferation of lung cancer stem cells both in cell culture and in animals,” said Fields.

“That further suggests that a drug like aurothiomalate could have an effect on tumors that are dependent on either Kras or PKCiota for growth and survival, and that is potentially a lot of cancers.

Aurothiomalate appears to be one of the few drugs available that can effectively target these critical cancer stem cells. In the clinic, however, it is likely that aurothiomalate will be most effective when combined with other agents designed to target other tumor survival pathways,” he added.

The study has been published in Cancer Research. (ANI)

Fat-rich junk food may alter genes linked with type II diabetes

London, September 8 (ANI): A team of scientists in Sweden have warned that gorging too much on fat-rich junk food may cause drastic changes to a gene that helps muscle cells burn fat.

Juleen Zierath, of the Karolinska Institute in Stockholm, says that her team’s findings may help improve the scientific understanding of how type II diabetes develops in adulthood.

“Somehow, the environment plays on the genes we have,” says the lead researcher, adding that her study provides new clues to how this happens.

She says that it may be possible that the altered cells become so engorged with unburnt fat that they become “diabetic”, and stop accepting signals from the hormone insulin, which normally triggers the absorption of glucose from the bloodstream.

However, proving that components in the diet can permanently alter genes is itself a breakthrough, as it provides the first evidence that the food people eat may change the function of their DNA, a process scientifically known as “epigenetics”.

During the study, the researchers observed that the DNA itself remained unchanged, except for a masking process called methylation that can permanently mothball a gene by capping individual chemical units or bases.

Before the researchers undertook this research, they had already found in a previous study that muscle cells from people with type II diabetes showed such telltale epigenetic alterations to their DNA, particularly in the PGC-1 gene, which orchestrates metabolic programmes critical to the burning of fat in mitochondria, the chambers in cells that generate energy.

In the current study, the researchers achieved the most significant result when they exposed the healthy muscle cells to the edible fatty acid, palmitic acid.

The team found that the PGC-1 gene became methylated, just as it is in people with diabetes.

“The palmitic acid essentially switches off the gene,” New Scientist magazine quoted Zierath as saying.

She says that the fact that fat produces such an effect is highly significant, as it means that over-consumption of junk food may cause the same response.

“It suggests that if you eat a fat-rich diet, something in that – either the fat itself or the build up of metabolites – triggers the methylation of genes. The net effect is that it switches off the gene,” says Zierath.

The team’s analyses also reveal that the shutdown of PGC-1 led to inactivation of other genes vital for burning or transporting fat.

Zierath says that her team’s next step will be to find out how different diets affect the methylation status of PGC-1 and other genes vital for burning energy, hoping that their efforts will lead to the discovery of a potential mechanism by which type II diabetes develops.

A research article on her study has been published in the journal Cell Metabolism. (ANI)

Missing protein in rare genetic brain disorder restored

Washington, Sep 7 (ANI): By using protease inhibitors, researchers at the University of California-San Francisco (UCSF) have restored to normal levels a key protein that is involved in early brain development, and causes the rare brain disorder lissencephaly.

Reduced levels of the protein called LIS1 have been shown to cause lissencephaly, which is characterized by brain malformations, seizures, severe mental retardation and very early death in human infants.

The findings in mice offer a proof-of-principle that the genetic equivalent to human lissencephaly, also known as “smooth brain” disease, can be treated during pregnancy and effectively reversed to produce more normal offspring.

The researchers are hoping that this approach could also be used to treat other defects in utero, or even those manifesting after birth, when caused by a partial deficiency in one gene, according to Dr. Anthony Wynshaw-Boris.

“Researchers have not considered it possible to treat such a pervasive, early developmental brain disorder as lissencephaly. Not only were we able to show a clear cellular effect from using these protease inhibitors, but also were able to treat the disorder in utero,” Nature quoted Wynshaw-Boris as saying.

The work is the culmination of 15 years of collaborative research into the cause and mechanisms of lissencephaly, which is caused by a deletion or loss of one copy of the LIS1 gene, and affects an estimated one in 50,000-100,000 infants.

In 1998, the researchers reported of producing a mouse with the same mutation that displayed defective brain development.

The current research used these mice, and found that the protein calpain degrades the LIS1 protein to less than half its normal levels near the surface of the cells.

The team then used a specific small-molecule protease inhibitor of calpain in these mice.

At a cellular level, the protease inhibitors enabled LIS1 protein to be expressed at near-normal levels.

The team then gave daily injections of a calpain inhibitor to pregnant mice whose foetuses had the mouse-model of this defect.

They observed that the resulting offspring had more normal brains and showed no sign of mental retardation.

“This study is really a proof-of-principle not only for treating complex developmental brain disorders, but also for any disorder with reduced protein levels where proteases normally play some role in breaking down that protein. This will be much more difficult to apply to humans, because of the safety issues involved, but it could lead to new therapies that might be effective for a wide range of developmental disorders,” said the researchers.

The findings have been published in the journal Nature Medicine. (ANI)

Spare gene in fish provides raw materials for evolution of new Traits

Washington, September 4 (ANI): In a new research, scientists have discovered that a duplicate copy of a gene involved in embryonic development of fish has taken up a newer role in the evolution of fish scales.

Scientists have suspected that spare parts in the genome-extra copies of functional genes that arise when genes or whole genomes get duplicated-might sometimes provide the raw materials for the evolution of new traits.

Now, researchers say that they have discovered a prime example of this in fish.

The researchers show that a duplicate copy of a gene involved in embryonic development has taken up a newer and decidedly less essential role in the development of fish scales.

Zebrafish carrying a mutant version of that extra fibroblast growth factor receptor 1 (fgfr1) gene show decreases in their scale formation.

What’s more, the spare fgfr1 gene is at the root of similar scale loss seen in domesticated carp, which have been selectively bred by humans for the last 2,000 years.

“Our finding is an excellent case for (gene) duplication supporting diverse forms,” said Matthew Harris of the Max Planck Institute for Developmental Biology.

“By ‘tweaking’ the use of one of the two copies of the fish fgfr1, the teleost order that contains zebrafish and carp have a specialized ‘toolbox’ gene that now controls adult-specific variation in form,” added Nicolas Rohner, also of the Max Planck Institute.

Fish species outnumber all other vertebrates combined and include many with spectacular features to match the diverse environments in which they live, according to Harris and Rohner.

Teleost fish in particular represent the largest assemblage of vertebrates, comprising over 26,000 species with astonishing diversity in their form and physiology.

Although little is known about the genetic basis of that diversity, it is clear that gene duplication is commonplace within teleost groups, providing a source of genetic raw material for selection.

To further explore in the new study, the researchers first examined mutant strains of zebrafish in search of those with changes to their fins, skulls, or scales, all structures that tend to vary among species.

They focused their attention on one with fewer scales and in an unusual pattern-an abnormality they traced to fgfr1.

“We were surprised to find severe coding mutations in such an important developmental gene to cause an adult-specific and viable phenotype,” Harris said.

Further study showed the reason why: zebrafish maintain two copies of fgfr1 that function redundantly during embryonic development. One of those two genes is also required for the formation of the scales in juveniles. (ANI)

‘Master switch’ gene may help control obesity

Washington, Sept 4 (ANI): Scientists from University of Michigan claim to have discovered a gene, which when switched off, can control obesity in mice and help them remain thin.

According to Alan Saltiel, the Mary Sue Coleman Director of the U-M Life Sciences Institute, deleting the gene, called IKKE, appears to protect mice against conditions that, in humans, lead to Type 2 diabetes, which is associated with obesity.

He said that if follow-up studies confirm IKKE is tied to obesity in humans, the gene and the protein it will be prime targets for the development of drugs to treat obesity and diabetes.

“We’ve studied other genes associated with obesity – we call them ‘obesogenes’ – but this is the first one we’ve found that, when deleted, stops the animal from gaining weight,” said Saltiel, senior author of a paper.

“The fact that you can disrupt all the effects of a high-fat diet by deleting this one gene in mice is pretty interesting and surprising,” Saltiel added.

During the study, the high-fat-diet mice were fed a lard-like substance with 45 percent of its calories from fat. Control mice were fed standard chow with 4.5 percent of its calories from fat.

The gene IKKE produces a protein kinase also known as IKKE. The IKKE protein kinase appears to target proteins, which, in turn, control genes that regulate the mouse metabolism.

When the high-fat diet is fed to a normal mouse, IKKE protein-kinase levels rise, the metabolic rate slows, and the animal gains weight. In that situation, the IKKE protein kinase acts as a brake on the metabolism.

The new study showed that knockout mice placed on the high-fat diet did not gain weight, apparently because deleting the IKKE gene releases the metabolic brake, allowing it to speed up and burn more calories, instead of storing those calories as fat.

The new study is published in the journal Cell. (ANI)

Single gene behind essential tremor, Parkinson’s disease identified

Washington, September 2 (ANI): A single gene promotes development of essential tremor in some patients and Parkinson’s disease in others has been identified by an international team of researchers.

In a study report published in Parkinsonism and Related Disorders, Mayo Clinic researchers in Florida and their collaborators worldwide note that patients with essential tremor shake when they move, while those with Parkinson’s disease shake when they are at rest.

They further state that a variant in LINGO1, a gene involved in neuronal survival, is the first proven evidence of a common genetic component in the development of both disorders.

Analysing their findings, the researchers have come to the conclusion that mutations in this gene are potentially responsible for five percent of patients with Parkinson’s disease, and five percent of patients with essential tremor.

Lead researcher Dr. Carles Vilarino-Guell, of Mayo Clinic, said: “There is a mutation in the gene that must be causing or contributing to Parkinson’s disease in some people and essential tremor in others.”

He, however, added that that did not mean that people with essential tremor have an increased risk of developing Parkinson’s disease.

The findings are intriguing because “although essential tremor and Parkinson’s disease are considered to be different diseases, researchers have been arguing for a long time about whether essential tremor is a milder, preliminary form of Parkinson’s disease, and they have been looking for the genetic connection between these disorders,” he said.

“Now we know LINGO1 is the first gene identified,” he added.

The scientists have yet to identify any specific mutation or mutations on LINGO1 responsible for either disorder.

“The easiest explanation is that there are two separate and clearly distinct mutations in the gene contributing to the disorders. But because this gene doubles the risk of developing either disease and it is found at the same frequency in both diseases, it is possibly the same mutation,” Dr. Vilarino-Guell said.

“Both diseases are also affected by environmental factors, and that may influence which disorder a person would be more likely to develop,” he added. (ANI)

Smoking, overweighing up breast cancer risk

Washington, September 2 (ANI): A study conducted in Canada has reinforced the correlation between being overweight, smoking and breast cancer.

Published in the Journal of Cancer Epidemiology, the study is unique because it did not include subjects who were diagnosed for BRCA1 and BRCA2 gene mutations, which predispose women to breast cancer.

The study entirely focused on lifestyle factors like smoking, exercise, nutrition and weight.

All women analysed in the study were direct ancestors of the first French colonists.

“To our knowledge, this is the first study conducted on a sample of women without BRCA1 and BRCA2 gene mutations, which are often found in French-Canadian women,” said lead researcher Vishnee Bissonauth, a graduate of the Universite de Montreal’s Department of Nutrition, and a researcher at the Sainte-Justine University Hospital Research Center.

The study found that weight gains after the age of 20 increased the risk of breast cancer.

Where the weight gain was more than 15.5 kilos, the risk was found to increase by an average of 68 percent.

Risk increases depending on how late in life the weight gain occurs, according to the study.

Women who gained more than 10 kilos after age 30, or more than 5.5 kilos after age 40, were found to be almost twice as likely to suffer from breast cancer as a those whose weight was stable.

The study showed that the risk tripled if the body mass index was at its maximum after age 50.

Smoking a pack a day for nine years was also found to increase breast cancer risks by 59 percent.

Though the impact of smoking seemed to decrease for menopausal women, it remained at 50 percent.

Bissonauth stressed the need for more research into the correlation between smoking and breast cancer.

The researchers revealed that moderate physical activity appeared to decrease cancer risks by 52 percent for pre-menopausal and post-menopausal women.

The correlation was also observed for women who did intense physical activity, but the difference was not significant, said the lead researcher.

That finding, said Bissonauth, may be down to the fact that women who did moderate physical activity were more likely to do it regularly, while those who did intense physical activity were likely to quit after a few weeks.

“Cancer is a complex disease and can be latent for several years. Therefore, it is important to work on the factors we can control and to lead a healthy lifestyle, which means watching one’s weight, avoid smoking and doing regular exercise,” said Bissonauth. (ANI)

Gene behind gum disease, osteoporosis, arthritis identified

Washington, Aug 31 (ANI): An international team of researchers have identified a gene that is common in the development of gum disease, rheumatoid arthritis, and osteoporosis.

Experts at Hospital for Special Surgery say that their findings about the gene, called interferon regulator factor-8 (IRF-8), may lead to new treatments in future.

“The study doesn’t have immediate therapeutic applications, but it does open a new avenue of research that could help identify novel therapeutic approaches or interventions to treat diseases such as periodontitis, rheumatoid arthritis or osteoporosis,” said Nature magazine quoted Dr. Baohong Zhao, a research fellow in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery located in New York City, as saying.

The researchers discovered that downregulation of IRF-8 (meaning that the gene produces less IRF-8 protein) increases the production of cells called osteoclasts that are responsible for breaking down bone.

In humans and animals, bone formation and bone resorption are closely coupled processes involved in the normal remodelling of bone. Enhanced development of osteoclasts, however, can create canals and cavities that are hallmarks of diseases such as periodontitis, osteoporosis and rheumatoid arthritis.

The genome-wide study showed that the expression of IRF-8 was reduced by 75 percent in the initial phases of osteoclast development.

The genetically engineered mice deficient in IRF-8 had decreased bone mass and severe osteoporosis.

The researchers concluded that IRF-8 suppresses the production of osteoclasts.

“This is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis (production of osteoclasts),” said Zhao.

“We hope that the understanding of this gene can contribute to understanding the regulatory network of osteoclastogenesis and lead to new therapeutic approaches in the future,” Zhao added.

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

Counting duplicated genome segments now possible with new computational method

London, August 31 (ANI): Counting copies of duplicated genome sequences and doing initial analyses of their contents are possible with the aid of a new computational method, according to a study.

Led by scientists at the University of Washington (UW), the study suggests that the number of copies of particular DNA segments can differ from one person to the next.

The researchers use the term mrFAST, an acronym for micro-read Fast Alignment Search Tool, to refer to the novel method.

In their study report, they have highlighted the fact that segmental duplications in the human genome have been associated with susceptibility and resistance to disease.

The report points out that duplicated segments have been linked to such disorders as lupus, Crohn’s disease, mental retardation, schizophrenia, colour blindness, psoriasis, and age-related macular degeneration.

It adds that segmental duplications often contain duplicated genes, many of which have an unknown function, and that individuals have different numbers of copies of some of these duplications.

The researchers write that determining the number, content, and location of segmental duplications is an important step in understanding the health significance of gene copy-number variation.

“New computational methods, combined with next-generation DNA sequencing technology, has provided for the first time an accurate census of specific genes that exist in varying number of copies,” Nature magazine quoted Alkan as saying.

“This is a way to deal with some of the most complex regions of the human genome and do what might appear to be a simple thing: Count whether a person has one, two, three or more copies of a gene. In fact, such counting is surprisingly difficult,” said Kidd.

The researchers say that next-generation technology for sequencing the human genome has far greater detection power, and costs substantially less than the traditional sequencing method known as Sanger sequencing.

According to them, the new technologies are beginning to distinguish subtle dissimilarities between nearly identical gene copies.

“This can provide researchers with a more accurate assessment of specific gene content and insight into functional constraints,” Alkan said.

“The newer, faster genome sequencing platforms may eventually make it feasible to detect the full-spectrum of genomic variation among many individuals, including patients suffering from diseases of genetic origin. Next-generation technology and computational methods promise low cost, rapid sequencing of different individuals and may lead to a fuller understanding of the patterns and significance of human genetic variation,” Alkan added.

The analytical method they devised is already being tapped for the 1000 Genome Project, an international effort to catalog and compare the genomes of hundreds of people from around the world.

Alkan, Kidd, and their colleagues note that the ability to accurately and systematically determine the absolute copy number for any genomic segment is a notable step toward a true and complete picture of individual genomes, and how the genome shapes a person’s characteristics.

“The next challenge will be defining variation in the sequence content and the structural organization of these dynamic and important regions of the human genome,” they wrote.

A research article describing their study has been published in the journal Nature Genetics. (ANI)

New, improved zebrafish cloning method may further human health research

London, August 31 (ANI): In what may eventually prove very useful in human health research, scientists at Michigan State University have come up with a more efficient method to clone zebra fish.

What makes this work an important achievement is the fact that zebra fish, which have served as an excellent model for understanding normal development and birth defects for more than 20 years, are quickly becoming the animal of choice for many researchers.

“After the mouse, it is the most commonly used vertebrate in genetic studies. It is used in cancer research and cardiovascular research because they have many of the same genes we have,” Nature magazine quoted Jose Cibelli, an MSU professor of Animal Science, as saying.

While previous methods of cloning zebra fish have had very low success rates, the MSU researchers say that their novel method can increase the number of cloned fish that can be obtained from an adult fin cell or an embryonic tail clip increased by 2 percent to 13 percent, respectively.

What makes zebra fish so useful in research is their eggs are transparent and the fish’s development is easy to follow.

Improving on the techniques of zebra fish cloning also is important because currently only the mouse remains the best model for gene targeting.

“So far the mouse is the only one from which you can delete genes in a reliable fashion. What researchers do is mutate a gene, abolish its function completely, and then study the consequences,” Cibelli said.

A research article describing the novel technique has been published in the journal Nature Methods. (ANI)

How plant tissues know which end is their growing tip

Washington, August 30 (ANI): A team of scientists has silenced nine genes in a multicellular organism, which allowed them to discover molecular secrets of how certain plant tissues know which end is their growing tip, also referred to as polarized growth.

The research was carried out by biologist Magdalena Bezanilla and colleagues at the University of Massachusetts Amherst, US.

The biologists conducted these experiments in a moss, but the findings illuminate processes in two tissues-root hairs and pollen tubes-found in all seed plants.

Root hairs are extremely fine individual cells that grow out of a plant’s root, greatly increasing its surface area to collect water, essential minerals and nutrients.

Pollen tubes travel down the flower to fertilize the plant’s egg.

Scientists have “a very limited knowledge” at the molecular level of how such cells determine the direction they’re growing, according to Bezanilla.

Knowing how to interrupt pollen tube formation in plants such as corn and soybeans, for example, could help prevent genetically engineered crops from interbreeding with wild populations.

Aiding root hair growth could boost drought-resistance to other economically important plants.he researchers focused on two proteins, actin and formin.

Actin, in this case a kind of scaffold-builder needed to form root hairs and pollen tubes, forms filamentous polymers and is important for many cellular processes in species ranging from yeast to man. ormins, like actin, are found in many species and help to control actin polymer formation. Formins are critical for actin-based cellular processes.

Tools in a biologist’s kit can now remove the function of specific proteins-usually one or two at a time-to silence a gene, but in this study, the researchers succeeded in silencing a remarkable nine genes at one time.

Bezanilla and colleagues systematically silenced the many actin-regulating formins and determined which members of this protein family are needed to generate cells for proper tip growth.ther tools in the researchers’ kit are methods for re-introducing the silenced genes, either normal or modified versions.

By “swapping parts” from closely related formin proteins and measuring tip growing activity for each combination, her research group eventually concluded that only one intact subclass of formins drives normal growth and controls how the plant recognizes its growing tip.

“If you take away any part of the formin, tip growth stops,” said Bezanilla.

Interestingly, the researchers also discovered that this particular subclass of formins is the fastest yet known in any organism. (ANI)

Novel method to make safer human stem cells uses just one gene

London, Aug 29 (ANI): Inching closer to curing diseases like Parkinson’s using cells generated from a patient’s own body, researchers have successfully reprogrammed human nerve cells back to an embryo-like state by using just a single gene.

It is known that embryonic stem cells are pluripotent – they can develop into any of the body’s cell types.

But such cells are not available in large numbers, as they can only be harvested from a donated egg or embryo, and, for ethical reasons, most countries have laws restricting their use.

In 2006, Shinya Yamanaka and his colleagues at Kyoto University in Japan successfully made mouse cells pluripotent by reprogramming skin cells into a state like embryo cells.

They did so by using retroviruses to insert four genes – known as “factors” – into the cells’ DNA.

They repeated the trick a year later with human cells.

However, using genes and retroviruses in this way increases the risk of the cell becoming cancerous, not just because tinkering with DNA has that effect, but also because two of the four factors are known to cause cancer.

In a bid to make these promising cells in a safe way, Hans Scholer’s team at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, has been working to achieve pluripotency using fewer factors.

Last year, they did this with the two factors that do not cause cancer, and now they have simplified the recipe further, doing it with just one.

“Remarkably, it turns out that three of these four essential factors are already expressed in human neural stem cells – although not in skin cells – so we only needed to add one factor, OCT4,” New Scientist quoted Boris Greber, a member of the team, as saying.

He said that the cells from neural tissue are much easier to reprogram than skin cells, and are less prone to mutations.

It is much harder to get a sample of neural stem cells than skin cells, as it can be done via extracting the cells from the dental pulp of teeth, said Greber.

Inserting even one gene into the chromosome of a cell still permanently modifies its DNA, which is why the new method will remain a lab tool instead of being allowed in the clinic.

However, the researchers are hoping that it will help them improve methods for producing embryonic stem cells.

“Ideally, we will be able to find a chemical that does the same job of expressing the factor without the need for a gene,” said Greber.

Earlier this year, researchers in California managed just that when they reprogrammed mouse fibroblasts using a cocktail of proteins.

That technique did not involve inserting genes, and, thus, shouldn’t raise the cancer risk. But that was far less efficient.

“Without stable intervention using viruses, the frequency of reprogramming goes down and you have to wait a long time. We don’t have the perfect method yet,” said Greber.

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