AT ONCE DATA

South Australia bioscience incubator launched

2008-10-25T20:41:00.000+05:30

South Australia bioscience incubator launched

SOUTH Australia's purpose-built bioscience incubator is up and running after SA Premier Mike Rann formally opened the facility this morning.

Photo courtesy of: Drew Lenman and Bio Innovation SA

The $12.9 million BioSA Incubator, which will be home to six early-stage tenants, is located in the state's high-technology hub in Therbarton, just west of the Adelaide central business district.

Rann said the incubator would help to fast-track the growth of the state's bioscience industry.

“The $12.9 million [BioSA Incubator] is unique in Australia – with a combination of tailored laboratories, office space and conference facilities," he said.

The BioSA Incubator is fully occupied already, with the Centre for Pharmaceutical Research, Jurlique Research, Pharmaceutical Packaging Products, Reproductive Health Sciences, Signostics and contract research company vivoPharm the inaugural tenants.

The facility is modelled on successful similar incubators in Europe, and is situated in proximity to more established South Australian life science companies Bionomics, Hospira and TGR Biosciences.

SA Science and Information Economy Minister Paul Caica said the precinct would help lure other life science companies to the state.

“Bringing businesses together in the BioSA Incubator will help lure further venture capital investment into a rapidly expanding sector," he said.

“It creates a huge advantage for South Australia's bioscience sector. It will not only foster our local bioscience start-ups but has the potential to encourage bioscience companies from other parts of Australia to move their operations to Adelaide."

Researchers Report Advances in Cell Conversion Technique

2008-08-28T18:28:00.000+05:30

Researchers Report Advances in Cell Conversion Technique

By NICHOLAS WADE

Biologists at Harvard have converted cells from a mouse’s pancreas into the insulin-producing cells that are destroyed in diabetes, suggesting that the natural barriers between the body’s cell types may not be as immutable as supposed.

This and other recent experiments raise the possibility that a patient’s healthy cells might be transformed into the type lost to a disease far more simply and cheaply than in the cumbersome proposals involving stem cells.

The new field depends on capturing master proteins called transcription factors that control which sets of genes are active in a cell and thus what properties the cell will possess. Each type of cell is thought to have a special set of transcription factors.

Last year a Japanese biologist, Shinya Yamanaka, showed that by inserting four transcription factors into an adult cell he could return it to its embryonic state.

In a variation of this technique, a team led by Qiao Zhou and Douglas A. Melton at Harvard has now identified three transcription factors active in the insulin-producing beta cells of the pancreas.

They hitched the genes for these three factors onto a virus that infects another type of pancreatic cell, known as an exocrine cell. In mice made diabetic by a drug that kills beta cells, the transformed exocrine cells generated insulin, allowing the mice to enjoy “a significant and long-lasting improvement” in their diabetic state, the researchers are reporting Thursday in the journal Nature.

Many steps remain before the technique could be considered for human use.

Besides producing insulin, the transformed exocrine cells looked like beta cells and ceased making proteins typical of exocrine cells. But they did not organize themselves into the pancreatic structures known as islets where beta cells usually cluster. The researchers claim only to have made “cells that closely resemble beta cells.”

Even so, Robert Blelloch, a cell biologist at the University of California, San Francisco, said, the Harvard experiment was “a very nice story — it’s pretty impressive that you can make such a switch just by adding three factors to a quite different cell type.”

Last month Patrick Seale and Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston showed how with a single transcription factor they could make white fat cells generate brown fat cells, a very different type of cell.

The Harvard work “is not occurring in a vacuum, but it’s a very important piece of work,” Dr. Blelloch said.

Two genes may prevent HIV infection: Canadian research centre

2008-07-19T11:55:00.000+05:30

Scientists have isolated two genes which may prevent people from contracting HIV or at least slow the rate at which they develop AIDS, a new study has found.

The genes were isolated by comparing the genetic profiles of people in their first year of HIV infection with those who managed to resist infection despite repeated exposure to the virus.

The "good" versions of the two genes were present in 12.2 percent of those who resisted infection compared with only 2.7 of patients in primary HIV infection.

Researchers are not yet sure how this protection works.

One of the genes codes for a receptor on the surface of the immune system's natural killer cells which destroy infected cells in the body.

The other codes for a protein which binds the first gene and dampens the natural killer cell activity.

The most likely explanation is that HIV prevents the protein that dampens the killer cell activity from being expressed, allowing the killer cells to destroy cells infected with HIV.

Since this can happen very soon after the initial infection, people carrying those genes may be able to more efficiently destroy infected cells and lower their chances of developing AIDS.

"More research is needed to determine the exact mechanism behind the protection we have observed, but these findings have revealed a promising avenue," said co-author Nicole Bernard of the Research Institute of the McGill University Health Centre in Montreal.

"In the future, our findings could be used to somehow 'boost' the innate immune system and thus fight the virus as soon as it enters the body."

The study was published Wednesday in the journal AIDS.

Kidney transplants less successful at night

2008-07-15T19:14:00.000+05:30

Study at Bonn University Clinic suggests delaying operations till the next day

Kidney transplants should be carried out during the day if possible. At least this is the conclusion suggested by a survey just published by urologists and internists at the University of Bonn (Transplantation Proceedings, vol. 40, p. 1341 ff.). Hence operations carried out at night require a further operation more than twice as often as other operations. Moreover, the risk of premature failure of the transplant is higher with operations taking place at night. The reason is probably that the surgeon is more alert and focused during the day. Particularly with a complicated procedure such as a transplant, surgical skill is a critical factor for success. Still, currently every third kidney transplant is performed at night, as donor organs should be as fresh as possible.

The medics from Dr. Guido Fechner and Professor Stefan Müller's Bonn team scrutinised a total of 260 kidney transplants. Over 60 per cent had been carried out during the day, the remainder between eight in the evening and eight o'clock in the morning. More than 16 per cent of all the 'night kidneys' had to be operated on a second time in the month following the transplant due to surgical complications. With the 'day kidneys', the complications rate was significantly less, being over six per cent.

On average transplanted kidneys last nine years, but there are also transplants that still work well after more than 20 years. The time when the operation took place here too seems to be a critical factor. 'For "day kidneys" there is a higher than 90 per cent chance that they will function flawlessly even five years after the transplant,' Dr. Guido Fechner explains. 'With "night kidneys" the figure is only 80 per cent.'

The reason presumed for this is that kidney transplants are comparatively complicated procedures. Accordingly, they require a brain that is alert. However, the donated organs are often transplanted during the night shift. 'It was long believed that kidneys had to be as fresh as possible, at all cost, for the transplant to be successful,' Guido Fechner says. It is currently perceived as ideal if the organ is reinserted 18 hours after its removal at the latest. 'Rescheduling a kidney transplant within this time frame, say from 5 a.m. to 8 a.m., without the transplant suffering, is definitely feasible,' he emphasises. 'Instead operations are performed as early as possible, even if that means the urologist has to work at night.'

An alternative is a living kidney donation during which the kidney is taken from a living donor and is immediately inserted into the recipicent. This always happens during the day

Families with children without a genetic or gestational link to their parents are functioning well

2008-07-06T10:21:00.000+05:30

The emotional well-being of families where children lack a genetic or gestational link to one or both of their parents � where the children have been conceived through surrogacy, egg donation or donor insemination � has long been a subject of debate. Now, in the first worldwide study of this issue, British scientists have shown that relationships within such families appear to be functioning well, and that there are few differences between them and families in whom children were conceived naturally.

Miss Polly Casey, from the Centre for Family Research, Cambridge University, UK, will tell the 24th annual conference of the European Society of Human Reproduction and Embryology this week that the study found that the egg donation, surrogacy, and donor insemination families showed more similarities than differences in the psychological well-being of the parents, the quality of parent-child relationships, and the psychological adjustment of the child. The potential negative consequences for such children have long been the subject of debate, with concern that parents may behave less positively towards them, and that the child may not feel fully accepted as part of the family.

The researchers have been following up 39 surrogacy families, 43 donor insemination families, 46 egg donation families, and 70 families where children had been conceived naturally. So far the data have been collected up to the time that the children are seven years old, but the researchers hope to continue following up these families for as long as possible. The findings to be presented are from approximately half of the families where the child has reached seven years old.

"We asked questions in a number of different areas to both parents and children," said Miss Casey. "We looked at such things as parental psychological wellbeing and parent-child relationships, and also questioned the mothers on any emotional and behavioural problems they felt that the child might have." In addition, researchers used the standardised Strengths and Difficulties Questionnaire, which produces an overall score of the child's adjustment along with individual scores for such things as conduct problems and emotional difficulties. Teachers completed the same questionnaire providing an independent assessment of children's adjustment.

The children's perception of the emotional closeness to their parents was also assessed. "We gave them a blank 'map' with concentric circles and told them that they were at the centre," said Miss Casey. "We then asked them to complete the map by placing family members and friends in the circle that represented the emotional closeness of each relationship."

A pictorial scale of perceived competence and social acceptance was also administered to the children. Pictures of children in different situations were presented by the researcher, against which the children were asked to evaluate themselves. This provided a measure of their cognitive competence, physical competence, maternal acceptance, and acceptance by their peers, all of which have been shown to be associated with the development of self-esteem in later childhood.

"We found that the family types did not differ in the overall quality of the relationship between mothers and their children and fathers and their children," said Miss Casey. "But the analysis did show some differences in the mother-child relationship between family types. For example, we found a minor trend towards greater sensitivity to their child's anxieties and worries among the egg donation and surrogacy mothers compared with the donor insemination mothers, and there was a minor trend towards greater emotional over-involvement with their children, and towards greater disciplinary indulgence, by assisted reproduction mothers as opposed to natural conception mothers."

The children in the different family types did not differ with respect to the Strengths and Difficulties Questionnaire as completed by their mothers. However, when the teachers completed the same exercise, a significant difference emerged. "The teachers reported a higher level of emotional difficulties among the assisted reproduction as opposed to the naturally conceived children, although these were not abnormally high," said Miss Casey.

The children's own assessments showed no significant difference between family types for self-esteem. In assessments of family relationships, there was no significant difference between the assisted reproduction children and the naturally conceived children in the location of their mother or father in the family maps, with 85% of assisted reproduction children and 88% of those naturally conceived placing their mother in the closest circle, and 73% of assisted reproduction and 76% of naturally conceived children placing their father in the closest circle.

"However," said Miss Casey "at the time of the child's seventh birthday, only 39% of egg donation parents, 29% of donor insemination parents, and 89% of surrogacy parents had told their children about the nature of their conception. This is markedly less than the proportion of parents who, when their child was one year old, reported that they planned to disclose this information � 56%, 46% and 100% of egg donation, donor insemination and surrogacy parents respectively," she said.

There are numerous and complex reasons for parents deciding not to inform children, the researchers say, including a desire to protect the father, since the mother may not want others to know about his infertility, and the fear that a child may feel less love for the non-genetic parent. "Previous studies have shown that parents want to protect their child, fearing that disclosure may upset them and have an adverse effect on parent-child relationships," said Miss Casey.

Analysis of the differences in the quality of parent-child relationships and the psychological adjustment of the child found significant disparities between those families who had disclosed information regarding conception, and those who had not. "Those mothers who had told their children about their conception showed higher levels of sensitivity to the child and, although there was no statistical difference, we also found that fathers in disclosing families tended to show greater warmth towards their children," said Miss Casey.

Mothers who had been open with children also reported greater marital satisfaction. The researchers also reported a non-significant trend towards lower levels of emotional difficulties among the children who had been told, as assessed by teachers.

"This study shows that families with children without a genetic or gestational link between the parents continue to function well as the child reaches early school years," said Miss Casey. "Where differences in mother-child relationship were found between the different family types, these were reflected in more involved parenting by the assisted reproduction mothers. Those who lacked a genetic or gestational relationship with their child � the egg donation and surrogacy mothers � tended towards greater involvement, as opposed to the donor insemination mothers. These findings are not surprising given the difficulties that the women underwent in achieving motherhood.

"The children themselves showed positive psychological adjustment and did not differ as to family type. We were particularly interested to find that, according to teachers, those children who had been told of their origins tended to do slightly better emotionally than those who had not, though of course this may simply be due to better communication within the family generally. We believe that our findings will benefit clinicians who counsel prospective parents about the implications of disclosing the means of conception to their child, as well as to parents, and, indeed, children, who will be able to learn from the experience of others in similar situations. It is essential that all developments in assisted reproduction are accompanied by studies of the wellbeing of the parents and children involved," said Miss Casey.

Mechanism for Hypertension, Insulin Resistance, and Immune Suppression in Rats Revealed

2008-07-01T15:12:00.000+05:30

Researchers have discovered a molecular mechanism in a strain of rats that explains why metabolic disorders like hypertension and diabetes often arise together in mammals. The University of California, San Diego’s Jacobs School of Engineering also showed that a common antibiotic reversed the animals’ symptoms of high blood pressure, insulin resistance, and immune suppression.

These studies indicate that hypertension and cell dysfunctions associated with metabolic syndrome may be part of an enzymatic auto-digestion process in which proteases in our body become uncontrolled and break down proteins, reports Geert Schmid-Schnbein, a professor of bioengineering.

Spontaneously hypertensive rats (SHR), a strain predisposed to develop high blood pressure, were used in the study. These rodents, like many people, develop other metabolic complications when high blood pressure arises.

The investigators found significant levels of proteases in the animals’ circulation. Natural enzyme inhibitors found in normal healthy rats did not lower the level of protease activity in the SHR strain to normal levels.

In these hypertensive rat, enzymes cleaved extracellular portions of several protein receptors such as the insulin receptor. Insulin could thus no longer bind and facilitate normal metabolism of glucose, the scientists report. The CD18 receptor, a binding receptor on the surface of infection-fighting leukocytes, was also cleaved. With the loss of CD18 receptors, leukocytes of the SHR animals were unable to bind to the wall of blood vessels, resulting in a compromised immune system, according to the researchers.

The team went on to test whether a protease-blocking drug doxycycline could reverse the multiple metabolic complications. They found that the compound halted the activity of certain proteases in the SHR rat strain.

The scientists had observed that protein receptors on the surface of SHR cells become clipped off as the animals develop hypertension. They found that after several weeks of ingesting doxycycline, however, the SHR rats developed cells that had normal CD18 and insulin receptors. The animals’ metabolic conditions simultaneously improved, blood pressure normalized, and symptoms of immune suppression disappeared, they report.

The study is published on June 30 in the online version of Hypertension.

More severe bone infections, health complications in children linked to MRSA, researchers find

2008-06-30T18:43:00.000+05:30

DALLAS – June 30, 2008 – The emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a major pathogen has led to more complications and longer hospital stays for children with acute bone infections, UT Southwestern Medical Center researchers report.

Acute osteomyelitis, a bone infection that predominantly occurs in children, is usually caused by the staph bacteria. Treatment has traditionally been straightforward because most S. aureus bacteria can be killed with existing antibiotics.

Recently, however, more children with osteomyelitis have been developing the more severe, antibiotic-resistant, community-associated MRSA, resulting in more complications and prolonged antibiotic therapy and hospital stays.

"This study shows the transition from the normal S. aureus to the methicillin-resistant one that everybody calls the superbug," said Dr. Octavio Ramilo, professor of pediatrics at UT Southwestern and senior author of a study available online and in the July/August issue of the Journal of Pediatric Orthopaedics. "What's important about this is not only that MRSA infections are harder to treat because they are more resistant to the traditional antibiotics, but they are also more aggressive and cause more severe disease manifestations. This is reflected very clearly in this study."

Dr. Asunción Mejías, assistant professor of pediatrics and co-lead author, said MRSA isn't a new problem among children.

"But the MRSA that we used to see was acquired in the hospital," she said. "This is a different strain that patients acquire in the community. Now, we see kids with osteomyelitis who have bone abscesses in the legs and who get blood clots that lead to pulmonary embolisms.

"We don't want to alarm parents, but kids who limp or have backaches and fever after an otherwise minor trauma need to be evaluated by a physician," Dr. Mejías said.

Dr. Ramilo said osteomyelitis might be more common in children because kids tend to be more accident-prone. Most commonly, the bones get infected when bacteria reach the bone through the blood supply. It is thought that minor trauma to the bone facilitates the start of the infection.

For the study, researchers culled the medical records of 290 children admitted to Children's Medical Center Dallas between January 1999 and December 2003 with acute osteomyelitis. The median age of those surveyed was 6 years and most children were white or Hispanic. Sixty percent were male. Symptoms such as localized pain, fever, tenderness, swelling and limping were observed in more than half the patients.

The researchers divided the patient population into two groups (January 1999 to June 2001 and July 2001 to December 2003) to verify whether MRSA infections were becoming more common and more severe.

They then compared patients with MRSA osteomyelitis to children with non-MRSA osteomyelitis, which included those with methicillin-sensitive S. aureus (MSSA) infections. They also reviewed outcomes, including duration of fever, the type and length of antibiotic therapy, and the frequency of complications, such as muscle inflammation, bone abscesses, disseminated disease and the need to drain the bone surgically.

Though the clinical characteristics of the participants didn't change significantly between the first and second study periods, children who were treated in the latter period for osteomyelitis fared far worse, possibly because MRSA infections were more common, Dr. Ramilo said.

For example, in the second study period, bone abscesses were observed in 69 percent of the patients with MRSA osteomyelitis versus 26 percent among those with MSSA infections. Children admitted with MRSA osteomyelitis during the second study period also spent an average of 42 days on antibiotics, almost two weeks longer than those diagnosed with MSSA.

Dr. Ramilo said the number of children who needed surgery was also striking. Seventy-eight percent of the patients with MRSA required surgery, compared with 49 percent of those with MSSA.

He said the findings underscore the need for multicenter studies to identify the best antibiotic regimens as well as the best surgical approaches for complications.

"For now, the key is to treat the infection as early as possible with appropriate antibiotics and if needed, surgical drainage of the bone," Dr. Ramilo said.

Higher temperatures helped new strain of West Nile virus spread

2008-06-27T09:55:00.000+05:30

Findings help explain spread of virus strain responsible for largest US epidemics

SANTA CRUZ, CA--Higher temperatures helped a new strain of West Nile virus invade and spread across North America, according to a study published in the June 27 issue of the journal PLoS Pathogens.

"The study shows that the warmer the temperature, the greater the advantage of the new strain. It also indicates that increases in temperatures due to global climate change would have major effects on transmission of the virus," said A. Marm Kilpatrick, first author of the paper and a senior research scientist for the Consortium for Conservation Medicine.

Kilpatrick, now an assistant professor of ecology and evolutionary biology at the University of California, Santa Cruz, joined with Laura Kramer and others at the New York State Department of Health's Wadsworth Center to conduct the study, which examined the effects of different temperatures on the transmission of two strains of West Nile virus.

The first occurrence of West Nile virus in North America was in New York City in 1999, when it caused a die-off of crows and other birds and 62 reported cases of human infections, including 7 deaths. In the two years after the introduction of the virus, the rate of transmission was relatively low. As it spread along the Atlantic seaboard, there were only 21 reported human cases in 2000 and 66 in 2001.

In 2002, however, a new strain of the virus emerged and rapidly spread throughout North America, completely displacing the old strain by 2005. Coincident with the spread of this new strain were two of the largest epidemics of West Nile virus recorded to date in North America, with 4,582 cases reported in 2002, 11,356 cases in 2003, and more than 270 deaths in both years. Since then, the number of reported cases per year has ranged from 2,500 to nearly 6,000, with more than 100 deaths each year.

Kilpatrick and Kramer set out to determine how the new strain of West Nile virus had displaced the first strain, and what effect temperature had on transmission by mosquitoes. They used laboratory tests to determine how soon mosquitoes are capable of transmitting the virus after feeding on infected blood. The results showed that the new strain is more efficiently transmitted than the older strain, and the advantage of the new strain increases with higher temperatures.

For both strains, increases in temperature greatly accelerated transmission by increasing the efficiency of viral replication in the mosquitoes. As a result, temperature increases of just a few degrees due to global warming could sharply accelerate transmission of the virus and possibly lead to more severe epidemics of West Nile virus in some cooler regions, Kilpatrick said. The researchers used the results to develop a model to predict the impact of increasing temperatures on West Nile virus transmission by mosquitoes.

"A previous study in our lab demonstrated that the new strain of the virus was more efficient at replicating in mosquitoes, which may have increased the intensity of epidemics in the field," Kramer said. "We wanted to examine whether temperature might have played a role in the invasion of the new strain, and whether its success may have been related to increasing temperatures."

Kramer's lab performed a series of studies that involved infecting one group of mosquitoes with the introduced 1999 strain of West Nile virus and siblings with the recently evolved strain. After holding the mosquitoes at different temperatures and for different lengths of time, researchers determined what fraction could transmit the virus. They found that the new strain was more efficient than the introduced strain at nearly all temperatures and time points after infection.

Kilpatrick, who analyzed the data and developed models to predict the impact of temperature on transmission, said the results provide a striking example of how climate and evolution can interact to increase the transmission of this virus. "These results also suggest that relatively small increases in temperature can have large impacts, due to the nonlinear acceleration of transmission with temperature," he said.

"This study shows how direct the impacts of climate change could be for us all," said Peter Daszak, executive director of the Consortium for Conservation Medicine, based at Wildlife Trust in New York. "It isn't just about a rise in sea level or the melting of a glacier in Alaska--it's about our health and our welfare."

BIO 2008: Comparing stem cells Joint NSW/Victorian project to compare three types of stem cells

2008-06-24T16:34:00.000+05:30

Scientists from Sydney IVF and the Australian Stem Cell Centre (ASCC) in Melbourne have launched a project to characterise and compare induced pluripotent stem cells, human embryonic stem cells and stem cells derived from somatic cell nuclear transfer.

The aim of the project is to develop a routine, repeatable way of making patient-specific stem cells within current legislative guidelines.

The NSW Minister for Science and Medical Research, Verity Firth, and the Victorian Minister for Innovation, Gavin Jennings, made the announcement today at the BIO 2008 convention in San Diego.

Each government has pledged $550,000 to the project. NSW will fund Sydney IVF to undertake the SCNT work, while Victoria has funded the ASCC to perform the characterisation and comparison of the stem cells.

The ASCC recently announced it was the first international group to import iPS cells, licensing them from Professor James Thomson at the University of Wisconsin. Thomson described the development of iPS cells in one of two ground-breaking papers in November last year.

"The combination of the international quality talent and significant resources of these two collaborative partners gives this project the potential to provide world-first advancements in these new biological frontiers," Firth said.

Firth, on her first trip to BIO since becoming a minister 18 months ago, said the project was a collaboration not only between scientists but between governments.

"We have real excellence in stem cell research both in NSW and Victoria," she said. "One thing you learn at BIO is that we are Australia here - it's a bit silly for the states to compete."

DNA study unlocks mystery to diverse traits in dogs

2008-06-22T15:34:00.000+05:30

ROCKVILLE, MD, June 22, 2008 � What makes a pointer point, a sheep dog herd, and a retriever retrieve? Why do Yorkshire terriers live longer than Great Danes? And how can a tiny Chihuahua possibly be related to a Great Dane?

Dogs vary in size, shape, color, coat length and behavior more than any other animal and until now, this variance has largely been unexplained. Now, scientists have developed a method to identify the genetic basis for this diversity that may have far-reaching benefits for dogs and their owners.

In the cover story of tomorrow's edition of the science journal Genetics, research reveals locations in a dog's DNA that contain genes that scientists believe contribute to differences in body and skull shape, weight, fur color and length � and possibly even behavior, trainability and longevity.

"This exciting breakthrough, made possible by working with leaders in canine genetics, is helping us piece together the canine genome puzzle which will ultimately translate into potential benefit for dogs and their owners," said study co-author Paul G. Jones, PhD, a Mars Veterinary� genetics researcher at the Waltham� Centre for Pet Nutrition � part of Mars� Incorporated, a world leader in pet care that has been studying canine genetic science for the past eight years. "By applying this research approach, we may be able to decipher how genes contribute to physical or behavioral traits that affect many breeds."

Dogs originally derived from the wolf more than 15,000 years ago � a blink of the eye in evolutionary terms. Selective breeding produced dogs with physical and behavioral traits that were well suited to the needs or desires of their human owners, such as herding or hunting ability, coat color and body and skull shape and size. This resulted in the massive variance seen among the more than 350 distinct breeds that make up today's dog population. Until now, the genetic drivers of this diversity have intrigued scientists who have been trying to explain how and why the difference in physical and behavioral traits in dogs changed so rapidly from its wolf origins.

An international team of researchers, which included scientists at the National Human Genome Research Institute, the University of Utah, Sundowners Kennels in Gilroy, California and Mars' Waltham Center for Pet Nutrition in the United Kingdom, studied simple genetic markers known as Single Nucleotide Polymorphisms, or SNPs, to find places in the dog genome that correlate with breed traits. Because many traits are "stereotyped" � or fixed within breeds � researchers can zero in on these "hot spots" to see what specific genes are in the area that might contribute to differences in traits.

The research used 13,000 dog DNA samples provided by Mars Veterinary, which holds one of the most comprehensive canine DNA banks in the world. This collection has been built up with the help of pet owners who have consented to their pets providing cheek swabs and blood samples for the database. Mars' DNA bank allowed the study to cover most of the American Kennel Club recognized breeds that span a wide variety of physical and behavioral traits and differences in longevity.

"With further refinement and additional data, this method could be used to tailor products that may benefit the health of pets," Jones said. "Pet owners and veterinarians may be able to develop better care regimes based on this knowledge. In addition, genetic information about behavioral traits, such as trainability and temperament, could also help veterinarians identify the most lifestyle-appropriate pet for an owner."

This research may also have implications for human health, as dogs suffer from many of the same diseases that we do.

Self-assembled Viruses Efficiently Carry Genes And Drug Molecules Into Tumor Cells

2008-06-20T11:39:00.000+05:30

ScienceDaily (June 20, 2008) — Viruses are true experts at importing genetic material into the cells of an infected organism. This trait is now being exploited for gene therapy, in which genes are brought into the cells of a patient to treat genetic diseases or genetic defects. Korean researchers have now made an artificial virus. As described in the journal Angewandte Chemie, they have been able to use it to transport both genes and drugs into the interior of cancer cells.

Natural viruses are extremely effective at transporting genes into cells for gene therapy; their disadvantage is that they can initiate an immune response or cause cancer. Artificial viruses do not have these side effects, but are not especially effective because their size and shape are very difficult to control—but crucial to their effectiveness. A research team headed by Myongsoo Lee has now developed a new strategy that allows the artificial viruses to maintain a defined form and size.

The researchers started with a ribbonlike protein structure (β-sheet) as their template. The protein ribbons organized themselves into a defined threadlike double layer that sets the shape and size. Coupled to the outside are “protein arms” that bind short RNA helices and embed them. If this RNA is made complementary to a specific gene sequence, it can very specifically block the reading of this gene. Known as small interfering RNAs (siRNA), these sequences represent a promising approach to gene therapy.

Glucose building blocks on the surfaes of the artificial viruses should improve binding of the artificial virus to the glucose transporters on the surfaces of the target cells. These transporters are present in nearly all mammalian cells. Tumor cells have an especially large number of these transporters.

Trials with a line of human cancer cells demonstrated that the artificial viruses very effectively transport an siRNA and block the target gene.

In addition, the researchers were able to attach hydrophobic (water repellant) molecules—for demonstration purposes a dye—to the artificial viruses. The dye was transported into the nuclei of tumor cells. This result is particularly interesting because the nucleus is the target for many important antitumor agents.

Zebra's Stripes, Butterfly's Wings: How Do Biological Patterns Emerge?

2008-06-20T11:13:00.000+05:30

ScienceDaily (June 20, 2008) — A zebra’s stripes, a seashell’s spirals, a butterfly’s wings: these are all examples of patterns in nature. The formation of patterns is a puzzle for mathematicians and biologists alike. How does the delicate design of a butterfly’s wings come from a single fertilized egg? How does pattern emerge out of no pattern?

Using computer models and live cells, researchers at Johns Hopkins have discovered a specific pattern that can direct cell movement and may help us understand how metastatic cancer cells move.

“Pattern formation is a classic problem in embryology,” says Denise Montell, Ph.D., a professor of biological chemistry at Hopkins. “At some point, cells in an embryo must separate into those that will become heart cells, liver cells, blood cells and so on. Although this has been studied for years, there is still a lot we don’t understand.”

As an example of pattern formation, the researchers studied the process of how about six cells in the fruit fly distinguish themselves from neighboring cells and move from one location in the ovary to another during egg development. “In order for this cell migration to happen, you have to have cells that go and cells that stay,” says Montell. “There must be a clear distinction — a separation between different types of cells, which on the surface look the same.”

Previous work identified a specific signal necessary for getting these fly egg cells to move; the problem is that this signal is “graded.” Like drops of ink spreading out on wet paper, this signal travels in between surrounding cells, gradually fading away as it moves outwards. But clear lines are required for pattern formation — there is no grey area between a zebra’s black and white stripes, between heart and liver cells and, in this case, between migrating cells and those that stay put.

How are graded signals converted to a clear move or stay signal? By examining flies containing mutations in different genes, the researchers discovered that one gene in particular, called apontic, is important for converting a graded signal. “When apontic is mutated, the distinction between migrating and nonmigrating cells is fuzzy,” says Michelle Starz-Gaiano, Ph.D., a postdoctoral fellow in biological chemistry. “In these mutants, we see a lot of cases where migrating cells do not properly detach from their neighbors but instead drag them along as they move away.” This showed that the graded signal alone was not sufficient to kick-start the proper number of cells, but instead needed help from apontic.

Once the team discovered that apontic is important for getting these cells to move, they set out to figure out how apontic works. Collaborating with mathematician Hans Meinhardt, Ph.D., a professor emeritus at the Max Planck Institute in Germany, they designed a computer model that could simulate how graded signals are converted to commands that tell cells to move or to stay.

By making certain assumptions about each gene and assigning functions to each protein, the team built a simple circuit that can predict a cell’s behavior using the graded signal, apontic, and another previously discovered protein called slbo (pronounced “slow-bo”). The computer model shows that in a cell, the graded signal turns on both apontic and slbo. But apontic and slbo work against and battle each other: when one gains a slight advantage, the other weakens, which in turn causes the first to gain an even bigger advantage. This continues until one dominates in each cell. If slbo wins, the cell moves but if apontic wins, the cell stays put; thus a clear separation between move or stay is achieved.

“Not only is this a new solution to the problem of how to create a pattern out of no pattern, but we have also discovered that apontic is a new regulator of cell migration,” says Montell.

Cell migration likely underlies the spreading of cancer cells beyond an original tumor to other areas of the body. Understanding and therefore being able to manipulate the cell migration pathway could potentially prevent the development of these new tumors. At this stage, Montell says, “it’s more about just understanding what the positive and negative regulators of cell migration are.”

The research was funded by the American Cancer Society and the National Institutes of Health.

This study was published in the May 13 issue of Developmental Cell. Authors on the paper are Starz-Gaiano, Mariana Melani, Xiaobo Wang, and Montell, all of Hopkins; and Hans Meinhardt of the Max-Planck-Institut, Tübingen, Germany.

Biotech crops seen helping to feed hungry world

2008-06-19T11:23:00.000+05:30

SAN DIEGO (Reuters) - Biotechnology in agricultural will be key to feeding a growing world population and overcoming climate challenges like crop-killing droughts, according to a group of leading industry players.

"It is critical we keep moving forward," said Thomas West, a director of biotechnology affairs at DuPont, interviewed on the sidelines of a biotechnology conference in San Diego. "We have to yield and produce our way out of this."

DuPont believes it can increase corn and soybean yields by 40 percent over the next decade. Corn seeds that now average about 150 bushels per acre could be at well over 200 bushels an acre, for example, DuPont officials said.

Crop shortages this year have sparked riots in some countries and steep price hikes in markets around the globe, and questions about how to address those issues were the subject of several meetings at the BIO International Convention being held this week.

Despite persistent reluctance in many nations and from some consumer and environmental groups, genetically modified crops, -- and the fortunes of the companies that make them -- have been on the rise. Growing food and biofuel demands have been helping push growth.

By using conventional and biotech genetic modification, crops can be made to yield more in optimum as well as harsh weather conditions, can be made healthier, and can be developed in ways that create more energy for use in ethanol production, according to the biotech proponents.

"You can bring a number to tools to bear with biotechnology to solve problems," said Syngenta seeds executive industry relations head director Jack Bernens. "As food prices increase ... it certainly brings a more practical perspective to the debate."

Syngenta is focusing on drought-resistant corn that it hopes to bring to market as early as 2014, as well as other traits to increase yields and protect plants from insect damage. Disease-resistant biotech wheat is also being developed.

Syngenta and other industry players are also developing biotech crops that need less fertilizer, and corn that more efficiently can be turned into ethanol.

Bayer CropScience, a unit of Germany's Bayer AG, has ongoing field trials with biotech canola that performs well even in drought conditions, said Bayer crop productivity group leader Michael Metzlaff.

Water scarcity is a problem seen doubling in severity over the next three decades even as the world population explodes, and will only be exacerbated by global warming climate change, he said.

With some 9 billion people expected to populate the planet by 2040 and 85 percent of the population seen in lesser developed countries, decreased land for agriculture and multiple demands on water use will come hand in hand with an expected doubling in food demand, said David Dennis CEO of Kingston, Ontario-based Performance Plants.

Performance Plants is working with the Africa Harvest Biotech Foundation International to develop and field test drought-tolerant white maize.

"The biggest problem we have in crops is environmental stresses and the biggest stress is drought," said Dennis.

Biotech crop opponents rebuke the idea that biotechnology is the answer, and say industry leaders continue to focus much of their efforts on plants that tolerate more chemicals even as they push up seed prices and make more farmers reliant on patented seed products that must be repurchased year after year.

"I know they love to talk about drought tolerance but that is not what they are really focusing on," said Bill Freese, science policy analyst at the Washington-based Center for Food Safety.

Freese said conventional breeding had the ability to address climate change and food needs, but funding cuts to public-sector crop breeders had reduced the ability of non-biotech groups to advance crop improvements.

"The facts on the ground clearly show that biotech companies have developed mainly chemical-dependent GM crops that have increased pesticide use, reduced yields and have nothing to do with feeding the world," Freese said. "The world cannot wait for GM crops when so many existing solutions are being neglected."

Infant play drives chimpanzee respiratory disease cycles

2008-06-18T11:28:00.000+05:30

The signature boom-bust cycling of childhood respiratory diseases was long attributed to environmental cycling. However, the effect of school holidays on rates of social contact amongst children is increasingly seen as another major driver. New research on chimpanzees suggests that this effect of social connectivity on disease cycling may long predate attendance of children at schools, with chimpanzee infant mortality rates cycling in phase with rates of social play amongst infants.

Published in the journal PLoS ONE, the new study examined more than two decades of infant mortality data from two chimpanzee communities in the Taï National Park, Côte d'Ivoire. Previous work by the authors, from the Max Planck Institute for Evolutionary Anthropology in Leipzig Germany, had shown that chimpanzees at the site were killed by respiratory viruses repeatedly introduced from humans. The new study found evidence for mortality cycling at two distinct intervals. On an annual scale, outbreak deaths peaked during the period of high food availability, when chimpanzees are most gregarious. However, infant mortality also cycled on a roughly three year period.

"What is fascinating about this three year cycle is that it appeared to be self-organized," said Hjalmar Kuehl, the lead author on the paper. "That is, the cycles were not forced by some extrinsic environmental cycle but emerged naturally from the demography, developmental ontogeny, and social behavior of chimpanzees." Climate cycles such as those caused by the El Nino Southern Oscillation were not good predictors of infant mortality patterns.

The key to the three year cycle was the ontogeny of playfulness in chimpanzee infants. Chimpanzee newborns are not very social but infants become increasingly playful with age, reaching a peak in social play at about two years old. Thus, each cycle started when an outbreak killed a group of infants, thereby synchronizing the reproductive cycles of their mothers. One year later, a large cohort of infants was born which, another two years further on, matured to peak play age. These highly playful infants produced a social bridge between community members who might otherwise engage in little direct interaction: ideal conditions for community-wide propagation of a new outbreak. The study provides a nice link between population dynamics and the behavioral issues traditionally studied by primatologists", said Yasmin Moebius, who did the analysis of play ontogeny.

It also has important implications for the conservation of chimpanzees, which are classed as Endangered by the World Conservation Union (IUCN), as well as Critically Endangered gorillas. Ape tourism has been heralded as a means of providing monetary value to governments and local communities. However, close approach to habituated gorillas and chimpanzees by tourists poses a serious disease transmission threat. "Our analyses not only tell us that disease transmission from tourists and researchers is a major problem", said Peter Walsh, another coauthor. "They tell us when the risk is greatest and, consequently, when measures such as vaccination would be most effective."

"We need to be more proactive about taking steps to minimize the disease transmission risk posed by both tourism and research," added Christophe Boesch, a coauthor who initiated the Tai Chimpanzee project in 1979. "We also need to expand our vision to include disease management measures such as vaccination as important parts of the ape conservation puzzle."

San Diego Teacher Wins Top Honor for Excellence in Biotechnology Education

2008-06-18T11:25:00.000+05:30

San Diego, CA (June 17, 2008) –The Biotechnology Institute announced that Jay Vavra, a teacher at High Tech High in San Diego, CA, as the recipient of the Genzyme-Invitrogen Biotech Educator Award, the nation’s top award for biotechnology education.

Sponsored by Genzyme Corporation and The Invitrogen Foundation, the award was presented June 16 during the Biotechnology Education Banquet at the Biotechnology Institute’s Conference on Biotechnology Education in San Diego, CA.

Established by the Biotechnology Institute, the national biotechnology education organization, the award recognizes premier high school level educators who provide an array of expertise to help improve the teaching and learning of biotechnology in their classrooms.

“These educators are nominated from among more than one thousand outstanding teachers in our National Biotechnology Teacher-Leader Program,” says Paul A. Hanle, president of the Biotechnology Institute. “The nominees are at the forefront of the Institute’s mission to educate teachers and students about the promise and achievements of biotechnology.”

“Teachers provide the spark of learning that ignites the promise of biotechnology for their students,” stated Michael Wyzga, chief financial officer and executive vice president of finance for Genzyme Corporation. “Through this award, Genzyme is pleased to honor these educators for their important role in translating biotechnology into life-long investigative learning.”

“The Invitrogen Foundation was established to do exactly what these educators do each and every day…inspire students to embrace science. It is an honor to continue our support of the Biotechnology Institute’s Biotech Educator Award for the fourth consecutive year,” said Pete Leddy, senior vice president, human resources for Invitrogen and Institute board member. “These educators have a profound impact on the next generation of scientists. We applaud their innovative approach to teaching and passion for making a difference.”

Ten finalists were identified from a nationwide applicant pool from among more than one thousand educators in the Biotechnology Institute’s National Teacher-Leader Program. Vavra, who received an award of $10,000, was chosen by a panel of judges for his proven leadership and excellence as an educator, his commitment to furthering the teaching of biotechnology by outreach to other educators, and the development of innovative ways to teach biotechnology.

Also honored was the second place winner, Michael Dunn of Capuchino High School in San Bruno, CA. who received $5,000. The third-place winner, Simon Holdaway of The Loomis Chaffee School of Windsor, CT, received $2,500.

The other seven finalists, who received a $1,000 product credit from Invitrogen, were:

Jennifer Albanese, Salesianum School, Wilmington, DE
Myron Blosser, Eastern Mennonite School, Harrisonburg, VA
Peggy Deichstetter, St. Edward High School, Elgin, IL
Mario Godoy-Gonzalez, Royal High School, Royal City, WA
Cheryl Powers, Cate School, Carpinteria, CA
Tamica Stubbs, E.E. Waddell High School, Charlotte, NC
John Taylor-Lehman, Tri-Valley High School, Dresden, OH

The Biotechnology Institute’s National Biotechnology Teacher–Leader Program is building a network of thousands of teachers committed to teaching biotechnology to students and serving as a resource for other teachers. Through professional development programs and resources, the Teacher-Leader Program provides educators with the skills and strategies to introduce biotechnology to their students and assist their peers to do the same.

PARTNERING TO INSPIRE STUDENTS ABOUT SCIENCE EDUCATION

2008-06-14T15:00:00.000+05:30

Arlington, VA (May 12, 2008) – Bayer HealthCare Pharmaceuticals, the San Francisco Bay Area’s second-largest biotechnology employer, and the Biotechnology Institute, the national biotechnology education organization, will launch an intensive program this spring to teach and inspire local young people to consider careers in science and technology. The two-pronged program will focus on students from less advantaged communities.

“We are taking a two-track approach to addressing critical pressure points, the high school and graduate level, where students must be inspired about science, particularly biotechnology, and its immense potential for solving human health, food and environmental problems,” says Paul A. Hanle, president of the Biotechnology Institute.

“Bayer shares with the Biotechnology Institute a recognition that the biotechnology industry is a major force for the future—economically, and through improving people’s lives,” noted Joerg Heidrich, Bayer’s senior vice president and global head of biotech product supply. “As an industry leader Bayer is committed to forging new generations of talented, imaginative professionals—and to providing concrete encouragement to all students, especially those traditionally underrepresented in the sciences, to train for jobs in this exciting field.”

The partnership will establish the “Bayer Minority Fellows Program,” a mentoring program pairing Bayer scientists and executives with ten top-quality graduate students and postdoctoral researchers in life sciences disciplines, particularly those with an interest in research and development and manufacturing. Bayer Minority Fellows will be selected from universities with proximity to Bayer’s West Coast facilities including Washington State, northern California, and San Diego.

With Bayer experts to guide them, Fellows will explore careers in the biotechnology industry, particularly research and development and biomanufacturing. Fellows will undergo rigorous professional development training in areas such as emerging technologies and industrial entrepreneurship. They will also receive coaching in career-building skills, including interviewing techniques and resume writing.

The program, modeled after the Institute’s national Minority Fellows Program, will kick off with a two-day training session, to be held May 21-23, 2008, at Bayer’s global biotech headquarters in Berkeley, CA. The initial meeting will be followed with ongoing interactions facilitated over subsequent months in order to strengthen Mentor-Fellow relationships.

The Bayer/Biotechnology Institute partnership also includes a two-day teacher professional development session on biotechnology for 20 middle and high school teachers from East Bay schools, particularly those in lower-income communities. The session, to be held at Bayer in November, will again tap the expertise of Bayer scientists, who will serve as subject matter experts and mentors.

The partnership with the Biotechnology Institute is an important addition to Bayer’s portfolio of science education initiatives. On the West Coast Bayer founded the award-winning Biotechnology Partners program in 1992 as a way to train disadvantaged local high school and community college students for careers in the booming industry. Other initiatives include Making Science Make Sense, the company’s national program that brings scientists into public schools for hands-on science training, and programs ranging from elementary school science curriculum development to fellowships for minority graduate and post-doctoral students.

About the Biotechnology Institute
The Biotechnology Institute is an independent, national nonprofit organization dedicated to education about the present and future impact of biotechnology. Its mission is to engage, excite and educate the public, particularly students and teachers, about biotechnology and its immense potential for solving human health, food and environmental problems. For more information, visitwww.biotechinstitute.org.

About Bayer HealthCare Pharmaceuticals
Bayer HealthCare Pharmaceuticals is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world’s leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the U.S., Bayer HealthCare Pharmaceuticals comprises the following business units: Women’s Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company’s aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

LINKS TO CAREER INFORMATION AND EMPLOYMENT OPPORTUNITIES IN BIO TECHNOLOGY

2008-06-14T14:56:00.000+05:30

LINKS TO CAREER INFORMATION AND EMPLOYMENT OPPORTUNITIES

Biotechnology in the United States is a dynaic industry so there are many opportunities for employment. Below are some links to job listings and information about careers in the biotech field.

ActionBioScience.org
Adsumo: A Life Sciences Career Website
America's Job Bank
America's Recruiting, Inc.
American Society of Plant Biologists
American Society for Microbiology
BioHealthRx
BioJobNet
Biojobnetwork
Biocom
Biocom Workforce
Bio-Link
BioSpace
Biotechnology Jobs, Seattle, WA
Chemistry.org
Eisenhower National Clearinghouse for Mathematics and Science Education
Hire Health
LifeWorks
Medzilla
NASA Kids Science News Network
Nature Jobs
NIH Careers
Pharmaopportunities Biotech Jobs
Science Jobs
SciWeb Biotechnology Career Center
Tiny Tech Jobs
Under the Microscope: Biotechnology Jobs in California
Vault
Wet Feet

ASCC scores iPS cellsAustralian scientists to study iPS cells from Thomson lab.

2008-06-14T14:48:00.000+05:30

Scientists from the Australian Stem Cell Centre (ASCC) will be the first in Australia to gain access to human induced pluripotent stem (iPS) cells from Professor James Thomson of the University of Wisconsin.

The iPS cells have been imported under an agreement with Thomson, who has developed the human iPS cell lines and was, at the same time as Professor Shinya Yamanaka from the University of Kyoto, the first to describe human iPS cells in November 2007.

Thomson was also the first scientist to identify and describe human embryonic stem cells in the scientific press in 1998 and has been a leader in the field of embryonic stem cell research since.

Both scientists use retroviruses to insert genes into human skin cells to reprogram them. Each uses slightly different genes in the procedure.

The human iPS cells arrived at the ASCC's Melbourne laboratories in late May. Drs Andrew Laslett and Naoki Nakayama, both senior scientists in the human embryonic stem cell laboratory, will be the first at the ASCC to work with them.

"We plan to comprehensively compare the iPS cell lines to existing human embryonic stem cell lines using the first class scientific infrastructure and innovative characterisation and differentiation strategies in place at the Australian Stem Cell Centre," Laslett said.

"These experiments will give us a greater understanding of the relative utility, advantages and potential barriers to the clinical use of iPS cells as compared directly to human embryonic stem cells."

Skin colour and skin cancer

2008-06-02T16:51:00.000+05:30

The team from Iceland's deCODE Genetics that identified sequence variations influencing hair, eye and skin pigmentation have found two more genetic determinants and two variants that confer an increased risk of melanoma.

The studies were published today in Nature Genetics, along with an Australian study identifying a new melanoma risk locus.

In October last year, deCODE reported novel single nucleotide polymorphisms (SNPs) influencing skin, eye and hair colour in Europeans.

They found that a SNP on chromosome 14 in the SLC24A4 gene is associated with an increased likelihood of blond rather than brown hair, and blue rather than green eyes. Blonde hair is also associated with a variant near the KITLG gene on chromosome 12.

A SNP on chromosome 6 is associated with freckles, as is a SNP in the tyrosinase (TYR) gene.

The team also confirmed previous studies associating red hair, freckles and sun sensitivity with the MC1R gene, and other variants near the OCA2 gene with eye and hair colour.

In the new studies, the team found a variant in the ASIP (encoding agouti signalling protein) gene, which has a well-documented role in pigmentation, which was very similar to those observed in MC1R. They also found two coding variants in TPCN2 that are associated with blond versus brown hair.

Importantly for skin cancer research, the team has found a haplotype near ASIP confers a significant risk of cutaneous melanoma, the highly aggressive cancer that causes the majority of deaths, and a risk of basal cell carcinoma, the more common but less deadly cancer.

A variant on TYR also conferred a risk of cutaneous melanoma and basal cell carcinoma.

In an independent study, Stuart McGregor, from the Queensland Institute of Medical Research, and colleagues found two SNPs on chromosome 20 conferred a risk of cutaneous melanoma. The SNPs are located in the region of ASIP but the team believes there are several other candidate loci.

deCODE papers: DOI: 10.1038/ng.160 and DOI: 10.1038/ng.161 MacGregor paper: DOI: 10.1038/ng.163

Prototype vaccine for West Nile virus

2008-06-02T16:49:00.000+05:30

Brisbane's Replikun Biotech has signed a licence agreement with UniQuest, the University of Queensland's commercialisation arm, to develop a new vaccine technology for West Nile virus.

The technology is based on research by UQ's Associate Professor Alex Khromykh and Dr Roy Hall and involves a developmental vaccine based on a modified form of the Kunjin virus, a benign flavivirus endemic to northern Australia.

The new technology will complement Replikun's core technology platform, Kunjin replicon gene delivery, the company's COO, Dr Lavinia Proctor said.

This technology provides a novel, persistent gene delivery system, which is anticipated to be suitable for immunotherapy, vaccine development and recombinant protein production, she said.

The Kunjin replicon is a self-replicating piece of RNA derived from the RNA genome of the Kunjin virus. It incorporates a vaccine or immunotherapy gene in place of deleted Kunjin virus structural genes.

The company said the removal of the Kunjin virus structural genes ensures that the Kunjin replicon cannot produce infectious particles. The Kunjin replicon retains the non-structural protein genes and several other elements essential for replicon self-replication.

The Kunjin replicon is well tolerated by cells, allowing vaccines to persist. Persistent vaccine antigen expression from the Kunjin replicon, combined with relatively low attendant inflammation, supports the formation and maintenance of protective immune responses, the company said.

Replikun is also developing a cancer immunotherapy candidate and a therapeutic HIV vaccine, both based on the Kunjin delivery system.

Under the agreement, Replikun will be responsible for all further development and commercialisation of the vaccine technology and will pay royalties to UniQuest on sales of licensed products.

West Nile virus has caused more than 1000 deaths in the US since it emerged in 1999 and is a growing problem in Europe. Khromykh and colleagues are also researching whether this type of vaccine could also be used against other flaviviruses such as dengue, tick-borne encephalitis and Japanese encephalitis viruses.

New disaster preparedness strategy announced

2008-05-06T13:23:00.000+05:30

New disaster proposal could legally protect physicians
In an unprecedented initiative, US and Canadian experts have developed a comprehensive framework to optimize and manage critical care resources during times of pandemic outbreaks or other mass critical care disasters. The new proposal suggests legally protecting clinicians who follow accepted protocols for the allocation of scarce resources when providing care during mass critical care events. The framework represents a major step forward to uniformly deliver sufficient critical care during catastrophes and maximize the number of victims who have access to potential life-saving interventions.

“Most countries, including the United States, have insufficient critical care resources to provide timely, usual care for a surge of critically ill and injured victims,” said Asha Devereaux, MD, FCCP, Task Force for Mass Critical Care. “If a mass casualty critical care event occurred tomorrow, many people with clinical conditions that are survivable under usual health-care system circumstances may have to forgo life-sustaining interventions due to deficiencies in supply, staffing, or space.” As a result, the Task Force for Mass Critical Care developed an emergency mass critical care (EMCC) framework for hospitals and public health authorities aimed to maximize effective critical care surge capacity.

Published as a supplement to the May issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP), Definitive Care for the Critically Ill During a Disaster offers guidance for hospitals, medical professionals, and public health authorities on how to prepare for and provide essential critical care when the need for critical care resources far exceeds availability.

Expanding Critical Care Resources for a Disaster
To prepare for a mass critical care event, the task force proposes that hospitals with ICUs aim to meet several standards, including the ability to provide sufficient critical care for at least triple their usual ICU capacity and sustain this surge for up to 10 days without external assistance. Suggested surge capacity requirements include stockpiling medical equipment, including mechanical ventilators; optimizing medication; designating auxiliary critical care areas; and augmenting critical care staff.

Trigger Event and Process
Prior to the rationing of critical care resources, hospitals and surrounding areas must first experience a “trigger” event that includes a declared state of emergency and lack of critical equipment or infrastructure. The decision to initiate EMCC must occur in conjunction with local and regional Medical Emergency Operations Command authority and not by individual hospitals.
Critical Care Resource Allocation

The task force advises rationing scarce critical care resources only after surge capacity has been exceeded and all attempts to use outside resources have been made. Under these circumstances, the task force proposes a formal EMCC triage and resource allocation protocol. Examples of the protocol include:
The hospital triage officer/team will assess and prioritize all patients for receipt of scarce interventions using objective medical criteria.
Palliative care for all patients will be a priority. However, patients will be ineligible for scarce critical care interventions if they have extreme organ failure and/or severe chronic illness with a short life expectancy.
Critical care resources will not be preferentially distributed to any specific population group.
Decisions regarding resource allocation will be documented, remain transparent, occur uniformly across all affected regions, and subject to rigorous quality assurance.
“Ideally, having an emergency mass critical care plan in place would prevent hospitals from needing to ration critical care resources,” said Lewis Rubinson, MD, PhD, Task Force for Mass Critical Care. “However, if the surge capacity is exceeded, the use of emergency mass critical care triage and rationing will help local health-care facilities minimize mortality and optimize survival.”
Physician Liability
EMCC protocol allows the triage officer and supporting triage team to make decisions that benefit the greatest number of patients with potentially limited resources. Consequently, lifesaving care may be withheld from one patient and given to another, prompting ethical and legal implications. To reassure critical care providers and ensure consistent allocation of critical care resources, the task force advocates for legal protection of health-care professionals and institutions that follow accepted EMCC protocols while providing care during times that require critical care resource rationing. Government endorsement of a protocol for EMCC triage and resource allocation ideally would shield practitioners and institutions acting in good faith from liability.

“The new EMCC framework provides a much needed foundation for disaster preparedness in the critical care setting. Suggestions proposed by the task force will facilitate ongoing discussions and allow for further input from the disaster planning community,” said Alvin V. Thomas, Jr., MD, FCCP, President of the ACCP. “Hospitals, communities, and government agencies must take the next steps to modify framework principles and implement them in critical care environments.”

Task Force for Mass Critical Care
Spearheaded by the ACCP, the task force consists of 37 senior-level participants with broad expertise relevant to EMCC, representing military medicine, medical societies and institutions, and government agencies, including the Centers for Disease Control and Prevention and the US Department of Health and Human Services. The task force also includes members of the Critical Care Collaborative (CCC), a group of medical professional societies who collectively represent more than 100,000 health-care professionals. Members of the CCC include the ACCP, the American Association of Critical-Care Nurses, Society of Hospital Medicine, and the American Society of Health-System Pharmacists.

South Korea reports new case of suspected bird flu

2008-04-29T14:38:00.000+05:30

SEOUL, April 29 (Reuters) - South Korea on Tuesday reported a suspected bird flu outbreak at a chicken farm in Ulsan City, which if confirmed would be the first in the southeast, as the country grapples with its worst outbreak of avian influenza।

South Korea previously confirmed 20 cases of the H5N1 strain in poultry in less than one month, despite having killed more than 5 million chickens and ducks, as the virus spreads at its fastest rate since the country reported its first case in 2003।

No human deaths from the disease have been reported in the country।On Tuesday, the Agriculture Ministry said a chicken farm in Ulsan, some 390 km (242 miles) southeast of Seoul, reported deaths of more than 100 chickens in a week and initial tests gave positive readings for the avian virus.

Seoul has stepped up the culling of birds in affected areas and launched an investigation into all of the country's 260 duck farms in a bid to prevent the spread of the virus.South Korea had to kill 5.29 million birds during the first outbreak between late 2003 and early 2004. The second outbreak in 2006-2007 saw about half that number culled.

(Reporting by Miyoung Kim; Editing by Ken Wills and Sanjeev Miglani)

Study finds that minimally invasive robotic bypass surgery provides health and economic benefits

2008-04-27T10:26:00.000+05:30

Study finds that minimally invasive robotic bypass surgery provides health and economic benefits

Added costs are offset by shorter hospital stay and fewer complications

Minimally invasive heart bypass surgery using a DaVinci robot means a shorter hospital stay and faster recovery for patients, as well as fewer complications and a better chance that the new bypass vessels will stay open. And, according to a University of Maryland study, robotic heart bypass surgery also makes good economic sense for hospitals. The study will be presented at the American Surgical Association on April 26, 2008.

Using a surgical robot increases the cost of each bypass case by about $8,000, according to Robert S. Poston, M.D., a cardiac surgeon formerly at the University of Maryland Medical Center who is the lead author of the study. He says those additional expenses, which are due to equipment and supplies, are offset by a shorter hospital stay, reduced need for transfusions and fewer post-surgical complications that would require a patient to be re-admitted to the hospital. Especially with high risk patients who have lung or kidney disease or other health problems, the researchers found that the minimally invasive, robotic approach saves costs.

“These findings are significant because payers are considering linking reimbursement for coronary artery bypass surgery to patient outcomes,” says Stephen T. Bartlett, M.D., professor and chairman of the Department of Surgery at the University of Maryland School of Medicine and chief of surgery at the University of Maryland Medical Center.

“Our study shows that there are health benefits to patients from the minimally invasive approach, both in terms of a shorter recovery and also looking at the function of the bypass graft months after the surgery,” adds Dr. Bartlett, who is one of the study’s co-authors.

While the DaVinci surgical robot is in widespread use for prostate surgery, the University of Maryland Medical Center is among only a few hospitals nationwide, and was one of the first in the U.S., to use the robot to perform multiple vessel heart bypass surgery.

The researchers studied 100 consecutive patients who had minimally invasive coronary bypass surgery using a robot at the University of Maryland Medical Center. The technique requires no incisions except for a few small holes to insert instruments. These cases were compared to a matched group of 100 patients who had the traditional “open” bypass surgery with a sternotomy, a surgical incision through the sternum.

The average length of the hospital stay for the patients with the minimally invasive surgery was about four days compared to seven days for the traditional bypass operation; however the difference was even greater among patients considered to be at high risk. In that group, the average stay was five days with robotic surgery compared to 12 days with the traditional technique.

The complication rate for those who had the robotic bypass was also much lower, with 88 percent of patients free of complications after having the minimally invasive surgery compared to 66 percent of those with the “open” operation.

The patients in the study were followed up one year after their surgery. Using a CT angiography scan, the researchers found that those who had the robotic bypass were much less likely to have narrowing or clots in the bypass graft than those with the traditional bypass surgery from six months to a year after the operation.

“We saw a long term benefit to patients after their bypass in terms of the patency, or openness, of the bypass graft, according to Bartley Griffith, M.D., head of Cardiac Surgery at the University of Maryland Medical Center and professor of surgery at the University of Maryland School of Medicine. Dr. Griffith, also a co-author of the study, says the grafted vessels of more than 99 percent of the patients who had robotically-assisted bypass surgery were still open and functioning well compared to about 80 percent of those who had the “open” operation.

The reason for the difference is that for patients who need multiple bypasses, surgeons can easily access two internal mammary arteries to use as the new bypass vessels rather than taking a section of vein from another part of the body. In traditional bypass operations, only one internal mammary artery is used while other bypasses are performed using a vein. The long-term success of the bypass, or patency of the target vessel, is superior with an internal mammary artery versus a vein.

Dr. Poston says hospitals have been waiting for data on the costs and benefits of robotic-assisted heart bypass programs before investing in them. “Our conclusion from this study is that robotically-assisted coronary artery revascularization presents quality of life benefits for patients along with financial savings for those hospitals which care for large numbers of high risk patients,” says Dr. Poston, who recently moved from the University of Maryland to be the chief of cardiac surgery at Boston Medical Center.

The study, “Superior Financial and Quality Metrics with Robotically-assisted (DaVinci) Coronary Artery Revascularization,” will be presented at the 128th annual meeting of the American Surgical Association in New York on April 26, 2008.

Gene Express Licenses Technology from USF to Develop a Prognostic Test for Chemotherapy Resistance

2008-04-22T15:38:00.000+05:30

Gene Express Licenses Technology from USF to Develop a Prognostic Test for Chemotherapy Resistance

GEN News Highlights

Gene Express is licensing certain gene-expression technologies from the University of South Florida (USF) to develop tests for cisplatin and irinotecan chemoresistance. The firm believes that it will submit a prognostic test to the FDA for approval in the first half of next year.

The deal, signed with the Division of Patents & Licensing Research Office at USF, includes the ERCC1 and RRM1 genes. USF researchers say that they have discovered a correlation between expression of ERCC1 (excision repair cross-complementing-1) and the survival of patients with non-small-cell lung cancer (NSCLC). They also found that RRM1 is a clinically important determinant of malignant behavior in NSCLC.

“By adding these genes to our growing collection of gene standards, we will be able to develop the most accurate, sensitive, and reproducible molecular diagnostic tests for identifying tumors that are resistant to specific chemotherapeutics,” remarks Jonathan D. Rowe, Ph.D., svp of strategy and clinical innovation for Gene Express.

Gene Express intends to complete clinical validation for correlation of gene expression versus chemoresistance for cisplatin treatment by April 2009 and submit a 510K class II prognostic test to the FDA by May 2009. The company anticipates receiving approval of the 510K medical prognostic test in August 2009 and commercial application completed by December 2009.

Genetic Variant Identified in African Americans that Aids Survival After Heart Failure

2008-04-22T15:27:00.000+05:30

Genetic Variant Identified in African Americans that Aids Survival After Heart Failure

GEN News Highlights

About 40% of African-Americans have a genetic variant in GRK5 that can protect them after heart failure and prolong their lives, according to researchers. GRK5 codes for the enzyme GRK5, which depresses the response to adrenaline and similar hormonal substances.

The human heart has two forms of GRK: GRK2 and GRK5. The researchers searched the DNA sequence of these genes in 96 people of European-American, African-American, or Chinese descent.

They found most people, no matter their race, had exactly the same DNA sequence in GRK2 and GRK5. There was one, however, one common variation called GRK5-Leu41 in the DNA sequence of more than 40% of African-Americans.

To determine the effect of the variant in GRK5, the team studied the course of progression of heart failure in 375 African-American patients. They looked for survival time or time to heart transplant, comparing people with the variant to those without. Some of these patients were taking beta blockers and some were not.

In patients who did not take beta blockers, the researchers found that those with the variant lived almost twice as long as those with the more common version of the GRK5 gene. Beta blockers prolonged life to the same degree as the protective GRK5 variant but did not further increase the already improved survival of those with the variant.

“These results offer an explanation for the confusion that has occurred in this area since clinical trials of beta blockers began,” says senior author Gerald W. Dorn II, M.D., professor of medicine, associate chairman for translational research, and director of the center for pharmacogenomics at Washington University. “Our study demonstrates a mechanism that should lay to rest the question about whether beta blockers are effective in African-Americans; they absolutely are in those who don't have this genetic variant.”

The investigators involved in the research were from Washington University, the University of Cincinnati, University of Michigan, Thomas Jefferson University, and University of Missouri. The study was published online on April 20 in Nature Medicine.

Two cases of coinfection with HIV and simian foamy virus (SFV) are reported

2008-04-21T15:44:00.000+05:30

Two cases of coinfection with HIV and simian foamy virus (SFV) are reported in the May 1st edition of the Journal of Infectious Diseases. Although the exact clinical significance of infection with SFV is unknown for HIV-positive individuals, there is some laboratory evidence that SFV may alter the natural history of SIV, which is similar to HIV, and that SFV-infected cells are more vulnerable to infection with HIV.

The investigators recommend that measures should be introduced to protect the blood supply from SFV, and that strategies to reduce human contact with mandrills and other primates should be developed to prevent transmission of SFV and other simian infections to humans. People in contact with nonhuman primates have a risk of infection with the parasites, viruses and bacteria with which these creatures can be infected. HIV originated as a simian virus and was subsequently spread by person-to-person contact showing the potential public health consequences of infections harboured by nonhuman primates.

SFV is a retrovirus that is common in nonhuman primates that are caught from the wild or held in captivity. It can be spread easily between nonhuman primates by contact with infected bodily fluids, usually through grooming, biting, and possibly sexual contact. Although laboratory studies have shown that SFV can damage the cells of nonhuman primates, it does not appear to cause disease in these species. There is a growing body of evidence suggesting transmission of SFV from nonhuman primates to humans is possible.

Transmission of SFV from a wide range of ape and monkey species, including chimpanzee, gorilla, macaque, African green monkey, baboon and mandrill to humans have been suggested. The ability of SFV to cause illness in humans, or be transmitted between humans is not yet fully understood, but no cases of disease in humans or sexual transmission between humans has been recorded so far. Little is known about the geographical distribution of SFV among humans, including those infected with HIV in west central Africa.

Investigators therefore conducted an analysis of blood samples obtained from 139 sex workers, 41 patients with sexually transmitted infection, and 179 blood donors . The commercial sex workers and individuals with sexually transmitted infections were located in the Democratic Republic of the Congo, and the blood donors in the Cameroon. Samples were obtained between 1985 and 2000. Of the 139 samples obtained from commercial sex workers, one (0.72%) was found to be infected with SFV. This sample was also infected with HIV and was obtained in 1985. In addition, one sample (0.56%) from the 179 blood donors in the Cameroon was also SFV-infected, and once again this sample came from an HIV-positive individual. Genetic analysis was performed on the sample from the blood donor and this showed that infection with SFV originated in a mandrill. “Our identification of what are, to our knowledge, the first reported cases of coinfection with SFV and HIV heightens the importance of defining the clinical and public health consequences of zoonotic SFV infection, especially in the context of AIDS”, write the investigators.

Although it is unclear if infection with SFV will cause illness in HIV-positive individuals, they point to laboratory evidence that suggests that this may be possible. For example, SFV may alter the course of SIV-associated disease in the gut of macaques that have SIV-associated immunosuppression. Laboratory studies also suggest that SFV-infected human cells are more “permissive” of infection with HIV. As SFV infection was found in both a sex worker and a blood donor, this suggests to the investigators that both sexual and bloodborne transmission of SFV may be possible.

They note that blood donations are not screened for SFV and propose that their findings may indicate that such precautions need to be introduced. Canada, for example, recently banned blood donations from individuals who had had contact with nonhuman primates “to prevent the introduction of SFV and other primate microbes into the blood supply.” Other studies in the Cameroon show that transmission of SFV, SIV and HTLV-1 from mandrills to humans has occurred, probably because of hunting and butchering. The investigators conclude, “these results suggest that frequent contact with mandrills in this region may explain the widespread zoonotic transmission of mandrill retroviruses.

Effective strategies to reduce hunting of mandrills and other nonhuman primates are needed to help preserve these endangered species and to prevent their viruses from being transmitted to humans.” Reference Switzer WM et al. Coinfection with HIV-1 and simian foamy virus in West Central Africans. J Infect Dis 197: 1 – 5, 2008.

Eastland’s under the tongue, Bionomics disrupts further, Novogen adds on and Mesoblast’s arthritic sheep.

2008-04-18T12:41:00.000+05:30

Eastland’s under the tongue, Bionomics disrupts further, Novogen adds on and Mesoblast’s arthritic sheep.

WA-based Eastland Medical Systems says it will become profitable this year after releasing early results of its sublingual malaria treatment ArTiMist proved positive.

Eastland has completed Phase 1 single-dose trials in Malaysia and Phase 1 multi-dose trials in South Africa of the under-the-tongue spray delivery.

Both trials showed the formulation was well-tolerated, the company said. It hopes to move into Phase III trials later this year.

SA's Bionomics presented data at the American Association of Cancer Research annual meeting this week that showed its lead anti-cancer compound, the vascular disrupting agent BNC105, has a dual mode of action.

Bionomics said the compound both disrupted blood vessels and inhibited tumour growth in animal models of human lung and brain cancers.

It is also being studied for breast, colon and prostate tumours. The data also showed that low doses of BNC105 in combination with the drug Avastin (bevacizumab) resulted in an enhanced anti-cancer effect on cancer blood vessels and tumours, the company said.

BNC105 is currently in clinical trial in patients with advanced cancer at three Melbourne cancer centres: the Peter MacCallum Cancer Centre, the Western Hospital and the Royal Melbourne Hospital.

Also at the AACR annual meeting, Sydney's Novogen announced a new compound in development, NV-128, with which it is targeting ovarian cancer.

NV-128 is an analogue of the company's phenoxodiol, which is in a Phase III multi-centre trial for late stage ovarian cancer, and triphendiol, which has FDA orphan drug status for pancreatic and bile duct cancers and late stage melanoma and enters Phase II late this year.

These drugs have been licensed to Marshall Edwards, a Novogen subsidiary that is listed on the Nasdaq index and was established to commercialise Novogen's multiple signal transduction regulators.

The company says NV-128 induces caspase-independent DNA degradation and cancer cell death.

Melbourne's Mesoblast has also been busy recently, announcing good long-term results in its osteoarthritis preclinical trials.

The mesenchymal stem cell specialist said a single injection of its allogeneic product into the arthritic knees of sheep provided sustained protection against cartilage destruction and degeneration for up to nine months.

"On the basis of these results, Mesoblast will proceed to commence its Phase II clinical trial program for cartilage protection in patients with osteoarthritis of the knee," the company said in a statement.

A new Excellence in Biotechnology Investment 2008 conference is being held next Monday and Tuesday at the Hilton Hotel in Sydney.

The event involves a gala awards dinner, with categories such as broker of the year, best CEO, transaction of the year and debut company of the year.

There's also a 'Legends' award, with contenders including Resmed's Dr Peter Farrell, CSL's Dr Brian McNamee, Cochlear's Dr Chris Roberts and everyone's Professor Ian Frazer.

Scientists Reprogram Fully Mature B Cells into Stem Cell Like State

2008-04-18T10:35:00.000+05:30

Scientists Reprogram Fully Mature B Cells into Stem Cell Like State

GEN News Highlights

Scientists found that fully mature, differentiated B cells can be reprogrammed to an embryonic stem cell like state without the use of an egg.

In previous research, induced pluripotent stem (IPS) cells had been created from fibroblasts, but it was unknown if they were fully differentiated. Mature B cells have a specific part of their DNA cut out as a final maturation step, giving researchers a way to make sure the resulting IPS cells were not from immature cells.

Similar to the process used to create IPS cells from fibroblast cells, the scientists successfully reprogrammed immature B cells into IPS cells by using retroviruses to transfer four genes (Oct4, Sox2, c-Myc, and Klf4) into the cells’ DNA. An additional factor CCAAT/enhancer-binding-protein-a, however, was needed to nudge mature B cells to be reprogrammed into IPS cells.

The IPS cells from both the mature and immature B cells could be used to create mice. The mice grown from the reprogrammed mature B cells were missing the same part of their DNA as the mature B cells, demonstrating that they were reprogrammed from fully differentiated cells.

This work offers the ability of creating new mouse models for autoimmune diseases such as multiple sclerosis and type 1 diabetes, according to the investigators. For example, mature B or T cells specific for glia could be reprogrammed to IPS cells and then used to create mice with an entire immune system primed to only attack the glia cells, thereby creating a mouse model to study multiple sclerosis.

The researcher was performed by investigators at Whitehead Institute for Biomedical Research and MIT. The study will be published in the April 18 issue of Cell.

Significantly Reduced Brain Atrophy and Tissue Loss over Five Years in Treatment-Naive Relapsing-Remitting Multiple Sclerosis Patients

2008-04-17T11:00:00.000+05:30

COPAXONE(R) Significantly Reduced Brain Atrophy and Tissue Loss over Five Years in Treatment-Naive Relapsing-Remitting Multiple Sclerosis Patients

News source: Business Wire

Final results from a five-year comparative imaging study examining the long-term effect of disease-modifying therapies (DMTs) in treatment-naive, early relapsing-remitting multiple sclerosis (RRMS) patients, demonstrated that COPAXONE(R)-(glatiramer acetate injection) treated patients experienced significantly less brain tissue loss, as measured by percent change in brain volume, compared with patients on other DMTs. In the study, patients receiving COPAXONE(R) experienced a reduced mean annualized rate of brain atrophy (ARBA) of -0.46 percent over five years, while patients receiving Avonex(R) or Betaseron(R)/Rebif(R) experienced mean ARBA of -0.52 percent and -0.64 percent, respectively. Patients in the untreated control group with an average follow-up of 15.2 months experienced the highest rate of brain atrophy (-0.95 percent). These data were presented at the 60th Annual Meeting of the American Academy of Neurology (AAN).

"Brain atrophy is a clinically relevant tool to measure disease progression and subsequent neurological disability in RRMS patients," said Omar Khan, M.D., Professor of Neurology, Director, Multiple Sclerosis Center, Wayne State University and lead investigator of the study. "Long-term brain volume measurements may be more appropriate than short-term examination to assess the ability of DMTs to affect brain tissue loss in RRMS. Although patients showed a significantly lower ARBA in all three treatment groups compared with the untreated group, COPAXONE(R)-treated patients demonstrated significantly reduced brain atrophy versus patients treated with either low-dose or high-dose interferon-beta."

About the Study

The study analyzed 309 treatment-naive RRMS patients who began and remained on the same DMT for five years. Patients included were those with disease duration of five years or less and an Expanded Disability Status Scale (EDSS) score of 3.0 or less at baseline. All patients had brain magnetic resonance imaging (MRI) scans (at onset of DMT and five years later) on the same 1.5T scanner. Untreated RRMS patients with follow-up ranging from 8 to 24 months were enrolled as controls. A fully automated technique known as SIENA was used to measure brain volume change. Image analysis was performed blinded to treatment allocation.

There were 121 patients on COPAXONE(R), 101 on high-dose interferon beta (Betaseron(R) or Rebif(R)) and 53 on Avonex(R). All treatment groups were well-matched at baseline. The mean ARBA over five years was -0.46 percent, -0.52 percent, and -0.64 percent in the COPAXONE(R), Avonex(R) and Betaseron(R)/Rebif(R) groups, respectively. The untreated control group with an average follow-up of 15.2 months had a mean ARBA of -0.95 percent. The ARBA was lower in all three treatment groups compared to the untreated group (p less than 0.0001).

COPAXONE(R)-treated patients demonstrated significantly reduced ARBA than patients treated with either Avonex(R) or Betaseron(R)/Rebif(R) (p=0.0336 and p less than 0.0001).

"This study also demonstrated that brain atrophy is a dynamic process that can be detected in mildly affected early MS patients. Therefore, in accordance with National MS Society recommendations, it is important to initiate therapy soon after the diagnosis of MS is confirmed," said Omar Khan, M.D.

The study was supported by Wayne State University Neuroscience Program.

About COPAXONE(R)

COPAXONE(R) (glatiramer acetate injection) is indicated for the reduction of the frequency of relapses in RRMS.
The most common side effects of COPAXONE(R) are redness, pain, swelling, itching, a lump or an indentation at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

COPAXONE(R) is now approved in 51 countries worldwide, including the United States, all European countries, Canada, Mexico, Australia, and Israel. In Europe, COPAXONE(R) is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, COPAXONE(R) is marketed by Teva Neuroscience, Inc.

See additional important information at http://www.COPAXONE.com/pi/index.html or call 1-800-887-8100 for electronic releases. For hardcopy releases, please see enclosed full prescribing information.

About Teva Neuroscience

Teva Neuroscience is dedicated to investigating, developing and marketing ground-breaking products and technologies, with emphasis on cutting-edge treatments for patients who are living with neurological conditions, including multiple sclerosis (MS) and Parkinson's disease (PD). Therapies developed by Teva Neuroscience include COPAXONE(R) (glatiramer acetate injection) for relapsing-remitting multiple sclerosis (RRMS) and AZILECT(R) (rasagiline tablets) for the treatment of PD.
Teva Neuroscience's suite of innovative products continues to demonstrate the company's commitment to fulfilling unmet medical needs and has helped the company evolve into a global leader in RRMS. Teva Neuroscience is a North American division of Teva Pharmaceutical Industries Ltd., the world's largest generic drug company. Teva Neuroscience is proud of the role it plays in providing effective treatment options to patients worldwide. For more information, please visit www.tevaneuro.com or www.tevaclinicaltrials.com.

Teva's Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause Teva's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: when and whether the proposed acquisition will be consummated, Teva's ability to rapidly integrate Bentley's' operations with its own operations and achieve expected synergies, the diversion of management time on merger-related issues, Teva's ability to accurately predict future market conditions, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Allegra(R), Neurontin(R), Lotrel(R), Famvir(R) and Protonix(R), Teva's ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which Teva may obtain U.S. market exclusivity for certain of its new generic products and regulatory changes that may prevent Teva from utilizing exclusivity periods, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the impact of consolidation of our distributors and customers, the effects of competition on our innovative products, especially Copaxone(R) sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the regulatory environment and changes in the health policies and structures of various countries, our ability to achieve expected results though our innovative R&D efforts, Teva's ability to successfully identify, consummate and integrate acquisitions, potential exposure to product liability claims to the extent not covered by insurance, dependence on the effectiveness of our patents and other protections for innovative products, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, environmental risks, fluctuations in currency, exchange and interest rates, and other factors that are discussed in Teva's Annual Report on Form 20-F and its other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

Biotechnology EDUCATION News

2008-04-12T18:07:00.000+05:30

Biotechnology EDUCATION news

Parkinson's Research Sends Burlington, NC, Student to China. After spending last summer researching a protein that's significant in Parkinson's disease, writing a research paper about it and presenting it to educators, a Burlington teen is heading to China to share what she's learned. Melanie Wiley, 18, who currently attends the N.C. School of Science and Mathematics in Durham, is one four students from the state representing the American delegation in Beijing, China this week at the Beijing Youth Science Creation Competition. Wiley and the others in the delegation won't actually compete while in China, but they will present their research. On March 14, Wiley won third place for the research in the biotechnology section at the N.C. Student Academy of Science competition. On Monday, she attended the Junior Science and Humanities Symposium hosted by the University of North Carolina at Charlotte where she won second place for a poster presentation of the same research. (Burlington Times News, 3/21/08.)

Distance Learning About Biotech. A cake isn't just a tasty treat. It's also a science experiment full of chemical reactions and molecular structures. Through the ACCESS Distance Learning program, teachers across Alabama recently got to watch a lesson on the science of cooking, including a group at Bob Jones High School. From Montgomery, Dr. Daniel Adamek and Judy Brown prepared 14 cakes, with variations in each cake's ingredients, to show how teachers can talk about science in what can seem like just an everyday activity. Brown, a state education specialist and a former culinary arts teacher at Bob Jones, said she had been working on the Savory Science& lesson since September. It is the first in what she hopes will be a series of distance learning programs. Adamek, who is with AZ Technologies in Huntsville, worked with Brown to develop their cake experiments, write the script for the ACCESS broadcast and to write a lesson plan teachers can use in their classes. About 80 teachers took part in the first lesson, heading to Bob Jones and eight other ACCESS sites after school. Huntsville's HudsonAlpha Institute for Biotechnology did the filming for Savory Science free of charge. (Huntsville Times, 3/17/08.)

Invitrogen Launches Philanthropic Foundation. Invitrogen Corporation, a provider of essential life science technologies for research, production and diagnostics, today announced the launch of the Invitrogen Foundation, a non-profit philanthropic organization aimed at increasing participation in and understanding of the life sciences among students, teachers, scientific professionals and the public. Invitrogen has granted an initial $1 million to the Foundation and plans to provide additional funding in the future. (Business Wire, 2/22/08.)

DC-Area Schools Heed Science Industry's Warning. Universities in the Washington region are in the forefront of a movement to train more people to enter science and technology professions and meet what industry leaders call an urgent need to expand the workforce to keep the U.S. economy competitive. At least eight schools in the District and Maryland are offering or drawing up plans for a two-year professional science master's degree. The PSM program is designed to provide more advanced training in science or mathematics -- with a dose of business skills -- and entice more students who receive bachelor of science degrees to stay in the field without having to pursue a doctorate. The PSM degree, sometimes described as a science version of the MBA degree, is being hailed as one of the most promising innovations in graduate education in years. Last year, Congress provided funding for schools to establish or improve PSM programs through the America Competes Act. About 1,300 students are enrolled in PSM programs at more than 50 schools nationwide, officials say. (Washington Post, 1/28/08.)

Gwinnett, GA, Students Try to Answer Organic Questions. The lesson called on students to detect GM (genetically modified) foods by PCR (polymerase chain reaction). Basically, students run an experiment to see if any food had its DNA altered. The activity is one of several high-level lessons students work on in the biotechnology program. The course lets Gwinnett high-schoolers perform experiments most students don't work on until junior year of college. Think of the course as a classroom version of the television show "CSI." (Atlanta Journal-Constitution, 1/28/08.)

Maryland and Swedish Students Compare Marine Biotechnology Projects. The Maryland Science Technology Engineering and Mathematics program is meant to challenge students and prepare them for college. Students from Carroll County high schools sank disks into waterways around their homes and schools in recent months, pulling them out to photograph and identify the organisms living in different environments, and to compare their results with what students in Sweden discovered. (The DC Examiner, 1/16/08.)

New Jersey State Education Program Supports Biotechnology. Monmouth University was awarded a portion of a $5.1 million grant to be used to ignite a biotechnology education program in the state. The Workforce Innovation in Regional Economic Development (WIRED) grant from the U.S. Department of Labor was awarded to the Central New Jersey BIO-1 regional partnership, which consists of key education and industry members in central New Jersey involved in supporting bioscience education and training programs necessary to support the pharmaceutical workforce. (Atlanticville News, 12/13/07.)

Amgen Scholars Program Accepting Applications. The Amgen Scholars Program, a partnership of the Amgen Foundation, Massachusetts Institute of Technology (MIT) and premier universities around the country, is now accepting applications for the summer of 2008. The annual Amgen Scholars Program provides undergraduates the opportunity for hands-on research at 10 of the nation's leading universities to explore an area of research under a faculty mentor beyond what they may be able to do as part of their regular undergraduate education. (Business Wire, 12/4/07.)

$1m for stem cell research

2008-04-12T17:55:00.000+05:30

NSW and Victoria join forces to fund stem cell research।

Kate McDonald 11/04/2008 11:42:41

The Victorian and NSW governments have announced a fund of $1 million for a collaborative stem cell research program।

Each state will provide $500,000 to the program, which will require research collaboration between both states, although national and international collaboration is being encouraged।

The grants will also require compliance with legislation involving human embryonic stem cells.
The main aim of the program is to improve the sustainability of techniques, technical expertise and the range of applications for stem cell research and in particular the advancement of somatic cell nuclear transfer (SCNT) techniques.

NSW Minister for Science and Medical Research, Verity Firth, said the new funding, along with regulatory certainty regarding human embryonic stem cell research, will help further research into producing tailored human stem cell lines for therapeutic use।

Guidelines and application forms are available from Business Victoria and the NSW Office for Science and Medical Research

Biomarkers may reduce need for biopsies

2008-04-10T21:41:00.000+05:30

Heart and lung transplant patients may no longer need biopsies and could receive personalized care from biomarkers

BOSTON, MA April 10, 2008 – Data presented at this week’s 28th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT) suggest the potential of a significant impact of using biomarkers to reduce the need for biopsies and personalize transplant patient care. Non-invasive testing using gene-based blood or urine samples called biomarkers could offer transplant patients personalized care and medication and may replace the need for costly, invasive biopsy procedures that can be risky for patients. The meeting will run through Saturday at the Boston Marriott Copley Place and Hynes Convention Center.
Personalized care is an integrative process of tailoring care to an individual patient’s characteristics or preferences, based on each individual’s unique biology, behavior and environment। At this year’s meeting, researchers are presenting data from gene and protein based blood testing that may be helpful for reducing immunosuppression. Related data suggests gene analysis may allow for prediction of future occurrence of cardiac allograft rejection and its diagnosis.

FEATURED DISCUSSION
Today’s plenary lectures provide current perspectives on biomarkers in transplantation. In Biomarkers: What Are They" How Might They Aid in Care of Allograft Recipients and Other Patients, Christopher J. O’Donnell, MD, MPH, from NIH National Heart, Lung and Blood Institute/Framingham Heart Study, Framingham, MA, will present data pertaining to personalized care, its benefits and future impact on heart and lung patients.
Following, Dr. Christoph Borchers, Director of the Genome Canada Proteomics Platform at the University of Victoria, British Columbia, will provide a look at the emerging strategies for plasma protein analysis in New Tools, Technologies and Results for Probing Proteomic Biomarkers in Plasma of Transplant Patients.
Finally, Dr। Ralph Weissleder from Massachusetts General Hospital/Harvard will discuss Imaging Biomarkers: New Horizons and Opportunities in Transplantation, and will share the latest information on imaging biomarkers and how advanced imaging techniques may soon help in the management of transplant patients. Three related biomarker abstracts are also slated for presentation during the session.

“In recent years, there has been an intensive focus on enhancing our ability to provide the most particular predictive, diagnostic, prognostic and therapeutic guidance for patients. This intent has been enabled by unbiased and targeted examination of genotypes and haplotypes that may convey risk or protection against certain disease processes like immune rejection, as well as by defining the molecular signatures of a disease process like rejection by measuring mRNA, proteins or metabolites in the blood or urine. Distillation of such data, along with clinical features, is intended to improve care, reduce costs, and make patients lives more enjoyable,” said Bruce McManus, MD, PhD, University of British Columbia, one of the Co-Chairs for the biomarkers plenary session.
Until recently, heart muscle biopsy was the only method available to rule out heart transplant rejection and guide treatment with anti-rejection, or immunosuppressive, therapy। Aside from the invasive and painful nature of the procedure, a biopsy is only able to detect rejection after damage has already occurred to the heart tissue. Similar dilemmas exist in the monitoring of lung transplant recipients.

Alternatively, non-invasive molecular testing of a routine blood sample allows analysis of gene expression in white blood cells, proteins in the plasma, and metabolites in blood and urine. The latter biomarkers provide information on the immune, inflammatory and injury status of the transplanted heart before tissue damage occurs. The new and original information on biomarkers and personalized care in lectures given at ISHLT will offer a deeper knowledge of this innovative direction that is revolutionizing health care. The discussion will also raise awareness of alternatives to biopsy procedures that are on the horizon.
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About ISHLT
The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases. Created in 1981, the society now includes more than 3,000 members from more than 45 countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.
ISHLT maintains two vital databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices. In fall 2006, ISHLT released the first international guidelines for heart failure patient management. For more information, visit http://www.ishlt.org/.

Small molecule miRNAs regulate female mouse fertility

2008-04-09T18:15:00.000+05:30

Small molecules known as miRNAs, which are generated naturally by the body,
regulate the conversion of genetic information into proteins.

New data, generated by Jiahuai Han and colleagues, at The Scripps Research Institute, La Jolla, have now indicated that miRNAs can control the fertility of female mice.

The generation of miRNAs is a complex process that involves a protein known as Dicer. In the study, mice expressing substantially lower levels of Dicer than normal mice (Dicerd/d mice) were found to have only one defect — the female mice were infertile. Infertility was a result of impaired functioning of the corpus luteum, the structure that forms at the site of release of the fertilized egg and that is required to maintain pregnancy at the early stages.

Detailed analysis indicated that the functioning of the corpus luteum was impaired because it was unable to form new blood vessels, and that this was associated with increased expression of the protein TIMP1, which inhibits blood vessel formation.

As injection of the miRNAs miR17-5p and let7b into the ovaries of Dicerd/d mice decreased expression of TIMP1 and increased the number of blood vessels in the corpus luteum, the authors concluded that the development and function of the corpus luteum in mice is tightly regulated by miRNAs.

###

TITLE: Impaired microRNA processing causes corpus luteum insufficiency and
infertility in mice

AUTHOR CONTACT:

Jiahuai Han
The Scripps Research Institute, La Jolla, California, USA.
Phone: (858) 784-8704; Fax: (858) 784-8665; E-mail: jhan@scripps.edu.

Scientists develop technique to "clean" stem cells

2008-04-08T16:34:00.000+05:30

Scientists in Singapore have developed a strategy to "clean up" embryonic stem cells, which researchers hope can one day be used to replace damaged tissues and for other tailor-made personal treatments.

Embryonic stem cells are master cells that can grow, or "differentiate", into any type of cell or tissue, and are subsequently transplanted into the body.
But some studies have shown that residual stem cells that fail to differentiate can turn cancerous later on.

In the journal Stem Cells, scientists in Singapore said they generated antibodies that successfully killed off these residual stem cells in mice.

"Although human embryonic stems cells are a very powerful source to make differentiated cells, like heart cells, the problem is that you can have residual cells and there is a safety concern because they can form ... a mass of tumour cells," said Andre Choo, senior scientist at the Bioprocessing Technology Institute in Singapore.

"So if you give a product that is 95 percent heart cells, but 5 percent embryonic stem cells, it may be a problem later on," he said by telephone.

The researchers managed to generate antibodies in mice after injecting human embryonic stem cells into the animals.

The antibodies were then harvested and added to cultured embryonic stem cells that had been newly differentiated on laboratory dishes.

"It (the antibody) specifically eliminated undifferentiated cells within 30 minutes but left differentiated cells untouched," the researchers wrote.

The mixture was later injected into a batch of mice, while another batch of mice were given untreated stem cells.

After 6 to 8 weeks, the researchers detected tumours in the mice that received untreated stem cells, but those that received the mixture of stem cells and antibodies were free of tumours even after 20 weeks.

"We made antibodies that can kill them (undifferentiated stem cells) ... it acts as a clean up step for you to remove any of these rogue cells or potentially problematic cells," Choo said. (Reporting by Tan Ee Lyn; Editing by Alex Richardson)

Cell Replacement Strategy for Parkinsons Disease Perhaps Not Effective, Study Finds GEN News Highlights

2008-04-08T16:10:00.000+05:30

Scientists reported that neurons grafted into the brain of a patient with Parkinsons disease 14 years ago developed Lewy body pathology, the defining pathology for the disease.

In the impacted study, individuals with Parkinsons disease received fetal cell transplants to reverse the loss in the brain of striatal dopamine. The patient affected, a woman with a 22-year history of Parkinsons disease who underwent transplantation in 1993, had the longest survival after transplantation that had been reported to date among the study’s participants.

The finding suggests that Parkinsons disease can affect cells grafted into the brain in the same way the disease affects host dopamine neurons in the substantia nigra of the brain, according to the researchers.

After transplantation, the patient experienced improvements in disease symptoms into1997, but exhibited progressive worsening of disease symptoms by 2004 and died in 2007.

Studies that followed did not establish clinical benefit although significant improvement was observed in a subpopulation of patients. Post-mortem studies of individuals in these studies showed a robust survival of grafted neurons, suggesting that the cells were not affected by Parkinsons, but the researchers now think that the individuals did not live long enough for the Parkinsons disease pathology to develop in the grafted cells.

Involved researchers came from Rush University Medical Center, Mt. Sinai School of Medicine, and the University of South Florida, Tampa. The study was published in the April 6 issue of Nature Medicine.

Generex Biotechnology Announces North American Initiation of Generex Oral-lyn Phase III

2008-04-08T15:59:00.000+05:30

Diabetes StudyMonday April 7, 9:30 am ET

Patient Screening Underway in North America for the Company's Non-Injectable Insulin That is Absorbed in the Lining of the Mouth and Does Not Enter the Lungs

WORCESTER, Mass., April 7, 2008 (PRIME NEWSWIRE) -- Generex Biotechnology Corporation (NasdaqCM:GNBT - News), the leader in drug delivery for metabolic diseases through the inner lining of the mouth, announced today that it has initiated the Phase III protocol in North America for its proprietary buccally-absorbed oral insulin spray product, Generex Oral-lyn(tm), with the commencement of patient screening. The first screening took place in late March in Texas. Other clinical sites participating in the study located in the United States are in Texas, Maryland, Minnesota and California, and in Canada in the province of Alberta.

The Phase III protocol, identified as GEN084-OL, calls for a six month trial which is expected to include 750 patients with Type-1 diabetes mellitus. The primary objective of the study is to compare the efficacy of Generex Oral-lyn and the RapidMist(tm) Diabetes Management System with that of standard regular injectable insulin therapy as measured by Hba1c in patients with Type-1 diabetes mellitus. Generex Oral-lyn is delivered into the mouth via the Company's proprietary RapidMist device. Unlike inhaled insulin products, buccally-absorbed Generex Oral-lyn does not enter the lungs.

``This clinical milestone represents a long history of research and development to optimization for Generex Oral-lyn which is now entering the final clinical stage in major jurisdictions,'' said George Markus, the Company's Vice President of Regulatory Affairs. ``Our product is designed to offer a safe and convenient alternative to prandial insulin injections which can improve treatment compliance and quality of life for patients with diabetes.''

Generex Oral-lyn is presently approved for commercial sale in India and Ecuador. The delivery of Generex Oral-lyn clinical supplies to global sites and centers, including Ukraine and Russia, is on-going with roll-out to other regions to follow.

About Generex

Generex is engaged in the research, development, and commercialization of drug delivery systems and technologies. Generex has developed a proprietary platform technology for the delivery of drugs into the human body through the oral cavity (with no deposit in the lungs). The Company's proprietary liquid formulations allow drugs typically administered by injection to be absorbed into the body by the lining of the inner mouth using the Company's proprietary RapidMist(tm) device. The Company's flagship product, oral insulin (Generex Oral-lyn(tm)), which is available for sale in Ecuador for the treatment of patients with Type-1 and Type-2 diabetes and which was approved for sale in India in October 2007, is in various stages of clinical development around the world. For more information, visit the Generex website at

http://www.generex.com.

Safe Harbor Statement: This release and oral statements made from time to time by Generex representatives concerning the same subject matter may contain ``forward-looking statements'' within the meaning of the Private Securities Litigation Reform Act of 1995. These statements can be identified by introductory words such as ``expects,'' ``plans,'' ``intends,'' ``believes,'' ``will,'' ``estimates,'' ``forecasts,'' ``projects'' or words of similar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statements frequently are used in discussing potential product applications, potential collaborations, product development activities, clinical studies, regulatory submissions and approvals, and similar operating matters. Many factors may cause actual results to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, some of which are known and others of which are not. Known risks and uncertainties include those identified from time to time in the reports filed by Generex with the Securities and Exchange Commission, which should be considered together with any forward-looking statement. No forward-looking statement is a guarantee of future results or events, and one should avoid placing undue reliance on such statements. Generex undertakes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Generex cannot be sure when or if it will be permitted by regulatory agencies to undertake additional clinical trials or to commence any particular phase of clinical trials. Because of this, statements regarding the expected timing of clinical trials cannot be regarded as actual predictions of when Generex will obtain regulatory approval for any ``phase'' of clinical trials. Generex claims the protection of the safe harbor for forward-looking statements that is contained in the Private Securities Litigation Reform Act.

First hybrid embryos created

2008-04-08T14:59:00.000+05:30

First hybrid embryos created

UK scientists have successfully created human-animal hybrid embryos using nuclear transfer.

Scientists from the UK's Newcastle University say they have successfully created hybrid embryos derived from human cells and a cow egg.

The team, led by Dr Lyle Armstrong, presented preliminary data to a conference in Israel last week but stressed that the results are only preliminary and have yet to
be validated by the peer review process.

In a statement, the university said the embryos were created from one of its human embryonic stem cell lines, Ncl-1. The human cells were injected into an
enucleated cow egg, which was then encouraged to divide. The team said the hybrid embryos survived for three days.

The university's Professor John Burn told the BBC that the team now had "preliminary data which looks promising but this is very much work in progress".

He said the next step was to "get the embryos to survive to around six days when we can hopefully derive stem cells from them".

Armstrong and his co-researcher Dr Majlinda Lako have a licence from the UK's Human Fertilisation and Embryology Authority (HFEA), granted in January, to
conduct the research.

The UK Parliament will debate next month further regulation of the research under its Human Fertilisation and Embryology Bill.

Under the current law, any hybrid embryos created have to be destroyed at 14 days

Organ growth, warts and allSalvador

2008-04-08T14:17:00.000+05:30

Organ growth, warts and allSalvador, Warts, Hippo and Yorkie are an eclectically named group of genes that form the core components of a signalling pathway in Drosophila that regulates
control of organ size and may have some important parallels with human cancer.

Dr Kieran Harvey from the Laboratory of Cell Growth and Proliferation at the PeterMac Centre in Melbourne is interested in how organ growth and size are
regulated during development by the newly discovered Salvador-Warts-Hippo (SWH) signalling pathway. Activation of this pathway restricts organ size by limiting
cell growth and proliferation and by stimulating cell death via apoptosis.

Harvey's primary interest is how this system works in Drosophila melanogaster, where the pathway was identified, but the work also has important implications for
human tumorigenesis as control of proliferation and cell survival are also central to the development of cancer.

At the Hunter Cell Biology meeting this week, Harvey will present his group's latest findings on this important signalling cascade in fruit flies and how this might
translate to human disease.

Harvey's interest in the pathway with the eclectic name is more than academic - he was part of its discovery. After completing a PhD in cell biology with Sharad
Kumar at the University of Adelaide in 2000, Harvey took up a five-year postdoctoral position at the Massachusetts General Hospital Cancer Center in Boston and
the University of California, Berkeley. In the laboratory of developmental cell biologist Iswar Hariharan, Harvey started working with Drosophila as a model organism
for the first time.

"We were screening flies for genes that gave cells a growth advantage, looking for outgrowth of tissues such as eyes and wings," Harvey says. The group identified
two components of a previously undiscovered pathway - a novel gene called Salvador, and a previously known gene called Warts (published in Cell, 2002).

They subsequently found Hippo and Yorkie, and together, these four genes comprise the core components of the Drosophila SWH pathway, required for normal cell
growth, proliferation and apoptosis.

Identifying Hippo and showing that it controlled tissue growth with Salvador and Warts comprised a second Cell paper for Harvey in 2003. Deregulation of the SWH
pathway causes a significant and abnormal increase in organ size, which is lethal for developing flies and clearly of more general biological significance.

Twelve components of the SWH pathway have now been identified in flies, mostly using clonal screens for genes that affect organ size. All of these have
mammalian counterparts and several have been implicated as tumour suppressors or oncogenes.

According to Harvey, many of these were known genes, discovered in the 1980s and 90s by different groups and later slotted into the SWH pathway. The
components belong to a range of protein classes: kinases (Hippo and Warts and Discs overgrown), scaffold molecules (Salvador), membrane-associated
signalling proteins (Expanded and Merlin), and cytoskeletal motors (Dachs) to transcriptional regulators (Yorkie).

Fat and tissue growth

In early 2006, Harvey moved back to Australia to set up a group at the Peter MacCallum Cancer Centre and continue his work on Salvador-Warts-Hippo signalling.

"Our major focus at the time was to fill out the pathway [as only five components were then known]," Harvey says.

"Initially we looked for a transmembrane receptor for the pathway that might signal to one or more of the so-far all intracellular components." Taking a candidate
approach, Harvey looked for plasma membrane proteins previously shown to regulate tissue growth in Drosophila and came across Fat, an atypical member of the
cadherin family of adhesion proteins.

According to Harvey, mutations in Fat were first discovered in flies in the 1920s with dominant alleles that affected wing size and abdomen shape.

"Then, in the late 1980s, Fat was shown to regulate tissue growth and cell proliferation, before cloning of the gene in the 90s identified it as a cadherin, but still no
one knew how it worked to regulate organ development."
Cadherins span the membranes of adjacent cells to stick them together and form a barrier, but are also important for signalling to intracellular pathways.
In the first part of his presentation at the Hunter meeting, Harvey will discuss how they identified Fat as a component of the SWH pathway. "Based on earlier work by
others, we did genetic studies in our flies and also stained Fat-mutant tissues for different target genes of the SWH pathway such as cyclin E, which drives cell
proliferation, and DIAP1, which inhibits apoptosis."

There were strong genetic interactions between Fat and multiple components in the pathway, and animals lacking Fat were phenotypically similar to those with
depressed SWH signalling.

Further studies revealed a potential mechanism by which Fat regulates SWH pathway activity. It seemed that Fat regulates the apical membrane localisation of an
intracellular protein called Expanded, another upstream regulatory protein in the pathway associated with the plasma membrane.

"We are not sure at the moment how all this happens," Harvey says. "Expanded sits at the apical membrane of developing cells and presumably acts as some sort
of bridge between the surface proteins and either the actin cytoskeleton or downstream signalling proteins. We therefore think that Fat restricts organ size by
stimulating downstream SWH pathway components to limit transcription."

The current goal of Harvey's group is to nut out the entire SWH pathway. "We now want to know exactly how Fat signals to the downstream components, but also
how Fat itself is regulated. Evidence is mounting in both Drosophila and mammals that the SWH pathway is controlled by cell adhesion, but we do not know how.
"Fat is a likely candidate to mediate adhesion dependent-signalling given that it is a cadherin, but other proteins might also be involved, such as another cadherin,
Dachsous."

Fat and Expanded

At the Hunter meeting, Harvey will also discuss new findings on the temporal control of SWH pathway activity throughout Drosophila development.

"To date, all pathway components were thought to function throughout development in flies. However, we have found that although the four core components of the
pathway act early on to regulate growth and proliferation and later on in development to drive apoptosis, other upstream components act differentially.

"In particular, Fat and Expanded appear to control organ size during the growth phase, but play no role in triggering apoptosis once the organ reaches critical size."
Harvey's group has also started to look at the role of SWH pathway components in different human cancers, and several members have been implicated already.

According to his recent article in Nature Reviews Cancer (Harvey and Tapon, 2007), "evidence from patient samples, cancer cell lines and mouse models indicate
that disruption of the analogous human pathway is involved in tumorigenesis".

At the Peter MacCallum Cancer Centre, Harvey has access to a large array of tumour samples from patients across the cancer spectrum. Using this resource, his
team will search for mutations in individual pathway genes, as well as staining tumours for expression of transcriptional enhancer protein, YAP, which is the
mammalian orthologue of the fly protein yorkie.

"Essentially, instead of going in and sequencing all known pathway components in each sample, we are looking for expression of this common key downstream
protein," Harvey says. "All of the upstream components of the pathway impinge on this one oncoprotein and regulate its stability, phosphorylation and shuttling
between nucleus and cytoplasm."

Once his team has found a class of tumours with increased YAP expression, they will sequence the tumour suppressor genes involved and do functional assays.
Career development

Kieran Harvey received funding from the Human Frontier Science Program (HFSP) in 2006 to set up his laboratory in Australia. HFSP is a prestigious international
granting body that has Australian membership through the National Health and Medical Research Council (NHMRC), involving more than $70 million in grants and
fellowships each year.

Harvey also won a Career Development Award from the Leukemia Lymphoma Society and a Peter MacCallum Cancer Centre Junior Investigator Award to help
kick-start his independent research career back in Australia.

As testament to those funding decisions, Harvey has continued to make pivotal findings in the field of development cell biology, and last year secured a four-year
Australia Career Development Award Fellowship from the NHMRC.

Thanks : Austalralian news

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2008-04-01T17:50:00.000+05:30

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