VATIS Update Biotechnology . Sep-Oct 2009

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Biotechnology Sep-Oct 2009

ISSN: 0971-5622

VATIS Update Biotechnology is published 4 times a year to keep the readers up to date of most of the relevant and latest technological developments and events in the field of Biotechnology. The Update is tailored to policy-makers, industries and technology transfer intermediaries.

Co-publisher: Biotech Consortium India Ltd
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Japan launches new biofuel made from rice

Japan has started selling a new biofuel made from rice which is expected to help the country reduce its dependence on imported petrol and make better use of deserted farmlands. The Niigata prefecture of Japan has begun selling the new biofuel, produced from domestically grown brown rice and blended up to three per cent with petrol.

According to Japans National Federation of Agricultural Cooperative Associations Zennoh (JA Zennoh), the bioethanol is equivalent to regular petrol both in quality and mileage, and will be available in a similar price range. The project will also promote effective utilization of rice paddies that are left uncultivated due to the governments rice-reduction programme, JA Zennoh said, adding that it is expecting an annual sale of about 33,000 kilolitres of the new fuel.

Japanese oil companies had started selling petrol blended with bio-ethanol in 2007 in some retail markets in the country, but none of the mixtures was previously made using rice-derived biofuel. The countrys annual petrol demand is estimated at 60 million kilolitres.

India to set up incubation units in leading research entities

SThe Department of Science and Technology (DST), Government of India, has allocated Rs 300 million (US$6.5 million) for setting up five incubation centres across the country within the next five years. DST has already identified two locations for the centres: the All India Institute of Medical Sciences (AIIMS), New Delhi, and the Indian Institute of Science (IISc), Bangalore, said Mr. Harkesh Kumar Mittal, Head, National Science and Technology Entrepreneurship Development Board, New Delhi.

The facility at AIIMS is being set up with the assistance of Indian Institute of Technology-Mumbai, and Stanford University, the United States. The incubator would help medical students and scientists who have worked and developed biomedical products. At IISc, which has a dedicated Society for Innovation & Development (SID) Entrepreneurship Centre, there are several companies engaged in biotech diagnostics and bioinformatics, including Bigtec and Strand Life Sciences.

First genetically engineered malaria vaccine to enter human trials

Scientists at the Walter and Eliza Hall Institute, Australia, have created a weakened strain of the malaria parasite that will be used as a live vaccine against the disease. The vaccine developed in collaboration with researchers from the United States, Japan and Canada will be trialled in humans from early next year. The human trials of the vaccine will take place at the Walter Reed Army Institute of Research in the United States.

Professor Alan Cowman, Head of the Institutes Infection and Immunity Division, said in developing the vaccine the research team had deleted two key genes in the Plasmodium falciparum parasite which causes the form of malaria most deadly to humans. By removing the genes, the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death.

Prof. Cowman said similar vaccines had been tested in mice and offered 100 per cent protection against malaria infection. He said it was hoped the vaccine would produce similar results in humans. This approach to vaccine development using a weakened form of the whole organism that causes a particular disease has proven successful in eradicating smallpox and controlling diseases such as flu and polio. Prof. Cowman said it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite.

United Kingdom to support GM crops for worlds poor

The United Kingdom is planning to spend up to 100 million to support genetically modified (GM) crops for the worlds poor despite not having allowed any of the controversial foods to be grown commercially at home. A new white paper shows the government is committed to dramatically increasing spending on high-tech agriculture in the next five years, much of which will be on GM crop research. Biofortified crops, containing added vitamins, will receive 80 million of development money, 60 million will go on researching drought-resistant maize for Africa and a further 24 million will be spent on pest resistance. In addition, support for an international network of GM crop research stations, in collaboration with GM companies, will be doubled. A further tranche of aid will go to a research initiative backed by Syngenta, genetically modified crop company, which is developing a strain of rice modified to increase vitamin A.

The white paper avoids the terms genetically modified. But scientists and development experts are clear that much of the money will be spent on GM. The government has in the past revealed its strong support of high-tech food for Africa as a way to reduce poverty and also gain acceptance for GM foods in the United Kingdom. Last year, the then science minister, Mr. Ian Pearson, said: If GM can demonstrably provide benefits for sub-Saharan Africathe public will want to support [it].

Artificial brain is about a decade away

A detailed, functional artificial human brain can be built within the next 10 years, a leading scientist has claimed. Dr. Henry Markram, Director of the Blue Brain Project a joint project of Ecole Polytechnique Fdrale de Lausanne of Switzerland and IBM company based in the United States has already simulated elements of a rat brain. Dr. Markram told the TED Global 2009 conference that a synthetic human brain would be of particular use in finding novel treatments for mental illnesses. Around two billion people are thought to suffer some kind of brain impairment, he said. It is not impossible to build a human brain and we can do it in 10 years, he said. Shared fabric, the Blue Brain Project, was launched in 2005 and aims to reverse engineer the mammalian brain from laboratory data.

Dr. Markrams team has focused on the neocortical column repetitive units of the mammalian brain known as the neocortex. It is a new brain, he explained. The mammals needed it because they had to cope with parenthood, social interactions complex cognitive functions. The evolution of neocortex is continuing, he said, at a great speed. Over the last 15 years, Dr. Markram and his team have picked apart the structure of the neocortical column.

The project now has a software model of tens of thousands of neurons each one of which is different which has allowed them to digitally construct an artificial neocortical column. While each neuron is unique, the team has found that circuitry in different brains have common patterns, which they think is species-specific. The team uses a supercomputer to make the model come alive. Simulations have started to give the team clues about how the brain works. For example, they can show the brain a picture and follow the electrical activity in the machine.
Source: news.

Europe issues guidelines for drugs from GM plants

The prospects of plant-derived pharmaceuticals in Europe have brightened with the recent publication of the first European guidelines for growing these genetically modified (GM) plants. Drawn up by the European Food Safety Authority (EFSA), the guidance describes how developers of GM plants grown for purposes such as producing pharmaceuticals or industrial enzymes will need to assess the potential risks to humans, animals and the environment. The guidelines are reported to compare favourably with the regulations in the United States.

In the view of the GMO Panel, the fundamental principle of comparative assessment comparing the properties of a GM plant with its unmodified parent line is valid for assessing the safety of molecular farming plants. In the case of pharmaceutical plants, EFSA asks plant manufacturers to provide comprehensive descriptions of the active substance and its properties as is the case with drug approvals. Risk assessments will also look at the probability of environmental exposure to the new substances and how high this exposure could be.


StemCyte to conduct clinical trials in India

After conducting clinical trials for spinal cord injuries in the United States and China, StemCyte Inc., the United States-based stemcell transplantation and therapeutics company, is planning to conduct the same in India next year. StemCyte has set up a first-of-its-kind umbilical cord blood (UCB) public bank for India in a joint venture with Apollo Hospitals and Cadila Pharmaceuticals in India. Set to be operational by the end of this year, the new entity called StemCyte India Therapeutics Pvt. Ltd. will aid in carrying out clinical trials in India.

Last year, StemCyte signed two research and licensing agreements for human UCB stem cell treatment for spinal cord injury, stroke, multiple sclerosis, Alzheimers disease, Parkinsons disease and other problems of the central nervous system. The initiatives are being developed by Dr. Wise Young, a neuroscientist at Rutgers, the State University of New Jersey, the United States, and Dr. John Lin, a professor at China Medical University Hospital, Taiwan, as part of a research agreement with StemCyte.

The cost of processing one unit of stem cell is estimated at Rs 0.5 million (US$108,000). The company plans to process and store 25,000 UCB units for treating patients throughout the world, including India, said Mr. Tushar Dalal, President, StemCyte India. Apollo Hospitals, in collaboration with StemCyte, has announced its plans to establish a Rs 600 million (US$13 million) stem cell research institute in Gujarat, to be completed by the year end.

Dow AgroSciences to acquire Pfister Hybrids

In the United States, Dow AgroSciences LLC is acquiring the majority of assets of Pfister Hybrids, the corn company. The addition of Pfister Hybrids will further expand Dow AgroSciences current seeds business, as the company anticipates the introduction of SmartStaxTM, a multi-event technology that it developed with Monsanto, in 2010 and its own Herbicide Tolerance Technology in corn in 2012. Under the terms of the agreement, Dow AgroSciences will acquire the Pfister brand and the sales and marketing areas, as well as the warehousing and administrative services of the business. Dow AgroSciences will continue to independently market seeds under the Pfister Seeds brand.

Ranbaxy to set up new drug making unit

Indicating that the ownership change has not altered the growth plans of Ranbaxy, the Indias largest drug maker has secured an approval from the Himachal Pradesh government to build a new drug manufacturing facility in Baddi. This is the first new manufacturing project of Ranbaxy since Japans Daiichi Sankyo became its major shareholder last year. Company sources declined to provide details of the project but said it is well on track to qualify for tax benefits. The estimated cost of the project is known to be around Rs 400 million (US$8.7 million). While the Baddi project is to augment domestic supplies, Ranbaxys Mohali pharma SEZ project, also in the process of execution, is meant for exports.

GSK investing millions in AIDS drugs for Africa

The worlds second biggest drugmaker, GlaxoSmithKline (GSK) based in the United Kingdom, plans to invest up to US$97 million over 10 years to improve research, development and access to AIDS drugs in Africa. It has also entered into a new free voluntary licensing agreement for AIDS drug abacavir (Ziagen) with South African generic drugmaker Aspen Pharmacare, in which it has a 16 per cent stake. Aspen will manufacture a cheaper generic version of the drug.

The latest steps, announced by GSK CEO Mr. Andrew Witty on a visit to Kenya, follow pressure from campaigners and some governments for drug companies to do more to provide life-saving medicines to the poor, particularly in sub-Saharan Africa. The company took a lead in February by promising to place many of its patents on drugs for tropical diseases into a free pool, but it stopped short of offering patents on medicines for HIV/AIDS, which GSK does not consider to be a neglected disease.

The United States biotech firm Alnylam Pharmaceuticals is the only other big drug company to have committed to pool some drug patents. GSKs new investments will see up to 50 million channelled into a fund to support non-governmental organizations working with pregnant women to prevent mother-to-child transmission of HIV. A further 10 million in seed funding will go to support public-private partnership work in developing AIDS medicines specifically for children.

Gilead and Tibotec to develop pill for HIV therapy

Gilead Sciences, the United States, and Tibotec Pharmaceuticals, Ireland, are joining forces to develop and market a once-daily pill for HIV. The fixed-dose antiretroviral regimen will contain Gileads Truvada (emtricitabine and tenofovir disoproxil fumarate) and Tibotecs investigational non-nucleoside reverse transcriptase inhibitor TMC278 (rilpivirine hydrochloride, 25 mg) for treatment-nave individuals. Tibotec is studying the combination in Phase III trials at present.

Gilead will take the lead role in the manufacture, registration, distribution and commercialization in industrialized countries, excluding Japan. Tibotec has the right to co-promote in Gileads regions and remains responsible for the commercialization of TMC278 as a stand-alone product. If approved, the new product would become the second such antiretroviral treatment regimen for HIV available in a single tablet taken once daily.
Source: www.

Sanofi acquires Shantha Biotechnics

Making the first big-ticket deal in the Indian biotech sector, the French drug maker Sanofi-Aventis will pick up a controlling stake in the Indian vaccine maker Shantha Biotechnics. Sanofis vaccine unit, Sanofi Pasteur, will acquire a subsidiary of French bioindustrial group Merieux Alliance, ShanH, which owns a majority stake in Shantha Biotechnics. The transaction, set to close before the end of the third quarter, values the Indian company at 550 million. Merieux Alliance had bought 60 per cent in Shanta in 2006, which it later raised to 80 per cent, said a Reuters report. Earlier this year, there were reports that both Sanofi and GlaxoSmithKline, the United Kingdom, were vying for control of Shantha via Merieux Alliance.

GE Healthcare and Geron to commercialize stem cell drug

GE Healthcare, the United Kingdom, and Geron Corp., the United States, have entered into a global alliance and exclusive licence agreement to develop and commercialize cellular assay products derived from human embryonic stem cells (hESCs) for use in drug discovery, development, and toxicity screening. The programme will use stem cells derived from hESC lines listed on the United States National Institutes of Health Human Pluripotent Stem Cell Registry.

Under the terms of the agreement, GE Healthcare has been granted an exclusive licence under Gerons extensive intellectual property product range covering the growth and differentiation of hESCs, as well as a sub-licence under Gerons rights to the foundational hESC patents held by the Wisconsin Alumni Research Foundation. GE Healthcare will fund the R&D programme and will look after manufacturing, sales, and distribution of the products developed. Under the terms of the agreement, intellectual property rights arising from the alliance programme research will be shared, with GE Healthcare getting rights for the development of drug discovery technologies, and Geron getting the rights for cell therapy applications.


Structure of HIV genome decoded

Scientists from the University of North Carolina at Chapel Hill, the United States, say they have decoded the entire genetic content of human immunodeficiency virus-1 (HIV-1) the main cause of acquired immunodeficiency syndrome (AIDS) in humans. They hope this will pave the way to a greater understanding of how the virus operates, and potentially accelerate the development of drug treatments.

The research, published in Nature, may allow scientists the chance to look at the information buried inside HIV-1, which carries its genetic information as single-stranded RNA rather than double-stranded DNA. The information enclosed in DNA is encoded in a relatively simple way, but in RNA this is more complex. The scientists said they planned to use the information to see if they could make tiny changes to the virus. If it doesnt grow as well when you disrupt the virus with mutations, then you know you have mutated or affected something that was important to the virus, says Dr. Ronald Swanstrom, professor of microbiology and immunology. We are also beginning to understand tricks the genome uses to help the virus escape detection by the human host, he said.

Gene linked to blood cancer

Researchers in the United States have identified a gene variant that carries nearly twice the risk of developing an increasingly common type of blood cancer. Investigators at the University of California at Berkeley (UCB) and the Translational Genomics Research Institute (TGen) found that mutations in a gene called C6orf15, or STG, are linked with the risk of developing follicular lymphoma, a cancer of the bodys disease-fighting network.

In the first genome-wide association study of non-Hodgkin lymphoma, the scientists identified a single nucleotide polymorphism (SNP) that could determine susceptibility to follicular lymphoma. The SNP, a DNA variant within the more than three billion base pairs in the human genome, was identified as rs6457327. The study was led by Dr. Christine Skibola, Associate Adjunct Professor at UCBs School of Public Health, and Dr. Kevin M. Brown, an Associate Investigator in the Integrated Cancer Genomics Division of TGen.

The researchers found that, for SNP rs6457327, the presence of the G allele protected against follicular lymphoma, while the presence of the A allele predicted an increased risk of developing the disease nearly doubling the risk. Dr. Skibola said more studies would be needed to determine the biological importance of other STG SNPs linked to rs6457327 that might change the function of the gene. This could help determine how they might influence risk of the disease.

Genetic trigger for disease-fighting antibodies

In the United States, a research team led by the La Jolla Institute for Allergy & Immunology has identified the specific gene that triggers the body to produce disease-fighting antibodies a seminal finding that clarifies the exact molecular steps taken by the body to mount an antibody defence against viruses and other pathogens. The finding has major implications for the development of new and more effective vaccines.

The La Jolla Institutes Dr. Shane Crotty was the lead researcher on the team, which also included scientists from Yale University led by Dr. Joseph Craft. The finding is important because it identified the molecular switch that tells the body to create antibodies. Antibody production is a multi-step process that involves interactions between many cellular players; key among them the CD4 helper T cells, which are disease-fighting white blood cells. There were different types of these CD4 helper T cells and, for many years the scientists had thought that one of the four varieties of CD4 helper type 2 cells (known as TH-2 cells) triggered the antibody process. But about a decade ago, they realized that there was a fifth variety of CD4 helper T cell that initiated antibody production. They named the cell TFH.

Studying the workings of the TFH pathway, Dr. Crottys team conclusively proved that the BCL6 gene was a master regulator in the process. If this gene is turned on, more TFH type cells are produced, and these cells signal the B cells to produce antibodies. The more TFH cells produced, the greater the antibody response.

Novel gene found for dilated cardiomyopathy

Researchers in the Heart Institute at Cincinnati Childrens Hospital Medical Centre, the United States, have discovered a novel gene responsible for heart muscle disease and chronic heart failure in some children and adults with dilated cardiomyopathy (DCM). Their study found that mutations in the ANKRD1 a gene that encodes a protein that plays a role in the structure and functional ability of the heart would cause DCM, which is the most common cause of chronic heart failure in young people.

Our study indicates that variants in ANKRD1 result in dysfunction of the contraction apparatus and signalling machinery of the heart, the method by which cells communicate to influence heart function, says Dr. Jeffrey Towbin, Co-Director of the Heart Institute and Director of Cardiology at Cincinnati Childrens. This clarifies the mechanisms by which these inherited mutations cause disease in a subset of DCM patients.

Dr. Towbins team screened 208 patients, mostly children and young adults, with DCM for gene mutations. They found three, disease-associated variants of the ANKRD1 gene. All four patients carrying the variants were male. This prevalence rate is consistent with prevalence data for most of the other known genes associated with DCM.

Active genes discovered in developing mammal brain

A study at the Pennsylvania State University, the United States, provides new information about the genes that are involved in a mammals early brain development, including those that contribute to neurological disorders. The study is the first to use high-throughput sequencing to uncover active genes in developing brains. The results of the research, which was led by Distinguished Professor of Biology Dr. Hong Ma and Associate Professor of Biology Dr. Gong Chen, one day could lead to the development of drugs or gene therapies that treat neurological disorders such as autism and mental retardation.

The scientists sequenced millions of messenger-RNA molecules, which carry genetic information from DNA molecules to protein molecules. They obtained the RNA from the brains of mice, and found that over 16,000 genes more than half of the mouses entire set of known genes are involved in the brains development and functions. They focused on two critical times during the development of brain: embryonic day 18 (E18) and post-natal day 7 (P7): two time points that represent major milestones during brain formation. Brain development in an 18-day-old embryo involves a significant amount of brain cells, or neurons. In contrast, brain development in a 7-day-old infant involves the formation of numerous connections between these neurons. Our goal was to determine which genes are active during these two critical times, said Dr. Ma.

The scientists examined genes that correspond to the RNA molecules from the cortex responsible for most cognitive and sensory abilities. They found that over 3,700 of the 16,000 genes identified have different levels of activity between the E18 and P7 time points. Some of the genes that the researchers found in mice are known to be matched to the human genes that are involved in neurological disorders, such as Alzheimers disease and autism. Our results can help pinpoint the specific time during brain development when the genes related to certain diseases are active, said Dr. Ma. This could help other scientists to develop drugs or gene therapies that can treat the diseases.

New Alzheimers gene discovered

In the United States, a University of California Irvine (UCI) study has found that a gene called TOMM40 appears twice as often in people with Alzheimers disease than in those without it. The harmful form of TOMM40 significantly increases ones susceptibility when other risk factors such as having a gene called ApoE-4 are present, the study reports. People with ApoE-4 are three to eight times more likely to develop Alzheimers.

The TOMM40 gene influences the ease with which molecules can get in and out of mitochondria, the energy production centre and stress mediator of cells. TOMM40 also processes materials that form amyloid plaque, a hallmark of Alzheimers, said Dr. Steven Potkin, lead author of the study and UCI Professor of Psychiatry & Human Behaviour. With aging, the number and function of mitochondria decrease, accompanied by a parallel increased risk of developing Alzheimers, he said. This study points to the use of therapies based on mitochondria for treating the disease.

A gene suspect in type 1 diabetes

Scientists at Stanford University, the United States, have identified a gene that may play a role in the development of type 1 diabetes. The study team, led by Dr. C. Garrison Fathman, examined genes from mice that develop a type 1 diabetes-like disease. The investigators found that cells in the pancreatic lymph nodes of mice make two forms of the same gene called deformed epidermal autoregulatory factor 1 (Deaf1). One form is full-length and functional and the other is a shorter, non-functional variant. The full-length Deaf1 controls the production of molecules needed to eliminate immune cells that can destroy insulin-producing cells. The presence of the Deaf1 variant was found to prevent the full-length Deaf1 protein from functioning normally. Further experiments showed that the variant form blocked the genes needed to produce certain molecules involved in immune regulation.

When the researchers measured the levels of these two forms in people with type 1 diabetes and in healthy individuals, levels of the variant form were found to be higher in people with type 1 diabetes compared with those in healthy controls. In addition, the variant form, as in mice, inhibited the full-length form from functioning normally.

The researchers propose that the development of type 1 diabetes may in part be due to increased levels of the Deaf1 variant protein in pancreatic lymph nodes of people with this disease. Higher levels of Deaf1 variant may, in turn, lead to reduced production of molecules that are required to educate the immune system not to attack the bodys own cells, including the insulin-producing cells of the pancreas. These results show that Deaf1 variant form is a risk factor for type 1 diabetes and provide a target for drug development to combat the disease.

Anti-aging gene connected to hypertension

Researchers at the University of Oklahoma Health Sciences Centre, the United States, have shown the first link between a newly discovered anti-aging gene and hypertension. Led by principal investigator Dr. Zhongjie Sun, the researchers tested the effect of the anti-aging gene called klotho on reducing hypertension. They found that by increasing the expression of the gene in laboratory models, they not only stopped blood pressure from continuing to rise, but also succeeded in lowering it. The most impressive result was the complete reversal of kidney damage, which is associated with prolonged high blood pressure. Scientists have been working with the klotho gene and its link to aging since 1997 when it was discovered by Japanese scientists.

The researchers used one injection of the klotho gene in hypertensive research models and were able to markedly reduce blood pressure by the second week. It continued to decline steadily for the length of the project 12 weeks. The klotho gene was delivered with a safe viral vector that is currently used for gene therapy. Researchers are studying the genes effect for longer periods to test its ability to return blood pressure levels to normal.


Defective transport protein causes plaque build-up in brain

A malfunction in the network of cells that forms the blood-brain barrier (BBB) allows the toxic build-up of amyloid plaque that characterizes Alzheimers disease, report scientists at the Saint Louis University School of Medicine, the United States. The scientists worked with a mouse model of human Alzheimers disease to study the action of low-density lipoprotein receptor related protein-1 (LRP-1), the major brain-to-blood transporter of amyloid-beta protein at BBB. For this purpose, they developed specific anti-sense RNA to block the synthesis of LRP-1 and thereby deplete it from the cells of BBB.

Results of this study revealed that these anti-sense RNAs in comparison to random anti-sense RNA selectively decreased LRP-1 expression, reduced BBB clearance of amyloid-beta protein, increased brain levels of amyloid-beta protein, and impaired learning ability and recognition memory in mice. Having confirmed the importance of LRP-1 in transporting amyloid-beta protein out of the brain, the investigators looked at the factors that could affect LRP-1s ability to function. They reported that inflammation was directly linked to the malfunction of LRP-1.

The scientists induced inflammation in the brains of mice with lipopolysaccharide and found that inflammation increased brain amyloid-beta protein levels by three mechanisms: increased influx, decreased efflux and increased neuronal production. The anti-inflammatory drug indomethacin prevented inhibition of LRP-1 in the mice and tended to lower the concentration of amyloid-beta protein in the brains of the animals.

We induced inflammation in mice and found that it turned off the LRP pump that lets amyloid-beta protein exit the brain into the bloodstream. It also revved up an entrance pump that transports amyloid-beta into the brain. Both of these actions would increase the amount of amyloid-beta protein in the brain, said Dr. William A. Banks, Professor of Geriatrics and Pharmacological and Physiological Science.

Urine protein may help diagnose kidney disease

In the United States, new data collected at Columbia University Medical Centre and the Mount Sinai School of Medicine are helping scientists understand the extent to which a protein Neutrophil Gelatinase-associated Lipocalin (NGAL) can play a significant role in marking chronic kidney disease resulting from human immunodeficiency virus (HIV), while at the same time distinguishing nephropathy from more common causes such as diabetes and hypertension.

HIV-associated nephropathy (HIVAN) is a major cause of kidney disease in HIV-infected patients. Antiretroviral therapy plays an important role in the treatment of HIVAN, yet despite advances in understanding HIVAN, current treatments have largely been based on observational data and can only definitively made after a kidney biopsy.

The researchers noted that NGAL, a protein found in damaged kidneys, was prominently expressed in kidney tissue and in the urine of humans and in mouse models of HIVAN. The high levels of the urine protein were out of proportion to the degree of chronic renal failure, for example, that typifies patients with other types of chronic glomerular diseases of both mice and humans. Most strikingly, it was noticed that the rise in urinary NGAL levels was in conjunction with the development of a specific type of lesion, namely tubular cysts that typify HIVAN. The association with these cysts consequently may justify their biopsy or an aggressive treatment with antiretroviral drugs when high levels of urine NGAL are discovered.

Human cells secrete cancer-killing protein

Human cells are able to secrete a cancer-killing protein, say scientists at the Markey Cancer Centre of University of Kentucky, the United States. The researchers led by Dr. Vivek Rangnekar, a professor of radiation medicine, have determined that the tumour-suppressor protein Par-4, initially thought to be active only within cells expressing the Par-4 gene, is in fact secreted by most human and rodent cells and can target large numbers of cancer cells by binding to receptors on the cell surface. This new finding means it is not necessary to make genetic modifications, or to employ recombinant viruses, to deliver the Par-4 gene to cancer cells, and it significantly expands the potential applications of Par-4 to selectively kill cancer cells, Dr. Rangnekar said.

The study by Dr. Rangnekar and his team found that when the Par-4 molecule binds to its receptor GRP78 on the surface of a tumour cell, it triggers apoptosis or cell suicide. Consistent with previous research by his laboratory that discovered intracellular Par-4, the newly discovered secreted Par-4 acts selectively against cancer cells, leaving healthy cells unharmed. Few other molecules are known to exhibit such selectivity.

A molecule, known as TRAIL, also exerts cancer-cell-specific effects. However, the current study discovered that apoptosis inducible by TRAIL is dependent upon extracellular Par-4 signalling via cell surface GRP78. Thus, the researchers conclude, Par-4 activates a novel pathway involving cell surface GRP78 receptor for induction of apoptosis. Without Par-4, TRAIL lacks the ability to cause apoptosis.

Protein level may serve to predict severe osteoarthritis

Little is known about osteoarthritis (OA), the most common joint disorder throughout the world and a leading cause of disability, and factors predicting a severe disease course have not been identified. For the first time, a new study has discovered a biomarker vascular cell adhesion molecule 1 (VCAM-1) as a strong predictor severe OA that might require hip and knee joint replacement.

The study led by Dr. Georg Schett of the University of Erlangen-Nuremberg, Germany, involved 912 healthy individuals in Bruneck, Italy, 60 of whom underwent hip or knee replacement surgery owing to severe OA in a 15-year follow-up period. Subjects underwent a baseline examination in 1990 and follow-ups were performed every five years until 2005. Blood samples were analysed for VCAM-1, a sialoglycoprotein (a sugar-protein combination) expressed on cells in the cartilage and connective tissue.

The results showed that VCAM-1 levels were substantially elevated in the 60 individuals who underwent joint replacement, with the highest baseline levels seen in those who underwent bilateral joint replacement. The inclusion of VCAM-1 levels in risk prediction models resulted in a more accurate classification of individuals. VCAM-1 promotes leukocyte adhesion and homing to sites of inflammation. In cartilage cells, VCAM-1 expression is induced by inflammatory cytokines (proteins released by immune system cells). The scientists suggest that increased VCAM-1 levels may therefore mirror active cartilage damage or an inflammatory component in OA.

Engineered protein-like molecule protects cells from HIV

With the help of the human immunodeficiency virus (HIV) and molecular engineering, researchers have designed synthetic protein-like mimics convincing enough to interrupt unwanted biological interactions between cells. In a fundamental study of how to control protein shape, Prof. Samuel Gellman at the University of Wisconsin-Madison, the United States, created a set of peptide-like molecules that successfully blocked HIV infection of human cells in laboratory experiments. By interacting with a piece of a crucial HIV protein called gp41, the synthetic molecules physically prevent the virus from infecting host cells. The idea shows promise as a new avenue for targeting other unwanted protein interactions also, Prof. Gellman says. The work was performed with scientists from the Weill Medical College of Cornell University, the United States.

Gellman and his team made structural tweaks to the backbones of their synthetic molecules to improve stability while retaining the 3-D shape necessary to recognize and interact with the HIV gp41 protein. The resulting molecules dubbed foldamers are hybrids of natural and unnatural amino acid building blocks, a combination that allows the scientists to control shape, structure and stability with much greater precision than is currently possible with natural amino acids alone. Foldamer has the additional advantage of being highly resistant to degradation by naturally occurring enzymes that are stymied by the foldamers unusual structure. This means the molecule can remain effective longer and at lower doses.


New strategy in tumour treatment

In the United States, a new strategy proposed by researchers at Dartmouth Medical School and Amtek may treat tumours that do not respond to conventional treatment. The study used a combination of two agents to selectively kill tumours while protecting healthy cells.

In previous studies, researchers discovered that a specific enzyme methylthioadenosine phosphorylase (MTAP) is missing in 35-70 per cent of lung, pancreatic and biliary tract cancer, melanoma, glioblastoma, osteosarcoma, soft-tissue sarcoma, mesothelioma and T-cell acute lymphoblastic leukemia. Since the discovery of MTAP-negative tumours, there have been several proposals to take advantage of the frequent absence of MTAP in so many lethal cancers. None of them, however, led to successful clinical use.

In the new strategy developed by Dr. Martin Lubin, Professor of Microbiology (Emeritus) at Dartmouth and Dr. Adam Lubin of Amtek, two agents are used: one drug is toxic both to cancer cells and to normal host tissues, while the other non-toxic drug protects normal tissues from the toxic action of the first agent. They go on to state that with their strategy, greatly increased doses of drugs could be used for tumours not susceptible to low doses, without harm to host tissues.
Source: www.

Vitamin D, curcumin may help clear amyloid plaques

In the United States, scientists from the University of California, at Los Angeles (UCLA) and at Riverside (UCR), and from the Human BioMolecular Research Institute (HBMRI) have found that a form of vitamin D, together with curcumin found in turmeric spice, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques that are considered the hallmark of Alzheimers disease. The research findings may lead to new approaches in preventing and treating Alzheimers by utilizing the property of vitamin D3, both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta.

The scientists isolated monocyte cells, which transform into macrophages that act as the immune systems clean-up crew, from blood samples of nine Alzheimers patients, one patient with mild cognitive impairment and three healthy control subjects. They incubated the macrophages with amyloid beta, vitamin D3 and curcumin.

The synthetic curcuminoid compounds were developed in the laboratory of Dr. John Cashman at HBMRI. Naturally occurring curcumin was not readily absorbed, it tended to break down quickly before it could be utilized and its potency level was low, making it less effective than the new synthetic curcuminoids. The team discovered that curcuminoids enhanced the surface binding of amyloid beta to macrophages and that vitamin D strongly stimulated the absorption of amyloid beta in macrophages in a majority of patients.

Previous research by the team had demonstrated that the immune genes MGAT III and TLR-3 are associated with the immune systems ability to better ingest amyloid beta. According to Dr. Milan Fiala from the UCLA David Geffen School of Medicine, this work showed that there are two types of Alzheimers patients: patients who respond positively to curcuminoids and patients who do not.

Induced pluripotent stem cells repair heart

In a proof-of-concept study, investigators at the Mayo Clinic, the United States, have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. In this study, the researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those that result from a heart attack, converting them into stem cells that fix heart damage caused by infarction. Bioengineered fibroblasts acquired the capacity to repair and regenerate infarcted hearts, says Dr. Timothy Nelson, first author of the study.

This is the first application of iPS-based technology for heart disease therapy. Previously iPS cells have been used on only three other disease models: Parkinsons disease, sickle cell anaemia and haemophilia A. The ultimate goal is to use iPS cells derived from patients to repair injury. Using a persons own cells in the process eliminates the risk of rejection and the need for anti-rejection drugs. This iPS innovation lays the groundwork for translational applications, says Dr. Andre Terzic, Mayo Clinic physician-scientist and senior author.

The Mayo Clinic team genetically reprogrammed fibroblasts via a stemness-related human gene set to differentiate into an iPS cell capable of then redifferentiating into new heart muscle. When transplanted into damaged mouse hearts, iPS cells engrafted after two weeks, and after four weeks significantly contributed to improved structure and function of the damaged heart, in contrast to ineffective ordinary fibroblasts.

Male germ cells can be directly converted into other cells

Researchers have found a way to directly convert spermatogonial stem cells (SSCs), the precursors of sperm cells, into tissues of the prostate, skin and uterus. Their approach may prove to be an effective alternative to the use of embryonic stem cells. The new method, developed at the University of Illinois, the United States, takes advantage of the unusual interaction of two tissue types: the epithelium and the mesenchyme. The epithelium lines the cavities and surfaces of glands and many organs, and secretes enzymes and other factors that are essential to the function of these tissues. The mesenchyme is the connective tissue in embryos. The epithelium takes its developmental instructions from the mesenchyme.

Veterinary biosciences professor Dr. Paul Cooke and post-doctoral researcher Dr. Liz Simon began the effort with an unlikely proposition: cause SSCs to directly change into other cell types by putting them with various mesenchymes and then growing them in the body. Surprisingly, the experiment did work. When SSCs from inbred mice were placed on prostate mesenchyme and the combination grafted into living mice, the SSCs became prostatic epithelium. When combined with skin mesenchyme and grown in vivo, the SSCs became skin epithelium. The researchers were even able to convert SSCs into uterine epithelium by using uterine mesenchyme. The new tissues had all the physical characteristics of prostate, skin or uterus, and produced the telltale markers of those tissue types. They also stopped looking and behaving like SSCs, Dr. Cooke said.

Drug compound kills breast cancer stem cells

Researchers in the United States have discovered a compound that can kill breast cancer stem cells, a kind of master cancer cell that resists conventional treatment, and explained why many cancers grow back. The discovery came using a new method of screening for drugs that specifically target and kill cancer stem cells. It could be used to find drugs targeting other cancer stem cells as well, said Dr. Piyush Gupta of the Massachusetts Institute of Technology and the Broad Institute, whose study appears in the journal Cell.

Dr. Guptas team devised a method for stabilizing cancer stem cells in the lab and getting them to multiply. They then tested the cells against 16,000 natural and commercial chemical compounds to see which ones were able to kill the cancer stem cells specifically. That turned up 32 contenders, buy they narrowed down this list to a few chemicals and tested these in the lab and in mice. A chemical called salinomycin was found to be 100 times more potent at killing breast cancer stem cells than the cancer drug paclitaxel. Cancer stem cells treated with salinomycin were far less able to start breast cancers when injected into mice than those treated by paclitaxel. The treatment also appeared to slow the growth of tumours in the mice.

Nanotech gene therapy kills ovarian cancer in mice

Tiny synthetic particles carrying a payload of toxin worked as well as chemotherapy at killing ovarian cancer cells in mice, without the bad side effects, researchers in the United States said. The treatment, which relies on the use of nanotechnology to deliver genetic material into cells, could be ready for human clinical trials in about a year. What we did was deliver DNA that basically tells cells to die. But it is only turned on in ovarian cells, said Dr. Dan Anderson of the Massachusetts Institute of Technology. The study highlights the potential of nanotechnology as a non-viral way of getting DNA into cells. To circumvent the safety issues, Dr. Andersons team created an artificial virus a biodegradable polymer that can get inside the cell and be absorbed by the body, in much the same way biodegradable sutures work.

We think that has got a variety of advantages, in particular, safety, said Dr. Anderson, who worked with a team at the Lankenau Institute. The team tested different compounds until they found a biodegradable polymer that would make a suitable delivery vehicle. To form the nanoparticle, the polymers are mixed with a gene that produces a modified form of the diphtheria toxin that is only harmful to ovarian cancer cells. When they injected the treatment into the abdominal cavity of animals with ovarian cancer, it worked as well or better than the traditional chemotherapy drug combination of cisplatin and paclitaxel, which can cause DNA damage and a variety of side-effects.

Genetically engineered bacteria succeed against IBD

For the first time, scientists have used a genetically engineered friendly bacterium to deliver a therapy. The treatment is for bowel disorders such as inflammatory bowel disease (IBD), which has no cure. The bacterium Bacteroides ovatus activates a protein when exposed to a specific type of sugar, xylan. The therapy has been proved to work in animals with colitis, one of the major forms of IBD. The bacterium is able to deliver the protein, a human growth factor called KGF-2, directly to the damaged cells that line the gut. Unlike other treatments, the patients would be able to control the medication themselves by ingesting xylan, perhaps in the form of a drink.

"This is the first time that anyone has been able to control a therapeutic protein in a living system using something that can be eaten, said lead author Prof. Simon Carding of the Institute of Food Research and University of East Anglia Medical School, the United Kingdom. The treatment had a significant effect. For example, it reduced rectal bleeding, hastened the healing of the gut lining, and reduced inflammation. It also prevented the onset of disease.


Gene experts see high-yield rice in flood zones

Researchers in Japan have identified two genes that make rice plants grow longer stems and survive floods, and hope this will enable farmers to grow high-yielding rice species in flood-prone areas. The long-stemmed, deepwater rice varieties grown at present in areas of frequent flooding have very low yields, according to Dr. Motoyuki Ashikari at Nagoya Universitys Bioscience and Biotechnology Centre. If we combine the deepwater genes with high-yielding rice, we can have the best combination, he said. In their experiment, Dr. Ashikaris team analysed the genes of a deepwater rice variety and found two genes that were unique to the plant. The genes Snorkel 1 and Snorkel 2 are present only in the deepwater variety and not in the non-deepwater variety.

The scientists discovered that rice plants begin producing a lot of the plant hormone ethylene when grown in deep water. As water levels rise, accumulation of the plant hormone ethylene triggers expression of the Snorkel genes, which in turn switches on rapid stem growth, they said. They later tested their findings by inserting the two genes into a non-deepwater variety of rice and found that it grew longer stems, enabling it to survive in deep water.

New tools for discovering DNA variations in crop genomes

In recent years, several million single-nucleotide polymorphisms (SNPs) have been identified from the whole-genome resequencing of multiple individuals, which have served as genetic markers to pinpoint genes controlling common human diseases. In contrast, the genome of a single cultivar or line is yet to be sequenced in its entirety for most crops of economic or societal importance. This is mostly because of the high costs and technical difficulties associated with sequencing crop genomes, which tend to be large in size and complex containing a high amount of repetitive DNA and duplicated genes that are highly similar in sequence.

Using high-throughput DNA sequencing technologies, it is now possible to cheaply and rapidly sequence hundreds of millions of bases in a matter of hours. In the United States, a team of scientists from the Cornell University, the United States Department of Agriculture-Agriculture Research Service, Cold Spring Harbour Laboratory, Roche Applied Science Corp. and 454 Life Sciences have developed molecular and computational tools for the efficient and accurate identification of gene-enriched SNPs in crops. The large, complex maize genome was used to evaluate these tools.

In this research collaboration, an existing molecular technique was modified to enable gene-enrichment and resequencing of maize inbred lines B73 and Mo17 with massively parallel pyrosequencing. In addition, a custom computational pipeline was developed to analyse and assemble short reads, identify correctly mapped reads, and call high quality SNPs. With the implementation of these methods, the authors identified 126,683 gene-enriched SNPs between B73 and Mo17 at high accuracy. The SNPs identified in this study can be used for high-resolution genetic mapping of agronomic traits, which could eventually lead to the development of improved commercial maize hybrids.

Genetic change could make crops thrive on salty soils

Scientists have genetically modified (GM) plants to tolerate high levels of salt, offering a potential solution to growing food in salty soils. Dr. Mark Tester, a fellow at the Australian Centre for Plant Functional Genomics, and colleagues developed a GM salt-tolerant Arabidopsis thaliana plant by introducing into its root a gene that diverts sodium ions into the roots rather than the shoots. While plants minimize this salt accumulation naturally, the added gene decreased salt levels in the shoots by up to two-thirds.

The main challenge is applying the technique to crop plants. Dr. Tester says the Arabidopsis gene has already performed well in rice, and the scientists are currently analysing rice, barley and wheat plants containing their own versions of the gene. He says the freely available technology can also alter the accumulation of other chemicals, with implications for human nutrition, plant growth and phytoremediation, all of which are important for developing countries.

Fungus-resistant soybean crops

A variety of soybean resistant to a devastating Asian rust will soon be widely available in West and Central Africa. The rust, a fungal disease that entered Africa in 1996, can wipe out 80 per cent of infected crops. Scientists from the International Institute of Tropical Agriculture (IITA), Nigeria, and the countrys National Cereals Research Institute (NCRI) developed the rust-resistant variety, named TGX 1835-10E. They say it will drastically reduce the rust problem as it has resistance genes for all known types of rust in Nigeria. The breakthrough is important because farmers can plant the new variety without applying expensive anti-rust chemicals. The new cultivar does not solve the general problem of all fungal disease on plants but it does provide relief to farmers faced with the challenges of rust disease without any other solution, said Dr. Olumide Shokalu, the NCRI pathologist who led trials. He says the seeds will be available to farmers by the start of the new cropping season in 2010.

Novel mechanism for raising recombinant protein yield in tobacco

Elastin-like polypeptides (ELPs) cause plants to store genetically modified (GM) proteins in special protein bodies, insulating them from normal cellular degradation processes and increasing the overall protein yield. Researchers in Canada have visualized the mechanism by which the synthetic biopolymer increases the accumulation of recombinant proteins. Dr. Rima Menassa worked with a team of researchers from Agriculture and Agri-Food Canada to develop and test the ELP tags by targeting an ELP-green fluorescent protein fusion to various organelles in the leaves of the tobacco plant (Nicotiana benthamiana).

Tobacco is well-suited as a production system for recombinant proteins but the mechanism by which ELP fusions increase production yields in transgenic tobacco leaves was unknown. ELP almost doubled the yield of green fluorescent protein to 11 per cent of total soluble protein when hyper-expressed in the endoplasmic reticulum (ER). Based on confocal and electron microscopy analyses, the scientists suggest that ELP fusions that target the ER induce the formation of novel mobile protein body-like structures in leaves, which appear similar in size and morphology to the prolamin-based protein bodies naturally found in plant seeds. Although the researchers targeted their ELP fusions to the cytoplasm, chloroplasts, apoplast and ER, they found that the ER was the only intracellular compartment in which the ELP notably enhanced recombinant protein accumulation. They therefore concluded, An ER-targeted ELP fusion approach provides an effective strategy for depositing large amounts of concentrated heterologous protein within the limited space of the cell.

New drought-tolerant rice

Researchers have been testing a new type of drought-tolerant rice that could be the next big thing for Indias agriculture industry, especially its dry eastern region. Sahbhagi dhan is the source of a 15-year effort by scientists at the Manila-based International Rice Research Institute (IRRI) and partners, including the Central Rainfed Upland Rice Research Station in Jharkhand, India. The variety has been shown to survive without water for as long as 12 days. According to the IRRI, two new sister lines of the rice have demonstrated improved productivity in drought-prone regions of India and the Philippines, and have been recommended for release to the farmers. The lines also tested well in aerobic and alternate wetting and drying situations, and have proven to be as high-yielding as the regular varieties.

Soybean plants resistant to aphids

Soybean aphids made their first appearance in North America in the summer of 2000, resulting in tremendous crop losses for farmers. Scientists from the University of Illinois (UoI), the United States, began searching immediately for a variety of soybean that is resistant to the new pest. Dowling and Jackson were the first resistant varieties to be identified. With additional screening, a third soybean resistant to aphids was found, Japanese variety known as PI 200538. After mapping the genes from these sources, the scientists discovered that Jackson and Dowling were likely have the same resistance gene, while PI 200538 had a different gene.

The scientists used traditional breeding techniques together with marker-assisted selection to quickly breed the resistance genes into varieties that are adapted to the Midwest. Unfortunately, while studying soybean plants, the scientists discovered a new type of aphid that can overcome the resistance gene for Dowling. In tests, this new aphid was able to infest Dowling as well as it could any susceptible genotype of soybean. The good news is that the PI 200538 gene for resistance is different than the one in Dowling and Jackson. We are currently breeding the PI 200538 gene into varieties, but it will be at least a few years before any varieties with this gene will be released, said Dr. Brian Diers, UoI Professor of Crop Science.

Experts identify fungus-resistant gene in rice

Researchers in Japan have identified a gene that allows rice plants to fight off a fungal disease called blast, which may open the way for farmers to cultivate hardier plants. Using genetic sequencing, they were also able to separate the gene, Pi21, from a nearby gene that is associated with a poor flavour, they wrote in a paper published in Science.

Currently, rice varieties that are resistant to blast are also non-sticky and hard, which many Japanese people consider to be of a poor quality. To test their findings, the team inserted the gene into a superior species of rice and the result was fungus-resistant rice that retained a superior flavour. The (blast) resistant rice was good...the rice was sticky and taste was good, said the leader of the team Dr. Shuichi Fukuoka at the Genomics Research Centre of the National Institute of Agrobiological Sciences. Dr. Fukuoka said that their finding would be useful in mountainous rice-cultivating areas in Japan where blast disease can cause serious damage. The research team would also be looking for other disease-resistant genes, which it hopes to combine with Pi21. Source:


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