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VATIS Update Biotechnology . Jan-Feb 2004

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Biotechnology Jan-Feb 2004

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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Contents

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IN THE NEWS

Global ban on therapeutic cloning averted

At the United Nations, a global ban on all medical applications of human cloning was averted by an eleventh-hour bargain. Discussions on a cloning treaty has been postponed until October 2004. All countries want a treaty that will ban the creation of cloned human babies. However, a United States-backed proposal put forward by Costa Rica sought to extend the ban to therapeutic cloning. This means that stem cells from cloned embryos can be used to treat diseases like Parkinsons, but required the embryo to be destroyed.


The matter appeared to reach a stalemate in November 2003, when the United Nations legal committee voted by 80 to 79 to postpone further debate on the treaty until 2005. However, Costa Rica rekindled the crisis by proposing a vote in the United Nations General Assembly. This move was intended to overturn the United Nations legal committees decision and then put the original proposal for a total ban to a direct vote. Both sides backed down in the end as neither was confident of winning. The last-minute deal did bring forward the resumption of the debate by a year. Although there was relief among backers of therapeutic cloning that a total ban was averted, legal tactics used by Costa Rica and the United States to force the issue attracted sharp criticism.


The controversial issue will come up for debate in the European Parliament. It will vote on a directive that could ban therapeutic cloning throughout the European Union. 


Website: www.newscientist.com 

WHO pre-qualifies Ranbaxys AIDS drug combination

The World Health Organization (WHO) has pre-qualified a triple drug anti-AIDS fixed doze combination developed by Ranbaxy Laboratories Ltd., India. Triviro-LNS 30 and 40 mg tablets are sold in India as Virolans. This medication is a mixture of two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI). Triviro-LNS is a first-line ARV treatment for HIV-positive patients who have been prescribed the regimen.
Ranbaxy states that Triviro-LNS is a bio-equivalent of the individual innovator drugs and is available in several developing countries. Triviro-LNS is being marketed in India from the past two years and costs about US$24 per month for a patient. The significance of pre-qualification by WHO is that it is a virtual endorsement of the drug and would guide countries looking to switch from a combination of ARVS or a multiple-pill regimen to a single pill therapy. Besides being convenient for patients, it is also less expensive. 


Chemical Weekly, 23 December 2003

Clinical trials of meningitis vaccine in Central Africa

Transgene Biotek Ltd., India, has obtained the mandatory international approvals from the Institutional Ethical Committee (IEC) and Institutional Biosafety Committee of the United States and African regulatory authorities to undertake phase III human clinical trials for polyvalent meningitis vaccine in the central African region (Niger and Burkina Faso). The quadruplet vaccine covers serogroups A, C, Y and W-135. Transgene is developing the vaccine with technical assistance from the United States-based JN International Medical Corp. Since both Niger and Burkina Faso fall into the meningitis belt in central Africa, the trials will provide protective and epidemiological data about the efficacy of the vaccine. Phase III trials will be conducted on 700 participants aged between 13 to 30 years. For a duration of eight weeks, which is the trial period, preliminary data will be submitted to the World Health Organization (WHO).


The demand for meningitis vaccines is about 500 million doses a year, with a selling price of US$1.50. Currently, GlaxoSmithKline and Aventis Pasteur are the two companies with the technology to manufacture quadrivalent vaccine and sell them for US$5.50 per dose. Transgene has proposed to negotiate and sell the vaccine at a lower cost to WHO. The company is currently working on a vaccine that will protect against the B-serogroup of meningococcal meningitis, for which animal trials have already been conducted. 


The Financial Express, 30 December 2003

Intel, Fred Hutchinson to explore the use of nanotechnology tools

At the BioSilico Seminar held at Stanford University, the United States, Intel Corp. and Fred Hutchinson Cancer Research Centre announced a combined research programme to apply Intels expertise in nanotechnology to develop improved methods of studying, diagnosing and preventing cancer. Mr. Andrew Berlin, lead researcher of Intels Precision Biology programme, informed that an Intel Raman Bioanalyser System was being built by Intel at the Cancer Research Centre. This instrument beams lasers on to tiny medical samples, such as blood serum, to create images that reveal the chemical structure of molecules. According to Mr. Berlin, it remains to be seen if this technology, previously employed to detect microscopic imperfections on silicon chips, can also detect subtle traces of diseases. Dr. Lee Hartwell, Nobel Laureate and the Centres President, feels that this could be a good method of studying the molecular structure of biology. 


Chronicle Pharmabiz, 18 December 2003

Viet Nam aims to become a biotech leader by 2010

The Deputy Prime Minister of Viet Nam declared at a conference on biotechnology, organized in Hanoi, that a 7-year plan had been drawn up to put Viet Nam at the forefront in the biotechnology sector by 2010. The Ministry of Science and Technology aims to develop the nations biotech industry over the next seven years. It is estimated that by 2010, biotech products in the agricultural sector will be valued at US$638.5 million, generating jobs for up to 700,000 rural labourers. The biotech sector would focus on developing artificial reproductive technologies, producing disease-free plant varieties and animal breeds, cleansing the aquaculture environment and controlling epidemic diseases. The ministry also hopes to train an additional 2,000 scientists between now and 2010.


Mr. Pham Gia Khiem, also urged the industry to rationalize the management of biotechnology and increase the use of information technology. He revealed that laws to regulate intellectual property rights and genetic modification were currently being made and called for strengthening training and international cooperation in the industry. To further raise the industrys professional capacity, the ministry has also suggested that the Government devise specific policies to attract foreign scientists and encourage Vietnamese scientists residing abroad to return home and work. 


Website: www.biotechknowledge.com 

Obesity genes isolated in Iceland

deCODE genetics Inc., a biotech company based in Reykjavik, Iceland, has identified two new genes that can predispose people to being obese. This discovery offers new targets for drug intervention. Scientists have long suspected a genetic link in determining how our bodies regulate weight. However, it is only recently, with breakthroughs in understanding the human genome, that they have begun to pinpoint genes that may be responsible. One of the genes appears to affect how the body stores and uses energy while the other is implicated in controlling appetite. The goal is to develop new drugs that can treat obesity the western worlds fastest-growing health problem by tapping into the human bodys own weight control mechanisms. 


Website: www.reuters.com 

Worlds first cloned deer

Researchers at the Texas A&M Universitys College of Veterinary Medicine, the United States, have cloned a white-tailed deer. Named Dewey after Ms. Duane Kraemer (one of the researchers), the fawn was born to a surrogate mother months ago. Dewey is believed to be the first successfully cloned deer. Texas A&M is the first academic institution in the world to have cloned five different species, since researchers have previously cloned cattle, goats, pigs and a cat. Announcement of the successful deer cloning was delayed until a DNA analysis could be performed to confirm the genetic identity. This breakthrough in deer cloning was a joint project with Viagen Inc. and may be useful in conserving endangered deer species.


The clone was produced using fibroblast cells segregated from skin samples derived from a deceased white-tailed buck, expanded in culture, then frozen and stored in liquid nitrogen. White-tailed deer oocytes were collected from the ovaries of does and matured in vitro. Two research teams led by Dr. Mark Westhusin and Dr. Duane Kraemer of Texas A&M University and Dr. Charles Long from Viagen Inc. performed the nuclear transfer procedures and transfer of the cloned embryos. According to Dr. Westhusin, Dewey is developing normally for a fawn his age and appears healthy. The fawn is under the medical care of Dr. Alice Blue-McClendon, a veterinarian at the College of Veterinary Medicine.


Dr. Westhusin stated that future scientific advances resulting from the successful cloning of the deer are expected. The cloning approach could be used to conserve endangered deer species as well as for deer farming and gaming. Breeding animals that die or are harvested could be cloned to protect desirable genetic characteristics. 


Express Pharma Pulse, 1 January 2004

Scientists warn on potential nanotech health risk

In the United Kingdom, Prof. Ken Donaldson from the University of Edinburgh and other scientists at the London Centre for Nanotechnology have called for more research into the safety of nanoparticles, materials so small that their dimensions can be measured in atoms, following evidence that they can lodge in the brain. Researchers believe that the real risk lies in breathing in designer materials so small that they can easily slip through membranes inside the body. Studies on rats have indicated that nanoparticles deposited in the nose can migrate to the brain and move from the lungs into the bloodstream.


According to Prof. Donaldson, modern humans breathe in considerable numbers of nanoparticles on a daily basis in traffic fumes and even from cooking. In some individuals this could trigger asthma or even cardiovascular complications, by setting off an inflammatory response from the bodys immune system. The real worry would be if a nanotechnology business designs nanoparticles that are fundamentally different from the ones humans are already exposed to and seem to cope with reasonably well. New materials being developed through nanotechnology which involves manipulating matter on a scale of a billionth of a metre or about 80,000 times smaller than the thickness of a human hair might trigger severe reactions. As such, scientists have called for more trials to establish how nanoparticles reach the brain and its impact.


Website: www.reuters.com

MARKET NEWS

Aceto to acquire distribution subsidiary of Roche Holding

Aceto Corp., the United States-based worldwide distributor of pharmaceutical as well as speciality chemicals, has signed a definitive agreement to acquire Pharma Waldhof, Germany, an ultimate subsidiary of Roche Holding AG, Switzerland, for an undisclosed amount. Once the formalities are completed, the new acquisition will be immediately accretive to Acetos earnings. The acquisition will foster a continuing relationship between Aceto and Roche, whereby Roche will continue to manufacture patent-protected, biologically derived active pharmaceutical ingredients (APIs) that Pharma Waldhof distributes to major worldwide ethical and generic pharmaceutical companies.


According to the Chairman, CEO and President of Aceto, this acquisition would spearhead their entry into the biopharmaceuticals market, broaden product offerings to the pharmaceutical industry, complement the companys strong position in chemically derived APIs and strengthen Acetos stance as an early participant in the generic biopharmaceutical business. Furthermore, the acquisition would establish a strategic relationship with Roche. 


Website: www.biospace.com 

Sigma-Aldrich to invest in Shapoorji Pallonji biotech park

Sigma-Aldrich Corp., a US$1.2 billion company based in the United States, has entered into an agreement with the Shapoorji Pallonji Biotech Park, which is a leading infrastructure promoter in the Genome Valley on the outskirts of Hyderabad, India, to set up a research and development centre as well as a pilot manufacturing facility. The firm is a leading provider of biochemical and organic chemical products and kits used in scientific and genomic research, biotechnology, pharmaceutical development, diagnosis of disease and chemical manufacturing. The company is likely to invest US$2.7 million in the new facility. Details on the land required to set up the project and investment are being worked out. 

Chemical Weekly, 30 December 2003


Sanmar Speciality acquires Bangalore Genei

In India, Sanmar Speciality Chemicals Ltd. has announced the acquisition of Bangalore Genei (P) Ltd., which manufacturers enzymes and related reagents for genetic engineering research. The latter also trades in certain micro-tubes, micro-tips, biochemicals and other consumables; small electrophoresis equipment and power supply to biology researchers. According to a press release from Sanmar, the acquisition will provide a platform for Sanmars entry into biotechnology and complement existing and growing chemistry research activities. 


Chemical Weekly, 23 December 2003

BioSante gains subcontract to develop anthrax vaccines

In the United States, BioSante Pharmaceuticals Inc. has been awarded a subcontract, by DynPort Vaccine Co. LLC (DVC), for developing anthrax vaccines for delivery through alternative routes of administration. This subcontract leverages the technology and expertise of BioSante to develop vaccines using nasal, oral and needle-free transcutaneous routes of administration. Under the agreement, BioSante will provide its proprietary nanotechnology-based vaccine adjuvant and delivery system, BioVant, while DVC will supply recombinant antigens to be utilized in potential vaccines against anthrax. The aim is to assess the immunogenic potential of BioVant when used in anthrax vaccines vs. the immunogenic response of anthrax vaccines that use Alhydrogel as the vaccine adjuvant.


BioSante would be responsible for developing formulations of BioVant with the anthrax vaccine antigens and conducting immunization studies in animals to determine the immunogenicity of the resulting BioVant/antigen vaccines compared with an anthrax vaccine formulated with Alhydrogel. According to the President and CEO of BioSante, Mr. Stephen M. Simes, this programme would be an important step towards the development of novel vaccines to protect against anthrax and takes advantage of BioSantes work in alternative routes of administering vaccines and therapies, such as insulin, using our BioVant nanotechnology.


Website: www.biospace.com 

Dyax Corp. and Baxter team up to discover anti-MIF antibody

In the United States, Dyax Corp. has entered into a research collaboration with Baxter Healthcare Corp. to utilize its proprietary phage display technology for discovering antibodies that obstruct macrophage migration inhibitory factor (MIF), a clinical target to which Baxter has an exclusive license from Cytokine PharmaSciences Inc. Under the terms of the agreement, Dyax and Baxter will conduct a research programme to identify and characterize antibodies that bind specifically to MIF and neutralize its activity. MIF is a cytokine involved in immune, infectious and malignant disorders. Neutralizing MIF activity will be useful in the treatment of a wide spectrum of diseases, including asthma, severe infections and certain types of cancers.


Baxter will have an exclusive right to develop and commercialize therapeutic products based on any antibody that Dyax identifies. Baxter will fund Dyax to perform its portion of the research programme and pay for milestones if the antibodies identified by Dyax comply with certain preclinical performance criteria. In addition, Dyax would be entitled to receive contingency-based milestone and royalty payments for a specified period of time upon Baxters successful commercialization of any therapeutic product based on antibodies identified by Dyax. 


Website: www.biospace.com 

Aventis and Crucell ink pact for novel influenza vaccines

Aventis S.A. of France and Crucell N.V. from the Netherlands have entered into a strategic agreement to further develop and commercialize novel influenza vaccine products based on Crucells proprietary PER.C6 cell line technology. The agreement covers both pandemic and epidemic influenza vaccines, which up to now have been part of Crucells in-house product development programme. As per the terms of this agreement, Aventis Pasteur, the vaccines business of Aventis, would receive an exclusive license to research, develop, manufacture and market cell-based influenza vaccines utilizing Crucells cell line technology. Crucell would receive milestone payments, annual payments and R&D funding totalling US$38 million, and royalties on future PER.C6-based influenza vaccine sales. For Japan, Crucell would retain the commercialization rights while Aventis Pasteur will supply finished vaccine products and receive royalty on sales made by Crucell.


According to the Executive Vice-president of R&D for Aventis Pasteur, Mr. Michel DeWilde, PER.C6 technology shows potential to deliver superior performance, which will allow for production of large quantities of influenza vaccine each year. Both companies believe that combining Crucells PER.C6 cell line technology with Aventis Pasteurs market leadership and R&D expertise in vaccines will lead to a new generation of cell-based influenza vaccines capable of significantly augmenting and potentially replacing current egg-based methods, which require enormous increases in physical production capacity. This will also allow Crucell to retain a considerable piece of the large and growing influenza vaccine market, and accelerate the global commercialization of a PER.C6-based product.


Website: www.biospace.com

INVENTIONS/NEW PRODUCTS

Scientists create Ebola vaccine

A team of scientists led by Dr. Steve Bavari at the United States Army Medical Research Institute of Infectious Diseases has successfully immunized mice against the deadly Ebola virus, which causes haemorrhagic fever, for which currently there are no available vaccines or therapies. The team used virus-like particles (VLPs) that are non-infectious but capable of triggering a strong response from the immune system. These VLPs resemble the outer covering of infectious viral particles, but lack the genetic material essential for replication.


VLPs were created from two Ebola virus proteins. When mice were vaccinated with VLPs three times at three-week intervals and exposed to the Ebola virus six weeks after the last vaccination, they did not exhibit any signs of illness and 100 per cent protection was achieved. According to the team, VLPs could provide a new tool to manufacture a protective immune response to Ebola. The next stage would be to test the vaccine in primates. 


Website: www.news.bbc.co.uk 

Agilent manufactures microarray kit to study rice

Agilent Technologies of the United States, in colloboration with National Institute of Agrobiological Sciences (NIAS) of Japan, has commercialized the first 60mer oligonucleotide microarray for the study of rice. Researchers can now utilize the Agilent Rice Oligo Microarray Kit to measure the activity of genes in rice and related cereal plants, thus enabling them to identify strains with greater tolerance to drought, salt, cold climate or pests, for planting in less arable lands.


The microarray includes genetic probes for over 21,000 genes from the genome of Oryza sativa L. ssp. japonica (cultivar Nipponbare), a rice strain mainly cultivated in Japan. This is believed to be approximately 50 per cent of the total rice genome, currently estimated at 40,000 to 50,000 genes. Agilent will manufacture the microarrays using ink jet-based technology, printing DNA in situ on to 1 3 inch glass slides to a length of 60 oligos, which the firm maintains provides 5-8 times greater sensitivity than 25mer probes. 


Genetic Engineering News, Vol. 23, No. 21, December 2003

New antibiotic and delivery mechanism

Scientists at the University of South Florida, the United States, have not only patented a new class of synthetic antibiotics for killing drug-resistant bacteria but have also developed a drug delivery vehicle that improves drug solubility, detection and treatment of infectious diseases. The new synthetic antibiotic belongs to a family of antibiotics called beta-lactams. It employs a new mode of action to stop methicillin-resistant staph (MRSA) bacteria. MRSA bacteria are responsible for a large part of hospital-borne infections becoming resistant to even the most powerful antibiotics. The novel antibiotic attacks such bacteria selectively and with more power than vancomycin (a drug presently being used as the last resort for MRSA infections). It acts particularly well on the nastiest strains of staph bacteria, for which there may not be any effective treatment.


Employing a process called micro-emulsion polymerization, researchers have created nanosized plastic spheres with the drug chemically bonded on to their surface. This tiny drug delivery vehicle can efficiently carry the antibiotic to the infection site. It can deliver less drug more effectively, potentially reducing unwanted side effects like toxicity and allergic responses. The nanosized plastic balls allow the drug to be dissolved in water, dramatically improving performance. As they are many times smaller than bacterial cells, bacteria willingly consume them as potential food. However, once inside, the balls release high concentrations of the drug which wreaks havoc on the internal machinery of the cell.


Scientists are hopeful that the new drug delivery vehicle would open new avenues to revolutionary changes in medicine, particularly detection and treatment of infectious diseases. They hope to design customized vehicles whose functions can be tailored to a wide variety of applications in the biomedical and nanotechnology fields. 


Express Pharma Pulse, 25 December 2003

GENOMICS

Chimp genome sequenced

The genome sequence of the chimpanzee Pan troglodytes has been assembled by a research team funded by the National Human Genome Research Institute (NHGRI) in the United States. Researchers deposited the initial assembly, which is based on four-fold sequence coverage of the chimp genome, into the public database of the National Institute of Health GenBank (Website: www.ncbi.nih.gov   /Genbank) making it available for use by scientists around the world. Researchers have also aligned the draft version of the chimp sequence with the human sequence in order to facilitate biomedical studies comparing regions of the chimp genome with similar regions in the human genome.


Chimpanzees are the most closely related species to humans. Consequently, comparative analysis of the human and chimp genomes may reveal unique types of information impossible to obtain from comparisons between the human genome and the genomes of other animals. The international team of scientists led by researchers at the University of Washington, Washington University and Eli & Edythe Broad Institute of Massachusetts Institute of Technology and Harvard University is presently comparing the chimp and human genome, and plans to publish results of its analysis in the next several months. 


Website: www.bio.com 

Scientists assemble genomic sequence of honeybee

A team of scientists led by Dr. Richard Gibbs at the Baylor College of Medicine, the United States, are the first to assemble the genome of honeybee. Genomic sequence of the bee, known scientifically as Apis mellifera, is published on the Internet for the use of researchers in biology and agriculture. Among the many databases where the sequence can be found is GenBank at the Website: www.ncbi.nih.gov/Genbank


The sequence has shown that the bee genome is about one-tenth the size of the human genome. It contains about 300 million DNA base pairs, or matching rungs on the ladder-like double helix that makes up DNA. This information will benefit biologists keen on finding out about human health issues such as allergies. The next step would be to find out the exact location and key functions of the genes. 


Website: www.reuters.com 

Coral reveals ancient origins of human genes

A study of corals conducted by Dr. Robert Saint, Australian National University, and molecular biologist Dr. David Miller of James Cook University, Australia, suggests that ancient members of the animal kingdom slithered through the Precambrian era with a hefty cache of genes in common with humans. Many of these genes are not shared with creatures such as flies and worms, even though these animals evolved millions of years after corals. This calls into question studies that use these model organisms for unravelling evolution of the human genome.


The study scrutinized about 1,300 gene sequences expressed in the coral Acropora millepora and found that about 500 sequences had matches in gene databases. The sequences, called expressed sequence tags, represent either single genes, different pieces of the same gene or expressed portions of DNA that do not contribute to a coding gene. Of these, 90 per cent were found in humans in specialized tissues of the nervous system, even though coral has only a simple nerve net. About 10 per cent were found in humans but not in the fruit fly Drosophila melanogaster or the nematode worm Caenorhabditis elegans. This finding suggests that many genes thought to be vertebrate-specific may in fact have much older origins and were lost during the evolution of the fly and worm.


Although fly and worm models are useful to study gene function in development and cellular processes, they may be of limited value in studies on the evolution of human genes. According to developmental biologist Mr. Alejandro Sanchez Alvarado at the University of Utah, the United States, many other animal genomes, that have not undergone the same degree of gene loss, need to be studied to understand the evolution and function of human genes and how they generate complexity. 


Website: www.nature.com 

Researchers find key gene in production of egg and sperm

A team of biologists led by Dr. Wojtek P. Pawlowski at the University of California, the United States, has now found a key gene involved in the first step of the sexual reproduction process. The gene, isolated from corn, allows chromosomes floating around in the cells nucleus to recognize and pair with their homologues (equivalents) in preparation for the later steps that lead to cell division. If this crucial first step fails, the whole chain of events break down and cells fail to produce eggs or sperm. This finding is an important step in understanding meiosis in many organisms as meiosis in corn has many similarities to the process in yeast, fruit flies, mice and humans.


Researchers found a corn mutant that prevented the duplicated chromosomes from finding and pairing with their homologues during meiosis. In the mutant, called poor homologous synapsis 1 (phs1), chromosomes paired up with the wrong partner and were zipped (synapsis) together. The gene phs1 appears to prevent the attachment of the protein machinery which causes meiotic recombination, because the process basically stops after zipping.


Dr. Pawlowski stressed that the ongoing research on the molecular function of phs1 gene will lead to understanding the molecular mechanisms by which chromosomes identify each other and pair during meiosis. Although scientists are not yet aware how the phs1 gene accomplishes all its functions, results clearly suggest that it possesses the ability to sense homology between two DNA molecules and this DNA recognition ability is the key to the process of chromosome pairing during production of gametes.


According to Mr. Enrique Martinez-Perez at the Stanford University in the United States and Mr. Graham Moore at the John Innes Centre in the United Kingdom, the function of phs1 lies at the core of coordination between the two events pairing and synapsis and the phs1 gene could now be used to identify new components of this coordinating mechanism. Researchers believe that understanding chromosome pairing in plants would eventually lead to understanding the same process in humans.


Website: www.sciencedaily.com

MEDICAL BIOTECH

Genetics of inflammatory bowel disease unravelled

A team of researchers led by Prof. Steven Brant at Johns Hopkins, the United States, has linked versions of two genes with the inflammatory bowel diseases (IBDs) known as Crohns disease and ulcerative colitis. The first discovery demonstrated that a version of the NFKBI gene was an important risk factor for ulcerative colitis. NFKBI is the gene that contains the DNA sequence for nuclear factor kappa B (NF-kappa B) protein, which is one of the foremost regulators of the immune system and programmed cell death.


Prof. Brant opines that evidence from the twin studies and the tendency for IBD to run in families strongly suggested a genetic component to the disease. Relatives of Crohns disease patients have a ten-fold risk of developing the disease, while those of ulcerative colitis patients have an eight-fold risk. The team hopes that by identifying gene abnormalities associated with IBD, they would be able to figure out the genes contribution to causing the disease. These discoveries are a critical step in developing treatments and prevention strategies for the disabling conditions that afflict millions of people. 


Express Pharma Pulse, 1 January 2004

Cancer spread could be halted

A study led by Dr. Timothy Hla at the University of Connecticut, the United States, has uncovered more evidence of a switch that allows breast cancer to grow and spread. This finding could lead to drugs precisely targeted to stop this process in its tracks. Scientists created a genetically modified mouse that produced large quantities of a chemical called COX-2 in its breast tissue in theory producing the perfect environment for a breast tumour to generate the necessary blood vessels to allow growth. Results indicated that blood vessel density increased prior to visible tumour growth in the mouse breast tissue and during progression, the density of the blood vessels increased exponentially. When drugs called COX-2 inhibitors designed to interfere with the workings of this chemical were added to the mix, tumour growth slowed and blood vessel density decreased, pointing again to the role of COX-2 in the process.


Experts believe that drugs that inhibit COX-2 could play a role in fighting breast cancer, the most common cancer afflicting women in the United Kingdom. Several commonplace household drugs including aspirin and ibuprofen have an inhibitory effect on COX-2, and this in theory could be used to prevent or hold back breast tumours. However, doctors could create a more specific drug, which avoids some of the dangerous side effects of long-term painkiller use, thus raising the chances for breast cancer patients. 


Website: www.bbc.co.uk 

New antibody with double impact

Domantis, a drug company in the United Kingdom, has developed a way to make antibodies that bind to two different targets, potentially doubling the effectiveness of the treatment. These dual specific antibodies would deliver a two-pronged assault on diseases such as cancer and arthritis. Mr. Ian Tomlinson, Chief Scientific Officer of the company, revealed that these products were identical to ordinary antibodies in every way, except that they bind to two targets instead of one. As such, they would be easier and cheaper to manufacture.


Manufacturing dual-target antibodies was a huge challenge earlier because of the difficulty in ensuring that each antibody got two different arms rather than two identical ones. Domantis modified the chains that made up each arm so each would bind to two different targets. Mr. Tomlinson states that the dual targets could enhance the specificity of the antibodies, thus sparing healthy cells, and be used to target cancer cells in an effective manner. 


Website: www.newscientist.com 

Insulin from fish on the cards

A study undertaken by researchers at the Bose Institute, India, has shown the possibility of deriving insulin from fish. The study revealed that insulin is released from carps adipocyte cells, and it has been recovered and purified. The insulin gene has shown expression in adipocyte by hybridizing carp adipocyte RNA with zebra fish and rat insulin DNA. The carp insulin gene has been cloned and sequenced, and has shown more than 90 per cent homology by nucleotide sequence analysis. The tudy indicates that insulin thus derived is very active and showed greater biological activity than the porcine insulin in rat models.


This finding opens up the possibility of a promising therapy for diabetes mellitus. Successful results could lead to the transfer of adipocyte insulin gene into a suitable host through genetic engineering for type-II diabetes and insulin-resistance research. 


Chemical Weekly, 30 December 2003

New drug for stroke and myocardial infarction

Dr. Sabita Dey and her co-researchers at Agharkar Research Institute, India, have isolated an efficient natural molecule with enormous medical potential, specifically in the area of clot lysis. The enzyme actinokinase is produced by a non-pathogenic, thermophilic Streptomyces sp. in 18 h. Downstream processing is also very simple because of less contaminating proteins at high fermentation temperature. It is highly thermostable with a long half-life at 37C and pH resistance.


Actinokinase is different from other available agents since it is plasminogen-independent, non-toxic, non-allergenic and non-haemolytic. These traits enable it to combat strokes, whereas currently available enzymes cause intracranial haemorrhage. Acute toxicity tests using rats, rabbits and guinea pigs reveal that LD50 of the enzyme is more than 2,000 mg/kg of the body weight. Actinokinase did not exhibit any adverse effect on the blood pressure and heart rate of the animals. Though actinokinase is a prokaryotic protein, activity-wise it resembles urokinase, a eukaryotic protein. The activity is N-terminal-dependent, which contains the catalytic triad. It can cleave fibrin chain randomly after arg- val-subunits.


The enzyme is now ready for different phases of clinical trials and available for collaboration at bench-scale level. A United States patent has been granted and the Indian patent has also been accepted. In addition, the mode of action of actinokinase on thrombus is being scrutinized to determine the effect on platelet disintegration. 


Contact: Dr. V.S. Rao, Director, Agharkar Research Institute, G.G. Agarkar Road, Pune 411 004, India. Tel: +91 (20) 5654 831; Fax: +91 (20) 5677 278; 


E-mail: srao@pn3.vsnl.net.in 


ARI News Release

SARS coronavirus part bird, part mammal

A study by Dr. David Guttman and Ph.D. student Mr. John Stavrinides at the University of Toronto, Canada, has shown that the Severe Acute Respiratory Syndrome (SARS) coronavirus, the cause of a deadly form of pneumonia, is the likely result of a rare recombination of viruses from both mammalian and avian hosts. This has resulted in a new virus unrecognisable to human immune systems. The study team deconstructed and compared the SARS virus genome to related coronaviruses using phylogenetic computational tools. They found that the protein encoded on the genomes left side was of mammalian origin (such as cats, cows and mice), while proteins on the right were of avian origin (like chickens and ducks). The middle gene, S gene (that encodes spike glycoprotein in all coronaviruses), encoded an altered protein owing to the merger of mammalian and avian viruses. This enable the pathogen to sneak past immune surveillance, which fails to recognize it as a foreign body.


Dr. Guttman believes that the virus was transmitted to humans by masked palm civets, which must have picked it up from a bird. This could have created the opportunity for a very rare recombination event that produced a virus with a new host range which then spread to humans because of poor hygiene and close contact in food markets. This recombinant virus is infectious to humans though the two parent viruses are not. Researchers believe that these recombination events have the potential to create an entirely new structure instantaneously, which could have far more dramatic consequences than simple genetic mutations, in which only small features in genes are changed at any one time. This work may contribute to designing specific and effective vaccines, and could be most useful in the development of tests for diagnosing new SARS outbreaks. 


Website: www.sciencedaily.com 

Discovery of brain disorder gene leads to genetic test

A team of scientists led by Dr. Douglas Marchuk at the Duke University Medical Centre, the United States, has identified the second of three genes that can each independently cause the disorder called cerebral cavernous malformations (CCM), characterized by vessel lesions in the brain. This finding could pave the way for a new genetic test for the rare familial disease, which typically lies dormant in patients for decades before the lesions are found on an MRI scan.


The newly identified CCM gene has been named malcavernin by researchers. According to genetic counsellor Mr. Tracey Leedom, identification of this gene will allow more people with a familial history of the disease to be tested early. If they were found to have the gene, physicians could then conduct an MRI and begin monitoring them carefully for any symptoms. The team will next seek out the last of the genes known to cause CCM. They have already started exploring the biological basis of CCM in mice with the disease. KRIT1 represents the first gene. 


Website: www.sciencedaily.com 

New strategy may help create novel anticancer drugs

Investigators at St. Jude Childrens Research Hospital, the United States, have discovered a new way by which an enzyme crucial to the cells ability to decode genes and duplicate chromosomes could be turned into poison inside cancer cells. The enzyme, called Topoisomerase 1 (Top 1), is crucial to the cells ability to unwind the DNA of chromosomes and separate the two strands.


Top 1 first clamps on to the spiralled DNA molecule like a pair of C-shaped pliers and then breaks a chemical bond between two adjacent building blocks of one DNA strand and uses that bond to bind itself to one of the cut ends of that strand. This process allows the DNA next to Top 1 to rotate and reduce some of the tension in that part, which in turn paves the way for other enzymes to unravel the DNA and either decode a specific gene or duplicate the entire chromosome.


Normally, Top 1 moves along the DNA, clipping the strand as it goes, while the other enzymes follow behind, unravelling the DNA. Researchers modified the top and bottom ends of the C-shaped enzyme so that the tips of the open ends of the enzyme were pulled together and locked Top 1 into place around the DNA. Top 1 then acted as a roadblock to the enzyme machinery behind it. Ms. Mary-Ann Bjornsti, one of the investigators, revealed that just acting as a roadblock to the enzyme machinery, moving along the DNA behind it, was enough to cause cell death.


This approach, unlike the anticancer drug camptothecin (CPT), could work irrespective of whether the cell was in S phase or just decoding a single gene. Thus, a drug based on the new strategy may be particularly versatile and a proof-of-principle for a new class of anticancer drugs that work in combination with CPT, which has already shown itself to be valuable in the treatment of cancer. Ms. Bjornsti hopes that by targeting Top 1 in a different way it might be possible to lessen the ability of cancer cells to become resistant to treatment, as they might when treated with CPT alone.


Website: www.sciencedaily.com 

Smart bomb delivery destroys tumours in mice

At the Biological Chemistry Department of Weizmann Institute, Israel, Prof. David Mirelman and colleagues have succeded in destroying malignant tumours in mice by using a chemical that occurs naturally in garlic. Allicin is the substance that gives garlic its distinctive flavour and aroma. Scientists have known that this chemical is as toxic as it is pungent. It is known to kill cancer cells, cells of disease-causing microbes and even healthy cells. However, the highly unstable allicin breaks down quickly once ingested.


The rapid breakdown and undiscriminating toxicity pose twin hurdles for developing an allicin-based therapy. To overcome these problems, researchers have designed a unique, two-step system for delivering the cancer-wrecking chemical straight to the tumour cells. The ingenious delivery method, which parallels the way allicin is synthesized in nature, works with the pinpoint accuracy of a smart bomb.


To zero in on the targeted tumour, scientists took advantage of the fact that most types of cancer cells exhibit distinctive receptors on their surface. An antibody that is programmed to recognize the tumours characteristic receptor was chemically bound to the alliinase. Injected into the bloodstream, the antibody sought out these cells and lodged itself and its passenger enzyme on the tumour cells. Scientists then injected the second component, alliin, at intervals. When it encountered alliinase, the resulting reaction turned the normally inert alliin molecules into lethal allicin molecules, which penetrate and kill the tumour cells; neighbouring healthy cells were not affected.


Using this method, the team succeeded in blocking the growth of gastric tumours in mice. The tumour-inhibiting effects were seen up to the end of the experimental period, long after the internally produced allicin was spent. According to scientists, this method could work for most types of cancer, as long as a specific antibody can be customized to recognize receptors unique to the cancer cells. It could prove invaluable in preventing metastasis following surgery.


Website: www.sciencedaily.com 

Humanized organs can be grown in animals

A team of scientists led by Dr. Esmail Zanjani at the University of Nevada, the United States, has created animal-human chimeras which, it hopes, will someday yield new cells genetically identical to a patients own for repairing damaged organs, and perhaps larger pieces for transplantation. Dr. Zanjanis original goal was to see if unborn children with genetic defects could be treated by injecting healthy stem cells into the foetus but during animal experiments he realized that this technique could also be used to grow humanized organs.


The team has managed to produce sheep-human chimeras with a surprisingly high proportion of human cells in some organs. According to the results, in some cases 7-15 per cent of all cells in the sheeps livers are human. The human cells are injected around halfway through gestation before the immune system of the foetus has learned the difference between its own and foreign cells, so that the animal does not reject them, but after the body plan has formed. This ensures that the resulting animals look like normal sheep rather than strange hybrids like the geep, created by fusing the embryos of a sheep and goat. In some cases, human liver cells cluster together to form functional and fully human liver units, which could be transplanted whole as auxiliary organs.


According to Dr. Zanjani, this technique takes advantage of the growing nature of the foetus and the human cells produced can be separated from that of the animal simply by modifying existing cell-sorting machines. Provided that the method really does produce normal human cells, they will not be rejected. Any stray animal cells would be killed by the recipients immune system. This technique, if perfected, could overcome some of the major stumbling blocks facing researchers who want to make tissues and organs for implants. It could yield significant quantities of just about any kind of cell or tissue, for instance, with no need to fiddle about with different culture conditions or growth factors. It would also allow doctors to obtain immune-compatible cells without having to create human embryos by therapeutic cloning.


Dr. Zanjani stressed that this technique would be an important advance in xenotransplantation as it would open the door to creating foetal heart cells for therapy. It could also be possible to grow a wide range of other tissues, e.g. insulin-producing islet cells to treat diabetes.


 Website: www.newscientist.com 

New drug treatment for Ebola

A study led by Mr. Tom Geisbert at the United States Army Medical Research Institute of Infectious Diseases has revealed that giving a shot of an anti-blood-clotting protein to monkeys infected with Ebola virus, showed promising results. Mr. Geisbert and colleagues infected 12 monkeys with Ebola. Nine were given shots of the protein rNAPc2 after either 10 minutes or 24 h. The others were given a saline control; controls from older experiments were also used for comparison. Three of the treated monkeys survived and were still alive and healthy 12 months later. The six treated monkeys that died lived longer than untreated monkeys 12 days on average compared with eight days.


rNAPc2 works by slowing the formation of blood clots caused by Ebola. According to Mr. Geisbert, the protein gave monkeys sufficient time for their immune systems to fight back against the virus, which causes death by clot-related organ failure. He believes that rNAPc2 could be a useful treatment in combination with a drug to target the virus itself. The World Health Organization has evinced interest in using rNAPc2 under a compassionate protocol for future human outbreaks in the Democratic Republic of Congo. The drug could even be useful in treating other viral hemorrhagic fevers.


Website: www.newscientist.com

BIOINFORMATICS

Genetic variation map

Applied Biosystems, the United States, has finished developing a genome-wide human genetic variation map based on SNPs. The company has also introduced a free, downloadable software tool to view these variations in the context of individual genes, chromosomal regions and the human genome. The SNPbrowser software is available at the website www.allsnps.com/snpbrowser


The software includes a gene-centric, genome-wide SNP map, study design parameters and links to TaqMan Assays-on-Demand products. One could query the physical locations of SNPs on the chromosome and linkage disequilibrium (LD) maps (the degree of statistical association between alleles of neighbouring sequence variants), assess the likely statistical power of a study and view the boundaries of putative haplotype blocks (regions of the genome in which certain allelic variations tend to be inherited together within a population).


The map is a result of analysis of over 40 million genotypes generated by the company through validation of its more than 150,000 SNP genotyping assays. SNPs were validated by individually genotyping 180 DNA samples from African-American, Caucasian, Japanese and Chinese individuals. This combined information, together with an intuitive visualization tool, could provide a resource for the study of SNPs within their genomic and genetic context, and is expected to simplify the process of designing disease association studies. Furthermore, unlike array-based methods and other fixed-set strategies, SNPbrowser enables the use of LD-map information for tailoring SNP selection and other study-design parameters for the most effective use of the research budget, without compromising the power of statists. 


Genetic Engineering News, December 2003

PROTEOMICS

A little stress may be beneficial

In the United States, a team of researchers at the Northwestern University has demonstrated that elevated levels of molecular chaperones (special protective proteins that respond to stress in a cell) promote longevity. Acute stress triggers a cascading reaction inside cells that results in the repair or elimination of misfolded proteins, prolonging life by preventing or delaying cell damage.


The team studied C. elegans, a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome is known. They found that when heat shock factor, the master gene that controls the expression of all chaperones, was under-expressed in adult animals, longevity was suppressed. When the heat shock factor was over-expressed, lifespan increased as it responds by turning on the genes that encode molecular chaperones. The molecular chaperones prevent misfolding of proteins or, in the case of already misfolded proteins (that leads to many neuro-degenerative diseases), detect them and prevent further accumulation. Results suggest that stressors, including oxygen stress, elevated temperatures, bacterial and viral infections, and exposure to toxins like heavy metals, which challenge the environment of the cell, have long-term benefits to the cell. 


Website: www.bio.com 

New pathway could lead to plant generation of human-like protein

In the United States, a team of researchers led by Prof. Lokesh Joshi have found a pathway whereby plants can generate human-like proteins. This discovery could lead to an effective and inexpensive means of producing medically important proteins in plants, in their correct form, for human use. Prof. Joshi is an associate professor at the Harrington Dept. of Bioengineering of the Ira A. Fulton School of Engineering.


In order to overcome the problem of plant-produced proteins being rejected by the bodys immune system as foreign, researchers found that the trigger for this action was the lack of specific sugar groups called sialic acids, attached to the sugar chains on protein molecules. When these groups are present on the proteins, the body does not act to rid itself of them. The teams discovery is a complex pathway, or set of chemical reactions, in plants that attach these sugar groups to the proteins. This pathway, in essence, is common to humans and plants. In humans, they are important for the half-life of proteins and immune system, but their role in plants is not known, says Prof. Joshi. It might be related to a plants ability to survive stressful conditions, like a lack of water or nutrients, or its role might be in plant-pathogen interaction.


Prof. Joshi explained that the team was concentrating on about 2-3 per cent of sialic acids on proteins made in plants and are investigating metabolic engineering methods to enhance the levels of enzymes involved in these reactions in the plant to get maximum yield. Knowing that the pathway exists opens up an avenue that can be used to make the correct glycoproteins for humans by plants. Researchers will continue their work on the new pathways, exploiting systems that exist in plants, regulating them and getting more and more sialic acids out of them. 


Website: www.bio.com 

Cancer protein relationship may aid new treatment

Scientists led by Prof. Tej Pandita at Washington University School of Medicine, the United States, have found that the absence of two proteins, which cells use to cope with heat stress, can make it easier for the cells to become cancerous. However, their absence also makes it harder for cancerous cells to survive exposure to heat and radiation. These findings mark the two proteins, Heat shock protein (Hsp) 70.1 and 70.3, as potential targets for gene therapy that could increase cancer cells vulnerability to treatments. This is the first time that heat shock proteins have been linked to the cancer cells response to ionizing radiation. Prof. Pandita believes that understanding the pathobiology of the genes that make these proteins how they function in normal circumstances and how they work in an unusual context like the cancer cell will help radiation oncologists devise gene therapy protocols that enhance cell kill from radiation treatments. 


Express Pharma Pulse, 1 January 2004

AGRI BIOTECH

Mustard root map breaks new ground tracking gene expression

Researchers led by biologist Dr. Philip Benfey at Duke University, the United States, have created a detailed mosaic of the root cells of a small flowering mustard plant Arabidopsis thaliana showing where and when about 22,000 of the plants roughly 28,000 genes are activated within the growing root tissue. This work was conducted in collaboration with New York University and the University of Arizona, and required high throughput techniques for harvesting, protoplasting (breaking down cell walls by enzymes) and sorting approximately 10 million cells in about 1 hours.


To track the lineage of individual cells as they developed into specific tissue, researchers conducted the process in three successive stages synchronously across five zones of cells and tissues in the root. They attached marker genes to genes characteristic of each of five different cell types or tissues. The marker genes produced traceable, green fluorescent protein (GFP) when the gene they were attached to got activated. These were then quickly sorted, isolated and identified to generate a visual map of 15 subgrids.


According to Dr. Benfey, this map is the first to demonstrate a high level of resolution of gene expression on a global basis for any organism and would serve as a proof-of-principle that similar approaches could be applied to other plant organs as well as other organisms. The map has laid the groundwork for looking at how various biological pathways interlink in transcriptional networks. It would help researchers to track the vast majority of an organisms genes as they are switched on and off as cells grow, continually divide and ultimately differentiate to build specialized tissue. 


Website: www.bio.com 

Short cut yields corn genome

Researchers at Cold Spring Harbor Laboratory, the United States, have developed a method to capture gene-rich regions while excluding junk (difficult-to-sequence) DNA. This filtering method promises to accelerate genome sequencing of crops and overcome significant challenges faced by researchers interested in crop improvement, plant molecular biology and genome evolution. The sequencing method uses a short cut called methylation filtration, developed in 1999 by Cold Spring Harbor Lab scientists Dr. Richard McCombie and Mr. Robert Martienssen. This method modifies the DNA of repetitive, gene-poor regions and captures unmethylated, gene-rich regions for analysis, removing 93 per cent of repetitive, gene-poor DNA. As such, researchers have been able to sequence and analyse gene-rich regions in the corn genome.


Dr. McCombie stressed that methylation filtration, combined with other simple techniques, could be used for successfully recovering and properly assembling complete genomic sequences from genomes that are otherwise extraordinarily difficult to decipher. Researchers have also shown that the gene-enriched draft DNA sequences can be converted into the complete sequence of the corn genes by using the much smaller rice genome which is about one-sixth the size of the corn genome as a guide. They believe that taking this short-cut approach has brought them very close to a final sequence map of the biologically important regions of the corn genome at a fraction of the cost of other approaches. 


Website: www.betterhumans.com 

Worlds first fungi-based fertilizer developed in India

The Energy Research Institute (ERI), India, has developed the worlds first fungal biofertilizer. ERI has developed technology that makes it possible to produce viable, healthy and genetically pure fungal propagules of high quality without any pathogenic contamination. The new biofertilizer, produced from the fungi Mycorrhiza, offers distinct benefits over conventional chemical-based fertilizers. Apart from increasing crop yield, it also helps reclaim arable land from ecologically damaged regions.


The Institute has applied for an Indian patent and has transferred the technology to two Indian companies, Cadila Pharmaceuticals and KCP Sugars, who have started commercial production and would be marketing under the brand name Josh and Ecorhiza, respectively. Negotiations for transfer of know-how and commercial production are underway with three other international fertilizer companies Bioraze (France), Premier Technologies (Canada) and Mycosym Triton (Switzerland). 


Website: www.cygnusindia.com 

EPA registers GM corn

Environmental Protection Agency (EPA), the United States, has granted registration to Monsantos YieldGard Plus, a genetically modified (GM) corn designed to control corn-borer and corn-rootworm pests. The gene incorporated in YieldGard Plus is a Bt gene (from the bacterium Bacillus thuringiensis). It would be the first GM crop in the world to shield against two insects concurrently. The new variety can protect itself against Western and Northern corn-rootworm larvae and the European corn-borer, together called Billion Dollar Worms as each causes an annual loss to the tune of US$1 billion. After ingesting a small quantity of the plant matter, the insect dies. Farmers cultivating the GM corn are required to follow the Insect Resistance Management (IRM) protocol, which is a regulatory necessity from EPA. 


Website: www.cygnusindia.com 

Worlds first genetically modified pigeonpea

Researchers at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), India, have developed the worlds first transgenic pigeonpea, known among Filipinos as kadyos. According to ICRISAT Director General Dr. William D. Dar, the GM pigeonpea is resistant to the destructive insect pest legume pod borer (Hilicoverpa armigera). This is a major scientific breakthrough as the pod borer has caused severe crop losses in the past. Dr. Dar has stressed that this is an important step that addresses the specific needs of resource-poor farmers in the semi-arid tropics through an effective biotechnological intervention.


The modified crop is currently undergoing field trials. Though on a limited scale, kadyos is being grown in some dry areas in the Philippines particularly Ilocos where it is called kardis. After contained field trials of the new GM pigeonpea, it will go through a second season of contained trial at ICRISAT. Once successful, ICRISAT will collaborate with its national agricultural research partners to implement open field trials.


Website: www.agbios.com

PUBLICATIONS

Metabolic Engineering in the Post-genomic Era

Engineering living cells continues to pose immense challenges to researchers. Many bioengineers have only just started to appreciate the full extent of the hierarchical control used by living systems. This book helps understand and deal with the plasticity of living cell factories and to turn the plasticity into the desired rather than the adverse direction. It brings together all the recent, most important breakthroughs in this exciting field and makes for essential reading for everyone with an interest in engineering living cells, including bioengineers, metabolic engineers, biotechnologists, molecular biologists, and pharmaceutical and biotechnology companies.

Transgenic Plants: Current Innovations and Future Trends

Major advances in transgenic plant technologies in recent years have generated a plethora of potential applications in agriculture and other areas (food safety, vaccine delivery, etc.). In this book, internationally acclaimed authors review the current state-of-the-art technologies as well as many of the potential applications. It contains chapters on a wide variety of topics, ranging from tree somatic embryogenesis and chloroplast transformation, to in planta transformation.


A unique feature of this book is its focus on the future of transgenic plants. Site-specific recombination systems and exciting applications such as edible vaccines and functional genomics will be part of future transgenic plant types. An essential volume for all plant science researchers, graduate students and advanced undergraduate students. It includes a useful index to help the reader.


For the above publications, contact: Horizon Scientific Press, P.O. Box 1, Wymondham, Norfolk 18 0EH, United Kingdom. Tel: +44 (1953) 601 106; Fax: +44 (1953) 603 068; E-mail: orders@ horizonpress.com.

Biotechnology: Applications and Career

The book addresses the young aspirants willing to make their careers in this upcoming area of science. Brief treatments of different branches of biotechnology including plant, animal, medicine, marine, bioinformatics, environment and industrial are provided for guidance, together with exhaustive lists of institutes, references and websites.


Contact: Mr. Vinod Vasishtha, Viva Books Pvt. Ltd., 4262/3, Ansari Road, Daryaganj, New Delhi 110 002, India. E-mail: viva@vivagroupindia.net.


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