biotech News - India

<p>Biotechnology provides a viable solution to almost every form of environmental damage, says Kiran Mazumdar-Shaw. . <a href="http://economictimes.indiatimes.com/quickiearticleshow/3370055.cms" target="_blank"><b>Weird and Wonderful Inventions!</b></a></p>

Dr Chandrika Varadachari’s “bio-release micronutrients” is making waves both internationally and in India as the technology maintains plant fertility by massively bringing down additional micronutrients during cultivation-dosage reduced to 1/10th-1/4th of current doses for micronutrient sulfates.

Fledgling biotechnology sector posted $2.56 billion (Rs.103 billion) in revenue during 2007-08, registering 20 per cent growth over the previous fiscal at $2.1 billion, an industry survey revealed.

Vaccine maker Panacea Biotec is foraying into the hospital business by setting up a 220-bed multi-specialty hospital with Gurgaon-based Umkal Medicals

It is good news that the government is expediting the process of setting up the national biotechnology regulatory authority, which is envisaged as a dextrous, one-stop facility.

Bayer BioScience Pvt Ltd, a Bayer CropScience Group company, on Tuesday announced the launch of Arize Dhani, a disease-resistant hybrid variety of rice in India.

With Nano technology applications finding place in every sphere, particularly health sector, a city institute is organising a one-day seminar on 'Bio and Nano Materials' on May seven, here.

Biotech major Biocon plans to set up a subsidiary unit for its research and development (R&D) this year contrary to the industry norm of spinning it off as a separate company.

Biovet has launched Asia's first Bio Safety Level-4 (BSL-4) manufacturing facility, specifically designed to enable product development and manufacturing of vaccines like Foot and Mouth Disease vaccine.

India’s largest biotechnology company Biocon on Tuesday reported a 13% increase in profit for 2007-08 to Rs 225 crore on improved revenues, especially in its contract research business.

A 20-member Italian delegation representing biotech and nanotech sectors, under the aegis of the Italian Trade Commission, has offered to tie-up with Indian firms.

India's top biotechnology firm, Biocon Ltd, is looking at overseas acquisitions for about $10 million to boost its sales globally and gain access to innovative drugs, its chairman said on Wednesday.

India on Sunday said developing microbicides was on the top of its priority list and they will be developed in the earliest possible time to prevent transmission of STDs and HIV/AIDS to women.

The deal will enable the Bangalore-based player to market its injectible insulin, generics, biosimilars and biologics in Europe.

Biotechnology firm Biocon on Monday announced the acquisition of a 70 per cent stake in German pharmaceutical company, AxiCorp GmbH, for Euro 30 million (over Rs 173 crore), as part of its plan to become a major player in the insulin segment in Europe.

An international seminar on ornamental fish trade has called for enforcement of strict bio-security measures in the industry and standardisation of breeding technologies.

Venture capitalists pumped a record $9.1 billion into privately-held US biotechnology and medical device companies last year, in hopes of making discoveries they can sell to larger drugmakers.

City-based International Centre for Genetic Engineering and Biotechnology has joined hands with US-based Emory Vaccine Center to develop vaccines for infectious diseases like HIV, tuberculosis and dengue.

Lauding the government's initiative of unveiling a National Biotechnology Policy, industry experts said that it was imperative that this policy was implemented in a time bound manner.

Researchers have developed a new biochip technology, which could soon put a stop to the use of animals for testing in the chemical and cosmetics industries.

After establishing Kolkata as a top IT/ITeS destination, the West Bengal government intends to replicate that success in the biotech turf.

A variant of a gene involved in communication among brain cells has a direct influence on alcohol consumption in mice, according to a new study by US scientists.

Biotech company Biocon is planning to launch its oral insulin drug in India by 2010 and is targeting sales of Rs 500 crore from the domestic market alone.

Biotech company Biocon is planning to launch its oral insulin drug in India by 2010 and is targeting sales of Rs 500 crore from the domestic market alone.

Glenmark Pharmaceuticals plans to acquire a distribution and marketing company in Indonesia, in a bid to increase its foothold in Asia’s emerging markets, the company’s top officials told ET.

Clinical research firm Manipal AcuNova Ltd on Monday announced it has completed the acquisition of ECRON GmbH, Europe.

US-based Generex Biotechnology Corporation on Friday said it has received approval from the Central Drugs Standards Control Organisation (CDSCO) for selling its non-injectable insulin in the country.

Biotechnology company Shreya Lifesciences has entered into an in-licensing agreement with US-based Generex Biotechnology Corp to market Oral-lyn, the country’s first needle-free insulin.

The Bombay High Court today took the Maharashtra government to task over an affidavit of its health department regarding implementation of bio-medical waste disposal in hospitals across the state.

Drug manufacturer Cipla said on Thursday it has received a notice from the government to pay Rs 49.47 crore for "alleged" overcharging on its drug Salbutamol, and said the same is "legally untenable".

Biotech company Biocon is in talks with various companies to outlicense some of its molecules to fund increasing investment in the research and development (R&D) division.

Multi-billion-dollar pharma ingredient and chemicals major DSM is in talks with Indian biotech companies to outlicense its exclusive technology, which uses human cells to develop biotech drugs.

Anand Mani, a pathology test vendor, wanted to gift his unborn child something special and his heart was set on saving the baby’s stem cells for a disease free future.

Bangalore-based biotechnology company Biocon plans to recruit 50 key persons from overseas to tide over domestic manpower shortage.

Joining Indian pharma majors who are targeting the $65-billion global biotech drug market.

India is the flavour of the season for the international business world. After the IT boom, now it’s the turn of the biotech sector. The last decade saw the tides of change in this sector with India starting to emerge as a global player.

The company will initiate European trials on three products which will be soon filed to the European Medicines Agency (EMEA) for regulatory approval.

A clutch of investors are set to pick up 47% stake in the Intas Biopharmaceuticals, the biotech arm of Ahmedabad-based pharma major Intas Pharmaceuticals.

Bioton, Poland's largest biotechnology company, will invest $ 35 mn in a joint venture that will operate in India, Finland, Russia and the UK, continuing its international expansion plan.

India and the United States on Thursday agreed to enhance cooperation in development of low-cost diagnostic and therapeutic medical technologies.

Two pharma cos may sign pact involving co-development of new biotech drugs & research services.

The tests will initially be only for cancer patients and Mr Saxena’s company, Acton Biotech, plans to cover other diseases later.

Biotechnology firm, Biocon on Monday said it has completed all activities related to the divestment of enzymes business to Novozymes South Asia Pvt Ltd.

Panacea Biotec has commissioned its new vaccine formulation plant in Baddi, which would double its capacity to two billion dosages per annum. The company has invested Rs 100 crore in the new plant.

The Wadias’ had objected to the Danone investment in Avesthagen citing violation of Press Note 1. They had alleged that the biotech company’s subsidiary Avesta Good Earth Foods had a similar line of business.

Indian drug makers have already become a formidable force in bringing out generic forms of chemically-synthesised medicines, especially in the US market, and now are gearing up to break into the follow-on biologics segment.

The government is planning to set up an export inspection agency for Ayurveda, Unani and Siddha (Ayush) products to put an end to frequent rejection of Indian exports.

Actis has set up Malaysia Telesta Diagnostics centre focusing on computer-aided diagnosis for breast cancer. Telesta is also willing for a technology transfer to Malaysia.

Chief Minister Parkash Singh Badal on Wednesday asked the Punjab State Council for Science and Technology (PSCST) to prepare a road map for the promotion of biotechnology and nanotechnology in the state.

US-based biotech company Biogen Idec, is looking for partnerships across the pharma value chain, including in-licensing of new experimental drugs and tie ups for its global clinical research projects.

Diversified major ITC Ltd has taken over Australian agri-biotech company Technico Pty Ltd for an undisclosed sum, as part of a strategy to strengthen its foods business.

Biocon Ltd said on Monday it had signed an agreement with Abu Dhabi's Neopharma for a joint venture company.

Professionals in pharma and biotechnology companies are increasingly taking the plunge to set up start-ups - a trend which investors describe as tip of the iceberg.

Riding on the success of Bt cotton, agriculture biotechnology has emerged as one of the fastest growing biotech industries in India in recent years, a latest report of the US Department of Agriculture (USDA) has said.

RFCL signs a definitive agreement to acquire Wipro BioMed, a leading provider of biomedical solutions.

Abl Biotechnologies Ltd said it has signed an MoU with Christian Medical College, Vellore, for joint research in several areas in management of various diseases prevalent in Indian sub-continent.

We were investing already in the biopharma segment which can deliver more than enzymes business, says Biocon CMD.

Under the agreement, Biocon will receive an upfront licensing fee, and following approval in the licensed territories, royalties from sales.

Big pharma companies such as Zydus Healthcare plans to focus on biotech in a big way.

Biotech firm Biovel Life Sciences to produce Human Growth Hormone.

Biotech firm Panacea Biotec on Thursday said it is planning to foray into oncology segment.

Dr. Reddy's Laboratories developing eight generic medicines using biotechnology.

Intas Biopharmaceuticals Ltd (IBPL) has received European Union-good manufacturing practices (EU-GMP) certification for its manufacturing facility in the city.

Complementing the rapid growth of the IT industry in India's silicon city, the emerging biotechnology (BT) sector will look for investments through partnerships and joint ventures at Bangalore Bio 2007, the three-day annual event beginning Thursday.

CMS of Biocon Ltd, Kiran Mazumdar Shaw says that lack of trained manpower is forcing us to import talent from overseas.

Sterling Biotech, the country's largest gelatin maker, on Thursday said it has raised 250 million dollars through issue of FCCBs, which have been listed at the Singapore Stock Exchange.

Hyderabad-Based Zenotech Laboratories, a biotech-based speciality injectables company, is looking at setting up a plasma fractionation facility at an investment of $20-25 million.

India, which was the largest user of BT crop last year, should now develop its own intellectual property in the area of biotechnology to serve its interest in agriculture better, a leading US biotech expert said.

Premier contract research company GVK Bioscience on Thursday appointed Manni Kantipudi, former chief information officer of Intel corporation as the President of company.

Leading biotech company Avesthagen and French plant breeding major Groupe Limagrain on Wednesday said they have jointly acquired majority stakes in two Indian seed companies.

The Supreme Court on Tuesday allowed the Centre to conduct approved field trials of genetically modified (GM) seeds in the country subject to certain restrictions.

To facilitate advanced stem cell research and development in Malaysia, Manipal Education and Medical Group (MEMG) has signed a Memorandum of Understanding with Malaysian Biotechnology corporation, a leading biotechnology agency in Malaysia.

Japanese scientists have genetically engineered silkworms to produce a specific colour, to avoid the trouble of dying silk.

The biotechnology sector in India, which has been growing at 37 per cent per annum is projected to touch five billion dollars mark by 2010, industry body CII said on Friday.

Suven Life Science has clocked a 33% growth in net profit to Rs 11.22 crore for the year ended March 2007.

Reliance Life Sciences today announced its partnership with US-based global investment management firm, MPM Capital LP.

Shantha Biotech seems to be abuzz with new activity after French healthcare major Merieux Alliance picked up 60% stake in the company last year.

After the success of its recomibant human insulin "Insugen", Biocon said clinical trials for the oral insulin would soon enter phase two.

The Company has posted a net profit of Rs 380.562 million for the quarter ended March 31, 2007 as compared to Rs 302.354 million for the quarter ended March 31, 2006.

After developing biotechnology park in Hyderabad, Shapoorji Pallonji Biotech Park is exploring Himachal Pradesh and Uttarakhand for its next biotech park. The company is in talks with the respective state governments for the same.

When asked whether Novartis was interested in buying U.S. biotechnology firm MedImmune , Vasella said biotech firms were "on our radar screen," but declined to comment further.

In a filing to BSE, Jupiter Bioscience said its board of directors have ratified the term sheet.

A global biotech drug research consortium developing AIDS vaccine - Collaboration for AIDS Vaccine Discovery (CAVD) - is keen to have a presence in India.

The firm said it would seek the approval for the proposal from its Board of Directors on April 12.

Maharashtra government has signed three MoUs with leading banks in a bid to provide fillip to bio-technology projects in the state.

Shares in Biocon ended down 0.24 per cent at Rs 465.05 in a firm market that rose 1.9 per cent.

DuPont India, subsidiary of the US-based $29-billion EI Du Pont de Nemours, will set up a plant biotech research centre at the DuPont Knowledge Center (DKC) in Hyderabad.

Integrated biotechnology firm Biocon on Wednesday said its subsidiary Syngene has entered into a research partnership with global pharma major Bristol-Myers Squibb.

The new immunosuppressants for renal therapy are at least 35-40 per cent cheaper than the MNC drug prices in the similar product category.

The Andhra Pradesh government along with the Federation of Asian Biotech Associations (FABA), the University of Hyderabad and the European Federation of Biotechnology is organising the fourth edition of annual BioAsia 2007 in Hyderabad.

Reliance LifeScience on Wednesday announced the acquisition of a 74% equity stake (1.1 billion shares) in the UK-based biotech firm.

Delhi-based biotechnolgy company Panacea Biotec has announced that it has registered 79% growth in net turnover.

Homegrown integrated biotechnology firm Biocon on Thursday posted 44.89 per cent increase in net profit at Rs 47.51 crore, as compared to Rs 32.79 cr in the year-ago period.

India’s Biocon is soon to establish a beachhead in the UK, and is setting up an office in London.

India's Biocon is soon to establish a beachhead in the UK, and is setting up an office in London.

The joint-venture with Neopharma is an important milestone for Biocon's global foray.

Biotech firm Biocon Ltd said on Tuesday that its has completed the Phase IV clinical trials for its insulin drug, Insugem.

Sandesara group’s Sterling Biotech plans to invest about Rs 600 crore to ramp up the manufacturing capacities of gelatin and coenzyme (Q10) at its facilities in Vadodara.

India is set to become the hub of global biotech industry and the country's share in the sector could touch $40 billion mark by 2015, Science and Technology Minister Kapil Sibal has said.

Fidelity Investments is in advanced talks to buy 12-14% stake in the Bangalore-based biotech firm Avesthagen for $10-12 million.

biotech News - World Wide

Background: Cardiovascular disease (CVD) and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO) on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480). Serum lipids of rats fed with high fat diet (HFD) and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT) assay. Results: Except for higher dose group, body weights decreased significantly. Total cholesterol (TC), LDL-cholesterol (LDL-C) of all dose groups, Triglycerides (TG) of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C), compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth. Conclusions: Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.

Background: Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods: Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results: Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion: Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.

Background: The goal of Canada's Compassionate Care Benefit (CCB) is to enable family members and other loved ones who are employed to take a temporary secured leave to care for a terminally ill individual at end of life. Successful applicants of the CCB can receive up to 55% of their average insured earnings, up to a maximum of CDN$435 per week, over a six week period to provide care for a gravely ill family member at risk of death within a six month period, as evidenced by a medical certificate. The goal of this study is to evaluate the CCB from the perspective of family caregivers providing care to individuals at end of life. There are three specific research objectives. Meeting these objectives will address our study purpose which is to make policy-relevant recommendations informed by the needs of Canadian family caregivers and input from other key stakeholders who shape program uptake. Being the first study that will capture family caregivers' experiences and perceptions of the CCB and gather contextual data with front-line palliative care practitioners, employers, and human resources personnel, we will be in a unique position to provide policy solutions/recommendations that will address concerns raised by numerous individuals and organizations. Methods: We will achieve the research goal and objectives through employing utilization-focused evaluation as our methodology, in-depth interviews and focus groups as our techniques of data collection, and constant comparative as our technique of data analysis. Three respondent groups will participate: (1) family caregivers who are providing or who have provided end of life care via phone interview; (2) front-line palliative care practitioners via phone interview; and (3) human resources personnel and employers via focus group. Each of these three groups has a stake in the successful administration of the CCB. A watching brief of policy documents, grey literature, media reports, and other relevant items will also be managed throughout data collection. DiscussionWe propose to conduct this study over a three year period beginning in October, 2006 and ending in October, 2009.

The MASS III Trial is a large project from a single institution, The Heart Institute of the University of Sao Paulo, Brazil (InCor), enrolling patients with coronary artery disease and preserved ventricular function. The aim of the MASS III Trial is to compare medical effectiveness, cerebral injury, quality of life, and the cost-effectiveness of coronary surgery with and without of cardiopulmonary bypass in patients with multivessel coronary disease referred for both strategies. The predefined primary end point was the incidence of cardiovascular mortality, cerebrovascular accident, nonfatal myocardial infarction, and refractory angina requiring revascularization. The secondary end points in this trial include noncardiac mortality, presence and severity of angina, quality of life based on the SF-36 Questionnaire, and cost-effectiveness at discharge and at 5-year follow-up. In this scenario, we will analyze the cost of the initial procedure, hospital length of stay, resource utilization, repeat hospitalization, and repeat revascularization events during the follow-up. Exercise capacity will be assessed at 6-months, 12-months, and the end of follow-up. A neurocognitive evaluation will be assessed in a subset of subjects using the Brain Resource Center computerized neurocognitive battery. Furthermore, magnetic resonance imaging will be made to detect any cerebral injury before and after procedures in patients who undergo coronary artery surgery with and without cardiopulmonary bypass. Clinical Trial registration information ISRCTN59539154 Off-pump vs. on-pump surgery in patients with Stable CAD MASS III

Background: Otitis media (OM) is the most common paediatric illness for which antibiotics are prescribed. In Australian Aboriginal children OM is frequently asymptomatic and starts at a younger age, is more common and more likely to result in hearing loss than in non-Aboriginal children. Absent transient evoked otoacoustic emissions (TEOAEs) may predict subsequent risk of OM. Methods: 100 Aboriginal and 180 non-Aboriginal children in a semi-arid zone of Western Australia were followed regularly from birth to age 2 years. Tympanometry was conducted at routine field follow-up from age 3 months. Routine clinical examination by an ENT specialist was to be done 3 times and hearing assessment by an audiologist twice. TEOAEs were measured at ages <1 and 1-2 months. Cox proportional hazards model was used to investigate the association between absent TEOAEs and subsequent risk of OM. Results: At routine ENT specialist clinics, OM was detected in 55% of 184 examinations in Aboriginal children and 26% of 392 examinations in non-Aboriginal children; peak prevalence was 72% at age 5-9 months in Aboriginal children and 40% at 10-14 months in non-Aboriginal children. Moderate-severe hearing loss was present in 32% of 47 Aboriginal children and 7% of 120 non-Aboriginal children aged 12 months or more. TEOAE responses were present in 90% (46/51) of Aboriginal children and 99% (120/121) of non-Aboriginal children aged <1 month and in 62% (21/34) and 93% (108/116), respectively, in Aboriginal and non-Aboriginal children at age 1-2 months. Aboriginal children who failed TEOAE at age 1-2 months were 2.6 times more likely to develop OM subsequently than those who passed. Overall prevalence of type B tympanograms at field follow-up was 50% (n=78) in Aboriginal children and 20% (n=95) in non-Aboriginal children. Conclusions: The burden of middle ear disease is high in all children, but particularly in Aboriginal children, one-third of whom suffer from moderate-severe hearing loss. In view of the frequently silent nature of OM, every opportunity must be taken to screen for OM. Measurement of TEOAEs at age 1-2 months to identify children at risk of developing OM should be evaluated in a routine health service setting.

Background: With a whole genome duplication event and wealth of biological data, salmonids are excellent model organisms for studying evolutionary processes, fates of duplicated genes and genetic and physiological processes associated with complex behavioral phenotypes. It is surprising therefore, that no salmonid genome has been sequenced. Atlantic salmon (Salmo salar) is a good representative salmonid for sequencing given its importance in aquaculture and the genomic resources available. However, the size and complexity of the genome combined with the lack of a sequenced reference genome from a closely related fish makes assembly challenging. Given the cost and time limitations of Sanger sequencing as well as recent improvements to next generation sequencing technologies, we examined the feasibility of using the Genome Sequencer (GS) FLX pyrosequencing system to obtain the sequence of a salmonid genome. Eight pooled BACs belonging to a minimum tiling path covering ~1 Mb of the Atlantic salmon genome were sequenced by GS FLX shotgun and Long Paired End sequencing and compared with a ninth BAC sequenced by Sanger sequencing of a shotgun library. Results: An initial assembly using only GS FLX shotgun sequences (average read length 248.5 bp) with ~30x coverage allowed gene identification, but was incomplete even when 126 Sanger-generated BAC-end sequences (~0.09x coverage) were incorporated. The addition of paired end sequencing reads (additional ~26x coverage) produced a final assembly comprising 175 contigs assembled into four scaffolds with 171 gaps. Sanger sequencing of the ninth BAC (~10.5x coverage) produced nine contigs and two scaffolds. The number of scaffolds produced by the GS FLX assembly was comparable to Sanger-generated sequencing; however, the number of gaps was much higher in the GS FLX assembly. Conclusions: These results represent the first use of GS FLX paired end reads for de novo sequence assembly. Our data demonstrated that this improved the GS FLX assemblies; however, with respect to de novo sequencing of complex genomes, the GS FLX technology is limited to gene mining and establishing a set of ordered sequence contigs. Currently, for a salmonid reference sequence, it appears that a substantial portion of sequencing should be done using Sanger technology.

Objectives Female gender and young age are known risk factors for psychological morbidity after a disaster, but this conclusion is based on studies without a pre-disaster assessment. The aim of this study in family practice was to investigate if these supposed risk factors would still occur in a study design with a pre-disaster measurement. Methods: A matched cohort study with pre-disaster (one year) and post-disaster (five years) data. Community controls (N=3164) were matched with affected residents (N=3164) on gender, age and socioeconomic status. Main outcome measures were utilization rates measured by family practice attendances and psychological, musculoskeletal and digestive health problems as registered by the family practitioner using the International Classification of Primary Care (ICPC). Results: Affected residents of female and male gender and in five age groups all showed increases in utilization rates in the first post-disaster year and in psychological problems when compared to their pre-disaster baseline levels. The increases showed no statistically significant changes, however, between women and men and between all age groups. Conclusion: Gender and age did not appear to be disaster-related risk factors in this study in family practice with a pre-disaster base line assessment, a comparison group and using existing registries. Family practitioners should not focus specifically on these risk groups.

Agressive angiomyxoma is a rare mesenchymal neoplasm. It mainly presents in females. We here present a case of angiomyxoma presenting as huge abdominal lump along with gluteal swelling. Case note is described along with brief review of literature.

Background: Receptors and scaffold proteins usually possess a high number of distinct binding domains inducing the formation of large multiprotein signaling complexes. Due to combinatorial reasons the number of distinguishable species grows exponentially with the number of binding domains and can easily reach several millions. Even by including only a limited number of components and binding domains the resulting models are very large and hardly manageable. A novel model reduction technique allows the significant reduction and modularization of these models. Results: We introduce methods that extend and complete the already introduced approach. For instance, we provide techniques to handle the formation of multi-scaffold complexes as well as receptor dimerization. Furthermore, we discuss a new modeling approach that allows the direct generation of exactly reduced model structures. The developed methods are used to reduce a model of EGF and insulin receptor crosstalk comprising 5,182 ordinary differential equations (ODEs) to a model with 87 ODEs. Conclusions: The methods, presented in this contribution, significantly enhance the available methods to exactly reduce models of combinatorial reaction networks.

Background: The reliable extraction of features from mass spectra is a fundamental step in the automated analysis of proteomic mass spectrometry (MS) experiments. Results: This contribution proposes a sparse template regression approach to peak picking called NITPICK. NITPICK is a Non-greedy, Iterative Template-based peak PICKer that deconvolves complex overlapping isotope distributions in multicomponent mass spectra. NITPICK is based on fractional averagine, a novel extension to Senko's well-known averagine model, and on a modified version of sparse, non-negative least angle regression, for which a suitable, statistically motivated early stopping criterion has been derived. The strength of NITPICK is the deconvolution of overlapping mixture mass spectra. Conclusions: Extensive comparative evaluation has been carried out and results are provided for simulated and real-world data sets. NITPICK outperforms pepex, to date the only alternate, publicly available, non-greedy feature extraction routine. NITPICK is available as software package for the R programming language and can be downloaded from http://hci.iwr.uni-heidelberg.de/mip/proteomics/.

Background: The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity. Results: We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants. Conclusion: Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.

Background: The occurrence of liver cancer is higher in males than in females, and the incident rate increases during aging. Signaling pathways regulated by retinoid x receptor alpha (RXRalpha) are involved in hepatocellular carcinogenesis. The phenotype of hepatocyte RXRalpha deficient mice is different between genders. To explore the impact of hepatocyte RXRalpha deficiency on gender-dependent hepatic gene expression, we compared the expression profiles of cancer-related genes in 6 and 24 month old male and female mice. Results: In 6 month old mice, male mutant mice showed more cancer-related genes with alteration in mRNA levels than females did (195 vs. 60). In aged mice (24 month), female mutant mice showed greater deviation in mRNA expression levels of cancer-related genes than their male counterparts (149 vs. 82). The genes were classified into five categories according to their role in carcinogenesis: apoptosis, metastasis, cell growth, stress, and immune response. In each category, dependent upon age and gender, the genes as well as the number of genes with altered mRNA levels due to RXRalpha deficiency varies. Conclusions: The change in hepatic cancer-related gene expression profiles due to RXRalpha deficiency was gender- and age-dependent. The alteration of mRNA levels of cancer-related genes implied that aberrant RXRalpha signaling could potentially increase the risk of liver cancer and that retinoid signaling might contribute to gender- and age-associated liver cancer incidence.

Background: Using the Internet to seek health information is becoming more common. Its consequences on health care utilisation are hardly known in the general population, in particular among children whose parents seek health information on the Internet. Our objective was to investigate the relationship between parental use of the Internet to seek health information and primary care utilisation for their child. Methods: This cross-sectional survey has been carried out in a population of parents of pre-school children in France. The main outcome measure was the self-reported number of primary care consultations for the child, according to parental use of the Internet to seek health information, adjusted for the characteristics of the parents and their child respectively, and parental use of other health information sources. Results: A total of 1 068 out of 2 197 questionnaires were returned (response rate of 49%). No association was found between parental use of the Internet to seek health information and the number of consultations within the last 12 months for their child. Variables related to the number of primary care consultations were characteristics of the child (age, medical conditions, homeopathic treatment), parental characteristics (occupation, income, stress level) and consultation of other health information sources (advice from pharmacist, relatives). Conclusion: We did not find any relationship between parental use of the Internet to seek health information and primary care utilisation for children. The Internet seems to be used as a supplement to health services rather than as a replacement.

Background: This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug.Results and conclusionsBayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential / non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

Background: Cytochrome P450 enzymes play critical roles in fungal biology and ecology. To support studies on the roles and evolution of cytochrome P450 enzymes in fungi based on rapidly accumulating genome sequences from diverse fungal species, an efficient bioinformatics platform specialized for this super family of proteins is highly desirable. Results: The Fungal Cytochrome P450 Database (FCPD) archives genes encoding P450s in the genomes of 66 fungal and 4 oomycete species (4,538 in total) and supports analyses of their sequences, chromosomal distribution pattern, and evolutionary histories and relationships. The archived P450s were classified into 16 classes based on InterPro terms and clustered into 141 groups using tribe-MCL. The proportion of P450s in the total proteome and class distribution in individual species exhibited certain taxon-specific characteristics. Conclusions: The FCPD will facilitate systematic identification and multifaceted analyses of P450s at multiple taxon levels via the web. All data and functions are available at the web site http://p450.riceblast.snu.ac.kr/.

Background: To compare the costs and effects of paliperidone extended release (ER), a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone) over a 1-year time period. Methods: A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. Results: The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 for risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole) with a lower cost compared to the other therapies examined (E7,030 compared to E7,034 for olanzapine, E7,082 for risperidone, E8,321 for quetiapine, E7,713 for ziprasidone and E7,807 for aripiprazole). During the sensitivity analysis, a +/-10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Conclusions: Treatment with paliperidone ER can lead to lower total cost and higher number of stable days in most of the cases examined.

No abstract available.

Background: In 1999, an Utstein Template for Uniform Reporting of Data following Major Trauma was published. Few papers have since been published based on that template, reflecting a lack of international consensus on its feasibility and use. The aim of the present revision was to further develop the Utstein Template, particularly with a major reduction in the number of core data variables and the addition of more precise definitions of data variables. In addition, we wanted to define a set of inclusion and exclusion criteria that will facilitate uniform comparison of trauma cases. Methods: Over a ten-month period, selected experts from major European trauma registries and organisations carried out an Utstein consensus process based on a modified nominal group technique. Results: The expert panel concluded that a New Injury Severity Score > 15 should be used as a single inclusion criterion, and five exclusion criteria were also selected. Thirty-five precisely defined core data variables were agreed upon, with further division into core data for Predictive models, System Characteristic Descriptors and for Process Mapping. Conclusions: Through a structured consensus process, the Utstein Template for Uniform Reporting of Data following Major Trauma has been revised. This revision will enhance national and international comparisons of trauma systems, and will form the basis for improved prediction models in trauma care.

Background: In a previous study we have reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (VV ) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure. Methods: Slides were obtained from blocks of the previous study and VV was assessed immunohistochemically and by point counting using a grid with 48 points, a 20x objective and a computer screen for a final magnification of 580x. Neutrophils were marked with myeloperoxidase antibody, macrophages with Mac-3, dendritic cells with fascin, B-lymphocytes with B220, CD4+ T-cells with CD4+ antibody, and CD8+T-cells with CD8-alpha. The significance of the differences was calculated using one-way analysis of variance. Results: Chronic smoke exposure increased neutrophil VV by 97%, macrophage by 107%, dendritic cell by 217%, B-lymphocyte by 436%, CD4+ by 524%, and CD8+ by 417%. The higher dose of roflumilast prevented the increase in neutrophil VV by 78%, macrophage by 82%, dendritic cell by 48%, B-lymphocyte by 100%, CD4+ by 98% and CD8+ VV by 88%. The lower dose of roflumilast did not prevent the increase in neutrophil, macrophage and B-cell VV but prevented dendritic cells by 42%, CD4+ by 55%, and CD8+ by 91%. Conclusions: These results indicate ((i) chronic exposure to cigarette smoke in mice results in a significant recruitment into the lung of inflammatory cells of both the innate and adaptive immune system; (ii) roflumilast at the higher dose exerts a protective effect against the recruitment of all these cells and at the lower dose against the recruitment of dendritic cells and T-lymphocytes; (iii) these findings underline the role of innate immunity in the development of pulmonary emphysema and (iiii) support previous results indicating that the inflammatory cells of the adaptive immune system do not play a central role in the development of cigarette smoke induced emphysema in mice.

Background: The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee) of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods: Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, lambda-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST) and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results: All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies populations and highly insensitive in the Trincomalee An. subpictus population. Conclusions: The complexity of the resistance segregating in these field populations underlines the need for new molecular tools to identify the genomic diversity, differential upregulation and different binding specificities of resistance conferring genes, and the presence of different subspecies with different vectorial capacities.

Surgical treatment of metastatic spinal cord compression with or without neural deficit is controversial. Karnofsky and Tokuhashi scores have been proposed for prognosis of spinal metastasis. Here, we conducted a retrospective analysis of Karnofsky and modified Tokuhashi scores in 57 consecutive patients undergoing surgery for secondary spinal metastases to evaluate the value of these scores in aiding decision making for surgery. Comparison of preoperative Karnofsky and modified Tokuhashi scores with the type of the surgical approach for each patient revealed that both scores not only reliably estimate life expectancy, but also objectively improved surgical decisions. When the general status of the patient is poor (i.e., Karnofsky score less than 40% or modified Tokuhashi score of 5 or greater), palliative treatments and radiotherapy, rather than surgery, should be considered.

Background: Caesarean section before labor or before ruptured membranes ("elective caesarean section", or ECS) has been introduced as an intervention for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Currently, no evidence that ECS versus vaginal delivery reduces the rate of MTCT of HBV has been generally provided. The aim of this review is to assess, from randomized control trails (RCTs), the efficacy and safety of ECS versus vaginal delivery in preventing mother-to-child HBV transmission. Results: We searched Cochrane Pregnancy and Childbirth Group's Trials Register (January, 2008), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2008, issue 1), PubMed (1950 to 2008), EMBASE (1974 to 2008), Chinese Biomedical Literature Database (CBM) (1975 to 2008), China National Knowledge Infrastructure (CNKI) (1979 to 2008), VIP database (1989 to 2008), as well as reference lists of relevant studies. Finally, four randomized trails involving 789 people were included. Based on meta-analysis, There was strong evidence that ECS versus vaginal delivery could effectively reduce the rate of MTCT of HBV (ECS: 10.5%; vaginal delivery: 28.0%). The difference between the two groups (ECS versus vaginal delivery) had statistical significance (RR 0.41, 95% CI 0.28 to 0.60, P<0.000001). No data regarding maternal morbidity or infant morbidity according to mode of delivery were available. Conclusions: ECS appears to be effective in preventing MTCT of HBV and no postpartum morbidity (PPM) was reported. However, the conclusions of this review must be considered with great caution due to high risk of bias in each included study (graded C).

Background: Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which potently inactivates glucocorticoids (e.g. cortisol) to inert forms (cortisone), allows increased access of maternal glucocorticoids to the fetus and 'programs' hypertension. Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11beta-HSD2 enzyme activity, and blood pressure at age 3 years. Methods: Among 286 newborns in Project Viva, a prospective pre-birth cohort study based in eastern Massachusetts, we measured cortisol (F) and cortisone (E) in venous cord blood and used the ratio of F/E as a marker for placental 11beta-HSD2 activity. We measured blood pressure (BP) when the offspring reached age 3 years. Using mixed effects regression models to control for BP measurement conditions, maternal and child characteristics, we examined the association between the F/E ratio and child BP. Results: At age 3 years, each unit increase in the F/E ratio was associated with a 1.6 mm Hg increase in systolic BP (95% CI 0.0 to 3.1). The F/E ratio was not associated with diastolic blood pressure or birth weight for gestational age z-score. Conclusions: A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11beta-HSD2 activity, was associated with higher systolic blood pressure at age 3 years. Our data suggest that increased fetal exposure to active maternal glucocorticoids may program later systolic blood pressure.

IntroductionGastric polyps exist in a wide variety of types, most of which are small and often benign. Discovery of gastric polyps during Endoscopy necessitates biopsies. Case presentationWe present a case report of an isolated diffuse hyperplastic gastric polyposis in a 26 years old Hispanic female when she was investigated for profound anemia. The Esophagogastroduodenoscopy revealed numerous gastric polyps filling the entire stomach. She was treated with near-total gastrectomy and her anemia resolved Conclusion: Isolated diffuse hyperplasic gastric polyposis with normal gastrin level is a rare entity and can present with severe anemia.

Background: Very little data about the conservative treatment of early stage glassy cell cervical cancer have been reported. Case presentationA 30-year old patient, nulligravida was admitted to the Gynecologic Oncology Unit of the Catholic University of Campobasso for irregular post-coital vaginal bleeding. The patients was staged as having FIGO stage IB1 (tumor diameter=2 cm) squamous cervical cancer. After extensive counseling of the patient and her family, laparoscopic pelvic lymphadenectomy and cold knife conization were performed. The final diagnosis was FIGO Stage IB1 glassy cell carcinoma. Currently, after a follow-up of 38 months, she has no evidence of disease. Conclusions: We reported a case of early stage glassy cell cancer patient, who was conservatively treated by conization and laparoscopic pelvic lymphadenectomy.

IntroductionThe occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. Case presentationWe present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. Conclusions: The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

Background: Patients with major depression refractory to repeated pharmacological trials (TRD) may remain symptomatic for many years after their index episode. Augmentation strategies (with lithium or an atypical antipsychotic) or combining an antidepressant with short-term psychotherapy have been used with relative success in these patients. The aim of this study was to assess the effectiveness of the concomitant administration of quetiapine, an atypical antipsychotic, or placebo, to cognitive-behavior therapy (CBT) in TRD. Methods. Thirty-one patients who met entrance criteria for unipolar major depression (TRD stage II or greater) underwent 3 weeks of lithium augmentation after which non-responders (N = 22) were randomized to receive either quetiapine or placebo as an adjunct to their 12 weekly CBT sessions (quetiapine/CBT or placebo/CBT groups). Primary efficacy measures were the Hamilton and the Montgomery-Asberg rating scales for depression. Results. Overall, there was a significant reduction in both primary efficacy measure scores at LOCF for the 11 patients in the quetiapine/CBT group but not in the placebo/CBT treated patients. Patients in the quetiapine/CBT group, compared to those receiving placebo/CBT, showed a significantly greater degree of improvement on one primary and one secondary efficacy measure, were more likely to complete the trial and, completed a greater number of CBT sessions. Conclusion. Although preliminary, our results suggest that the adjunctive administration of quetiapine to CBT may prove useful in the treatment of stage II TRD. Trial Registration. Current Controlled Trials ISRCTN12638696.

Background: Recent studies have documented an increased risk of cardiovascular disease (CVD) in persons with systolic blood pressures of 120-139mmHg and/or diastolic blood pressures of 80-89mmHg, classified as prehypertension in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. In this paper we estimate the prevalence of prehypertension in Jamaica and evaluate the relationship between prehypertension and other risk factors for CVD. Methods: The study used data from participants in the Jamaica Lifestyle Survey conducted from 2000-2001. A sample of 2012 persons, 15-74 years old, completed an interviewer administered questionnaire and had anthropometric and blood pressure measurements performed by trained observers using standardized procedures. Fasting glucose and total cholesterol were measured using a capillary blood sample. Analysis yielded crude, and sex-specific prevalence estimates for prehypertension and other CVD risk factors. Odds ratios for associations of prehypertension with CVD risk factors were obtained using logistic regression. Results: The prevalence of prehypertension among Jamaicans was 30% (95% confidence interval [CI] 27%- 33%). Prehypertension was more common in males, 35% (CI 31%-39%), than females, 25% (CI 22%-28%). Almost 46% of participants were overweight; 19.7% were obese; 14.6% had hypercholesterolemia; 7.2% had diabetes mellitus and 17.8% smoked cigarettes. With the exception of cigarette smoking and low physical activity, all the CVD risk factors had significantly higher prevalence in the prehypertensive and hypertensive groups (p for trend <0.001) compared to the normotensive group. Odds of obesity, overweight, high cholesterol and increased waist circumference were significantly higher among younger prehypertensive participants (15-44 years-old) when compared to normotensive young participants, but not among those 45-74 years-old. Among men, being prehypertensive increased the odds of having >/=3 CVD risk factors versus no risk factors almost three-fold (odds ratio [OR] 2.8[CI 1.1-7.2]) while among women the odds of >/=3 CVD risk factors was increased two-fold (OR 2.0[CI 1.3-3.8]) Conclusions: Prehypertension occurs in 30% of Jamaicans and is associated with increased prevalence of other CVD risk factors. Health-care providers should recognize the increased CVD risk of prehypertension and should seek to identify and treat modifiable risk factors in these persons.

Background: Resistance to soil waterlogging stress is an important plant breeding objective in high rainfall or poorly drained areas across many countries in the world. The present study was conducted to identify quantitative trait loci (QTLs) associated with waterlogging tolerance (e.g. leaf chlorosis, plant survival and biomass reduction) in barley and compare the QTLs identified across two seasons and in two different populations using a composite map constructed with SSRs, RFLP and Diversity Array Technology (DArT) markers. Results: Twenty QTLs for waterlogging tolerance related traits were found in the two barley double haploid (DH) populations. Several of these QTLs were validated through replication of experiments across seasons or by co-location across populations. Some of these QTLs affected multiple waterlogging tolerance related traits, for example, QTL Qwt4-1 contributed not only to reducing barley leaf chlorosis, but also increasing plant biomass under waterlogging stress, whereas other QTLs controlled both leaf chlorosis and plant survival. Conclusion: Improving waterlogging tolerance in barley is still at an early stage compared with other traits. QTLs identified in this study have made it possible to use marker assisted selection (MAS) in combination with traditional field selection to significantly enhance barley breeding for waterlogging tolerance. There may be some degree of homoeologous relationship between QTLs controlling barley waterlogging tolerance and that in other crops as discussed in this study.

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