Brain immune cells express a unique set of genes; surprising results in aging brains

November 15, 2013, 4:08 am

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Microglia, a type of macrophage, which act as the immune surveillance cells in the brain, express a unique set of genes to be termed the ‘microglial sensome’. That’s according to a new paper on healthy adult and aged mice from the Massachusetts General Hospital Centre for Immunology and Inflammatory Diseases and Division of Infectious Diseases just published online in Nature Neuroscience. Microglia scan the brain environment and respond to invading pathogens, toxins and cellular debris.

This exciting study represents the first gene expression 'snapshot' of any mammalian brain cell and it intriguingly suggests that with aging, expression of genes with potentially neural-destructive products was down-regulated while the expression of neuroprotective genes, for example those involved in microbe recognition and host defence, were up-regulated. This is in contrast to previous studies suggesting that neurotoxicity increases with age. The study’s authors suggest that the divergence in results is due to previous studies not looking the cells' full expression profile. Also, studies were often done in cultured cells rather than in vivo in animals.

The research group employed a novel direct RNA sequencing technique in the study, without amplification or cDNA synthesis. Findings were by fluorescence dual in situ hybridization, unbiased proteomic analysis and quantitative PCR.

This work establishing the ‘microglial sensome’ under normal conditions opens the way for further studies on the situation under pathological conditions. Two of the genes identified in the study have been linked to increased risk of Alzheimer’s disease and it is known that microglia become more neurotoxic as Alzheimer's disease and other neurodegenerative disorders progress. The group hope to extend their work to the ‘microglial sensome’ in humans and identify how it changes in central nervous system disorders, with the eventual aim of therapeutic pharmacological manipulation.

Sources

HICKMAN, S.E.., KINGERY, N.D., OHSUMI, T.K., BOROWSKY, M.L., WANG, L.-C., MEANS, T.K. and EL KHOURY, J., 2013. The microglial sensome revealed by direct RNA sequencing. Nature Neuroscience, 2013; DOI: 10.1038/nn.3554

Massachusetts General Hospital. "Genes uniquely expressed by brain's immune cells." ScienceDaily, 14 Nov. 2013. [Accessed 15 Nov. 2013].

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Beloranib, a prospective obesity drug, scores highly in phase II trial by Zafgen

November 15, 2013, 4:36 am

≫ Next: OMICS 5th World congress on Biotechnology | Valencia | June 25th -27th, 2014

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Zafgen Inc. has released positive Phase II trial data on a prospective new obesity drug, beloranib, which is a selective inhibitor of methionine aminopeptidase 2 (MetAP2). The trial was a randomized, double-blind, placebo-controlled trial carried out on 147 severely obese individuals, mainly women, over twelve weeks to measure efficacy and safety. Patients ate normally during the trial and did not modify their exercise routine.

The trial data indicated significant weight loss and cardiometabolic risk marker improvements. This positive efficacy outcome was in conjunction with reassuring safety data. In fact, the drug triggered improvements in systolic blood pressure. There were no serious adverse events (AEs) reported to be due to the drug and no clinically significant abnormal laboratory measures, vital signs, or electrocardiography (ECG) findings. Some more minor adverse events such as nausea, diarrhoea, headache, injection site bruising, and insomnia were reported but were generally transient. Insomnia at the higher doses, however, caused some patients to drop out.

Obesity is a public health issue that has become extremely problematic in the developed world. While the benefits of a healthy diet and exercise regime are promoted in public health campaigns, once a person becomes obese, their fat metabolism changes so that they store more and more fat, making it increasingly difficult to lose weight. Beloranib is a novel compound which is designed to target methionine aminopeptidase 2 (MetAP2), a key enzyme in the fat metabolism process which controls the production and utilization of fatty acids. MetPA2 inhibitors work in various ways, for example by reducing feelings of hunger but also by reducing new fatty acid molecule production by the liver and assisting in fat conversion to energy. Beloranib is being developed as a twice-weekly subcutaneous injection for severe obesity.

The next step for Zafgen is to conduct a 6-12 month Phase IIb study in 2014 with a group of about 200 patients to allow fine-tuning of the dosage and observation of long-term impact on weight and blood pressure. The company are also already carrying out a study on Prader – Willy syndrome patients who experience insatiable hunger to be completed later this year or early in 2014. If results continue to be positive for Beloranib it should offer new hope for obese patients.

Sources

http://www.prnewswire.com/news-releases/...40651.html (Zafgen press release) [Accessed 15 November 2013].

http://www.fiercebiotech.com/story/zafge...2013-11-15 [Accessed 15 November 2013].

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OMICS 5th World congress on Biotechnology | Valencia | June 25th -27th, 2014

November 15, 2013, 5:02 am

≫ Next: Hot Locations Around the world for Biotech Jobs

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5th World congress on Biotechnology

Organisers: OMICS Group International

Dates: June 25th -27th, 2014

Location: Valencia Conference Centre (Palacio de Congresos de Valencia), Valencia, Spain.

Website: http://biotechnologycongress.com/index.php
The very detailed website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Conference theme
"Biotechnology: Meeting the Needs of a Changing World."

Purpose of the conference
The conference aims to facilitate the bringing together of experts, researchers and decision makers both from academia, Biotech, Pharmaceutical and healthcare industry from all over the world to exchange their knowledge, experience and research innovations and build a biotechnology community. This forum enables a common platform where any participant can discuss their research in order to establish a scientific network that binds industry and academia together to foster collaboration and to evaluate emerging issues, technologies and innovations in the arena of biotechnology and allied fields to explore new possibilities and improve the existed opportunities.

Topics:
• Current Scenario of Biotechnology
• Biotechnology in Agriculture
• Biotechnology in Health Care
• Food and Bioprocess Technology
• Petroleum and Environmental Biotechnology
• Immunology and Stem Cell Therapy
• Genetic Engineering and rDna Technology
• Biochemistry, Cell and Molecular biology
• Microbiology and Microbial World
• Animal Biotechnology and Cell Culture
• Bioinformatics and Biosensor
• Marine Biotechnology and Renewable Energy technology

Confirmed Speakers
Ara Kanekanian, Cardiff Metropolitan University, UK
Graciela Brelles-Mariño, Universidad Nacional de La Plata, Argentina
Robert S. Marks, Ben-Gurion University, Israel
Manuel Perez-Alonso, The University of Valencia, Spain

Publication opportunity
All accepted abstracts will be published in respective OMICS Group Journals

Who are the organisers?
OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. They were established in 2007 with the aim of making the sciences and technology information ‘Open Access’. They publish 300 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology. Their main stakeholders are Research Scholars, Students, Libraries, Educational Institutions, Research centres and the industry. They organise 100 International conferences annually where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions.

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Hot Locations Around the world for Biotech Jobs

November 15, 2013, 5:19 am

≫ Next: EMBL Microfludics Conference | July 23rd to 25th 2014 | Heidelberg

≪ Previous: OMICS 5th World congress on Biotechnology | Valencia | June 25th -27th, 2014

The best locations around the world to hunt for jobs in Biotech and BioPharma sector is enlisted by GEN (Genetic Engineering and Biotech News) through one of its recently conducted survey/ analysis. GEN included multiple job sites, the most offered job locations by various Biotech sectors and direct people survey in its analysis to find out the different regions around the world (inside and outside United States) holding more space for Biotech and BioPharma jobs. Based on the results of the analysis the identified locations with promising Biotech jobs and BioPharma jobs are,

Bavaria, Germany, Moscow - Russian Federation, North Rhine – WestPhalia (Germany), East of England UK including Cambridge, London and Oxford, IIe-de-France region (France), China (Shangai region), NewYork, Boston / Cambridge, San Francisco, Philadelphia, Los Angeles, Chicago and Washington including Maryland and Virginia, San Diego and Seattle.

The various collaborations between bio firms, the new ventures in Biotech and pharmaceutical industries, the proposal to expand the business, the support from various foundations and government agencies to extend the research activities, the increase in profit from the Bio business over the years are the key factors creating more jobs in the above mentioned locations.

In another event BioSpace, a life science employment and news wire in an effort to identify and expose the prospects of biotech sector, carried out a project which resulted in the launch of the campaign called “2013 – 2014 BioForest Hot bed campaign”. This campaign is designed exclusively to expose the picture of Biotech sectors in Washington State. BioSpace uses a unique strategy of presenting the information regarding the Biotech sector of Washington State in a map format. The map displays the logo of the company and a 3D representation of the company’s infrastructure located on the Washington States geographical area which enables the job hunters and policy makers to get the information like various events and activities going on in each and every Biotech sector, Pharma industry and Biomedical instruments industry of the State precisely.

So people looking for new biotech jobs and preferring to change the work location can check out the hot locations listed by GEN to grab the opportunity.

References
http://www.genengnews.com/insight-and-in.../77899937/

http://www.genengnews.com/insight-and-in.../77899929/

http://www.biospace.com/hotbed.aspx?regionid=15

http://www.sacbee.com/2013/11/14/5911528...ngton.html

http://enewsletters.biospace.com/images/...forest.pdf

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EMBL Microfludics Conference | July 23rd to 25th 2014 | Heidelberg

November 15, 2013, 5:20 am

≫ Next: E1224: Phase II trial data for Chagas disease

≪ Previous: Hot Locations Around the world for Biotech Jobs

EMBL Conference: Microfluidics 2014

Organisers: European Molecular Biology Laboratory (EMBL):
Scientific Organisers: Christoph Merten, EMBL Heidelberg, Germany; Stephen Quake, Department of Bioengineering, James H. Clark Center, Stanford University, USA;
Conference Organiser: Gwen Sanderson, EMBL Heidelberg, Germany

Dates: July 23rd to 25th 2014

Location: EMBL Heidelberg, Germany

Website: http://www.embl.de/training/events/2014/...index.html
The website gives all the necessary information on abstract submission, fees, registration, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
Microfluidics stands at the interface of physics, engineering, chemistry and biology and uses a variety of applications relevant to biotechnology. These include (but are not limited to) chemical synthesis, nucleotide sequencing, functional genomics and single molecule/ single cell/ single organism studies. Many of these applications, including next-generation sequencing devices, have been revolutionised by miniaturisation, paving the way for global gene analysis and hence transforming biology.
The EMBL Microfluidics Conference 2014 aims to bring together top researchers in the field and to spark scientific exchange, also across different disciplines. The latest Lab-on-a-Chip technologies and applications will be presented.

Confirmed Speakers:
• Helene Andersson Svahn, Science for Life Laboratory, Sweden
• Andrew deMello, ETH Zurich, Switzerland
• Petra Dittrich, Laboratorium für Organische Chemie, ETH Zurich, Switzerland
• Albert Folch, University of Washington, USA
• Carl Hansen, University of British Columbia, Canada
• Amy E. Herr, UC Berkeley, USA
• Andreas Manz, Universität des Saarlandes, Germany
• Christoph Merten, European Molecular Biology Laboratory, Germany
• Steve Quake, Stanford University, USA
• Vincent Studer, CNRS, France
• Patrick Tabeling, ESPCI Paris, France
• Savas Tay, ETH Zurich, Switzerland
• Jean-Louis Viovy, CNRS, France
• Dave Weitz, Harvard University, USA
• Aaron Wheeler, University of Toronto, Canada
• Roland Zengerle, University of Freiburg, Germany

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E1224: Phase II trial data for Chagas disease

November 15, 2013, 7:23 am

≫ Next: Prevent Sleeping Sickness with Genetically Engineered Bacteria

≪ Previous: EMBL Microfludics Conference | July 23rd to 25th 2014 | Heidelberg

A ground-breaking Phase II clinical trial has been carried out in Bolivia, the first ever to be run in that country. The trial was carried out by the Drugs for Neglected Diseases initiative (DNDi) to test the safety and efficacy of the experimental drug candidate E1224 on the the parasite that causes Chagas disease. The results of the trial were presented this week at the Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).

According to the DNDi, Chagas disease is endemic in 21 countries across Latin America, and it kills more people in this region annually than malaria or any other parasite-born disease. Patient numbers are growing in non-endemic, developed countries, carried unwittingly by Latin American immigrants. The disease is caused by the parasite Trypanosoma cruzi, and has both acute and chronic clinical stages. Primary transmission is by large, blood-sucking reduviid insects but also via blood transfusion, organ transplantation, as well as congenital and oral transmission.

The E1224 drug candidate was developed by the Japanese company Eisai, with support from the Wellcome Trust. The Phase II trial was a double-blind, randomized, controlled trial on 231 adult patients with chronic indeterminate (showing no symptoms) Chagas disease, comparing E1224 to both placebo and to the current treatment, benznidazole. E1224 monotherapy was found to clear the Trypanosoma cruzi in patients compared both to placebo and to benznidazole, however parasite clearance was only maintained after 12 months in less than one third of patients treated with E1224 compared to greater than 80% of patients treated with benznidazole.

Despite this demonstration of ineffectiveness of E1224 monotherapy, the drug still holds great promise as an adjunct therapy to be used with existing drugs. Benznidazole, for example, is associated with unpleasant side-effects and treatment typically lasts for 60 days. In this trial, few patients receiving even the highest dose of E1224 stopped treatment due to side effects. The E1224 trial Project Leader, Dr Isabela Ribeiro, Head of the Chagas Clinical Programme at DNDi, is very satisfied with the outcomes, stating : “We now have clear safety and efficacy data on two compounds that will be very useful in guiding future Chagas disease drug research efforts."

The way forward for E1224 is to no longer be tested as monotherapy for Chagas disease, but the researchers are hopeful of testing E1224 in combination therapy with benznidazole. As a result of this study in an endemic country, there is now increased hope for the millions of patients who suffer from this neglected illness, with the prospect of increased treatment access and options.

Sources

http://www.dndi.org/diseases-projects/di...hagas.html [Accessed 15 November 2013].

Drugs for Neglected Diseases Initiative. "Drug trial for top parasitic killer of the Americas." ScienceDaily, 14 Nov. 2013. [Accessed 15 November 2013].

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Prevent Sleeping Sickness with Genetically Engineered Bacteria

November 18, 2013, 10:35 pm

≫ Next: Enanta Hepatitis C drug ABT-450 passes phase III trial; interferon-free treatment

≪ Previous: E1224: Phase II trial data for Chagas disease

The use of the genetically engineered bacterium Sodalis glossinidius against the parasite Trypanosoma brucei could be a solution to control and prevent the fatal disease “sleeping sickness”.

African trypanosomiasis commonly called as sleeping sickness is a deadly endemic disease native of Africa. The disease is been continuously reported in majority of the population and the outcome of a recent study on the risk of infection among the population revealed the fact that about 69.3 million people are in the risk category of being infected.

Sleeping sickness is a parasitic infection caused by the parasite Trypanosoma brucei. Tsetse flies acts as a host for this particular protozoan species and aids the transmission of this parasite into humans through bites. Trypanosoma brucei enters the blood stream of a healthy individual following a bite by the tsetse fly and continue to multiply in the body fluid of the infected individual and has the potential to cross the blood brain barrier thus affecting the brain of the infected individual. Infection by this parasite deteriorates both physical and mental health of the individual and causes some disturbance in the regular sleep pattern, thus acquiring the name sleeping sickness. Also the transmission of the parasite from human to the tsetse fly occurs when the fly stings an infected person.

The rate of infection is accelerating due to the lack of proper prevention and treatment methods. Recently US research scientists spelled out the names of two bacteria Sodalis glossinidius which forms a part of the gut flora of the tsetse fly and Wolbachia which is established in the reproductive system of the fly as tools to prevent and control the Trypanosoma brucei infection. As a first step Sodalis glossinidius is genetically modified to express resistance to the Trypanosome brucei parasites present in the fly and with an effort to pass on the genetically reconstructed bacteria Sodalis glossinidius to successive fly population (progeny), the team used Wolbachia as a tool. Paratransgenesis is the method used which will ensure the absence of the parasite in successive progeny of the fly.The outcome of the research is identified as a fruitful approach in eliminating the deadly disease if established properly.

If the above discovery gets acknowledged in eradicating sleeping sickness then it will pave way for eradicating other insect transmitted diseases (e.g. Malaria) in a similar manner.

Reference

http://london-student.net/science/11/16/...-sickness/
http://en.wikipedia.org/wiki/African_try...cite_ref-7
http://m.scidev.net/global/gm/news/gm-ba...kness.html
http://www.itg.be/itg/generalsite/Defaul...ID=252&L=E

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Enanta Hepatitis C drug ABT-450 passes phase III trial; interferon-free treatment

November 19, 2013, 6:44 am

≫ Next: Biotechnology and batteries: modified viruses build electrodes

≪ Previous: Prevent Sleeping Sickness with Genetically Engineered Bacteria

Enanta Pharmaceuticals, Inc. (ENTA) have announced positive new results from the phase III SAPPHIRE-I study being conducted by AbbVie for hepatitis C virus (HCV) genotype 1 (GT1) treatment. The trial tested Enanta’s lead protease inhibitor ABT-450 in a 3D regimen comprising three direct-acting anti-viral agents, i.e. boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. This study, along with five other hepatitis C virus (HCV) genotype 1 (GT1) phase III studies being conducted by AbbVie, is addressing the need to develop interferon-free treatment regimens for hepatitis C virus (HCV) infection, as discussed previously on this forum (http://www.biotechnologyforums.com/thread-2564.html). This is because some patients are interferon-intolerant, and so interferon-based therapy for chronic hepatitis C is limited by both efficacy and tolerability.

In the SAPPHIRE-I study, the 3D regimen plus ribavirin was used. 631 non-cirrhotic, GT1a and GT1b HCV-infected, treatment-naïve adult patients were enrolled in this global, multi-centre, randomised, double-blind, placebo-controlled study for 12 weeks of treatment. The majority of patients were GT1a, the more difficult-to-treat subtype. The results indicated that a sustained virologic response after 12 weeks (SVR12) was achieved for 96% of patients. There was a low rate of relapse (1.7% of patients on the 3D regimen). The treatment regimen was well tolerated, with the most commonly reported adverse events being fatigue, headache and nausea and discontinuation of treatment occurred in equal percentages (0.6%) in both the placebo and 3D groups. This positive phase III data follows on from previous positive phase II studies on tolerability and efficacy of ABT-450 in various combination treatment regimes. Results of the remaining five phase III trials using ABT-450 will be available in the coming months, with regulatory submissions to begin in the second quarter of 2014.These current findings raise hopes that pegylated interferon-free regimens have the potential to cure a high proportion of HCV genotype 1-infected patients.

Sources
http://www.biospace.com/News/abbvie-enan...s-c/316030 [Accessed 19 November 2013].

LAWITZ, E. et al., 2013. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. Journal of Hepatology, 59(1), pp. 18-23

POORDAD, F. et al., 2013. Exploratory study of oral combination antiviral therapy for hepatitis C. The New England Journal of Medicine, 368(1), pp. 45-53

STEDMAN, C.A.M., 2013. Current prospects for interferon-free treatment of hepatitis C in 2012. Journal of Gastroenterology and Hepatology, 28(1), pp. 38-45

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Biotechnology and batteries: modified viruses build electrodes

November 19, 2013, 9:05 am

≫ Next: 2013 Malaria Vaccine Technology Roadmap

≪ Previous: Enanta Hepatitis C drug ABT-450 passes phase III trial; interferon-free treatment

A new article in Nature Communications from a research group in MIT has made innovative use of a genetically modified virus called M13 to build a network of cross-linked nanowires to serve as an electrode in a lithium-air battery. Lithium-air batteries are the subject of intense research interest as they have the potential to produce greatly increased power per battery weight compared to other batteries, which for example would be advantageous in increasing the driving range of electric cars. However, development of these batteries has been frustrated by issues such as the need to develop better, more durable materials for the batteries' electrodes and improving the capacity of the batteries for multiple charging-discharging cycles.

In the Nature Communications study, M13 was used to make nanowires of manganese oxide, which is a favoured material for manufacture of lithium-air batteries’ cathodes. The surface area of the nanowires was increased compared to wires built by chemical methods due to their rough, spiky surface. This should have the advantage of improving the rate of charging-discharging. Also, the process was much less hazardous than conventional methods that involve high temperatures and hazardous chemicals whereas this process was performed at room temperature using a water-based process. The three-dimensional structure of the virally-constructed wires also provides increased electrode stability. Conductivity of the nanowires was improved by including a small amount of palladium. Thus the need for expensive materials such as pure or highly concentrated metals is reduced as compared to conventional methods. Taken together, the potential is there to build batteries with greatly increased power per battery weight compared to lithium-ion batteries.

This research is at an early stage and would not yet be viable for commercial production. It looked only at cathode production and was only successfully tested through 50 charging/discharging cycles whereas for practical use a battery must be capable of withstanding thousands of these cycles. But the potential is there for biotechnology to help build more powerful batteries with positive impact on our environment in the future.

Sources

Massachusetts Institute of Technology. "Better batteries through biology? Modified viruses boost battery performance." ScienceDaily, 13 Nov. 2013. [Accessed 19 November 2013]
.
Dahyun Oh, D. et al, 2013. Biologically enhanced cathode design for improved capacity and cycle life for lithium-oxygen batteries. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3756

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2013 Malaria Vaccine Technology Roadmap

November 19, 2013, 2:34 pm

≫ Next: FDA Approves the New Blood Cancer Drug- Imbruvica

≪ Previous: Biotechnology and batteries: modified viruses build electrodes

The World Health Organisation's (WHO) Global Malaria Programme has set an ambitious target for malaria vaccination by 2030. The updated 2013 Malaria Vaccine Technology Roadmap, launched this week, envisages availability of vaccines capable both of reducing malaria cases by 75% and of substantially reducing parasite transmission and hence of malaria incidence. Despite advances in treatment, malaria still affects millions of people each year and kills hundreds of thousands according to WHO figures.

This updated Roadmap is the result of a review process facilitated by the World Health Organisation (WHO), working with the Malaria Vaccine Funders Group to update the vision and strategic goals of the original 2006 Roadmap publication. The Roadmaps forms a strategic framework that underpins the activities of the global malaria vaccine research and development (R&D) community. The scaling up of malaria control measures that occurred as a result of the strategies of the 2006 Roadmap has resulted in positive changes in malaria epidemiology, including reduction in malaria transmission and an increase in the peak age of clinical malaria to older children, as well as an increase in the median age of malaria-related hospitalisation in some settings. These changes have resulted in a 26% reduction in the global malaria death rate over the last decade. They have encouraged an expansion of the Roadmap goals and the launch of the updated Roadmap.

One goal of the original 2006 Roadmap was having a licensed vaccine against Plasmodium falciparum malaria, the most deadly form of the disease, available for children under 5 years of age in sub-Saharan Africa by 2015. This is almost within reach, as Phase III trial final results of the most advanced vaccine candidate, RTS,S/AS01, will be available by 2015. Dependent on these results and the outcome of the regulatory review by the European Medicines Agency, a WHO recommendation for use and subsequent prequalification of this first vaccine could occur in late 2015. The new, more ambitious 2030 targets are for development of vaccines that are directed against both the Plasmodium falciparum and Plasmodium vivax species of malaria. Importantly, the goals are also focused on expanding on promising early work on so-called transmission-blocking malaria vaccines. Such vaccines should be suitable for administration in mass campaigns.

The focused approach achieved by the coordination of activities of the global malaria vaccine research and development (R&D) community has already achieved important reductions in malaria transmission. The new goals aim to progressively eliminate the scourge of malaria and ultimately eradicate this disease.

Sources

http://www.who.int/immunization/topics/m...oadmap/en/ [Accessed 19 November 2013]

World Health Organization. "New malaria vaccines roadmap targets next generation products by 2030." ScienceDaily, 14 Nov. 2013. [Accessed 19 November 2013]

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FDA Approves the New Blood Cancer Drug- Imbruvica

November 19, 2013, 10:23 pm

≫ Next: Production of penicillin - Optimal ph

≪ Previous: 2013 Malaria Vaccine Technology Roadmap

The drug Imbruvica developed by Pharmacyclics and Johnson and Johnson to treat a rare type of blood cancer termed as Mantle cell Lymphoma is approved by Food and Drug Administration (FDA) on 13th November 2013.

The drug Imbruvica with its generic name Ibrutinib is designed to treat the recurrence of the Mantle cell lymphoma in patients who have been subjected to a therapy before. Mantle cell lymphoma is an atypical condition considered one among the non-Hodgkin’s lymphomas and is categorized under B cell lymphoma. Mantle cell lymphoma is associated with somatic cell mutation and is characterized by the hyper expression of the cell cycle gene called as cyclin D1 which in turn accelerates the unusual proliferation of the cancer cells. Since the disease is a result of somatic cell mutation it is not inheritable in nature. The survival of a patient with mantle cell lymphoma is calculated to be about 6 years in recent times. The possible locations where the cancer cells of mantle cell lymphoma can spread are identified as lymph nodes, spleen and bone marrow. The drug Imbruvica is designed to target and restrict the synthesis of a specific protein called Bruton’s Tyrosine Kinase, a key molecule supporting the growth and existence of B cells which turns out as cancerous cells in Mantle cell lymphoma.

Last year, Imbruvica was acknowledged by FDA as a breakthrough therapy for three different types of cancer which led to the much earlier approval of the drug this year prior to the stipulated time. Imbruvica grabbed FDA’s approval following the results of the clinical trials of the drug. The outcomes of the clinical trials are,

No. of patients tested: 111 (patients included in the study had recurrence of cancer even after a prior therapy).

Reduction in the condition observed: 49% out of 111 patients

Condition vanished in: 17% out of 111 patients.

Dosage: 4 capsules at a time once a day

Cost per capsule: $ 91

Side effects of the drug: low platelet counts, bleeding, susceptible to infections, fatigue and muscular pain, diarrhea, diminished white blood cell count and difficulty in breathing.

Other Approved Drugs against Mantle cell Lymphoma: Revlimid by Celgene, Velcade by Takeda and Rituxan by Genentech.

The approval of the drug Imbruvica by FDA had positive impact on the share values and stocks of the companies involved in the development of the drug.

At present Pharmacyclics and Johnson and Johnson are in the process of gaining approval of the drug Imbruvica for the treatment of chronic lymphocytic leukemia.

Reference
http://www.nytimes.com/2013/11/14/busine....html?_r=0
http://www.drugs.com/imbruvica.html
http://en.wikipedia.org/wiki/Mantle_cell_lymphoma
http://guardianlv.com/2013/11/fda-approv...-lymphoma/

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Production of penicillin - Optimal ph

November 20, 2013, 3:44 am

≫ Next: Experimental RSV vaccine gives promising pre-clinical results in animals

≪ Previous: FDA Approves the New Blood Cancer Drug- Imbruvica

What is the optimal ph for production of penicillin?

some books say a neutral ph of around 7 to 7.5 ,but some sat its around 5 to 6.5.

can someone clarify ?

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Experimental RSV vaccine gives promising pre-clinical results in animals

November 20, 2013, 2:45 pm

≫ Next: Deadly Nipah Virus and its Key Protein Structure

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A recent study in the journal Science describes an experimental vaccine directed against respiratory syncytial virus (RSV), which is the second only to malaria in worldwide deaths of infants between one to twelve months of age. The vaccine was tested in both mice and macaques and elicited high levels of RSV-specific antibodies. The tests were so promising that early-stage human clinical trials are planned, as soon as clinical grade material can be produced.

The research, from a team in the Vaccine Research Centre (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), built on an earlier work also published in Science. In this previous work the group obtained atomic-level details of the fusion (F) glycoprotein of RSV bound to a broadly neutralising human RSV antibody. The researchers found that a region they termed antigenic site zero was exposed in RSV before it fuses with a cell and is particularly vulnerable to broadly neutralising antibodies. However, following cell fusion, the antigenic site zero effectively disappears due to F glycoprotein rearrangement. Antibodies to antigenic site zero are much more strongly neutralising than other anti-RSV antibodies, so the research team reasoned that a vaccine directed against pre-fusion F glycoprotein would be more effective than one directed against post-fusion RSV as it would elicit a more powerful antibody response. In the new study, the researchers acted on this by engineering stable variants of the F glycoprotein viral antigen which retained antigenic site zero in the absence of bound antibody. Stabilised versions of the F glycoprotein were generated that were able to withstand extremes of pH, osmolality, and temperature. Examination of X-ray crystallographic structures revealed that introduction of cysteine residues and filled hydrophobic cavities improved stability. Testing of variants on mice and macaques revealed that increased variant stability was directly related to the levels of neutralising antibody response elicited. One of the engineered antigens elicited a response ten times greater than that produced by post-fusion F protein vaccination and well in excess of threshold levels needed to protect against RSV infection.

Dr Graham, one of the lead authors of the study, points out that this is an example of a case in which “information gained from structural biology has provided the insight needed to solve an immunological puzzle and apply the findings to address a real-world public health problem”. The human clinical tests are expected to proceed in the next 18 to 24 months and will provide hope for a vaccine at last against this devastating disease.

Sources

NIH/National Institute of Allergy and Infectious Diseases. "Scientists develop candidate vaccine against respiratory syncytial virus." ScienceDaily, 31 Oct. 2013. [Accessed 20 Nov. 2013].

McLELLAN, J.S., CHEN, M., JOYCE, M. G., SASTRY, M., STEWART-JONES, G. B. E., YANG, Y., ZHANG, B., CHEN, L., SRIVATSAN, S., ZHENG, A., ZHOU, T., GRAEPEL, K. W., KUMAR, A., MOIN, S., BOYINGTON, J. C., CHUANG, G.-Y., SOTO, C., BAXA, U., BAKKER, A. Q., SPITS, H., BEAUMONT, T., ZHENG, Z., XIA, N., KO, S.-Y., TODD, J.-P., RAO, S., GRAHAM, B. S. and KWONG, P. D., 2013. Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus. Science, 2013; 342 (6158): 592 DOI: 10.1126/science.1243283

MCLELLAN, J.S., CHEN, M., LEUNG, S., GRAEPEL, K. W., DU, X., YANG, Y., ZHOU, T., BAXA, U., YASUDA, E., BEAUMONT, T., KUMAR, A., MODJARRAD, K., ZHENG, Z., ZHAO, M., XIA, N., KWONG, P. D. and GRAHAM, B. S., 2013. Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody. Science, 2013; 340 (6136): 1113 DOI: 10.1126/science.1234914

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Deadly Nipah Virus and its Key Protein Structure

November 20, 2013, 10:02 pm

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Could the identification of the structure of the key protein in the dangerous Nipah virus be a step towards drug development against Nipah virus infection?

Scientists from The Scripps Research Institute (TSRI) in their untiring effort to understand the proteins of the most harmful Nipah virus finally unraveled the structure of the key protein present in the Virus.

Nipah Virus, the most deadly virus classified under the Biosafety Level 4 pathogen is known to habitat the south East Asian countries like Malaysia, Bangladesh and India and also Australia. The virus belongs to the family of paramyxoviridae and fruit bats were identified to be the hosts of this virus. The first ever outbreak of Nipah virus infection was recorded in the year 1999 in Malaysia. Though the virus is known to infect domestic animals like dogs, cats, sheep and goat, the most susceptible species are pigs and humans where the Nipah virus infection proves to be fatal.

Fruit bats being the carriers of the Nipah virus spread the virus among farm animals and also deliver the virus to other places of their migration. The mode of transmission of Nipah virus is as follows,
- Enter pigs though oral route
- Infected pigs to healthy pigs
- Infected pigs to humans

Nipah virus worsens the health of the infected individual causing severities like coma and death of the individual. Though the pathogenicity of the virus is known, there is no antiviral drug developed/available to treat Nipah virus infection till date.

The research carried out by Jessica Bruhn along with fellow researchers guided by prof. Erica Ollmann Saphire in The Scripps Research Institute on Nipah virus resulted in the identification of the structure of the key protein “phospho protein or Nipah Virus P protein” which acts as a significant tool in Nipah virus replication. The Rutherford Appleton lab’s software AMPLE supported the research work in determining the structure of the protein. Researchers found that P protein is a tetramer with curly structure and also the team was baffled by noticing the similarities between the identified P protein structure and the protein present in mumps and measles virus.

The identification of the P protein structure of Nipah virus opens door to the development of antiviral drug to treat Nipah virus infection which seems to be very essential as Nipah virus being the Biosafety Level 4 pathogen.

Reference
http://www.popsci.com/article/science/ch...ipah-virus
http://www.scripps.edu/newsandviews/e_20...nipah.html
http://topnews.net.nz/content/230897-str...rus-solved
http://www.spc.int/lrd/ext/disease_manua...ction.html
Image source: Wikipedia (User:Rhys)

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Tips to Be Successful When Taking Online Courses in Australia

November 21, 2013, 7:28 pm

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It is best to set up an exclusive study area. For homemakers, the place would be off limits to their children during study time. The area should also be devoid of possible distractions such as a television.

Construct a schedule that takes into account priorities and activities so as not to feel inundated by so much at one time.

Organization is an advantage. It is best to keep printouts in a folder that is within reach. This applies to organizing files on the computer too.

Family and friends can be great supporters. They can provide the necessary encouragement when the temptation to dilly-dally starts to set in.

In addition to the exclusive materials provided for the online education classes, it is also helpful to check out books related to the course. Other possible resources would be published materials on the web and in print.
Take advantage of the opportunity to interact with the course tutor. Many reputable distance education providers now offer unlimited tutor support by email correspondence.

Set goals to remind oneself of the purpose for taking up an online course. It helps to write these down on a piece of paper and post it within the study area.

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BRSV spread in cattle can be controlled

November 7, 2013, 11:26 am

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A study published this week in the journal Veterinary Record from a research group in the Norwegian School of Veterinary Science suggests that the prevalence of respiratory diseases in cattle could be controlled. The study examined incidence of infection of cattle herds in Norway with the bovine respiratory synctial virus (BRSV), which is a major cause of respiratory infection in cattle.

BRSV is an enveloped, negative sense, single-stranded RNA virus of the pneumovirus genus and Paramyxoviridae family. Alone, this virus causes severe disease in calves. It also predisposes calves to secondary infections with bacteria including Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex. This is the major cause of feed-lot cattle morbidity and mortality. It is reckoned it can cause losses to the cattle industry approaching $1 billion annually, with deaths to cattle along with reduced feeding efficiency, reproductive impact and milk production loss, as well as costs of vaccinations and treatments. On an immunological level, BRSV infection inhibits the CD8 T cytotoxic cell response and promotes a Th2 response, which can in turn further dampen the Th1 response. There have been some promising developments in terms of safe, stable, attenuated virus vaccine candidates. However, the epidemiology and evolution of the virus and the mechanisms by which it establishes infection are not fully understood.

The current Norwegian study looked at 134 herds. The herds were tested twice at intervals of six months and were classified as BRSV-positive if at least one animal between 150 and 365 days old tested positive for antibodies against BRSV. While the prevalence of positive herds at both samplings was high, at 34 per cent and 41 per cent, respectively, there was variation between regions. Importantly, negative herds were found in close proximity to positive herds and some of these remained negative even when new infections arose nearby, implying that it is possible to avoid herd infection even in proximity to infected herds nearby. In addition, one third of the herds that originally tested positive managed to get rid of the virus and tested negative on the next test.

The authors of the study suggest that prevalence and impact of BRSV could be reduced by employing effective surveillance of herds and putting a high biosecurity focus on the negative herds. Research on mechanisms of BRSV infection are therefore even more imperative.

Sources

GERSHWIN, L.J., 2012. Immunology of bovine respiratory syncytial virus infection of cattle. Comparative immunology, microbiology and infectious diseases, 35(3), pp. 253-257

KLEM, T.B., GULLIKSEN, S.M., LIE, K.- I. , LOKEN, T.,OSTERAS, O., and STOKSTAD, M., 2013. Bovine respiratory syncytial virus: infection dynamics within and between herds. Veterinary Record, 2013; DOI: 10.1136/vr.101936

SACCO, R.E. et al., 2013. Respiratory Syncytial Virus Infection in Cattle. Veterinary pathology, 2013

SARMIENTO-SILVA, R., NAKAMURA-LOPEZ, Y. and VAUGHAN, G., 2012. Epidemiology, molecular epidemiology and evolution of bovine respiratory syncytial virus. Viruses, 4(12), pp. 3452-3467

Norwegian School of Veterinary Science. "The prevalence of colds and pneumonia in cows can be controlled." ScienceDaily, 5 Nov. 2013. [Accessed 7 Nov. 2013]

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FDA Approves the New Drug OLYSIO To Fight Chronic Hepatitis C

November 23, 2013, 5:32 am

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The new drug Olysio developed by Johnson and Johnson to fight the infectious disease chronic hepatitis C is approved by Food and Drug Administration on 22nd November 2013.

Hepatitis C is a viral disease caused by the Hepatitis C virus which belongs to the genus Hepacivirus categorized under the Flaviviridae family. Liver is the primary organ affected by Hepatitis C virus infection and the disease is either acute or chronic. But it is evident that 80% of the infected individuals develop chronic hepatitis C resulting in cirrhosis and liver cancer. Hepatitis C viruses are of different genotypes classified accordingly from genotype 1 to genotype 7. However it is estimated the about 70% of the Hepatitis C disease is due to the infection by the Hepatitis virus C of the genotype 1. The rate of virus replication in an infected individual results in the production of about 10^12 viral units per day.

The new drug Olysio also called as simeprevir approved by FDA inhibits the protease enzyme essential for the synthesis of a protein required by the Hepatitis C virus to replicate inside the infected individual and hence termed as protease inhibitor. The new drug Olysio restricts the multiplication of the Hepatitis C virus by blocking the synthesis of the protein used by the virus thus exhibiting control over the disease. Olysio is recommended to be used as a combination drug.

Combination: Olysio + pegylated interferon + ribavirin
To Treat: Hepatitis C virus genotype 1 infection

Patient category:
Individuals detected with chronic hepatitis C disease with no prior treatment
Individuals detected with chronic hepatitis C disease who have received prior available treatment for the same.

Dosage: Once a day along with the above mentioned combination

The reduced effect of the drug Olysio along with the combinations was observed in chronic Hepatitis C patients with Q80K genotype 1a (polymorphism). Hence it is suggested for chronic hepatitis c patients to screen for the presence of the Q80K genotype 1a before initiating the treatment with the drug Olysio. Also the data on safety and efficacy of the drug in children below the age group of 18 is not available.
The results of the drug study showing complete recovery of patients from the disease chronic Hepatitis C makes Olysio a promising therapy against the disease.

Reference
http://www.4-traders.com/JOHNSON--JOHNSO...ic-1748941
http://www.startribune.com/lifestyle/hea...95971.html
http://www.bloomberg.com/news/2013-11-22...-pill.html
http://en.wikipedia.org/wiki/Hepatitis_C
http://www.prnewswire.com/news-releases/...91621.html

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Professinal indeminety insurance not underwriting advice on GM crops? why?

November 23, 2013, 6:11 pm

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I have tried hard in Australia to find a Professional Indemnity policy to underwrite advice on transgenic crops, I have clients increasingly ask me about GM opportunities, but have to keep my mouth shut

Whats going on? is this only a east coast Australia thing?

Does anybody know a insurance company that will underwrite GM advice and its professional indemnity risks in Agriculture /Horticulture?

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Professinal indeminety insurance not underwriting advice on GM crops? why?

November 23, 2013, 6:11 pm

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Tumour cell movement from the fruit fly

November 24, 2013, 4:06 pm

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Researchers in the Morphogenesis in Drosophila lab at Institute for Research in Biomedicine in Barcelona (IRB Barcelona) have used the similarities between tracheal development in the fruit fly Drosophila melanogaster and bronchial development in humans to propose a novel new idea about how groups of cells move as a unit in tissue formation. The results of their experiments, published this week in the Journal of Cell Science, could have implications in understanding more about both normal tissue development but also about how angiogenesis, or formation of new blood vessels, occurs during benign tumour transformation to malignancy.

The group tracked a group of seven cells in vivo over seven hours during formation of a Drosophila melanogaster tracheal branch. They found that movement of the whole group of cells was triggered by one ‘leader’ which was the only one to express receptors for fibroblast growth factor (FGF). FGF initiates a signalling pathway within the leader cell that results in it promoting the motility of the entire group. This work, which is the first to show this kind of mass movement triggered by a single cell, should give novel insights into the synchronised movements of groups of cells which are key to angiogenesis during malign tumour formation. The work is unique in that it was carried out entirely in vivo. How cells move as a group and form new capillaries is an area of intense interest in the field of tumourigenesis research. Having this kind of information should in the future contribute to therapeutic manipulation of angiogenesis in the tumour development pathway in a focused and subtle fashion.

Sources

Institute for Research in Biomedicine (IRB Barcelona). "Insight on cell migration, movement of cancer cells." ScienceDaily, 21 Nov. 2013. [Accessed 25 November 2013].

LEBRETON, G. and CASANOVA J., 2013. Specification of leading and trailing cell features during collective migration in the Drosophila trachea. J Cell Sci., November 2013

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