The European Food Safety Authority (EFSA) has proposed that guidance levels for exposure to two members of the neonicotinoid class of pesticide, namely imidacloprid (IMI) and acetamiprid (ACE), be reduced. They have based this proposal on studies that indicate these pesticides may have greater than previously thought effects on developing mammalian brains and nervous systems. These pesticides are used worldwide to protect crops from pest insects and domestic animals from fleas and have become the most prominent class of insecticides in the world. Their popularity has grown as they are perceived as being less harmful to human health and to the environment than older pesticides. However, the European Union (EU) had already introduced a two year moratorium on the use of these pesticides on crops attractive to bees amid growing evidence that their increasingly widespread use was harmful to bees.

The concerns on possible detrimental effects on the developing human nervous systems have arisen from the results of studies on, for example, neonatal rat cerebellar neurons. The neonicotinoids are agonists of nicotinic acetylcholine receptors (nAChRs). They were considered to be have selective binding affinity for insect nAChRs, hence their toxicity to insects. However, a growing body of evidence suggested that they could also have greater than previously thought stimulatory effects on mammalian nAChRs. Studies on neonatal rat cerebellar neurons showed that both ACE and IMI induced significant excitatory Ca2+ influxes at concentrations greater than 1 µM in small neurons in cerebellar cultures expressing mRNA of the α3, α4, and α7 nAChR subunits. These effects were significantly inhibited by nAChR inhibitors. In other studies, young rodents exposed to IMI experienced effects including brain shrinkage, weight loss and reduced movement. Exposure in utero to IMI resulted in decreased sensorimotor performance in neonatal rats while IMI has also been shown to stimulate human α4β2 nAChR subtypes.

The EFSA has acknowledged that the available evidence is limited but maintains that the concerns raised are sufficient to suggest that the current guidelines "may not be protective enough to protect against developmental neurotoxicity and should be reduced". The chemical companies concerned are now being invited to comment on the research findings prior to a possible amendment of the reference values by March 2014. Other experts suggest that the EFSA is precautionary. For example Prof Alan Boobis of Imperial College London has pointed out that “the conclusions of EFSA do not suggest that exposure of humans to these compounds at the levels that occur normally in food or in the environment is a cause for concern."

Sources

Kimura-Kuroda, J., Komuta, Y., Hayashi, M. and Kawano, H., 2012. Nicotine-Like Effects of the Neonicotinoid Insecticides Acetamiprid and Imidacloprid on Cerebellar Neurons from Neonatal Rats. PLoS ONE 7(2): e32432. doi:10.1371/journal.pone.0032432.

http://www.bbc.co.uk/news/science-environment-25421199

http://www.efsa.europa.eu/en/press/news/130116.htm

The US Food and Drug Administration (FDA) have raised concerns over health risks of substances in antibacterial soaps and handwashes. As a result, the organisation has called for a safety review of such products. This has come about due to recent studies which have suggested that ingredients such as triclosan in liquid soaps and triclocarban in bar soaps may be contributing to the huge public health issue of bacterial resistance to antibiotics, according to a statement released on Monday by Dr Colleen Rogers, a lead FDA microbiologist. The statement also raises concerns that these ingredients may also have "unanticipated hormonal effects that are of concern" according to in vivo animal studies. Dr Rogers’s statement points out that "New data suggest that the risks associated with long-term, daily use of antibacterial soaps may outweigh the benefits." Furthermore, according to Dr Rogers, there is no current evidence to suggest that over-the-counter antibacterial soap products are any more effective at preventing illness than plain soap and water. The FDA took up the matter following a federal appeals court decision in March to approve a lawsuit by the non-profit Natural Resources Defense Council, which aimed to force the FDA to review the health impacts of triclosan.

In the light of these questions and concerns, the FDA has proposed a rule that will require manufacturers to prove that these antibacterial products are safe and more effective against infection than plain soap and water. Hitherto, laboratory tests to evaluate the effectiveness of these products have not included any test of the product on infection rates; the proposed new FDA rule would change that. It would not, however apply to the types of alcohol-based hand-sanitizers that are typically used in healthcare settings. The FDA has given manufacturers until the end of 2014 to submit the results of clinical trials on their products and they aim to have new regulations finalised in 2016. The FDA is collaborating with the Environmental Protection Agency (EPA), which is responsible for regulation of triclosan in its other role as a pesticide, to ensure consistency across government agencies.

Meanwhile, the FDA is encouraging consumers, clinicians, environmental groups, scientists, industry representatives and others to submit their views on the proposed new rule; this comment period is available for 180 days. The FDA continues to emphasise that appropriate hand washing remains one of the most important ways to avoid becoming sick or passing on infections to others. They recommend consulting the Centers for Disease Control and Prevention (CDC) website for advice on hand washing at http://www.cdc.gov/handwashing.

Sources

http://www.fda.gov/ForConsumers/Consumer...378393.htm

http://www.bbc.co.uk/news/world-us-canada-25405037

A research group based in Cambridge University in the UK have published a study in today’s issue of the journal Biofabrication in which they demonstrate successful use of inkjet printing technology to print eye cells for the very first time. The group used a piezoelectric printhead to print two types of rat central nervous system (CNS) cells, namely retinal ganglion cell (RGC) neurons and retinal glia. Although this is a preliminary study and there is a long way to go before possible human trials, this is potentially significant for blindness as many blinding eye diseases feature loss of retinal nerve cells. The paper’s co-authors, Professor Keith Martin and Dr Barbara Lorber, from the John van Geest Centre for Brain Repair, University of Cambridge have stated that “the aim is to develop this technology for use in retinal repair in the future”.

The researchers performed different tests on the printed cells to check their cell number and viability and their survival and RGC neural outgrowth in culture. They found that the cells were not appreciably deformed upon exiting the printhead, despite being subjected to significant shear pressure. However, final cell counts were lower than for non-printed control cells, probably due to sedimentation. Importantly, cell viability was unaffected. In addition, there were no significant differences in cell survival or neurite outgrowth in culture after 5 days between control and printed RGCs or in survival of control or printed retinal glia. Finally, RGCs grew longer neurites when plated on a glial substrate and this occurred to a similar extent whether the RGCs and glia were printed or not prior to plating.

The authors plan to extend their studies to other cells of the retina and determine if light-sensitive photoreceptors can be printed using this technology. This would be the key to possible cures for some forms of blindness. They also would like to translate their work from their current printer system to a commercial, multi-nozzle printhead such as MicroFab.

Sources

LORBER, B., HSIAO, W.-K. , HUTCHINGS, I.M. and MARTIN, K.R., 2014. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. Biofabrication, 6(1), pp. 015001.

http://www.bbc.co.uk/news/health-25405542

http://www.cam.ac.uk/research/news/cells...first-time

Flow Chemistry India 2014

Organisers: Flow Chemistry Society

Dates: January 23rd- 24th, 2014

Location: CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

Website: http://selectbiosciences.com/conferences...conf=FCI14

The website gives all the necessary information on registration, abstract submission, fees, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
Following a one-day workshop in Mumbai in 2012, this will be the first full conference to be held in India under the auspices of the Flow Chemistry Society. The society aims to unite and represent those who are actively working on this rapidly developing field. This meeting is dedicated to the integration of flow chemistry into everyday practice throughout the world by delivering the latest knowledge and making it available for the entire chemistry community. Training courses in Micro and Continuous Flow Reactors for Industrial Scale Organic Synthesis will be available.

Topics:
Aspects of the following topics will feature:
• Catalysis
• Flow Chemistry - From Lab to Industrial Scale
• Flow Nanotechnology
• Meso Flow Chemistry
• Microfluidic Flow Chemistry
• Microwave Assisted Flow Synthesis
• Novel Applications of Flow Chemistry
• Process Analysis and Control

Speakers

Keynote speakers
• Ferenc Darvas, President, Flow Chemistry Society
• Oliver Kappe, Professor/Director, Karl Franzens University of Graz
• Vivek Ranade, Deputy Director and Chair, National Chemical Laboratory
• Paul Watts, Professor & Research Chair in Microfluidic Bio/Chemical Processing, Nelson Mandela Metropolitan University

Other speakers
• Robert Ashe, Managing Director, AM Technology
• Kirti Sahu, Assistant Professor, Indian Institute of Technology Hyderabad
• P Sai Prasad, Chief Scientist, Indian Institute of Chemical Technology
• Amol Kulkarni, Scientist, National Chemical Laboratory
• Anil Kumar, Professor, Indian Institute of Technology Bombay
• Akhilesh Verma, Associate Professor, University of Delhi
• Aiichiro Nagaki, Senior Lecturer, Kyoto University
• Vijay Kirpalani, Director, Sharon Bio-Medicine Ltd & CEO-Pi
• Ravi Arun, Scientist, CSIR-CMERI
• Kumar Oza, Chief Chemistry Officer, Pi- Process Intensification Experts LLP.
• Aria Farjam, Vice President, Microfluidic Chipshop GmbH
• V Kumaran, Professor, Indian Institute of Science
• Usha Virendra, Sr Principal Scientist, Indian Institute of Chemical Technology
• Dipankar Bandyopadhyay, Assistant Professor, Indian Institute of Technology Guwahati
• P Selvam, Professor, Indian Institute of Technology Madras
• Mahender Siripragada, Vice President, Panacea Biotec Ltd
• Amin Ismaili, Sr. General Manager, Cadila Pharmaceutical Ltd.

Important dates:
Poster Submission Deadline: 31 December 2013

Who are the organisers?

The Flow Chemistry Society was formed by internationally recognized flow chemistry experts in 2010 to unite and represent those who are actively working on this rapidly developing field. The Society is dedicated to enhance the public appreciation of flow chemistry and its integration into everyday practice throughout the world by delivering the latest knowledge and making it available for the entire chemistry community. Their website address is: http://www.flowchemistrysociety.com/

A bio-based oil for use as an insulating fluid for high-voltage electrical transformers and a less wasteful method for producing the chemicals used in polymerase chain reaction (PCR) were among the winners of the 2013 Presidential Green Chemistry Challenge Awards announced last week and awarded by the U.S. Environmental Protection Agency.

One award went to Cargill Inc. who developed a vegetable-oil-based transformer fluid called EnvirotempTM FR3TM dielectric fluid. As the fluid is based on vegetable, it is much less flammable than petroleum-based mineral oil commonly used in transformers, which may also be toxic to aquatic species. EnvirotempTM FR3TM dielectric fluid is also less hard on the insulating material used in transformers, often cellulose. Testing of a transformer called BEES® 4.0, a transformer using FR3TM fluid, across its lifecycle revealed that the carbon footprint is significantly reduced to about 55-times lower than a mineral oil based transformer, for example in terms of raw materials, manufacturing, and transportation phases. The EnvirotempTM FR3TM dielectric fluid is also more biodegradable, less toxic and based on a renewable source material. There has yet to be a known fire or explosion caused by any of the hundreds of thousands of transformers using the Cargill fluid.

In terms of the less wasteful process for making PCR chemicals, researchers at the company Life Technologies devised a three-step process using only one pot to synthesise deoxyribonucleotide triphosphates (dNTPs), which are the DNA building blocks essential in PCR. Conventional processes for synthesising dNTPs entail complex multiple-step processes using various hazardous reagents and chemicals. The Life Technologies process eliminates much of these reagents and improves the process E-factor (the ratio of amount of waste to amount of product) by about a factor of 10. The company implemented this technology in their manufacturing plant in Austin, Texas in 2011 and since then have reduced organic solvent consumption by up to 95% and other hazardous waste products by up to 65%. This has also led to substantial financial savings.

Sources

http://www.scientificamerican.com/articl...me-plating [Accessed 18 December 2013].

http://www2.epa.gov/green-chemistry/2013...cals-award [Accessed 18 December 2013].

http://www2.epa.gov/green-chemistry/2013...ways-award [Accessed 18 December 2013].

Dogs may indeed be man’s best friends in ways not envisaged when the old saying was coined. It has been recognised for some time that raising of children from birth in the presence of animals, including farm livestock and domestic pets, appears to have a protective effect against development of allergies. New research from groups in the University of California, the University of Michigan, Henry Ford Health System in Detroit and Georgia Regents University in Augusta has cast light on the mechanism behind this protective effect. Prevalence of allergic asthma and other allergic diseases has reached almost epidemic proportions in westernised countries and imposes a significant human and economic cost.

The new research, published online this week in the Proceedings of the National Academy of Sciences (PNAS), has shown that mice exposed to dust taken from a household with a dog exhibited a much reduced inflammatory response to subsequent exposure to either ovalbumin or cockroach allergen compared to mice exposed to dust from a pet-free household or to no dust. This included a reduction in many of the elements typically associated with allergic responses, including airway T cells, Th2-related airway responses, IgE levels and mucin secretion. The study used PCR to confirm previous observations that a higher amount of dust was collected from the household with the dog and it contained a range of bacterial species, whereas the dust from the no pet household gave no 16S rRNA product and had a low bacterial burden. Intriguingly, the study confirmed that the composition of the gut microbial community, known as the microbiome, was very different in the protected animals compared to the other groups, with significant enrichment of bacterial species including Lactobacillus johnsonii. The group examined L. johnsonii further, and found that wild type mice to which this bacterial species was orally administered were protected from inflammatory responses to both airway allergen challenge and to infection with respiratory syncytial virus. However, the level of protection afforded by L. johnsonii was not equal to that of the whole dust sample from the dog-containing household, indicating that other species contribute to the protective effect.

These results suggest that in the future, manipulation of the gut microbiome to include ‘helpful’ species such as L. johnsonii may help protect us against both allergy and pulmonary diseases. Dr Susan Lynch of the University of California and the lead author on the study has confirmed that studies are on-going on human samples in a National Institute of Allergy and Infectious Diseases (NIAID)-funded large multi-institutional collaborative study.

Sources
FUJIMURA, K.E., DEMOOR, T., RAUCH, M., FARUQI, A.A., JANG, S., C. JOHNSON, C., BOUSHEY, H.A., ZORATTI, E., OWNBY, D., LUKACS, N.W. and LYNCH, S.V., 2013. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proceedings of the National Academy of Sciences, 2013. DOI: 10.1073/pnas.1310750111

FUJIMURA, K.E., JOHNSON, C.C., OWNBY, D.R., COX, M.J., BRODIE, E.L., HAVSTAD, S.L., ZORATTI, E.M., WOODCROFT, K.J., BOBBITT, K.R., WEGIENKA, G., BOUSHEY, H.A. and LYNCH, S.V., 2010. Man's best friend? The effect of pet ownership on house dust microbial communities. The Journal of Allergy and Clinical Immunology, 126(2), pp. 410-412.e3

University of California - San Francisco. "How household dogs protect against asthma and infection." ScienceDaily, 16 Dec. 2013. [Accessed 17 Dec. 2013].

A research group in the University of Colorado Cancer Centre has found that the ALK and ROS1 gene rearrangements that characterise some subsets of lung cancer are also found in a subset of colorectal cancer (CRC) patients. The research group used fluorescence in situ hybridization (FISH) in a painstaking search of tumour samples from 236 patients from an Australian clinical trial. They discovered the ALK rearrangement in one patient and the ROS1 rearrangement in 2 patients. Surprisingly, results confounded conventional wisdom as not only did the group find that different regions of the same tumour had different oncogenic mutations but also in some regions more than one alteration was observed. For example ALK rearrangement co-existed with KRAS alteration while ROS1 mutations were observed to co-exist in one specimen with BRAF, another oncogenic mutation.

Although the number of CRC patients carrying these oncogenes was small, the significance for this subset of patients lies in the fact that there are FDA-approved drugs available, for example crizotinib, that were licenced to treat ALK-positive lung cancer which may now prove to be beneficial to some CRC patients also harbouring this mutation. Crizotinib belongs to a class of drugs known as tyrosine-kinase inhibitors (TKIs) which "turn off" ALK and ROS1 gene mutations and reduce cell proliferation. Although lung cancers harbouring ALK rearrangements eventually become resistant to crizotinib, there are other experimental drugs currently under development which may overcome this drawback, including Pfizer’s PF-06463922, which potently inhibits both ALK and ROS1 in mouse models of cancers driven by these oncogenes. The discovery of these mutations in CRC patients offers renewed hope that the therapeutic potential of such drugs may extend to subsets of CRC and other cancers.

Sources

AISNER, D.L., NGUYEN, T.T., PASKULIN, D.D., LE, A.T., HANEY, J., SCHULTE, N., CHIONH, F., HARDINGHAM, J., MARIADASON, J., TEBBUTT, N., DOEBELE, R.C., WEICKHARDT, A.J. and VARELLA-GARCIA, M., 2013. ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intra-tumoral Heterogeneity for Molecular Drivers. Molecular Cancer Research, 2013. DOI: 10.1158/1541-7786.MCR-13-0479-T

University of Colorado Cancer Center. "Study finds known lung cancer oncogenes also drive colorectal cancer." ScienceDaily, 17 Dec. 2013. [Accessed 17 Dec. 2013].

American Association for Cancer Research. "Targeted investigational therapy potential to overcome crizotinib resistance in lung cancers." ScienceDaily, 20 Oct. 2013. [Accessed 17 Dec. 2013].

American Society for Radiation Oncology. "Crizotinib reduces tumor size in patients with ALK positive lung cancer." ScienceDaily, 6 Sep. 2012. [Accessed 17 Dec. 2013].

Biotherapeutics Analytical Summit

Organisers: Cambridge Healthtech Insitute (CHI)

Dates: March 24th-28th, 2014

Location: Hyatt Regency, Baltimore, Maryland, USA.

Website: http://www.biotherapeuticsanalyticalsummit.com/
The website gives all the necessary information on registration, break-out discussions, short courses available, fees, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
Industry, regulatory and biosimilar professionals should attend this event if they want to gain insight into analytical characterisation and comparability for change in biotherapeutics. The summit features different programmes of talks and break-out discussions on relevant topics as well as short courses, with unique opportunities for networking.

Topics:

Programmes: all programmes will feature related break-out discussions
• Post-translational modifications
 -PTM profiling and structure-function relationship
 -Charge isoforms, deamidation and oxidation
 -PTMs and developability assessment

• Analytical characterisation of biotherapeutics
 -Advances with analytical technologies
 -Analysis of variants

• Comparability and developability
 -Characterization for comparability
 -Comparability case studies
 -Limits of acceptable variation
 -Regulatory perspectives on characterization and comparability

Short courses:
• Impurities measurement, characterisation and impact
• Glycobiology of antibodies
• The science and regulation of process changes for biologics
• Strategy for entering the biosimilars market

Important dates:

‘Early bird’ registration by January 10th 2014
Advance registration discount by February 21st 2014
Poster abstract submission by February 21st 2014

Sponsorship
Companies who sponsor the conference can avail of the following benefits:
• Podium Presentations — Available within Main Agenda!
• Invitation-Only VIP Dinner/Hospitality Suite
• Focus Groups
• User Group Meeting/Custom Event
• Exhibits
• Additional branding and promotional opportunities:
o Conference Tote Bags
o Literature Distribution (Tote Bag Insert or Chair Drop)
o Badge Lanyards
o Program Guide Advertisement
o Padfolios and More...

All of us are now aware of the overwhelming evidence linking cigarette smoking to cancer. However, Norwegian researchers working in the Rikshospitalet in Oslo and in the University of Oslo have carried out studies that surprisingly suggest that cigarette smoking and coffee drinking can have a potentially beneficial effect on risk of developing a particular liver cancer, namely Primary Sclerosing Cholangitis (PSC). This rare cancer is extremely severe and affects mainly young adults (30-40 years). It is associated with high risk of cancer of the bile ducts. There are few treatment options open to patients and PSC is a leading reason for liver transplants.

The Norwegian research is an Article in Press in the journal Clinical Gastroenterology and Hepatology. It aimed to investigate non-genetic, environmental risk factors for PSC development. It involved analysis of responses to a questionnaire which was distributed to PSC patients recruited from Oslo University Hospital Rikshospitalet through 2011, and randomly chosen control individuals from the Norwegian Bone Marrow Donor Registry. Responses from 240 PSC patients and 245 age- and gender-matched control subjects were analysed. The results indicated that fewer patients versus control subjects were daily coffee drinkers, either currently or at age 18 years. 20% of PSC patients reported having ever been daily smokers as compared to 43% of control subjects. The results suggested that having ever smoked or having been a daily coffee drinker at the age of 18 were significantly negatively associated with PSC diagnosis. Thus the researchers’ surprising conclusions are that coffee consumption and cigarette smoking may be protective in avoiding this one particular cancer. The results are however consistent with other studies that have suggested that coffee may be protective in other liver diseases and with studies by others that also indicated that cigarette smoking may be a protective factor in PSC risk.

Sources

ANDERSEN, I.M., TENGESDAL, G., LIE, B.A., BOBERG, K.M., KARLSEN, T.H. and HOV, J.R., 2013. Effects of Coffee Consumption, Smoking, and Hormones on Risk for Primary Sclerosing Cholangitis. W.B. Saunders for the American Gastroenterological Association. Clinical Gastroenterology and Hepatology, 2013; DOI: 10.1016/j.cgh.2013.09.024

Oslo University Hospital. "Coffee and cigarettes may protect against liver disease." ScienceDaily, 14 Dec. 2013. [Accessed 17 Dec. 2013].

On this forum, we have previously reported on the potential of the zebrafish as a model organism for drug discovery, following the entry into Phase II trials of ProHema, the first drug to be developed using zebrafish (http://www.biotechnologyforums.com/thread-2562.html). This potential apparently extends to zebrafish embryos, following the publication last week of a paper from the laboratory of Dr. C. Duan of the University of Michigan in the journal Cell Death and Differentiation. The study used zebrafish embryos to examine the role of calcium deficiency in epithelial cell proliferation and colon cancer risk. It uncovered a novel interaction between low calcium availability, the calcium transport channels TRPV5/6 and activation of the growth factor pathway insulin growth factor 1 receptor (IGF1R)-PI3K-Akt.

TRPV5 and 6 are members of the superfamily of transient receptor potential (TRP) channels, subfamily vanilloid. They are mainly expressed in epithelia of organs including digestive tract, kidney, testis, ovaries and skin. Up-regulation of TRPV5/6 expression has been correlated to progression of a number of different cancers including prostate, colon, breast, thyroid, and ovarian. Chemical inhibitors of TRPV6 have been proposed as potential drug candidates in cancers of epithelial origin while TRPV6 silencing has been shown to reduce basal calcium influx and cell proliferation in breast cancer cell lines. Microarray analysis indicated that TRPV6 is up-regulated in estrogen receptor (ER)-negative breast tumours and in HER2-positive tumours and that high TRPV6 levels was correlated to decreased survival. However, the mechanism of how TRPV5/6 might be involved in, for example, cell proliferation is poorly understood. Calcium deficiency has also been correlated to development of epithelial cancers such as colon and breast cancer, again via poorly understood mechanisms.

Dr Duan’s group exploited the fact that zebrafish embryo skin contains accessible Ca2+-transporting epithelial cells known as ionocytes. This offers an advantage over other models where the calcium-importing epithelial cells lie chiefly in internal organs. The numbers of ionocytes in zebrafish embryos increase significantly when the embyos are placed in a low calcium ion environment. By using BrdU pulse-labelling experiments, the group showed that pre-existing ionocytes re-entered the cell cycle in response to low calcium ion concentration and underwent a strong, sustained activation of the of IGF1R-PI3K-Akt signalling pathway. The ionocytes were shown to express both the IGF binding protein, Igfbp5a and the Ca2+-selective channel Trpv5/6. Knock-down or chemical inhibition experiments showed that inhibition of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuated low calcium induced ionocyte proliferation. Moreover, although inhibition of Trpv5/6 resulted in elevated pAkt levels and increased ionocyte proliferation in the presence of normal calcium levels, when calcium was depleted, TrpV5/6 inhibition induced Akt activation. Having established these results in zebrafish embryos, the group then turned their attention to human colon cancer cells and showed that, just in the zebrafish ionocytes, low calcium induced PI3K-PDK1-Akt signalling in a TRPV6-dependent manner.

The study authors conclude that their results indicate a novel and evolutionarily conserved signalling interaction that sheds light on the abnormal epithelial proliferation associated with Ca2+ deficiency. Understanding this mechanism opens the way for future drug development.

Sources

BOLANZ, K.A., KOVACS, G.G., LANDOWSKI, C.P. and HEDIGER, M.A., 2009. Tamoxifen inhibits TRPV6 activity via estrogen receptor-independent pathways in TRPV6-expressing MCF-7 breast cancer cells. Molecular Cancer Research: MCR, 7(12), pp. 2000-2010.

DAI, W., BAI, Y., HEBDA, L., ZHONG, X., LIU, J., KAO, J. and DUAN, C., 2013. Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation. Cell death and differentiation, 2013

HU, H., BANDELL, M., GRANDL, J. and PETRUS, M., 2011. High-Throughput Approaches to Studying Mechanisms of TRP Channel Activation. TRP Channels, .

KONDRATSKYI, A., YASSINE, M., KONDRATSKA, K., SKRYMA, R., SLOMIANNY, C. and PREVARSKAYA, N., 2013. Calcium-permeable ion channels in control of autophagy and cancer. Frontiers In Physiology, 4, pp. 272-272.

LANDOWSKI, C.P., BOLANZ, K.A., SUZUKI, Y. and HEDIGER, M.A., 2011. Chemical inhibitors of the calcium entry channel TRPV6. Pharmaceutical Research, 28(2), pp. 322-330.

LEHEN'KYI, V., RAPHAëL, M. and PREVARSKAYA, N., 2012. The role of the TRPV6 channel in cancer. The Journal of Physiology, 590, pp. 1369-1376.

PETERS, A.A., SIMPSON, P.T., BASSETT, J.J., LEE, J.M., DA SILVA, L., REID, L.E., SONG, S., PARAT, M., LAKHANI, S.R., KENNY, P.A., ROBERTS-THOMSON, S. and MONTEITH, G.R., 2012. Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer. Molecular Cancer Therapeutics, 11(10), pp. 2158-2168.

ZHENG, Y., ZHOU, H., MODZELEWSKI, J.R.K., KALAK, R., BLAIR, J.M., SEIBEL, M.J. and DUNSTAN, C.R., 2007. Accelerated bone resorption, due to dietary calcium deficiency, promotes breast cancer tumor growth in bone. Cancer research, 67(19), pp. 9542-9548.

4th Annual International Conference on Advances in Biotechnology (BioTech 2014)


Organisers: Global Science and Technology Forum (GSTF)

Dates: March 10th-11th, 2014

Location: BITS-Pilani Dubai Campus, Dubai, United Arab Emirates

Website: http://www.advbiotech.org/index.html
The website gives all the necessary information on registration, abstract submission, presenting, fees, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
This multi-disciplinary conference aims to provide a challenging forum and vibrant opportunity for researchers and industry practitioners to share their original research results and practical development experiences on specific new challenges and emerging issues.

Topics:

Biotechnology Topics:

• Microbial & Biochemical Technology
• Microorganism Technology
• Microbiology
• Bioremediation & Biodegradation
• Clinical and Cellular Immunology
• Petroleum & Environmental Biotechnology
• Biotechnology and its Applications
• Biosensors, Bioelectronics & Biochips, Tissue chips
• Marine and Ocean Biotechnology
• Omics Technologies
• Medical Biotechnology and Biomedical Engineering
• Stem Cell Research & Tissue Science Engineering
• Environmental Biotechnology
• Industrial Biotechnology
• Food Processing & Technology
• Pharmaceutical Biotechnology
• Agricultural Biotechnology
• Nano science & Nanotechnology
• Regulatory And Economical Aspects In Biotechnology
• Neuroscience and Neuroengineering
• Biosecurity
• Disease Outbreak Assessment
• Bioenvironmental Engineering and Risk Assessment
• Applied Biotechnology
Algae and photobiotechnology
Bioeconomy
Bio-based products: materials
Biocatalysis and biotransformation
Bioengineering at the µ-Scale
Biomaterials engineering and nanomedicine
Bio-nanoparticles
Biopharmaceuticals production
Bioprocess engineering, modelling, measurement & control
Biorefineries
Downstream processing and separation science
Membrane technology
Metabolic engineering
Molecular, cellular and process biothermodynamics
Renewables, biofuels and bioenergy
Systems bio(techno)logy
Synthetic biology
Thermodynamics of chemical and pharmaceutical systems
Tissue engineering

Bioinformatics and Computational Biology Topics:

• DNA Computing
• Neural Computing
• Evolutionary Computing
• Immuno-Computing
• Swarm-Computing
• Cellular-Computing
• Gene Expression Array Analysis
• Structure Prediction and Folding
• Molecular Sequence Alignment and Analysis
• Metabolic Pathway Analysis
• RNA and Protein Folding and Structure Prediction
• Analysis and Visualization of Large Biological Data Sets
• Motif Detection
• Molecular Evolution and Phylogenetics
• Systems and Synthetic Biology
• Modelling, Simulation and Optimization of Biological Systems
• Robustness and Evolvability of Biological Networks
• Emergent Properties in Complex Biological Systems
• Ecoinformatics and Applications to Ecological Data Analysis
• Medical Imaging and Pattern Recognition
• Medical Image Analysis
• Biomedical Data Modelling and Mining
• Treatment Optimisation
• Biomedical Model Parameterisation
• Brain Computer Interface

Important dates:
‘Early bird’ registration by January 10th 2014
Late registration by February 10th 2014

Keynote speakers
Dr. Farhad Memarzadeh , National Institutes of Health (NIH), USA
Prof. Sanjay Kumar Verma, Birla Institute of Technology & Science

Publication opportunities

The Conference Proceedings (Print ISSN: 2251-2489, E-Periodical ISSN: 2251-2497) will be indexed by Ulrichsweb, EBSCO, CrossRef, Proquest and will be submitted to Scopus, ScienceDirect and Cabell's Directories amongst others, where applicable.

Book: Selected authors will be invited to contribute book chapters in "Applications of Biotechnology in Developing Countries" to be published by GSTF. The book will be edited by Dr. Farhad Memarzadeh.

Journal: Eligible research articles will be invited for publication in the GSTF Journal of BioSciences (JBio) (Print ISSN: 2251-3159, E-periodical: 2251-3140) which is indexed by EBSCO, CrossRef, ProQuest and Cabell's Directories.

Prizes will be awarded for Best Papers and Best Student Papers.

The Tyndall National Institute in Ireland announced last week that they have developed a diagnostic toolkit called Flukeless, which is designed to be used in the fight against liver fluke. A flatworm called Fasciola Hepatica causes liver fluke, a parasitic disease, in grazing animals including cattle, sheep and goats. It is observed in animals throughout the world and is estimated to cost the international livestock and food industries in the region of €2.5 billion every year. The incidence of liver fluke is on the rise with, for example, a twelve-fold increase in many European Union countries over recent years. The disease causes decreases in meat and milk production and also impacts on fertility of animals. In severe cases, the disease can cause death of animals, particularly lambs, due to associated anaemia. It is also associated with emergence of other animal diseases such as salmonellosis and Tuberculosis.

The Flukeless toolkit, whose development was announced on Friday last, has been developed at the Tyndall National Institute with collaboration from other bodies including Teagasc, the Irish agriculture and food development authority, University College Dublin, Zoetis, The Enfer Group and the Irish Cattle Breeding Federation. It will combine a range of technologies comprising state-of-the-art diagnostic devices, tracking systems and immunity and DNA testing in order to serve farmers, vets and policy analysts in the fight against liver fluke. Use of the kit should enable farmers to more rapidly detect the parasite in their livestock and take steps to immediately intervene in issues including reduced weights, calving rates and yield of milk. The development of the kit has been funded under the Irish Government’s Research Stimulus Fund (RSF) and is part of government strategy to support sustainable and competitive agricultural production practices and policies as well as build the knowledge economy in Ireland in general and the agriculture industry in particular.

Dr Alan O’Riordan, who is the Principal Investigator on the project at the Tyndall Institute said the Flukeless package is a: “pioneering, multidimensional package including on-farm fluke diagnostics, the results of which will be uploaded to geographical information system for disease mapping and also feed into breeding programmes. This approach has broad application and will save significant time, energy and money”. The project will be on-going for the next four years and the package should be available to farmers within five years.

Sources

http://www.science.ie/science-news/tynda...eless.html
http://www.teagasc.ie/
http://www.agritrading.ie/files/Farm_Foc..._Fluke.pdf

Researchers in the University of Utrecht in the Netherlands and the Paul Scherrer Institute in Switzerland have identified a substance that can protect nerve cells from the effect of the deadly toxin, botulinum (BoNT/A). (BoNT/A) is best known for its use in tiny amounts in the beauty product Botox. However, in amounts of just 15 ng, it is lethal, causing paralysis of nerves, and is used in biological weapons. It is also used in small amounts in antidotes to conditions such as migraine. In nature, it mainly kills waterfowl and fish.

In a study published recently in Nature, the researchers examined one of the receptors for BoNT/A, namely the synaptic vesicle glycoprotein 2 (SV2) family. In this study, they developed high resolution crystal structures of the BoNT/A receptor binding domain (BoNT/A-RBD) complexed to the SVC2 luminal domain (SVC2-LD). They determined the backbone-backbone interactions that occurred between toxin and receptor, which resembled those of inter-strand interactions in amyloid structures. They then introduced peptides to determine if they could inhibit formation of the complex between toxin and receptor. This enabled the researchers to identify an inhibitory peptide that prevented absorption of the toxin into nerve cells. This peptide could, the researchers maintain, be the basis to an antidote to BoNT/A poisoning and could be protective against the effects of biological weapons based on this lethal toxin.

Sources
Roger M. Benoit, R.M. et al (2013) Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A Nature (2013) doi:10.1038/nature12732

http://www.uu.nl/university/research/EN/...toxin.aspx

Selection Guide for Monoclonal vs. Polyclonal Antibodies

The biggest difference between polyclonal and monoclonal antibodies is that polyclonal antibodies recognize multiple epitopes and monoclonal antibodies are specific to a single epitope. This primary difference impacts various features of these antibody types which need to be considered to identify the best choice for your applications including:

1.Epitope specificity
2.Volume needed
3.Continuity of supply
4.Tolerance to changes to the antigen
5.Cross-reactivity
6.Use across related species
7.Turnaround time
8.Cost

The umbilical cord (also known as funiculus umbilicalis) is the connection between the placenta and the fetus in its developmental stages. The usual components of the umbilical cord are two arteries and a singular vein that lie inside the Wharton’s jelly. The length of the umbilical cord is 20 inches and its diameter being 0.75 inches (1).

HISTORY OF UMBILICAL CORD BANKING:

Year - Event
• 1988 - Transplantation of umbilical cord blood in a Fanconi anemia patient with cord blood from a sibling who had the same HLA (human leukocyte antigen)
• 1991 - Opening of the 1st unrelated Cord Blood Bank (CBB) with the help of voluntary donors in New York.
• After 1996 - The need to build Cord Blood Units (CBUs) of high quality to coordinate the transplantation of cord blood.
• 1998 - In order to coordinate the data in each CBB, both nationally and internationally, NETCORD was set up
• Currently- Cord Blood Banking is flourishing

The accreditation of CBBs the world over is done by NetCord-FACT (NetCord- Foundation for the Accreditation of Cellular Therapy) (2).

Since the last 25 years, the concept of umbilical cord banking has slowly gained importance in this country (3). India has three public umbilical cord banks: Relicord, Jeevan Cord and Stemcyte. The private umbilical cord banks are seven in number; they are Life Cell, Cryo Banks, Cryosave, Cord Life, Baby Cell, Stem One and ISSL (International Stem Cell Service) (4).

TYPES OF UMBILICAL CORD BANKING:

• Cord Blood Banking- After a child’s birth, the collection and storage of blood from the inside of the umbilical cord is done. This is called cord blood banking. The cord blood is stored by two types of banks:

1. Public - These banks store the cord blood by marking it anonymously. One cannot get back the donated cord blood back from the bank.

2. Private - Personalized use by the entire family. Some amount of money has to be paid to take advantage of this set up.

The regulation of cord blood banks is done by the U.S. Food and Drug Administration (5).

• Cord Tissue Banking- It is the collection, testing, processing and preserving the cord tissue for further treatment processes.

The distinguishing factor between cord blood stem cells and cord tissue stem cells:

The main difference is the type of stem cells that are present in both of them. Cord blood contains haematopoietic stem cells whereas cord tissue contains mesenchymal stem cells (6).

BENEFITS:

1. Collecting the cord blood from the newborn is fully risk free and does not require much effort. There is no inconvenience caused either to the mother or her baby.

2. It can be used anytime as per requirements after completing the due process of collection and the necessary tests. The storage of the cord blood is done in a freezer.

3. Transplantation of cord blood does not necessitate that the donor and the recipient have to match fully; a partial match will also make the process a success.

4. The complications seen in patients of cord blood transplants are very few. Even viruses have a very slim chance of spreading infection in the patient (7).


5. If the cord blood stem cells are kept for personalized use in the future, there is an assurance of a match and the sample can be taken up for use immediately (8).

6. The use of umbilical cord blood cells in research dispels many doubts that come up in the field of embryonic stem cell research (as the embryo is not destroyed) (9).


7. The umbilical cord banks contain cord blood and cord tissue. The cord tissue is composed of mesenchymal stem cells that are genetically very stable. This is of great help in clinical trials for various diseases such as Crohn’s disease, multiple sclerosis etc (10).

APPLICATIONS OF UMBILICAL CORD BLOOD STEM CELLS:

1. Some genetic diseases can be taken care of by transfusing cord blood to the patient e.g. sickle cell anemia (6).

2. In the pediatric population malignancy of the blood can be treated with cord blood transplants (this is for those patients who do not have a family donor).

3. Neurological diseases can be treated with umbilical cord stem cells as they exhibit plasticity. In suitable conditions, they are capable of self-differentiation into cells such as neural cells, cardiac cells etc (7).

4. The stem cells in umbilical cord blood contribute in regenerating insulin, one of the methods to treat juvenile diabetes.

5. In immunotherapy, umbilical cord blood samples act as sources of Treg cells. Treg cells are CD4+ T helper cells that help in immune cell homeostasis (3), (11).

LATEST NEWS REGARDING UMBILICAL CORD STEM CELLS:

1. Development of artificial skin from umbilical cord stem cells (12).

2. Increase in survival rates of patients suffering from leukemia & lymphoma, using UCB stem cells (13).


3. Treating a small child with cerebral palsy using UCB autologous stem cells (14).

4. Reducing pain in the knees through stem cells from umbilical cords (15).

REFERENCES:

1. http://en.wikipedia.org/wiki/Umbilical_cord

2. Navarrete C, Contreras M. Cord Blood Banking: a historical perspective. British Journal of Haematology. 2009; 147: 236-245.

3. http://health.india.com/diseases-conditi...treatment/

4. McKenna D, Sheth J. Umbilical cord Blood: Current status & promise for the future. Indian J Med Res 134. 2011; 261-269.

5. http://kidshealth.org/parent/_cancer_cen...blood.html

6. http://www.cryo-cell.com/cord-tissue-banking

7. http://www.disabled-world.com/news/resea...atment.php

8. http://specialsections.suntimes.com/heal...blood.html

9. Umbilical Cord Blood Banking. RANZCOG College Statement (C-Obs 18). 2013; 1-3.

10. Gong W, Han Z, et al. Banking human umbilical cord-derived mesenchymal stromal cells for clinical use. Cell Transplantation. 2012; 21: 207-216.

11. http://www.ebioscience.com/cell-type/t-r...-cells.htm

12. http://health.india.com/news/scientists-...ical-cord/

13. http://www.sciencedaily.com/releases/201...104923.htm

14. http://www.prnewswire.co.uk/news-release...24971.html

15. http://www.king5.com/health/New-stem-cel...46291.html

Written and emailed by Ms. Deepti Narayan ( also writes on BiotechArticles.com)

3rd International Conference on FUNDAMENTAL and APPLIED RESEARCH in BIOLOGY FARB 2014

Dates: February 24th -27th, 2014

Location: Donetsk, Ukraine

Website: http://www.farb.com.ua/
The website gives all the necessary information on abstract submission, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
Young scientists from around the world are invited to gather in Donetsk in Ukraine from February 24th -27th, 2014 to take part in “fruitful exchange of ideas, the strengthening of international cooperation, and the involvement of scientists in international research projects and programs". The conference will focus on fundamental and applied aspects associated with the botany, zoology, biotechnology, molecular biology, ecology and rational use of natural resources, plant & fungi physiology, animal & human physiology etc. The conference will be dedicated to the 50th anniversary of the Faculty of Biology, Donetsk National University.

Topics
• Botany (Anatomy, Morphology, Vegetation & Taxonomy);
• Zoology (Taxonomy, Fauna);
• Plants and Fungi Physiology & Biochemistry;
• Selection of Plants and Fungi;
• Microbiology & Virology;
• Ecology, Problems of Preservation & Rational Use of Natural Resources;
• Human and Animal Physiology;
• Biotechnologies;
• Biophysics;
• Molecular Biology;
• Methodology of Biology and Ecology Teaching.

Important dates
15.12.2013 – deadline for registration, admission of reports, and the organization fee
01.02.2014 – sending the second circular of the conference
05.02.2014 – deadline for confirming internal participation
24.02.2014 - opening of the FARB 2014
27.02.2014 - closing of the FARB 2014

The difficult international economic conditions have hit the biotechnology industry hard, with many companies severely scaling back their research and development activities and many smaller companies struggling to survive. One of the latest casualties is Galderma Labs, a dermatology company based in Fort Worth, Texas, which was originally established by Nestle and L’Oreal in 1981. The company has just announced that it will be restructuring the company, resulting in lay-offs across the spectrum of employees. While there is no information on the number of employees who will lose their jobs, the company has confirmed that the effects will extend from their home office across other sites in the USA. This news follows the departure of the company’s president, Francois Fournier earlier this year.

Although Galderna Labs had won approval for its rosacea drug Mirvaso earlier in the year and had begun marketing this drug, they received a blow when their prospective impetigo drug auriclosene failed a Phase IIb study. The results of this trial have not been released; the company merely released a statement that they were reviewing the results with a view to trying to decide how to proceed. The departure of Francois Fournier followed soon after this failed trial. The future of Galderma Labs remains uncertain after the restructuring exercise. There has been recent speculation in Bloomberg that Nestle may opt to merge it with Allergan, another company which has been suffering in the on-going worldwide recession.

Source

http://www.fiercebiotech.com/story/galde...2013-12-12

Bristol-Myers and Astra Zeneca have received a welcome recommendation from an FDA advisory panel on their proposed diabetes drug dapagliflozin. This is all the more welcome as the same panel previously came out against the same drug in 2011, resulting in FDA rejection, due to concerns over incidences of bladder cancer in trial treatment groups.

Dapagliflozin is one of a range of new anti-diabetes medications being developed in response to the near-epidemic levels of diabetes, particularly in westernised countries. It is an inhibitor of the SGLT2 member of the family of sodium-dependent glucose transport proteins (SGLT), comprising SGLT1, SGLT2 and SGLT3. SGLT2 is mainly found in the S1 segment of the proximal tubule of the kidney and is chiefly responsible for mediation of renal glucose reabsorption. By inhibiting SGLT2, dapagliflozin can help improve glycaemic control in type 2 diabetes mellitus (T2DM) patients due to reduction of renal glucose reabsorption leading to urinary glucose excretion (glucuresis). The previous FDA rejection of dapagliflozin had initially led to fears that the whole class of drugs could be rejected. However, in the meantime Johnson and Johnson won FDA approval for their SGLT2 inhibitor canagliflozin.

Since the initial rejection, Astra Zeneca and Bristol-Myers have worked on the safety profile of dapagliflozin and for example have demonstrated that the drug has beneficial effects on CV risk factors in T2DM patients. The extra data has been enough to sway the FDA advisory panel that the potential benefits of dapagliflozin outweigh the risks. In addition, the drug is already available in Europe under the name of Forxiga. The delay in approval has inevitably eroded the prospective market share in the USA for dapagliflozin. Estimates of its potential value to the companies have been reduced from $700 million to $300 million per year. However, the companies are now hopeful that the opinion of the advisory committee will result in FDA approval by February 2014.

Sources

CASTANEDA-SCEPPA, C. and CASTANEDA, F., 2011. Sodium-dependent glucose transporter protein as a potential therapeutic target for improving glycemic control in diabetes. Nutrition reviews, 69(12), pp. 720-729.

GUDE, D., 2012. Red carpeting the newer antidiabetics. Journal Of Pharmacology & Pharmacotherapeutics, 3(2), pp. 127-131.

KASICHAYANULA, S., LIU, X., LACRETA, F., GRIFFEN, S.C. and BOULTON, D.W., 2013. Clinical Pharmacokinetics and Pharmacodynamics of Dapagliflozin, a Selective Inhibitor of Sodium-Glucose Co-transporter Type 2. Clinical pharmacokinetics, .

PTASZYNSKA, A., HARDY, E., JOHNSSON, E., PARIKH, S. and LIST, J., 2013. Effects of dapagliflozin on cardiovascular risk factors. Postgraduate medicine, 125(3), pp. 181-189.

ZHANG, M., ZHANG, L., WU, B., SONG, H., AN, Z. and LI, S., 2013. Dapagliflozin treatment for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes/metabolism research and reviews, .

http://www.fiercebiotech.com/story/fda-p...2013-12-12

Hello everyone,

I am a final year B.Tech Nanotechnology student and i have a few doubts about degradation of plant extracts namely; the general temperature range for degradation of plant extracts and whether the milky latex of Calotropis will adsorb onto nanoparticles if synthesized using green synthesis methods using Calotropis sap.

This is part of my final year project and i would appreciate any advice regarding this.

Actin is a ubiquitous multifunctional protein that participates in cytoskeletal dynamics, cellular motility, intracellular signaling, and regulating gene expression, among other key cellular roles. Its functions rely critically upon the regulation of its polymerization. Although much is known about the structure and roles of filamentous actin (F-actin), the mechanisms by which actin nucleation occurs are still being elucidated.

A recent Cell paper revealed that Actin is a ubiquitous multifunctional protein that participates in cytoskeletal dynamics, cellular motility, intracellular signaling, and regulating gene expression, among other key cellular roles. Its functions rely critically upon the regulation of its polymerization. Although much is known about the structure and roles of filamentous actin (F-actin), the mechanisms by which actin nucleation occurs are still being elucidated.

A recent Cell paper revealed new insights into how actin nucleation occurs. The VopL effector protein binds three actin monomers at once and organizes them into a spatial arrangement close to that found in the canonical actin filament. Structural similarities with the more widely studied Arp2/3 complex and formin proteins suggest that this may be a general mechanism for actin nucleation.

This study used gene synthesis of native and mutant sequences encoding VopL-C-terminal domain peptides in order to obtain a crystal structure revealing how VopL binds to actin. Gene Synthesis from GenScript provides customized bioreagents for cell biology research, including investigations of:
cell cycle progression
cell polarity and cilia formation
neuronal filopodia formation
biosynthetic pathways that regulate cell metabolism
subcellular responses to reactive oxygen species
and the role of cytoskeletal elements in viral infection and parasitic invasion]new insights into how actin nucleation occurs[/url]. The VopL effector protein binds three actin monomers at once and organizes them into a spatial arrangement close to that found in the canonical actin filament. Structural similarities with the more widely studied Arp2/3 complex and formin proteins suggest that this may be a general mechanism for actin nucleation.

This study used gene synthesis of native and mutant sequences encoding VopL-C-terminal domain peptides in order to obtain a crystal structure revealing how VopL binds to actin. Gene Synthesis from GenScript provides customized bioreagents for cell biology research, including investigations of:
cell cycle progression
cell polarity and cilia formation
neuronal filopodia formation
biosynthetic pathways that regulate cell metabolism
subcellular responses to reactive oxygen species
and the role of cytoskeletal elements in viral infection and parasitic invasion