Epitope Mapping Services by GenScript

December 10, 2013, 6:43 pm

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The discovery and development of new antibody therapies and vaccines require knowing the epitope that the antibody interacts with. Regulatory bodies including the FDA and EMEA now require the specific binding sites between an antibody drug and its target to be included in the regulatory filing. GenScript provides a peptide based epitope mapping service with speedy turnaround time.

Service Highlights:
Proprietary advanced FlexPeptide? technology
Optimized detection to minimize nonspecific interactions
High-throughput epitope profiling for a large number of candidate antibodies against a defined target
Speedy delivery, starting from 4 weeks

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Engineered "Twincretin" peptide containing both GLP-1 and GIP sequences reduces obesi

December 11, 2013, 8:26 pm

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A recent study in Science Translational Medicine* describes the development and testing of a potential new therapeutic for treating obesity and diabetes. The therapeutic peptide (which was playfully termed "Twincretin"), was engineered by combining sequences from the incretin peptide hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The resulting peptide was subsequently engineered with a PEGylation modification to enhance pharmacokinetics.


Need PEGylated peptides for incretin therapeutics or other peptide-based diabetes/obesity drug candidates? Try GenScript's peptide synthesis service.


GLP-1 has previously been the focus of incretin therapies, due to its ability to suppress appetite, which results in weight loss, and its agonistic effect on the GLP-1 receptor which leads to increased β cell (cells that secrete insulin) survival and proliferation. Overexpression of GIP has been shown to improve body weight and glycemic control. Administration of the twincretin peptide resulted in weight loss in mice and was shown to be more effective than treatment with either peptide alone. In additional experiments, the insulinotropic effect of the twincretin peptide in mice was shown to be translatable to monkeys and humans.

Hydrogel with potential for craniofacial reconstruction

December 12, 2013, 4:12 am

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Bioengineering researchers in Rice University in Texas have made a major step forward in the field of craniofacial reconstruction with the development of a modified hydrogel that is liquid at room temperature but solidifies into a gel at body temperature. The researchers have published their results in a ‘Just Accepted’ manuscript in the American Chemical Society journal Biomacromolecules. The hydrogel can ‘fit’ into irregular three-dimensional spaces, relevant in the case of craniofacial reconstruction following illness or injury, and in a preliminary encapsulation assay was shown to be capable of delivering mesenchymal stem cells (MSC). This would be highly relevant in tissue engineering to encourage delivery of growth factors and cell proliferation to ultimately direct new bone formation.

The study builds on other research considering the applicability of thermosensitive technologies as an alternative to prefabricated scaffolds in craniofacial reconstruction. The researchers introduced chemical modifications to a polymer called poly(N-isopropylacrylamide) ( PNiPAAm) which improved its properties in terms of biodegradability and hydrogel shrinkage. Inadequate biodegradability causes physical barriers to tissue repair and leaves the patient prone to inflammation while shrinkage has a negative effect on nutrient diffusion and on tissue integration. In addition, they carried out in vitro cytocompatibility assays on rat fibroblast cells using their modified hydrogel and were able to demonstrate cytocompatibility of the hydrogel degradation products. Importantly in terms of the potential of this hydrogel for cell delivery applications in tissue engineering projects such as craniofacial reconstruction, MSC encapsulation studies were carried out. MSCs in serum-containing media were successfully encapsulated in the hydrogel, with live cells being supported for up to 7 days. This did not affect hydrogel cross-linking.

The potential of this is enormous as the macromolecule can be injected, be converted to a gel at body temperature and support bone tissue growth and then be readily removed by being converted back into a liquid form. The authors of the study are continuing their research and the lead investigator, Antonius Mikos is hopeful that development of this thermosensitive hydrogel will have ‘enormous implications for the development of novel therapeutics for craniofacial bone regeneration’.

Sources

Rice University. "Liquid to gel to bone: Temperature-sensitive gelling scaffolds made to regenerate craniofacial bone." ScienceDaily, 11 Dec. 2013. [Accessed 12 Dec. 2013]

VO, T.N., EKENSEAIR, A.K., KASPER, F.K. and MIKOS, A.G. (2013). Synthesis, Physicochemical Characterization, and Cytocompatibility of Bioresorbable, Dual-Gelling Injectable Hydrogels. Biomacromolecules, 2013; : 131210033924002 DOI: 10.1021/bm401413c

Genome sequencing reveals new drug candidates for rhabdomyosarcoma

December 12, 2013, 6:11 am

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A gene sequencing project carried out by researchers in US centres including St. Jude’s Children’s Research Hospital in Memphis, Tennessee, the Washington University School of Medicine in St. Louis, Missouri, UT Southwestern Medical Centre in Dallas, Texas and Seattle Children’s Hospital has shed new light on reasons for recurrence and potential treatments for rhabdomyosarcoma. Rhabdomyosarcoma is a cancer predominantly of childhood. It is a soft-tissue sarcoma and has two major histological subtypes, namely embryonal (approximately 60% of patients) and alveolar (approximately 25% of patients). These two subtypes have distinct features in terms of their clinical and genetic features.

The project exploited the experience of researchers in the Genome Institute at Washington University School of Medicine in whole-genome sequencing and analysis of tumour recurrence. The study, published this week in Cancer Cell describes the results of next generation, whole genome sequencing of both the tumour and the normal genomes of 16 tumours from 13 rhabdomyosarcoma patients and subsequent validation by more focussed sequencing of tumours from 37 further patients. The results showed that there were different genetic origins for the two tumour subtypes and that there were many more genomic alterations, including chromosomal rearrangements and mutations, in the embryonal compared to the alveolar subtype. Alveolar rhabdomyosarcoma indeed appeared to be the result of a single chromosomal rearrangement that fuses FOX01 with either PAX3 or PAX 7. In the embryonal rhabdomyosarcoma patients who were at high risk, it was observed that there were mutations in genes of the RAS pathway which by contrast were not observed in alveolar rhabdomyosarcoma. It was also observed that there was a high level of oxidative stress in the embryonal rhabdomyosarcoma tumours. A drug screen on tumour cells from three embryonal rhabdomyosarcoma patients, using primary cultures derived from xenografts, found that while RAS-targeting drugs had little effect, the use of oxidative stress-inducing drugs resulted in tumour cell death and enhancement of chemotherapeutic effects. The study’s authors concluded that the increase of oxidative stress on already stressed tumour cells was enough to push the balance towards cell death. These results offer a potentially new and exciting way to use existing oxidative stress-enhancing drugs to complement chemotherapy in embryonal rhabdomyosarcoma patients. It also gives a telling insight into why these tumours sometimes recur.

Sources

Chen, X. et al (2103). Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. Cancer Cell, 2013; 24 (6): 710 DOI: 10.1016/j.ccr.2013.11.002

St. Jude Children's Research Hospital. "Gene sequencing project finds drugs with promise for treating childhood tumor." ScienceDaily, 9 Dec. 2013. [Accessed 12 Dec. 2013]

BIO Asia International Conference | 8-9 April 2014 | Tokyo

December 12, 2013, 6:35 am

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11th Annual BIO Asia International Conference

Organisers: Biotechnology Industry Organization

Dates: April 8th-9th, 2014

Location: Grand Hyatt, Tokyo, Japan.

Website: http://www.bio.org/events/conferences/bi...conference

The website gives all the necessary information on registration, presenting, one-on-one meetings, fees, conference agenda, hotel, exhibitions and other important facts.

Purpose of the conference
The BIO Asia International Conference has a very specific remit, i.e. to unite U.S. and European drug development companies with Asian biotech and pharmaceutical companies to help foster research collaborations and licensing agreements.
BIO One-on-One Partnering proprietary computer software will be used to private, pre-arranged meetings between senior-level executives. It is billed as the premier dedicated biotech partnering event in Asia and offers an unrivalled opportunity to meet with the leading international pharmaceutical and biotech companies in one place at one time.

Topics:

Aspects of the following broad topics will feature:
• Healthcare
• Emerging companies
• Intellectual property
• Food and Agriculture
• Public policy
• Industrial & Environmental

Important dates:
‘Early bird’ registration by February 18th 2014

Sponsorship
Companies who sponsor the conference can avail of the following benefits:
• Prominent speaking opportunities
• Dedicated sponsor suites for private meetings
• Priority customer service & partnering meeting scheduling
• High-visibility branding opportunities
• Complimentary registrations
• Corporate recognition on event marketing materials:
o Conference website
o Pre-conference marketing collateral
o Advertisement in on-site

Who are the organisers?
The Biotechnology Industry Organization (BIO) is the world’s largest biotechnology trade association. BIO is a 501©(6) non-profit organization headquartered in Washington, D.C. They provide advocacy, business development, and communications services for more than 1,100 members worldwide. They state their mission to be the champion of biotechnology and the advocate for their member organizations - both large and small.

Recent studies shed light on the mechanisms of actin filament formation and other sec

December 12, 2013, 7:35 pm

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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 [url=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

Degradation temperature of plant extracts

December 12, 2013, 9:49 pm

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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.

Diabetes drug dapagliflozin wins support of FDA advisory committee

December 13, 2013, 4:34 am

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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

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Galderna Labs faces restructuring and staff lay-offs

December 13, 2013, 4:52 am

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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

FUNDAMENTAL and APPLIED RESEARCH in BIOLOGY FARB 2014 | February 24-27 2014 | Ukraine

December 13, 2013, 5:09 am

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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

Umbilical Cord Banking Benefits and Applications

December 13, 2013, 5:46 am

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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)

How to choose the optimal antibody for your application?

December 15, 2013, 6:43 pm

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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

Beauty product or biological weapon? An inhibitory peptide developed for botulinum

December 15, 2013, 11:48 pm

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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

Flukeless: Irish scientists develop a diagnostic test kit for liver fluke

December 16, 2013, 5:31 am

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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

BioTech 2014 | March 10-11 2014 | Dubai, UAE

December 16, 2013, 6:35 am

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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.

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Zebrafish embryos reveal signalling link between calcium deficiency and cancer

December 17, 2013, 4:03 am

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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.

Coffee drinking and smoking may be protective against rare liver cancer PSC

December 17, 2013, 4:33 am

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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].

Biotherapeutics Analytical Summit| March 24-28 2014 | Baltimore USA

December 17, 2013, 5:06 am

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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...

Lung cancer ALK and ROS1 oncogenes found in CRC tumours; therapeutic implications

December 17, 2013, 2:26 pm

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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].

How your pet dog may protect your children from allergies

December 17, 2013, 3:37 pm

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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].