alphabeta T cell receptors as predictors of health and disease

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR \u27signatures\u27 raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome

Biological activities of fusarochromanone: a potent anti-cancer agent

BACKGROUND: Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. RESULTS: Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC(50) ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. CONCLUSIONS: Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101’s molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery

Agriculture Emergencies: A Primer for First Responders

Over the past several years, the primary focus of emergency preparedness has been on terrorism, and how a CBRNE event would directly affect human health. Limited emphasis has been placed on the direct (eg, zoonotic infections) and indirect (eg, mental health, financial loss) effects that an agricultural emergency event can have on human health outcomes, and how they relate to emergency preparedness. We critically reviewed the resources and information readily accessible to our target audience, emergency responders; the resources included military and civilian books, personal communications, internet sites, GAO reports, and peer-reviewed journals. Among more than 2,000 bioterrorism-related articles, we found 51 that addressed either agroterrorism and/or veterinary public health: 2 cross-sectional studies, 28 review papers, and 21 commentary papers. In order to properly respond to future agriculture emergencies, emergency response professionals need to understand the nature and implications of the event as well as their roles and responsibilities, but the availability of educational and training opportunities is limited. The results of our review are consistent with the hypothesis that more resources, education, and training opportunities should be available to responders as well as to producers, importers and shippers, international travelers, and the general public. Increased education and training will raise awareness among these groups of the relationship between animal and human health