Models of T cell antigen receptor activation: the puzzle still remained

T cell antigen receptor (TCR) is a protein-complex expressed on all T cells of the immune system and is responsible for the activation of T cells when infectious agent is presented by an antigen presenting cell (APC) in the form of peptides bound to the major histocompatibility complex (pMHC). Despite numerous studies it is not clear what biochemical changes upon binding of antigen ligand to the extracellular domains of TCR leads to activation of intracellular signaling (a process known as TCR triggering). This review summarizes possible biochemical mechanisms for TCR triggering and discusses their comparative limitations and advantages in explaining various experimental observations.Keywords: T cell antigen receptor; activation; modelDOI: http://dx.doi.org/10.3126/njb.v2i1.5684Nepal Journal of Biotechnology Jan.2012, Vol.2(1): 62-7

Association analysis for yield and related traits in fenugreek (Trigonella foenum-graecum L.) under different environmental conditions

Sixteen diverse genotypes of fenugreek (Trigonella foenum-graecum L.) were grown in five (E1 to E5) environments which were created by different date of sowing during the rabi seasons at the Vegetable Farm of CCS HAU, Hisar. (29°15?N, 75°69?E) during 2012-13. Observations were recorded on ten randomly selected plants from each genotypes in each replications for characters viz. field emergence index, days to 50 % flowering, plant height, number of pods per plant, number of branches per plant, number of seeds per pod, pod length, seed yield (q/ha), test weight, seed germination, seed vigour index-I and II. The estimation of genotypic and phenotypic coefficients (GCV and PCV) variation in all the environments was consistently decreasing with the delaying in sowing date for all the character studied except plant height and test weight indicating that the environmental influence was comparatively more pronounced for these characters in expressing the phenotypic performance of different genotypes. Highest GCV and PCV was estimated as 50.36 % and 55.93 %, respectively for seed vigour index-I in E1. High value of heritability estimated for characters seed yield, seed vigour index-II, seed germination and branches per plant (above 70 %) in E1 revealed that these were less influenced by environment and low heritability estimated for days to 50 % flowering in E2, plant height in E2, seeds per pod in E3, field emergence index in E5 indicated high influence of environment. Based on environmental indices, the environment E2 was most favourable for all the characters studied except field emergence index

Potential of Moringa oleifera and Okra as Coagulants in Sustainable Treatment of Water and Wastewater

Chemical/synthetic coagulants are widely used to remove suspended solids and organic loads from water, but they pose several environmental and public health issues due to their chronic toxicity. The study evaluated the performance of these natural coagulants individually and in blended combinations with a synthetic coagulant, Alum, in terms of the percentage removal of turbidity, TSS, BOD, and COD after water treatment at optimum dosages. The blended use of all three coagulants in equal proportion showed the best performance (turbidity removal = 91.91%; TSS removal = 51.18%; BOD removal = 41.67%; and COD removal = 55.56%), but increased the pH of treated water from 7.10 to 7.95. The treatment cost analysis showed that Alum had the lowest treatment cost (Rs. 0.78 per 1,000 L); while the blended use of Moringa oleifera and Okra (Abelmoschus esculentus) at the optimum dosage of 120 mg/L had the lowest cost (Rs. 31.20 per 1,000 L) among the natural coagulants. Despite higher cost of treatment, the use of natural coagulants in water and wastewater treatment provide sustainable solutions while reducing the negative impact of synthetic coagulants on the environment and public health

Quantitative Analysis of Protein Phosphorylations and Interactions by Multi-Colour IP-FCM as an Input for Kinetic Modelling of Signalling Networks

BACKGROUND: To understand complex biological signalling mechanisms, mathematical modelling of signal transduction pathways has been applied successfully in last few years. However, precise quantitative measurements of signal transduction events such as activation-dependent phosphorylation of proteins, remains one bottleneck to this success. METHODOLOGY/PRINCIPAL FINDINGS: We use multi-colour immunoprecipitation measured by flow cytometry (IP-FCM) for studying signal transduction events to unrivalled precision. In this method, antibody-coupled latex beads capture the protein of interest from cellular lysates and are then stained with differently fluorescent-labelled antibodies to quantify the amount of the immunoprecipitated protein, of an interaction partner and of phosphorylation sites. The fluorescence signals are measured by FCM. Combining this procedure with beads containing defined amounts of a fluorophore allows retrieving absolute numbers of stained proteins, and not only relative values. Using IP-FCM we derived multidimensional data on the membrane-proximal T-cell antigen receptor (TCR-CD3) signalling network, including the recruitment of the kinase ZAP70 to the TCR-CD3 and subsequent ZAP70 activation by phosphorylation in the murine T-cell hybridoma and primary murine T cells. Counter-intuitively, these data showed that cell stimulation by pervanadate led to a transient decrease of the phospho-ZAP70/ZAP70 ratio at the TCR. A mechanistic mathematical model of the underlying processes demonstrated that an initial massive recruitment of non-phosphorylated ZAP70 was responsible for this behaviour. Further, the model predicted a temporal order of multisite phosphorylation of ZAP70 (with Y319 phosphorylation preceding phosphorylation at Y493) that we subsequently verified experimentally. CONCLUSIONS/SIGNIFICANCE: The quantitative data sets generated by IP-FCM are one order of magnitude more precise than Western blot data. This accuracy allowed us to gain unequalled insight into the dynamics of the TCR-CD3-ZAP70 signalling network

Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy

Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti-angiogenic treatment has limited efficacy due to therapy-induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy-induced resistance. We show that Apelin inhibition potently remodels the tumor microenvironment, reducing angiogenesis, and effectively blunting tumor growth. Functionally, targeting Apelin improves vessel function and reduces polymorphonuclear myeloid-derived suppressor cell infiltration. Importantly, in mammary and lung cancer, Apelin prevents resistance to anti-angiogenic receptor tyrosine kinase (RTK) inhibitor therapy, reducing growth and angiogenesis in lung and breast cancer models without increased hypoxia in the tumor microenvironment. Apelin blockage also prevents RTK inhibitorinduced metastases, and high Apelin levels correlate with poor prognosis of anti-angiogenic therapy patients. These data identify a druggable anti-angiogenic drug target that reduces tumor blood vessel densities and normalizes the tumor vasculature to decrease metastases

Biology: Ultimate Science of the 21^st Century

25-28<span style="font-size:11.0pt;font-family:Cambria; mso-fareast-font-family:" times="" new="" roman";mso-bidi-font-family:"times="" roman";="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="">Biology is fast becoming the science of the 21st century opening up a fair amount of career avenues.</span