CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery

The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide–major histocompatibility (pMHC) ligands and by facilitating the recruitment of a kinase to the TCR–pMHC complex that is essential for initiating signaling. Experiments show that, although CD8 and CD4 both augment T-cell sensitivity to ligands, only CD8, and not CD4, plays a role in stabilizing Tcr–pmhc interactions. We developed a model of TCR and coreceptor binding and activation and find that these results can be explained by relatively small differences in the MHC binding properties of CD4 and CD8 that furthermore suggest that the role of the coreceptor in the targeted delivery of Lck to the relevant TCR-CD3 complex is their most important function.National Institutes of Health (U.S.) (Grant 1PO1AI071195/01

Land surface phenological response to decadal climate variability across Australia using satellite remote sensing

© 2014 Author(s). Land surface phenological cycles of vegetation greening and browning are influenced by variability in climatic forcing. Quantitative spatial information on phenological cycles and their variability is important for agricultural applications, wildfire fuel accumulation, land management, land surface modeling, and climate change studies. Most phenology studies have focused on temperature-driven Northern Hemisphere systems, where phenology shows annually recurring patterns. However, precipitation-driven non-annual phenology of arid and semi-arid systems (i.e., drylands) received much less attention, despite the fact that they cover more than 30% of the global land surface. Here, we focused on Australia, a continent with one of the most variable rainfall climates in the world and vast areas of dryland systems, where a detailed phenological investigation and a characterization of the relationship between phenology and climate variability are missing. To fill this knowledge gap, we developed an algorithm to characterize phenological cycles, and analyzed geographic and climate-driven variability in phenology from 2000 to 2013, which included extreme drought and wet years. We linked derived phenological metrics to rainfall and the Southern Oscillation Index (SOI). We conducted a continent-wide investigation and a more detailed investigation over the Murray-Darling Basin (MDB), the primary agricultural area and largest river catchment of Australia. Results showed high inter-and intra-annual variability in phenological cycles across Australia. The peak of phenological cycles occurred not only during the austral summer, but also at any time of the year, and their timing varied by more than a month in the interior of the continent. The magnitude of the phenological cycle peak and the integrated greenness were most significantly correlated with monthly SOI within the preceding 12 months. Correlation patterns occurred primarily over northeastern Australia and within the MDB, predominantly over natural land cover and particularly in floodplain and wetland areas. Integrated greenness of the phenological cycles (surrogate of vegetation productivity) showed positive anomalies of more than 2 standard deviations over most of eastern Australia in 2009-2010, which coincided with the transition from the El Niño-induced decadal droughts to flooding caused by La Niña

Sequential application of hyperspectral indices for delineation of stripe rust infection and nitrogen deficiency in wheat

© 2015, Springer Science+Business Media New York. Nitrogen (N) fertilization is crucial for the growth and development of wheat crops, and yet increased use of N can also result in increased stripe rust severity. Stripe rust infection and N deficiency both cause changes in foliar physiological activity and reduction in plant pigments that result in chlorosis. Furthermore, stripe rust produce pustules on the leaf surface which similar to chlorotic regions have a yellow color. Quantifying the severity of each factor is critical for adopting appropriate management practices. Eleven widely-used vegetation indices, based on mathematic combinations of narrow-band optical reflectance measurements in the visible/near infrared wavelength range were evaluated for their ability to discriminate and quantify stripe rust severity and N deficiency in a rust-susceptible wheat variety (H45) under varying conditions of nitrogen status. The physiological reflectance index (PhRI) and leaf and canopy chlorophyll index (LCCI) provided the strongest correlation with levels of rust infection and N-deficiency, respectively. When PhRI and LCCI were used in a sequence, both N deficiency and rust infection levels were correctly classified in 82.5 and 55 % of the plots at Zadoks growth stage 47 and 75, respectively. In misclassified plots, an overestimation of N deficiency was accompanied by an underestimation of the rust infection level or vice versa. In 18 % of the plots, there was a tendency to underestimate the severity of stripe rust infection even though the N-deficiency level was correctly predicted. The contrasting responses of the PhRI and LCCI to stripe rust infection and N deficiency, respectively, and the relative insensitivity of these indices to the other parameter makes their use in combination suitable for quantifying levels of stripe rust infection and N deficiency in wheat crops under field conditions

GUI based Testing Tool for Transformer

The objective of this paper is to develop an educational toolbox using GUI for analysis of transformers for students and lecturers.  GUI figure file is developed for Open Circuit & Short Circuit Test, Sumpner’s Test, All day efficiency (Energy efficiency) of transformer and parallel operation of two transformers.  All this kinds of problems consists of various methods of mathematical calculation which is difficult to perform by using manual calculation (formula and calculator). The existence of this educational toolbox will help the user to calculate the parameter hence the calculation become faster and easier. The user can enter the data and obtained the results quickly in the form of data or figures.  The students can also observe the effect of variation of input parameters on performance of transformer.   This educational toolbox was developed by using MATLAB software.DOI:http://dx.doi.org/10.11591/ijece.v4i3.521

On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p

Application-Aware Deadlock-Free Oblivious Routing

Conventional oblivious routing algorithms are either not application-aware or assume that each flow has its own private channel to ensure deadlock avoidance. We present a framework for application-aware routing that assures deadlock-freedom under one or more channels by forcing routes to conform to an acyclic channel dependence graph. Arbitrary minimal routes can be made deadlock-free through appropriate static channel allocation when two or more channels are available. Given bandwidth estimates for flows, we present a mixed integer-linear programming (MILP) approach and a heuristic approach for producing deadlock-free routes that minimize maximum channel load. The heuristic algorithm is calibrated using the MILP algorithm and evaluated on a number of benchmarks through detailed network simulation. Our framework can be used to produce application-aware routes that target the minimization of latency, number of flows through a link, bandwidth, or any combination thereof

Peroxiredoxin II Regulates Effector and Secondary Memory CD8+ T cell Responses

Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role in cellular responses. However, the effect of increased H2O2on an antigen-specific CD8+ T cell response was unknown. Following T cell receptor (TCR) stimulation, the expression and oxidation of peroxiredoxin II (PrdxII), a critical antioxidant enzyme, increased in CD8+ T cells. Deletion of PrdxII increased ROI, S phase entry, division, and death during in vitro division. During primary acute viral and bacterial infection, the number of effector CD8+ T cells in PrdxII-deficient mice was increased, while the number of memory cells were similar to those of the wild-type cells. Adoptive transfer of P14 TCR transgenic cells demonstrated that the increased expansion of effector cells was T cell autonomous. After rechallenge, effector CD8+ T cells in mutant animals were more skewed to memory phenotype than cells from wild-type mice, resulting in a larger secondary memory CD8+ T cell pool. During chronic viral infection, increased antigen-specific CD8+ T cells accumulated in the spleens of PrdxII mutant mice, causing mortality. These results demonstrate that PrdxII controls effector CD8+ T cell expansion, secondary memory generation, and immunopathology

Identification of XMRV Infection-Associated microRNAs in Four Cell Types in Culture

INTRODUCTION: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS) in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA), which regulate gene expression, were so far not identified in cells infected with XMRV in culture. METHODS: Two prostate cell lines (LNCaP and DU145) and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. RESULTS: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs). miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. DISCUSSION: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types

In situ approach for rapid characterization to aid on farm conservation of coconut germplasm - A case study of two ecotypes from West coast of India

Characterization and evaluation of coconut germplasm have conventionally been undertaken in ex situ gene banks, which take a minimum duration of fifteen years. On the other hand, utilization of coconut populations in situ can effectively reduce the time required for characterization of the populations. Hence, a concept to make a paradigm shift in the existing approach of coconut germplasm characterization is advocated in this study with a view to broaden the conservation base and facilitate inclusion of identified diverse ecotypes. The methodology has been applied to identify, locate and characterize two tall coconut ecotypes viz., Bedakam and Kuttiyadi, from northern Kerala. Agronomic traits, viz., higher number of nuts per palm, higher copra content and better performance under marginal management conditions along with adaptation to the environment, were the major reasons for preference of these ecotypes among the farmers. Comparison of the two ecotypes revealed that the traits, trunk girth, length of internode, number of leaves, number of bunches with nuts, number of nuts, shell weight, husked fruit weight and fruit weight were higher in Kuttiyadi than in Bedakam ecotype. On the other hand, number of leaf scars per meter, length of inflorescence, fruit breadth, husk weight, nut cavity volume and copra weight were higher in Bedakam compared to Kuttiyadi ecotype. Relevance, utility and importance of the study are discussed from the perspective of effective utilization of the coconut diversity in situ and their possible further use in coconut improvement efforts through conservation strategies