RasGRP1 Transduces Low-Grade TCR Signals which Are Critical for T Cell Development, Homeostasis, and Differentiation

AbstractTwo important Ras-guanyl nucleotide exchange factors, Sos and RasGRP1, control Ras activation in thymocytes. However, the relative contribution of these two exchange factors to Ras/ERK activation and their resulting impact on positive and negative selection is unclear. We have produced two lines of RasGRP1−/− TCR transgenic mice to determine the effect of RasGRP1 in T cell development under conditions of defined TCR signaling. Our results demonstrate that RasGRP1 is crucial for thymocytes expressing weakly selecting TCRs whereas those that express stronger selecting TCRs are more effective at utilizing RasGRP1-independent mechanisms for ERK activation and positive selection. Analysis of RasGRP1−/− peripheral T cells also revealed hitherto unidentified functions of RasGRP1 in regulating T cell homeostasis and sustaining antigen-induced developmental programming

Knowledge, attitude and practice among consumers about adverse drug reaction reporting

Background: Background: Adverse Drug Reaction (ADR) reporting by consumers is quite low in India. Assessing knowledge and attitude of consumers regarding ADR reporting and observing practice of ADR reporting among them can help explore probable causes for underreporting of ADRs by consumers.Methods: This was a cross-sectional study conducted in a tertiary care teaching hospital using investigator-administered questionnaire and interviewing indoor patients of Surgery, Medicine, Obstetrics & Gynaecology and Dermatology departments. The questionnaire was prepared to assess knowledge, attitude and practice of consumers about ADR reporting. Data was analysed using mean, standard deviation and percentages.Result: A total of 820 consumers of medicines were included. It was found that 32.2% consumers were not aware that a drug can produce adverse effects. After being explained about adverse drug reactions, 94.6% consumers felt that adverse drug reactions should be reported. However, 98.8% consumers were not aware of Pharmacovigilance Programme of India. After consulting about consumer reporting programme, majority of respondents (96.1%) felt that the direct consumer reporting programme helps reporting of ADRs. Moreover, 93.7% of consumers were willing to use it to report ADRs in future. Consumers preferred the Telephonic method with a Toll free number for ADR reporting followed by informing a health care professional.Conclusion: Poor knowledge and awareness about ADR reporting is the major factor for low to nearly absent ADR reporting by consumers in India

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation

Response of nitrogen and sulphur levels on productivity and profitability of QPM hybrid (Zea mays) under dryland condition of Eastern Uttar Pradesh

A field experiments was conducted during, 2009-2010 and 2010-2011 at Varanasi , under dryland condition to assess the growth, yield, quality, nutrient content and economics of QPM hybrids (Zea mays L.) under different nitrogen and sulphur levels. Twenty four treatment combination arranged in split plot design replicated three times with four nitrogen levels control, 50 kg N/ha, 100 kg N/ha and 150 kg N/ha in main plot treatments, two QPM hybrids Shaktiman-2 and Shaktiman-4 and three sulphur levels 15 kg S/ha, 30 kg S/ha and 45 kg S/ha as sub-plot treatments. Significant differences were observed among the treatments for all the parameters studied. Dry matter accumulation (g/plant), cob diameter (cm), test weight, protein content (%), protein yield (q/ha), N, P2O5, K2O and S content in plant was increased significantly as a result of nitrogen and sulphur levels. Application of 150 kg N/ha recorded significantly higher grain yield 43.94% and 43.43% over 0 kg N/ha in 1st and 2nd years, respectively. The highest net return (65.76% and 64.07%) and B: C ratio (39.08% and 38.72%) was recorded under 150 kg N/ha in 1st and 2nd years, respectively over 0 kg N/ha. QPM hybrid, Shaktiman-4 proved significantly higher growth, yield attributes, quality, net return and B: C ratio compared to Shaktiman-2. Shaktiman-4 recorded 3.55% and 2.62% higher grain yield over Shaktiman-2 in 1st and 2nd years, respectively. Application of 45 kg S/ha obtained 10.77% and 10.25% highest grain yield during 1st and 2nd years, respectively over 15 kg S/ha. The highest net return (12.56% and 11.69%) and B: C ratio (3.15% and 3.52%) was recorded under 45 kg S/ha in 1st and 2nd years, respectively over 15 kg S/ha

Measurements of dense fuel hydrodynamics in the NIF burning plasma experiments using backscattered neutron spectroscopy

The hydrodynamics of the dense confining fuel shell is of great importance in defining the behaviour of the burning plasma and burn propagation regimes of inertial confinement fusion experiments. However, it is difficult to probe due to its low emissivity in comparison to the central fusion core. In this work, we utilise the backscattered neutron spectroscopy technique to directly measure the hydrodynamic conditions of the dense fuel during fusion burn. Experimental data is fit to obtain dense fuel velocities and apparent ion temperatures. Trends of these inferred parameters with yield and velocity of the burning plasma are used to investigate their dependence on alpha heating and low mode drive asymmetry. It is shown that the dense fuel layer has an increased outward radial velocity as yield increases showing burn has continued into re-expansion, a key signature of hotspot ignition. Comparison with analytic and simulation models show that the observed dense fuel parameters are displaying signatures of burn propagation into the dense fuel layer, including a rapid increase in dense fuel apparent ion temperature with neutron yield

Phylotastic! Making Tree-of-Life Knowledge Accessible, Reusable and Convenient

Scientists rarely reuse expert knowledge of phylogeny, in spite of years of effort to assemble a great "Tree of Life" (ToL). A notable exception involves the use of Phylomatic, which provides tools to generate custom phylogenies from a large, pre-computed, expert phylogeny of plant taxa. This suggests great potential for a more generalized system that, starting with a query consisting of a list of any known species, would rectify non-standard names, identify expert phylogenies containing the implicated taxa, prune away unneeded parts, and supply branch lengths and annotations, resulting in a custom phylogeny suited to the user's needs. Such a system could become a sustainable community resource if implemented as a distributed system of loosely coupled parts that interact through clearly defined interfaces. Results: With the aim of building such a "phylotastic" system, the NESCent Hackathons, Interoperability, Phylogenies (HIP) working group recruited 2 dozen scientist-programmers to a weeklong programming hackathon in June 2012. During the hackathon (and a three-month follow-up period), 5 teams produced designs, implementations, documentation, presentations, and tests including: (1) a generalized scheme for integrating components; (2) proof-of-concept pruners and controllers; (3) a meta-API for taxonomic name resolution services; (4) a system for storing, finding, and retrieving phylogenies using semantic web technologies for data exchange, storage, and querying; (5) an innovative new service, DateLife.org, which synthesizes pre-computed, time-calibrated phylogenies to assign ages to nodes; and (6) demonstration projects. These outcomes are accessible via a public code repository (GitHub.com), a website (www.phylotastic.org), and a server image. Conclusions: Approximately 9 person-months of effort (centered on a software development hackathon) resulted in the design and implementation of proof-of-concept software for 4 core phylotastic components, 3 controllers, and 3 end-user demonstration tools. While these products have substantial limitations, they suggest considerable potential for a distributed system that makes phylogenetic knowledge readily accessible in computable form. Widespread use of phylotastic systems will create an electronic marketplace for sharing phylogenetic knowledge that will spur innovation in other areas of the ToL enterprise, such as annotation of sources and methods and third-party methods of quality assessment.NESCent (the National Evolutionary Synthesis Center)NSF EF-0905606iPlant Collaborative (NSF) DBI-0735191Biodiversity Synthesis Center (BioSync) of the Encyclopedia of LifeComputer Science

First order phase transition from ferromagnetism to antiferromagnetism in Ce(Fe0.96_{0.96}Al0.04_{0.04})2_2

Taking the pseudobinary C15 Laves phase compound Ce(Fe$_{0.96}$Al$_{0.04}$)$_2$ as a paradigm for studying a ferromagnetic to antiferromagnetic phase transition, we present interesting thermomagnetic history effects in magnetotransport as well as magnetisation measurements across this phase transition. A comparison is made with history effects observed across the ferromagnetic to antiferromagnetic transition in R$_{0.5}$Sr$_{0.5}$MnO$_3$ crystals.Comment: 11 pages of text and 4 figures; submitted to Physical Review Letter

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

© 2018 The Author(s). Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (∼60% patients) and after/during commencement of treatment (∼40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis

First order metamagnetic transition in CeFe2_2 based pseudobinary alloys

We present results of dc magnetisation study showing that the low temperature antiferromagnetic state in various CeFe$_2$-based pseudobinary alloys can be transformed into ferromagnetic state through a magnetic field induced phase transition. We highlight the presence of hysteresis and phase coexistence across this metamagnetic transition and argue that the observed phase transition is of first order in nature.Comment: 11 pages of text and 9 figures ; to appear in Journal of Physics: Condens. Matte