235 research outputs found

    Evolution of a novel gene pair from a canonical toxin-antitoxin module in Escherichia coli

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    Free-living bacteria are continuously subjected to environmental stress. This stress can be in the form of a change in temperature, pH, osmolarity or nutritional starvation. Most bacterial species contain gene modules known as Toxin-Antitoxin (TA) systems that reversibly inhibit cellular growth in response to stress; thereby helping the cells cope with a changing environment. One mechanism that bacteria have developed to combat fluctuations in environmental temperature is the cold-shock response. This response helps exponentially growing cells buffer themselves against a downshift in temperature from their optimal growing temperature; typically a shift from 37??C to 15??C for Escherichia coli (E. coli). Cold-shock proteins (Csp) are synthesized at this time. Protein Y (PY), the protein product of gene yfiA in E. coli is suggested to be a cold-shock related protein. It prevents ribosomes from dissociation during cold-shock, and in stationary phase, thereby blocking translational elongation and inhibiting cell growth. This mechanism resembled that of a typical TA system toxin. We identified a small gene, b2596, upstream of yfiA and propose that the b2596-yfiA module evolved from a true proteic TA system that functioned in cold-shock conditions; Protein X (PX), product of b2596, being the antitoxin and PY the toxin. The module still retains some of its TA system characteristics: both genes encode small proteins, have opposing charges and show sequence similarity to known TA genes. Also, like a true TA system b2596, the proposed antitoxin gene, precedes yfiA, the proposed toxin gene. However, we found that the two genes have independent transcriptional start sites. Also b2596 encodes a leaderless mRNA with UUG start and thus we predict that it cannot be translated well in vivo. PY inhibits growth of E. coli cells and functions in helping the bacterial population to survive cold-shock. Our data suggest that b2596 and yfiA have evolved from a canonical proteic TA module that was functional in cold shock. The two genes are now independent and responsive to cold shock.M.S.Includes bibliographical references (p. 56-60)

    K-theory with R/Z coefficients and von Neumann algebras

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    This paper provides a realization of K-theory with R/Z coefficients and proves an R/Z index theorem

    Ultrasonic attenuation in semi-metallie GdX single crystals (X=P,As,Sb and Bi) in the temperature range 10 to 300 K

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    510-513Ultrasonic attenuation studies have been made in semi-metallic GdX single crystals (X= P, As, Sb and Bi) in the temperature range 10-300 K. Attenuation due to e-p interaction has been studied from 10 to 80K and due to p-p interaction between 100-300 K. Morse potential has been used to evaluate second and third order elastic constants at 0 K and then at higher temperatures. Mason's approach has been used to evaluate ultrasonic attenuation. Results have been discussed, at neel-temperature slight kink in ultrasonic attenuation is observed in all the cases

    Spatial distribution of R, K and LS factor.

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    Spatial distribution of R, K and LS factor.</p

    Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro

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    Reproducing the characteristics and the functional responses of the blood–brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation

    K values for different soil textural classes in the study area.

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    K values for different soil textural classes in the study area.</p

    HIF-1 alpha is involved in blood-brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis

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    Bacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from blood to the brain across the blood-cerebrospinal fluid barrier or the blood-brain barrier (BBB). The underlying mechanisms are still poorly understood. Current treatment strategies include adjuvant dexamethasone for inflammation and cerebral edema, followed by antibiotics. The success of dexamethasone is however inconclusive, necessitating new therapies for controlling edema, the primary reason for neurological complications. Since we have previously shown a general activation of hypoxia inducible factor (HIF-1α) in bacterial infections, we hypothesized that HIF-1α, via induction of vascular endothelial growth factor (VEGF) is involved in transmigration of pathogens across the BBB. In human, murine meningitis brain samples, HIF-1α activation was observed by immunohistochemistry. S. pneumoniae infection in brain endothelial cells (EC) resulted in in vitro upregulation of HIF-1α/VEGF (Western blotting/qRT-PCR) associated with increased paracellular permeability (fluorometry, impedance measurements). This was supported by bacterial localization at cell-cell junctions in vitro and in vivo in brain ECs from mouse and humans (confocal, super-resolution, electron microscopy, live-cell imaging). Hematogenously infected mice showed increased permeability, S. pneumoniae deposition in the brain, along with upregulation of genes in the HIF-1α/VEGF pathway (RNA sequencing of brain microvessels). Inhibition of HIF-1α with echinomycin, siRNA in bEnd5 cells or using primary brain ECs from HIF-1α knock-out mice revealed reduced endothelial permeability and transmigration of S. pneumoniae. Therapeutic rescue using the HIF-1α inhibitor echinomycin resulted in increased survival and improvement of BBB function in S. pneumoniae-infected mice. We thus demonstrate paracellular migration of bacteria across BBB and a critical role for HIF-1α/VEGF therein and hence propose targeting this pathway to prevent BBB dysfunction and ensuing brain damage in infections

    Life Skills integration in Self Learning Materials of Social Science: A Quality Measure

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    EFA Goals had suggested “Ensuring that the learning needs of all young people and adults are met through equitable access to appropriate learning and life-skills programmes” as well as “Improving all aspects of the quality of education and ensuring excellence of all so that recognized and measurable learning outcomes are achieved by all, especially in literacy, numeracy and essential life skills”. It is now widely accepted that ‘Life Skills’ is an important aspect of quality education. The relevance and significance of life skills education cannot be denied. // In the face to face formal system, learners have the opportunity to learn life skills from teachers. However, ODL learners are deprived of this, as they are not a part of face to face teaching-learning set up. NIOS, India came up with an innovation for enabling the learners of secondary level (class 10) to learn life skills by integrating them in the self learning material in all subjects. The author was a part of this Project (which was completed in 2012-13) in the capacity of author, editor and mentor in the subject of Social Science. Before all the study materials were revised and life skills incorporated, a project was undertaken by NIOS with UNFPA support, wherein a few model lessons were developed. This project was reported by NIOS in PCF6, which was held in Kochi, India.// In this paper, the focus will be on Social Science study materials. How life skills were incorporated in it will be demonstrated through examples. The participants will be encouraged to discuss the importance of life skills, life skills integration in self learning materials of NIOS, Examples of life skill integration in Social Science study materials, etc. The sub-theme is Equity and Inclusion and the strand is Quality. // Paper ID 20

    Query specific re-ranking for improved cross-modal retrieval

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    Cross-modal retrieval tasks like image-to-text, audio-to-image retrieval, etc. are an important area of research. Different algorithms have been developed to address these tasks. In this work, we propose a novel query specific re-ranking based approach to improve the retrieval performance of any given baseline approach. For each query, the top K-retrieved results of the baseline algorithm are used to compute its class-rank order feature. Based on this feature of the query and the highly relevant examples within the top K-retrieved results, each training example is given a score indicating its relevance to the query, which is finally used to train the query-specific regressor. The new score given by this regressor to each retrieved example is then used to re-rank them. The proposed approach does not require knowledge of the baseline algorithm, and also does not extract additional features from the data. Thus it can be used as an add-on to any existing algorithm for improved retrieval performance. Experiments with several state-of-the-art cross-modal algorithms across different datasets show the effectiveness of the proposed re-ranking algorithm. (C) 2017ElsevierB. V. Allrightsreserved
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