116 research outputs found

    Tuboenterocutaneous fistula following caesarean section

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    Fistulous communication between fallopian tube, sigmoid colon and the skin after caesarean section is an unreported entity so far. Here we report a case of tuboenterocutaneous fistula which developed after wound complication following lower segment caesarean section (LSCS). Computed tomography (CT) was used to diagnose the case and laparotomy was done as definitive surgery

    Structure-Based Phylogeny as a Diagnostic for Functional Characterization of Proteins with a Cupin Fold

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    The members of cupin superfamily exhibit large variations in their sequences, functions, organization of domains, quaternary associations and the nature of bound metal ion, despite having a conserved beta-barrel structural scaffold. Here, an attempt has been made to understand structure-function relationships among the members of this diverse superfamily and identify the principles governing functional diversity. The cupin superfamily also contains proteins for which the structures are available through world-wide structural genomics initiatives but characterized as "hypothetical". We have explored the feasibility of obtaining clues to functions of such proteins by means of comparative analysis with cupins of known structure and function.A 3-D structure-based phylogenetic approach was undertaken. Interestingly, a dendrogram generated solely on the basis of structural dissimilarity measure at the level of domain folds was found to cluster functionally similar members. This clustering also reflects an independent evolution of the two domains in bicupins. Close examination of structural superposition of members across various functional clusters reveals structural variations in regions that not only form the active site pocket but are also involved in interaction with another domain in the same polypeptide or in the oligomer.Structure-based phylogeny of cupins can influence identification of functions of proteins of yet unknown function with cupin fold. This approach can be extended to other proteins with a common fold that show high evolutionary divergence. This approach is expected to have an influence on the function annotation in structural genomics initiatives

    Analysis of conformational variation in macromolecular structural models

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    Experimental conditions or the presence of interacting components can lead to variations in the structural models of macromolecules. However, the role of these factors in conformational selection is often omitted by in silico methods to extract dynamic information from protein structural models. Structures of small peptides, considered building blocks for larger macromolecular structural models, can substantially differ in the context of a larger protein. This limitation is more evident in the case of modeling large multi-subunit macromolecular complexes using structures of the individual protein components. Here we report an analysis of variations in structural models of proteins with high sequence similarity. These models were analyzed for sequence features of the protein, the role of scaffolding segments including interacting proteins or affinity tags and the chemical components in the experimental conditions. Conformational features in these structural models could be rationalized by conformational selection events, perhaps induced by experimental conditions. This analysis was performed on a non-redundant dataset of protein structures from different SCOP classes. The sequence-conformation correlations that we note here suggest additional features that could be incorporated by in silico methods to extract dynamic information from protein structural models

    PeptideMine - A webserver for the design of peptides for protein-peptide binding studies derived from protein-protein interactomes

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    <p>Abstract</p> <p>Background</p> <p>Signal transduction events often involve transient, yet specific, interactions between structurally conserved protein domains and polypeptide sequences in target proteins. The identification and validation of these associating domains is crucial to understand signal transduction pathways that modulate different cellular or developmental processes. Bioinformatics strategies to extract and integrate information from diverse sources have been shown to facilitate the experimental design to understand complex biological events. These methods, primarily based on information from high-throughput experiments, have also led to the identification of new connections thus providing hypothetical models for cellular events. Such models, in turn, provide a framework for directing experimental efforts for validating the predicted molecular rationale for complex cellular processes. In this context, it is envisaged that the rational design of peptides for protein-peptide binding studies could substantially facilitate the experimental strategies to evaluate a predicted interaction. This rational design procedure involves the integration of protein-protein interaction data, gene ontology, physico-chemical calculations, domain-domain interaction data and information on functional sites or critical residues.</p> <p>Results</p> <p>Here we describe an integrated approach called "PeptideMine" for the identification of peptides based on specific functional patterns present in the sequence of an interacting protein. This approach based on sequence searches in the interacting sequence space has been developed into a webserver, which can be used for the identification and analysis of peptides, peptide homologues or functional patterns from the interacting sequence space of a protein. To further facilitate experimental validation, the PeptideMine webserver also provides a list of physico-chemical parameters corresponding to the peptide to determine the feasibility of using the peptide for <it>in vitro </it>biochemical or biophysical studies.</p> <p>Conclusions</p> <p>The strategy described here involves the integration of data and tools to identify potential interacting partners for a protein and design criteria for peptides based on desired biochemical properties. Alongside the search for interacting protein sequences using three different search programs, the server also provides the biochemical characteristics of candidate peptides to prune peptide sequences based on features that are most suited for a given experiment. The PeptideMine server is available at the URL: <url>http://caps.ncbs.res.in/peptidemine</url></p

    Strength and microstructure of mortar with sand substitutes

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    U radu se razmatra čvrstoća i mikrostruktura morta u kojem se kao zamjena za riječni pijesak (RS) koriste drobljeni pijesak (MS) i granitni prah (GP) u raznim udjelima. Za postizanje maksimalne tlačne čvrstoće i vlačne čvrstoće pri cijepanju, optimalni težinski udio GP u RS iznosi 15 %. Svojstva čvrstoće morta koji sadrži MS bolja su od odgovarajućih svojstava mortova RS i GP, bez obzira na vrijeme njege. Za mortove MS i GP provedena je toplinska analiza, mikrostrukturna analiza i mineraloška analiza, a pritom su korišteni postupci TGA, SEM, XRD i FT-IR.The strength and microstructure of mortars incorporating manufactured sand (MS) and various levels of granite powder (GP) as substitutes for river sand (RS) are considered in the paper. The optimum RS substitution by GP is 15 % by mass for the maximum compressive and splitting tensile strength. Strength properties of mortars containing MS are better when compared to RS and GP mortars, irrespective of the curing period. The thermal analysis, microstructural analysis, and mineralogical analysis are conducted on MS and GP mortars using TGA, SEM, XRD and FT-IR techniques

    Rebar properties in sand-substitute mortars after exposure to high temperatures

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    U ovom se radu istražuje utjecaj zagrijavanja, metoda hlađenja i debljine zaštitnog sloja na ponašanje (čvrstoću i duktilnost) rebraste armature promjera 12 mm ugrađene u mort u kojem je riječni pijesak zamijenjen granitnim prahom i proizvedenim pijeskom, pri čemu debljina zaštitnog sloja iznosi 30 i 50 mm. Na temperaturama iznad 500 °C, toplinsko naprezanje uzrokovalo je nasumično ljuskanje zaštitnog sloja, a vlačna ispitivanja upozorila su na smanjenje čvrstoće i povećanje duktilnosti armature pri hlađenju na zraku, dok je suprotna pojava uočena pri gašenju vodom.This study investigates the effects of fire, cooling methods, and cover thickness, on the behaviour (strength and ductility) of 12-mm diameter rebars embedded in mortars with river sand (RS) substitutes such as granite powder and manufactured sand, with 30 and 50 mm cover thickness. Beyond 500°C, thermal stress induced random spalling of mortar cover, and tension test results showed strength decrement and ductility increment of rebars for air cooling, while the vice versa was observed for water quenching

    JWST/NIRCam coronagraph: mask design and fabrication

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    The NIRCam instrument on the James Webb Space Telescope will provide coronagraphic imaging from λ =1-5 μm of high contrast sources such as extrasolar planets and circumstellar disks. A Lyot coronagraph with a variety of circular and wedge-shaped occulting masks and matching Lyot pupil stops will be implemented. The occulters approximate grayscale transmission profiles using halftone binary patterns comprising wavelength-sized metal dots on anti-reflection coated sapphire substrates. The mask patterns are being created in the Micro Devices Laboratory at the Jet Propulsion Laboratory using electron beam lithography. Samples of these occulters have been successfully evaluated in a coronagraphic testbed. In a separate process, the complex apertures that form the Lyot stops will be deposited onto optical wedges. The NIRCam coronagraph flight components are expected to be completed this year

    Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A.

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    Staphylococcus aureus (S. aureus) is an aggressive opportunistic pathogen of prominent virulence and antibiotic resistance. These characteristics are due in part to the accessory gene regulator (agr) quorum-sensing system, which allows for the rapid adaptation of S. aureus to environmental changes and thus promotes virulence and the development of pathogenesis. AgrA is the agr system response regulator that binds to the P2 and P3 promoters and upregulates agr expression. In this study, we reveal that S. aureus AgrA is modified by covalent binding of CoA (CoAlation) in response to oxidative or metabolic stress. The sites of CoAlation were mapped by liquid chromatography tandem mass spectrometry (LC-MS/MS) and revealed that oxidation-sensing Cys199 is modified by CoA. Surface plasmon resonance (SPR) analysis showed an inhibitory effect of CoAlation on the DNA-binding activity, as CoAlated AgrA had significantly lower affinity towards the P2 and P3 promoters than non-CoAlated AgrA. Overall, this study provides novel insights into the mode of transcriptional regulation in S. aureus and further elucidates the link between the quorum-sensing and oxidation-sensing roles of the agr system

    Lysine Deacetylase (KDAC) Regulatory Pathways: an Alternative Approach to Selective Modulation

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    Protein lysine deacetylases (KDACs), including the classic Zn2+-dependent histone deacetylases (HDACs) and the nicotinamide adenine dinucleotide (NAD+)-requiring sirtuins, are enzymes that play critical roles in numerous biological processes, particularly the epigenetic regulation of global gene expression programs in response to internal and external cues. Dysregulation of KDACs is characteristic of several human diseases, including chronic metabolic, neurodegenerative, and cardiovascular diseases and many cancers. This has led to the development of KDAC modulators, two of which (HDAC inhibitors vorinostat and romidepsin) have been approved for the treatment of cutaneous T cell lymphoma. By their nature, existing KDAC modulators are relatively nonspecific, leading to pan-KDAC changes and undesired side effects. Given that KDACs are regulated at many levels, including transcriptional, post-translational, subcellular localization, and through their complexation with other proteins, it should be possible to affect specific KDAC activity through manipulation of endogenous signaling pathways. In this Minireview, we discuss our present knowledge of the cellular controls of KDAC activity and examples of their pharmacologic regulation

    JWST/NIRCam coronagraph: mask design and fabrication

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    The NIRCam instrument on the James Webb Space Telescope will provide coronagraphic imaging from λ =1-5 μm of high contrast sources such as extrasolar planets and circumstellar disks. A Lyot coronagraph with a variety of circular and wedge-shaped occulting masks and matching Lyot pupil stops will be implemented. The occulters approximate grayscale transmission profiles using halftone binary patterns comprising wavelength-sized metal dots on anti-reflection coated sapphire substrates. The mask patterns are being created in the Micro Devices Laboratory at the Jet Propulsion Laboratory using electron beam lithography. Samples of these occulters have been successfully evaluated in a coronagraphic testbed. In a separate process, the complex apertures that form the Lyot stops will be deposited onto optical wedges. The NIRCam coronagraph flight components are expected to be completed this year
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