161 research outputs found

    Preservation of York Minster historic limestone by hydrophobic surface coatings

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    Magnesian limestone is a key construction component of many historic buildings that is under constant attack from environmental pollutants notably by oxides of sulfur via acid rain, particulate matter sulfate and gaseous SO 2 emissions. Hydrophobic surface coatings offer a potential route to protect existing stonework in cultural heritage sites, however, many available coatings act by blocking the stone microstructure, preventing it from 'breathing' and promoting mould growth and salt efflorescence. Here we report on a conformal surface modification method using self-assembled monolayers of naturally sourced free fatty acids combined with sub-monolayer fluorinated alkyl silanes to generate hydrophobic (HP) and super hydrophobic (SHP) coatings on calcite. We demonstrate the efficacy of these HP and SHP surface coatings for increasing limestone resistance to sulfation, and thus retarding gypsum formation under SO/H O and model acid rain environments. SHP treatment of 19th century stone from York Minster suppresses sulfuric acid permeation

    Identification of a myometrial molecular profile for dystocic labor

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    <p>Abstract</p> <p>Background</p> <p>The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.</p> <p>Methods</p> <p>Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR.</p> <p>Results</p> <p>Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3</p> <p>Conclusion</p> <p>These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.</p

    Cytotoxic isolates of Helicobacter pylori from Peptic Ulcer Diseases decrease K(+)-dependent ATPase Activity in HeLa cells

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    BACKGROUND: Helicobacter pylori is a Gram negative bacterium that plays a central role in the etiology of chronic gastritis and peptic ulcer diseases. However, not all H. pylori positive cases develop advanced disease. This discriminatory behavior has been attributed to the difference in virulence of the bacteria. Among all virulence factors, cytotoxin released by H. pylori is the most important factor. In this work, we studied variation in H. pylori isolates from Indian dyspeptic patients on the basis of cytotoxin production and associated changes in K(+)-dependent ATPase (one of its targets) enzyme activity in HeLa cells. METHODS: The patients were retrospectively grouped on the basis of endoscopic and histopathological observation as having gastritis or peptic ulcer. The HeLa cells were incubated with the broth culture filtrates (BCFs) of H. pylori isolates from patients of both groups and observed for the cytopathic effects: morphological changes and viability. In addition, the K(+)-dependent ATPase activity was measured in HeLa cells extracts. RESULTS: The cytotoxin production was observed in 3/7 (gastritis) and 4/4 (peptic ulcer) H. pylori isolates. The BCFs of cytotoxin producing H. pylori strains reduced the ATPase activity of HeLa cells to 40% of that measured with non-cytotoxin producing H. pylori strains (1.33 μmole Pi/mg protein and 3.36 μmole Pi/mg protein, respectively, p < 0.05). The decreased activity of ATPase enzyme or the release of cytotoxin also correlated with the increased pathogenicity indices of the patients. CONCLUSIONS: Our results suggest that the isolation of cytotoxic H. pylori is more common in severe form of acid peptic diseases (peptic ulcer) than in gastritis patients from India. Also the cytotoxin released by H. pylori impairs the ion-transporting ATPase and is a measure of cytotoxicity

    Spatial Clustering and Risk Factors for Malaria Infections and Marker of Recent Exposure to Plasmodium falciparum from a Household Survey in Artibonite, Haiti.

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    Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions

    HCMV Targets the Metabolic Stress Response through Activation of AMPK Whose Activity Is Important for Viral Replication

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    Human Cytomegalovirus (HCMV) infection induces several metabolic activities that have been found to be important for viral replication. The cellular AMP-activated protein kinase (AMPK) is a metabolic stress response kinase that regulates both energy-producing catabolic processes and energy-consuming anabolic processes. Here we explore the role AMPK plays in generating an environment conducive to HCMV replication. We find that HCMV infection induces AMPK activity, resulting in the phosphorylation and increased abundance of several targets downstream of activated AMPK. Pharmacological and RNA-based inhibition of AMPK blocked the glycolytic activation induced by HCMV-infection, but had little impact on the glycolytic pathway of uninfected cells. Furthermore, inhibition of AMPK severely attenuated HCMV replication suggesting that AMPK is an important cellular factor for HCMV replication. Inhibition of AMPK attenuated early and late gene expression as well as viral DNA synthesis, but had no detectable impact on immediate-early gene expression, suggesting that AMPK activity is important at the immediate early to early transition of viral gene expression. Lastly, we find that inhibition of the Ca2+-calmodulin-dependent kinase kinase (CaMKK), a kinase known to activate AMPK, blocks HCMV-mediated AMPK activation. The combined data suggest a model in which HCMV activates AMPK through CaMKK, and depends on their activation for high titer replication, likely through induction of a metabolic environment conducive to viral replication

    The Management of Disclosure in Children’s Accounts of Domestic Violence: Practices of Telling and Not Telling

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    Children and young people who experience domestic violence are often represented as passive witnesses, too vulnerable to tell the stories of their own lives. This article reports on findings from a 2 year European research project (Understanding Agency and Resistance Strategies, UNARS) with children and young people in Greece, Italy, Spain and the UK, who had experienced domestic violence. It explores children and young people’s understandings of their own capacity to reflect on and disclose their experiences Extracts from individual interviews with 107 children and young people (age 8–18) were analysed. Three themes are presented, that illustrate children and young people’s strategies for managing disclosure: (1) “Being silenced or choosing silence?”, explores children and young people’s practices of self-silencing; (2) “Managing disclosures: Finding ways to tell” outlines how children and young people value self-expression, and the strategies they use to disclose safely; and in (3) “Speaking with many voices” considers how children and young people’s accounts of their experiences are constituted relationally, and are often polyvocal. The article concludes that children and young people can be articulate, strategic and reflexive communicators, and that good support for families struggling with domestic violence must enable space for children and young people’s voice to be heard. This is possible only in an integrated framework able to encompass multiple layers and perspectives, rather than privileging the adult point of view. Practitioners who work with families affected by domestic violence need to recognize that children and young people are able to reflect on and speak about their experiences. This requires that attention is paid to the complexity of children and young people’s communication practices, and the relational context of those communications

    The regulatory role of long-term depression in juvenile and adult mouse ocular dominance plasticity

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    The study of experience-dependent ocular dominance (OD) plasticity has greatly contributed to the understanding of visual development. During the critical period, preventing input from one eye results in a significant impairment of vision, and loss of cortical responsivity via the deprived eye. Residual ocular dominance plasticity has recently been observed in adulthood. Accumulating evidence suggests that OD plasticity involves N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD). Here we report that the administration of a selective LTD antagonist prevented the ocular dominance shift during the critical period. The NMDAR co-agonist D-serine facilitated adult visual cortical LTD and the OD shift in short-term monocularly deprived (MD) adult mice. When combined with reverse suture, D-serine proved effective in restoring a contralaterally-dominated visual input pattern in long-term MD mice. This work suggests LTD as a key mechanism in both juvenile and adult ocular dominance plasticity, and D-serine as a potential therapeutic in human amblyopic subjects

    Detection and Alignment of 3D Domain Swapping Proteins Using Angle-Distance Image-Based Secondary Structural Matching Techniques

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    This work presents a novel detection method for three-dimensional domain swapping (DS), a mechanism for forming protein quaternary structures that can be visualized as if monomers had “opened” their “closed” structures and exchanged the opened portion to form intertwined oligomers. Since the first report of DS in the mid 1990s, an increasing number of identified cases has led to the postulation that DS might occur in a protein with an unconstrained terminus under appropriate conditions. DS may play important roles in the molecular evolution and functional regulation of proteins and the formation of depositions in Alzheimer's and prion diseases. Moreover, it is promising for designing auto-assembling biomaterials. Despite the increasing interest in DS, related bioinformatics methods are rarely available. Owing to a dramatic conformational difference between the monomeric/closed and oligomeric/open forms, conventional structural comparison methods are inadequate for detecting DS. Hence, there is also a lack of comprehensive datasets for studying DS. Based on angle-distance (A-D) image transformations of secondary structural elements (SSEs), specific patterns within A-D images can be recognized and classified for structural similarities. In this work, a matching algorithm to extract corresponding SSE pairs from A-D images and a novel DS score have been designed and demonstrated to be applicable to the detection of DS relationships. The Matthews correlation coefficient (MCC) and sensitivity of the proposed DS-detecting method were higher than 0.81 even when the sequence identities of the proteins examined were lower than 10%. On average, the alignment percentage and root-mean-square distance (RMSD) computed by the proposed method were 90% and 1.8Å for a set of 1,211 DS-related pairs of proteins. The performances of structural alignments remain high and stable for DS-related homologs with less than 10% sequence identities. In addition, the quality of its hinge loop determination is comparable to that of manual inspection. This method has been implemented as a web-based tool, which requires two protein structures as the input and then the type and/or existence of DS relationships between the input structures are determined according to the A-D image-based structural alignments and the DS score. The proposed method is expected to trigger large-scale studies of this interesting structural phenomenon and facilitate related applications
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