337 research outputs found

    High Precision GPS Aided In-pipe Distance Calibration For Satellite Image-based Pipeline Mapping

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    Asset management and pipe condition assessment (CA) activities in the water industry usually require locating buried pipes accurately to minimise inspection and maintenance costs. A typical challenge in practice is locating an anomaly detected by an in-pipe inspection tool from aboveground in order to dig up a pipe for replacement. Accumulated in-pipe errors over longer distances in particular can easily lead to selecting the wrong pipe section for further investigation or exhumation. In fact, some in-pipe CA providers suggest utility personnel dig up a number of sections of pipe around the suggested location so as to ensure finding the target section. In this paper we propose a mechanism to accurately correlate a 3D pipeline profile built from GPS surveying results of aboveground pipeline features with in-pipe chainage distances, so as to establish an accurate link between above-ground GPS coordinates and inpipe distance measurements. This approach naturally characterises and corrects for some of the most prominent in-pipe chainage measurement errors that can lead to uncertainties about the reported location of a buried pipeline from above-ground. The detailed pipeline information can then be projected onto satellite imagery as an accurate easy-to-understand reference for efficient decision making

    Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

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    Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

    Bacterial Porin Disrupts Mitochondrial Membrane Potential and Sensitizes Host Cells to Apoptosis

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    The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (Delta psi(m)). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of Delta psi(m). The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce Delta psi(m) loss and apoptosis, demonstrating that dissipation of Delta psi(m) is a requirement for cell death caused by neisserial infection

    Revealing mammalian evolutionary relationships by comparative analysis of gene clusters

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    Many software tools for comparative analysis of genomic sequence data have been released in recent decades. Despite this, it remains challenging to determine evolutionary relationships in gene clusters due to their complex histories involving duplications, deletions, inversions, and conversions. One concept describing these relationships is orthology. Orthologs derive from a common ancestor by speciation, in contrast to paralogs, which derive from duplication. Discriminating orthologs from paralogs is a necessary step in most multispecies sequence analyses, but doing so accurately is impeded by the occurrence of gene conversion events. We propose a refined method of orthology assignment based on two paradigms for interpreting its definition: by genomic context or by sequence content. X-orthology (based on context) traces orthology resulting from speciation and duplication only, while N-orthology (based on content) includes the influence of conversion events

    Evaluation of Hepatoprotective Effect of Leaves of Cassia sophera Linn.

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    In the present study, the hepatoprotective activity of ethanolic extracts of Cassia sophera Linn. leaves was evaluated against carbon-tetrachloride- (CCl4-) induced hepatic damage in rats. The extracts at doses of 200 and 400 mg/kg were administered orally once daily. The hepatoprotection was assessed in terms of reduction in histological damage, changes in serum enzymes, serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (ALP), total bilirubin, and total protein levels. The substantially elevated serum enzymatic levels of AST, ALT, ALP, and total bilirubin were restored towards the normalization significantly by the extracts. The decreased serum total protein level was significantly normalized. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that Cassia sophera leaves have potent hepatoprotective action against carbon tetrachloride-induced hepatic damage in rats. This study suggests that possible activity may be due to the presence of flavonoids in the extracts

    Local diagnostic reference levels for skeletal surveys in suspected physical child abuse

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    Introduction: The purpose was to determine if an age based, local diagnostic reference level for paediatric skeletal surveys could be established using retrospective data. Methods: All children below two years of age referred for a primary skeletal survey as a result of suspected physical abuse during 2017 or 2018 (n=45) were retrospectively included from a large Danish university hospital . The skeletal survey protocol included a total of 33 images. Dose Area Product (DAP) and acquisition parameters for all images were recorded from the Picture Archival and Communication System (PACS) and effective dose was estimated. The 75th percentile for DAP was considered as the diagnostic reference level (DRL). Results: The 75th percentile for DAP was 314 mGy*cm2, 520 mGy*cm2 and 779 mGy*cm2 for children <1 month, 1-11 months and 12<24 months of age respectively. However, only the age group 1-11 months had a sufficient number of children (n=27) to establish a local DRL. Thus, for the other groups the DAP result must be interpreted with caution. Effective dose was 0.19, 0.26 and 0.18 mSv for children <1, 1-11 months and 12<24 months of age respectively. Conclusion: For children between 1 and 11 months of age, a local diagnostic reference level of 520 mGy*cm2 was determined. This may be used as an initial benchmark for primary skeletal surveys as a result of suspected physical abuse for comparison and future discussion.acceptedVersio

    Evaluation of hepatoprotective and antioxidant activity of Ichnocarpus frutescens (Linn.) R.Br. on paracetamol-induced hepatotoxicity in rats

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    Purpose: The entire plant including the flowers, of Ichnocarpus frutescens R.Br. (Apocynaceae) has been used for the treatment of cancer, skin infections, diabetes and liver disorder. The present study is aimed at evaluating the hepatoprotective effect of chloroform and methanol extract (CEIF and MEIF) of whole plant of I. frutescens (Linns) by paracetamol-induced liver damage in rats. Methods: The chloroform and methanolic extracts of I. frutescens (CEIF and MEIF) were studied for their hepatoprotective and antioxidant effects on paracetamol (750mg/kg) induced acute liver damage on Wistar albino rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin and total protein. Further, the effects of both extracts on lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were estimated. Results: CEIF and MEIF at a dose level of 250mg/kg and 500mg/kg produce significant (

    Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children

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    T cell responses against liver stage Plasmodium help protect against reinfection, but the antigens and epitopes targeted by these T cells are largely unknown. This knowledge gap has impeded mechanistic studies to identify the effector functions most critical for protection. We performed a bioinformatic analysis of gene expression datasets to identify plasmodial genes that are highly and selectively expressed during liver stage infection and predict epitopes within them likely to bind MHC-II molecules prevalent in Uganda. We then tested their recognition by malaria-exposed Ugandan children. In over two-thirds of the children, we detected a peripheral blood CD4+ T cell response to one or more antigens. The most highly targeted antigen, LISP1, contained several epitopes, including one that was promiscuously presented and recognized by most participants. These novel liver stage P. falciparum epitopes should be explored as potential vaccine targets and will facilitate the development of tools to interrogate antimalarial immunity at the single-cell level and inform future vaccine development efforts

    Proteomic analysis identifies proteins that continue to grow hepatic stem-like cells without differentiation

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    To understand the molecular mechanism underlying vigorous proliferative activity of hepatic stem-like (HSL) cells, we performed two-dimensional electrophoresis to identify the proteins statistically more abundant in rapidly growing undifferentiated HSL cells than in sodium butyrate-treated differentiated HSL cells. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry and Mascot search identified 6 proteins including prohibitin, vimentin, ezrin, annexin A3, acidic ribosomal phosphoprotein P0 and Grp75. Prohibitin and vimentin control the mitogen-activated protein (MAP) kinase pathway. Ezrin is phosphorylated by various protein-tyrosine kinases and modulates interactions between cytoskeletal and membrane proteins. Annexin A3 has a role in DNA synthesis. Acidic ribosomal phosphoprotein P0 and Grp75 play in protein synthesis. These results suggest that the proteins related to the MAP kinase cascade had some role in continuous proliferation of HSL cells without differentiation

    KIR gene content diversity in four Iranian populations

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    Killer cell immunoglobulin-like receptors (KIR) regulate natural killer cell response against infection and malignancy. KIR genes are variable in the number and type, thereby discriminating individuals and populations. Herein, we analyzed the KIR gene content diversity in four native populations of Iran. The KIR genomic diversity was comparable between Bakhtiari and Persian and displayed a balance of A and B KIR haplotypes, a trend reported in Caucasian and African populations. The KIR gene content profiles of Arab and Azeri were comparable and displayed a preponderance of B haplotypes, a scenario reported in the natives of America, India, and Australia. A majority of the B haplotype carriers of Azeri and Arab had a centromeric gene-cluster (KIR2DS2-2DL2-2DS3-2DL5). Remarkably, this cluster was totally absent from the American natives but occurred at highest frequencies in the natives of India and Australia in combination with another gene cluster at the telomeric region (KIR3DS1-2DL5-2DS5-2DS1). Therefore, despite having similar frequencies of B haplotypes, the occurrence of B haplotype-specific KIR genes, such as 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3, and 2DS5 in Azeri and Arab were substantially different from the natives of America, India, and Australia. In conclusion, each Iranian population exhibits distinct KIR gene content diversity, and the Indo-European KIR genetic signatures of the Iranians concur with geographic proximity, linguistic affinity, and human migrations
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