39 research outputs found

    Giardia Cyst Wall Protein 1 Is a Lectin That Binds to Curled Fibrils of the GalNAc Homopolymer

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    The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique β-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWPLRR) and a C-terminal conserved Cys-rich region (CWPCRR). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (~400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (~1.2 µm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1LRR. In contrast, neither MBP alone nor MBP fused to CWP1CRR bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase. Author SummaryWhile the walls of plants and fungi contain numerous sugar homopolymers (cellulose, chitin, and β-1,3-glucans) and dozens of proteins, the cyst wall of Giardia is relatively simple. The Giardia wall contains a unique homopolymer of β-1,3-linked N-acetylgalactosamine (GalNAc) and at least three cyst wall proteins (CWPs), each of which is composed of Leu-rich repeats and a C-terminal Cys-rich region. The three major discoveries here are: 1) Fibrils of the GalNAc homopolymer are curled and form a lattice that is compressed into a narrow plane by bound protein in intact cyst walls. 2) Leu-rich repeats of CWP1 form a novel lectin domain that is specific for fibrils of the GalNAc homopolymer, which can be isolated by methods used to deproteinate fungal walls. 3) A cyst-specific glycohydrolase is able to degrade deproteinated fibrils of the GalNAc homopolymer. We incorporate these findings into a new curled fiber and lectin model of the intact Giardia cyst wall and a protease and glycohydrolase model of excystation.National Institutes of Health (AI048082, AI44070, GM31318, RR1088

    Derangement in renal & liver function in geriatric population with anaemia - A cross sectional study

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    Background: Across the globe several studies have shown different etiologies of anemia in old age, likely to belief anemia is not a consequence of senescence. Objectives: Primary objective was to estimate prevalence of Renal & Hepatic impairment and secondary objective was to determine any association between Renal or Hepatic impairment with variable degrees of anemia. Methods: This was a cross-sectional descriptive observational study. 278 samples were included of above 60yrs old suffering from Anemia. Prevalence of kidney & liver disease was calculated in percentages. Association between kidney and liver disease with severity of anemia was measured by prevalence ratio. Result: The prevalence of derangement in renal and hepatic function were found 14.1% (95%CI: 10.5,18.9) and 6.1% (95%CI:3.3,8.9) respectively. Prevalence ratio of moderate to severe anemia with impaired renal function in comparison to healthy kidney function is 1.6(95%CI: 1.2,2.2) and this same ratio with deranged hepatic function is 1.7(95%CI:1.1,2.6). Conclusion: The magnitude of kidney and liver disease in our study population was found to be above 10% and 5% respectively, and also have an association with severity of anemia. Hence anemia should always be looked for & renal & hepatic functions need to be monitored in the geriatric population

    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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    Measurement of the W boson polarisation in ttˉt\bar{t} events from pp collisions at s\sqrt{s} = 8 TeV in the lepton + jets channel with ATLAS

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    Charged-particle distributions at low transverse momentum in s=13\sqrt{s} = 13 TeV pppp interactions measured with the ATLAS detector at the LHC

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    Measurement of the bbb\overline{b} dijet cross section in pp collisions at s=7\sqrt{s} = 7 TeV with the ATLAS detector

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    Measurement of jet fragmentation in Pb+Pb and pppp collisions at sNN=2.76\sqrt{{s_\mathrm{NN}}} = 2.76 TeV with the ATLAS detector at the LHC

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    Search for new phenomena in events containing a same-flavour opposite-sign dilepton pair, jets, and large missing transverse momentum in s=\sqrt{s}= 13 pppp collisions with the ATLAS detector

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