4,012 research outputs found

    Holey goats: multiple cases of supratrochlear foramina in the humerus of caprines from the New Kingdom pharaonic town of Amara West, northern Sudan

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    Supratrochlear foramina (STF) were recorded in fifteen per cent of goat and sheep/goat humeri from the New Kingdom pharaonic town of Amara West, in modern northern Sudan. To the authors’ knowledge, this trait has never before been reported in the published literature for goats or sheep, whether from archaeological or modern contexts. The aim of this work is twofold: to contribute to the growing corpus of studies addressing the incidence and aetiology of STF, and to raise awareness for their possible presence in caprines, thus encouraging their identification and recording in archaeological assemblages

    Women as moral pioneers? Experiences of first trimester antenatal screening

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    Copyright @ 2005 Elsevier Ltd.The implementation of innovative medical technologies can raise unprecedented ethical, legal and social dilemmas. This is particularly so in the area of antenatal screening, which is dominated by the language of risk and probabilities. Second trimester serum screening for Down's syndrome and neural tube defects has a well-established place in antenatal care. Increasingly, first trimester screening with biochemical and ultrasound markers is being proposed as advance on this, yielding higher detection rates of Down's syndrome at an earlier gestational age. This article explores the experiences of 14 women offered innovative first trimester screening, which takes place within the context of a detailed ultrasound scan. The study is set within the UK, where recent policy changes mean that the offer of screening for fetal anomalies, particularly Down's syndrome, will become a routine part of antenatal care and offered to all pregnant women. This paper focuses on the significance of the scan in first trimester screening, and some of the potential dilemmas for women that can result from this. It then discusses the ways in which women made their decisions about screening, in particular, their work as ‘moral pioneers’. We found that the part played by the ultrasound scan in first trimester screening, particularly in relation to the higher-quality images now being obtained, has the potential to introduce new and novel ethical dilemmas for pregnant women. Although concerns have been raised about pregnant women viewing ultrasound scans as benign, many of the women reported having thought carefully through their own moral beliefs and values prior to screening. It seems that whatever other implications they may have, first trimester screening technologies will continue the tradition of pregnant women acting as ‘moral pioneers’ in increasingly complex settings.ESRC/MRC Innovative Health Technologies Programme for funding the project (grant no: L218252042). CW acknowledges the support of The Wellcome Trust Biomedical Ethics Programme in funding her postdoctoral fellowship, which enabled her to work on this project

    Ringtail Blues

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    Ringtailed lemurs playing music for other animalshttps://scholarsjunction.msstate.edu/cht-sheet-music/13373/thumbnail.jp

    Characterization of Mycobacterium tuberculosis Mycolic Acids by Multiple-Stage Linear Ion-Trap Mass Spectrometry

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    Mycobacterium tuberculosis (Mtb) cells are known to synthesize very long chain (C60-90) structurally complex mycolic acids with various functional groups. In this study, we applied linear ion-trap (LIT) multiple-stage mass spectrometry (MSn), combined with high-resolution mass spectrometry to study the mechanisms underlying the fragmentation processes of mycolic acid standards desorbed as lithiated adduct ions by ESI. This is followed by structural characterization of a Mtb mycolic acid family (Bovine strain). Using the insight fragmentation processes gained from the study, we are able to achieve a near complete characterization of the whole mycolic acid family, revealing the identity of the α-alkyl chain, the location of the functional groups including methyl, methoxy, and keto groups along the meroaldehyde chain in each lipid species. This study showcased the power of LIT MSn toward structural determination of complex lipids in a mixture, which would be otherwise very difficult to define using other analytical techniques

    Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

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    Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis. Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Computational design-of-experiment unveils the conformational reaction coordinate of GH125 α-mannosidases

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    Conformational analysis of enzyme-catalyzed mannoside hydrolysis has revealed two predominant conformational itineraries through B 2,5 or 3H 4 transitionstate (TS) conformations. A prominent unassigned catalytic itinerary is that of exo-1,6-α-mannosidases belonging to CAZy family 125. A published complex of Clostridium perfringens GH125 enzyme with a nonhydrolyzable 1,6-α-thiomannoside substrate mimic bound across the active site revealed an undistorted 4 C 1 conformation and provided no insight into the catalytic pathway of this enzyme. We show through a purely computational approach (QM/MM metadynamics) that sulfur-for-oxygen substitution in the glycosidic linkage fundamentally alters the energetically accessible conformational space of a thiomannoside when bound within the GH12S active site. Modeling of the conformational free energy landscape (FEL) of a thioglycoside strongly favors a mechanistically uninformative 4 C 1 conformation within the GH125 enzyme active site, but the FEL of corresponding O-glycoside substrate reveals a preference for a Michaelis complex in an oS 2 conformation (consistent with catalysis through a B 2,5 TS). This prediction was tested experimentally by determination of the 3D X-ray structure of the pseudo-Michaelis complex of an inactive (D220N) variant of C. perfringens GH125 enzyme in complex with 1,6-α-mannobiose. This complex revealed unambiguous distortion of the -1 subsite mannoside to an oS 2 conformation, matching that predicted by theory and supporting an oS 2 → B 2,5 → 1S 5 conformational itinerary for GH125 α-mannosidases. This work highlights the power of the QM/MM approach and identified shortcomings in the use of nonhydrolyzable substrate analogues for conformational analysis of enzymebound species
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