473 research outputs found
Automated glycan assembly of <sup>19</sup>F labelled glycan probes enables highâthroughput NMR studies of proteinâglycan interactions
Proteinâglycan interactions mediate important biological processes, including pathogen host invasion and cellular communication. Major challenges to monitoring these low affinity interactions are the required high sensitivity of a biophysical assay and to cover a breath of synthetic wellâdefined structures. Here, we showcase an expedite approach that integrates automated glycan assembly (AGA) of 19 F labelled probes and highâthroughput NMR methods, enabling the study of proteinâglycan interactions. Synthetic Lewis type 2 antigens were screened against seven glycan binding proteins (GBPs), including DCâSIGN and BambL, respectively involved in HIVâ1 and lung infections in immunocompromised patients, confirming the preference for fucosylated glycans (Le x , H type 2, Le y ). Previously unknown glycanâlectin weak interactions were detected, and thermodynamic data were obtained. Enzymatic reactions were monitored in realâtime, delivering kinetic parameters. These results demonstrate the utility of AGA combined with 19 F NMR for the discovery and characterization of glycanâprotein interactions, opening up new perspectives for 19 F labelled complex glycans
The Mass of the Black Hole in LMC X-3
We analyze a large set of new and archival photometric and spectroscopic
observations of LMC X-3 to arrive at a self-consistent dynamical model for the
system. Using echelle spectra obtained with the MIKE instrument on the 6.5m
Magellan Clay telescope and the UVES instrument on the second 8.2m Very Large
Telescope we find a velocity semiamplitude for the secondary star of
km s, where the uncertainty includes an estimate of
the systematic error caused by X-ray heating. Using the spectra, we also find a
projected rotational velocity of km s.
From an analysis of archival and light curves as well as new and
light curves from the SMARTS 1.3m telescope, we find an inclination of
for models that do not include X-ray heating and an
inclination of for models that incorporate X-ray
heating. Adopting the latter inclination measurement, we find masses of
and for the companion star
and the black hole, respectively. We briefly compare our results with earlier
work and discuss some of their implications.Comment: 31 pages, 15 figures, substantial revisions, ApJ, accepte
PSICIC: Noise and Asymmetry in Bacterial Division Revealed by Computational Image Analysis at Sub-Pixel Resolution
Live-cell imaging by light microscopy has demonstrated that all cells are spatially and temporally organized. Quantitative, computational image analysis is an important part of cellular imaging, providing both enriched information about individual cell properties and the ability to analyze large datasets. However, such studies are often limited by the small size and variable shape of objects of interest. Here, we address two outstanding problems in bacterial cell division by developing a generally applicable, standardized, and modular software suite termed Projected System of Internal Coordinates from Interpolated Contours (PSICIC) that solves common problems in image quantitation. PSICIC implements interpolated-contour analysis for accurate and precise determination of cell borders and automatically generates internal coordinate systems that are superimposable regardless of cell geometry. We have used PSICIC to establish that the cell-fate determinant, SpoIIE, is asymmetrically localized during Bacillus subtilis sporulation, thereby demonstrating the ability of PSICIC to discern protein localization features at sub-pixel scales. We also used PSICIC to examine the accuracy of cell division in Esherichia coli and found a new role for the Min system in regulating division-site placement throughout the cell length, but only prior to the initiation of cell constriction. These results extend our understanding of the regulation of both asymmetry and accuracy in bacterial division while demonstrating the general applicability of PSICIC as a computational approach for quantitative, high-throughput analysis of cellular images
Reverse-Design toward Optimized Labeled Chemical Probes â Examples from the Endocannabinoid System
Labeled chemical probes are of utmost importance to bring drugs from the laboratory through the clinic and ultimately to market. They support and impact all research and discovery phases: target verification and validation; assay development; lead optimization; and biomarker engagement in the context of preclinical studies and human trials. Probes should display high potency and selectivity as well as fulfill specific criteria in connection with absorption, distribution, metabolism, excretion and toxicology (ADMET) profile. Progress in fields such as imaging and proteomics increased the need for specialized probes to support drug discovery. Labeled probes carrying an additional reporter group are valuable tools to meet specific application requirements, but pose significant challenges in design and construction. In the reverse-design approach, small molecules previously optimized in medicinal chemistry programs form the basis for the generation of such high-quality probes. We discuss the reverse design concept for the generation of labeled probes targeting the endocannabinoid system (ECS), a complex lipid signaling network that plays a key role in many human health and disease conditions. The examples highlighted include diverse reporter units for a range of applications. In several cases the reported probes were the product of mutually rewarding and highly cross-fertilizing collaborations among academic and industry research programs, a strategy that can serve as a blueprint for future probe generation efforts
Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: A case-control study
Objective: To assess the role of foot dermatomycosis ( tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. Methods: A case-control study, including 243 patients ( cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (+/-5 years), hospital and admission date (+/-2 months). Results: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. Conclusions: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy. Copyright (C) 2004 S. Karger AG, Basel
Bioinformatics advances in saliva diagnostics
There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance
basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval,
integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart
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