46 research outputs found

    Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1

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    Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    How Gintong Alay Won Gold: Policy Evaluation of the Elite Sport Flagship Project under the Marcos Administration, 1978-1981

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    This study made use of the SPLISS (Sport Policy Factors that Lead to International Sporting Success) framework by De Bosscher, et. al. to help determine the key policy factors behind the international medal success of Project: Gintong Alay, the national elite sport development (ESD) program under the Marcos administration. The study focuses elements of elite sports influenced by national policies from the program’s establishment in 1979 up to its first real test in the 1981 Manila SEA Games. Using data from the sports pages of three major newspapers at the time— Bulletin Today, the Philippine Daily Express, and the Times Journal—feature articles in WHO and Philippine Panorama magazines, and various presidential documents (e.g. Executive Orders, Letters of Instruction, Presidential Decrees, etc.), it was concluded that most of Gintong Alay’s medal success can be attributed to three (3) critical factors: 1) the efficient use of resources through the prioritization of sports with a high possibility of medal returns, 2) the creation of an athlete-centric model for national team training, and 3) the continuous exposure of elite athletes to high levels of international competition. It was also concluded that Gintong Alay succeeded despite failing to achieve some of the SPLISS model’s key success factors because of its unique historical context, that being a sports program under an authoritarian regime known for its crony capitalism and love for propaganda/image building

    Play and Propaganda: The Sports of the Ilustrados in Nineteenth-Century Europe

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    The adoption of nineteenth-century European sporting practices was a component in the ilustrados’ creation of a national identity. By highlighting the ilustrados’ participation in modernizing individual sports (e.g., gymnastics, fencing, and pistol shooting), the article shows how the adoption of foreign sports promised these young men from the Spanish Philippines an opportunity to stand on equal footing with their supposed betters. The constant training of the body was treated as a tool to maintain health, a weapon against vices, and an avenue to achieve excellence in a modern cultural space associated with ideals of masculinity and civilization

    Adaptation of Cyanobacteria to the Endolithic Light Spectrum in Hyper-Arid Deserts

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    In hyper-arid deserts, endolithic microbial communities survive in the pore spaces and cracks of rocks, an environment that enhances water retention and filters UV radiation. The rock colonization zone is enriched in far-red light (FRL) and depleted in visible light. This poses a challenge to cyanobacteria, which are the primary producers of endolithic communities. Many species of cyanobacteria are capable of Far-Red-Light Photoacclimation (FaRLiP), a process in which FRL induces the synthesis of specialized chlorophylls and remodeling of the photosynthetic apparatus, providing the ability to grow in FRL. While FaRLiP has been reported in cyanobacteria from various low-light environments, our understanding of light adaptations for endolithic cyanobacteria remains limited. Here, we demonstrated that endolithic Chroococcidiopsis isolates from deserts around the world synthesize chlorophyll f, an FRL-specialized chlorophyll when FRL is the sole light source. The metagenome-assembled genomes of these isolates encoded chlorophyll f synthase and all the genes required to implement the FaRLiP response. We also present evidence of FRL-induced changes to the major light-harvesting complexes of a Chroococcidiopsis isolate. These findings indicate that endolithic cyanobacteria from hyper-arid deserts use FRL photoacclimation as an adaptation to the unique light transmission spectrum of their rocky habitat

    Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection

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    Fil: Villar, Juan Carlos. Department of Medicine, Universidad Autónoma de Bucaramanga; Colombia.Fil: Perez, Juan Guillermo. Fundación Cardioinfantil Instituto de Cardiología, Bogota; Colombia.Fil: Cortes, Olga Lucia. Fundación Cardioinfantil Instituto de Cardiología, Bogota; ColombiaFil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Pepper, Micah. School of Public Health, Boston University, Boston; Estados Unidos.Fil: Marin-Neto, José Antônio. Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto; Brasil.Fil: Guyatt, Gordon H. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton; Canada.Prevention of chronic chagasic cardiomyopathy (CCC) by treating infected populations with trypanocidal therapy (TT) remains a challenge. Despite a renewed enthusiasm for TT, uncertainty regarding its efficacy, concerns about its safety and limited availability remain barriers for a wider use of conventional drugs. We have updated a previous version of this review

    UP-BEAT (Upper Limb Baby Early Action-observation Training): protocol of two parallel randomised controlled trials of action-observation training for typically developing infants and infants with asymmetric brain lesions

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    Introduction: Infants with asymmetric brain lesions are at high risk of developing congenital hemiplegia. Action-observation training (AOT) has been shown to effectively improve upper limb motor function in adults with chronic stroke. AOT is based on action observation, whereby new motor skills can be learnt by observing motor actions. This process is facilitated by the Mirror Neuron System, which matches observed and performed motor actions. This study aims to determine the efficacy of AOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb activity of infants with asymmetric brain lesions
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