Yeast Mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages

We have examined the effects of various mannans, glycoproteins, oligosaccharides, monosaccharides, and sugar phosphates on the binding and phagocytosis of yeast cell walls (zymosan) by mouse peritoneal macrophages. A phosphonomannan (PO(4):mannose ratio = 1:8:6) from kloeckera brevis was the most potent inhibitor tested; it inhibited binding and phagocytosis by 50 percent at concentrations of approximately 3-5 μg/ml and 10 μg/ml, respectively. Removal of the phosphate from this mannan by mild acid and alkaline phosphatase treatment did not appreciably reduce its capacity to inhibit zymosan phagocytosis. The mannan from saccharomyces cerevisiae mutant LB301 inhibits phagocytosis by 50 percent at 0.3 mg/ml, and a neutral exocellular glucomannan from pichia pinus inhibited phagocytosis by 50 percent at 1 mg/ml. Cell wall mannans from wild type S. cervisiae X2180, its mnn2 mutant which contains mannan with predominantly 1(arrow)6- linked mannose residues, yeast exocellular mannans and O-phosphonomannans were less efficient inhibitors requiring concentrations of 1-5 mg/ml to achieve 50 percent reduction in phagocytosis. Horseradish peroxidase, which contains high-mannose type oligosaccharides, was also inhibitory. Mannan is a specific inhibitor of zymosan binding and phagocytosis. The binding and ingestion of zymosan but not of IgG- or complement-coated erythrocytes can be obliterated by plating macrophages on substrates coated with poly-L-lysin (PLL)-mannan. Zymosan uptake was completely abolished by trypsin treatment of the macrophages and reduced by 50-60 percent in the presence of 10 mM EGTA. Pretreatment of the macrophages with chloroquine inhibited zymosan binding and ingestion. These results support the proposal that the macrophage mannose/N-acetylglucosamine receptor (P. Stahl, J.S. Rodman, M.J. Miller, and P.H. Schlesinger, 1978, Proc. Natl. Acad. Sci. U.S.A. 75:1399-1403, mediates the phagocytosis of zymosan particles

CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection.

Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target a host cell surface molecule, and successful HIV-1 entry blockade by this C-C chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We hypothesized that MVC intensification impacts immunization responses, T-cell phenotype, function and delayed type hypersensitivity (DTH) in HIV-1+ subjects. A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to suppressive antiretroviral therapy in HIV-1+ persons was performed. Subjects received DTH tests, intramuscular tetanus, meningococcal and oral cholera immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced meningococcal neo-immunization, blunted cholera response and expedited lymphoproliferation to tetanus boost, without affecting recall humoral response. Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased. Activated CD4+ CD38+ human leukocyte antigen (HLA)-DR+ T-cells declined, and costimulation shifted to coinhibition. DTH was unchanged. Maraviroc intensification, through antagonism of the cell surface molecule CCR5, favorably influences immune profiles of HIV-1+ patients, supporting its immunomodulatory use in HIV-1 infection and potentially in other immunologically relevant settings

NUTRItion and CLIMate (NUTRICLIM): investigating the relationship between climate variables and childhood malnutrition through agriculture, an exploratory study in Burkina Faso

Malnutrition remains a leading cause of death in children in low- and middle-income countries; this will be aggravated by climate change. Annually, 6.9 million deaths of children under 5 were attributable directly or indirectly to malnutrition. Although these figures have recently decreased, evidence shows that a world with a medium climate (local warming up to 3–4 °C) will create an additional 25.2 million malnourished children. This proof of concept study explores the relationships between childhood malnutrition (more specifically stunting), regional agricultural yields, and climate variable through the use of remote sensing (RS) satellite imaging along with algorithms to predict the effect of climate variability on agricultural yields and on malnutrition of children under 5. The success of this proof of purpose study, NUTRItion and CLIMate (NUTRICLIM), should encourage researchers to apply both concept and tools to study of the link between weather variability, crop yield, and malnutrition on a larger scale. It would also allow for linking such micro-level data to climate models and address the challenge of projecting the additional impact of childhood malnutrition from climate change to various policy relevant time horizons

GWASdb v2: an update database for human genetic variants identified by genome-wide association studies

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Off-grid solar photovoltaic systems for rural electrification and emissions mitigation in India

Over one billion people lack access to electricity and many of them in rural areas far from existing infrastructure. Off-grid systems can provide an alternative to extending the grid network and using renewable energy, for example solar photovoltaics (PV) and battery storage, can mitigate greenhouse gas emissions from electricity that would otherwise come from fossil fuel sources. This paper presents a model capable of comparing several mature and emerging PV technologies for rural electrification with diesel generation and grid extension for locations in India in terms of both the levelised cost and lifecycle emissions intensity of electricity. The levelised cost of used electricity, ranging from $0.46–1.20/kWh, and greenhouse gas emissions are highly dependent on the PV technology chosen, with battery storage contributing significantly to both metrics. The conditions under which PV and storage becomes more favourable than grid extension are calculated and hybrid systems of PV, storage and diesel generation are evaluated. Analysis of expected price evolutions suggest that the most cost-effective hybrid systems will be dominated by PV generation around 2018

Simulation-based analysis of micro-robots swimming at the center and near the wall of circular mini-channels

Swimming micro robots have great potential in biomedical applications such as targeted drug delivery, medical diagnosis, and destroying blood clots in arteries. Inspired by swimming micro organisms, micro robots can move in biofluids with helical tails attached to their bodies. In order to design and navigate micro robots, hydrodynamic characteristics of the flow field must be understood well. This work presents computational fluid dynamics (CFD) modeling and analysis of the flow due to the motion of micro robots that consist of magnetic heads and helical tails inside fluid-filled channels akin to bodily conduits; special emphasis is on the effects of the radial position of the robot. Time-averaged velocities, forces, torques, and efficiency of the micro robots placed in the channels are analyzed as functions of rotation frequency, helical pitch (wavelength) and helical radius (amplitude) of the tail. Results indicate that robots move faster and more efficiently near the wall than at the center of the channel. Forces acting on micro robots are asymmetrical due to the chirality of the robot’s tail and its motion. Moreover, robots placed near the wall have a different flow pattern around the head when compared to in-center and unbounded swimmers. According to simulation results, time-averaged for-ward velocity of the robot agrees well with the experimental values measured previously for a robot with almost the same dimensions

Physical mapping integrated with syntenic analysis to characterize the gene space of the long arm of wheat chromosome 1A

Background: Bread wheat (Triticum aestivum L.) is one of the most important crops worldwide and its production faces pressing challenges, the solution of which demands genome information. However, the large, highly repetitive hexaploid wheat genome has been considered intractable to standard sequencing approaches. Therefore the International Wheat Genome Sequencing Consortium (IWGSC) proposes to map and sequence the genome on a chromosome-by-chromosome basis. Methodology/Principal Findings: We have constructed a physical map of the long arm of bread wheat chromosome 1A using chromosome-specific BAC libraries by High Information Content Fingerprinting (HICF). Two alternative methods (FPC and LTC) were used to assemble the fingerprints into a high-resolution physical map of the chromosome arm. A total of 365 molecular markers were added to the map, in addition to 1122 putative unique transcripts that were identified by microarray hybridization. The final map consists of 1180 FPC based or 583 LTC based contigs. Conclusions/Significance: The physical map presented here marks an important step forward in mapping of hexaploid bread wheat. The map is orders of magnitude more detailed than previously available maps of this chromosome, and the assignment of over a thousand putative expressed gene sequences to specific map locations will greatly assist future functional studies. This map will be an essential tool for future sequencing of and positional cloning within chromosome 1A