489 research outputs found

    Potential of Equatorial Atlantic Variability to Enhance El Nino Prediction

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    Extraordinarily strong El Niño events, such as those of 1982/83 and 1997/98, have been poorly predicted by operational seasonal forecasts made before boreal spring, despite significant advances in understanding, improved models, and enhanced observational networks. The Equatorial Atlantic Zonal Mode – a phenomenon similar to El Niño but much weaker and peaking in boreal summer – impacts winds over the Pacific, and hence affects El Niño, and also potentially its predictability. Here we use a climate model to perform a suite of seasonal predictions with and without SST in the Atlantic restored to observations. We show for the first time that knowledge of Equatorial Atlantic sea surface temperature (SST) significantly improves the prediction across boreal spring of major El Niño events and also weaker variability. This is because Atlantic SST acts to modulate El Niño variability, rather than triggering events. Our results suggest that better prediction of major El Niño events might be achieved through model improvement in the Equatorial Atlantic

    Increased muscle tension and reduced elasticity of affected muscles in recent-onset Graves' disease caused primarily by active muscle contraction

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    In 3 patients with Graves' disease of recent onset, length-tension diagrams were made during surgery for squint under eyedrop anesthesia. The affected muscles were found to be very stiff when the other eye looked straight ahead. It was expected that these stiff muscles would be able to shorten to some extent but would be unable to lengthen, due to fibrosis of the muscle. We found that the affected muscles did not shorten very much when the other eye looked into the field of action of the muscle. Unexpectedly however, they lengthenend considerably when the other eye looked out of the field of action of the muscle. This finding implies that the raised muscle tension and reduced elasticity of affected muscles in these cases of Graves' disease of recent onset were primarily caused by active muscle contraction, not by fibrosis

    Phenotype-genotype association grid: a convenient method for summarizing multiple association analyses

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    BACKGROUND: High-throughput genotyping generates vast amounts of data for analysis; results can be difficult to summarize succinctly. A single project may involve genotyping many genes with multiple variants per gene and analyzing each variant in relation to numerous phenotypes, using several genetic models and population subgroups. Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association. RESULTS: To facilitate visual display and summary of large numbers of association tests of genetic loci with multiple phenotypes, we developed a Phenotype-Genotype Association (PGA) grid display. A database-backed web server was used to create PGA grids from phenotypic and genotypic data (sample sizes, means and standard errors, P-value for association). HTML pages were generated using Tcl scripts on an AOLserver platform, using an Oracle database, and the ArsDigita Community System web toolkit. The grids are interactive and permit display of summary data for individual cells by a mouse click (i.e. least squares means for a given SNP and phenotype, specified genetic model and study sample). PGA grids can be used to visually summarize results of individual SNP associations, gene-environment associations, or haplotype associations. CONCLUSION: The PGA grid, which permits interactive exploration of large numbers of association test results, can serve as an easily adapted common and useful display format for large-scale genetic studies. Doing so would reduce the problem of publication bias, and would simplify the task of summarizing large-scale association studies

    Neuronal deletion of the circadian clock gene Bmal1 induces cell-autonomous dopaminergic neurodegeneration

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    Circadian rhythm dysfunction is a hallmark of Parkinson disease (PD), and diminished expression of the core clock gene Bmal1 has been described in patients with PD. BMAL1 is required for core circadian clock function but also serves nonrhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and it can exacerbate dopaminergic neurodegeneration in response to the toxin MPTP. Here we examined the effect of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, postnatal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase+ (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc). This was not replicated by light-induced disruption of behavioral circadian rhythms and was not induced by astrocyte- or microglia-specific Bmal1 deletion. However, either pan-neuronal or TH neuron-specific Bmal1 deletion caused cell-autonomous loss of TH+ neurons in the SNpc. Bmal1 deletion did not change the percentage of TH neuron loss after α-synuclein fibril injection, though Bmal1-KO mice had fewer TH neurons at baseline. Transcriptomics analysis revealed dysregulation of pathways involved in oxidative phosphorylation and Parkinson disease. These findings demonstrate a cell-autonomous role for BMAL1 in regulating dopaminergic neuronal survival and may have important implications for neuroprotection in PD

    Benzene Metabolite 1,2,4-Benzenetriol Induces Halogenated DNA and Tyrosines Representing Halogenative Stress in the HL-60 Human Myeloid Cell Line

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    Background: Although benzene is known to be myelotoxic and to cause myeloid leukemia in humans, the mechanism has not been elucidated

    Slow myosin in developing rat skeletal muscle.

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    Cirene : air-sea iInteractions in the Seychelles-Chagos thermocline ridge region

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    Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 90 (2009): 1337-1350, doi:10.1175/2008BAMS2499.1.The Vasco—Cirene program ex-plores how strong air—sea inter-actions promoted by the shallow thermocline and high sea surface temperature in the Seychelles—Chagos thermocline ridge results in marked variability at synoptic, intraseasonal, and interannual time scales. The Cirene oceano-graphic cruise collected oceanic, atmospheric, and air—sea flux observations in this region in Jan-uary—February 2007. The contem-poraneous Vasco field experiment complemented these measure-ments with balloon deployments from the Seychelles. Cirene also contributed to the development of the Indian Ocean observing system via deployment of a moor-ing and 12 Argo profilers. Unusual conditions prevailed in the Indian Ocean during Janu-ary and February 2007, following the Indian Ocean dipole climate anomaly of late 2006. Cirene measurements show that the Seychelles—Chagos thermocline ridge had higher-than-usual heat content with subsurface anomalies up to 7°C. The ocean surface was warmer and fresher than average, and unusual eastward currents prevailed down to 800 m. These anomalous conditions had a major impact on tuna fishing in early 2007. Our dataset also sampled the genesis and maturation of Tropical Cyclone Dora, including high surface temperatures and a strong diurnal cycle before the cyclone, followed by a 1.5°C cool-ing over 10 days. Balloonborne instruments sampled the surface and boundary layer dynamics of Dora. We observed small-scale structures like dry-air layers in the atmosphere and diurnal warm layers in the near-surface ocean. The Cirene data will quantify the impact of these finescale features on the upper-ocean heat budget and atmospheric deep convection.CNES funded the Vasco part of the experiment; INSU funded the Cirene part. R/V Suroît is an Ifremer ship. The contributions from ODU, WHOI, and FOI (Sweden) are supported by the National Science Foundation under Grant Number 0525657. The participation of the University of Miami group was funded though NASA (NNG04HZ33C). PMEL participation was supported through NOAA’s Office of Climate Observation

    Living Invisible: HTLV-1-Infected Persons and the Lack of Care in Public Health

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    Human T-cell lymphotropic virus type 1 (HTLV-1) infection is commonly confounded with Human Immunodeficiency Virus (HIV) infection and it is unknown to many health professionals. It is endemic in many countries and there is no effective treatment available. Although a few individuals have severe symptoms, most patients remain asymptomatic throughout their lives. Further, HTLV-1 is considered a neglected public health problem and limited studies cover specific patients' needs and emotional experiences. To better understand how women and men living with HTLV-1 experience the disease and what issues exist in their healthcare processes, we conducted a qualitative study of both symptomatic and asymptomatic patients at an outpatient clinic at the Emílio Ribas Infectious Diseases Institute in São Paulo, Brazil. We found that the main focus of health staff was on illness risk, but not identifying infected relatives and preventing new infections. This point of view, ultimately neglected patients' complex demands, and overshadows the prevention of new infections and contributes to the lack of care in public health for HTLV-1 infected subjects. Furthermore, this perpetuates the infection among these populations and the patients experience an “invisibility” of their specific needs, such as reproductive rights and feel that their rights as citizens are ignored

    Spherical Lactic Acid Bacteria Activate Plasmacytoid Dendritic Cells Immunomodulatory Function via TLR9-Dependent Crosstalk with Myeloid Dendritic Cells

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    Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-α that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-pathogenic microbiota that are in wide industrial dietary use, such as lactic acid bacteria (LAB). In this study, we screened for LAB strains, which induce pDC activation and IFN-α production using murine bone marrow (BM)-derived Flt-3L induced dendritic cell culture. Microbial strains with such activity on pDC were absent in a diversity of bacillary strains, but were observed in certain spherical species (Lactococcus, Leuconostoc, Streptococcus and Pediococcus), which was correlated with their capacity for uptake by pDC. Detailed study of Lactococcus lactis subsp. lactis JCM5805 and JCM20101 revealed that the major type I and type III interferons were induced (IFN-α, -β, and λ). IFN-α induction was TLR9 and MyD88-dependent; a slight impairment was also observed in TLR4-/- cells. While these responses occurred with purified pDC, IFN-α production was synergistic upon co-culture with myeloid dendritic cells (mDC), an interaction that required direct mDC-pDC contact. L. lactis strains also stimulated expression of immunoregulatory receptors on pDC (ICOS-L and PD-L1), and accordingly augmented pDC induction of CD4+CD25+FoxP3+ Treg compared to the Lactobacillus strain. Oral administration of L. lactis JCM5805 induced significant activation of pDC resident in the intestinal draining mesenteric lymph nodes, but not in a remote lymphoid site (spleen). Taken together, certain non-pathogenic spherical LAB in wide dietary use has potent and diverse immunomodulatory effects on pDC potentially relevant to anti-viral immunity and chronic inflammatory disease
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