2,183 research outputs found

    Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

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    Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

    Study of the Baryon-Antibaryon Low-Mass Enhancements in Charmless Three-body Baryonic B Decays

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    The angular distributions of the baryon-antibaryon low-mass enhancements seen in the charmless three-body baryonic B decays B+ -> p pbar K+, B0 -> p pbar Ks, and B0 -> p Lambdabar pi- are reported. A quark fragmentation interpretation is supported, while the gluonic resonance picture is disfavored. Searches for the Theta+ and Theta++ pentaquarks in the relevant decay modes and possible glueball states G with 2.2 GeV/c2 < M-ppbar < 2.4 GeV/c2 in the ppbar systems give null results. We set upper limits on the products of branching fractions, B(B0 -> Theta+ p)\times B(Theta+ -> p Ks) Theta++ pbar) \times B(Theta++ -> p K+) G K+) \times B(G -> p pbar) < 4.1 \times 10^{-7} at the 90% confidence level. The analysis is based on a 140 fb^{-1} data sample recorded on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.Comment: 14 pages, 13 figure files, update of hep-ex/0409010 for journal submisssio

    Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood

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    Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation

    Properties of Light Flavour Baryons in Hypercentral quark model

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    The light flavour baryons are studied within the quark model using the hyper central description of the three-body system. The confinement potential is assumed as hypercentral coulomb plus power potential (hCPPνhCPP_\nu) with power index ν\nu. The masses and magnetic moments of light flavour baryons are computed for different power index, ν\nu starting from 0.5 to 1.5. The predicted masses and magnetic moments are found to attain a saturated value with respect to variation in ν\nu beyond the power index ν>\nu> 1.0. Further we computed transition magnetic moments and radiative decay width of light flavour baryons. The results are in good agreement with known experimental as well as other theoretical models.Comment: Accepted in Pramana J. of Physic

    A Mathematical Approach Lights up The Way to End Cholera Transmission

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    Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1-14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies.We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions

    Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

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    The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

    GLOBAL STABILITY AND BIFURCATIONS ANALYSIS OF AN EPIDEMIC MODEL WITH CONSTANT REMOVAL RATE OF THE INFECTIVE

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    In this thesis we consider an epidemic model with a constant removal rate of infective individuals is proposed to understand the effect of limited resources for treatment of infective on the disease spread. It is found that it is unnecessary to take such a large treatment capacity that endemic equilibria disappear to eradicate the disease. It is shown that the outcome of disease spread may depend on the position of the initial states for certain range of parameters. It is also shown that the model undergoes a sequence of bifurcations including saddle-node bifurcation, subcritical Hopf bifurcation. Keyword: Epidemic model, nonlinear incidence rate, basic reproduction number, local and global stabilit

    Studies of the Decay B+- -> D_CP K+-

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    We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter
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