Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

No evidence for association between SLC11A1 and visceral leishmaniasis in India.

BACKGROUND: SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. METHODS: Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). RESULTS: No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. CONCLUSIONS: This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Identifying hypermethylated CpG islands using a quantile regression model

<p>Abstract</p> <p>Background</p> <p>DNA methylation has been shown to play an important role in the silencing of tumor suppressor genes in various tumor types. In order to have a system-wide understanding of the methylation changes that occur in tumors, we have developed a differential methylation hybridization (DMH) protocol that can simultaneously assay the methylation status of all known CpG islands (CGIs) using microarray technologies. A large percentage of signals obtained from microarrays can be attributed to various measurable and unmeasurable confounding factors unrelated to the biological question at hand. In order to correct the bias due to noise, we first implemented a quantile regression model, with a quantile level equal to 75%, to identify hypermethylated CGIs in an earlier work. As a proof of concept, we applied this model to methylation microarray data generated from breast cancer cell lines. However, we were unsure whether 75% was the best quantile level for identifying hypermethylated CGIs. In this paper, we attempt to determine which quantile level should be used to identify hypermethylated CGIs and their associated genes.</p> <p>Results</p> <p>We introduce three statistical measurements to compare the performance of the proposed quantile regression model at different quantile levels (95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%), using known methylated genes and unmethylated housekeeping genes reported in breast cancer cell lines and ovarian cancer patients. Our results show that the quantile levels ranging from 80% to 90% are better at identifying known methylated and unmethylated genes.</p> <p>Conclusions</p> <p>In this paper, we propose to use a quantile regression model to identify hypermethylated CGIs by incorporating probe effects to account for noise due to unmeasurable factors. Our model can efficiently identify hypermethylated CGIs in both breast and ovarian cancer data.</p

Healthy obesity and risk of accelerated functional decline and disability

BACKGROUND/OBJECTIVES: Some obese adults have a normal metabolic profile and are considered 'healthy', but whether they experience faster ageing than healthy normal-weight adults is unknown. We compared decline in physical function, worsening of bodily pain, and likelihood of future mobility limitation and disability between these groups. SUBJECTS/METHODS: This was a population-based observational study using repeated measures over 2 decades (Whitehall II cohort data). Normal-weight (body mass index (BMI) 18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (⩾30.0 kg/m(2)) adults were considered metabolically healthy if they had 0 or 1 of 5 risk factors (hypertension, low high-density lipoprotein cholesterol, high triacylglycerol, high blood glucose, and insulin resistance) in 1991/94. Decline in physical function and worsening of bodily pain based on change in Short Form Health Survey items using 8 repeated measures over 18.8 years (1991/94-2012/13) was compared between metabolic-BMI groups using linear mixed models. Odds of mobility limitation based on objective walking speed (slowest tertile) and of disability based on limitations in ⩾1 of 6 basic activities of daily living, each using 3 repeated measures over 8.3 years (2002/04-2012/13), were compared using logistic mixed models. RESULTS: In multivariable-adjusted mixed models on up to 6635 adults (initial mean age 50 years; 70% male), healthy normal-weight adults experienced a decline in physical function of -3.68 (95% CI=-4.19, -3.16) score units per decade; healthy obese adults showed an additional -3.48 (-4.88, -2.08) units decline. Healthy normal-weight adults experienced a -0.49 (-0.12, 1.11) score unit worsening of bodily pain per decade; healthy obese adults had an additional -2.23 (-0.69, -3.78) units worsening. Healthy obesity versus healthy normal-weight conferred 3.39 (2.29, 5.02) times higher odds of mobility limitation and 3.75 (1.94, 7.24) times higher odds of disability. CONCLUSIONS: Our results suggest that obesity, even if metabolically healthy, accelerates age-related declines in functional ability and poses a threat to independence in older age.International Journal of Obesity accepted article preview online, 21 February 2017. doi:10.1038/ijo.2017.51

Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution.<br /

Uptake of health services for common mental disorders by first-generation Turkish and Moroccan migrants in the Netherlands

Abstract Background Migration and ethnic minority status have been associated with higher occurrence of common mental disorders (CMD), while mental health care utilisation by non-Western migrants has been reported to be low compared to the general population in Western host countries. Still, the evidence-base for this is poor. This study evaluates uptake of mental health services for CMD and psychological distress among first-generation non-Western migrants in Amsterdam, the Netherlands. Methods A population-based survey. First generation non-Western migrants and ethnic Dutch respondents (N = 580) participated in structured interviews in their own languages. The interview included the Composite International Diagnostic Interview (CIDI) and the Kessler psychological distress scale (K10). Uptake of services was measured by self-report. Data were analysed using weighting techniques and multivariate logistic regression. Results Of subjects with a CMD during six months preceding the interview, 50.9% reported care for mental problems in that period; 35.0% contacted specialised services. In relation to CMD, ethnic groups were equally likely to access specialised mental health services. In relation to psychological distress, however, Moroccan migrants reported less uptake of primary care services (OR = 0.37; 95% CI = 0.15 to 0.88). Conclusion About half of the ethnic Dutch, Turkish and Moroccan population in Amsterdam with CMD contact mental health services. Since the primary purpose of specialised mental health services is to treat "cases", this study provides strong indications for equal access to specialised care for these ethnic groups. The purpose of primary care services is however to treat psychological distress, so that access appears to be lower among Moroccan migrants

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

An investigation of the phase locking index for measuring of interdependency of cortical source signals recorded in the EEG

The phase locking index (PLI) was introduced to quantify in a statistical sense the phase synchronization of two signals. It has been commonly used to process biosignals. In this article, we investigate the PLI for measuring the interdependency of cortical source signals (CSSs) recorded in the Electroencephalogram (EEG). To this end, we consider simple analytical models for the mapping of simulated CSSs into the EEG. For these models, the PLI is investigated analytically and through numerical simulations. An evaluation is made of the sensitivity of the PLI to the amount of crosstalk between the sources through biological tissues of the head. It is found that the PLI is a useful interdependency measure for CSSs, especially when the amount of crosstalk is small. Another common interdependency measure is the coherence. A direct comparison of both measures has not been made in the literature so far. We assess the performance of the PLI and coherence for estimation and detection purposes based on, respectively, a normalized variance and a novel statistical measure termed contrast. Based on these performance measures, it is found that the PLI is similar or better than the CM in most cases. This result is also confirmed through analysis of EEGs recorded from epileptic patients

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania.

BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. METHODS: The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time. RESULTS: While the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event. CONCLUSIONS: While the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes