Multiple ectoparasites infest Microcebus griseorufus at Beza Mahafaly Special Reserve, Madagascar

The mouse lemur Microcebus griseorufus at the Beza Mahafaly Special Reserve and general vicinity in southwestern Madagascar were surveyed for ectoparasites as part of a year-long behavioral and ecological study. Of 249 individual mouse lemurs examined, 74 were positively identified as hosting ectoparasites. Ticks from 20 mouse lemurs and lice in a subset of two individuals captured in a 90 ha gallery forest (Parcel 1) were preserved in 70 % ethanol or EDTA and stored for analysis and for identification. Two species of Haemaphysalis ticks are represented in the sample, H. lemuris and possibly H. simplex, a tick previously reported on tenrecs, birds and rats. Synchronous development of ticks may pose a risk for vector - borne diseases at the reserve especially during the dry season. The louse represented in the sample belongs to the order Anoplura (sucking lice), and resembles Lemurpediculus verruculosus, previously reported on Microcebus rufus in eastern Madagascar.RÉSUMÉUn inventaire d’ectoparasites a été réalisé dans le cadre d’une étude de longue durée portant sur le comportement et l’écologie de Microcebus griseorufus dans trois parcelles forestières de Beza Mahafaly et ses environs. Sur les 249 microcèbes observés, 74 individus étaient infestés d’ectoparasites. La majorité de ces individus infestés, soit 97,3 % , provenait de la parcelle 1 de la réserve. Des poux et des tiques recensés sur ces animaux ont été immédiatement retirés puis préservés dans l’éthanol 70 % ou dans l’EDTA à des fins d’analyse et d’identification. Deux espèces de tiques ont été identifiées, Haemaphysalis lemuris et probablement H. simplex, cette dernière n’était préalablement connue que pour infester les tenrecs, les oiseaux et les rats. Les rongeurs jouent un rôle significatif en tant qu’hôtes pour près de la moitié des larves et des nymphes d’ixodes de tiques du monde, y compris H. simplex. Les rats sont connus pour être des porteurs d’une population importante de différentes tiques. Ils sont ainsi les hôtes avec la plus grande tolérance. Une nouvelle forme de transmission a été identifiée à Beza Mahafaly dans laquelle H. simplex et d’autres espèces de tiques ont simultanément infesté des tenrecs. Ce chevauchement de plusieurs parasites forme une sorte de réserve et favorise la transmission des agents pathogènes à travers les espèces hôtes. Les tiques immatures jouent un rôle significatif dans la transmission des maladies véhiculées par les hôtes car les nymphes ainsi infectées peuvent transmettre des pathogènes aux hôtes et aux larves engorgées. À Beza Mahafaly, le microcèbe pourrait être l’hôte des formes immatures des tiques de H. lemuris et H. simplex chez lesquelles le stade larvaire et le stade nymphal sont synchrones. Ces formes immatures de tiques se nourrissent ensemble sur des individus de microcèbes. Les poux appartiennent à l’ordre des Anoploures (poux suceurs) et ressemblent à Lemurpediculus verruculosus qui n’était connu que pour infester Microcebus rufus des forêts humides de Ranomafana.Il est possible que M. griseorufus accueille sa propre espèce de Lemurpediculus, si ce n’est le cas, il faudra admettre que la spécificité de cet arthropode serait moins limitée qu’elle ne le semblait. Pour comprendre la dynamique des parasites de la réserve, des études sur l’écologie des tiques et des poux sont recommandées afin de pouvoir contribuer effectivement à l’amélioration de la protection de la réserve

The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.

Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observed during embryonic and early postnatal ages than in young adulthood. We obtained biochemical evidence indicating that the bulk of dysbindin from brain exists as a stable component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), a multi-subunit protein complex involved in intracellular membrane trafficking and organelle biogenesis. Selective biochemical interaction between brain BLOC-1 and a few members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) superfamily of proteins that control membrane fusion, including SNAP-25 and syntaxin 13, was demonstrated. Furthermore, primary hippocampal neurons deficient in BLOC-1 displayed neurite outgrowth defects. Taken together, these observations suggest a novel role for the dysbindin-containing complex, BLOC-1, in neurodevelopment, and provide a framework for considering potential effects of allelic variants in DTNBP1--or in other genes encoding BLOC-1 subunits--in the context of the developmental model of schizophrenia pathogenesis

Proliferation of Tau 304-380 Fragment Aggregates through Autocatalytic Secondary Nucleation.

The self-assembly of the protein tau into neurofibrillary tangles is one of the hallmarks of Alzheimer's disease and related tauopathies. Still, the molecular mechanism of tau aggregation is largely unknown. This problem may be addressed by systematically obtaining reproducible in vitro kinetics measurements under quiescent conditions in the absence of triggering substances. Here, we implement this strategy by developing protocols for obtaining an ultrapure tau fragment (residues 304-380 of tau441) and for performing spontaneous aggregation assays with reproducible kinetics under quiescent conditions. We are thus able to identify the mechanism of fibril formation of the tau 304-380 fragment at physiological pH using fluorescence spectroscopy and mass spectrometry. We find that primary nucleation is slow, and that secondary processes dominate the aggregation process once the initial aggregates are formed. Moreover, our results further show that secondary nucleation of monomers on fibril surfaces dominates over fragmentation of fibrils. Using separate isotopes in monomers and fibrils, through mass spectroscopy measurements, we verify the isotope composition of the intermediate oligomeric species, which reveals that these small aggregates are generated from monomer through secondary nucleation. Our results provide a framework for understanding the processes leading to tau aggregation in disease and for selecting possible tau forms as targets in the development of therapeutic interventions in Alzheimer's disease

Measurement of Aerosols at the Pierre Auger Observatory

The air fluorescence detectors (FDs) of the Pierre Auger Observatory are vital for the determination of the air shower energy scale. To compensate for variations in atmospheric conditions that affect the energy measurement, the Observatory operates an array of monitoring instruments to record hourly atmospheric conditions across the detector site, an area exceeding 3,000 square km. This paper presents results from four instruments used to characterize the aerosol component of the atmosphere: the Central Laser Facility (CLF), which provides the FDs with calibrated laser shots; the scanning backscatter lidars, which operate at three FD sites; the Aerosol Phase Function monitors (APFs), which measure the aerosol scattering cross section at two FD locations; and the Horizontal Attenuation Monitor (HAM), which measures the wavelength dependence of aerosol attenuation.Comment: Contribution to the 30th International Cosmic Ray Conference, Merida Mexico, July 2007; 4 pages, 4 figure

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies

Background: There is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes. Methods: We developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes. Results: Of 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality. Conclusion: Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs