Effects of altitude on circadian rhythm of adult locomotor activity in Himalayan strains of Drosophila helvetica

BACKGROUND: We recently reported that the altitude of origin altered the photic and thermal sensitivity of the circadian pacemaker controlling eclosion and oviposition rhythms of high altitude Himalayan strains of Drosophila ananassae. The present study was aimed at investigating the effects of altitude of origin on the pacemaker controlling the adult locomotor activity rhythm of D. helvetica. METHODS: Locomotor activity rhythms of the high altitude Himalayan (haH) strain (Hemkund-Sahib, 4,121 m above sea level) and the low altitude Himalayan (laH) strain (Birahi, 1,132 m a.s.l.) of D. helvetica were assayed by two experiments. The first experiment examined the natural entrainment pattern in light-dark (LD) cycles at the breeding site of each strain. The second experiment examined the entrainment parameters in LD 12:12 cycles and the period of free-running rhythm in constant darkness (DD) under controlled laboratory conditions. RESULTS: When entrained by natural or artificial LD cycles, the haH strain had an unimodal activity pattern with a single peak that commenced in the forenoon and continued till evening, while the laH strain had a bimodal activity pattern in which the morning peak occurred before lights-on and was separated by about 4 h from the evening peak. Unimodality of the haH strain was retained in DD; however, bimodality of the laH strain was abolished in DD since the evening peak disappeared immediately after the trasfer from LD 12:12 to DD. The period of the free-running rhythm of the haH strain was ~26.1 h, whereas that of the laH strain was ~21.7 h. CONCLUSION: Parameters of entrainment and free-running rhythm of the adult locomotor activity of the haH strain of D. helvetica were strikingly different from those of the laH strain and were likely due to ecological adaptations to the prevailing environmental conditions at the altitude where the species evolved

Radiative Transfer for Exoplanet Atmospheres

Remote sensing of the atmospheres of distant worlds motivates a firm understanding of radiative transfer. In this review, we provide a pedagogical cookbook that describes the principal ingredients needed to perform a radiative transfer calculation and predict the spectrum of an exoplanet atmosphere, including solving the radiative transfer equation, calculating opacities (and chemistry), iterating for radiative equilibrium (or not), and adapting the output of the calculations to the astronomical observations. A review of the state of the art is performed, focusing on selected milestone papers. Outstanding issues, including the need to understand aerosols or clouds and elucidating the assumptions and caveats behind inversion methods, are discussed. A checklist is provided to assist referees/reviewers in their scrutiny of works involving radiative transfer. A table summarizing the methodology employed by past studies is provided.Comment: 7 pages, no figures, 1 table. Filled in missing information in references, main text unchange

Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms

Cultured Vestibular Ganglion Neurons Demonstrate Latent HSV1 Reactivation

Objectives/Hypothesis: Vestibular neuritis is a common cause of both acute and chronic vestibular dysfunction. Multiple pathologies have been hypothesized to be the causative agent of vestibular neuritis; however, whether herpes simplex type I (HSV1) reactivation occurs within the vestibular ganglion has not been demonstrated previously by experimental evidence. We developed an in vitro system to study HSV1 infection of vestibular ganglion neurons (VGNs) using a cell culture model system. Study Design: basic science study. Results: Lytic infection of cultured rat VGNs was observed following low viral multiplicity of infection (MOI). Inclusion of acyclovir suppressed lytic replication and allowed latency to be established. Upon removal of acyclovir, latent infection was confirmed with reverse-transcription polymerase chain reaction and by RNA fluorescent in situ hybridization for the latencyassociated transcript (LAT). A total of 29% cells in latently infected cultures were LAT positive. The lytic ICP27 transcript was not detected by reverse-transcription polymerase chain reaction (RT-PCR). Reactivation of HSV1 occurred at a high frequency in latently infected cultures following treatment with trichostatin A (TSA), a histone deactylase inhibitor. Conclusions: VGNs can be both lytically and latently infected with HSV1. Furthermore, latently infected VGNs can be induced to reactivate using TSA. This demonstrates that reactivation of latent HSV1 infection in the vestibular ganglion can occur in a cell culture model, and suggests that reactivation of HSV1 infection a plausible etiologic mechanism of vestibular neuritis

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility

Diphyllobothriasis in a nine-year-old child in India: a case report

<p>Abstract</p> <p>Introduction</p> <p>The <it>Diphyllobothrium </it>genus belongs to the <it>Diphyllobothridea </it>order of tapeworms. <it>Diphyllobothrium </it>spp., which is commonly known as fish tapeworm, is generally transmitted in humans, but also in other species, such as bears, dogs, cats, foxes, and other terrestrial carnivores. Although worldwide in distribution, the original heartland of <it>Diphyllobothrium </it>spp. spreads across Scandinavia, northern Russia, and western Serbia. We report a rare case that occurred in India.</p> <p>Case presentation</p> <p>A nine-year-old south Indian girl was brought to the casualty at the Prathima Institute of Medical Sciences with complaints of vomiting and loose stools that had started three days earlier. The vomit did not have a foul smell and contained no blood or mucus, but it did contain undigested food particles. The patient described a history of recurrent abdominal pain. She was a non-vegetarian and said she had a history of eating fish.</p> <p>Conclusion</p> <p>The incidence of <it>Diphyllobothrium </it>spp. infection is infrequent in India. Since this is only the fourth reported case in India, and since the previously reported cases also involved observed pediatric patients, we emphasize the need for clinical microbiologists and pediatricians to suspect fish tapeworm infection and recommend epidemiological study of <it>Diphyllobothrium </it>spp. infection.</p

Careers of an elite cohort of U.S. basic life science postdoctoral fellows and the influence of their mentor's citation record

<p>Abstract</p> <p>Background</p> <p>There is general agreement that the number of U.S. science PhDs being trained far exceeds the number of future academic positions. One suggested approach to this problem is to significantly reduce the number of PhD positions. A counter argument is that students are aware of the limited academic positions but have chosen a PhD track because it opens other, non-academic, opportunities. The latter view requires that students have objective information about what careers options will be available for them.</p> <p>Methods</p> <p>The scientific careers of the 1992-94 cohort of NIH National Institute of General Medical Sciences (NIGMS) Kirchstein-NRSA F32 postdoctoral fellows (PD) was determined by following their publications (PubMed), grants (NIH and NSF), and faculty and industry positions through 2009. These basic life science PDs receive support through individual grant applications and represent the most successful class of NIH PDs as judged by academic careers and grants. The sex dependence of the career and grant success and the influence of the PD mentor's citation record were also determined</p> <p>Results</p> <p>Of the 439 1992-94 NIGMS F32 fellows, the careers of 417 could be determined. Although females had significantly higher rates of dropping out of science (22% females, 9% males) there was no significant difference in the fraction of females that ended up as associate or full professors at research universities (22.8% females, 29.1% for males). More males then females ended up in industry (34% males, 22% females). Although there was no significant correlation between male grant success and their mentor's publication record (h index, citations, publications), there was a significant correlation for females. Females whose mentor's h index was in the top quartile were nearly 3 times as likely to receive a major grant as those whose mentors were in the bottom quartile (38.7% versus 13.3%).</p> <p>Conclusions</p> <p>Sixteen years after starting their PD, only 9% of males had dropped out of science. More females (28%) have dropped out of science, primarily because fewer went into industry positions. The mentor's publication record does not affect the future grant success of males but it has a dramatic effect on female grant success.</p

Into the UV: The Atmosphere of the Hot Jupiter HAT-P-41b Revealed

For solar system objects, ultraviolet spectroscopy has been critical in identifying sources of stratospheric heating and measuring the abundances of a variety of hydrocarbon and sulfur-bearing species, produced via photochemical mechanisms, as well as oxygen and ozone. To date, fewer than 20 exoplanets have been probed in this critical wavelength range (0.2–0.4 μm). Here we use data from Hubble's newly implemented WFC3 UVIS G280 grism to probe the atmosphere of the hot Jupiter HAT-P-41b in the ultraviolet through optical in combination with observations at infrared wavelengths. We analyze and interpret HAT-P-41b's 0.2–5.0 μm transmission spectrum using a broad range of methodologies including multiple treatments of data systematics as well as comparisons with atmospheric forward, cloud microphysical, and multiple atmospheric retrieval models. Although some analysis and interpretation methods favor the presence of clouds or potentially a combination of Na, VO, AlO, and CrH to explain the ultraviolet through optical portions of HAT-P-41b's transmission spectrum, we find that the presence of a significant H− opacity provides the most robust explanation. We obtain a constraint for the abundance of H−, $\mathrm{log}({{\rm{H}}}^{-})=-8.65\pm 0.62$, in HAT-P-41b's atmosphere, which is several orders of magnitude larger than predictions from equilibrium chemistry for a ~1700–1950 K hot Jupiter. We show that a combination of photochemical and collisional processes on hot hydrogen-dominated exoplanets can readily supply the necessary amount of H− and suggest that such processes are at work in HAT-P-41b and the atmospheres of many other hot Jupiters

Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa

Background: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear. Methods: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya. Results: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect. Conclusion: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women

NIH Disease Funding Levels and Burden of Disease

BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade