The HY5-PIF regulatory module coordinates light and temperature control of photosynthetic gene transcription

The ability to interpret daily and seasonal alterations in light and temperature signals is essential for plant survival. This is particularly important during seedling establishment when the phytochrome photoreceptors activate photosynthetic pigment production for photoautotrophic growth. Phytochromes accomplish this partly through the suppression of phytochrome interacting factors (PIFs), negative regulators of chlorophyll and carotenoid biosynthesis. While the bZIP transcription factor long hypocotyl 5 (HY5), a potent PIF antagonist, promotes photosynthetic pigment accumulation in response to light. Here we demonstrate that by directly targeting a common promoter cis-element (G-box), HY5 and PIFs form a dynamic activation-suppression transcriptional module responsive to light and temperature cues. This antagonistic regulatory module provides a simple, direct mechanism through which environmental change can redirect transcriptional control of genes required for photosynthesis and photoprotection. In the regulation of photopigment biosynthesis genes, HY5 and PIFs do not operate alone, but with the circadian clock. However, sudden changes in light or temperature conditions can trigger changes in HY5 and PIFs abundance that adjust the expression of common target genes to optimise photosynthetic performance and growth

Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes

The Impact of Socio-Demographic and Religious Factors upon Sexual Behavior among Ugandan University Students

INTRODUCTION: More knowledge is needed about structural factors in society that affect risky sexual behaviors. Educational institutions such as universities provide an opportune arena for interventions among young people. The aim of this study was to investigate the relationship between sociodemographic and religious factors and their impact on sexual behavior among university students in Uganda. METHODS: In 2005, 980 university students (response rate 80%) were assessed by a self-administered questionnaire. Validated instruments were used to assess socio-demographic and religious factors and sexual behavior. Logistic regression analyses were applied. RESULTS: Our findings indicated that 37% of the male and 49% of the female students had not previously had sex. Of those with sexual experience, 46% of the males and 23% of the females had had three or more sexual partners, and 32% of the males and 38% of the females did not consistently use condoms. For those who rated religion as less important in their family, the probability of early sexual activity and having had a high number of lifetime partners increased by a statistically significant amount (OR = 1.7; 95% CI: 1.2-2.4 and OR = 1.6; 95% CI: 1.1-2.3, respectively). However, the role of religion seemed to have no impact on condom use. Being of Protestant faith interacted with gender: among those who had debuted sexually, Protestant female students were more likely to have had three or more lifetime partners; the opposite was true for Protestant male students. CONCLUSION: Religion emerged as an important determinant of sexual behavior among Ugandan university students. Our findings correlate with the increasing number of conservative religious injunctions against premarital sex directed at young people in many countries with a high burden. of HIV/AIDS. Such influence of religion must be taken into account in order to gain a deeper understanding of the forces that shape sexual behavior in Uganda

3D finite compartment modeling of formation and healing of bruises may identify methods for age determination of bruises

Simulating the spatial and temporal behavior of bruises may identify methods that allow accurate age determination of bruises to assess child abuse. We developed a numerical 3D model to simulate the spatial kinetics of hemoglobin and bilirubin during the formation and healing of bruises. Using this model, we studied how skin thickness, bruise diameter and diffusivities affect the formation and healing of circular symmetric bruises and compared a simulated bruise with a natural inhomogeneous bruise. Healing is faster for smaller bruises in thinner and less dense skin. The simulated and natural bruises showed similar spatial and temporal dynamics. The different spatio-temporal dynamics of hemoglobin and bilirubin allows age determination of model bruises. Combining our model predictions with individual natural bruises may allow optimizing our model parameters. It may particularly identify methods for more accurate age determination than currently possible to aid the assessment of child abuse

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Mortality in adult patients with culture-positive and culture-negative meningitis in the Botswana national meningitis survey: a prevalent cohort study.

BACKGROUND: CNS infections are a leading cause of HIV-related deaths in sub-Saharan Africa, but causes and outcomes are poorly defined. We aimed to determine mortality and predictors of mortality in adults evaluated for meningitis in Botswana, which has an estimated 23% HIV prevalence among adults. METHODS: In this prevalent cohort study, patient records from 2004-15 were sampled from the Botswana national meningitis survey, a nationwide audit of all cerebrospinal fluid (CSF) laboratory records from patients receiving a lumbar puncture for evaluation of meningitis. Data from all patients with culture-confirmed pneumococcal and tuberculous meningitis, and all patients with culture-negative meningitis with CSF white cell count (WCC) above 20 cells per μL were included in our analyses, in addition to a random selection of patients with culture-negative CSF and CSF WCC of up to 20 cells per μL. We used patient national identification numbers to link CSF laboratory records from the national meningitis survey to patient vital registry and HIV databases. Univariable and multivariable Cox proportional hazards models were used to evaluate clinical and laboratory predictors of mortality. FINDINGS: We included data from 238 patients with culture-confirmed pneumococcal meningitis, 48 with culture-confirmed tuberculous meningitis, and 2900 with culture-negative CSF (including 1691 with CSF WCC of up to 20 cells per μL and 1209 with CSF WCC above 20 cells per μL). Median age was 37 years (IQR 31-46), 1605 (50%) of 3184 patients were male, 2188 (72%) of 3023 patients with registry linkage had documentation of HIV infection, and median CD4 count was 139 cells per μL (IQR 63-271). 10-week and 1-year mortality was 47% (112 of 238) and 49% (117 of 238) for pneumococcal meningitis, 46% (22 of 48) and 56% (27 of 48) for tuberculous meningitis, and 41% (1181 of 2900) and 49% (1408 of 2900) for culture-negative patients. When the analysis of patients with culture-negative CSF was restricted to those with known HIV infection, WCC (0-20 cells per μL vs >20 cells per μL) was not predictive of mortality (average hazard ratio 0·93, 95% CI 0·80-1·09). INTERPRETATION: Mortality from pneumococcal, tuberculous, and culture-negative meningitis was high in this setting of high HIV prevalence. There is an urgent need for improved access to diagnostics, to better define aetiologies and develop novel diagnostic tools and treatment algorithms. FUNDING: National Institutes of Health, President's Emergency Plan for AIDS Relief, National Institute for Health Research

Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis

This study examined fiber type-dependent differences in the regulation of protein synthesis in individual muscle fibers found within the same whole muscle. Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse plantaris muscle, in response to food deprivation (FD), and mechanical overload induced by synergist ablation (SA). The results show that 48 h of FD induced a greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1 and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in total S6 protein and Ser240/244 S6 phosphorylation, respectively. Moreover, only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional area (CSA). Ten days of SA also induced fiber type-dependent responses, with type 2B fibers having the smallest SA-induced increases in protein synthesis, CSA and Ser240/244 S6 phosphorylation, but the largest increase in total S6 protein. Embryonic myosin heavy chain (MHCEmb) positive fibers were also found in SA muscles and the protein synthesis rates, levels of S6 Ser240/244 phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold greater than that found in fibers from control muscles, respectively. Overall, these results reveal differential responses in the regulation of protein synthesis and fiber size between fiber types found within the same whole muscle. Moreover, these findings demonstrate that changes found at the whole muscle level do not necessarily reflect changes in individual fiber types

Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection

BACKGROUND: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought. METHODOLOGY: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay. CONCLUSIONS: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni