Terminal Redundancy Heterozygotes Involving the First-Step-Transfer Region of the Bacteriophage T5 Chromosome

Individual progeny of two-factor crosses between A1am and A2am T5 phages give rise to bursts containing more than one type of plaque. The simplest explanation for these mixed bursts is that the A1 and A2 genes are located within the terminally repeated portion of the T5 genome and that the mixed bursts are made by "terminal redundancy heterozygotes". The observation of genetic heterozygosity means that the A1 and A2 genes are repeated intact. This implies that the terminal segments of T5 are genetically interchangeable.     

Effects of Timber Harvests and Silvicultural Edges on Terrestrial Salamanders

Balancing timber production and conservation in forest management requires an understanding of how timber harvests affect wildlife species. Terrestrial salamanders are useful indicators of mature forest ecosystem health due to their importance to ecosystem processes and sensitivity to environmental change. However, the effects of timber harvests on salamanders, though often researched, are still not well understood. To further this understanding, we used artificial cover objects to monitor the relative abundance of terrestrial salamanders for two seasons (fall and spring) pre-harvest and five seasons post-harvest in six forest management treatments, and for three seasons post-harvest across the edge gradients of six recent clearcuts. In total, we recorded 19,048 encounters representing nine species of salamanders. We observed declines in mean encounters of eastern red-backed salamanders (Plethodon cinereus) and northern slimy salamanders (P. glutinosus) from pre- to post-harvest in group selection cuts and in clearcuts. However, we found no evidence of salamander declines at shelterwoods and forested sites adjacent to harvests. Edge effects induced by recent clearcuts influenced salamanders for approximately 20 m into the forest, but edge influence varied by slope orientation. Temperature, soil moisture, and canopy cover were all correlated with salamander counts. Our results suggest silvicultural techniques that remove the forest canopy negatively affect salamander relative abundance on the local scale during the years immediately following harvest, and that the depth of edge influence of clearcuts on terrestrial salamanders is relatively shallow (<20 m). Small harvests (<4 ha) and techniques that leave the forest canopy intact may be compatible with maintaining terrestrial salamander populations across a forested landscape. Our results demonstrate the importance of examining species-specific responses and monitoring salamanders across multiple seasons and years. Long-term monitoring will be necessary to understand the full impacts of forest management on terrestrial salamanders.     

Estimating demographic parameters for fisheries management using acoustic telemetry

Reviews in Fish Biology and Fisheries - Mark-recapture approaches are among the most powerful fisheries methods for estimating demographic parameters relating to survival, components of mortality...     

Engagement with HIV Prevention Treatment and Care among Female Sex Workers in Zimbabwe: a Respondent Driven Sampling Survey

Objective(S)

To determine the HIV prevalence and extent of engagement with HIV prevention and care among a representative sample of Zimbabwean sex workers working in Victoria Falls, Hwange and Mutare.

Design

Respondent driven sampling (RDS) surveys conducted at each site.

Methods

Sex workers were recruited using respondent driven sampling with each respondent limited to recruiting 2 peers. Participants completed an interviewer-administered questionnaire and provided a finger prick blood sample for HIV antibody testing. Statistical analysis took account of sampling method.

Results

870 women were recruited from the three sites. HIV prevalence was between 50 and 70%. Around half of those confirmed HIV positive were aware of their HIV status and of those 50-70% reported being enrolled in HIV care programmes. Overall only 25-35% of those with laboratory-confirmed HIV were accessing antiretroviral therapy. Among those reporting they were HIV negative, 21-28% reported having an HIV test in the last 6 months. Of those tested HIV negative, most (65-82%) were unaware of their status. Around two-thirds of sex workers reported consistent condom use with their clients. As in other settings, sex workers reported high rates of gender based violence and police harassment.

Conclusions

This survey suggests that prevalence of HIV is high among sex workers in Zimbabwe and that their engagement with prevention, treatment and care is sub-optimal. Intensifying prevention and care interventions for sex workers has the potential to markedly reduce HIV and social risks for sex workers, their clients and the general population in Zimbabwe and elsewhere in the region.     

The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current I_Na and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on I_Na. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca²⁺ and Na⁺ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.     

A simple model of the hydrophobic effect for molecular simulation of interfacial phenomena

A coarse-grained model for simulation of interfacial phenomena in aqueous systems has been developed. The model captures the hydrophobic effect by only considering the structure and cohesiveness of water. Monte Carlo (MC) simulations of water-oil mixtures show that low concentrations of oil are solvated with little perturbation of the hydrogen bonding network structure of the water, while high concentrations of oil are excluded altogether. Analysis of the water structure in the simulations indicates that the water molecules maintain close to four coordination in the presence of solutes and the distribution of bond angles is not markedly affected by the presence of solutes. MC simulations of an alkane oligomer in water and a poly(ethylene oxide) (PEO) oligomer in water indicate that the chains are quite flexible and also do not perturb the network structure of the water phase.     

The epidemiology and public health importance of toxocariasis: A zoonosis of global importance

Toxocariasis, caused by infection with larvae of Toxocara canis, and to a lesser extent by Toxocara cati and other ascaridoid species, manifests in humans in a range of clinical syndromes. These include visceral and ocular larva migrans, neurotoxocariasis and covert or common toxocariasis. Toxocara canis is one of the most widespread public health and economically important zoonotic parasitic infections humans share with dogs, cats and wild canids, particularly foxes. This neglected disease has been shown through seroprevalence studies to be especially prevalent among children from socio-economically disadvantaged populations both in the tropics and sub-tropics and in industrialised nations. Human infection occurs by the accidental ingestion of embryonated eggs or larvae from a range of wild and domestic paratenic hosts. Most infections remain asymptomatic. Clinically overt infections may go undiagnosed, as diagnostic tests are expensive and can require serological, molecular and/or imaging tests, which may not be affordable or available. Treatment in humans varies according to symptoms and location of the larvae. Anthelmintics, including albendazole, thiabendazole and mebendazole may be given together with anti-inflammatory corticosteroids. The development of molecular tools should lead to new and improved strategies for the treatment, diagnosis and control of toxocariasis and the role of other ascaridoid species in the epidemiology of Toxocara spp. Molecular technologies may also help to reveal the public health importance of T. canis, providing new evidence to support the implementation of national control initiatives which have yet to be developed for Toxocara spp. A number of countries have implemented reproductive control programs in owned and stray dogs to reduce the number of young dogs in the population. These programs would positively impact upon T. canis transmission since the parasite is most fecund and prevalent in puppies. Other control measures for T. canis include the regular and frequent anthelmintic treatment of dogs and cats, starting at an early age, education and enforcement of laws for the disposal of canine faeces, dog legislation and personal hygiene. The existence of wild definitive and paratenic hosts complicates the control of T. canis. Increasing human and dog populations, population movements and climate change will all serve to increase the importance of this zoonosis. This review examines the transmission, diagnosis and clinical syndromes of toxocariasis, its public health importance, epidemiology, control and current research needs.     

Supplementation with α-Lipoic Acid,CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice

Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10) on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group) and divided into trained (8 wks treadmill running) (n = 12/group) and untrained groups (n = 24/group). Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05). Furthermore, antioxidant-supplemented females (untrained) showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris) (p ≤ 0.05), reduced oxidative damage to muscle proteins (p ≤ 0.05), and increased expression of mitochondrial proteins (p ≤ 0.05) compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α) (p ≤ 0.05) via activation of AMP-activated protein kinase (AMPK) (p ≤ 0.05) by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations.     

Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene

Non-somatic synaptic and axonal compartments of neurons are primary pathological targets in many neurodegenerative conditions, ranging from Alzheimer disease through to motor neuron disease. Axons and synapses are protected from degeneration by the slow Wallerian degeneration (Wld(s)) gene. Significantly the molecular mechanisms through which this spontaneous genetic mutation delays degeneration remain controversial, and the downstream protein targets of Wld(s) resident in non-somatic compartments remain unknown. In this study we used differential proteomics analysis to identify proteins whose expression levels were significantly altered in isolated synaptic preparations from the striatum of Wld(s) mice. Eight of the 16 proteins we identified as having modified expression levels in Wld(s) synapses are known regulators of mitochondrial stability and degeneration (including VDAC1, Aralar1, and mitofilin). Subsequent analyses demonstrated that other key mitochondrial proteins, not identified in our initial screen, are also modified in Wld(s) synapses. Of the non-mitochondrial proteins identified, several have been implicated in neurodegenerative diseases where synapses and axons are primary pathological targets (including DRP-2 and Rab GDP dissociation inhibitor beta). In addition, we show that downstream protein changes can be identified in pathways corresponding to both Ube4b (including UBE1) and Nmnat1 (including VDAC1 and Aralar1) components of the chimeric Wld(s) gene, suggesting that full-length Wld(s) protein is required to elicit maximal changes in synaptic proteins. We conclude that altered mitochondrial responses to degenerative stimuli are likely to play an important role in the neuroprotective Wld(s) phenotype and that targeting proteins identified in the current study may lead to novel therapies for the treatment of neurodegenerative diseases in humans.