Retrovirus-induced spongiform neurodegeneration is mediated by unique central nervous system viral targeting and expression of env alone

Certain murine leukemia viruses (MLVs) can induce progressive noninflammatory spongiform neurodegeneration similar to that caused by prions. The primary MLV determinants responsible have been mapped to within the env gene; however, it has remained unclear how env mediates disease, whether non-Env viral components are required, and what central nervous system (CNS) cells constitute the critical CNS targets. To address these questions, we examined the effect of transplanting engraftable C17.2 neural stem cells engineered to pseudotype, disseminate, and trans-complement neurovirulent (CasBrE, CasE, and CasES) or non-neurovirulent (Friend and SFF-FE) env sequences (SU or SU/TM) within the CNS using either the "non-neurovirulent" amphotropic helper virus, 4070A, or pgag-polgpt (a nonpackaged vector encoding Gag-Pol). These studies revealed that acute MLV-induced spongiosis results from two separable activities of Env. First, Env causes neuropathology through unique viral targeting within the CNS, which was efficiently mediated by ecotropic Envs (CasBrE and Friend), but not 4070A amphotropic Env. Second, Env induces spongiosis through a toxin activity that is MLV-receptor independent and does not require the coexpression of other viral structural proteins. CasBrE and 4070A Envs possess the toxin activity, whereas Friend Env does not. Although the identity of the critical viral target cell(s) remains unresolved, our results appear to exclude microglia and oligodendrocyte lineage cells, while implicating viral entry into susceptible neurons. Thus, MLV-induced disease parallels prionopathies in that a single protein, Env, mediates both the CNS targeting and the toxicity of the infectious agent that manifests itself as progressive vacuolar neurodegeneration.     

Reactivity of δ-substituted α,β-unsaturated cyclic lactones with antileishmanial activity

The present study examines a set of 43 compounds for their antileishmanial activities and cytotoxicities. Negative lowest unoccupied molecular orbitas and similar values for the electrophilic Fukui function condensed at the β-position for a subset of δ-substituted α,β-unsaturated cyclic lactones classify them as strong Michael acceptors. There was a well-defined trend of increasing antileishmanial activity with increasing cytotoxicity and large selectivity indices for the most active compounds. Softer compounds were more active than harder ones as observed from the experimental data and rationalised by calculated reactivity indices.     

Longer and Less Overlapping Food Webs in Anthropogenically Disturbed Marine Ecosystems: Confirmations from the Past

The human exploitation of marine resources is characterised by the preferential removal of the largest species. Although this is expected to modify the structure of food webs, we have a relatively poor understanding of the potential consequences of such alteration. Here, we take advantage of a collection of ancient consumer tissues, using stable isotope analysis and SIBER to assess changes in the structure of coastal marine food webs in the South-western Atlantic through the second half of the Holocene as a result of the sequential exploitation of marine resources by hunter-gatherers, western sealers and modern fishermen. Samples were collected from shell middens and museums. Shells of both modern and archaeological intertidal herbivorous molluscs were used to reconstruct changes in the stable isotopic baseline, while modern and archaeological bones of the South American sea lion Otaria flavescens, South American fur seal Arctocephalus australis and Magellanic penguin Spheniscus magellanicus were used to analyse changes in the structure of the community of top predators. We found that ancient food webs were shorter, more redundant and more overlapping than current ones, both in northern-central Patagonia and southern Patagonia. These surprising results may be best explained by the huge impact of western sealing on pinnipeds during the fur trade period, rather than the impact of fishing on fish populations. As a consequence, the populations of pinnipeds at the end of the sealing period were likely well below the ecosystem''s carrying capacity, which resulted in a release of intraspecific competition and a shift towards larger and higher trophic level prey. This in turn led to longer and less overlapping food webs.     

Neutral-red reaction is related to virulence and cell wall methyl-branched lipids in Mycobacterium tuberculosis

Searching for virulence marking tests for Mycobacterium tuberculosis, Dubos and Middlebrook reported in 1948 that in an alkaline aqueous solution of neutral-red, the cells of the virulent H37Rv M. tuberculosis strain fixed the dye and became red in color, whereas the cells of the avirulent H37Ra M. tuberculosis strain remained unstained. In the 1950 and 1960s, fresh isolates of M. tuberculosis were tested for this neutral-red cytochemical reaction and it was reported that they were neutral-red positive, whereas other mycobacteria of diverse environmental origins that were non-pathogenic for guinea pigs were neutral-red negative. However, neutral-red has not really been proven to be a virulence marker. To test if virulence is in fact correlated to neutral-red, we studied a clinical isolate of M. tuberculosis that was originally neutral-red positive but, after more than 1 year passing through culture mediums, turned neutral-red negative. We found that, in comparison to the original neutral-red positive strain, this neutral-red negative variant was attenuated in two murine models of experimental tuberculosis. Lipid analysis showed that this neutral-red negative natural mutant lost the capacity to synthesize pthiocerol dimycocerosates, a cell wall methyl-branched lipid that has been related to virulence in M. tuberculosis. We also studied the neutral-red of different gene-targeted M. tuberculosis mutants unable to produce pthiocerol dimycocerosates or other cell wall methyl-branched lipids such as sulfolipids, and polyacyltrehaloses. We found a negative neutral-red reaction in mutants that were deficient in more than one type of methyl-branched lipids. We conclude that neutral-red is indeed a marker of virulence and it indicates important perturbations in the external surface of M. tuberculosis cells.     

The Influence of Age and Gender on Skin-Associated Microbial Communities in Urban and Rural Human Populations

Differences in the bacterial community structure associated with 7 skin sites in 71 healthy people over five days showed significant correlations with age, gender, physical skin parameters, and whether participants lived in urban or rural locations in the same city. While body site explained the majority of the variance in bacterial community structure, the composition of the skin-associated bacterial communities were predominantly influenced by whether the participants were living in an urban or rural environment, with a significantly greater relative abundance of Trabulsiella in urban populations. Adults maintained greater overall microbial diversity than adolescents or the elderly, while the intragroup variation among the elderly and rural populations was significantly greater. Skin-associated bacterial community structure and composition could predict whether a sample came from an urban or a rural resident ~5x greater than random.     

Excitation energy transfer to Photosystem I in filaments and heterocysts of Nostoc punctiforme

Cyanobacteria adapt to varying light conditions by controlling the amount of excitation energy to the photosystems. On the minute time scale this leads to redirection of the excitation energy, usually referred to as state transitions, which involves movement of the phycobilisomes. We have studied short-term light adaptation in isolated heterocysts and intact filaments from the cyanobacterium Nostoc punctiforme ATCC 29133. In N.punctiforme vegetative cells differentiate into heterocysts where nitrogen fixation takes place. Photosystem II is inactivated in the heterocysts, and the abundancy of Photosystem I is increased relative to the vegetative cells. To study light-induced changes in energy transfer to Photosystem I, pre-illumination was made to dark adapted isolated heterocysts. Illumination wavelengths were chosen to excite Photosystem I (708 nm) or phycobilisomes (560 nm) specifically. In heterocysts that were pre-illuminated at 708 nm, fluorescence from the phycobilisome terminal emitter was observed in the 77 K emission spectrum. However, illumination with 560 nm light caused quenching of the emission from the terminal emitter, with a simultaneous increase in the emission at 750 nm, indicating that the 560 nm pre-illumination caused trimerization of Photosystem I. Excitation spectra showed that 560 nm pre-illumination led to an increase in excitation transfer from the phycobilisomes to trimeric Photosystem I. Illumination at 708 nm did not lead to increased energy transfer from the phycobilisome to Photosystem I compared to dark adapted samples. The measurements were repeated using intact filaments containing vegetative cells, and found to give very similar results as the heterocysts. This demonstrates that molecular events leading to increased excitation energy transfer to Photosystem I, including trimerization, are independent of Photosystem II activity.     

Effect of lead on the reaction of O-demethylase in p-nitro anisole in the cladoceran Moina macrocopa

The presence of the Mixed-Function Oxydase (MFO) system, in Moina macrocopa was detected through the transformation of p-nitroanisole to para-nitrophenol. The presence of this enzymatic system suggested that this cladoceran participates in the biotransformation of xenobiotics in aquatic ecosystems. This capacity, in conjunction with the aquatic flea's high tolerance to environmental stress, suggested that M. macrocopa could be used in bioremediation efforts to increase ecosystem health. The effects of lead on the MFO system in M. macrocopa, were also studied. Lead acted as an inhibitor of the enzymatic complex. Therefore, induction of MFO-activity as an early warning may not work in waterbodies affected by both inducers of MFO and inhibitors like lead.     

Species sorting and mass effect along forest succession: Evidence from taxonomic,functional, and phylogenetic diversity of amphibian communities

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Multiple Consecutive Infections Might Explain the Lack of Protection by BCG

Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG.