Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Improvements to water purification and sanitation infrastructure may reduce the diarrheal burden in a marginalized and flood prone population in remote Nicaragua

<p>Abstract</p> <p>Background</p> <p>The isolated northern region of Nicaragua has one of the highest rates of diarrheal disease in Central America. Political and environmental hardships faced by inhabitants of this region are contributing factors to this health inequity. The aim of this study was to assess the relationship between water and latrine infrastructure and the prevalence of diarrhea in this region.</p> <p>Methods</p> <p>A population-based, cross-sectional survey of women of reproductive age was conducted in the Sahsa region of northern Nicaragua in July, 2009. Households were selected by two stage cluster sampling methodology. A questionnaire was administered in Spanish and Miskito with assessment of household and socioeconomic conditions, sanitation practices, and health care access. Diarrhea prevalence differences at the household level over a two week reporting period were estimated with a standardized instrument which included assessment of water treatment and latrine use and maintenance.</p> <p>Results</p> <p>There were 189 women enrolled in the current study. The use of water purification methods, such as chlorine and filters, and latrine ownership were not associated with reduced prevalence of household diarrhea in the two week reporting period. Latrine overflow, however, was associated with an increased prevalence of diarrhea during the same two week period [adjusted prevalence difference and 95% CI: 0.19 (0.03, 0.36)].</p> <p>Conclusions</p> <p>Simple, low cost interventions that improve water and latrine infrastructure may reduce the prevalence of diarrheal disease in the isolated regions of Nicaragua and Central America.</p

‘PRi special edition: The intersections between public relations and neoliberalism’ – The road to nowhere: Re-examining activists’ role in civil societies

The French sociologist Pierre Bourdieu (1977) argued that the presence of critical counter-voices and powers is a fundamental element of any genuine democracy. However, in Australia these counter-voices are increasingly marginalized and threatened by controversial laws that would limit the legal standing of conservation groups and the use of overseas donations for advocacy purposes based on the argument that “systematic, well-funded” environmental campaigns are threatening the nation’s economic prosperity. Drawing on social movement theory and Bourdieu’s theory of practice, this case study details the final months of the Save Beeliar Wetlands campaign in the lead up to the 2017 West Australian state election. The author challenges three common assumptions in the extant PR activism literature: The existence of activists in opposition to organizations and governments, the presence of a ‘zone of compromise’ between activists and the organizations or governments whose actions they are opposing and the conceptualization of activists as homogenous entity. Evolving into a colorful collective of over 35 local groups, five local councils and thousands of individuals, Beeliar Wetland Defenders successfully created an alternative narrative to the State and Federal Governments’ neoliberal agenda. Activists thereby contributed significantly to a change in leadership and the termination of a $1.9billion infrastructure project. This paper argues that activist groups’ interventions in public debate perform a valuable societal voice as critical counter-voices in challenging established hierarchies and power relationships. However, in mounting and framing their arguments within the neoliberal framework, activist groups may also inadvertently reinforce this worldview

Field Assessment of a Novel Household-Based Water Filtration Device: A Randomised, Placebo-Controlled Trial in the Democratic Republic of Congo

BACKGROUND: Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases. However, current methods of treating water at home have certain shortcomings, and there is evidence of bias in the reported health impact of the intervention in open trial designs. METHODS AND FINDINGS: We undertook a randomised, double-blinded, placebo-controlled trial among 240 households (1,144 persons) in rural Democratic Republic of Congo to assess the field performance, use and effectiveness of a novel filtration device in preventing diarrhea. Households were followed up monthly for 12 months. Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform (TTC) levels in influent and effluent water samples. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages. Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit. Over the 12-month follow-up period, data were collected for 11,236 person-weeks of observation (81.8% total possible). After adjusting for clustering within the household, the longitudinal prevalence ratio of diarrhoea was 0.85 (95% confidence interval: 0.61-1.20). The filters achieved a 2.98 log reduction in TTC levels while, for reasons that are unclear, the placebos achieved a 1.05 log reduction (p<0.0001). After 8 months, 68% of intervention households met the study's definition of current users, though most (73% of adults and 95% of children) also reported drinking untreated water the previous day. The filter maintained a constant flow rate over time, though 12.4% of filters were damaged during the course of the study. CONCLUSIONS: While the filter was effective in improving water quality, our results provide little evidence that it was protective against diarrhea. The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03844341

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The HIV Tat protein affects processing of ribosomal RNA precursor

<p>Abstract</p> <p>Background</p> <p>Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.</p> <p>Results</p> <p>To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in <it>Drosophila melanogaster </it>strain transgenic for HIV-<it>tat </it>gene. Here we show that Tat localizes in the nucleoli of <it>Drosophila </it>oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.</p> <p>Conclusion</p> <p>Our data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells.</p

In Silico and Biochemical Analysis of Physcomitrella patens Photosynthetic Antenna: Identification of Subunits which Evolved upon Land Adaptation

Background. In eukaryotes the photosynthetic antenna system is composed of subunits encoded by the light harvesting complex (Lhc) multigene family. These proteins play a key role in photosynthesis and are involved in both light harvesting and photoprotection. The moss Physcomitrella patens is a member of a lineage that diverged from seed plants early after land colonization and therefore by studying this organism, we may gain insight into adaptations to the aerial environment. Principal Findings. In this study, we characterized the antenna protein multigene family in Physcomitrella patens, by sequence analysis as well as biochemical and functional investigations. Sequence identification and analysis showed that some antenna polypeptides, such as Lhcb3 and Lhcb6, are present only in land organisms, suggesting they play a role in adaptation to the sub-aerial environment. Our functional analysis which showed that photo-protective mechanisms in Physcomitrella patens are very similar to those in seed plants fits with this hypothesis. In particular, Physcomitrella patens also activates Non Photochemical Quenching upon illumination, consistent with the detection of an ortholog of the PsbS protein. As a further adaptation to terrestrial conditions, the content of Photosystem I low energy absorbing chlorophylls also increased, as demonstrated by differences in Lhca3 and Lhca4 polypeptide sequences, in vitro reconstitution experiments and low temperature fluorescence spectra. Conclusions. This study highlights the role of Lhc family members in environmental adaptation and allowed proteins associated with mechanisms of stress resistance to be identified within this large family

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases