Comparative (Meta)genomic Analysis and Ecological Profiling of Human Gut-Specific Bacteriophage φB124-14

Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape within the human gut microbiome

MCL-1 is a prognostic indicator and drug target in breast cancer

Analysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options. Deletion of MCL-1 in the mammary epithelium of genetically engineered mice revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical applicability of these findings was tested through a combination of approaches including knock-down or inhibition of MCL-1 to show triple-negative breast cancer cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that high MCL-1 protein expression is associated with poor outcome in breast cancer and support the therapeutic targeting of MCL-1 in this disease

Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia

BACKGROUND: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. OBJECTIVE: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. ANIMALS: Six healthy horses. METHODS: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non‐EEG measurements were also recorded. RESULTS: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. CONCLUSIONS AND CLINICAL IMPORTANCE: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose

Água de consumo humano como fator de risco à saúde em propriedades rurais Drinking water in rural farms as a risk factor to human health

OBJETIVO: Verificar a qualidade higiênico-sanitária da água de consumo humano em propriedades rurais por meio da contagem de indicadores microbiológicos de potabilidade. MÉTODOS: Foram colhidas 180 amostras de água utilizada para consumo humano das fontes, reservatórios e ponto de consumo em 30 propriedades rurais, situadas na região Nordeste do Estado de São Paulo. Determinou-se o número mais provável de coliformes totais, Escherichia coli e o número de microrganismos mesófilos. Foi verificada a presença de medidas de proteção das fontes de abastecimento. RESULTADOS: Os resultados evidenciaram que 90% das amostras de água das fontes, 90% dos reservatórios e 96,7% de água de consumo humano, colhidas no período de chuvas, e 83,3%, 96,7% e 90%, daquelas colhidas respectivamente nos mesmos locais, durante a estiagem, estavam fora dos padrões microbiológicos de potabilidade para água de consumo humano. CONCLUSÕES: A água utilizada nas propriedades rurais foi considerada um importante fator de risco à saúde dos seres humanos que a utilizam. A adoção de medidas preventivas, visando à preservação das fontes de água, e o tratamento das águas já comprometidas são as ferramentas necessárias para diminuir consideravelmente o risco de ocorrência de enfermidades de veiculação hídrica.<br>OBJECTIVE: To assess the sanitary quality of drinking water in rural farms through counts of microbiological indicators. METHODS: A total of 180 drinking water samples from sources, reservoirs and water from site of consumption were collected in 30 rural farms located in the northeast region of the sate of São Paulo. The most probable number of total coliforms, Escherichia coli and mesophilic microorganisms were determined. Also, the presence of protection measures for water supplies wase verified. RESULTS: The study results showed that 90.0% of drinking water samples from sources, 90.0% from reservoirs, and 96.7% from sites of consumption, collected during the rainy season, and 83.3%, 96.7% and 90.0% of samples collected in dry season were below the quality control standards for drinking water. CONCLUSIONS: Drinking water in rural farms was considered a potential human health threat. Preventive measures for protecting water sources and water treatment are necessary to significantly reduce the occurrence of waterborne diseases