18 research outputs found

    Ciprofloxacin-Resistant Neisseria meningitidis, Delhi, India

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    Decreased susceptibility of Neisseria meningitidis isolates to ciprofloxacin emerged from an outbreak in Delhi, India. Results of antimicrobial susceptibility testing of the meningococcal isolates to ciprofloxacin and further sequencing of DNA gyrase A quinolone-resistance–determining region confirmed the emergence of ciprofloxacin resistance in the outbreak

    linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

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    Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open-reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here, we show that two putative lincRNAs (linc-mipep, also called lnc-rps25, and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings reveal a key missing link in the evolution of vertebrate brain cell development and illustrate a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease

    Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

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    BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an

    Pseudonocardia antarctica sp. nov. an Actinomycetes from McMurdo Dry Valleys, Antarctica

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    Strain DVS 5a1 was isolated from a moraine sample from the McMurdo Dry Valleys region of Antarctica. The strain is aerobic, Gram-positive, with white aerial mycelia and brown substrate mycelia, sporulating, has meso-diaminopimelic acid, arabinose and galactose in the cell wall, MK-8 (H4) as the major menaquinone and a mol% G+C content of DNA of 71% thus confirming to the description of the genus Pseudonocardia. Phylogenetic analysis based on the 16S rRNA gene sequence analysis further confirms that DVS 5a1 which forms a robust clade with P. alni, P. compacta, P. autotrophica and P. kongjuensis is closely related to the genus Pseudonocardia and exhibits maximum similarity of 99.7% with Pseudonocardia alni. However, at whole genome level as determined by DNA-DNA hybridisation DVS 5a1 exhibits a similarity of only 50% with Pseudonocardia alni. Further, DVS 5a1 differs from Pseudonocardia alni in that it does not produce acid from D-arabinose, meso- erythritol, melizitose, sorbitol, sucrose, D-trehalose; but produces acid from D-mannitol, D-galactose, D-maltose, D-mannose, inulin, D-ribose and D-xylose. Further, compared to Pseudonocardia alni, it has two additional fatty acids namely Me-C18:0 and Me-C19:0 and also possesses one additional unidentified lipid. It also shows distinct differences with P. compacta, P. autotrophica and P. kongjuensis and the other species of Pseudonocardia. It is proposed to assign DVS 5a1 the status of a new species for which the name Pseudonocardia antarctica sp. nov. is suggested

    Bacillus arsenicus sp. nov., an arsenic-resistant bacterium isolated from a siderite concretion in West Bengal, India

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    Strain Con a/3T is a Gram-positive, motile, endospore-forming, rod-shaped and arsenic-resistant bacterium, which was isolated from a concretion of arsenic ore obtained from a bore-hole. The bacterium grew in the presence of 20 mM arsenate and 0·5 mM arsenite. Diaminopimelic acid was present in the cell wall peptidoglycan, MK-7 was the major menaquinone, and iso-C15:0, anteiso-C15:0, iso-C16:0 and C16:1(δ7cis) were the major fatty acids. Based on its phenotypic, chemotaxonomic and phylogenetic characteristics, strain Con a/3T was identified as a member of the genus Bacillus. It exhibited maximum similarity (97%) at the 16S rRNA gene level with Bacillus barbaricus (DSM 14730T); however, the DNA-DNA relatedness value with B. barbaricus was 60%. Strain Con a/3T also exhibited a number of phenotypic differences from B. barbaricus (DSM 14730T). Strain Con a/3T was therefore identified as representing a novel species of the genus Bacillus, for which the name Bacillus arsenicus sp. nov. is proposed. The type strain is Con a/3T (=MTCC 4380T=DSM 15822T=JCM 12167T)

    Importance of trmE for Growth of the Psychrophile Pseudomonas syringae at Low Temperatures▿ †

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    Transposon mutagenesis of Pseudomonas syringae Lz4W, a psychrophilic bacterium capable of growing at temperatures between 2 and 30°C, yielded 30 cold-sensitive mutants, and CSM1, one of these cold-sensitive mutants, was characterized. Growth of CSM1 was retarded when it was cultured at 4°C but not when it was cultured at 22°C and 28°C compared to the growth of wild-type cells, indicating that CSM1 is a cold-sensitive mutant of P. syringae Lz4W. The mutated gene in CSM1 was identified as trmE (coding for tRNA modification GTPase), and evidence is provided that this gene is induced at low temperatures. Further, the cold-inducible nature of the trmE promoter was demonstrated. In addition, the transcription start site and the various regulatory elements of the trmE promoter, such as the −10 region, −35 region, UP element, cold box, and DEAD box, were identified, and the importance of these regulatory elements in promoter activity were confirmed. The importance of trmE in rapid adaptation to growth at low temperatures was further highlighted by plasmid-mediated complementation that alleviated the cold-sensitive phenotype of CSM1

    Psychrophilic Planococcus maitriensis sp.nov. from Antarctica

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    An orange pigmented bacterium, S1, was isolated from a cyanobacterial mat sample collected in the vicinity of Schirmacher Oasis, Maitri, the Indian station, in Antarctica. The bacterium is Gram-positive and possesses all the characteristics of the genus Planococcus. It is non-sporulating, motile and has A4α type peptidoglycan, MK-7 and MK-8 as the major menaquinones and anteiso-C<SUB>15:0</SUB> as the major fatty acid. Based on the phylogenetic characteristics, the bacterium S1 is identified as a close relative of Planococcus citreus with which it shares 98.12% similarity at the 16S rRNA gene level but exhibits a low similarity of 52% at the whole genome level. Apart from the above major differences, S1 also exhibits phenotypic differences with Planococcus citreus and other members of the genus Planococcus. Based on these differences, the bacterium S1 is identified as a new species of the genus Planococcus for which the name Planococcus maitriensis is proposed. The type strain of Planococcus maitriensis is S1<SUP>T</SUP> (= MTCC 4827; DSM 15305)

    Purification and characterisation of extracellular protease produced by Clostridium sp. from Schirmacher oasis, Antarctica

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    One anaerobic, proteolytic bacterium isolated from Schirmacher oasis, Antarctica was characterised taxonomically. Based on morphology, biochemical characteristics and 16S rRNA sequence the isolate was identified as Clostridium species with closest similarity with Clostridium subterminale. Isolate was psychrotrophic forming maximum cell mass between 5 and 10 °C and produced extracellular protease. Growth was observed in the pH range of 6.5-8.5 with optimum at pH 8. Protease was purified 12.7-fold with a total yield of 26.2%. Effect of temperature, pH and salt concentration on enzyme activity were studied. Protease was found to be a serine-type metaloenzyme, which is active in a broad range of pH. It was moderately thermolabile and resistant to SDS. Enzyme kinetics revealed a tendency to decrease Km with increase in temperature for casein substrate

    The Reliability and Validity of the MATRICS Functional Assessment Battery

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    ObjectivesThe Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was designed to encourage the development of cognitive enhancing agents for schizophrenia. For a medication to receive this indication, regulatory agencies require evidence of improvement in both cognition and functional outcome. Functional capacity measures typically used in clinical trials as intermediate measures of functional outcome must be adapted to fit different cultural contexts for use internationally. We examined the psychometric properties of the MATRICS Functional Assessment Battery (MFAB), comprised of 2 subtests from the UCSD Performance-based Skills Assessment (UPSA) and one from the Test of Adaptive Behavior in Schizophrenia (TABS) that were rated by experts in a previous study to be the most appropriate functional capacity assessments across different cultural contexts.MethodFour sites in India administered the MFAB, a brief version of the UPSA, the MATRICS Cognitive Consensus Battery, measures of symptomatology, and a measure of global functional outcome to 141 individuals with schizophrenia at a baseline assessment and at 4 weeks later.ResultsTest-retest reliability based on the intraclass correlation coefficient was significantly better for the UCSD Performance-Based Skills Assessment-Brief (UPSA-B). Pearson correlation coefficients over time were not significantly different for the 2 measures. Only the MFAB was significantly correlated with functional outcome as measured by the Specific Levels of Functioning Scale.ConclusionsThe psychometric properties of the MFAB and UPSA-B were similar. The MATRICS scientific board chose to translate the MFAB into multiple languages for potential use in studies of novel medications seeking an indication for improving cognition in schizophrenia
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