214 research outputs found

    Public Talks and Science Listens: A Community-Based Participatory Approach to Characterizing Environmental Health Risk Perceptions and Assessing Recovery Needs in the Wake of Hurricanes Katrina and Rita

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    In response to the human health threats stemming from Hurricanes Katrina and Rita, inter-disciplinary working groups representing P30-funded Centers of the National Institute Environmental Health Sciences were created to assess threats posed by mold, harmful alga blooms, chemical toxicants, and various infectious agents at selected sites throughout the hurricane impact zone. Because of proximity to impacted areas, UTMB NIEHS Center in Environmental Toxicology was charged with coordinating direct community outreach efforts, primarily in south Louisiana. In early October 2005, UTMB/NIEHS Center Community Outreach and Education Core, in collaboration with outreach counterparts at The University of Texas MD Anderson Cancer Center @ Smithville TX/Center for Research in Environmental Disease sent two groups into southern Louisiana. One group used Lafourche Parish as a base to deliver humanitarian aid and assess local needs for additional supplies during local recovery/reclamation. A second group, ranging through New Iberia, New Orleans, Chalmette, rural Terrebonne, Lafourche and Jefferson Parishes and Baton Rouge met with community environmental leaders, emergency personnel and local citizens to 1) sample public risk perceptions, 2) evaluate the scope and reach of ongoing risk communication efforts, and 3) determine how the NIEHS could best collaborate with local groups in environmental health research and local capacity building efforts. This scoping survey identified specific information gaps limiting efficacy of risk communication, produced a community “wish list” of potential collaborative research projects. The project provided useful heuristics for disaster response and management planning and a platform for future collaborative efforts in environmental health assessment and risk communication with local advocacy groups in south Terrebonne-Lafourche parishes

    Estudio cinético de la fotodegradación del ión p-hidroxibencenodiazonio en medio polar

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    A study on the photodecomposition of p-hydroxybenzenediazonium ion (PDQ) has been made using chromatographicand spectrophotometric data obtained from UV-irradiated (254 nm) PDQ solutions in acetonitrile and aqueous media.The HPLC and HPLC-mass results indicate that 4-acetamidophenol is the main product formed after the irradiationof PDQ in acetonitrile. This is explained as a consequence of the initial formation of the aryl cation which is laterinvolved in a Ritter’s reaction. A kinetic analysis of the spectrophotometric data reveals that PDQ photodegradation isfaster in acetonitrile (observed rate constant (kobs) = 0.1442 s-1) than in acidifi ed acetonitrile (kobs = 0.009 s-1) indicatinga higher photostability of the protonated species derived from PDQ. The second order constant (0.062 M s-1) found forthe PDQ photodecomposition in phosphate buffer (pH 7) is explained in term of the equilibrium between protonatedand non-protonated species coming from the acid dissociation of PDQSe ha realizado un estudio sobre la fotodescomposición del ión p-hidroxibencenodiazonio (PDQ) basado en los datosespectrofotométricos y cromatográfi cos obtenidos con disoluciones de PDQ expuestas a irradiación UV (254 nm) enmedio de acetonitrilo y agua. Los resultados de HPLC y HPLC-masa (HPLC/MS) indican que el 4-acetamidofenoles el principal producto que se forma tras la irradiación de PDQ en acetonitrilo. Esto se explica como consecuenciade la formación inicial del catión arilo, que posteriormente participa en una reacción de Ritter. El análisis cinéticode los datos espectrofotométricos revela que la fotodegradación de PDQ es más rápida en acetonitrilo (constantede velocidad observada, kobs, = 0,1442 s-1) que en acetonitrilo acidifi cado (kobs = 0,009 s-1), lo que indica una mayorfotoestabilidad de la especie protonada derivada de PDQ. La constante de segundo orden (0,062 M s-1) encontradapara la fotodescomposición de PDQ en tampón fosfato (pH 7) se justifi ca por el establecimiento de un equilibrioentre las especies protonada y no protonada procedentes de la disociación ácida de PDQ

    Prevalence of hazardous alcohol use among Spanish primary care providers

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    BackgroundAlcohol use by health care professionals is one of the potential factors that may affect the prevention of hazardous drinking in Primary Care (PC). The objective of the study was to estimate the prevalence of hazardous alcohol use by PC professionals and assess the existing relationship between socio-demographic and occupational variables of PC professionals and their alcohol use.MethodsA descriptive, cross-sectional, observational, multicenter study was performed. Location: PC sites of the Spanish National Health Care System (NHS). Participants: Physicians and nurses, who completed an online questionnaire intended to identify the pattern of hazardous alcohol use through the AUDIT-C test. The study population was recruited through random sampling stratified by regions of the PC sites in the NHS. The primary measurements: Frequency of alcohol use, number of drinks containing alcohol on a typical day, frequency of six or more drinks on one occasion.ResultsOne thousand seven hundred sixty professionals completed the questionnaire. Hazardous alcohol use was detected in 27.80% (95% CI: 25.5-29.7) of PC providers. The prevalence of hazardous alcohol use was higher in males (34.2%) [95% CI: 30.4-37.6] and professionals aged 56years or over (34.2%) [95% CI: 28.2-40.2]. The multiple logistic regression analysis revealed a higher hazardous use in males (OR=1.52; 95% CI: 1.22-1.90), PC physicians (OR=1.42; 95% CI: 1.01-2.02) and professionals with more time worked (OR=1.03; 95% CI: 1.01-1.05).ConclusionOur study shows the current prevalence of hazardous alcohol use among Spanish PC providers, revealing a higher percentage of hazardous alcohol use in healthcare professionals compared to the Spanish general population. Further interventions are required to increase the awareness of negative consequences derived from alcohol use among PC professionals and its impact on the clinical setting

    The genome of Streptococcus pneumoniae is organized in topology-reacting gene clusters

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    The transcriptional response of Streptococcus pneumoniae was examined after exposure to the GyrB-inhibitor novobiocin. Topoisomer distributions of an internal plasmid confirmed DNA relaxation and recovery of the native level of supercoiling at low novobiocin concentrations. This was due to the up-regulation of DNA gyrase and the down-regulation of topoisomerases I and IV. In addition, >13% of the genome exhibited relaxation-dependent transcription. The majority of the responsive genes (>68%) fell into 15 physical clusters (14.6–85.6 kb) that underwent coordinated regulation, independently of operon organization. These genomic clusters correlated with AT content and codon composition, showing the chromosome to be organized into topology-reacting gene clusters that respond to DNA supercoiling. In particular, down-regulated clusters were flanked by 11–40 kb AT-rich zones that might have a putative structural function. This is the first case where genes responding to changes in the level of supercoiling in a coordinated manner were found organized as functional clusters. Such an organization revealed DNA supercoiling as a general feature that controls gene expression superimposed on other kinds of more specific regulatory mechanisms

    Interplay of DNA supercoiling and catenation during the segregation of sister duplexes

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    The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo

    Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication

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    DNA topology plays a crucial role in all living cells. In prokaryotes, negative supercoiling is required to initiate replication and either negative or positive supercoiling assists decatenation. The role of DNA knots, however, remains a mystery. Knots are very harmful for cells if not removed efficiently, but DNA molecules become knotted in vivo. If knots are deleterious, why then does DNA become knotted? Here, we used classical genetics, high-resolution 2D agarose gel electrophoresis and atomic force microscopy to show that topoisomerase IV (Topo IV), one of the two type-II DNA topoisomerases in bacteria, is responsible for the knotting and unknotting of sister duplexes during DNA replication. We propose that when progression of the replication forks is impaired, sister duplexes become loosely intertwined. Under these conditions, Topo IV inadvertently makes the strand passages that lead to the formation of knots and removes them later on to allow their correct segregation

    Ascl1 (Mash1) Defines Cells with Long-Term Neurogenic Potential in Subgranular and Subventricular Zones in Adult Mouse Brain

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    Ascl1 (Mash1) is a bHLH transcription factor essential for neural differentiation during embryogenesis but its role in adult neurogenesis is less clear. Here we show that in the adult brain Ascl1 is dynamically expressed during neurogenesis in the dentate gyrus subgranular zone (SGZ) and more rostral subventricular zone (SVZ). Specifically, we find Ascl1 levels low in SGZ Type-1 cells and SVZ B cells but increasing as the cells transition to intermediate progenitor stages. In vivo genetic lineage tracing with a tamoxifen (TAM) inducible Ascl1CreERT2 knock-in mouse strain shows that Ascl1 lineage cells continuously generate new neurons over extended periods of time. There is a regionally-specific difference in neuron generation, with mice given TAM at postnatal day 50 showing new dentate gyrus neurons through 30 days post-TAM, but showing new olfactory bulb neurons even 180 days post-TAM. These results show that Ascl1 is not restricted to transit amplifying populations but is also found in a subset of neural stem cells with long-term neurogenic potential in the adult brain

    Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination

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    Basic helix-loop-helix transcription factors Olig1 and Olig2 critically regulate oligodendrocyte development. Initially identified as a downstream effector of Olig1, an oligodendrocyte-specific zinc finger transcription repressor, Zfp488, cooperates with Olig2 function. Although Zfp488 is required for oligodendrocyte precursor formation and differentiation during embryonic development, its role in oligodendrogenesis of adult neural progenitor cells is not known. In this study, we tested whether Zfp488 could promote an oligodendrogenic fate in adult subventricular zone (SVZ) neural stem/progenitor cells (NSPCs). Using a cuprizone-induced demyelination model in mice, we examined the effect of retrovirus-mediated Zfp488 overexpression in SVZ NSPCs. Our results showed that Zfp488 efficiently promoted the differentiation of the SVZ NSPCs into mature oligodendrocytes in vivo. After cuprizone-induced demyelination injury, Zfp488-transduced mice also showed significant restoration of motor function to levels comparable to control mice. Together, these findings identify a previously unreported role for Zfp488 in adult oligodendrogenesis and functional remyelination after injury

    Expression of Neurog1 Instead of Atoh1 Can Partially Rescue Organ of Corti Cell Survival

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    In the mammalian inner ear neurosensory cell fate depends on three closely related transcription factors, Atoh1 for hair cells and Neurog1 and Neurod1 for neurons. We have previously shown that neuronal cell fate can be altered towards hair cell fate by eliminating Neurod1 mediated repression of Atoh1 expression in neurons. To test whether a similar plasticity is present in hair cell fate commitment, we have generated a knockin (KI) mouse line (Atoh1KINeurog1) in which Atoh1 is replaced by Neurog1. Expression of Neurog1 under Atoh1 promoter control alters the cellular gene expression pattern, differentiation and survival of hair cell precursors in both heterozygous (Atoh1+/KINeurog1) and homozygous (Atoh1KINeurog1/KINeurog1) KI mice. Homozygous KI mice develop patches of organ of Corti precursor cells that express Neurog1, Neurod1, several prosensory genes and neurotrophins. In addition, these patches of cells receive afferent and efferent processes. Some cells among these patches form multiple microvilli but no stereocilia. Importantly, Neurog1 expressing mutants differ from Atoh1 null mutants, as they have intermittent formation of organ of Corti-like patches, opposed to a complete ‘flat epithelium’ in the absence of Atoh1. In heterozygous KI mice co-expression of Atoh1 and Neurog1 results in change in fate and patterning of some hair cells and supporting cells in addition to the abnormal hair cell polarity in the later stages of development. This differs from haploinsufficiency of Atoh1 (Pax2cre; Atoh1f/+), indicating the effect of Neurog1 expression in developing hair cells. Our data suggest that Atoh1KINeurog1 can provide some degree of functional support for survival of organ of Corti cells. In contrast to the previously demonstrated fate plasticity of neurons to differentiate as hair cells, hair cell precursors can be maintained for a limited time by Neurog1 but do not transdifferentiate as neurons
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