341 research outputs found

    Meningitis due to Fusobacterium necrophorum in an adult

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    BACKGROUND: Fusobacterium necrophorum may cause a number of clinical syndromes, collectively known as necrobacillosis. Meningitis is a significant cause of mortality, rarely reported in the adult population. CASE PRESENTATION: We report a fatal case of meningitis, caused by Fusobacterium necrophorum, secondary to otitis media in an alcoholic male. Diagnosis was delayed due to the typical slow growth of the organism. The clinical course was complicated by encephalitis and by hydrocephalus. The patient failed to respond to metronidazole and penicillin. The patient died on day 12 from increased intracranial pressure and brain stem infarction. CONCLUSIONS: This case emphasizes the need for a high index of clinical suspicion to make the diagnosis of Fusobacterium necrophorum meningitis. We recommend the use of appropriate anaerobic culture techniques and antimicrobial coverage for anaerobic organisms when the gram stain shows gram negative bacilli

    Gene expression and matrix turnover in overused and damaged tendons

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    Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

    A method for studying protistan diversity using massively parallel sequencing of V9 hypervariable regions of small-subunit ribosomal RNA genes

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    Š 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 4 (2009): e6372, doi:10.1371/journal.pone.0006372.Massively parallel pyrosequencing of amplicons from the V6 hypervariable regions of small-subunit (SSU) ribosomal RNA (rRNA) genes is commonly used to assess diversity and richness in bacterial and archaeal populations. Recent advances in pyrosequencing technology provide read lengths of up to 240 nucleotides. Amplicon pyrosequencing can now be applied to longer variable regions of the SSU rRNA gene including the V9 region in eukaryotes. We present a protocol for the amplicon pyrosequencing of V9 regions for eukaryotic environmental samples for biodiversity inventories and species richness estimation. The International Census of Marine Microbes (ICoMM) and the Microbial Inventory Research Across Diverse Aquatic Long Term Ecological Research Sites (MIRADA-LTERs) projects are already employing this protocol for tag sequencing of eukaryotic samples in a wide diversity of both marine and freshwater environments. Massively parallel pyrosequencing of eukaryotic V9 hypervariable regions of SSU rRNA genes provides a means of estimating species richness from deeply-sampled populations and for discovering novel species from the environment.This work was supported by grants from the W.M. Keck Foundation and the Woods Hole Center for Oceans and Human Health from the National Institutes of Health and National Science Foundation (NIH/NIEHS 1 P50 ES012742-01 and NSF/OCE 0430724-J) (LAZ and SH)

    Cigarette Smoking and Cognitive Function in Chinese Male Schizophrenia: A Case-Control study

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    Schizophrenic patients have higher smoking rates than the general population. Studies show that smoking may be a form of self-medication in an attempt to alleviate cognitive deficits in schizophrenic patients of European background. This study examined the relationships between smoking and cognitive deficits in Chinese schizophrenic patients, which have previously received little systemic study. We recruited 580 male chronic patients meeting DSM-IV criteria for schizophrenia and 175 male control subjects who were matched on age and education. The subjects completed a detailed cigarette smoking questionnaire, the Fagerstrom Test for Nicotine Dependence (FTND), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). All five RBANS subscales except for the Visuospatial/Constructional index showed significantly lower cognitive performance for schizophrenics than normal controls. The schizophrenic smokers scored lower than the schizophrenic non-smokers on the RBANS total score and the Visuospatial/Constructional and Immediate Memory indices. Similarly, the control smokers scored lower than the control non-smokers on the RBANS total score and the Immediate Memory index . Also, the schizophrenic smokers consistently performed the poorest on the cognitive domains of the RBANS. Among the schizophrenic patients, smokers displayed significantly fewer negative symptoms than non-smokers. Using multivariate regression analysis the following variables were independently associated with the RBANS total score: years of education, PANSS negative symptom score, age at schizophrenia onset, and number of hospitalizations. Our results show that smoking is associated with significant cognitive impairment in both schizophrenic patients and normal controls, but the smokers with schizophrenia had a reduced level of negative symptoms, suggesting that the benefits of smoking for those with schizophrenia may be limited to certain aspects of a given clinical phenotype

    Reconstruction of Ribosomal RNA Genes from Metagenomic Data

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    Direct sequencing of environmental DNA (metagenomics) has a great potential for describing the 16S rRNA gene diversity of microbial communities. However current approaches using this 16S rRNA gene information to describe community diversity suffer from low taxonomic resolution or chimera problems. Here we describe a new strategy that involves stringent assembly and data filtering to reconstruct full-length 16S rRNA genes from metagenomicpyrosequencing data. Simulations showed that reconstructed 16S rRNA genes provided a true picture of the community diversity, had minimal rates of chimera formation and gave taxonomic resolution down to genus level. The strategy was furthermore compared to PCR-based methods to determine the microbial diversity in two marine sponges. This showed that about 30% of the abundant phylotypes reconstructed from metagenomic data failed to be amplified by PCR. Our approach is readily applicable to existing metagenomic datasets and is expected to lead to the discovery of new microbial phylotypes

    Bioinformatics for the human microbiome project

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    Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, particularly since microbial dysbioses have now been implicated in a number of human diseases [1]–[3]. Dysbiosis, the disruption of the normal microbial community structure, however, is impossible to define without first establishing what “normal microbial community structure” means within the healthy human microbiome. Recent advances in sequencing technologies have made it feasible to perform large-scale studies of microbial communities, providing the tools necessary to begin to address this question [4], [5]. This led to the implementation of the Human Microbiome Project (HMP) in 2007, an initiative funded by the National Institutes of Health Roadmap for Biomedical Research and constructed as a large, genome-scale community research project [6]. Any such project must plan for data analysis, computational methods development, and the public availability of tools and data; here, we provide an overview of the corresponding bioinformatics organization, history, and results from the HMP (Figure 1).National Institutes of Health (U.S.) (NIH U54HG004969)National Institutes of Health (U.S.) (grant R01HG004885)National Institutes of Health (U.S.) (grant R01HG005975)National Institutes of Health (U.S.) (grant R01HG005969

    Gut-central nervous system axis is a target for nutritional therapies

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    Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies

    High-Resolution X-Ray Structure of the Trimeric Scar/WAVE-Complex Precursor Brk1

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    The Scar/WAVE-complex links upstream Rho-GTPase signaling to the activation of the conserved Arp2/3-complex. Scar/WAVE-induced and Arp2/3-complex-mediated actin nucleation is crucial for actin assembly in protruding lamellipodia to drive cell migration. The heteropentameric Scar/WAVE-complex is composed of Scar/WAVE, Abi, Nap, Pir and a small polypeptide Brk1/HSPC300, and recent work suggested that free Brk1 serves as a homooligomeric precursor in the assembly of this complex. Here we characterized the Brk1 trimer from Dictyostelium by analytical ultracentrifugation and gelfiltration. We show for the first time its dissociation at concentrations in the nanomolar range as well as an exchange of subunits within different DdBrk1 containing complexes. Moreover, we determined the three-dimensional structure of DdBrk1 at 1.5 Å resolution by X-ray crystallography. Three chains of DdBrk1 are associated with each other forming a parallel triple coiled-coil bundle. Notably, this structure is highly similar to the heterotrimeric α-helical bundle of HSPC300/WAVE1/Abi2 within the human Scar/WAVE-complex. This finding, together with the fact that Brk1 is collectively sandwiched by the remaining subunits and also constitutes the main subunit connecting the triple-coil domain of the HSPC300/WAVE1/Abi2/ heterotrimer to Sra1(Pir1), implies a critical function of this subunit in the assembly process of the entire Scar/WAVE-complex
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