Erratum: Correction: Kujawski et al. Autonomic and Cognitive Function Response to Normobaric Hyperoxia Exposure in Healthy Subjects. Preliminary Study. Medicina 2020, 56, 172 (Medicina (Kaunas, Lithuania) (2020) 56 4 PII: 255)

There was an error in the original publication [...]

Growth differentiation factor-11 causes neurotoxicity during ischemia in vitro

Age-related neuronal dysfunction can be overcome by circulating factors present inyoung blood. Growth differentiation factor-11 (GDF-11), a systemic factor that declineswith age, can reverse age-related dysfunction in brain, heart and skeletal muscle. Giventhat age increases susceptibility to stroke, we hypothesized that GDF-11 may be directlyprotective to neurons following ischemia. Primary cortical neurons were isolated fromE18 Wistar rat embryos and cultured for 7–10 days. Neurons were deprived of oxygenand glucose (OGD) to simulate ischemia. Neuronal death was assessed by lactatedehydrogenase, propidium iodide or CellToxTMgreen cytotoxicity assays. 40 ng/mLGDF-11 administration during 2 h OGD significantly increased neuronal death following24 h recovery. However, GDF-11 pre-treatment did not affect neuronal death during 2 hOGD. GDF-11 treatment during the 24 h recovery period after 2 h OGD also did notalter death. Real-time monitoring for 24 h revealed that by 2 h OGD, GDF-11 treatmenthad increased neuronal death which remained raised at 24 h. Co-treatment of 1µMSB431542 (ALK4/5/7 receptor inhibitor) with GDF-11 prevented GDF-11 neurotoxicityafter 2 h OGD and 24 h OGD. Transforming growth factor beta (TGFβ) did not increaseneuronal death to the same extent as GDF-11 following OGD. GDF-11 neurotoxicity wasalso exhibited following neuronal exposure to hydrogen peroxide. These results revealfor the first time that GDF-11 is neurotoxic to primary neurons in the acute phase ofsimulated stroke through primarily ALK4 receptor signaling

Calculating unreported confidence intervals for paired data

<p>Abstract</p> <p>Background</p> <p>Confidence intervals (or associated standard errors) facilitate assessment of the practical importance of the findings of a health study, and their incorporation into a meta-analysis. For paired design studies, these items are often not reported. Since the descriptive statistics for such studies are usually presented in the same way as for unpaired designs, direct computation of the standard error is not possible without additional information.</p> <p>Methods</p> <p>Elementary, well-known relationships between standard errors and <it>p</it>-values were used to develop computation schemes for paired mean difference, risk difference, risk ratio and odds ratio.</p> <p>Results</p> <p>Unreported confidence intervals for large sample paired binary and numeric data can be computed fairly accurately using simple methods provided the <it>p</it>-value is given. In the case of paired binary data, the design based 2 × 2 table can be reconstructed as well.</p> <p>Conclusions</p> <p>Our results will facilitate appropriate interpretation of paired design studies, and their incorporation into meta-analyses.</p

Prefracture functional level evaluated by the New Mobility Score predicts in-hospital outcome after hip fracture surgery

BACKGROUND AND PURPOSE: Clinicians need valid and easily applicable predictors of outcome in patients with hip fracture. Adjusting for previously established predictors, we determined the predictive value of the New Mobility score (NMS) for in-hospital outcome in patients with hip fracture. PATIENTS AND METHODS: We studied 280 patients with a median age of 81 (interquartile range 72-86) years who were admitted from their own homes to a special hip fracture unit. Main outcome was the regain of independence in basic mobility, defined as. independence in getting in and out of bed, sitting down and standing up from a chair, and walking with an appropriate walking aid. The Cumulated Ambulation score was used to evaluate basic mobility. Predictor variables were NMS functional level before fracture, age, sex, fracture type, and mental and health status. RESULTS: Except for sex, all predictor variables were statistically significant in univariate testing. In multiple logistic regression analysis, only age, NMS functional level before fracture, and fracture type were significant. Thus, patients with a low prefracture NMS and/or an intertrochanteric fracture would be 18 and 4 times more likely not to regain independence in basic mobility during the hospital stay, respectively, than patients with a high prefracture level and a cervical fracture, respectively. The model was statistically stable and correctly classified 84% of cases. INTERPRETATION: The NMS functional level before fracture, age, and fracture type facilitate prediction of the in-hospital rehabilitation potential after hip fracture surgery

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Failure to detect tuberculosis in Black lechwe antelopes (Kobus leche smithemani) in Zambia

<p>Abstract</p> <p>Background</p> <p>Two types of lechwe antelopes exclusively exist in their natural ecosystems in Zambia; the Black lechwe (<it>Kobus leche smithemani</it>) and the Kafue lechwe (<it>Kobus leche kafuensis</it>). Despite inhabiting similar ecosystems, tuberculosis has been reported in Kafue lechwe without its documentation in Black lechwe antelopes. However, the past few decades have seen a drastic decline in both lechwe populations. Whereas studies have postulated that infectious diseases such as tuberculosis are having a negative impact on the Kafue lechwe population, no information is available on Black lechwe antelopes. Thus this study was conducted to investigate tuberculosis in Black lechwe antelopes of the Bangweulu swamps in comparison with the Kafue lechwe antelopes of Lochinvar.</p> <p>Findings</p> <p>A total of 44 lechwe antelopes (Black (<it>n </it>= 30): Kafue (<it>n </it>= 14) were sampled from Bangweulu and Lochinvar respectively. A positive case was defined with findings of gross lesions with Ziehl Nielsen and culture confirmation. Out of the 14 animals examined in Lochinvar, 21.4% [95% CI: 15.4, 44.4%] had necropsy lesions consistent with tuberculosis. The corresponding samples from 30 Black lechwe of Bangweulu yielded negative results on all the three tests.</p> <p>Conclusions</p> <p>Current findings from this study intimate the possible absence of tuberculosis in Black lechwe antelopes whilst confirming the presence of tuberculosis in Kafue lechwe of the Kafue basin. The absence of tuberculosis in the Black lechwe suggests that the observed population decline may not be caused by tuberculosis. However, without detailed molecular epidemiological studies it is not possible to determine the association of <it>M. bovis </it>infection in sympatric animal populations. The possible role of transmission of tuberculosis between wildlife and cattle is discussed herein. <b>Findings</b></p

Clustered ChIP-Seq-defined transcription factor binding sites and histone modifications map distinct classes of regulatory elements

<p>Abstract</p> <p>Background</p> <p>Transcription factor binding to DNA requires both an appropriate binding element and suitably open chromatin, which together help to define regulatory elements within the genome. Current methods of identifying regulatory elements, such as promoters or enhancers, typically rely on sequence conservation, existing gene annotations or specific marks, such as histone modifications and p300 binding methods, each of which has its own biases.</p> <p>Results</p> <p>Herein we show that an approach based on clustering of transcription factor peaks from high-throughput sequencing coupled with chromatin immunoprecipitation (Chip-Seq) can be used to evaluate markers for regulatory elements. We used 67 data sets for 54 unique transcription factors distributed over two cell lines to create regulatory element clusters. By integrating the clusters from our approach with histone modifications and data for open chromatin, we identified general methylation of lysine 4 on histone H3 (H3K4me) as the most specific marker for transcription factor clusters. Clusters mapping to annotated genes showed distinct patterns in cluster composition related to gene expression and histone modifications. Clusters mapping to intergenic regions fall into two groups either directly involved in transcription, including miRNAs and long noncoding RNAs, or facilitating transcription by long-range interactions. The latter clusters were specifically enriched with H3K4me1, but less with acetylation of lysine 27 on histone 3 or p300 binding.</p> <p>Conclusion</p> <p>By integrating genomewide data of transcription factor binding and chromatin structure and using our data-driven approach, we pinpointed the chromatin marks that best explain transcription factor association with different regulatory elements. Our results also indicate that a modest selection of transcription factors may be sufficient to map most regulatory elements in the human genome.</p

Interaction between Ammonium Toxicity and Green Tide Development Over Seagrass Meadows:A Laboratory Study

Eutrophication affects seagrasses negatively by increasing light attenuation through stimulation of biomass of fast-growing, bloom-forming algae and because high concentrations of ammonium in the water can be toxic to higher plants. We hypothesized nevertheless, that moderate amounts of nitrophilic macroalgae that coexists with seagrasses under eutrophic conditions, can alleviate the harmful effects of eutrophication on seagrasses by reducing ammonium concentrations in the seawater to non-toxic levels because such algae have a very large capacity to take up inorganic nutrients. We studied therefore how combinations of different ammonium concentrations (0, 25 and 50 μM) and different standing stocks of macroalgae (i.e. 0, 1 and 6 layers of Ulva sp.) affected survival, growth and net production of the seagrass Zostera noltei. In the absence of Ulva sp., increasing ammonium concentrations had a negative influence on the performance of Z. noltei. The presence of Ulva sp. without ammonium supply had a similar, but slightly smaller, negative effect on seagrass fitness due to light attenuation. When ammonium enrichment was combined with presence of Ulva sp., Ulva sp. ameliorated some of negative effects caused by high ammonium availability although Ulva sp. lowered the availability of light. Benthic microalgae, which increased in biomass during the experiment, seemed to play a similar role as Ulva sp.--they contributed to remove ammonium from the water, and thus, aided to keep the ammonium concentrations experienced by Z. noltei at relatively non-toxic levels. Our findings show that moderate amounts of drift macroalgae, eventually combined with increasing stocks of benthic microalgae, may aid seagrasses to alleviate toxic effects of ammonium under eutrophic conditions, which highlights the importance of high functional diversity for ecosystem resistance to anthropogenic disturbance

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers.</p> <p>Methods</p> <p>Mice carrying human (FaDu_dd) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared.</p> <p>Results</p> <p>In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu_dd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker.</p> <p>Conclusions</p> <p>The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.</p