GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask

Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools

A rescued dataset of sub-daily meteorological observations for Europe and the southern Mediterranean region, 1877–2012

Sub-daily meteorological observations are needed for input to and assessment of high-resolution reanalysis products to improve understanding of weather and climate variability. While there are millions of such weather observations that have been collected by various organisations, many are yet to be transcribed into a useable format. Under the auspices of the Uncertainties in Ensembles of Regional ReAnalyses (UERRA) project, we describe the compilation and development of a digital dataset of 8.8 million meteorological observations of essential climate variables (ECVs) rescued across the European and southern Mediterranean region. By presenting the entire chain of data preparation, from the identification of regions lacking in digitised sub-daily data and the location of original sources, through the digitisation of the observations to the quality control procedures applied, we provide a rescued dataset that is as traceable as possible for use by the research community. Data from 127 stations and of 15 climate variables in the northern African and European sectors have been prepared for the period 1877 to 2012. Quality control of the data using a two-step semi-automatic statistical approach identified 3.5 % of observations that required correction or removal, on par with previous data rescue efforts. In addition to providing a new sub-daily meteorological dataset for the research community, our experience in the development of this sub-daily dataset gives us an opportunity to share some suggestions for future data rescue projects. All versions of the dataset, from the raw digitised data to data that have been quality controlled and converted to standard units, are available on PANGAEA: https://doi.org/10.1594/PANGAEA.886511 (Ashcroft et al., 2018)

Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample

BACKGROUND: Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population. METHODS: A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory. RESULTS: Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms. CONCLUSIONS: The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account

Reprogramming of Escherichia coli K-12 Metabolism during the Initial Phase of Transition from an Anaerobic to a Micro-Aerobic Environment

Background: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Methods and Findings: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Conclusion: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions

PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients