Corticotropin-releasing hormone exerts direct effects on neuronal progenitor cells: implications for neuroprotection

Neurogenesis during embryonic and adult life is tightly regulated by a network of transcriptional, growth and hormonal factors. Emerging evidence indicates that activation of the stress response, via the associated glucocorticoid increase, reduces neurogenesis and contributes to the development of adult diseases.As corticotrophin-releasing hormone (CRH) or factor is the major mediator of adaptive response to stressors, we sought to investigate its involvement in this process. Accordingly, we found that CRH could reverse the damaging effects of glucocorticoid on neural stem/progenitor cells (NS/PCs), while its genetic deficiency results in compromised proliferation and enhanced apoptosis during neurogenesis. Analyses in fetal and adult mouse brain revealed significant expression of CRH receptors in proliferating neuronal progenitors. Furthermore, by using primary cultures of NS/PCs, we characterized the molecular mechanisms and identified CRH receptor-1 as the receptor mediating the neuroprotective effects of CRH. Finally, we demonstrate the expression of CRH receptors in human fetal brain from early gestational age, in areas of active neuronal proliferation. These observations raise the intriguing possibility for CRH-mediated pharmacological applications in diseases characterized by altered neuronal homeostasis, including depression, dementia, neurodegenerative diseases, brain traumas and obesity

Atomic order and cluster energetics of a 17 w.t.% Si-based glass versus the liquid phase

Aerodynamic levitation of a multi component 17 w.t.% Si glass formed by rapid quenching of the melt phase was studied by high resolution X-ray diffraction (XRD) and Reverse Monte Carlo (RMC) modeling. The main local atomic order features comprised of interactions between Si, Fe and Mg polyhedra, the stereochemistry of which was on a par with literature. Both the glass and the liquid state appeared to consist of the same fundamental Si-O, Fe-O and Mg-O clusters, with only the relative number of each varying between the two. Transition from liquid to the glass involved a 3-fold decrease in uncoordinated O (to within the first minimum of the total g(r)) and a marked increase of Fe-Si-Mg polyhedra bridging O. Octahedral Fe coordination was not suggested by the RMC data. All-electron open-shell Density Functional Theory (DFT) calculations of the most prominent clusters suggested independence between the Fe oxidation state and its polyhedra O-coordination. Of secondary thermodynamic importance were indications of network-forming Fe2+ and Fe3+ distorted trigonal and tetrahedral polyhedra. In all occasions, the Fe ferrous and ferric states involved comparable binding energies within similar clusters which indicate a dynamic equilibrium between the two

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation.Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR.Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-?B, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased.Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained ‘perpetual cycle’ of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity

GeoTriples: Transforming geospatial data into RDF graphs using R2RML and RML mappings

A lot of geospatial data has become available at no charge in many countries recently. Geospatial data that is currently made available by government agencies usually do not follow the linked data paradigm. In the few cases where government agencies do follow the linked data paradigm (e.g., Ordnance Survey in the United Kingdom), specialized scripts have been used for transforming geospatial data into RDF. In this paper we present the open source tool GeoTriples which generates and processes extended R2RML and RML mappings that transform geospatial data from many input formats into RDF. GeoTriples allows the transformation of geospatial data stored in raw files (shapefiles, CSV, KML, XML, GML and GeoJSON) and spatially-enabled RDBMS (PostGIS and MonetDB) into RDF graphs using well-known vocabularies like GeoSPARQL and stSPARQL, but without being tightly coupled to a specific vocabulary. GeoTriples has been developed in European projects LEO and Melodies and has been used to transform many geospatial data sources into linked data. We study the performance of GeoTriples experimentally using large publicly available geospatial datasets, and show that GeoTriples is very efficient and scalable especially when its mapping processor is implemented using Apache Hadoop

Bio-psychosocial determinants of cardiovascular disease in a rural population on Crete, Greece: formulating a hypothesis and designing the SPILI-III study

Background: In 1988, the SPILI project was established in order to evaluate the cardiovascular disease (CVD) risk profile of the inhabitants of Spili, in rural Crete, Greece. The first reports from this project revealed that against the unfavourable risk factors’ profile observed, only a few men with a previous myocardial infarction were encountered. A follow-up study (SPILI II) was performed twelve years after the initial examination, and the unfavourable cardiovascular risk profile was re-confirmed. Presentation of the Hypothesis: This paper presents a hypothesis formulated on the basis of previous research to investigate if dynamic psycho-social determinants, including social coherence of the local community, religiosity and spirituality, are protective against the development of coronary heart disease in a well-defined population. Testing the Hypothesis: A follow-up examination of this Cretan cohort is currently being performed to assess the link between psychosocial factors and CVD. Psychosocial factors including sense of control, religiosity and spirituality are assessed in together with conventional CVD risk factors. Smoking and alcohol consumption, as well as dietary habits and activity levels are recorded. Oxidative stress and inflammatory markers, as well as ultrasound measurement of carotid intima media thickness, a preclinical marker of atherosclerosis, will also be measured. Implications of the hypothesis tested: The issue of the cardio-protective effect of psycho-social factors would be revisited based on the results of this Cretan cohort; nevertheless, further research is needed across different subpopulations in order to establish a definite relationship. A comprehensive approach based on the aspects of biosocial life may result in more accurate CVD risk management

A Novel Role of Peripheral Corticotropin-Releasing Hormone (CRH) on Dermal Fibroblasts

Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh−/−) had higher proliferation and migration rates and compromised production of IL-6 and TGF-β1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF1 antagonist antalarmin recapitulated the findings in the Crh−/− cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis

On the Energy Transfer Performance of Mechanical Nanoresonators Coupled with Electromagnetic Fields

We study the energy transfer performance in electrically and magnetically coupled mechanical nanoresonators. Using the resonant scattering theory, we show that magnetically coupled resonators can achieve the same energy transfer performance as for their electrically coupled counterparts, or even outperform them within the scale of interest. Magnetic and electric coupling are compared in the Nanotube Radio, a realistic example of a nano-scale mechanical resonator. The energy transfer performance is also discussed for a newly proposed bio-nanoresonator composed of a magnetosomes coated with a net of protein fibers.Comment: 9 Pages, 3 Figure

Effect of religiosity/spirituality and sense of coherence on depression within a rural population in Greece: the Spili III project

Background: Recent research has addressed the hypothesis that religiosity/spirituality and sense of coherence buffer the negative effects of stress on numerous health issues. The aim of the current study was to further this work by exploring potential links between psycho-social factors such as religiosity/ spirituality and sense of coherence with depression. Methods: A total of 220 subjects of the SPILI III cohort (1988-2012) attending a primary care setting in the town of Spili on rural Crete represented the target group. All participants underwent a standardized procedure. Validated questionnaires were used to evaluate sense of coherence, depression levels and religious and spiritual beliefs. A multiple linear regression analysis of the Beck Depression Inventory Scale (BDI) in relation to demographic characteristics, scores on the Royal Free Interview for Spiritual and Religious Beliefs scale (RFI-SRB) and Sense of Coherence scale (SOC) was used. Results: A significant inverse association was found between BDI and RFI-SRB scale (B-coef=-0.6999, p<0.001), as well as among BDI and SOC scale (B-coef=-0.556, p<0.001). Conclusions: The findings of the current observational study indicate that highly religious participants are less likely to score high in the depression scale. Furthermore, participants with high SOC scored significantly low in the BDI scale. Further research is required in order to explore the potential effect of SOC and religiosity/spirituality in mental health