miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia

Background: miRNA-based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity-independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT- PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia

Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6. However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6. Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time. After only four weeks of culture, for all iPSC lines studied, such tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiological sarcomere length (2.2 µm) and density of mitochondria (30%), the presence of transverse tubules, oxidative metabolism, a positive force-frequency relationship and functional calcium handling. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, supporting the utility of this tissue model for studies of cardiac development and disease.The authors acknowledge funding support from the National Institutes of Health of the USA (NIBIB and NCATS grant EB17103 (G.V.-N.); NIBIB, NCATS, NIAMS, NIDCR and NIEHS grant EB025765 (G.V.-N.); NHLBI grants HL076485 (G.V.-N.) and HL138486 (M.Y.); Columbia University MD/PhD program (S.P.M., T.C.); University of Minho MD/PhD program (D.T.); Japan Society for the Promotion of Science fellowship (K.M.); and Columbia University Stem Cell Initiative (D.S., L.S., M.Y.). We thank S. Duncan and B. Conklin for providing human iPSCs, M.B. Bouchard for assistance with image and video analysis, and L. Cohen-Gould for transmission electron microscopy services.info:eu-repo/semantics/publishedVersio

Direct and indirect effects of climate and fishing on changes in coastal ecosystem services: a historical perspective from the North Sea

Humanity depends on the marine environment for a range of vital ecosystem services, at global (e.g. climate regulation), regional (e.g. commercial fisheries) and local scales (e.g. coastal defence and recreation). At the same time, marine ecosystems have been exploited for centuries, and many systems today are under stress from multiple sources. Recent studies have shown how both climate change and fishing have caused long-term changes in the marine environment. However, there is still poor understanding of how these changes influence change in coastal ecosystem services. In this paper, an integrated modelling approach is used to assess how the final delivery of marine ecosystem services to coastal communities is influenced by the direct and indirect effects of changes in ecosystem processes brought about by climate and human impacts, using fisheries of the North Sea region as a case study. Partial least squares path analysis is used to explore the relationships between drivers of change, marine ecosystem processes and services (landings). A simple conceptual model with four variables—climate, fishing effort, ecosystem process and ecosystem services—is applied to the English North Sea using historic ecological, climatic and fisheries time series spanning 1924–2010 to identify the multiple pathways that might exist. As expected, direct and indirect links between fishing effort, ecosystem processes and service provision were significant. However, links between climate and ecosystem processes were weak. This paper highlights how path analysis can be used for analysing long-term temporal links between ecosystem processes and services following a simplified pathway

Climate induced temperature effects on growth performance, fecundity and recruitment in marine fish: developing a hypothesis for cause and effect relationships in Atlantic cod (Gadus morhua) and common eelpout (Zoarces viviparus).

Effects of global warming on animal distribution and performance become visible in many marine ecosystems. The present study was designed to develop a concept for a cause and effect understanding with respect to temperature changes and to explain ecological findings based on physiological processes. The concept is based on a wide comparison of invertebrate and fish species with a special focus on recent data obtained in two model species of fish. These fish species are both characterized by northern and southern distribution limits in the North Atlantic: eelpout (Zoarces viviparus), as a typical non-migrating inhabitant of the coastal zone and the cod (Gadus morhua), as a typical inhabitant of the continental shelf with a high importance for fisheries. Mathematical modelling demonstrates a clear significant correlation between climate induced temperature fluctuations and the recruitment of cod stocks. Growth performance in cod is optimal at temperatures close to 10 degreesC, regardless of the population investigated in a latitudinal cline. However, temperature specific growth rates decrease at higher latitudes. Also, fecundity is less in White Sea than in North and Baltic Sea cod or eelpout populations. These findings suggest that a cold-induced shift in energy budget occurs which is unfavorable for growth performance and fecundity. Thermal tolerance limits shift depending on latitude and are characterized by oxygen limitation at both low or high temperatures. Oxygen supply to tissues is optimized at low temperature by a shift in hemoglobin isoforms and oxygen binding properties to lower affinities and higher unloading potential. Protective stimulation of heat shock protein synthesis was not observed. According to a recent model of thermal tolerance the downward shift of tolerance limits during cold adaptation is associated with rising mitochondrial densities and, thus, aerobic capacity and performance in the cold. especially in eurythermal species. At the same time the costs of mitochondrial maintenance reflected by mitochondrial proton leakage should rise leaving a lower energy fraction for growth and reproduction. The preliminary conclusion can be drawn that warming will cause a northern shift of distribution limits for both species with a rise in growth performance and fecundity larger than expected from the Q(10) effect in the north and lower growth or even extinction of the species in the south. Such a shift may heavily affect fishing activities in the North Sea

Mapping protein sequence spaces by recurrence quantification analysis: a case study on chimeric structures

Recurrence quantification analysis (RQA) was used to characterize the folding properties of 22 chimeric sequences derived from two parent proteins of similar length but different three-dimensional arrangement. A non-linear relation between sequence data and their RQA representation was revealed, which points to new information carried by this method as compared with classical best-alignment methods. This new information is significantly correlated with the folding properties of the hybrid polypeptide chains, as substantiated by careful statistical analysis of the recurrence plots' numerical descriptors, thus encouraging their systematic use to complement sequence data in both proteomics and protein engineering tasks. Even the direct visual screening of the qualitative graphical features of recurrence plots is shown to provide useful hints to discriminate between different recurrence structures of protein sequences

Stima dell'individualità psico-fisiologica in operatori di call center.

Alcuni importanti indicatori psicologici (ricavati da test psicometrici) e fisiologici (frequenza cardiaca e attività elettrodermica cutanea) sono stati registrati nel corso della normale attività lavorativa in un gruppo di operatori di call center. Differenze interindividuali relativamente stabili nel tempo sono più facilmente evidenziabili per mezzo degli indicatori psicologici e, fra quelli fisiologici, i più sensibili in tale contesto risultano la frequenza cardiaca e la sua variabilità. L’attività elettrodermica cutanea, d’altra parte, si conferma, in tutti gli individui, come il più sensibile e rapido indicatore di risposta alle sollecitazioni dell’ambiente di lavoro

Breaking down the climate effects on cod recruitment by principal component analysis and canonical correlation

The pattern of temporal correlations between cod recruitment and sea temperature, in conjuction with the climate variability of atmospheric pressure anomalies (NAO index) was investigated by means of a combined use of principal component analysis (PCA) and canonical correlation analysis (CCA), using time series collected in the area surrounding the Kola peninsula (Barents Sea) and in the North Sea. The proposed data analysis strategy, namely to carry out a PCA of the temperature, cod recruitment and NAO time series followed by a CCA between the component spaces of all the possible data sets couples (recruitment vs temperature, recruitment vs NAO and NAO vs temperature), allowed us to sketch a general model of correlation between climate and cod recruitment dynamics. Two independent effects of temperature variability on cod recruitment emerged for the Kola region, pointing to the existence of at least 2 different mechanisms of comparable importance by which temperature may affect cod recruitment. In the North Sea the situation is somewhat simpler, and the data are compatible with only 1 major interaction mechanism. Moreover, the general effect of temperature on cod recruitment was opposite in the 2 regions: direct correlation for the Barents Sea, inverse correlation for the North Sea. This is probably due to the existence of an optimal temperature regime for cod recruitment lying in between the 'cold' Barents Sea and the 'warm' North Sea