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Campos Nieves posted an update 1 month, 3 weeks ago
Voltage-dependent anion channel (VDAC), the most abundant mitochondrial outer membrane protein, is important for a variety of mitochondrial functions including metabolite exchange, calcium transport, and apoptosis. While VDAC’s role in shuttling metabolites between the cytosol and mitochondria is well established, there is a growing interest in understanding the mechanisms of its regulation of mitochondrial calcium transport. Here we review the current literature on VDAC’s role in calcium signaling, its biophysical properties, physiological function, and pathology focusing on its importance in cardiac diseases. We discuss the specific biophysical properties of the three VDAC isoforms in mammalian cells-VDAC 1, 2, and 3-in relationship to calcium transport and their distinct roles in cell physiology and disease. Highlighting the emerging evidence that cytosolic proteins interact with VDAC and regulate its calcium permeability, we advocate for continued investigation into the VDAC interactome at the contact sites between mitochondria and organelles and its role in mitochondrial calcium transport.Gradual ocean warming and marine heatwaves represent major threats for marine organisms already facing other anthropogenic-derived hazards, such as chemical contamination in coastal areas. In this study, the combined effects of thermal stress and exposure to gadolinium (Gd), a metal used as a contrasting agent in medical imaging which enters the aquatic environment, were investigated in the embryos and larvae of the sea urchin Paracentrotus lividus. Embryos were exposed to six treatments of three temperatures (18 °C, 21 °C, 24 °C) and two Gd concentrations (control 0 μM; treated 20 μM). With respect to developmental progression, increased temperature accelerated development and achievement of the larval stage, while Gd-exposed embryos at the control temperature (18 °C) showed a general delay in development at 24 h post-fertilization (hpf), and a stunting effect and impaired skeleton growth at 48 hpf. Elevated temperatures at near-future projections (+3 °C, 21 °C) reduced the negative effects of Gd on developm Gd-exposure on P. lividus larval development and biomineralization will be mitigated by a near-future ocean warming, up to a thermotolerance threshold when negative synergistic effects were evident. Our data highlight the use of biomarkers as sensitive tools to detect environmental impacts as well as the need for a better understanding of the interactions between the multiple stressors faced by marine species in coastal environments.Bipolar disorder is associated with cognitive deficits and cortical changes for which the developmental dynamics are not well understood. The dopamine D2 receptor (DRD2) gene has been associated with both psychiatric disorders and cognitive variability. Here we examined the mediating role of brain structure in the relationship between DRD2 genomic variation and cognitive performance, with target cortical regions selected based on evidence of association with DRD2, bipolar disorder and/or cognition from prior literature. Participants (n = 143) were aged 12-30 years and comprised 62 first-degree relatives of bipolar patients (deemed ‘at-risk’), 55 controls, and 26 patients with established bipolar disorder; all were unrelated Caucasian individuals with complete data across the three required modalities (structural magnetic resonance imaging, neuropsychological and genetic data). A DRD2 haplotype was derived from three functional polymorphisms (rs1800497, rs1076560, rs2283265) associated with alternative splicing (i.e., D2-short/-long isoforms). Moderated mediation analyses explored group differences in relationships between this DRD2 haplotype, three structural brain networks which subsume the identified cortical regions of interest (frontoparietal, dorsal-attention, and ventral-attention), and three cognitive indices (intelligence, attention, and immediate memory). Controls who were homozygous for the DRD2 major haplotype demonstrated greater cognitive performance as a result of dorsal-attention network mediation. However, this association was absent in the ‘at-risk’ group. This study provides the first evidence of a functional DRD2-brain-cognition pathway. The absence of typical brain-cognition relationships in young ‘at-risk’ individuals may reflect biological differences that precede illness onset. click here Further insight into early pathogenic processes may facilitate targeted early interventions.Bioproduction of medium chain carboxylic acids has recently emerged as an alternative strategy to valorize low-value organic waste and side-streams. Key to this route is chain elongation, an anaerobic microbial process driven by ethanol, lactic acid, or carbohydrates. Because these technologies use wastes as feedstocks, mixed microbial communities are often considered as biocatalysts. Understanding and steering these microbiomes is key to optimize bioprocess performance. From a meta-analysis of publicly available sequencing data, we (i) explore how the current collection of isolated chain elongators compares to microbiome members, (ii) discuss the main beneficial and antagonistic interactions with community partners, and (iii) identify the key research gaps and needs to help understand chain elongation microbiomes, and design/steer these novel bioproduction processes.
To systematically and meta-analytically pool the existing evidence regarding the prognostic impact of preoperative anemia (hemoglobin level <12 mg/dl) in patients with endometrial cancer.
Four (PubMed, Embase, Scopus and Web of Science) databases were searched from inception to 20-August-2020. We assessed the risk of bias using the Newcastle-Ottawa Scale. We estimated the pooled prevalence of preoperative anemia in the included studies. We pooled odds ratios (ORs) and hazard ratios (HRs) with their 95 % confidence intervals (95 % CIs) to evaluate the correlation between preoperative anemia and its impact on clinicopathologic parameters and survival outcomes. Analyses were performed under random- or fixed-effects meta-analysis models depending on data heterogeneity.
Seven studies met the inclusion criteria comprising 1495 patients with endometrial cancer. Nearly all studies had low risk of bias. The pooled prevalence of preoperative anemia was 26.5 % (95 % CI 18.6%-36.2%). Preoperative anemia significantly correlated with advanced FIGO stage III-IV (OR = 5.