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The changes in the expression of these proteins suggest that the proteins are important for RWW survival in winter. Copyright © 2020 Xinxin, Shuang, Xunming, Shang, Juhong and Jinghui.Characterizing brain activity at rest is of paramount importance to our understanding both of general principles of brain functioning and of the way brain dynamics is affected in the presence of neurological or psychiatric pathologies. We measured the time-reversal symmetry of spontaneous electroencephalographic brain activity recorded from three groups of patients and their respective control group under two experimental conditions (eyes open and closed). We evaluated differences in time irreversibility in terms of possible underlying physical generating mechanisms. The results showed that resting brain activity is generically time-irreversible at sufficiently long time scales, and that brain pathology is generally associated with a reduction in time-asymmetry, albeit with pathology-specific patterns. The significance of these results and their possible dynamical etiology are discussed. Some implications of the differential modulation of time asymmetry by pathology and experimental condition are examined. Copyright © 2020 Zanin, Güntekin, Aktürk, Hanoğlu and Papo.Vasculogenesis, angiogenesis and arteriogenesis represent three crucial mechanisms involved in the formation and maintenance of the vascular network in embryonal and post-natal life. It has long been known that endothelial Ca2+ signals are key players in vascular remodeling; indeed, multiple pro-angiogenic factors, including vascular endothelial growth factor, regulate endothelial cell fate through an increase in intracellular Ca2+ concentration. Transient Receptor Potential (TRP) channel consist in a superfamily of non-selective cation channels that are widely expressed within vascular endothelial cells. In addition, TRP channels are present in the two main endothelial progenitor cell (EPC) populations, i.e., myeloid angiogenic cells (MACs) and endothelial colony forming cells (ECFCs). TRP channels are polymodal channels that can assemble in homo- and heteromeric complexes and may be sensitive to both pro-angiogenic cues and subtle changes in local microenvironment. These features render TRP channels the moss featured by abnormal vascularization, including cancer, ischemic disorders, retinal degeneration and neurodegeneration. Copyright © 2020 Negri, Faris, Berra-Romani, Guerra and Moccia.The stinging catfish, Heteropneustes fossilis, can tolerate high concentrations of environmental ammonia. Previously, it was regarded as ureogenic, having a functional ornithine-urea cycle (OUC) that could be up-regulated during ammonia-loading. However, contradictory results indicated that increased urea synthesis and switching to ureotelism could not explain its high ammonia tolerance. Hence, we re-examined the effects of exposure to 30 mmol l-1 NH4Cl on its ammonia and urea excretion rates, and its tissue ammonia and urea concentrations. Our results confirmed that H. fossilis did not increase urea excretion or accumulation during 6 days of ammonia exposure, and lacked detectable carbamoyl phosphate synthetase I or III activity in its liver. However, we discovered that it could actively excrete ammonia during exposure to 8 mmol l-1 NH4Cl. As active ammonia excretion is known to involve Na+/K+-ATPase (Nka) indirectly in several ammonia-tolerant fishes, we also cloned various nkaα-subunit isoforms from the gills of H. fossilis, and determined the effects of ammonia exposure on their branchial transcripts levels and protein abundances. Results obtained revealed the presence of five nkaα-subunit isoforms, with nkaα1b having the highest transcript level. Exposure to 30 mmol l-1 NH4Cl led to significant increases in the transcript levels of nkaα1b (on day 6) and nkaα1c1 (on day 1 and 3) as compared with the control. In addition, the protein abundances of Nkaα1c1, Nkaα1c2, and total NKAα increased significantly on day 6. Therefore, the high environmental ammonia tolerance of H. fossilis is attributable partly to its ability to actively excrete ammonia with the aid of Nka. Copyright © 2020 Chew, Tan, Ip, Pang, Hiong and Ip.Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction. The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility. Here, we investigated whether O-GlcNAc affects the inflammatory response and cardiovascular dysfunction associated with sepsis. Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS. The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressitted to cecal ligation and puncture (CLP), a sepsis model. In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention. Copyright © 2020 Silva, Olivon, Mestriner, Zanotto, Ferreira, Ferreira, Silva, Luiz, Alves, Fazan, Cunha, Alves-Filho and Tostes.Despite a 30% decline in mortality since 2000, malaria still affected 219 million subjects and caused 435,000 deaths in 2017. Red blood cells (RBC) host Plasmodium parasites that cause malaria, of which Plasmodium falciparum is the most pathogenic. The deformability of RBC is markedly modified by invasion and development of P. falciparum. Surface membrane area is potentially impacted by parasite entry and development, the cytoskeleton is modified by parasite proteins and cytosol viscosity is altered by parasite metabolism. RBC hosting mature parasites (second half of the asexual erythrocytic cycle) are abnormally stiff but the main reason for their absence from the circulation is their adherence to endothelial cells, mediated by parasite proteins exposed at the infected-RBC surface. By contrast, the circulation of non-adherent rings and gametocytes, depends predominantly on deformability. Altered deformability of rings and of uninfected-RBC altered by malaria infection is an important determinant of malaria pathogenesis. It also impacts the response to antimalarial therapy. Unlike conventional antimalarials that target mature stages, currently recommended first-line artemisinin derivatives and the emerging spiroindolones act on circulating rings. Methods to investigate the deformability of RBC are therefore critical to understand the clearance of infected- and uninfected-RBC in malaria. Herein, we review the main methods to assess the deformability of P. falciparum infected-RBC, and their contribution to the understanding of how P. falciparum infection causes disease, how the parasite is transmitted and how antimalarial drugs induce parasite clearance. Copyright © 2020 Depond, Henry, Buffet and Ndour.Familial dilated cardiomyopathy (DCM), clinically characterized by enlargement and dysfunction of one or both ventricles of the heart, can be caused by variants in sarcomeric genes including TNNC1 (encoding cardiac troponin C, cTnC). Here, we report the case of two siblings with severe, early onset DCM who were found to have compound heterozygous variants in TNNC1 p.Asp145Glu (D145E) and p.Asp132Asn (D132N), which were inherited from the parents. We began our investigation with CRISPR/Cas9 knockout of TNNC1 in Xenopus tropicalis, which resulted in a cardiac phenotype in tadpoles consistent with DCM. Despite multiple maneuvers, we were unable to rescue the tadpole hearts with either human cTnC wild-type or patient variants to investigate the cardiomyopathy phenotype in vivo. We therefore utilized porcine permeabilized cardiac muscle preparations (CMPs) reconstituted with either wild-type or patient variant forms of cTnC to examine effects of the patient variants on contractile function. Incorporation of 50% WT/50% D145E into CMPs increased Ca2+ sensitivity of isometric force, consistent with prior studies. In contrast, incorporation of 50% WT/50% D132N, which had not been previously reported, decreased Ca2+ sensitivity of isometric force. CMPs reconstituted 50-50% with both variants mirrored WT in regard to myofilament Ca2+ responsiveness. Sinusoidal stiffness (SS) (0.2% peak-to-peak) and the kinetics of tension redevelopment (k TR) at saturating Ca2+ were similar to WT for all preparations. Modeling of Ca2+-dependence of k TR support the observation from Ca2+ responsiveness of steady-state isometric force, that the effects on each mutant (50% WT/50% mutant) were greater than the combination of the two mutants (50% D132N/50% D145E). Further studies are needed to ascertain the mechanism(s) of these variants. Copyright © 2020 Landim-Vieira, Johnston, Ji, Mis, Tijerino, Spencer-Manzon, Jeffries, Hall, Panisello-Manterola, Khokha, Deniz, Chase, Lakhani and Pinto.Background Many processes contributing to the functional and structural regulation of the coronary circulation have been identified. A proper understanding of the complex interplay of these processes requires a quantitative systems approach that includes the complexity of the coronary network. The purpose of this study was to provide a detailed quantification of the branching characteristics and local hemodynamics of the human coronary circulation. Methods The coronary arteries of a human heart were filled post-mortem with fluorescent replica material. The frozen heart was alternately cut and block-face imaged using a high-resolution imaging cryomicrotome. From the resulting 3D reconstruction of the left coronary circulation, topological (node and loop characteristics), topographic (diameters and length of segments), and geometric (position) properties were analyzed, along with predictions of local hemodynamics (pressure and flow). AZD9291 research buy Results The reconstructed left coronary tree consisted of 202,184 segments wit and VanBavel.Mild normobaric hypoxia (NH) and modest exercise have multiple beneficial effects on health, but the changes in physiological function induced by NH and/or exercise remain unclear. The purpose of this investigation was to examine the specific effects of NH and/or exercise on cardiac function and myocardial structure and behavior including sleep-activity and negative geotaxis in aged Drosophila. We also assessed the survival rate of flies after hypoxia and/or exercise. One-thousand wild-type w1118 virgin female flies were randomly divided into four groups and treated with NH and/or exercise from ages 3-6 weeks. We found that exercise remarkably delayed the decline of actin and myosin and the age-related changes in cardiac structure, improved abnormal cardiac contraction, and enhanced the cardiac pumping force by inducing cardiac hypertrophy and delaying deterioration of cardiac contractility and diastolic compliance, and improved abnormal heart contraction. NH also increased the content of actin and myosin, but induced a decrease in heart diameter and heart rate, as well as an increase in the number of mitochondria and deeper sleep, which may be the manifestation of energy saving under long-term hypoxia.