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Enzyme-free impedimetric biosensor-based molecularly produced plastic regarding frugal determination of L-hydroxyproline.
Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.Phenotypic variation among populations is thought to be generated from spatial heterogeneity in environments that exert selection pressures that overcome the effects of gene flow and genetic drift. Here, we tested for evidence of isolation by distance or by ecology (i.e., ecological adaptation) to generate variation in early life history traits and phenotypic plasticity among 13 wood frog populations spanning 1200 km and 7° latitude. Proteasome inhibitor We conducted a common garden experiment and related trait variation to an ecological gradient derived from an ecological niche model (ENM) validated to account for population density variation. Shorter larval periods, smaller body weight, and relative leg lengths were exhibited by populations with colder mean annual temperatures, greater precipitation, and less seasonality in precipitation and higher population density (high-suitability ENM values). After accounting for neutral genetic variation, the QST-FST analysis supported ecological selection as the key process generating population divergence. Further, the relationship between ecology and traits was dependent upon larval density. Specifically, high-suitability/high-density populations in the northern part of the range were better at coping with greater conspecific competition, evidenced by greater postmetamorphic survival and no difference in body weight when reared under stressful conditions of high larval density. Our results support that both climate and competition selection pressures drive clinal variation in larval and metamorphic traits in this species. Range-wide studies like this one are essential for accurate predictions of population's responses to ongoing ecological change.Landscape features shape patterns of gene flow among populations, ultimately determining where taxa lay along the continuum between panmixia to complete reproductive isolation. Gene flow can be restricted, leading to population differentiation in two non-exclusive ways "physical isolation", in which geographic distance in combination with the landscape features restricts movement of individuals promoting genetic drift, and "ecological isolation", in which adaptive mechanisms constrain gene flow between different environments via divergent natural selection. In central Iberia, two fire salamander subspecies occur in parapatry across elevation gradients along the Iberian Central System mountains, while in the adjacent Montes de Toledo Region only one of them occurs. By integrating population and landscape genetic analyses, we show a ubiquitous role of physical isolation between and within mountain ranges, with unsuitable landscapes increasing differentiation between populations. However, across the Iberian Central System, we found strong support for a significant contribution of ecological isolation, with low genetic differentiation in environmentally homogeneous areas, but high differentiation across sharp transitions in precipitation seasonality. These patterns are consistent with a significant contribution of ecological isolation in restricting gene flow among subspecies. Overall, our results suggest that ecological divergence contributes to reduce genetic admixture, creating an opportunity for lineages to follow distinct evolutionary trajectories.Disruptions to sensory pathways in the lower urinary tract commonly occur and can give rise to lower urinary tract symptoms (LUTS). The unmet clinical need for treatment of LUTS has stimulated research into the molecular mechanisms that underlie neuronal control of the bladder and transient receptor potential (TRP) channels have emerged as key regulators of the sensory processes that regulate bladder function. TRP channels function as molecular sensors in urothelial cells and afferent nerve fibres and can be considered the origin of bladder sensations. TRP channels in the lower urinary tract contribute to the generation of normal and abnormal bladder sensations through a variety of mechanisms, and have demonstrated potential as targets for the treatment of LUTS in functional disorders of the lower urinary tract.Since the introduction of insulin almost a century ago, more than 80 peptide drugs have reached the market for a wide range of diseases, including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain. In this Perspective, we summarize key trends in peptide drug discovery and development, covering the early efforts focused on human hormones, elegant medicinal chemistry and rational design strategies, peptide drugs derived from nature, and major breakthroughs in molecular biology and peptide chemistry that continue to advance the field. We emphasize lessons from earlier approaches that are still relevant today as well as emerging strategies such as integrated venomics and peptide-display libraries that create new avenues for peptide drug discovery. We also discuss the pharmaceutical landscape in which peptide drugs could be particularly valuable and analyse the challenges that need to be addressed for them to reach their full potential.For more complex nonlinear systems, where the amplitude of excitation can vary in time or where time-dependent external disturbances appear, an analysis based on the frequency response curve may be insufficient. In this paper, a new tool to analyze nonlinear dynamical systems is proposed as an extension to the frequency response curve. A new tool can be defined as the chart of bistability areas and area of unstable solutions of the analyzed system. In the paper, this tool is discussed on the basis of the classic Duffing equation. The numerical approach was used, and two systems were tested. Both systems are softening, but the values of the coefficient of nonlinearity are significantly different. Relationships between both considered systems are presented, and problems of the nonlinearity coefficient and damping influence are discussed.Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.
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