Notes

"The Knife or even the Hook for Exceptional Vena Cava syndrome"?
However, all three live vaccines significantly outperformed formalin-killed HikoV, supporting the idea that live OCV usage will bolster current cholera control practices. The potency of OCVs was found to be challenge strain-dependent, emphasizing the importance of appropriate strain selection for cholera challenge studies. Our findings and experimental approaches will be valuable for guiding the development of live OCVs and oral vaccines for additional pathogens.The number and activity of Cav1.2 channels in the cardiomyocyte sarcolemma tunes the magnitude of Ca2+-induced Ca2+ release and myocardial contraction. β-Adrenergic receptor (βAR) activation stimulates sarcolemmal insertion of CaV1.2. This supplements the preexisting sarcolemmal CaV1.2 population, forming large "superclusters" wherein neighboring channels undergo enhanced cooperative-gating behavior, amplifying Ca2+ influx and myocardial contractility. Here, we determine this stimulated insertion is fueled by an internal reserve of early and recycling endosome-localized, presynthesized CaV1.2 channels. βAR-activation decreased CaV1.2/endosome colocalization in ventricular myocytes, as it triggered "emptying" of endosomal CaV1.2 cargo into the t-tubule sarcolemma. We examined the rapid dynamics of this stimulated insertion process with live-myocyte imaging of channel trafficking, and discovered that CaV1.2 are often inserted into the sarcolemma as preformed, multichannel clusters. Similarly, entire clusters were removed from the sarcolemma during endocytosis, while in other cases, a more incremental process suggested removal of individual channels. The amplitude of the stimulated insertion response was doubled by coexpression of constitutively active Rab4a, halved by coexpression of dominant-negative Rab11a, and abolished by coexpression of dominant-negative mutant Rab4a. In ventricular myocytes, βAR-stimulated recycling of CaV1.2 was diminished by both nocodazole and latrunculin-A, suggesting an essential role of the cytoskeleton in this process. Functionally, cytoskeletal disruptors prevented βAR-activated Ca2+ current augmentation. Moreover, βAR-regulation of CaV1.2 was abolished when recycling was halted by coapplication of nocodazole and latrunculin-A. These findings reveal that βAR-stimulation triggers an on-demand boost in sarcolemmal CaV1.2 abundance via targeted Rab4a- and Rab11a-dependent insertion of channels that is essential for βAR-regulation of cardiac CaV1.2.Developing organisms typically mature earlier and at larger sizes in favorable growth conditions, while in rarer cases, maturity is delayed. The rarer reaction norm is easily accommodated by general life history models, whereas the common pattern is not. Theory suggests that a solution to this paradox lies in the existence of critical size thresholds at which maturation or metamorphosis can commence, and in the evolution of these threshold sizes in response to environmental variation. For example, ephemeral environments might favor the evolution of smaller thresholds, enabling earlier maturation. The threshold model makes two unique and untested predictions. First, reaction norms for age and size should steepen, and even change sign, with decreases in threshold size; second, food reductions at sizes below the threshold should delay maturation, while those occurring after the threshold should accelerate maturation. We test these predictions through food manipulations in five damselfly species that theory suggests should differ in threshold size. The results provide strong support for the threshold model's predictions. In all species, early food reductions delayed maturation, while late reductions accelerated maturation. Reaction norms were steeper, and the effect of food reductions changed from decelerating to accelerating at a much smaller size in species from ephemeral habitats. These results support the view that developmental thresholds can account for the widespread observation of negative correlations between age and size at maturity. Moreover, evolution of the threshold appears to be both predictable and central to the observed diversity of reaction norms for age and size at maturity.Using a gain-of-function screen in Drosophila, we identified the Krüppel-like factor Cabut (Cbt) as a positive regulator of cell cycle gene expression and cell proliferation. Enforced cbt expression is sufficient to induce an extra cell division in the differentiating fly wing or eye, and also promotes intestinal stem cell divisions in the adult gut. Although inappropriate cell proliferation also results from forced expression of the E2f1 transcription factor or its target, Cyclin E, Cbt does not increase E2F1 or Cyclin E activity. Instead, Cbt regulates a large set of E2F1 target genes independently of E2F1, and our data suggest that Cbt acts via distinct binding sites in target gene promoters. Although Cbt was not required for cell proliferation during wing or eye development, Cbt is required for normal intestinal stem cell divisions in the midgut, which expresses E2F1 at relatively low levels. The E2F1-like functions of Cbt identify a distinct mechanism for cell cycle regulation that may be important in certain normal cell cycles, or in cells that cycle inappropriately, such as cancer cells.We conducted a meta-analysis of carbon and oxygen isotopes from tree ring chronologies representing 34 species across 10 biomes to better understand the environmental drivers and physiological mechanisms leading to historical changes in tree intrinsic water use efficiency (iWUE), or the ratio of net photosynthesis (Anet) to stomatal conductance (gs), over the last century. We show a ∼40% increase in tree iWUE globally since 1901, coinciding with a ∼34% increase in atmospheric CO2 (Ca), although mean iWUE, and the rates of increase, varied across biomes and leaf and wood functional types. While Ca was a dominant environmental driver of iWUE, the effects of increasing Ca were modulated either positively or negatively by climate, including vapor pressure deficit (VPD), temperature, and precipitation, and by leaf and wood functional types. A dual carbon-oxygen isotope approach revealed that increases in Anet dominated the observed increased iWUE in ∼83% of examined cases, supporting recent reports of global increases in Anet, whereas reductions in gs occurred in the remaining ∼17%. This meta-analysis provides a strong process-based framework for predicting changes in tree carbon gain and water loss across biomes and across wood and leaf functional types, and the interactions between Ca and other environmental factors have important implications for the coupled carbon-hydrologic cycles under future climate. Our results furthermore challenge the idea of widespread reductions in gs as the major driver of increasing tree iWUE and will better inform Earth system models regarding the role of trees in the global carbon and water cycles.Airborne pollen has major respiratory health impacts and anthropogenic climate change may increase pollen concentrations and extend pollen seasons. While greenhouse and field studies indicate that pollen concentrations are correlated with temperature, a formal detection and attribution of the role of anthropogenic climate change in continental pollen seasons is urgently needed. selleck chemicals Here, we use long-term pollen data from 60 North American stations from 1990 to 2018, spanning 821 site-years of data, and Earth system model simulations to quantify the role of human-caused climate change in continental patterns in pollen concentrations. We find widespread advances and lengthening of pollen seasons (+20 d) and increases in pollen concentrations (+21%) across North America, which are strongly coupled to observed warming. Human forcing of the climate system contributed ∼50% (interquartile range 19-84%) of the trend in pollen seasons and ∼8% (4-14%) of the trend in pollen concentrations. Our results reveal that anthropogenic climate change has already exacerbated pollen seasons in the past three decades with attendant deleterious effects on respiratory health.Living turtles are characterized by extraordinarily low species diversity given their age. The clade's extensive fossil record indicates that climate and biogeography may have played important roles in determining their diversity. We investigated this hypothesis by collecting a molecular dataset for 591 individual turtles that, together, represent 80% of all turtle species, including representatives of all families and 98% of genera, and used it to jointly estimate phylogeny and divergence times. We found that the turtle tree is characterized by relatively constant diversification (speciation minus extinction) punctuated by a single threefold increase. We also found that this shift is temporally and geographically associated with newly emerged continental margins that appeared during the Eocene-Oligocene transition about 30 million years before present. In apparent contrast, the fossil record from this time period contains evidence for a major, but regional, extinction event. These seemingly discordant findings appear to be driven by a common global process global cooling and drying at the time of the Eocene-Oligocene transition. This climatic shift led to aridification that drove extinctions in important fossil-bearing areas, while simultaneously exposing new continental margin habitat that subsequently allowed for a burst of speciation associated with these newly exploitable ecological opportunities.Citations are important building blocks for status and success in science. We used a linked dataset of more than 4 million authors and 26 million scientific papers to quantify trends in cumulative citation inequality and concentration at the author level. Our analysis, which spans 15 y and 118 scientific disciplines, suggests that a small stratum of elite scientists accrues increasing citation shares and that citation inequality is on the rise across the natural sciences, medical sciences, and agricultural sciences. The rise in citation concentration has coincided with a general inclination toward more collaboration. While increasing collaboration and full-count publication rates go hand in hand for the top 1% most cited, ordinary scientists are engaging in more and larger collaborations over time, but publishing slightly less. Moreover, fractionalized publication rates are generally on the decline, but the top 1% most cited have seen larger increases in coauthored papers and smaller relative decreases in fractional-count publication rates than scientists in the lower percentiles of the citation distribution. Taken together, these trends have enabled the top 1% to extend its share of fractional- and full-count publications and citations. Further analysis shows that top-cited scientists increasingly reside in high-ranking universities in western Europe and Australasia, while the United States has seen a slight decline in elite concentration. Our findings align with recent evidence suggesting intensified international competition and widening author-level disparities in science.Underlying sociopolitical factors have emerged as important determinants of wildlife population trends and the effectiveness of conservation action. Despite mounting research into the impacts of climate change on nature, there has been little consideration of the human context in which these impacts occur, particularly at the global scale. We investigate this in two ways. First, by modeling the climatic niches of terrestrial mammals and birds globally, we show that projected species loss under climate change is greatest in countries with weaker governance and lower Gross Domestic Product, with loss of mammal species projected to be greater in countries with lower CO2 emissions. Therefore, climate change impacts on species may be disproportionately significant in countries with lower capacity for effective conservation and lower greenhouse gas emissions, raising important questions of international justice. Second, we consider the redistribution of species in the context of political boundaries since the global importance of transboundary conservation under climate change is poorly understood.
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