Notes

Real-world efficacy along with protection associated with anlotinib while third- or further-line therapy within refractory modest mobile or portable cancer of the lung.
Liquid-liquid phase separation (LLPS) compartmentalizes transcriptional condensates for gene expression, but little is known about how this process is controlled. Here, we showed that depletion of IPMK, encoding inositol polyphosphate multikinase, promotes autophagy and lysosomal function and biogenesis in a TFEB-dependent manner. Cytoplasmic-nuclear trafficking of TFEB, a well-characterized mechanism by which diverse signaling pathways regulate TFEB activity, is not evidently altered by IPMK depletion. We demonstrated that nuclear TFEB forms distinct puncta that colocalize with the Mediator complex and with mRNAs of target lysosomal genes. TFEB undergoes LLPS in vitro. IPMK directly interacts with and inhibits LLPS of TFEB and also dissolves TFEB condensates. Depletion of IPMK increases the number of nuclear TFEB puncta and the co-localization of TFEB with Mediator and mRNAs of target genes. Our study reveals that nuclear-localized IPMK acts as a chaperone to inhibit LLPS of TFEB to negatively control its transcriptional activity.Defense against stress and active suppression of growth are two complementary strategies by which plants respond to adverse environments. Although beneficial for plant survival, active growth inhibition is often undesirable for crop productivity. Compared with the knowledge on how plants defend against stress-caused cellular impairment, much less is known about how stress signaling regulates plant growth and vice versa. Here, we review recent progress in this area and discuss recent studies suggesting that reciprocal regulation between stress-response and growth-control pathways occurs at multiple levels. Understanding this regulatory network will be critical for resetting the balance between stress resistance and growth in order to engineer stress-resistant and high-yielding crops.Recently in Nature, using biologically inspired design principles to recapitulate native crypt-villi topography and luminal flow, Nikolaev et al. engineered an intestinal organotypic culture system that is capable of long-term epithelial homeostasis. Mini-gut tubes were used in month-long studies of parasite-host interactions and completely regenerated following injury.In this issue of Developmental Cell, Cui et al. use a mouse model of maternal infection to identify that the embryonic choroid plexus propagates maternal inflammatory signals into the developing brain by enhancing macrophage infiltration across the choroid plexus barrier and releasing pro-inflammatory cytokines.The expression of autophagy and lysosomal genes is coordinated by the transcription factor EB (TFEB). In this issue of Developmental Cell, Chen et al. identify an evolutionary conserved mode of TFEB regulation, which entails the inhibition of TFEB phase separation in the nucleus by inositol polyphosphate multikinase.DNA cross-linking agents are common chemotherapeutics for cancer treatment, but their effect on normal cells is largely unknown. In this issue of Developmental Cell, Seldin and Macara (2020) show that such compounds induce epithelial hyperplasia and stem cell fate mis-specification in a non-cell-autonomous manner via inflammasome activation in dermal fibroblasts.Catheter ablation improves clinical outcomes in atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, the role of catheter ablation in HF with a preserved ejection fraction (HFpEF) is less clear. We performed a literature search and systematic review of studies that compared AF recurrence at one year after catheter ablation of AF in patients with HFpEF versus those with HFrEF. Risk ratio (RR; where a RR less then 1.0 favors the HFpEF group) and mean difference (MD; where MD less then 0 favors the HFpEF group) 95% confidence intervals (CI) were measured for dichotomous and continuous variables, respectively. Six studies with a total of 1,505 patients were included, of which 764 (51%) had HFpEF and 741 (49%) had HFrEF. Patients with HFpEF experienced similar recurrence of AF 1 year after ablation on or off antiarrhythmic drugs compared with those with HFrEF (RR 1.01; 95% CI 0.76, 1.35). Fluoroscopy time was significantly shorter in the HFpEF group (MD -5.42; 95% CI -8.51, -2.34), but there was no significant difference in procedure time (MD 1.74; 95% CI -11.89, 15.37) or periprocedural adverse events between groups (RR 0.84; 95% CI 0.54,1.32). There was no significant difference in hospitalizations between groups (MD 1.18; 95% CI 0.90, 1.55), but HFpEF patients experienced significantly less mortality (MD 0.41; 95% CI 0.18, 0.94). In conclusion, based on the results of this meta-analysis, catheter ablation of AF in patients with HFpEF appears as safe and efficacious in maintaining sinus rhythm as in those with HFrEF.Studies of the ecological effects of global change often focus on one or a few species at a time. Consequently, we know relatively little about the changes underway at real-world scales of biological communities, which typically have hundreds or thousands of interacting species. Here, we use COI mtDNA amplicons from monthly samples of environmental DNA to survey 221 planktonic taxa along a gradient of temperature, salinity, dissolved oxygen and carbonate chemistry in nearshore marine habitat. The result is a high-resolution picture of changes in ecological communities using a technique replicable across a wide variety of ecosystems. We estimate community-level differences associated with time, space and environmental variables, and use these results to forecast near-term community changes due to warming and ocean acidification. We find distinct communities in warmer and more acidified conditions, with overall reduced richness in diatom assemblages and increased richness in dinoflagellates. Individual taxa finding more suitable habitat in near-future waters are more taxonomically varied and include the ubiquitous coccolithophore Emiliania huxleyi and the harmful dinoflagellate Alexandrium sp. These results suggest foundational changes for nearshore food webs under near-future conditions.Climate change is altering the biogeochemical and physical characteristics of the Arctic marine environment, which impacts sea ice algal and phytoplankton bloom dynamics and the vertical transport of these carbon sources to benthic communities. Little is known about whether the contribution of sea ice-derived carbon to benthic fauna and nitrogen cycling has changed over multiple decades in concert with receding sea ice. We combined compound-specific stable isotope analysis of amino acids with highly branched isoprenoid diatom lipid biomarkers using archived (1982-2016) tissue of benthivorous Atlantic walrus to examine temporal trends of sea ice-derived carbon, nitrogen isotope baseline and trophic position of Atlantic walrus at high- and mid-latitudes in the Canadian Arctic. Associated with an 18% sea ice decline in the mid-Arctic, sea ice-derived carbon contribution to Atlantic walrus decreased by 75% suggesting a strong decoupling of sea ice-benthic habitats. By contrast, a nearly exclusive amount of sea ice-derived carbon was maintained in high-Arctic Atlantic walrus (98% in 1996 and 89% in 2006) despite a similar percentage in sea ice reduction. Nitrogen isotope baseline or the trophic position of Atlantic walrus did not change over time at either location. These findings indicate latitudinal differences in the restructuring of carbon energy sources used by Atlantic walrus and their benthic prey, and in turn a change in Arctic marine ecosystem functioning between sea ice-pelagic-benthic habitats.The ecology of coral reefs is rapidly shifting from historical baselines. One key-question is whether under these new, less favourable ecological conditions, coral reefs will be able to sustain key geo-ecological processes such as the capacity to accumulate carbonate structure. Here, we use data from 34 Caribbean reef sites to examine how the carbonate production, net erosion and net carbonate budgets, as well as the organisms underlying these processes, have changed over the past 15 years in the absence of further severe acute disturbances. We find that despite fundamental benthic ecological changes, these ecologically shifted coral assemblages have exhibited a modest but significant increase in their net carbonate budgets over the past 15 years. However, contrary to expectations this trend was driven by a decrease in erosion pressure, largely resulting from changes in the abundance and size-frequency distribution of parrotfishes, and not by an increase in rates of coral carbonate production. Although in the short term, the carbonate budgets seem to have benefitted marginally from reduced parrotfish erosion, the absence of these key substrate grazers, particularly of larger individuals, is unlikely to be conducive to reef recovery and will thus probably lock these reefs into low budget states.General intelligence has been a topic of high interest for over a century. Traditionally, research on general intelligence was based on principal component analyses and other dimensionality reduction approaches. check details The advent of high-speed computing has provided alternative statistical tools that have been used to test predictions of human general intelligence. In comparison, research on general intelligence in non-human animals is in its infancy and still relies mostly on factor-analytical procedures. Here, we argue that dimensionality reduction, when incorrectly applied, can lead to spurious results and limit our understanding of ecological and evolutionary causes of variation in animal cognition. Using a meta-analytical approach, we show, based on 555 bivariate correlations, that the average correlation among cognitive abilities is low (r = 0.185; 95% CI 0.087-0.287), suggesting relatively weak support for general intelligence in animals. We then use a case study with relatedness (genetic) data to demonstrate how analysing traits using mixed models, without dimensionality reduction, provides new insights into the structure of phenotypic variance among cognitive traits, and uncovers genetic associations that would be hidden otherwise. We hope this article will stimulate the use of alternative tools in the study of cognition and its evolution in animals.Through the Habitats Directive (92/43/EEC) and the financial investments of the LIFE projects, Europe has become an experimental arena for biological conservation. With an estimated annual budget of €20 billion, the EU Biodiversity Strategy for 2030 has set an ambitious goal of classifying 30% of its land and sea territory as Protected Areas and ensuring no deterioration in conservation trends and the status of protected species. We analysed LIFE projects focused on animals from 1992 to 2018 and found that investment in vertebrates was six times higher than that for invertebrates (€970 versus €150 million), with birds and mammals alone accounting for 72% of species and 75% of the total budget. In relative terms, investment per species towards vertebrates has been 468 times higher than that for invertebrates. Using a trait-based approach, we show that conservation effort is primarily explained by species' popularity rather than extinction risk or body size. Therefore, we propose a roadmap to achieve unbiased conservation targets for 2030 and beyond.
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