Carltonphelps4184

Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.Biodiversity loss can alter ecosystem functioning; however, it remains unclear how it alters decomposition-a critical component of biogeochemical cycles in the biosphere. Here, we provide a global-scale meta-analysis to quantify how changes in the diversity of organic matter derived from plants (i.e. litter) affect rates of decomposition. We find that the after-life effects of diversity were significant, and of substantial magnitude, in forests, grasslands, and wetlands. Changes in plant diversity could alter decomposition rates by as much as climate change is projected to alter them. Specifically, diversifying plant litter from mono- to mixed-species increases decomposition rate by 34.7% in forests worldwide, which is comparable in magnitude to the 13.6-26.4% increase in decomposition rates that is projected to occur over the next 50 years in response to climate warming. Thus, biodiversity changes cannot be solely viewed as a response to human influence, such as climate change, but could also be a non-negligible driver of future changes in biogeochemical cycles and climate feedbacks on Earth.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The woman's gut microbiota during pregnancy may support nutrient acquisition, is associated with diseases, and has been linked to infant health. However, there is limited information on gut microbial characteristics and dependence in pregnant women. In this study, we provide a comprehensive overview of the gut microbial characteristics of 1479 pregnant women using 16S rRNA gene sequencing of fecal samples. We identify a core microbiota of pregnant women, which displays a similar overall structure to that of age-matched nonpregnant women. Our data show that the gestational age-associated variation in the gut microbiota, from the ninth week of gestation to antepartum, is relatively limited. Building upon rich metadata, we reveal a set of exogenous and intrinsic host factors that are highly correlated with the variation in gut microbial community composition and function. These microbiota covariates are concentrated in basic host properties (e.g., age and residency status) and blood clinical parameters, suggesting that individual heterogeneity is the major force shaping the gut microbiome during pregnancy. Moreover, we identify microbial and functional markers that are associated with age, pre-pregnancy body mass index, residency status, and pre-pregnancy and gestational diseases. The gut microbiota during pregnancy is also different between women with high or low gestational weight gain. Our study demonstrates the structure, gestational age-associated variation, and associations with host factors of the gut microbiota during pregnancy and strengthens the understanding of microbe-host interactions. The results from this study offer new materials and prospects for gut microbiome research in clinical and diagnostic fields.During extension, the continental lithosphere thins and breaks up, forming either wide or narrow rifts depending on the thermo-mechanical state of the extending lithosphere. Wide continental rifts, which can reach 1,000 km across, have been extensively studied in the North American Cordillera and in the Aegean domain. Yet, the evolutionary process from wide continental rift to continental breakup remains enigmatic due to the lack of seismically resolvable data on the distal passive margin and an absence of onshore natural exposures. Here, we show that Eocene extension across the northern margin of the South China Sea records the transition between a wide continental rift and highly extended ( less then 15 km) continental margin. On the basis of high-resolution seismic data, we document the presence of dome structures, a corrugated and grooved detachment fault, and subdetachment deformation involving crustal-scale nappe folds and magmatic intrusions, which are coeval with supradetachment basins. The thermal and mechanical weakening of this broad continental domain allowed for the formation of metamorphic core complexes, boudinage of the upper crust and exhumation of middle/lower crust through detachment faulting. The structural architecture of the northern South China Sea continental margin is strikingly similar to the broad continental rifts in the North American Cordillera and in the Aegean domain, and reflects the transition from wide rift to continental breakup.Natural gas vehicles (NGVs) have been promoted in China to mitigate air pollution, yet our measurements and analyses show that NGV growth in China may have significant negative impacts on climate change. We conducted real-world vehicle emission measurements in China and found high methane emissions from heavy-duty NGVs (90% higher than current emission limits). These emissions have been ignored in previous emission estimates, leading to biased results. Applying our observations to life-cycle analyses, we found that switching to NGVs from conventional vehicles in China has led to a net increase in greenhouse gas (GHG) emissions since 2000. With scenario analyses, we also show that the next decade will be critical for China to reverse the trend with the upcoming China VI standard for heavy-duty vehicles. Implementing and enforcing the China VI standard is challenging, and the method demonstrated here can provide critical information regarding the fleet-level CH4 emissions from NGVs.Mapping aboveground forest biomass is central for assessing the global carbon balance. However, current large-scale maps show strong disparities, despite good validation statistics of their underlying models. Here, we attribute this contradiction to a flaw in the validation methods, which ignore spatial autocorrelation (SAC) in data, leading to overoptimistic assessment of model predictive power. To illustrate this issue, we reproduce the approach of large-scale mapping studies using a massive forest inventory dataset of 11.8 million trees in central Africa to train and validate a random forest model based on multispectral and environmental variables. check details A standard nonspatial validation method suggests that the model predicts more than half of the forest biomass variation, while spatial validation methods accounting for SAC reveal quasi-null predictive power. This study underscores how a common practice in big data mapping studies shows an apparent high predictive power, even when predictors have poor relationships with the ecological variable of interest, thus possibly leading to erroneous maps and interpretations.Efficient generation of phonons is an important ingredient for a prospective electrically-driven phonon laser. Hybrid quantum systems combining cavity quantum electrodynamics and optomechanics constitute a novel platform with potential for operation at the extremely high frequency range (30-300 GHz). We report on laser-like phonon emission in a hybrid system that optomechanically couples polariton Bose-Einstein condensates (BECs) with phonons in a semiconductor microcavity. The studied system comprises GaAs/AlAs quantum wells coupled to cavity-confined optical and vibrational modes. The non-resonant continuous wave laser excitation of a polariton BEC in an individual trap of a trap array, induces coherent mechanical self-oscillation, leading to the formation of spectral sidebands displaced by harmonics of the fundamental 20 GHz mode vibration frequency. This phonon "lasing" enhances the phonon occupation five orders of magnitude above the thermal value when tunable neighbor traps are red-shifted with respect to the pumped trap BEC emission at even harmonics of the vibration mode. These experiments, supported by a theoretical model, constitute the first demonstration of coherent cavity optomechanical phenomena with exciton polaritons, paving the way for new hybrid designs for quantum technologies, phonon lasers, and phonon-photon bidirectional translators.The protein high-mobility group box 1 (HMGB1) is released into the extracellular space in response to many inflammatory stimuli, where it is a potent signaling molecule. link2 Although research has focused on downstream HMGB1 signaling, the means by which HMGB1 exits the cell is controversial. Here we demonstrate that HMGB1 is not released from bone marrow-derived macrophages (BMDM) after lipopolysaccharide (LPS) treatment. We also explore whether HMGB1 is released via the pore-forming protein gasdermin D after inflammasome activation, as is the case for IL-1β. HMGB1 is only released under conditions that cause cell lysis (pyroptosis). When pyroptosis is prevented, HMGB1 is not released, despite inflammasome activation and IL-1β secretion. During endotoxemia, gasdermin D knockout mice secrete HMGB1 normally, yet secretion of IL-1β is completely blocked. Together, these data demonstrate that in vitro HMGB1 release after inflammasome activation occurs after cellular rupture, which is probably inflammasome-independent in vivo.Development of the surface morphology and shape of crystalline nanostructures governs the functionality of various materials, ranging from phonon transport to biocompatibility. However, the kinetic pathways, following which such development occurs, have been largely unexplored due to the lack of real-space imaging at single particle resolution. Here, we use colloidal nanoparticles assembling into supracrystals as a model system, and pinpoint the key role of surface fluctuation in shaping supracrystals. Utilizing liquid-phase transmission electron microscopy, we map the spatiotemporal surface profiles of supracrystals, which follow a capillary wave theory. link3 Based on this theory, we measure otherwise elusive interfacial properties such as interfacial stiffness and mobility, the former of which demonstrates a remarkable dependence on the exposed facet of the supracrystal. The facet of lower surface energy is favored, consistent with the Wulff construction rule. Our imaging-analysis framework can be applicable to other phenomena, such as electrodeposition, nucleation, and membrane deformation.Early therapeutic interventions are essential to prevent Alzheimer Disease (AD). The association of several inflammation-related genetic markers with AD and the early activation of pro-inflammatory pathways in AD suggest inflammation as a plausible therapeutic target. Inflammatory Caspase-1 has a significant impact on AD-like pathophysiology and Caspase-1 inhibitor, VX-765, reverses cognitive deficits in AD mouse models. Here, a one-month pre-symptomatic treatment of Swedish/Indiana mutant amyloid precursor protein (APPSw/Ind) J20 and wild-type mice with VX-765 delays both APPSw/Ind- and age-induced episodic and spatial memory deficits. VX-765 delays inflammation without considerably affecting soluble and aggregated amyloid beta peptide (Aβ) levels. Episodic memory scores correlate negatively with microglial activation. These results suggest that Caspase-1-mediated inflammation occurs early in the disease and raise hope that VX-765, a previously Food and Drug Administration-approved drug for human CNS clinical trials, may be a useful drug to prevent the onset of cognitive deficits and brain inflammation in AD.