CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.

The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease.

Thrombotic Long-Term Consequences of SARS-CoV-2 Infection in Patients with Compensated Cirrhosis: A Propensity Score-Matched Analysis of a U.S. Database.

Background: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2's impact on hemostasis in compensated patients with cirrhosis.

Sinus Tachycardia Following COVID-19 and Its Implications.

Background Within the cardiovascular system, sinus tachycardia has been a noted finding in patients with post-COVID-19 syndrome (symptoms persisting beyond 12 weeks post-infection). To better understand post-COVID-19 tachycardia, we examined the prevalence of sinus tachycardia 12-16 weeks after diagnosis of SARS-COV-2 infection and its correlation with intensive care utilization, ventilator use, and mortality in vaccinated and unvaccinated patients. Methods We identified adult patients in the TriNetX COVID-19 Research Network with confirmed SARS-COV-2 diagnosis from January 20th, 2020, to February 14th, 2022, and sinus tachycardia 12-16 weeks after diagnosis.

CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.

The sheer complexity of the brain has complicated our ability to understand the cellular and molecular mechanisms underlying its function in health and disease. Genome-wide association studies have uncovered genetic variants associated with specific neurological phenotypes and diseases. In addition, single-cell transcriptomics have provided molecular descriptions of specific brain cell types and the changes they undergo during disease.

Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.

Loss of function (LoF) of TAR-DNA binding protein 43 (TDP-43) and mis-localization, together with TDP-43-positive and hyperphosphorylated inclusions, are found in post-mortem tissue of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those carrying LoF variants in the progranulin gene (GRN). Modeling TDP-43 pathology has been challenging in vivo and in vitro. We present a three-dimensional induced pluripotent stem cell (iPSC)-derived paradigm-mature brain organoids (mbOrg)-composed of cortical-like-astrocytes (iA) and neurons.

Astroglial toxicity promotes synaptic degeneration in the thalamocortical circuit in frontotemporal dementia with GRN mutations.

Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit in Grn-/- mice, the exact mechanism for neurodegeneration in FTLD-GRN remains unclear. By performing comparative single-cell transcriptomics in the thalamus and frontal cortex of Grn-/- mice and patients with FTLD-GRN, we have uncovered a highly conserved astroglial pathology characterized by upregulation of gap junction protein GJA1, water channel AQP4, and lipid-binding protein APOE, and downregulation of glutamate transporter SLC1A2 that promoted profound synaptic degeneration across the two species.

Fuel connectivity, burn severity, and seed bank survivorship drive ecosystem transformation in a semiarid shrubland.

A key challenge in ecology is understanding how multiple drivers interact to precipitate persistent vegetation state changes. These state changes may be both precipitated and maintained by disturbances, but predicting whether the state change will be fleeting or persistent requires an understanding of the mechanisms by which disturbance affects the alternative communities. In the sagebrush shrublands of the western United States, widespread annual grass invasion has increased fuel connectivity, which increases the size and spatial contiguity of fires, leading to postfire monocultures of introduced annual grasses (IAG).

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

Astrocytes become reactive in response to insults to the central nervous system by adopting context-specific cellular signatures and outputs, but a systematic understanding of the underlying molecular mechanisms is lacking. In this study, we developed CRISPR interference screening in human induced pluripotent stem cell-derived astrocytes coupled to single-cell transcriptomics to systematically interrogate cytokine-induced inflammatory astrocyte reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-κB activation drove two distinct inflammatory reactive signatures, one promoted by STAT3 and the other inhibited by STAT3.

Warming weakens the night-time barrier to global fire.

Night-time provides a critical window for slowing or extinguishing fires owing to the lower temperature and the lower vapour pressure deficit (VPD). However, fire danger is most often assessed based on daytime conditions, capturing what promotes fire spread rather than what impedes fire. Although it is well appreciated that changing daytime weather conditions are exacerbating fire, potential changes in night-time conditions-and their associated role as fire reducers-are less understood.

Increasing Access to Medications and Devices for the Care of Low-Risk Childbearing Families: An Analysis of Existing Law and Strategies for Advocacy.

Limited access to medications and devices relevant to the care of low-risk childbearing families acts as a barrier to the successful integration of high-quality midwifery care into health care systems. Families who live in clinically underserved areas, whether urban or rural, are particularly in need of perinatal professionals who can provide comprehensive care. This article reviews existing US laws that impact whether families who choose community-based care with direct entry midwives have access, through their chosen provider, to the medications and devices relevant to their normal perinatal and postpartum care.

Risky Development: Increasing Exposure to Natural Hazards in the United States.

Losses from natural hazards are escalating dramatically, with more properties and critical infrastructure affected each year. Although the magnitude, intensity, and/or frequency of certain hazards has increased, development contributes to this unsustainable trend, as disasters emerge when natural disturbances meet vulnerable assets and populations. To diagnose development patterns leading to increased exposure in the conterminous United States (CONUS), we identified earthquake, flood, hurricane, tornado, and wildfire hazard hotspots, and overlaid them with land use information from the Historical Settlement Data Compilation data set.

Range dynamics mediated by compensatory life stage responses to experimental climate manipulations.

The expectations of polar or upslope distributional shifts of species ranges in response to warming climate conditions have been recently questioned. Diverse responses of different life stages to changing temperature and moisture regimes may alter these predicted range dynamics. Furthermore, the climate driver(s) influencing demographic rates, and the contribution of each demographic rate to population growth rate (λ), may shift across a species range.

Cross-scale interaction of host tree size and climatic water deficit governs bark beetle-induced tree mortality.

The recent Californian hot drought (2012-2016) precipitated unprecedented ponderosa pine (Pinus ponderosa) mortality, largely attributable to the western pine beetle (Dendroctonus brevicomis; WPB). Broad-scale climate conditions can directly shape tree mortality patterns, but mortality rates respond non-linearly to climate when local-scale forest characteristics influence the behavior of tree-killing bark beetles (e.g.

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.

Background: Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients.

An update on human astrocytes and their role in development and disease.

Human astrocytes provide trophic as well as structural support to the surrounding brain cells. Furthermore, they have been implicated in many physiological processes important for central nervous system function. Traditionally astrocytes have been considered to be a homogeneous class of cells, however, it has increasingly become more evident that astrocytes can have very different characteristics in different regions of the brain, or even within the same region.

Local forest structure variability increases resilience to wildfire in dry western U.S. coniferous forests.

A 'resilient' forest endures disturbance and is likely to persist. Resilience to wildfire may arise from feedback between fire behaviour and forest structure in dry forest systems. Frequent fire creates fine-scale variability in forest structure, which may then interrupt fuel continuity and prevent future fires from killing overstorey trees.

Community turnover by composition and climatic affinity across scales in an alpine system.

Premise: Examining community turnover across climate gradients at multiple scales is vital to understanding biogeographic response to climate change. This approach is especially important for alpine plants in which the relative roles of topographic complexity and nonclimatic or stochastic factors vary across spatial scales.

Methods: We examined the structure of alpine plant communities across elevation gradients in the White Mountains, California.

Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib.

The mesenchymal-to-epithelial transition (MET) gene is altered and becomes a driver mutation in up to 5% of non-small-cell lung cancer (NSCLC). We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib. We identified cases of NSCLC with METex14 mutations using an institutionally developed or commercial next-generation sequencing assay.

Parsing propagule pressure: Number, not size, of introductions drives colonization success in a novel environment.

Predicting whether individuals will colonize a novel habitat is of fundamental ecological interest and is crucial to conservation efforts. A consistently supported predictor of colonization success is the number of individuals introduced, also called propagule pressure. Propagule pressure increases with the number of introductions and the number of individuals per introduction (the size of the introduction), but it is unresolved which process is a stronger driver of colonization success.

Effects of topoclimatic complexity on the composition of woody plant communities.

Topography can create substantial environmental variation at fine spatial scales. Shaped by slope, aspect, hill-position and elevation, topoclimate heterogeneity may increase ecological diversity, and act as a spatial buffer for vegetation responding to climate change. Strong links have been observed between climate heterogeneity and species diversity at broader scales, but the importance of topoclimate for woody vegetation across small spatial extents merits closer examination.

Aboveground Net Primary Productivity in a Riparian Wetland Following Restoration of Hydrology.

This research presents the initial results of the effects of hydrological restoration on forested wetlands in the Mississippi alluvial plain near Memphis, Tennessee. Measurements were carried out in a secondary channel, the Loosahatchie Chute, in which rock dikes were constructed in the 1960s to keep most flow in the main navigation channel. In 2008-2009, the dikes were notched to allow more flow into the secondary channel.

Extraction of Phospholipids from Human Erythrocyte Membranes by Hemoglobin Oxidation Products.

This investigation examines oxidation conditions under which hemoglobin extracts membrane phospholipid from erythrocytes and model membranes. In erythrocytes made echinocytic with exogenous phospholipid, addition of hemoglobin oxidized with hydrogen peroxide (H2O2) or Vitamin C (conditions that result in the formation of significant quantities of choleglobin), but not ferricyanide (which produces predominantly methemoglobin), induced dose-dependent shape reversion to less echinocytic forms, consistent with extraction of phospholipids from the exofacial side of the membrane. Erythrocytes preloaded with radiolabeled phosphatidylcholine or NBD-labeled phosphatidylcholine, phosphatidylglycerol or phosphatidic acid, exhibited greatest extraction of radiolabel or fluorescence signal with exogenous hemoglobin oxidized via H2O2 or Vitamin C, but not ferricyanide.