GARD-LENS: A downscaled large ensemble dataset for understanding future climate and its uncertainties.

This article introduces the Generalized Analog Regression Downscaling method Large Ensemble (GARD-LENS) dataset, comprised of daily precipitation, mean temperature, and temperature range over the Contiguous U.S., Alaska, and Hawaii at 12-km, 4-km, and 1-km resolutions, respectively.

Characterizing the Origins of Primary Aldosteronism.

Background: Renin-independent aldosterone production in normotensive people increases risk for developing hypertension. In parallel, normotensive adrenal glands frequently harbor aldosterone-producing micronodules with pathogenic somatic mutations known to induce primary aldosteronism (PA). A deeper understanding of these phenomena would inform the origins of PA and its role in hypertension pathogenesis.

The High-resolution Urban Meteorology for Impacts Dataset (HUMID) daily for the Conterminous United States.

Many current gridded surface meteorological datasets are inadequate for quantifying near-surface spatiotemporal variability because they do not fully represent the impacts of land surface heterogeneity. Of note, explicit representation of the spatial structure and magnitude of local urban warming are usually lacking. Here we enhance the representation of spatial meteorological variability over urban areas in the conterminous United States (CONUS) by employing the High-Resolution Land Data Assimilation System (HRLDAS), which accounts for the fine-scale impacts of spatiotemporally varying land surfaces on weather.

Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines.

Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range.

Methods: Adult participants were recruited at two academic centers.

Semaphorin heterodimerization in cis regulates membrane targeting and neocortical wiring.

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving epilepsy, intellectual disability, speech delay, and craniofacial defects.

Saline suppression testing-induced hypocalcemia and implications for clinical interpretations.

Background: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.

Methods: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).

Protein translation rate determines neocortical neuron fate.

The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes.

De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome.

Background: Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae. Juveniles occupy progressively deeper waters as they mature and grow, and adults have been caught as deep as 2500 m, living on or in just above the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. As apex predators, they are a key part of the food web, feeding on a variety of prey, including krill, squid, and other fish.

A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy.

Epilepsy is one of the common neurological diseases that affects not only adults but also infants and children. Because epilepsy has been studied for a long time, there are several pharmacologically effective anticonvulsants, which, however, are not suitable as therapy for all patients. The genesis of epilepsy has been extensively investigated in terms of its occurrence after injury and as a concomitant disease with various brain diseases, such as tumors, ischemic events, etc.

Srsf1 and Elavl1 act antagonistically on neuronal fate choice in the developing neocortex by controlling TrkC receptor isoform expression.

The seat of higher-order cognitive abilities in mammals, the neocortex, is a complex structure, organized in several layers. The different subtypes of principal neurons are distributed in precise ratios and at specific positions in these layers and are generated by the same neural progenitor cells (NPCs), steered by a spatially and temporally specified combination of molecular cues that are incompletely understood. Recently, we discovered that an alternatively spliced isoform of the TrkC receptor lacking the kinase domain, TrkC-T1, is a determinant of the corticofugal projection neuron (CFuPN) fate.

Exploring the association of Brownfield remediation status with socioeconomic conditions in Wayne County, MI.

Urban neighborhoods with locations of environmental contamination, known as brownfields, impact entire neighborhoods, but corrective environmental remedial action on brownfields is often tracked on an individual property basis, neglecting the larger neighborhood-level impact. This study addresses this impact by examining spatial differences between brownfields with unmitigated environmental concerns (open site) and sites that are considered fully mitigated or closed in urban neighborhoods (closed site) on the US census tract scale in Wayne County, MI. Michigan's Department of Environment, Great Lakes, and Energy's leaking underground storage tank (LUST) database provided brownfield information for Wayne County.

Acute association between heatwaves and stillbirth in six US states.

Background: Heatwaves are becoming more frequent and may acutely increase the risk of stillbirth, a rare and severe pregnancy outcome.

Objectives: Examine the association between multiple heatwave metrics and stillbirth in six U.S.

A population of ultraviolet-dim protoclusters detected in absorption.

Galaxy protoclusters, which will eventually grow into the massive clusters we see in the local Universe, are usually traced by locating overdensities of galaxies. Large spectroscopic surveys of distant galaxies now exist, but their sensitivity depends mainly on a galaxy's star-formation activity and dust content rather than its mass. Tracers of massive protoclusters that do not rely on their galaxy constituents are therefore needed.

How Did the COVID-19 Pandemic Affect Trends in Facial Trauma?

Study Design: Retrospective cohort analysis.

Objective: To examine the impact the COVID-19 pandemic and its accompanying societal measures had on the incidence, characteristics, and management of maxillofacial traumatic injuries.

Methods: This cohort analysis compared facial trauma injuries presenting to the highest-volume Level I Trauma Center in New Jersey, USA from January 1 to July 31 in 2020 and 2019.

Pathogenic Mechanisms of Cytosolic and Membrane-Enriched α-Synuclein Converge on Fatty Acid Homeostasis.

α-Synuclein (αS) plays a key role in Parkinson's disease. Although Parkinson's disease is typically "sporadic," inherited αS missense mutations provide crucial insights into molecular mechanisms. Here, we examine two clinical mutants, E46K and G51D, which are both in the conserved N-terminus that mediates transient αS-membrane interactions.

Angiolymphoid Hyperplasia with Eosinophilia: Many Syllables, Many Unanswered Questions.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign inflammatory vasoproliferation. The literature is divided regarding whether it embodies a vascular neoplasm or a reactive process secondary to various stimuli. ALHE presents as solitary or clustered papules or nodules primarily on the head and neck, especially on or around the auricle.

Targeting /HP1γ Induces LEF-1 and IL-21R to Promote Tumor-Infiltrating CD8 T-Cell Persistence.

Immune checkpoint blockade (ICB) relieves CD8 T-cell exhaustion in most mutated tumors, and TCF-1 is implicated in converting progenitor exhausted cells to functional effector cells. However, identifying mechanisms that can prevent functional senescence and potentiate CD8 T-cell persistence for ICB non-responsive and resistant tumors remains elusive. We demonstrate that targeting /HP1γ in CD8 T cells augments transcription initiation and chromatin remodeling leading to increased transcriptional activity at and .

Excess membrane binding of monomeric alpha-, beta- and gamma-synuclein is invariably associated with inclusion formation and toxicity.

α-Synuclein (αS) has been well-documented to play a role in human synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). First, the lesions found in PD/DLB brains-Lewy bodies and Lewy neurites-are rich in aggregated αS. Second, genetic evidence links missense mutations and increased αS expression to familial forms of PD/DLB.

Time-series analysis of daily ambient temperature and emergency department visits in five US cities with a comparison of exposure metrics derived from 1-km meteorology products.

Background: Ambient temperature observations from single monitoring stations (usually located at the major international airport serving a city) are routinely used to estimate heat exposures in epidemiologic studies. This method of exposure assessment does not account for potential spatial variability in ambient temperature. In environmental health research, there is increasing interest in utilizing spatially-resolved exposure estimates to minimize exposure measurement error.