RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.

Pre-mRNA 3' processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3' processing in human cells.

Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment.

Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components of the HCC tumor microenvironment (TME) is tumor-associated macrophages (TAMs), which play a pivotal role in modulating tumor growth, immune evasion, and metastasis. Macrophages are divided into two major subtypes: pro-inflammatory M1 and anti-inflammatory M2, both of which may exist in TME with altered function and proportion.

AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.

Ventilatory drive is modulated by a variety of neurochemical inputs that converge on spatially oriented clusters of cells within the brainstem. This regulation is required to maintain energy homeostasis and is essential to sustain life across all mammalian organisms. Therefore, the anatomical orientation of these cellular clusters during development must have a defined mechanistic basis with redundant genomic variants.

The Critical Role of Autophagy and Phagocytosis in the Aging Brain.

As the organism ages, there is a decline in effective energy supply, and this retards the ability to elaborate new proteins. The consequences of this are especially marked in the gradual decline in brain function. The senescence of cells and their constituent organelles is ultimately the cause of aging of the entire nervous system.

A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.

Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.

The changing relationship between racial identity and skin color in Brazil.

In recent years, Brazil's non-White (Brown and Black) population became a numerical majority for the first time since the 19th century. Although we know this change was mostly due to racial reclassification, we do not know how such changes are related to skin color, the primary marker of race in Brazil. Using data from six Latin American Public Opinion Project (LAPOP), or America's Barometer, surveys from 2010 to 2023, we examine how changes in racial self-identification (White, Brown, or Black) are related to respondent skin color (light, medium, or dark).

Unraveling climate change-induced compound low-solar-low-wind extremes in China.

China's pursuit of carbon neutrality targets hinges on a profound shift towards low-carbon energy, primarily reliant on intermittent and variable, yet crucial, solar and wind power sources. In particular, low-solar-low-wind (LSLW) compound extremes present a critical yet largely ignored threat to the reliability of renewable electricity generation. While existing studies have largely evaluated the impacts of average climate-induced changes in renewable energy resources, comprehensive analyses of the compound extremes and, particularly, the underpinning dynamic mechanisms remain scarce.

Evaluation of LLMs accuracy and consistency in the registered dietitian exam through prompt engineering and knowledge retrieval.

Large language models (LLMs) are fundamentally transforming human-facing applications in the health and well-being domains: boosting patient engagement, accelerating clinical decision-making, and facilitating medical education. Although state-of-the-art LLMs have shown superior performance in several conversational applications, evaluations within nutrition and diet applications are still insufficient. In this paper, we propose to employ the Registered Dietitian (RD) exam to conduct a standard and comprehensive evaluation of state-of-the-art LLMs, GPT-4o, Claude 3.

Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow.

Background: Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature can be detrimental to the host. Recent work has demonstrated that Toxoplasma gondii infects and lyses central nervous system (CNS) endothelial cells that form the blood-brain barrier (BBB).

Task relevant autoencoding enhances machine learning for human neuroscience.

In human neuroscience, machine learning can help reveal lower-dimensional neural representations relevant to subjects' behavior. However, state-of-the-art models typically require large datasets to train, and so are prone to overfitting on human neuroimaging data that often possess few samples but many input dimensions. Here, we capitalized on the fact that the features we seek in human neuroscience are precisely those relevant to subjects' behavior rather than noise or other irrelevant factors.

YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution.

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.

Enhanced Killing of Methicillin-Resistant Staphylococcus aureus with Ceftaroline or Vancomycin in Combination with Carbapenems.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure, even when antibiotics showing in vitro susceptibility are used. Early optimization of therapy is crucial to reduce morbidity and mortality. Building on our previous research on carbapenem therapy for methicillin-susceptible S.

Integrating microfluidic and bioprinting technologies: advanced strategies for tissue vascularization.

Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels.

Bathymetry of the Antarctic continental shelf and ice shelf cavities from circumpolar gravity anomalies and other data.

Bathymetry critically influences the intrusion of warm Circumpolar Deep Water onto the continental shelf and under ice shelf cavities in Antarctica, thereby forcing ice melting, grounding line retreat, and sea level rise. We present a novel and comprehensive bathymetry of Antarctica that includes all ice shelf cavities and previously unmeasured continental shelf areas. The new bathymetry is based on a 3D inversion of a circumpolar compilation of gravity anomalies constrained by measurements from the International Bathymetric Chart of the Southern Ocean, BedMachine Antarctica, and discrete seafloor measurements from seismic and ocean robotic probes.

Escalation of genome defense capacity enables control of an expanding meiotic driver.

From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases.

G Protein Regulation by RGS Proteins in the Pathophysiology of Dilated Cardiomyopathy.

Regulators of G protein signaling (RGS) proteins finetune signaling via heterotrimeric G proteins to maintain physiologic homeostasis in various organ systems of the human body including the brain, kidney, heart, and the vasculature. Impaired regulation of G protein signaling by RGS proteins is implicated in the pathogenesis of several human diseases including various forms of cardiomyopathy such as hypertrophic cardiomyopathy and dilated cardiomyopathy (DCM). Both genetic and non-genetic changes that impinge on G protein signaling in cardiomyocytes are implicated in the etiology of DCM, and there is accumulating evidence that such genetic and non-genetic changes affecting G protein signaling in cell types other than cardiomyocytes could serve as a DCM trigger in humans.

Contrasting Summertime Trends in Vehicle Combustion Efficiency in Los Angeles, CA and Salt Lake City, UT.

Policy interventions and technological advances are mitigating emissions of air pollutants from motor vehicles. As a result, vehicle fleets are expected to progressively combust fuel more efficiently, with a declining ratio of carbon monoxide to carbon dioxide (CO/CO) in their emissions. We assess trends in traffic combustion efficiency in Los Angeles (LA) and Salt Lake City (SLC) by measuring changes in summertime on-road CO/CO between 2013 and 2021 using mobile observations.

Structural Characterization of Encapsulin in Complex with Dye-Decolorizing Peroxide.

(Mtb) is the causative agent of tuberculosis, the world's deadliest infectious disease. Mtb uses a variety of mechanisms to evade the human host's defenses and survive intracellularly. Mtb's oxidative stress response enables Mtb to survive within activated macrophages, an environment with reactive oxygen species and low pH.

Variable Assembly and Procapsid Binding of Bacteriophage P22 Terminase Subunits in Solution.

Concatemeric viral DNA is packaged into bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds the dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme.

Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes.

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease.

Esterase-Mediated Pyrethroid Resistance in Populations of an Invasive Malaria Vector from Ethiopia.

Background: The swift expansion of the invasive malaria vector throughout Africa presents a major challenge to malaria control initiatives. Unlike the native African vectors, thrives in urban settings and has developed resistance to multiple classes of insecticides, including pyrethroids, organophosphates, and carbamates.

Methods: Insecticide susceptibility tests were performed on field-collected mosquitoes from Awash Sebac Kilo, Ethiopia, to assess insecticide resistance levels.

Electrochemical sensors: Types, applications, and the novel impacts of vibration and fluid flow for microfluidic integration.

Electrochemical sensors are part of a diverse and evolving world of chemical sensors that are impacted by high demand and ongoing technological advancements. Electrochemical sensors offer benefits like cost-efficiency, short response time, ease of use, good limit of detection (LOD) and sensitivity, and ease of miniaturization while providing consistent analytical results. These sensors are employed in various fields-such as healthcare and diagnostics, environmental monitoring, and the food industry-to detect bacteria, viruses, heavy metals, pesticides, and more.

Genomic basis of schistosome resistance in a molluscan vector of human schistosomiasis.

Freshwater snails are obligate intermediate hosts for the transmission of schistosomiasis, one of the world's most devastating parasitic diseases. To decipher the mechanisms underlying snail resistance to schistosomes, recombinant inbred lines (RILs) were developed from two well-defined homozygous lines (iM line and iBS90) of the snail . Whole-genome sequencing (WGS) was used to scan the genomes of 46 individual RIL snails, representing 46 RILs, half of which were resistant or susceptible to .

Patient activation improves with a multi-component personalized mHealth intervention in older patients at risk of cardiovascular disease: a pilot randomized controlled trial.

Aims: This study aimed to determine the effect of a multi-component mHealth intervention on patient activation and examine its predictors among older adults at risk of cardiovascular disease (CVD).

Methods And Results: This pilot randomized controlled trial compared two groups: Get FIT (control), who received healthy lifestyle counselling from a licensed health coach, a mHealth app (MyFitnessPal) with push alerts, and an activity tracker, and Get FIT + (intervention), who received the same interventions and had personalized text messages with 3- and 6-month follow-up periods. Patient activation was measured using the 13-item Patient Activation Measure; higher scores indicated better activation.

Evidence for microbially-mediated tradeoffs between growth and defense throughout coral evolution.

Background: Evolutionary tradeoffs between life-history strategies are important in animal evolution. Because microbes can influence multiple aspects of host physiology, including growth rate and susceptibility to disease or stress, changes in animal-microbial symbioses have the potential to mediate life-history tradeoffs. Scleractinian corals provide a biodiverse, data-rich, and ecologically-relevant host system to explore this idea.