Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.

Purpose: During ocular trauma, excessive proliferation and transdifferentiation of corneal stromal fibroblasts cause haze/fibrosis in the cornea. Transforming growth factor β (TGFβ) plays a key role in corneal fibrosis through the Smad signaling pathway. The aberrant activity of TGFβ signaling during ocular trauma (viz.

Calcineurin governs baseline and homeostatic regulations of non-rapid eye movement sleep in mice.

Sleep need accumulates during waking and dissipates during sleep to maintain sleep homeostasis (process S). Besides the regulation of daily (baseline) sleep amount, homeostatic sleep regulation commonly refers to the universal phenomenon that sleep deprivation (SD) causes an increase of sleep need, hence, the amount and intensity of subsequent recovery sleep. The central regulators and signaling pathways that govern the baseline and homeostatic sleep regulations in mammals remain unclear.

Dentate gyrus norepinephrine ramping facilitates aversive contextual processing.

Dysregulation in aversive contextual processing is believed to affect several forms of psychopathology, including post-traumatic stress disorder (PTSD). The dentate gyrus (DG) is an important brain region in contextual discrimination and disambiguation of new experiences from prior memories. The DG also receives dense projections from the locus coeruleus (LC), the primary source of norepinephrine (NE) in the mammalian brain, which is active during stressful events.

Dentate Gyrus Norepinephrine Ramping Facilitates Aversive Contextual Processing.

Dysregulation in aversive contextual processing is believed to affect several forms of psychopathology, including post-traumatic stress disorder (PTSD). The dentate gyrus (DG) is an important brain region in contextual discrimination and disambiguation of new experiences from prior memories. The DG also receives dense projections from the locus coeruleus (LC), the primary source of norepinephrine (NE) in the mammalian brain, which is active during stressful events.

The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.

The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells increased double-strand breaks (DSBs).

A nature-inspired HIF stabilizer derived from a highland-adaptation insertion of plateau pika Epas1 protein.

Hypoxia-inducible factors (HIFs) play pivotal roles in numerous diseases and high-altitude adaptation, and HIF stabilizers have emerged as valuable therapeutic tools. In our prior investigation, we identified a highland-adaptation 24-amino-acid insertion within the Epas1 protein. This insertion enhances the protein stability of Epas1, and mice engineered with this insertion display enhanced resilience to hypoxic conditions.

ARGV: 3D genome structure exploration using augmented reality.

Over the past two decades, scientists have increasingly realized the importance of the three-dimensional (3D) genome organization in regulating cellular activity. Hi-C and related experiments yield 2D contact matrices that can be used to infer 3D models of chromosome structure. Visualizing and analyzing genomes in 3D space remains challenging.

MuscleX: data analysis software for fiber diffraction patterns from muscle.

MuscleX is an integrated, open-source computer software suite for data reduction of X-ray fiber diffraction patterns from striated muscle and other fibrous systems. It is written in Python and runs on Linux, Microsoft Windows or macOS. Most modules can be run either from a graphical user interface or in a `headless mode' from the command line, suitable for incorporation into beamline control systems.

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis.

Mast cells are hematopoietic-derived immune cells that possess numerous cytoplasmic granules containing immune mediators such as cytokines and histamine. Antigen stimulation triggers mast cell granule exocytosis, releasing granule contents in a process known as degranulation. We have shown that Rho GTPase signaling is an essential component of granule exocytosis, however, the proteins that regulate Rho GTPases during this process are not well defined.

Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study.

Purpose: The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non-small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti-PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported.

Methods: Patients were randomly assigned 1:1 (stratified by histology, best response to last anti-PD-(L)1-containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m intravenous infusion on day 1) in 21-day cycles.

The Diagnostic Accuracy of First-Year Ophthalmology Residents on Call: Considerations for Postgraduate Year 2 (PGY-2) Standardizations of Call Structure.

Background Ophthalmology is a unique specialty with limited exposure during medical school. To improve the transition to ophthalmology residency, the Accreditation Council for Graduate Medical Education (ACGME) announced in 2017 that all ophthalmology residency programs would move to a combined post-graduate year (PGY) 1 year with mandatory integration by 2023. Currently, there are no standardized guidelines from the American Board of Ophthalmology (ABO) or the Accreditation Council for Graduate Medical Education (ACGME) to address ophthalmology resident competence prior to becoming the primary contact for inpatient and emergency room (ER) consultations as a PGY-2.

TDP-43 deficiency in suprachiasmatic nucleus perturbs rhythmicity of neuroactivity in prefrontal cortex.

Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities.

Selective Use of CT Fractional Flow at a Large Academic Medical Center: Insights from Clinical Implementation after 1 Year of Practice.

Purpose This special report outlines a retrospective observational study of CT fractional flow reserve (CT-FFR) analysis using dual-source coronary CT angiography (CTA) scans performed without heart rate control and its impact on clinical outcomes. Materials and Methods All patients who underwent clinically indicated coronary CTA between August 2020 and August 2021 were included in this retrospective observational study. Scans were performed in the late systolic to early diastolic period without heart rate control and analyzed at the interpreting physician's discretion.

Comparison of Risk Factors Between Syndesmotic Screws With and Without Breakage.

Background Screw fixation continues to be a commonly used treatment for syndesmotic disruption; however, screw breakage remains a complication post-fixation. Despite this complication, investigation on the variability of surgical placement in conjunction with syndesmotic screw characteristics affecting breakage has not been fully elucidated. The purpose of this study is to compare patients with syndesmotic screw breakage versus those with intact screws based on surgically controlled variables.

Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals.

Most animals require sleep, and sleep loss induces serious pathophysiological consequences, including death. Previous experimental approaches for investigating sleep impacts in mice have been unable to persistently deprive animals of both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Here, we report a "curling prevention by water" paradigm wherein mice remain awake 96% of the time.

Long-Term Molecular Monitoring Using Aptamer-Graphene Microtransistors.

Long-term, real-time molecular monitoring in complex biological environments is critical for our ability to understand, prevent, diagnose, and manage human diseases. Aptamer-based electrochemical biosensors possess the promise due to their generalizability and a high degree of selectivity. Nevertheless, the operation of existing aptamer-based biosensors is limited to a few hours.

Disrupted circadian rhythms in the plateau pika.

The plateau pika (Ochotona curzoniae) is the most populous mammal on the 'third pole', the Qinghai-Tibet Plateau, and is presumed to have inhabited the region before the plateau rose up from sea level. Herein we discuss the disrupted circadian rhythm in the plateau pika and the gene polymorphism behind this phenotype, placing these findings in the broader context of circadian rhythms under extreme conditions.

Toxicological effects of ocular acrolein exposure to eyelids in rabbits in vivo.

Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple occasions and is readily accessible commercially. Our earlier studies revealed acrolein's toxicity to the cornea and witnessed damage to other ocular tissues.

Generation of LexA enhancer-trap lines in Drosophila by an international scholastic network.

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons.

Expression of Isoforms in Human Brain: Impact of Alzheimer's Disease Neuropathology and Genetics.

The single nucleotide polymorphisms rs35349669 and rs10933431 within Inositol Polyphosphate-5-Phosphatase D () are strongly associated with Alzheimer's Disease risk. To better understand expression in the brain, we investigated isoform expression as a function of rs35349669 and rs10933431, as well as Alzheimer's disease neuropathology, by qPCR and isoform-specific primers. In addition, allelic expression imbalance was evaluated relative to rs1141328 within exon 1.

Distribution and inflammatory cell response to intracranial delivery of radioluminescent Y2(SiO4)O:Ce particles.

Due to increasing advances in their manufacture and functionalization, nanoparticle-based systems have become a popular tool for in vivo drug delivery and biodetection. Recently, scintillating nanoparticles such as yttrium orthosilicate doped with cerium (Y2(SiO4)O:Ce) have come under study for their potential utility in optogenetic applications, as they emit photons upon low levels of stimulation from remote x-ray sources. The utility of such nanoparticles in vivo is hampered by rapid clearance from circulation by the mononuclear phagocytic system, which heavily restricts nanoparticle accumulation at target tissues.