Backbone and Sidechain H, N and C Resonance Assignments of a Multidrug Efflux Membrane Protein using Solution and Solid-State NMR.

EmrE is a bacterial membrane-embedded multidrug transporter that functions as an asymmetric homodimer. EmrE is implicated in antibiotic resistance, but is now known to confer either resistance or susceptibility depending on the identity of the small molecule substrate. Here, we report both solution- and solid-state NMR assignments of S64V-EmrE at pH 5.

A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.

Coronaviruses (CoV) encode sixteen non-structural proteins (nsps), most of which form the replication-transcription complex (RTC). The RTC contains a core composed of one nsp12 RNA-dependent RNA polymerase (RdRp), two nsp8s and one nsp7. The core RTC recruits other nsps to synthesize all viral RNAs within the infected cell.

Enhancer Dynamics and Spatial Organization Drive Anatomically Restricted Cellular States in the Human Spinal Cord.

Here, we report the spatial organization of RNA transcription and associated enhancer dynamics in the human spinal cord at single-cell and single-molecule resolution. We expand traditional multiomic measurements to reveal epigenetically poised and bivalent active transcriptional enhancer states that define cell type specification. Simultaneous detection of chromatin accessibility and histone modifications in spinal cord nuclei reveals previously unobserved cell-type specific cryptic enhancer activity, in which transcriptional activation is uncoupled from chromatin accessibility.

Experimental, Theoretical, and Studies of Potential CDC7 Kinase Inhibitors.

In this work, we present the synthesis, solid-state characterization, and studies of two pyrazole derivatives: 5-(2-methylphenoxy)-3-methyl-1-phenyl-1-pyrazole-4-carbaldehyde (I) and 5-(4-methylphenoxy)-3-methyl-1-phenyl-1-pyrazole-4-carbaldehyde (II). The molecular crystal properties, in terms of intermolecular hydrogen bonds and other weak interactions, are analyzed using single crystal X-ray diffraction. The Hirshfeld surfaces computational method is used to quantify the intermolecular interactions, density functional theory for theoretical structural optimization, and its comparison with the experimental structure and studies using docking and molecular dynamics studies of I and II with CDC7-kinase.

Prioritizing emergency department antibiotic stewardship interventions for skin and soft tissue infections using judgment analysis.

Objective: Skin and soft tissue infections (SSTIs) account for over 2.8 million annual emergency department (ED) visits and often result in suboptimal antibiotic therapy. The objective of this study was to evaluate a set of interventions in minimizing inappropriate prescription of antibiotics for presumed SSTIs in the ED.

Reference genome of Calochortus tolmiei Hook. & Arn. (Liliaceae), a cat's ear mariposa lily.

Calochortus tolmiei Hook. & Arn., a bulbous monocot with cat's ear flowers in the angiosperm family Liliaceae, is a perennial herb native to northern California, Oregon, and Washington.

#natural, #vegan, #healing: A Content Analysis of Health Content Among Instagram Posts Focused on Cannabis Edibles.

Background: Despite limited scientific evidence, public perceptions of cannabis as health enhancing are significant. As food products, cannabis edibles (edibles), may also leverage food-related associations that convey health. Social media is a prominent and influential source of largely unregulated cannabis information and a potential place to correct misinformation.

Factors Associated with Persisting Post-Concussion Symptoms Among Collegiate Athletes and Military Cadets: Findings from the NCAA-DoD CARE Consortium.

Background: Persisting post-concussion symptoms (PPCS) is a condition characterized by prolonged recovery from a mild traumatic brain injury (mTBI) and compromised quality of life. Previous literature, on the basis of small sample sizes, concludes that there are several risk factors for the development of PPCS.

Objective: We seek to identify protective and risk factors for developing slow recovery or persisting post-concussion symptoms (PPCS) by analyzing medical history, contact sport level, setting, and the Sport Concussion Assessment Tool (SCAT) and Brief Symptom Inventory (BSI-18) assessments at baseline and post-injury.

Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons.

Background: Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

Role of protein and lipid oxidation in hardening of high-protein bars during storage.

Protein bar hardening negatively impacts shelf life, quality, and consumer acceptance. Although oxidation is known to negatively affect the flavor and texture of foods, the specific roles of lipid and protein oxidation in bar hardening have not been thoroughly investigated. Furthermore, most research has concentrated on dairy proteins, with a notable lack of studies addressing the hardening of plant-based protein bars.

MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER.

Background: Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic BD individuals to identify potential protein biomarkers.

Methods: We employed nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2,000 CSF proteins in 374 individuals from two independent clinical cohorts (n=164+89 and 66+55 cases and controls, respectively).

The ACTION VAD registry: A collective five-year experience.

Background: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) began in 2018 as a collaborative learning health system committed to improving outcomes in pediatric heart failure, including children and adults with congenital heart disease, supported with ventricular assist devices (VADs). This report describes patient and device characteristics, and outcomes through 1-year post-implant.

Methods: The ACTION VAD registry report was created from data submitted to the ACTION learning network from April 2018 to June 2023.

Higher Rates of Visualization for Axillary Reverse Mapping Using Indocyanine Green Fluorescence Compared With Blue Dye.

Introduction: Successful axillary reverse mapping (ARM) during lymph node surgery for breast cancer has the potential to reduce risk of lymphedema. Standard of care uses blue dye for ARM; however, recent imaging advances with near-infrared indocyanine green (ICG) fluorescence has demonstrated potential to improve intraoperative ARM imaging. The objective was to determine the feasibility of using ICG fluorescence through the OnLume Avata System for ARM.

Novel synaptic markers predict early tau pathology and cognitive deficit in an asymptomatic population at risk of Alzheimer's disease.

Cognitive dysfunction in Alzheimer's disease (AD) correlates closely with pathology in the neuronal microtubule-associated protein tau. Tau pathology may spread via neural synapses. In a population of cognitively unimpaired elderly at elevated risk of AD, we investigated four cerebrospinal (CSF) markers of synaptic dysfunction and degeneration.

Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer.

The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide.

A case study on postoperative radiation therapy of the big toe.

Sweat gland cancers, particularly eccrine sweat gland carcinomas, are rare and challenging to treat due to their aggressive nature and inconspicuous clinical presentation. Aggressive digital papillary adenocarcinoma, a rare subtype, frequently presents with delays in diagnosis, increasing the risk of metastasis and recurrence. Surgical excision remains the standard treatment, but the role of postoperative radiation therapy is not well-established due to the paucity of data.

Rates of Return to Sexual Activity Are High In Patients Undergoing Hip Arthroscopy And Occurs Within Six Weeks Postoperatively In Most Patients: A Systematic Review.

Purpose: To provide an aggregate review of literature on 1) outcomes related to the quality of intercourse (frequency, postoperative pain during intercourse, postoperative sexual dysfunction) after hip arthroscopy and 2) patient-reported outcomes regarding postoperative sexual function after hip arthroscopy.

Methods: This systematic review followed The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Cochrane Controlled Register of Trials (CENTRAL), and Scopus were queried in March 2024.

Changes in Contraceptive Method Use, Access, and Experiences of Care During a Statewide Contraceptive Initiative.

Objective: To examine changes in contraceptive use, access, and care experiences during a statewide contraceptive access initiative, Delaware Contraceptive Access Now.

Study Design: We used responses from the Delaware/Maryland Survey of Women at the early wave (11/2016-3/2017) and late wave (2/2021-10/2021). Our cross-sectional sample included 6,467 respondents at risk of unintended pregnancy.

A study of internal structure validity for the American board of surgery in training examination.

Background: As principles of competency-based medical education are implemented into graduate medical education [GME] programs, it is imperative that the assessments employed are reliable and valid. Internal structure is a core component of validity evidence that has been under studied. In this study, we examined elements of the internal structure for the American Board of Surgery In-Training Examination [ABSITE].

ReBreed21-ET: Evaluation of a rapid resynchronization program that allows timed embryo transfer every 21 days.

This study evaluated the efficiency of a rapid resynchronization of ovulation program to allow timed embryo transfer (TET) every 21d in heifer embryo recipients. Holstein heifers (n = 510) had synchronized ovulation using a modified 5d CoSynch program for a TET (D7) after induced ovulation (D0). After TET, heifers were blocked by number of previous TETs and randomized into one of two resynchronization of ovulation programs: Resynch28 (n = 279), a traditional resynch program for TET 35d after previous TET; or ReBreed21-ET, a program designed to allow TET 21d after previous TET.

homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort study.

Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens.

Microphytobenthos spatio-temporal dynamics across an intertidal gradient in a tropical estuary using Sentinel-2 imagery.

Intertidal mudflats are among the most productive coastal ecosystems, largely because of the activity of the photosynthetic microbial community on the sediment surface, known as microphytobenthos (MPB). While the dynamics of MPB have been extensively studied in temperate estuaries, there is limited research in tropical estuaries. To address this knowledge gap, we investigated the spatio-temporal dynamics of MPB in the Nicoya Gulf (Costa Rica), one of the world's most productive tropical estuaries, using Sentinel-2 images at 10 m spatial resolution from 2018 to 2022.