Triacylglycerol mobilization underpins mitochondrial stress recovery.

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response.

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.

Objectives: To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.

Methods: In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).

S-Adenosylmethionine (SAMe) for Liver Health: A Systematic Review.

Background/objectives: S-adenosylmethionine (SAMe) is a natural compound implicated in the treatment of liver dysfunction. In this systematic review, our objective was to determine the efficacy, safety, and optimal dose of SAMe in liver diseases.

Methods: Using the PRISMA methodology, we searched PubMed, CINAHL, and Web of Science using key MeSH search terms.

A simple active fluid model unites cytokinesis, cell crawling, and axonal outgrowth.

While the structural organization and molecular biology of neurons are well characterized, the physical process of axonal elongation remains elusive. The classic view posited elongation occurs through the deposition of cytoskeletal elements in the growth cone at the tip of a stationary array of microtubules. Yet, recent studies reveal axonal microtubules and docked organelles flow forward in bulk in the elongating axons of , chick sensory, rat hippocampal, and neurons.

Statewide Outbreak of Neisseria meningitidis Serogroup Y, Sequence Type 1466 - Virginia, 2022-2024.

Invasive meningococcal disease (IMD) is a severe illness that can have devastating effects; outbreaks are uncommon in the United States. Vaccination is the preferred control measure for IMD outbreaks when a defined population at risk (e.g.

Altered mRNA transport and local translation in iNeurons with RNA binding protein knockdown.

Neurons rely on mRNA transport and local translation to facilitate rapid protein synthesis in processes far from the cell body. These processes allow precise spatial and temporal control of translation and are mediated by RNA binding proteins (RBPs), including those known to be associated with neurodegenerative diseases. Here, we use proteomics, transcriptomics, and microscopy to investigate the impact of RBP knockdown on mRNA transport and local translation in iPSC-derived neurons.

S-Adenosylmethionine (SAMe) for Central Nervous System Health: A Systematic Review.

S-adenosylmethionine (SAMe) is a natural compound used to improve mood-related symptoms. Our aim was to determine the efficacy, safety, and optimal dose of SAMe in Central Nervous System (CNS) signs (e.g.

The effect of localized disturbance on the acoustic behavior of the common tern (Sterna hirundo).

In this study, passive acoustic monitoring was used to assess the impact of investigator disturbance on the acoustic behavior of a colony of common terns. A graded antipredator response in the colony was hypothesized, which would result in an increase in acoustic energy with increased proximity to investigator disturbance. Human disturbance was found to result in a significant increase in acoustic energy within 20 meters of recorders, though not from farther distances.

Use of the threshold of toxicological concern (TTC) approach as an alternative tool for regulatory purposes: A case study with an inert ingredient used in pesticide products.

This study investigates the potential of the Threshold of Toxicological Concern (TTC) as an alternative to traditional animal testing in pesticide regulatory risk assessments. The TTC is a principle that establishes exposure threshold values for chemicals with certain structural features, below which there is no appreciable risk to human health. A case study was conducted with α-terpineol, an inert ingredient proposed to be used at low concentrations in pesticide products, to compare a conventional risk assessment using animal data with one using the TTC method.

Implementation of an Approach to Equitable Allocation of SARS-CoV-2 Monoclonal Antibodies for Preexposure Prophylaxis: Experience From a Single Medical Center.

Background: During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials.

Mercury bioaccumulation in three colonial seabird species in the Gulf of Maine.

The methylated form of mercury, MeHg, is a neurotoxin that bioaccumulates and biomagnifies through aquatic food webs, reaching high concentrations in top trophic species. Many seabird species are wide-ranging and feed on forage fish, so they can be used as sentinel species to assess the level of mercury in pelagic or coastal food webs because they integrate the signal from large areas and from lower trophic levels. The Gulf of Maine provides habitat for many seabirds, including endangered roseate terns (Sterna dougalii), common terns (Sterna hirundo), and the southernmost breeding population of black guillemots (Cepphus grylle).

MMIL: A novel algorithm for disease associated cell type discovery.

Single-cell datasets often lack individual cell labels, making it challenging to identify cells associated with disease. To address this, we introduce Mixture Modeling for Multiple Instance Learning (MMIL), an expectation maximization method that enables the training and calibration of cell-level classifiers using patient-level labels. Our approach can be used to train e.

A simple active fluid model unites cytokinesis, cell crawling, and axonal outgrowth.

Axonal outgrowth, cell crawling, and cytokinesis utilize actomyosin, microtubule-based motors, cytoskeletal dynamics, and substrate adhesions to produce traction forces and bulk cellular motion. While it has long been appreciated that growth cones resemble crawling cells and that the mechanisms that drive cytokinesis help power cell crawling, they are typically viewed as unique processes. To better understand the relationship between these modes of motility, here, we developed a unified active fluid model of cytokinesis, amoeboid migration, mesenchymal migration, neuronal migration, and axonal outgrowth in terms of cytoskeletal flow, adhesions, viscosity, and force generation.

Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

Background: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease.

Using Pre-training and Interaction Modeling for ancestry-specific disease prediction in UK Biobank.

Recent genome-wide association studies (GWAS) have uncovered the genetic basis of complex traits, but show an under-representation of non-European descent individuals, underscoring a critical gap in genetic research. Here, we assess whether we can improve disease prediction across diverse ancestries using multiomic data. We evaluate the performance of Group-LASSO INTERaction-NET (glinternet) and pretrained lasso in disease prediction focusing on diverse ancestries in the UK Biobank.

Unique characteristics of the J-domain proximal regions of Hsp70 cochaperone Apj1 in prion propagation/elimination and its overlap with Sis1 function.

J-domain proteins (JDPs) are obligate cochaperones of Hsp70s. The Class A JDP Apj1 of the yeast cytosol has an unusually complex region between the N-terminal J-domain and the substrate binding region-often called the G or GF region in Class A and B JDPs because of its typical abundance of glycine. The N-terminal 161-residue Apj1 fragment is known to be sufficient for Apj1 function in prion curing, driven by the overexpression of Hsp104.

Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity.

Chaperone function in Fe-S protein biogenesis: Three possible scenarios.

Among the six known iron‑sulfur (FeS) cluster biogenesis machineries that function across all domains of life only one involves a molecular chaperone system. This machinery, called ISC for 'iron sulfur cluster', functions in bacteria and in mitochondria of eukaryotes including humans. The chaperone system - a dedicated J-domain protein co-chaperone termed Hsc20 and its Hsp70 partner - is essential for proper ISC machinery function, interacting with the scaffold protein IscU which serves as a platform for cluster assembly and subsequent transfer onto recipient apo-proteins.

Comparative structural and functional analysis of the glycine-rich regions of Class A and B J-domain protein cochaperones of Hsp70.

J-domain proteins are critical Hsp70 co-chaperones. A and B types have a poorly understood glycine-rich region (G) adjacent to their N-terminal J-domain (J). We analyzed the ability of J/G segments of yeast Class B Sis1 and a suppressor variant of Class A, Ydj1, to rescue the inviability of sis1-∆.

The malignant transformation of endometriosis: Is there a left lateral predisposition of ovarian clear cell and endometrioid carcinomas?

Introduction: Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis.

CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity.

Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over the course of 5 years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients.