Suppressing Tymovirus replication in plants using a variant of ubiquitin.

RNA viruses have evolved numerous strategies to overcome host resistance and immunity, including the use of multifunctional proteases that not only cleave viral polyproteins during virus replication but also deubiquitinate cellular proteins to suppress ubiquitin (Ub)-mediated antiviral mechanisms. Here, we report an approach to attenuate the infection of Arabidopsis thaliana by Turnip Yellow Mosaic Virus (TYMV) by suppressing the polyprotein cleavage and deubiquitination activities of the TYMV protease (PRO). Performing selections using a library of phage-displayed Ub variants (UbVs) for binding to recombinant PRO yielded several UbVs that bound the viral protease with nanomolar affinities and blocked its function.

Inhibition of Src signaling induces autophagic killing of Toxoplasma gondii via PTEN-mediated deactivation of Akt.

The intracellular protozoan Toxoplasma gondii manipulates host cell signaling to avoid targeting by autophagosomes and lysosomal degradation. Epidermal Growth Factor Receptor (EGFR) is a mediator of this survival strategy. However, EGFR expression is limited in the brain and retina, organs affected in toxoplasmosis.

The WHO Disease Outbreak News during the Covid-19 pandemic.

During the Covid-19 pandemic, the World Health Organization (WHO) was an important public source of information - not only about the pandemic, but also thousands of other potential health emergencies. Here, we examine the 242 reports published in the WHO Disease Outbreak News (DON) during the first four years of the Covid-19 pandemic (2020 to 2023), and document the diseases and regions that were reported. We find that multinational epidemics of diseases like Ebola virus and MERS-CoV continue to dominate the DON.

Geospatial and econometric approaches or older driver safety: Analysis of crash injury severity of regional highways.

This study tried to focus on the older drivers' group and explore the impact factors of injury severity involving older drivers from geo-spatial analysis. To reach the goal, a spatial analysis was proposed employing geographic information systems (GIS) with a case study application to two counties in Nevada. First, crash clusters were explored using Density-Based Spatial Clustering of Applications with Noise (DBSCAN) approach to investigate the spatial crash pattern for older drivers, and determine high risk locations of injury severity.

Examining Mammalian facial behavior using Facial Action Coding Systems (FACS) and combinatorics.

There has been an increased interest in standardized approaches to coding facial movement in mammals. Such approaches include Facial Action Coding Systems (FACS), where individuals are trained to identify discrete facial muscle movements that combine to create a facial configuration. Some studies have utilized FACS to analyze facial signaling, recording the quantity of morphologically distinct facial signals a species can generate.

Case-area targeted interventions and free chlorine residual in household drinking water: An observational cohort study during a cholera outbreak in Northeast Nigeria.

Background: Cholera outbreaks are surging worldwide. Growing research supports case-area targeted interventions (CATIs), whereby teams provide a package of interventions to case and neighboring households, as an effective strategy in cholera outbreak control, particularly in humanitarian settings. While research exists on individual CATI interventions, research gaps exist on outcomes of integrated interventions during CATI responses.

Measuring self-reliance and wellbeing among forcibly displaced women enrolled in a gender-focused economic empowerment program: A protocol for a pilot randomized controlled trial in Colombia.

Colombia currently hosts nearly three million Venezuelan refugees and migrants and is home to seven million internally displaced Colombians. For forcibly displaced populations in Colombia, and especially for women, gender-based violence (GBV) poses a threat during transit and in their new homes where xenophobia, lack of accessible and adequate services, limited safe economic opportunities, and lack of information on access to services, further increase risk. The dearth of livelihood opportunities also affects forcibly displaced populations, especially women.

From impact metrics and open science to communicating research: Journalists' awareness of academic controversies.

This study sheds light on how journalists respond to evolving debates within academia around topics including research integrity, improper use of metrics to measure research quality and impact, and the risks and benefits of the open science movement. It does so through a codebook thematic analysis of semi-structured interviews with 19 health and science journalists from the Global North. We find that journalists' perceptions of these academic controversies vary widely, with some displaying a highly critical and nuanced understanding and others presenting a more limited awareness.

Coordinated neuron-glia regeneration through Notch signaling in planarians.

Some animals can regenerate large missing regions of their nervous system, requiring mechanisms to restore the pattern, numbers, and wiring of diverse neuron classes. Because injuries are unpredictable, regeneration must be accomplished from an unlimited number of starting points. Coordinated regeneration of neuron-glia architecture is thus a major challenge and remains poorly understood.

More on mobility and sedentism: Changes in adaptation from Upper Paleolithic to Incipient Jomon, Tanegashima Island, southern Japan.

Sedentism is an adaptive alternative in human societies which is often associated with the emergence of complex societies in the Holocene. To elucidate the factors and processes of the emergence of sedentary societies, continuous accumulation of case studies based on robust evidence from across the world is required. Given abundant archaeological and geological evidence from the late Pleistocene to early Holocene, Tanegashima Island, situated in the southern Japanese Archipelago of the northwestern Pacific Rim, has significant potential to unravel factors and processes of sedentism.

Maternal mental health matters: Indicators for perinatal mental health-A scoping review.

Perinatal mental health disorders are a significant contributor to morbidity and mortality in childbearing women. The World Health Organization recommends all women be screened for mental health disorders postnatally and have diagnostic and management services available. There are, however, currently no global indicators in use which measure the status and progress of perinatal mental health.

Generalized functional varying-index coefficient model for dynamic synergistic gene-environment interactions with binary longitudinal traits.

The genetic basis of complex traits involves the function of many genes with small effects as well as complex gene-gene and gene-environment interactions. As one of the major players in complex diseases, the role of gene-environment interactions has been increasingly recognized. Motivated by epidemiology studies to evaluate the joint effect of environmental mixtures, we developed a functional varying-index coefficient model (FVICM) to assess the combined effect of environmental mixtures and their interactions with genes, under a longitudinal design with quantitative traits.

Metabolomic analysis of murine tissues infected with Brucella melitensis.

Brucella is a gram negative, facultative intracellular bacterial pathogen that constitutes a substantial threat to human and animal health. Brucella can replicate in a variety of tissues and can induce immune responses that alter host metabolite availability. Here, mice were infected with B.

Distinguishing benign and malignant myxoid soft tissue tumors: Performance of radiomics vs. radiologists.

Introduction: Benign and malignant myxoid soft tissue tumors have shared clinical, imaging, and histologic features that can make diagnosis challenging. The purpose of this study is comparison of the diagnostic performance of a radiomic based machine learning (ML) model to musculoskeletal radiologists.

Methods: Manual segmentation of 90 myxoid soft tissue tumors (45 myxomas and 45 myxofibrosarcomas) was performed on axial T1, and T2FS or STIR magnetic resonance imaging sequences.

Intramolecular Fluoroacylation Enabled by TrBF-Catalyzed Fluoride Recycling.

Alkyne- and alkene-tethered acyl fluorides undergo intramolecular carbofluorination via fluoride recycling using catalytic TrBF. Excellent stereoselectivity is observed for the alkyne addition, enabling access to novel fluorinated indan-2-ones (all ≥95:5 /) and cyclopentan-2-ones (85:15 /). Fluorinated chroman-2-ones and tertiary alkyl fluorides can also be synthesized using this method, comparing favorably to previously reported protocols that employ expensive metal catalysts under harsher conditions.

Identifying the Molecular Signatures of Organic Matter Leached from Land-Applied Biosolids via 21 T FT-ICR Mass Spectrometry.

Intensification of wastewater treatment residual (i.e., biosolid) applications to watersheds can alter the amount and composition of organic matter (OM) mobilized into waterways.

Complementary Peptide Interactions Support the Ultra-Rigidity of Polymers of De Novo Designed Click-Functionalized Bundlemers.

Computationally designed 29-residue peptides yield tetra-α-helical bundles with symmetry. The "bundlemers" can be bifunctionally linked via thiol-maleimide cross-links at their N-termini, yielding supramolecular polymers with unusually large, micrometer-scale persistence lengths. To provide a molecularly resolved understanding of these systems, all-atom molecular modeling and simulations of linked bundlemers in explicit solvent are presented.

Iron-histidine Coordination in Cytochrome b5: A Local Vibrational Mode Study.

We analyzed the intrinsic strength of distal and proximal FeN bonds and the stiffness of the axial NFeN bond angle in a series of cytochrome b5 proteins isolated from various species, including bacteria, animals, and humans. Ferric and ferrous oxidation states were considered. As assess- ment tool, we employed local vibrational stretching force constants ka(FeN) and bending force constants ka(NFeN) derived from our local mode theory.

Homochiral BINOL-Based Metal-Organic Frameworks for Luminescence Sensing of Hydrobenzoin Enantiomers.

Luminescent chiral metal-organic frameworks (CMOFs) are promising candidates for the enantioselective sensing of important chiral molecules. Herein, we report the synthesis and characterization of Zn and Cd CMOFs based on 1,1'-bi-2-naphthol (BINOL)-derived 3,3',6,6'-tetra(benzoic acids), H-OEt and H-OH. Four CMOFs, -OEt, -OH, -OEt, and -OH, based on these ligands were crystallographically characterized.

A Granzyme B-Cleavable T Cell-Targeted Bispecific Cell Vesicle Connector for Reversing New-Onset Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disorder in which pancreatic β-cells are destroyed by CD8 T cells. Anti-CD3 antibody effectively treats early-stage T1D when β-cell autoantibodies are detected but before symptoms appear. However, it impairs the immune system temporarily, exposing individuals to infection.

Finding new ways to treat overdoses.

Reversing opioid overdoses in rats using a drug that does not enter the brain prevents the sudden and severe withdrawal symptoms associated with therapeutics that target the central nervous system.

CSF cytokine, chemokine and injury biomarker profile of glial fibrillary acidic protein (GFAP) autoimmunity.

Defining the CSF cytokine/chemokine and injury biomarker signature of glial fibrillary acidic protein (GFAP) autoimmunity can inform immunopathogenesis. CSF GFAP-IgG-positive samples (N = 98) were tested for 17 cytokines/chemokines, neurofilament light chain (NfL), and GFAP (ELLA, Bio-Techne). Controls included non-inflammatory (N = 42), AQP4-IgG-positive (N = 83), CNS infections (N = 13), and neurosarcoidosis (N = 32).

Structural and Kinetic Characterization of an Acetoacetyl-Coenzyme A: Acetate Coenzyme A Transferase from the Extreme Thermophile Thermosipho melanesiensis.

CtfAB from the extremely thermophilic bacterium, Thermosipho melanesiensis, has been used for in vivo acetone production up to 70°C. This enzyme has tentatively been identified as the rate-limiting step, due to its relatively low binding affinity for acetate. However, existing kinetic and mechanistic studies on this enzyme are insufficient to evaluate this hypothesis.

Cognitive Impairment in Psychotic Disorders Is Associated with Brain Reductive Stress and Impaired Energy Metabolism as Measured by 31P Magnetic Resonance Spectroscopy.

Background And Hypothesis: Convergent evidence shows the presence of brain metabolic abnormalities in psychotic disorders. This study examined brain reductive stress and energy metabolism in people with psychotic disorders with impaired or average range cognition. We hypothesized that global cognitive impairment would be associated with greater brain metabolic dysregulation.

Surveillance of SARS-CoV-2 in Pets of Harris County, Texas, Revealed More Common Pet Infections in Households With Human COVID-19 Cases.

Local health departments can play a critical role in zoonoses surveillance at the human-domestic animal interface, especially when existing public health services and close relationships with community groups can be leveraged. Investigators at Harris County Veterinary Public Health employed a community-based surveillance tool for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in dogs and cats in June--December 2021. Diagnosis was made using both RT-qPCR testing of oral and nasal swabs and plaque reduction neutralization testing of serum samples.