Targeting Tiam1 enhances hippocampal-dependent learning and memory in the adult brain and promotes NMDA receptor-mediated synaptic plasticity and function.

Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood.

Integrated NMR-crystallography-computational approach for molecular recognition studies of human Gαi3 protein by a small molecule inhibitor.

The small molecule IGGi-11 targets Gαi subunits of heterotrimeric guanine nucleotide-binding proteins. Gα subunits are activated by G-protein-coupled receptors in response to extracellular stimuli by accelerating the exchange of GDP for GTP, but they are also activated by intracellular proteins like GIV, of which elevated levels correlate with increased cell migration and cancer metastasis. IGGi-11 disrupts the interaction of Gαi proteins with GIV and inhibits pro-invasive traits of metastatic breast cancer cells without interfering with GPCR signaling.

Inflammaging contributes to osteoarthritis development and human microbiota variations and vice versa: A systematic review.

Objective: To report evidence on microbiota and its relationship with inflammaging, the innate immune system and osteoarthritis (OA) in human patients.

Design: A systematic review was performed in accordance with PRISMA and following the PICO model. Web of Science, Scopus, Cochrane Library for clinical trials and PubMed were searched.

Longitudinal stability of molecular endotypes of knee osteoarthritis patients.

Objective: To assess the longitudinal stability of biomarker-based molecular endotypes of knee osteoarthritis (KOA) participants from APPROACH and to evaluate the consistency of findings in an independent KOA population.

Methods: Nineteen biomarkers were measured longitudinally in 295 KOA participants from the APPROACH cohort. K-means clustering was used to identify the structural damage, inflammation, and low tissue turnover endotypes at the six-, 12-, and 24-month follow-ups.

An exploratory analysis of associations of genetic variation with the efficacy of tocilizumab in severe COVID-19 patients. A pharmacogenetic study based on next-generation sequencing.

Background: In the context of the cytokine storm the takes place in severe COVID-19 patients, the () pathway emerges as one of the key pathways involved in the pathogenesis of this hyperinflammatory state. The strategy of blocking the inflammatory storm by targeting the is a promising therapy to mitigate mortality. The use of Tocilizumab was recommended by the World Health Organization (WHO) to treat severe COVID-19 patients.

Exploring the effects of ageing on instrumental and sensory characteristics of meat from Lidia breed females: A comparative study of two commercial types.

The aim of this study was to assess the influence of ageing on instrumental and sensory qualities in Longissimus thoracis et lumborum (LTL) from heifers (n = 200) and cows (n = 100) of Lidia breed. The animals were slaughtered as heifers (24-48 months) or cull cows (> 48 months). For instrumental analysis, pars Thoracis aged at 7, 14 and 28 days was used; for sensory analysis, pars Lumborum aged at 14 and 28 days was evaluated.

Structural and biochemical characterization of the C-terminal region of the human RTEL1 helicase.

RTEL1 is an essential DNA helicase which plays an important role in various aspects of genome stability, from telomere metabolism to DNA replication, repair and recombination. RTEL1 has been implicated in a number of genetic diseases and cancer development, including glioma, breast, lung and gastrointestinal tumors. RTEL1 is a FeS helicase but, in addition to the helicase core, it comprises a long C-terminal region which includes a number of folded domains connected by intrinsically disordered loops and mediates RTEL1 interaction with factors involved in pivotal cellular pathways.

Correction: Taguatagua 3: A new late Pleistocene settlement in a highly suitable lacustrine habitat in central Chile (34°S).

[This corrects the article DOI: 10.1371/journal.pone.

PCNA molecular recognition of different PIP motifs: Role of Tyr211 phosphorylation.

The coordination of enzymes and regulatory proteins for eukaryotic DNA replication and repair is largely achieved by Proliferating Cell Nuclear Antigen (PCNA), a toroidal homotrimeric protein that embraces the DNA duplex. Many proteins bind PCNA through a conserved sequence known as the PCNA interacting protein motif (PIP). PCNA is further regulated by different post-translational modifications.

Severity and progression of structural hand OA is not associated with progression of structural knee OA: The IMI-APPROACH cohort.

Objective: To investigate whether structural hand OA or its progression is associated with structural knee OA progression after two years in a population with symptomatic knee OA.

Methods: We used baseline and two-year follow-up data from the IMI-APPROACH cohort. Symptomatic hand and knee OA were defined using ACR criteria.

Bacteriuria and phenotypic antimicrobial susceptibility testing in 45 min by point-of-care Sysmex PA-100 System: first clinical evaluation.

Purpose: This study compared the results of the new Sysmex PA-100 AST System, a point-of-care analyser, with routine microbiology for the detection of urinary tract infections (UTI) and performance of antimicrobial susceptibility tests (AST) directly from urine.

Methods: Native urine samples from 278 female patients with suspected uncomplicated UTI were tested in the Sysmex PA-100 and with reference methods of routine microbiology: urine culture for bacteriuria and disc diffusion for AST.

Results: The analyser delivered bacteriuria results in 15 min and AST results within 45 min.

Metabolic syndrome is not associated with erosive hand osteoarthritis: a cross-sectional study using data from the PROCOAC cohort.

To delineate the phenotype of erosive hand osteoarthritis (EHOA) in a Spanish population and assess its correlation with metabolic syndrome. We conducted a cross-sectional study using baseline data from the Prospective Cohort of Osteoarthritis from A Coruña (PROCOAC). Demographic and clinical variables, obtained through questionnaires, clinical examinations, and patient analytics, were compared among individuals with hand OA, with and without EHOA.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

Background: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA.

Results: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies.

Cortical acetylcholine dynamics are predicted by cholinergic axon activity and behavior state.

Even under spontaneous conditions and in the absence of changing environmental demands, awake animals alternate between increased or decreased periods of alertness. These changes in brain state can occur rapidly, on a timescale of seconds, and neuromodulators such as acetylcholine (ACh) are thought to play an important role in driving these spontaneous state transitions. Here, we perform the first simultaneous imaging of ACh sensors and GCaMP-expressing axons , to examine the spatiotemporal properties of cortical ACh activity and release during spontaneous changes in behavioral state.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

Objective: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions.

Methods: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions.

Anti-Inflammatory Activity of APPA (Apocynin and Paeonol) in Human Articular Chondrocytes.

Osteoarthritis (OA) is a chronic joint disease leading to cartilage loss and reduction in the joint space which results in pain. The current pharmacological treatment of OA is inadequate and pharmacological interventions focus on symptom management. APPA, a combination of apocynin (AP) and paeonol (PA), is a potential drug for treating OA.

OMERACT Core outcome measurement set for shared decision making in rheumatic and musculoskeletal conditions: a scoping review to identify candidate instruments.

Objectives: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health.

Integral Electron Scattering Cross Sections from NO for Impact Energies Ranging from 1 to 1000 eV.

Accurate total cross sections (TCS), within 5%, for electron scattering by NO molecules have been measured with a magnetically confined electron transmission apparatus for impact energies ranging from 1 to 200 eV. For higher energies, these measurements have been complemented with our independent atom-based screening corrected additivity rule, including interference (IAM-SCAR + I) method to determine a complete reference TCS data set in the energy range (1-1000 eV). After a critical discussion that includes our calculated integral elastic and ionization cross sections and the theoretical and experimental data available in the literature, a complete set of integral elastic and inelastic (rotational, vibrational, and electronic excitation, ionization and electron attachment) cross sections, consistent with the reference TCS data, have been derived.

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

Objective: The objective of this study was to discover autoantibodies to non-modified proteins associated with the presence/absence of ACPAs in RA.

Methods: The autoantibody repertoire of 80 ACPA-negative and 80 ACPA-positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls.

Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI.

Objective: To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA).

Design: A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.

Prognostic model to predict the incidence of radiographic knee osteoarthritis.

Objective: Early diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting the incidence of radiographic KOA (rKOA) in non-radiographic osteoarthritic subjects and stratify individuals at high risk of developing the disease.

Methods: Subjects without radiographic signs of KOA according to the Kellgren and Lawrence (KL) classification scale (KL=0 in both knees) were enrolled in the OA initiative (OAI) cohort and the Prospective Cohort of A Coruña (PROCOAC).

Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls.

Objective: To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA).

Method: We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n ​= ​12), mild signs of joint damage (n ​= ​13) and end-stage OA (n ​= ​12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut.