Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.

Objective: Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations.

Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.

The main protease M is a clinically validated target to treat infections by the coronavirus SARS-CoV-2. Among the first reported M inhibitors was the peptidomimetic α-ketoamide , whose cocrystal structure with M paved the way for multiple lead-finding studies. We established structure-activity relationships for the series by modifying residues at the P1', P3, and P4 sites.

Macrolide resistance due to (55).

Unlabelled: Antimicrobial resistance (AMR) is a global threat. The identification and characterization of novel resistance genes is integral to AMR surveillance. The (55) gene was originally identified through whole genome sequencing of macrolide-resistant strains of .

Prior influenza virus infection alleviates an arbovirus encephalitis by reducing viral titer, inflammation, and cellular infiltrates in the central nervous system.

Unlabelled: Respiratory and encephalitic virus infections represent a significant risk to public health globally. Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis.

Screening a library of temperature-sensitive mutants to identify secretion factors in .

Protein secretion is an essential cell process in bacteria, required for cell envelope biogenesis, export of virulence factors, and acquisition of nutrients, among other important functions. In the Sec secretion pathway, signal peptide-bearing precursors are recognized by the SecA ATPase and pushed across the membrane through a translocon channel made of the proteins SecY, SecE, and SecG. The Sec pathway has been extensively studied in the model organism , but the Sec pathways of other bacteria such as the human pathogen differ in important ways from this model.

Evidence of dissemination of a -type integrative and conjugative element to , mediating acquisition of and other resistance determinants.

A strain positive for the metallo-beta-lactamase gene and resistant to trimethoprim-sulfamethoxazole was unexpectedly isolated from a surveillance rectal swab. The characterization of the strain revealed carriage of a 91 kb integrative and conjugative element (ICE) harboring several resistance determinants [, , , , ∆, , and ], closely related with a group of -type ICEs widespread among and other pseudomonads. Results highlighted the possible spreading of similar elements to , mediating the acquisition of relevant resistances.

Prolonged incubation time unwarranted for acute periprosthetic joint infections.

Unlabelled: Current laboratory protocols for periprosthetic joint infections (PJIs) involve a standard 10- to 14-day incubation period. However, recent evidence indicates considerable variability in the time to diagnosis (TTD) between acute and chronic PJIs. TTD is also influenced by the employed culture media and sample types.

Evaluating the clinical utility of , and bronchoalveolar PCRs for the diagnosis of invasive pulmonary infections in patients with hematological malignancies.

Invasive pulmonary infections are a significant cause of morbidity and mortality in patients with hematological malignancies and hematopoietic stem cell transplantation (HCT) recipients. A delay in identifying a causative agent may result in late initiation of appropriate treatment and adverse clinical outcomes. We examine the diagnostic utility of PCR-based assays in evaluating invasive pulmonary infections from bronchoalveolar lavage (BAL).

Multiple sclerosis and infection: history, EBV, and the search for mechanism.

SUMMARYInfection has long been hypothesized as the cause of multiple sclerosis (MS), and recent evidence for Epstein-Barr virus (EBV) as the trigger of MS is clear and compelling. This clarity contrasts with yet uncertain viral mechanisms and their relation to MS neuroinflammation and demyelination. As long as this disparity persists, it will invigorate virologists, molecular biologists, immunologists, and clinicians to ascertain how EBV potentiates MS onset, and possibly the disease's chronic activity and progression.

is a putative producer of polyunsaturated fatty acids in the gut soil of the composting earthworm .

Polyunsaturated fatty acids (PUFAs) play a crucial role in aiding bacteria to adapt to extreme and stressful environments. While there is a well-established understanding of their production, accrual, and transfer within marine ecosystems, knowledge about terrestrial environments remains limited. Investigation of the intestinal microbiome of earthworms has illuminated the presence of PUFAs presumably of microbial origin, which contrasts with the surrounding soil.

Comparing field and lab quantitative stable isotope probing for nitrogen assimilation in soil microbes.

Unlabelled: Soil microbial communities play crucial roles in nutrient cycling and can help retain nitrogen in agricultural soils. Quantitative stable isotope probing (qSIP) is a useful method for investigating taxon-specific microbial growth and utilization of specific nutrients, such as nitrogen (N). Typically, qSIP is performed in a highly controlled lab setting, so the field relevance of lab qSIP studies remains unknown.

Identification and functional characterization of a fructose-inducible phosphotransferase system in Sp7.

Plant growth-promoting rhizobacterium Sp7 utilizes fructose efficiently via a fructose phosphotransferase system (Fru-PTS). Its genome encodes two putative Fru-PTS, each consisting of FruB (EIIA), FruK (Pfk), and FruA (EIIBC) proteins. We compared the proteomes of Sp7 grown with malate or fructose as sole carbon source, and noticed upregulation of the constituent proteins of Fru-PTS1 only on fructose.

Adaptation of clinical bacteriology techniques for remote polar research.

Unlabelled: Remote polar regions offer unique opportunities and significant challenges for antimicrobial resistance research in a near-pristine environment. While core microbiology techniques continue to have an important role in supporting environmental research, the severe cold climate presents considerable challenges to laboratory research. We explore adaptations required for core bacteriology investigations in polar regions on an unsupported remote expedition c.

Target-agnostic identification of human antibodies to sexual forms reveals cross-stage recognition of glutamate-rich repeats.

Circulating sexual stages of ) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of in the form of gametes and gametocyte extracts.

Tinagl1 restores tamoxifen sensitivity and blocks fibronectin-induced EMT by simultaneously blocking the EGFR and β1-integrin/FAK signaling pathways in tamoxifen-resistant breast cancer cells.

Tamoxifen (TAM) is employed to treat premenopausal ER-positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM-resistant MCF-7 breast cancer cells (MCF-7R).

Ecological Drivers of Evolution of Swine Influenza in the United States: A Review.

Influenza A viruses (IAVs) pose a major public health threat due to their wide host range and pandemic potential. Pigs have been proposed as "mixing vessels" for avian, swine, and human IAVs, significantly contributing to influenza ecology. In the United States, IAVs are enzootic in commercial swine farming operations, with numerous genetic and antigenic IAV variants having emerged in the past two decades.

Single-Cell RNA Sequencing Analysis Reveals Exercise-Induced Transcriptional Dynamics in Half-Marathon Runners.

Previous studies in sports science suggested that regular exercise has a positive impact on human health. However, the effects of endurance sports and their underlying mechanisms are still not completely understood. One of the main debates regards the modulation of immune dynamics in high-intensity exercise.

Defining the Critical Requisites for Accurate Simulation of SARS-CoV-2 Viral Dynamics: Patient Characteristics and Data Collection Protocol.

Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact of patient characteristics in shaping the temporal viral load trajectory and (2) establish a data collection protocol (DCP) to reliably reconstruct individual viral load trajectories.

Risk Factors for Co-Infections in Patients With Severe Fever With Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and notable public health impact, caused by a novel phlebovirus, primarily transmitted through infected tick bites. This study aimed to assess the prevalence of co-infections among hospitalized patients with SFTS, characterize isolated pathogens, and evaluate demographics, clinical features, and laboratory variations to identify potential risk factors for co-infections. In a cohort of 78 SFTS patients categorized into co-infection and non-co-infection groups, 44.

Evolution and spread of subsp. in the São Paulo, Brazil, citrus belt inferred from 758 novel genomes.

The São Paulo state citrus belt in Brazil is a major citrus production region. Since at least 1957, citrus plantations in this region have been affected by citrus canker, an economically damaging disease caused by subsp. ().

The iMab antibody selectively binds to intramolecular and intermolecular i-motif structures.

i-Motifs (iMs) are quadruplex nucleic acid conformations that form in cytosine-rich regions. Because of their acidic pH dependence, iMs were thought to form only in vitro. The recent development of an iM-selective antibody, iMab, has allowed iM detection in cells, which revealed their presence at gene promoters and their cell cycle dependence.

Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones.

(CECT7484 and CECT7485) and (CECT7483) enhance actin cytoskeleton and CYP1A1 expression restoring epithelial permeability alterations induced by irritable bowel syndrome mediators.

Irritable bowel syndrome (IBS) is a multifactorial condition with heterogeneous pathophysiology, including intestinal permeability alterations. The aim of the present study was to assess the ability of a probiotic blend (PB) consisting of two strains (CECT7484 and CECT7485) and one strain of (CECT7483) to recover the permeability increase induced by mediators from IBS mucosal biopsies and to highlight the underlying molecular mechanisms. Twenty-one IBS patients diagnosed according to ROME IV criteria (11 IBS-D and 10 IBS-M) and 7 healthy controls were enrolled.

Patterns and trends in burden of asthma and its attributable risk factors from 1990 to 2021 among south Asian countries: a systematic analysis for the Global Burden of Disease Study 2021.

Objective: Asthma poses a significant health burden in South Asia, with increasing incidence and mortality despite a global decline in age-standardized prevalence rates. This study aims to analyze asthma trends from 1990 to 2021, focusing on prevalence, incidence, mortality, and disability-adjusted life years (DALYs) across South Asia. The study also assesses the impact of risk factors like high body mass index (BMI), smoking, and occupational exposures on asthma outcomes.

Green Synthesis of ZnO Nanoparticles Using Ficus benghalensis for Visible Light-Driven Photocatalytic Degradation of Crystal Violet and Antibacterial and Antibiofilm Activities.

Crystal Violet (CV) is a vibrant and harmful dye known for its toxicity to aquatic life and potential carcinogenic effects on humans. This study explores the removal of CV through photocatalysis driven by visible light, as well as examining the antibacterial and antibiofilm characteristics of zinc oxide nanoparticles (ZnO NPs) synthesized from the aerial roots of Ficus benghalensis. Various characterization techniques were employed to confirm the optical properties, crystal lattices, and morphology of ZnO NPs.