Membrane association and polar localization of the T4SS DotO ATPase mediated by two nonredundant receptors.

The Dot/Icm type IVB secretion system (T4BSS) is a large, multisubunit complex that exports a vast array of substrates into eukaryotic host cells. DotO, a distant homolog of the T4ASS ATPase VirB4, associates with the bacterial inner membrane despite lacking hydrophobic transmembrane domains. Employing a genetic approach, we found DotO's membrane association is mediated by three inner-membrane Dot/Icm components, IcmT, and a combined DotJ-DotI complex (referred to as DotJI).

Investigating the WNT and TGF-beta pathways alterations and tumor mutant burden in young-onset colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the United States. Recent epidemiological evidence demonstrates an increasing incidence of young-onset CRC cases, defined as CRC cases in individuals 50 years old or younger. Studies have established that alterations in both the WNT and TGF-Beta signaling pathways have contributed to CRC development.

Xylitol is prothrombotic and associated with cardiovascular risk.

Background And Aims: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.

Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across Diverse Cancer Indications.

Purpose: In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications.

Acquisition of Resistance to PEGylated Branched Polyethylenimine Increases Pseudomonas Aeruginosa Susceptibility to Aminoglycosides.

PEGylated branched polyethylenimine (PEG-BPEI) has antibacterial and antibiofilm properties. Exposure to PEG-BPEI through serial passage leads to resistant P. aeruginosa strains.

Low-Molecular Weight Branched Polyethylenimine Reduces Cytokine Secretion from Human Immune System Monocytes Stimulated with Bacterial and Fungal PAMPs.

The innate immune system is an evolutionarily conserved pathogen recognition mechanism that serves as the first line of defense against tissue damage or pathogen invasion. Unlike the adaptive immunity that recruits T-cells and specific antibodies against antigens, innate immune cells express pathogen recognition receptors (PRRs) that can detect various pathogen-associated molecular patterns (PAMPs) released by invading pathogens. Microbial molecular patterns, such as lipopolysaccharide (LPS) from Gram-negative bacteria, trigger signaling cascades in the host that result in the production of pro-inflammatory cytokines.

Slings and arrows: sRNAs mediate intragenomic competition.

Bacterial genomes are littered with exogenous: competing DNA elements. Here, Sprenger et al. demonstrate that the Vibrio cholerae prophage VP882 modulates host functions via production of regulatory sRNAs to promote phage development.

Understanding Public Perception of Naloxone: A Study of FAQs and Answer Source Credibility.

Purpose: The most commonly used intervention for opioid overdoses is naloxone. With naloxone soon to be sold over-the-counter in the United States, the goal of this paper is to categorize frequently asked questions (FAQs) and answers about naloxone using internet sources in a cross-sectional fashion.

Methods: Terms "narcan" and "naloxone" were searched on a clean Google Chrome browser using the "People also asked" tab to find FAQs and their answer sources.

Sex estimation research trends in forensic anthropology between 2000 and 2022 in five prominent journals.

In forensic anthropology, osteological sex estimation methods are continuously reevaluated and updated to improve classification accuracies. Therefore, to gain a comprehensive understanding of recent trends in sex estimation research in forensic anthropology, a content analysis of articles published between 2000 and 2022 in Forensic Science International, the Journal of Forensic Sciences, the International Journal of Legal Medicine, the American Journal of Biological Anthropology, and Forensic Anthropology, was performed. The main goals of this content analysis were to (1) examine trends in metric versus morphological research, (2) examine which areas of the skeleton have been explored, (3) examine which skeletal collections and population affinities have been most frequently utilized, and (4) determine which statistical methods were commonly implemented.

Neutralizing PAMPs that Trigger Cytokine Release from THP-1 Monocytes.

Innate immunity has considerable specificity and can discriminate between individual species of microbes. In this regard, pathogens are "seen" as dangerous to the host and elicit an inflammatory response capable of destroying the microbes. This immune discrimination is achieved by toll-like receptors on host cells recognizing pathogens, such as , and microbe-specific pathogen-associated molecular pattern (PAMP) molecules, such as lipoteichoic acid (LTA).

A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk.

Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE).

Replication cycle timing determines phage sensitivity to a cytidine deaminase toxin/antitoxin bacterial defense system.

Toxin-antitoxin (TA) systems are ubiquitous two-gene loci that bacteria use to regulate cellular processes such as phage defense. Here, we demonstrate the mechanism by which a novel type III TA system, avcID, is activated and confers resistance to phage infection. The toxin of the system (AvcD) is a deoxycytidylate deaminase that converts deoxycytidines (dC) to dexoyuridines (dU), while the RNA antitoxin (AvcI) inhibits AvcD activity.

Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm.

Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers.

Frequently asked questions about mobility devices among older adults.

Purpose: To assess frequently asked questions (FAQs) about mobility devices among older adults.

Materials And Methods: We searched multiple terms on Google to find FAQs. Rothwell's classification, JAMA benchmark criteria, and Brief DISCERN were used to categorize and assess each entry.

The role of immune checkpoint inhibitors for patients with advanced stage microsatellite stable colorectal cancer and high tumor mutation burden: quantity or quality?

Introduction: The US Food and Drug Administration (FDA) approved pembrolizumab for patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) of ≥ 10 mutations/megabase. However, the clinical implications of this universal cutoff of TMB ≥ 10 for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) remain debatable.

Areas Covered: In this review, we discuss the tissue agnostic approval of pembrolizumab, its efficacy, and clinical relevance in the management of patients with MSS CRC patients with high TMB (defined as TMB ≥ 10).

Effects of statin therapies on individuals taking antipsychotics: a systematic review.

Patients taking antipsychotics to treat severe mental illness may develop adverse effects such as dyslipidaemia. We aimed to provide an update to a previous systematic review showing statin therapy lowering lipid levels in individuals taking antipsychotics, while further identifying any safety concerns or changes in BMI or blood pressure. In August 2022, we searched MEDLINE, Embase, PsycINFO, PubMed and Cochrane Central Register of Controlled Trials for studies on the effects of statins on lipid profile measures for individuals with severe mental illness taking first- or second-generation antipsychotic medications.

New Insights into Vibrio cholerae Biofilms from Molecular Biophysics to Microbial Ecology.

With the discovery that 48% of cholera infections in rural Bangladesh villages could be prevented by simple filtration of unpurified waters and the detection of Vibrio cholerae aggregates in stools from cholera patients it was realized V. cholerae biofilms had a central function in cholera pathogenesis. We are currently in the seventh cholera pandemic, caused by O1 serotypes of the El Tor biotypes strains, which initiated in 1961.

GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55-74 at enrollment in 1993-2001.

Eradicating Biofilms of Carbapenem-Resistant Enterobacteriaceae by Simultaneously Dispersing the Biomass and Killing Planktonic Bacteria with PEGylated Branched Polyethyleneimine.

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging pathogens that cause variety of severe infections. CRE evade antibiotic treatments because these bacteria produce enzymes that degrade a wide range of antibiotics including carbapenems and β-lactams. The formation of biofilms aggravates CRE infections, especially in a wound environment.

Antibiofilm Activity of PEGylated Branched Polyethylenimine.

Biofilm formation is an adaptive resistance mechanism that pathogens employ to survive in the presence of antimicrobials. is an infectious Gram-negative bacterium whose biofilm allows it to withstand antimicrobial attack and threaten human health. Chronic wound healing is often impeded by infections and the associated biofilms.

Public awareness of cardiopulmonary resuscitation and cardiac arrest in association with Christian Eriksen.

Objectives: During the Union of European Football Association EURO 2020 Football Championship, Danish football player Christian Eriksen experienced a cardiac arrest on the field of play. With prompt intervention and cardiopulmonary resuscitation (CPR), Erikson had a positive outcome and survived the arrest. Our goal is to determine the extent to which this event informed the general population about cardiac arrests and CPR.