PgpP is a broadly conserved phosphatase required for phosphatidylglycerol lipid synthesis.

The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents and its production is essential for growth in many bacteria. All the enzymes required for PG biogenesis in have been identified and characterized decades ago.

Emergence and evolution of heterocyte glycolipid biosynthesis enabled specialized nitrogen fixation in cyanobacteria.

Heterocytes, specialized cells for nitrogen fixation in cyanobacteria, are surrounded by heterocyte glycolipids (HGs), which contribute to protection of the nitrogenase enzyme from oxygen. Diverse HGs preserve in the sediment and have been widely used as evidence of past nitrogen fixation, and structural variation has been suggested to preserve taxonomic information and reflect paleoenvironmental conditions. Here, by comprehensive HG identification and screening of HG biosynthetic gene clusters throughout cyanobacteria, we reconstruct the convergent evolutionary history of HG structure, in which different clades produce the same HGs.

A single-cell atlas of the Culex tarsalis midgut during West Nile virus infection.

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and virus infection dynamics are scarce, and in Culex tarsalis-an extremely efficient vector of West Nile virus (WNV)-nonexistent. We performed single-cell RNA sequencing on Cx.

Evaluation of nationwide analysis surveillance for methicillin-resistant within Genomic Medicine Sweden.

National epidemiological investigations of microbial infections greatly benefit from the increased information gained by whole-genome sequencing (WGS) in combination with standardized approaches for data sharing and analysis. To evaluate the quality and accuracy of WGS data generated by different laboratories but analysed by joint pipelines to reach a national surveillance approach. A national methicillin-resistant (MRSA) collection of 20 strains was distributed to nine participating laboratories that performed in-house procedures for WGS.

Distinct Ocular Surface Microbiome in Keratoconus Patients Correlate With Local Immune Dysregulation.

Purpose: Keratoconus (KC) is characterized by irregular astigmatism along with corneal stromal weakness and is associated with altered immune status. Tissue resident microbiomes are known to influence the immune status in other organs, but such a nexus has not been described in ocular conditions. Therefore, we examined the ocular surface microbiome of patients with KC and correlated it to the immune cell and tear molecular factor profiles.

An IgM Cleaving Enzyme for Clearance of Anti-Pig Xenoreactive Antibodies in a Nonhuman Primate Model.

Background: The removal of preformed antibodies with cleaving enzyme like IdeS (Imlifidase) has demonstrated therapeutic potential in organ transplantation for sensitized recipients. However, preformed xenoreactive antibodies (XAbs) against porcine glycans are predominantly IgM and considered detrimental in pig-to-human xenotransplantation.

Methods: Recombinant IceM, an endopeptidase cleaving IgM, was generated in Escherichia coli.

Occurrence and clinical correlates of SARS-CoV-2 viremia in two German patient cohorts.

Viremia defined as detectable SARS-CoV-2 RNA in the blood is a potential marker of disease severity and prognosis in COVID-19 patients. Here, we determined the frequency of viremia in serum of two independent COVID-19 patient cohorts within the German National Pandemic Cohort Network (German: tionales andemie horten etzwerk, NAPKON) with diagnostic RT-PCR against SARS-CoV-2. A cross-sectional cohort with 1,122 COVID-19 patients (German: , SUEP) and 299 patients recruited in a high-resolution platform with patients at high risk to develop severe courses (German: , HAP) were tested for viremia.

A Novel HTNV Budding Inhibitor Interferes the Interaction Between Viral Glycoprotein and Host ESCRT Accessory Protein ALIX.

Virus budding is a critical step in the replication cycle of enveloped viruses, closely linked to viral spread, disease progression, and clinical outcomes. The budding of many enveloped RNA viruses is facilitated by the hijacking of the host endosomal sorting complex required for transport (ESCRT) proteins through viral late domains. These late domains are essential for progeny virus production and are highly conserved, making the interaction between late domains and host ESCRT proteins a potential target for the development of antiviral therapeutics.

Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States.

Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities.

Effector genes of type III secretion system and biofilm formation in virulent isolates carrying and genes in hospital environment.

In critically ill patients, the occurrence of multidrug-resistant infection is a significant concern, given its ability to acquire multidrug-resistant, form biofilms and secrete toxic effectors. In Brazil, limited data are available regarding the prevalence of dissemination, and the impact of the type III secretion system (T3SS) on toxin production and biofilm formation in clinical isolates of . This study investigates the dissemination of virulent harbouring the and genes, the presence of T3SS genes and their biofilm-forming capability.

Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.

OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on the surface of activated T cells. Upon interaction with its cognate ligand, OX40L, OX40 transmits costimulatory signals to antigen-primed T cells, promoting their activation, differentiation, and survivalprocesses essential for the establishment of adaptive immunity. Although the OX40-OX40L interaction has been extensively studied in the context of disease treatment, developing a substitute for the naturally expressed membrane-bound OX40L, particularly a multimerized OX40L trimers, that effectively regulates OX40-driven T cell responses remains a significant challenge.

Massive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells.

Introduction: HIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol-dependent and involves transient disruption of cortical actin.

Identifying targets for antibiotic stewardship interventions in pediatric patients in Punjab, Pakistan: point prevalence surveys using AWaRe guidance.

Introduction: Surveillance of antibiotic use is crucial for identifying targets for antibiotic stewardship programs (ASPs), particularly in pediatric populations within countries like Pakistan, where antimicrobial resistance (AMR) is escalating. This point prevalence survey (PPS) seeks to assess the patterns of antibiotic use in pediatric patients across Punjab, Pakistan, employing the WHO AWaRe classification to pinpoint targets for intervention and encourage rational antibiotic usage.

Methods: A PPS was conducted across 23 pediatric wards of 14 hospitals in the Punjab Province of Pakistan using the standardized Global-PPS methodology developed by the University of Antwerp.

Targeted barcoding of variable antibody domains and individual transcriptomes of the human B-cell repertoire using Link-Seq.

Here, we present Link-Seq, a highly efficient droplet microfluidic method for combined sequencing of antibody-encoding genes and the transcriptome of individual B cells at large scale. The method is based on 3' barcoding of the transcriptome and subsequent single-molecule PCR in droplets, which freely shift the barcode along specific gene regions, such as the antibody heavy- and light-chain genes. Using the immune repertoire of COVID-19 patients and healthy donors as a model system, we obtain up to 91.

Imputation for Lipidomics and Metabolomics (ImpLiMet): a web-based application for optimization and method selection for missing data imputation.

Motivation: Missing values are prevalent in high-throughput measurements due to various experimental or analytical reasons. Imputation, the process of replacing missing values in a dataset with estimated values, plays an important role in multivariate and machine learning analyses. The three missingness patterns, including missing completely at random, missing at random, and missing not at random, describe unique dependencies between the missing and observed data.

Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28-day mortality rate of 34.

Neuroevolution gives rise to more focused information transfer compared to backpropagation in recurrent neural networks.

Artificial neural networks (ANNs) are one of the most promising tools in the quest to develop general artificial intelligence. Their design was inspired by how neurons in natural brains connect and process, the only other substrate to harbor intelligence. Compared to biological brains that are sparsely connected and that form sparsely distributed representations, ANNs instead process information by connecting all nodes of one layer to all nodes of the next.

Molecular characterization and genome sequencing of selected highly resistant clinical isolates of and its association with the clustered regularly interspaced palindromic repeat/Cas system.

The presence of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system in the superbug presents a unique opportunity to precisely target and edit bacterial genomes to modify their drug resistance. The objective was to detect the prevalence of CRISPR in extensively and pan-drug-resistant and to determine the utility of whole-genome sequencing (WGS) for the analysis of the entire genome for such strains. The antimicrobial susceptibilities of one hundred isolates were assessed using the antibiotic susceptibility test (AST) card of the VITEK system.

Evaluation of a surrogate virus neutralization assay for detecting neutralizing antibodies against SARS-CoV-2 in an African population.

The global resurgence of coronaviruses and the move to incorporate COVID-19 vaccines into the expanded program for immunization have warranted for a high-throughput and low-cost assay to measure and quantify mounted neutralizing antibodies as an indicator for protection against SARS-CoV-2. Hence, we evaluated the surrogate-virus-neutralization-assay (sVNT) as an alternative assay to the pseudo-virus neutralization assay (pVNT). The sVNT was used to measure neutralizing antibodies among 119 infected and/or vaccinated blood samples, against wild-type SARS-CoV-2 (WT) and the Omicron-variant with reference to the pVNT.

FOXR2 in cancer development: emerging player and therapeutic opportunities.

Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.

Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Involvement of metformin and aging in salivary expression of ACE2 and TMPRSS2.

SARS-CoV-2-related proteins, ACE2 and TMPRSS2, are determinants of SARS-CoV-2 infection. Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full-length ACE2, which has both a fully functional enzyme catalytic site and high-affinity SARS-CoV-2 spike S1-binding sites, was more highly expressed in salivary glands than in oral mucosal epithelial cells and the lungs.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.