The SWIB domain-containing DNA topoisomerase I of mediates DNA relaxation.

The obligate intracellular bacterial pathogen, (Ct), has a distinct DNA topoisomerase I (TopA) with a C-terminal domain (CTD) homologous to eukaryotic SWIB domains. Despite the lack of sequence similarity at the CTDs between TopA (CtTopA) and TopA (EcTopA), full-length CtTopA removed negative DNA supercoils and complemented the growth defect of an mutant. We demonstrated that CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies.

Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies.

Intracellular bacterial pathogens are distinctive tools for fighting cancer, as they can proliferate in tumors and deliver therapeutic payloads to the eukaryotic cytosol. Cytosol-dwelling bacteria have undergone extensive preclinical and clinical testing, yet the mechanisms of activating innate immunity in tumors are unclear. We report that phylogenetically distinct cytosolic pathogens, including , , and species, elicited anti-tumor responses in poorly immunogenic melanoma and lymphoma in mice.

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.

In recent years, pathogenic variants in ARS genes, encoding aminoacyl-tRNA synthetases (aaRSs), have been associated with human disease. Patients harbouring pathogenic variants in ARS genes have clinical signs partly unique to certain aaRSs defects, partly overlapping between the different aaRSs defects. Diagnosis relies mostly on genetics and remains challenging, often requiring functional validation of new ARS variants.

Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study.

Background: Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested.

Inference-Based Cognitive Behavioral Therapy versus Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: A Multisite Randomized Controlled Non-Inferiority Trial.

Introduction: Although cognitive behavioral therapy (CBT) effectively treats obsessive-compulsive disorder (OCD), many patients refuse CBT or drop out prematurely, partly because of anxiety regarding exposure and response prevention (ERP) exercises. Inference-based cognitive behavioral therapy (I-CBT) focuses on correcting distorted inferential thinking patterns, enhancing reality-based reasoning, and addressing obsessional doubt by targeting underlying dysfunctional reasoning, without incorporating an ERP component. We hypothesized that I-CBT would be non-inferior to CBT.