M. groll

Food fortification with micronutrients is widely implemented to reduce micronutrient deficiencies and related outcomes. While many factors affect the success of fortification programs, high population coverage is needed to have a public health impact. We aimed to provide recent global coverage estimates of salt, wheat flour, vegetable oil, maize flour, rice, and sugar among countries with mandatory fortification legislation. The indicators were the proportion of households consuming the: food, fortifiable food (i...

The development of novel anti-infectives requires unprecedented strategies targeting pathways which are solely present in pathogens but absent in humans. Following this principle, we developed inhibitors of lipoic acid (LA) salvage, a crucial pathway for the survival of LA auxotrophic bacteria and parasites but non-essential in human cells. An LA-based probe was selectively transferred onto substrate proteins via lipoate protein ligase (LPL) in intact cells, and their binding sites were determined by mass spectrometry...

Modification of the polyketide anthraquinone AQ-256 in the entomopathogenic Photorhabdus luminescens involves several O-methylations, but the biosynthetic gene cluster antA-I lacks corresponding tailoring enzymes. We here describe the identification of five putative, highly homologous O-methyltransferases encoded in the genome of P. luminescens. Activity assays in vitro and deletion experiments in vivo revealed that three of them account for anthraquinone tailoring by producing three monomethylated and two dimethylated species of AQ-256...

Landornamide A is a ribosomally synthesized and post-translationally modified peptide (RiPP) natural product with antiviral activity. Its biosynthetic gene cluster encodes─among other maturases─the peptide arginase OspR, which converts arginine to ornithine units in an unusual post-translational modification. Peptide arginases are a recently discovered RiPP maturase family with few characterized representatives. They show little sequence similarity to conventional arginases, a well-characterized enzyme family catalyzing the hydrolysis of free arginine to ornithine and urea...

BACKGROUND: Parvovirus B19 (B19V) infection following pediatric hematopoietic cell transplantation (HCT) is a rare complication and available data is scarce. Therefore, we present the experience with B19V Infection in allogeneic pediatric HCT recipients at our transplant center together with a systematic review of the literature. METHODS: Pediatric HCT patients with Parvovirus B19 infection treated at the University Children's Hospital Münster between 1999 and 2021 were retrospectively identified and clinical data were analyzed...

To evaluate the genetic diversity and clustering rates of M. tuberculosis strains to better understand transmission among persons deprived of liberty (PDL) in Rio Grande do Sul (RS), southern Brazil. This is a cross-sectional study, including strains of M. tuberculosis isolated from PDL, stored at the Central Laboratory of RS, in the period from 2013 to 2018. The molecular characterization was performed using the MIRU-VNTR 15 loci method. A total of 598 M. tuberculosis strains were genotyped, and 37.5% were grouped into 53 clusters...

PURPOSE: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. METHODS: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients...

Elasmobranchs (sharks and rays) are charismatic cartilaginous fish, popular in public aquaria. Almost 200 shark and ray species are listed as threatened by the International Union for Conservation of Nature (IUCN), demonstrating the importance of captive breeding and research programmes. Limited studies investigate diseases of elasmobranchs in captive and free-living environments, and among available literature neoplasia is rarely reported, with even fewer cases of lymphoid neoplasia documented. This article outlines the first reports of lymphoid neoplasia in three elasmobranch species in which haematopoietic neoplasms have not been reported to date...

BACKGROUND: Public safety personnel (PSP) are exposed to potentially psychologically traumatic events (PPTE) far more often than the general public, which increases the risk for various post-traumatic stress injuries (PTSIs). While there are many evidence-based psychological interventions for PTSI, the effectiveness of each intervention for PSP remains unclear. OBJECTIVES: The current study assessed the effectiveness and acceptability of psychological interventions for PTSI among PSPs...

OBJECTIVES: Relative fundamental frequency (RFF) is an acoustic measure of changes in fundamental frequency during voicing transitions. The physiological mechanisms underlying RFF remain unclear. Recent modeling suggests that changes in RFF during voicing offset are due to decreases in overall system stiffness as a direct result of the cessation of vocal fold collision. To evaluate this finding empirically, here we examined whether variable timing between the end of vocal fold collision and the final voicing cycle used to calculate RFF explained the variability in RFF across individual voicing offset utterances...

The objective of this study was to investigate the electroencephalographic reaction pattern and FOS protein expression in male piglets undergoing surgical castration under light isoflurane anaesthesia with or without local anaesthesia. The experiment was conducted under isoflurane anaesthesia to exclude the effect of the affective components of pain on the measurements. Changes in the oscillatory activity of the cerebral cortex over a 90 s period after noxious stimulation or simulated interventions were analysed...

Dioxygenases catalyze stereoselective oxygen atom transfer in metabolic pathways of biological, industrial, and pharmaceutical importance, but their precise chemical principles remain controversial. The α-ketoglutarate (αKG)-dependent dioxygenase AsqJ synthesizes biomedically active quinolone alkaloids via desaturation and subsequent epoxidation of a carbon-carbon bond in the cyclopeptin substrate. Here, we combine high-resolution X-ray crystallography with enzyme engineering, quantum-classical (QM/MM) simulations, and biochemical assays to describe a peroxidic intermediate that bridges the substrate and active site metal ion in AsqJ...

Understanding antibiotic resistance mechanisms is critical for developing anti-infective therapies and genomics-based drug discovery. Yet, many knowledge gaps remain with respect to novel types of antibiotics from less explored producers such as anaerobes (clostridia). By genome editing and functional assays we found that CtaZ confers self-resistance against the copper chelator and gyrase inhibitor closthioamide (CTA) in Ruminiclostridium cellulolyticum. Biochemical analyses, bioinformatics, and X-ray crystallography revealed CtaZ as a founding member of a new subgroup of GyrI-like proteins...

BACKGROUND: Epidemiology of Clostridioides difficile infection (CDI) in paediatric cancer patients is uncertain. The primary objective was to describe the prevalence of CDI outcomes among paediatric patients receiving cancer treatments. Secondary objectives were to describe clinical features of CDI, propose a definition of severe CDI and to determine risk factors for CDI clinical outcomes. METHODS: A multi-centre retrospective cohort study that included paediatric patients (1-18 years of age) receiving cancer treatments with CDI...

PURPOSE: Children and adolescents undergoing treatment for cancer or allogeneic hematopoietic cell transplantation are at increased risk for methicillin-resistant Staphylococcus aureus (MRSA). We therefore examined the occurrence and outcome of MRSA colonization and infection in patients of a large European pediatric cancer center. METHODS: In a prospective observational cohort study conducted between 2007 and 2018, nasopharyngeal swabs for culture of MRSA were obtained from all admitted patients...

The heterotrimeric CCAAT-binding complex (CBC) is a fundamental eukaryotic transcription factor recognizing the CCAAT box. In certain fungi, like Aspergilli, the CBC cooperates with the basic leucine zipper HapX to control iron metabolism. HapX functionally depends on the CBC, and the stable interaction of both requires DNA. To study this cooperative effect, X-ray structures of the CBC-HapX-DNA complex were determined. Downstream of the CCAAT box, occupied by the CBC, a HapX dimer binds to the major groove...

Lima1 is an extensively studied prognostic marker of malignancy and is also considered to be a tumour suppressor, but its role in a developmental context of non-transformed cells is poorly understood. Here, we characterise the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We identify that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing, as well as for proper mitochondrial energetics in embryonic stem cells...

Fasciolosis caused by the trematode Fasciola hepatica is an important parasitosis in both livestock and humans across the globe. Chronic infections in cattle are associated with considerable economic losses. As a prerequisite for an effective control and prevention of fasciolosis in cattle fine-scale predictive models on farm-level are needed. Since disease transmission will only occur where the mollusc intermediate host is present, the objective of our research was to develop a regression model that allows to predict the local presence or absence of Galba truncatula as principal intermediate host for Fasciola hepatica in Switzerland...

INTRODUCTION: Knowledge about the factors that contribute to the correctional officer's (CO) mental health and well-being, or best practices for improving the mental health and well-being of COs, have been hampered by the dearth of rigorous longitudinal studies. In the current protocol, we share the approach used in the Canadian Correctional Workers' Well-being, Organizations, Roles and Knowledge study (CCWORK), designed to investigate several determinants of health and well-being among COs working in Canada's federal prison system...

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0...