Siderophore systems at play: system interactions as drivers of diversification in pathogenic .

Unlabelled: The -HPI genomic island encodes the salicylate-type siderophore piscibactin, a key virulence factor in several pathogenic species. To advance our understanding of the siderophore metabolome (siderome) in , we combined high-resolution metabolomics with genetic and phenotypic analyses of biosynthetic mutants. LC-MS/MS and Feature-Based Molecular Networking (FBMN) revealed the presence of known siderophores, vanchrobactin and piscibactin/photoxenobactin-like siderophores, alongside two non-reported catecholate analogs of the formed siderophores, 2-hydroxypiscibactin (2-OH-Pcb) and 2-hydroxyphotoxenobactin E (2-OH-PxbE).

Genetic and biochemical insights into siderophore biosynthesis in the marine fish pathogen Tenacibaculum maritimum.

Siderophore production is a key fitness trait for bacteria, particularly in iron-limited environments such as marine ecosystems and host tissues. In this study, we identify the tenABECDC2D2hp1-4 gene cluster as responsible for siderophore biosynthesis in Tenacibaculum maritimum, confirmed through genome analysis and a tenCD-inactivated mutant. This cluster, highly similar to the desferrioxamine biosynthesis system in Streptomyces coelicolor, features a unique tenCD duplication/fusion, essential for siderophore formation.

: Circulating Strains After the Introduction of the Rotavirus Vaccine (Rotarix) in Luanda Province of Angola.

(. ) remains the leading cause of pediatric diarrhea. Although Angola introduced Rotarix, the human monovalent .

Genetics of Growth Hormone Deficiency: Insights from a Cohort of 203 Patients.

Context: Growth Hormone (GH) deficiency is a rare disorder characterized by severe short stature, which can result from genetic mutations affecting hypothalamic-pituitary development and function.

Objective: To determine the genetic basis of GH deficiency in a Portuguese cohort.

Design, Setting, Patients: Multicentre cohort of 203 GH-deficient patients (78 with Isolated GH Deficiency (IGHD) and 125 with Combined Pituitary Hormone Deficiency (CPHD)) were analysed.

Novel XAD-LC/MS-FBMN-IMS Strategy for Screening Hydroxamate Siderophores: Siderome Analysis of the Pathogenic Bacterium .

Hydroxamate siderophores are key virulence factors in multiple pathogens, and their structures present interesting scaffolds for potential biotechnological applications such as the design of novel antimicrobials. However, their variable and scarce production, their low stability, and occurrence as complex mixtures in natural samples complicate their analysis. Herein, we present a new strategy, named XAD-LC/MS-FBMN-IMS, which enables the analysis of the -hydroxamate siderophore composition from microbial cultures by integrating traditional XAD resin extraction, modern Feature-Based Molecular Networking (FBMN) tools, and a novel direct infusion ion mobility mass spectrometry validation approach.

Household iodized salt consumption and iodine status in women of reproductive age in Angola: a cross-sectional study.

Background: The first evaluation of iodine nutritional status in Angola was carried out in 2006. This involved a limited survey of urinary iodine concentration (UIC) among school-aged children, conducted in 24 schools within the municipalities of Bié Province. Almost all the children had moderate to high levels of iodine deficiency, with a median UIC below 100 μg/L.

Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis.

Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic pituitary adenomas (i.e.

High Detection Rate of Rotavirus Infection Among Children Admitted with Acute Gastroenteritis to Six Public Hospitals in Luanda Province After the Introduction of Rotarix Vaccine: A Cross-Sectional Study.

Rotavirus group A (RVA) is a major cause of pediatric acute gastroenteritis (AGE). Vaccination is an effective public health strategy and Angola implemented it in 2014. This hospital-based study aimed to estimate the prevalence of RVA infection and the severity of AGE in children under five years of age treated at six hospitals in Luanda Province.

First complete genome sequence of serotype O4, a rising threat in marine aquaculture.

is a Gram-negative marine fish pathogen. Here, we present the complete genome sequence of strain SP9.1, representing the emerging serotype O4.

Kallmann Syndrome: Functional Analysis of a Missense Variant Shows Aberrant RNA Splicing.

Kallmann syndrome is a rare disorder characterized by hypogonadotropic hypogonadism and an impaired sense of smell (anosmia or hyposmia) caused by congenital defects in the development of the gonadotropin-releasing hormone (GnRH) and olfactory neurons. Mutations in several genes have been associated with Kallmann syndrome. However, genetic testing of this disorder often reveals variants of uncertain significance (VUS) that remain uninterpreted without experimental validation.

Outer membrane vesicles (OMVs) from Tenacibaculum maritimum as a potential vaccine against fish tenacibaculosis.

Outer membrane vesicles (OMVs) have been gained increasing attention in vaccinology due to their ability to induce strong protective humoral and cell-mediated immunity. The Gram-negative bacterium Tenacibaculum maritimum, the causative agent of marine tenacibaculosis, poses a significant challenge to the global aquaculture industry due to its difficult prophylaxis. In previous studies, we demonstrated that OMV production is a key virulence mechanism in T.

Predicted mechanistic impacts of human protein missense variants.

Genome sequencing efforts have led to the discovery of tens of millions of protein missense variants found in the human population with the majority of these having no annotated role and some likely contributing to trait variation and disease. Sequence-based artificial intelligence approaches have become highly accurate at predicting variants that are detrimental to the function of proteins but they do not inform on mechanisms of disruption. Here we combined sequence and structure-based methods to perform proteome-wide prediction of deleterious variants with information on their impact on protein stability, protein-protein interactions and small-molecule binding pockets.

Promoting advanced medical services in the framework of 3PM-a proof-of-concept by the "Centro" Region of Portugal.

Unlabelled: Multidisciplinary team from three universities based in the "Centro" Region of Portugal developed diverse approaches as parts of a project dedicated to enhancing and expanding Predictive, Preventive, and Personalized Medicine (3PM) in the Region. In a sense, outcomes acted as a proof-of-concept, in that they demonstrated the feasibility, but also the relevance of the approaches. The accomplishments comprise defining a new regional strategy for implementing 3PM within the Region, training of human resources in genomic sequencing, and generating good practices handbooks dedicated to diagnostic testing via next-generation sequencing, to legal and ethical concerns, and to knowledge transfer and entrepreneurship, aimed at increasing literacy on 3PM approaches.

Remodulation of bacterial transcriptome after acquisition of foreign DNA: the case of -HPI high-pathogenicity island in .

The high-pathogenicity island -HPI is widespread in and encodes the siderophore piscibactin, as well as the regulator PbtA that is essential for its expression. In this work, we aim to study whether PbtA directly interacts with -HPI promoters. Furthermore, we hypothesize that PbtA, and thereby the acquisition of -HPI island, may also influence the expression of other genes elsewhere in the bacterial genome.

The impact of biological clock and sex hormones on the risk of disease.

Molecular clocks are responsible for defining 24-h cycles of behaviour and physiology that are called circadian rhythms. Several structures and tissues are responsible for generating these circadian rhythms and are named circadian clocks. The suprachiasmatic nucleus of the hypothalamus is believed to be the master circadian clock receiving light input via the optic nerve and aligning internal rhythms with environmental cues.

Hypoparathyroidism, deafness and renal dysplasia syndrome caused by a splice site mutation leading to the activation of a cryptic splice site.

The HDR syndrome is a rare autosomal dominant disorder characterised by Hypoparathyroidism, Deafness, and Renal dysplasia, and is caused by inactivating heterozygous germline mutations in the gene. We report an 11-year-old girl with HDR syndrome caused by a heterozygous mutation located at the splice acceptor site of exon 5 of the gene (NM_001002295.2: c.

The secretome of the fish pathogen includes soluble virulence-related proteins and outer membrane vesicles.

, the etiological agent of tenacibaculosis in marine fish, constitutively secretes extracellular products (ECPs) in which protein content has not been yet comprehensively studied. In this work, the prevalence of extracellular proteolytic and lipolytic activities related to virulence was analyzed in 64 strains belonging to the O1-O4 serotypes. The results showed the existence of a great intra-specific heterogeneity in the enzymatic capacity, particularly within serotype O4.

The Sigma Factor AsbI Is Required for the Expression of Acinetobactin Siderophore Transport Genes in .

subsp. (), a Gram-negative bacterium causing furunculosis in fish, produces the siderophores acinetobactin and amonabactins in order to extract iron from its hosts. While the synthesis and transport of both systems is well understood, the regulation pathways and conditions necessary for the production of each one of these siderophores are not clear.

Structural Requirements for Ga Coordination in Synthetic Analogues of the Siderophore Piscibactin Deduced by Chemical Synthesis and Density Functional Theory Calculations.

Stereoselective total synthesis of several analogues of piscibactin (Pcb), the siderophore produced by different pathogenic Gram-negative bacteria, was performed. The acid-sensitive αmethylthiazoline moiety was replaced by a more stable thiazole ring, differing in the configuration of the OH group at the C-13 position. The ability of these Pcb analogues to form complexes with Ga as a mimic of Fe showed that the configuration of the hydroxyl group at C-13 as 13 is crucial for the chelation of Ga to preserve the metal coordination, while the presence of a thiazole ring instead of the αmethylthiazoline moiety does not affect such coordination.

Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes.

Drug efficacy is dependent on the pharmacokinetics and pharmacodynamics of therapeutic agents. Tight junctions, detoxification enzymes, and drug transporters, due to their localization on epithelial barriers, modulate the absorption, distribution, and the elimination of a drug. The epithelial barriers which control the pharmacokinetic processes are sex steroid hormone targets, and in this way, sex hormones may also control the drug transport across these barriers.

A Common Variant in the Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the (rs2359536), (rs10763170) and (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population.