Self-Resistance Gene-Guided Discovery of the Molecular Basis for Biosynthesis of the Fatty Acid Synthase Inhibitor Cerulenin.

Cerulenin (1) is the first reported natural fatty acid synthase inhibitor and has been intensively researched for its antifungal, anticancer and anti-obesity properties. However, the molecular basis for its biosynthesis has remained a mystery for six decades. Here, we have identified the polyketide biosynthetic gene cluster (cer) responsible for the biosynthesis of 1 from two Sarocladium species using a self-resistance gene mining approach, which we validated via heterologous reconstitution of cer cluster in an Aspergillus nidulans host.

Systemic neutrophil degranulation and emergency granulopoiesis in patients with Clostridioides difficile infection.

Objectives: Clostridioides difficile infection (CDI) is characterized by neutrophilia in blood, with a high leukocyte count accompanying severe infection. In this study, we characterized peripheral blood neutrophil activation and maturity in CDI by (i) developing a method to phenotype stored neutrophils for disease-related developmental alterations and (ii) assessing neutrophil-associated biomarkers.

Methods: We stored fixed leukocytes from blood collected within 24 h of diagnosis from a cohort of hospitalized patients with acute CDI.

A Multisource Process Evaluation of a Community-Based Healthy Lifestyle Programme for Child and Adolescent Obesity.

Whānau Pakari is a healthy lifestyle assessment and intervention programme for children and adolescents with obesity in Taranaki (Aotearoa/New Zealand), which, in this region, replaced the nationally funded Green Prescription Active Families (GRxAF) programme. We compared national referral rates from the GRxAF programme (age 5-15 years) and the B4 School Check (B4SC, a national preschool health and development assessment) with referral rates in Taranaki from Whānau Pakari. We retrospectively analysed 5 years of clinical data (2010-2015), comparing referral rates before, during, and after the Whānau Pakari clinical trial, which was embedded within the programme.

Genomic Heterogeneity of Cryptosporidium parvum Isolates From Children in Bangladesh: Implications for Parasite Biology and Human Infection.

Cryptosporidium species are a major cause of diarrhea and associated with growth failure. There is currently only limited knowledge of the parasite's genomic variability. We report a genomic analysis of Cryptosporidium parvum isolated from Bangladeshi infants and reanalysis of sequences from the United Kingdom.

Infants Eligible for Neonatal Hypoglycemia Screening: A Systematic Review.

Importance: Neonatal hypoglycemia is common, occurring in up to 50% of infants at risk for hypoglycemia (infant of diabetic mother [IDM], small for gestational age [SGA], large for gestational age [LGA], and preterm) and is associated with long-term neurodevelopmental impairment. Guidelines recommend screening infants at risk of hypoglycemia. The proportion of infants who require screening for neonatal hypoglycemia is unknown.

Clustering predicted structures at the scale of the known protein universe.

Proteins are key to all cellular processes and their structure is important in understanding their function and evolution. Sequence-based predictions of protein structures have increased in accuracy, and over 214 million predicted structures are available in the AlphaFold database. However, studying protein structures at this scale requires highly efficient methods.

Children develop Immunity to cryptosporidiosis in a high transmission intensity area.

Background: is one of the top causes of diarrhea in Bangladesh infants. infections lead to the production of antibody immune responses, which were associated with a decrease in parasite burden and decreased disease severity in subsequent infections.

Methods: We conducted a longitudinal study of cryptosporidiosis from birth to five years of age in an urban slum of Dhaka Bangladesh.

Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis.

There is no vaccine to protect from cryptosporidiosis, a leading cause of diarrhea in infants in low- and middle-income countries. Here, we comprehensively identified parasite antigens associated with protection from reinfection. A Cryptosporidium protein microarray was constructed by in vitro transcription and translation of 1,761 C.

Fast and accurate protein structure search with Foldseek.

As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein against a database by describing tertiary amino acid interactions within proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of Dali, TM-align and CE, respectively.

CAGECAT: The CompArative GEne Cluster Analysis Toolbox for rapid search and visualisation of homologous gene clusters.

Background: Co-localized sets of genes that encode specialized functions are common across microbial genomes and occur in genomes of larger eukaryotes as well. Important examples include Biosynthetic Gene Clusters (BGCs) that produce specialized metabolites with medicinal, agricultural, and industrial value (e.g.

Trauma-Disclosure, Meaning-Making, and Help-Seeking in Mothers Experiencing Homelessness: Results From a Trauma-Focused, Clinical Ethnographic Narrative Intervention.

Mothers experiencing homelessness are seldom asked about past trauma that may be causal to housing instability and poor health. There are also few validated trauma-focused interventions in family shelters. To address this gap, we tested the feasibility and acceptability of the trauma-focused clinical ethnographic narrative intervention (CENI-TF) in increasing mothers' trauma disclosure, appraisal of its meaning in their lives, and help-seeking behaviors.

Stereodivergent Hydroxylation of Berkeleylactones by .

has previously been reported to produce A26771B, a 16-membered macrocyclic polyketide with activity against Gram-positive bacteria, mycoplasma, and fungi, as well as the structurally related compounds berkeleylactone E and berkeleylactones I-O. In this work, large-scale cultivation of NRRL 5630 on rice yielded seven new berkeleylactone analogues, berkeleylactone E methyl ester, 14--berkeleylactone F, berkeleylactones P-R, 12--berkeleylactone Q, and 13--berkeleylactone R, and six previously reported analogues, A26771B and berkeleylactones E-G and J-K. The structures of the berkeleylactones were elucidated by detailed analysis of spectroscopic data, molecular modeling, and comparison with literature values.

Fiber-Specific Measures of White Matter Microstructure and Macrostructure Are Associated With Internalizing and Externalizing Symptoms in Children Born Very Preterm and Full-term.

Background: Tensor-based investigations suggest that delayed or disrupted white matter development may relate to adverse behavioral outcomes in individuals born very preterm (VP); however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine white matter microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years.

Methods: Diffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP and 29 FT at 7 years, 125 VP and 44 FT at 13 years).

Excitatory and inhibitory neuron imbalance in the intrauterine growth restricted fetal guinea pig brain: Relevance to the developmental origins of schizophrenia and autism.

Neurodevelopmental disorders such as schizophrenia and autism are thought to involve an imbalance of excitatory and inhibitory signaling in the brain. Intrauterine growth restriction (IUGR) is a risk factor for these disorders, with IUGR onset occurring during critical periods of neurodevelopment. The aim of this study was to determine the impact of IUGR on excitatory and inhibitory neurons of the fetal neocortex and hippocampus.

The Dynamics of Adaptation to Stress from Standing Genetic Variation and de novo Mutations.

Adaptation from standing genetic variation is an important process underlying evolution in natural populations, but we rarely get the opportunity to observe the dynamics of fitness and genomic changes in real time. Here, we used experimental evolution and Pool-Seq to track the phenotypic and genomic changes of genetically diverse asexual populations of the yeast Saccharomyces cerevisiae in four environments with different fitness costs. We found that populations rapidly and in parallel increased in fitness in stressful environments.

UFCG: database of universal fungal core genes and pipeline for genome-wide phylogenetic analysis of fungi.

In phylogenomics the evolutionary relationship of organisms is studied by their genomic information. A common approach to phylogenomics is to extract related genes from each organism, build a multiple sequence alignment and then reconstruct evolution relations through a phylogenetic tree. Often a set of highly conserved genes occurring in single-copy, called core genes, are used for this analysis, as they allow efficient automation within a taxonomic clade.

Repressed Ang 1-7 in COVID-19 Is Inversely Associated with Inflammation and Coagulation.

The coronavirus SARS-CoV-2 infects host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which belongs to an anti-inflammatory, anti-thrombotic counter-regulatory arm of the renin-angiotensin system (RAS). ACE2 dysfunction and RAS dysregulation has been explored as a driving force in acute respiratory distress syndrome (ARDS), but data from COVID-19 patients has been inconsistent and inconclusive. We sought to identify disruptions of the classical (ACE)/angiotensin (Ang) II/Ang II type-1 receptor (ATR) and the counter-regulatory ACE2/Ang 1-7/ Receptor (R) pathways in patients with COVID-19 and correlate these with severity of infection and markers of inflammation and coagulation.

Determinants of exclusive breastfeeding for wāhine Māori.

Aim: Breastfeeding is a fundamental aspect of tikanga Māori (Māori cultural traditions/practices) requiring protection and promotion. This study identifies determinants of exclusive breastfeeding in wāhine Māori.

Methods: Wāhine Māori enrolled in the Growing Up in New Zealand child cohort study participated (n=1060).

Development of regional brain gray matter volume across the first 13 years of life is associated with childhood math computation ability for children born very preterm and full term.

Very preterm birth (VP; <32 weeks' gestation) is associated with altered brain gray matter development and lower math ability. In typically developing children, the neural correlates of math ability may change dynamically with age, though evidence in VP children is limited. In a prospective longitudinal cohort of children born VP and full term (FT), we aimed to investigate associations between 1) concurrent regional brain volumes and math ability at 7 (n = 148 VP; n = 34 FT) and 13-years (n = 130 VP; n = 46 FT), and 2) regional volumetric growth across childhood (term-equivalent age (TEA) to 7-years; 7 to 13-years) and math ability from 7 to 13-years, and improvement in ability from 7 to 13 years.

Corrigendum: ArfX2 GTPase Regulates Trafficking From the Trans-Golgi to Lysosomes and Is Necessary for Liver Abscess Formation in the Protozoan Parasite .

[This corrects the article DOI: 10.3389/fcimb.2021.

Prevalence and Distribution of spp. and in Rural and Urban Communities of South Africa.

Objective: Enteric diseases remain a serious health problem globally. High prevalence is evident in regions with poor socioeconomic conditions, poor sanitation, and inadequate clean water supply, such as South Africa. Designing an effective strategy, however, requires local knowledge, which can be particularly challenging to acquire in low-and middle-income countries.

Randomised controlled trial of nebulised gentamicin in children with bronchiectasis.

Aim: Following trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis.

Methods: This is a randomised, double-blind, placebo-controlled, crossover trial of 12-week nebulised placebo/gentamicin, 6-week washout, 12-week gentamicin/placebo. Participants were children (5-15 years) with bronchiectasis, chronic infection (any pathogen), and able to perform spirometry from a hospital bronchiectasis clinic.

The relationship between diet and sleep in 2-y-old children: Results from Growing Up in New Zealand.

Objectives: This study aimed to examine the relationship between dietary practices and sleep in young children.

Methods: In this study, 2-y-old children (n = 6327) and their mothers were enrolled at birth and during pregnancy, respectively. The study obtained maternal demographic, health, and lifestyle data during late pregnancy.