MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Cytogenetic bands and sharp peaks of Alu underlie large-scale segmental regulation of nuclear genome architecture.

Cytogenetic bands reflect genomic organization in large blocks of DNA with similar properties. Because banding patterns are invariant, this organization may often be assumed unimportant for genome regulation. Results here challenge that view.

Differences in Alu vs L1-rich chromosome bands underpin architectural reorganization of the inactive-X chromosome and SAHFs.

The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built.

Metagenomic data reveals type I polyketide synthase distributions across biomes.

Microbial polyketide synthase (PKS) genes encode the biosynthesis of many biomedically or otherwise commercially important natural products. Despite extensive discovery efforts, metagenomic analyses suggest that only a small fraction of nature's polyketide biosynthetic potential has been realized. Much of this potential originates from type I PKSs (T1PKSs), which can be further delineated based on their domain organization and the structural features of the compounds they encode.

Metagenomic Data Reveal Type I Polyketide Synthase Distributions Across Biomes.

Unlabelled: Microbial polyketide synthase (PKS) genes encode the biosynthesis of many biomedically important natural products, yet only a small fraction of nature's polyketide biosynthetic potential has been realized. Much of this potential originates from type I PKSs (T1PKSs), which can be delineated into different classes and subclasses based on domain organization and structural features of the compounds encoded. Notably, phylogenetic relationships among PKS ketosynthase (KS) domains provide a method to classify the larger and more complex genes in which they occur.

The Natural Product Domain Seeker version 2 (NaPDoS2) webtool relates ketosynthase phylogeny to biosynthetic function.

The Natural Product Domain Seeker (NaPDoS) webtool detects and classifies ketosynthase (KS) and condensation domains from genomic, metagenomic, and amplicon sequence data. Unlike other tools, a phylogeny-based classification scheme is used to make broader predictions about the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes in which these domains are found. NaPDoS is particularly useful for the analysis of incomplete biosynthetic genes or gene clusters, as are often observed in poorly assembled genomes and metagenomes, or when loci are not clustered, as in eukaryotic genomes.

Structure and Candidate Biosynthetic Gene Cluster of a Manumycin-Type Metabolite from .

A new manumycin-type natural product named pacificamide () and its candidate biosynthetic gene cluster () were discovered from the marine actinobacterium CNT-855. The structure of the compound was determined using NMR, electronic circular dichroism, and bioinformatic predictions. The gene cluster is unique to and found in only two of the 119 genomes analyzed across nine species.

ZNF146/OZF and ZNF507 target LINE-1 sequences.

Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent transposable elements must be repressed to maintain genomic stability, mutated and fragmented transposable elements comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here, we analyzed published ChIP-seq data sets to identify proteins broadly enriched on transposable elements in the human genome.

Pediatric Hospitalist Resuscitation Skills Refresher Training With Pauses for Deliberate Practice.

Introduction Pediatric hospitalists are expected to lead resuscitative efforts for cardiopulmonary arrests, but the infrequency of these events and pediatric advanced life support (PALS) re-certifications are insufficient to maintain skill proficiency.We created a novel resuscitation refresher curriculum for pediatric hospitalists with strategic pauses during simulations for expert and peer coaching of procedural skills. Methods In a tertiary care academic pediatric hospital between September 2018 to June 2019, pediatric hospitalists and fellows voluntarily participated in a series of three quarterly two-hour training sessions taught by expert peer facilitators.

SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin.

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction.

Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.

Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin, and most nuclear RNA from the nucleus but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome "scaffold.

Phylogenetic analysis of the salinipostin γ-butyrolactone gene cluster uncovers new potential for bacterial signalling-molecule diversity.

Bacteria communicate by small-molecule chemicals that facilitate intra- and inter-species interactions. These extracellular signalling molecules mediate diverse processes including virulence, bioluminescence, biofilm formation, motility and specialized metabolism. The signalling molecules produced by members of the phylum Actinobacteria generally comprise γ-butyrolactones, γ-butenolides and furans.

Mechanisms and regulation of IL-22-mediated intestinal epithelial homeostasis and repair.

Aims: Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic inflammatory disorders of the intestine for which key elements in disease initiation and perpetuation are defects in epithelial barrier integrity. Achieving mucosal healing is essential to ameliorate disease outcome and so new therapies leading to epithelial homeostasis and repair are under investigation. This study was designed to determine the mechanisms by which IL-22 regulates intestinal epithelial cell function.

Pediatric Thoracic Trauma Mortality in Iraq and Afghanistan Compared to the United States National Trauma Data Bank.

Introduction: The authors compared pediatric thoracic patients in the Joint Theatre Trauma Registry (JTTR) to those in the National Trauma Data Bank (NTDB) to assess differences in patient mortality rates and mortality risk accounting for age, injury patterns, and injury severity.

Materials And Methods: Patients less than 19 years of age with thoracic trauma were identified in both the JTTR and NTDB. Multiple logistic regression, χ2, Student's t-test, or Mann-Whitney U test were used as indicated to compare the two groups.

Expansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products.

Bacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in species and display species-specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus based on their antimalarial properties.

Extending the Salinilactone Family.

Five new members of the salinilactone family, salinilactones D-H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or shortened alkyl side chains relative to the recently reported salinilactones A-C. They were identified by GC/MS, gas chromatographic retention index, and comparison with synthetic samples.

Strengthening Public Health Leadership in Africa: An Innovative Fellowship Program.

Problem: The Ebola virus disease crisis in West Africa revealed critical weaknesses in health policy and systems in the region, including the poor development and retention of policy leaders able to set sound policy to improve health. Innovative models for enhancing the capabilities of emerging leaders while retaining their talent in their countries are vital.

Approach: Chatham House (London, United Kingdom) established the West African Global Health Leaders Fellowship to help develop the next generation of West African public health leaders.

Experimental Evolution of Escherichia coli K-12 at High pH and with RpoS Induction.

Experimental evolution of K-12 W3110 by serial dilutions for 2,200 generations at high pH extended the range of sustained growth from pH 9.0 to pH 9.3.

Pediatric Thoracic Trauma in Iraq and Afghanistan.

Introduction: The objective of this study is to review available data on pediatric thoracic trauma seen at U.S. military treatment facilities in Iraq and Afghanistan and describe the scope of injuries, patterns seen, and associated mortality.

RNA: a window into the broader role of RNA in nuclear chromosome architecture.

RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of into a trisomic autosome demonstrates remarkable capacity of RNA to localize and comprehensively silence that autosome.

Acid Evolution of Escherichia coli K-12 Eliminates Amino Acid Decarboxylases and Reregulates Catabolism.

Acid-adapted strains of K-12 W3110 were obtained by serial culture in medium buffered at pH 4.6 (M. M.

Benzoate- and Salicylate-Tolerant Strains of Escherichia coli K-12 Lose Antibiotic Resistance during Laboratory Evolution.

Unlabelled: Escherichia coli K-12 W3110 grows in the presence of membrane-permeant organic acids that can depress cytoplasmic pH and accumulate in the cytoplasm. We conducted experimental evolution by daily diluting cultures in increasing concentrations of benzoic acid (up to 20 mM) buffered at external pH 6.5, a pH at which permeant acids concentrate in the cytoplasm.