Nanoscaled Discovery of a Shunt Rifamycin from Using a Three-Color GFP-Tagged Macrophage Infection Assay.

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment.

Functional biology and biotechnology of thermophilic viruses.

Viruses have developed sophisticated biochemical and genetic mechanisms to manipulate and exploit their hosts. Enzymes derived from viruses have been essential research tools since the first days of molecular biology. However, most viral enzymes that have been commercialized are derived from a small number of cultivated viruses, which is remarkable considering the extraordinary diversity and abundance of viruses revealed by metagenomic analysis.

Correlative metabologenomics of 110 fungi reveals metabolite-gene cluster pairs.

Natural products research increasingly applies -omics technologies to guide molecular discovery. While the combined analysis of genomic and metabolomic datasets has proved valuable for identifying natural products and their biosynthetic gene clusters (BGCs) in bacteria, this integrated approach lacks application to fungi. Because fungi are hyper-diverse and underexplored for new chemistry and bioactivities, we created a linked genomics-metabolomics dataset for 110 Ascomycetes, and optimized both gene cluster family (GCF) networking parameters and correlation-based scoring for pairing fungal natural products with their BGCs.

A Survey of Didemnin Depsipeptide Production in .

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family , recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria .

Novel Viral DNA Polymerases From Metagenomes Suggest Genomic Sources of Strand-Displacing Biochemical Phenotypes.

Viruses are the most abundant and diverse biological entities on the planet and constitute a significant proportion of Earth's genetic diversity. Most of this diversity is not represented by isolated viral-host systems and has only been observed through sequencing of viral metagenomes (viromes) from environmental samples. Viromes provide snapshots of viral genetic potential, and a wealth of information on viral community ecology.

Whose Right Is It Anyway? The Duties Owed to a Deceased and to Surviving Family Members When Dealing with a Corpse: Brennan v City of Bradford Metropolitan District Council and Leeds Teaching Hospitals NHS Trust [2021] 1 WLUK 429.

This commentary considers the case of Brennan, in which surviving family members successfully brought a Human Rights Act 1998 (HRA) claim against a hospital and a council for the way in which they both treated a body post-mortem. Their failure to freeze it led to such a state of decomposition that it was unfit for viewing. The family argued this constituted an unjustified interference with their rights to family and private life.

Improving the delivery of palliative care through predictive modeling and healthcare informatics.

Objective: Access to palliative care (PC) is important for many patients with uncontrolled symptom burden from serious or complex illness. However, many patients who could benefit from PC do not receive it early enough or at all. We sought to address this problem by building a predictive model into a comprehensive clinical framework with the aims to (i) identify in-hospital patients likely to benefit from a PC consult, and (ii) intervene on such patients by contacting their care team.

Discovery of Novel Biosynthetic Gene Cluster Diversity From a Soil Metagenomic Library.

Soil microorganisms historically have been a rich resource for natural product discovery, yet the majority of these microbes remain uncultivated and their biosynthetic capacity is left underexplored. To identify the biosynthetic potential of soil microorganisms using a culture-independent approach, we constructed a large-insert metagenomic library in from a topsoil sampled from the Cullars Rotation (Auburn, AL, United States), a long-term crop rotation experiment. Library clones were screened for biosynthetic gene clusters (BGCs) using either PCR or a NGS (next generation sequencing) multiplexed pooling strategy, coupled with bioinformatic analysis to identify contigs associated with each metagenomic clone.

Diversity and Distribution of a Novel Genus of Hyperthermophilic Viruses Encoding a Proof-Reading Family-A DNA Polymerase.

Despite the high abundance of in many geothermal systems, these bacteria are difficult to culture and no viruses infecting members of this phylum have been isolated. Here, we describe the complete, circular dsDNA Uncultivated Virus Genome (UViG) of Octopus Spring virus (TOSV), derived from metagenomic data, along with eight related UViGs representing three additional viral species. Despite low overall similarity among viruses from different hot springs, the genomes shared a high degree of synteny, and encoded numerous genes for nucleotide metabolism, including a PolA-type DNA polymerase polyprotein with likely accessory functions, a DNA Pol III sliding clamp, a thymidylate kinase, a DNA gyrase, a helicase, and a DNA methylase.

Interventions to help coral reefs under global change-A complex decision challenge.

Climate change is impacting coral reefs now. Recent pan-tropical bleaching events driven by unprecedented global heat waves have shifted the playing field for coral reef management and policy. While best-practice conventional management remains essential, it may no longer be enough to sustain coral reefs under continued climate change.

Rapid counting and spectral sorting of live coral larvae using large-particle flow cytometry.

Research with coral embryos and larvae often requires laborious manual counting and sorting of individual specimens, usually via microscopy. Because many coral species spawn only once per year during a narrow temporal window, sample processing is a time-limiting step for research on the early life-history stages of corals. Flow cytometry, an automated technique for measuring and sorting particles, cells, and cell-clusters, is a potential solution to this bottleneck.

Immobilisation of living coral embryos and larvae.

Embedding and immobilisation of living cells and microorganisms is used in a variety of research and commercial applications. Here we report the successful extended immobilisation of coral larvae in a low-gelling temperature agarose. Embryos and larvae of five broadcast-spawning Scleractinian species were immobilised in agarose gel and tested in a series of exploratory survival and settlement assays.

Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics.

A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol ( Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acetyl-3-butanoylchloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol.

The Complete Genome Sequence of Hyperthermophile DSM 6724™ Reveals a Specialized Carbohydrate Fermentor.

Here we report the complete genome sequence of the chemoorganotrophic, extremely thermophilic bacterium, , which is a Gram negative, strictly anaerobic bacterium. and together form the phylum. The two genomes are highly syntenic, and both are distantly related to spp.

Molecular Modeling and Functional Analysis of Exome Sequencing-Derived Variants of Unknown Significance Identify a Novel, Constitutively Active FGFR2 Mutant in Cholangiocarcinoma.

Purpose: Genomic testing has increased the quantity of information available to oncologists. Unfortunately, many identified sequence alterations are variants of unknown significance (VUSs), which thus limit the clinician's ability to use these findings to inform treatment. We applied a combination of in silico prediction and molecular modeling tools and laboratory techniques to rapidly define actionable VUSs.

Proteolytic Cleavage of the Immunodominant Outer Membrane Protein rOmpA in Rickettsia rickettsii.

, the causative agent of Rocky Mountain spotted fever, contains two immunodominant proteins, rOmpA and rOmpB, in the outer membrane. Both rOmpA and rOmpB are conserved throughout spotted fever group rickettsiae as members of a family of autotransporter proteins. Previously, it was demonstrated that rOmpB is proteolytically processed, with the cleavage site residing near the autotransporter domain at the carboxy-terminal end of the protein, cleaving the 168-kDa precursor into apparent 120-kDa and 32-kDa fragments.

Molecular Diagnostic Field Test for Point-of-Care Detection of Ebola Virus Directly From Blood.

A molecular diagnostic method for robust detection of Ebola virus (EBOV) at the point of care (POC) directly from blood samples is described. This assay is based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) of the glycoprotein gene of EBOV. Complete reaction formulations were lyophilized in 0.

Complete genome sequences of Geobacillus sp. WCH70, a thermophilic strain isolated from wood compost.

Geobacillus sp. WCH70 was one of several thermophilic organisms isolated from hot composts in the Middleton, WI area. Comparison of 16 S rRNA sequences showed the strain may be a new species, and is most closely related to G.

Complete genome of Staphylococcus aureus Tager 104 provides evidence of its relation to modern systemic hospital-acquired strains.

Background: Staphylococcus aureus (S. aureus) infections range in severity due to expression of certain virulence factors encoded on mobile genetic elements (MGE). As such, characterization of these MGE, as well as single nucleotide polymorphisms, is of high clinical and microbiological importance.

Erratum to: Complete genome sequences of Geobacillus sp. Y412MC52, a xylan-degrading strain isolated from obsidian hot spring in Yellowstone National Park.

[This corrects the article DOI: 10.1186/s40793-015-0075-0.].

Complete genome sequences of Geobacillus sp. Y412MC52, a xylan-degrading strain isolated from obsidian hot spring in Yellowstone National Park.

Geobacillus sp. Y412MC52 was isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. The genome was sequenced, assembled, and annotated by the DOE Joint Genome Institute and deposited at the NCBI in December 2011 (CP002835).

Complete Genome Sequence of Thermus aquaticus Y51MC23.

Thermus aquaticus Y51MC23 was isolated from a boiling spring in the Lower Geyser Basin of Yellowstone National Park. Remarkably, this T. aquaticus strain is able to grow anaerobically and produces multiple morphological forms.

Complete genome sequence of Geobacillus thermoglucosidasius C56-YS93, a novel biomass degrader isolated from obsidian hot spring in Yellowstone National Park.

Geobacillus thermoglucosidasius C56-YS93 was one of several thermophilic organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. Comparison of 16 S rRNA sequences confirmed the classification of the strain as a G. thermoglucosidasius species.