BK channels promote action potential repolarization in skeletal muscle but contribute little to myotonia.

Patients with myotonia congenita suffer from slowed relaxation of muscle (myotonia), due to hyperexcitability caused by loss-of-function mutations in the ClC-1 chloride channel. A recent study suggested that block of large-conductance voltage- and Ca- activated K channels (BK) may be effective as therapy. The mechanism underlying efficacy was suggested to be lessening of the depolarizing effect of build-up of K in t-tubules of muscle during repetitive firing.

Unveiling the microbial realm with VEBA 2.0: a modular bioinformatics suite for end-to-end genome-resolved prokaryotic, (micro)eukaryotic and viral multi-omics from either short- or long-read sequencing.

The microbiome is a complex community of microorganisms, encompassing prokaryotic (bacterial and archaeal), eukaryotic, and viral entities. This microbial ensemble plays a pivotal role in influencing the health and productivity of diverse ecosystems while shaping the web of life. However, many software suites developed to study microbiomes analyze only the prokaryotic community and provide limited to no support for viruses and microeukaryotes.

Unveiling the Microbial Realm with VEBA 2.0: A modular bioinformatics suite for end-to-end genome-resolved prokaryotic, (micro)eukaryotic, and viral multi-omics from either short- or long-read sequencing.

The microbiome is a complex community of microorganisms, encompassing prokaryotic (bacterial and archaeal), eukaryotic, and viral entities. This microbial ensemble plays a pivotal role in influencing the health and productivity of diverse ecosystems while shaping the web of life. However, many software suites developed to study microbiomes analyze only the prokaryotic community and provide limited to no support for viruses and microeukaryotes.

Efficient formation of single-copy human artificial chromosomes.

Large DNA assembly methodologies underlie milestone achievements in synthetic prokaryotic and budding yeast chromosomes. While budding yeast control chromosome inheritance through ~125-base pair DNA sequence-defined centromeres, mammals and many other eukaryotes use large, epigenetic centromeres. Harnessing centromere epigenetics permits human artificial chromosome (HAC) formation but is not sufficient to avoid rampant multimerization of the initial DNA molecule upon introduction to cells.

Genus-Wide Transcriptional Landscapes Reveal Correlated Gene Networks Underlying Microevolutionary Divergence in Diatoms.

Marine microbes like diatoms make up the base of marine food webs and drive global nutrient cycles. Despite their key roles in ecology, biogeochemistry, and biotechnology, we have limited empirical data on how forces other than adaptation may drive diatom diversification, especially in the absence of environmental change. One key feature of diatom populations is frequent extreme reductions in population size, which can occur both in situ and ex situ as part of bloom-and-bust growth dynamics.

Differential network analysis of oral microbiome metatranscriptomes identifies community scale metabolic restructuring in dental caries.

Dental caries is a microbial disease and the most common chronic health condition, affecting nearly 3.5 billion people worldwide. In this study, we used a multiomics approach to characterize the supragingival plaque microbiome of 91 Australian children, generating 658 bacterial and 189 viral metagenome-assembled genomes with transcriptional profiling and gene-expression network analysis.

Plateau potentials contribute to myotonia in mouse models of myotonia congenita.

It has long been accepted that myotonia (muscle stiffness) in patients with muscle channelopathies is due to myotonic discharges (involuntary firing of action potentials). In a previous study, we identified a novel phenomenon in myotonic muscle: development of plateau potentials, transient depolarizations to near -35 mV lasting for seconds to minutes. In the current study we examined whether plateau potentials contribute to myotonia.

VEBA: a modular end-to-end suite for in silico recovery, clustering, and analysis of prokaryotic, microeukaryotic, and viral genomes from metagenomes.

Background: With the advent of metagenomics, the importance of microorganisms and how their interactions are relevant to ecosystem resilience, sustainability, and human health has become evident. Cataloging and preserving biodiversity is paramount not only for the Earth's natural systems but also for discovering solutions to challenges that we face as a growing civilization. Metagenomics pertains to the in silico study of all microorganisms within an ecological community in situ, however, many software suites recover only prokaryotes and have limited to no support for viruses and eukaryotes.

Microbial functional diversity across biogeochemical provinces in the central Pacific Ocean.

Enzymes catalyze key reactions within Earth's life-sustaining biogeochemical cycles. Here, we use metaproteomics to examine the enzymatic capabilities of the microbial community (0.2 to 3 µm) along a 5,000-km-long, 1-km-deep transect in the central Pacific Ocean.

A Silent Operon of Photorhabdus luminescens Encodes a Prodrug Mimic of GTP.

With the overmining of actinomycetes for compounds acting against Gram-negative pathogens, recent efforts to discover novel antibiotics have been focused on other groups of bacteria. Teixobactin, the first antibiotic without detectable resistance that binds lipid II, comes from an uncultured , a betaproteobacterium; odilorhabdins, from , are broad-spectrum inhibitors of protein synthesis, and darobactins from target BamA, the essential chaperone of the outer membrane of Gram-negative bacteria. and are symbionts of the nematode gut microbiome and attractive producers of secondary metabolites.

The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle.

Excitation-contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, intensive care unit acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a narrow range of resting potentials.

The mechanism underlying transient weakness in myotonia congenita.

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease.

Predicting antimicrobial mechanism-of-action from transcriptomes: A generalizable explainable artificial intelligence approach.

To better combat the expansion of antibiotic resistance in pathogens, new compounds, particularly those with novel mechanisms-of-action [MOA], represent a major research priority in biomedical science. However, rediscovery of known antibiotics demonstrates a need for approaches that accurately identify potential novelty with higher throughput and reduced labor. Here we describe an explainable artificial intelligence classification methodology that emphasizes prediction performance and human interpretability by using a Hierarchical Ensemble of Classifiers model optimized with a novel feature selection algorithm called Clairvoyance; collectively referred to as a CoHEC model.

Reference-guided metagenomics reveals genome-level evidence of potential microbial transmission from the ISS environment to an astronaut's microbiome.

Monitoring microbial communities aboard the International Space Station (ISS) is essential to maintaining astronaut health and the integrity of life-support systems. Using assembled genomes of ISS-derived microbial isolates as references, recruiting metagenomic reads from an astronaut's nasal microbiome revealed no recruitment to a isolate from samples before launch, yet systematic recruitment across the genome when sampled after 3 months aboard the ISS, with a median percent identity of 100%. This suggests that either a highly similar .

Dinoflagellates alter their carbon and nutrient metabolic strategies across environmental gradients in the central Pacific Ocean.

Marine microeukaryotes play a fundamental role in biogeochemical cycling through the transfer of energy to higher trophic levels and vertical carbon transport. Despite their global importance, microeukaryote physiology, nutrient metabolism and contributions to carbon cycling across offshore ecosystems are poorly characterized. Here, we observed the prevalence of dinoflagellates along a 4,600-km meridional transect extending across the central Pacific Ocean, where oligotrophic gyres meet equatorial upwelling waters rich in macronutrients yet low in dissolved iron.

Revealing ocean-scale biochemical structure with a deep-diving vertical profiling autonomous vehicle.

Vast and diverse microbial communities exist within the ocean. To better understand the global influence of these microorganisms on Earth's climate, we developed a robot capable of sampling dissolved and particulate seawater biochemistry across ocean basins while still capturing the fine-scale biogeochemical processes therein. Carbon and other nutrients are acquired and released by marine microorganisms as they build and break down organic matter.

Author Correction: Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection.

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. The effects of influenza infection on the upper respiratory tract (URT) microbiome are largely unknown. Here, we report a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets.

Applications of weighted association networks applied to compositional data in biology.

Next-generation sequencing technologies have generated, and continue to produce, an increasingly large corpus of biological data. The data generated are inherently compositional as they convey only relative information dependent upon the capacity of the instrument, experimental design and technical bias. There is considerable information to be gained through network analysis by studying the interactions between components within a system.

TRPV4 Antagonism Prevents Mechanically Induced Myotonia.

Objective: Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious and associated with side effects. Myotonia can be triggered by voluntary movement (electrically induced myotonia) or percussion (mechanically induced myotonia).

Universal loop assembly: open, efficient and cross-kingdom DNA fabrication.

Standardized type IIS DNA assembly methods are becoming essential for biological engineering and research. These methods are becoming widespread and more accessible due to the proposition of a 'common syntax' that enables higher interoperability between DNA libraries. Currently, Golden Gate (GG)-based assembly systems, originally implemented in host-specific vectors, are being made compatible with multiple organisms.

Genomic adaptations in information processing underpin trophic strategy in a whole-ecosystem nutrient enrichment experiment.

Several universal genomic traits affect trade-offs in the capacity, cost, and efficiency of the biochemical information processing that underpins metabolism and reproduction. We analyzed the role of these traits in mediating the responses of a planktonic microbial community to nutrient enrichment in an oligotrophic, phosphorus-deficient pond in Cuatro Ciénegas, Mexico. This is one of the first whole-ecosystem experiments to involve replicated metagenomic assessment.