Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity.

Insulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous, however, this association remains controversial. The aim of this study was to perform an in-depth multifactorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active, = 9), individuals with obesity (Obese, = 9), and individuals with obesity, insulin resistance, and type 2 diabetes (T2D, = 22). Mitochondrial capacity was assessed by ex vivo mitochondrial respiration with fatty-acid and glycolytic-supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity).

The proteome and phosphoproteome of circulating extracellular vesicle-enriched preparations are associated with characteristic clinical features in type 1 diabetes.

Introduction: There are no validated clinical or laboratory biomarkers to identify and differentiate endotypes of type 1 diabetes (T1D) or the risk of progression to chronic complications. Extracellular vesicles (EVs) have been studied as biomarkers in several different disease states but have not been well studied in T1D.

Methods: As the initial step towards circulating biomarker identification in T1D, this pilot study aimed to provide an initial characterization of the proteomic and phosphoproteomic landscape of circulating EV-enriched preparations in participants with established T1D (N=10) and healthy normal volunteers (Controls) (N=7) (NCT03379792) carefully matched by age, race/ethnicity, sex, and BMI.

A single nuclei atlas of aging human abdominal subcutaneous white adipose tissue.

White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq to characterize the cellular landscape of human subcutaneous WAT in a prospective cohort of 10 Younger (≤ 30 years) and 10 Older individuals (≥ 65 years) balanced for sex and body mass index (BMI).

Isolation of nuclei from frozen human subcutaneous adipose tissue for full-length single-nuclei transcriptional profiling.

Automated single-cell dispensing is incompatible with white adipose tissue (WAT) due to lipid-laden adipocytes. Single-nuclei RNA-Seq permits transcriptional profiling of all cells from WAT. Human WAT faces unique technical challenges in isolating nuclei compared to rodent tissue due to greater extra-cellular matrix content and larger lipid droplets.

Single cell full-length transcriptome of human subcutaneous adipose tissue reveals unique and heterogeneous cell populations.

White adipose tissue (WAT) is a complex mixture of adipocytes and non-adipogenic cells. Characterizing the cellular composition of WAT is critical for identifying where potential alterations occur that impact metabolism. Most single-cell (sc) RNA-Seq studies focused on the stromal vascular fraction (SVF) which does not contain adipocytes and have used technology that has a 3' or 5' bias.

Pancreatic Ductal Adenocarcinoma (PDAC) circulating tumor cells influence myeloid cell differentiation to support their survival and immunoresistance in portal vein circulation.

The portal venous circulation provides a conduit for pancreatic ductal adenocarcinoma (PDAC) tumor cells to the liver parenchyma sinusoids, a frequent site of metastasis. Turbulent flow in the portal circulation promotes retention of PDAC shed circulating tumor cells (CTC) and myeloid-derived immunosuppressor cells (MDSC). Excessive colony stimulating factor-1 receptor (CSF1R) signaling can induce myeloid differentiation to MDSC and transformation of MDSC to myeloid-derived fibroblasts (M-FB).

Skeletal muscle transcriptome response to a bout of endurance exercise in physically active and sedentary older adults.

Age-related declines in cardiorespiratory fitness and physical function are mitigated by regular endurance exercise in older adults. This may be due, in part, to changes in the transcriptional program of skeletal muscle following repeated bouts of exercise. However, the impact of chronic exercise training on the transcriptional response to an acute bout of endurance exercise has not been clearly determined.

A Metabolomic Signature of Glucagon Action in Healthy Individuals With Overweight/Obesity.

Context: Glucagon is produced and released from the pancreatic alpha-cell to regulate glucose levels during periods of fasting. The main target for glucagon action is the liver, where it activates gluconeogenesis and glycogen breakdown; however, glucagon is postulated to have other roles within the body.

Objective: We sought to identify the circulating metabolites that would serve as markers of glucagon action in humans.

An improvement in skeletal muscle mitochondrial capacity with short-term aerobic training is associated with changes in Tribbles 1 expression.

Exercise training and physical activity are known to be associated with high mitochondrial content and oxidative capacity in skeletal muscle. Metabolic diseases including obesity and insulin resistance are associated with low mitochondrial capacity in skeletal muscle. Certain transcriptional factors such as PGC-1α are known to mediate the exercise response; however, the precise molecular mechanisms involved in the adaptation to exercise are not completely understood.

Skeletal Muscle Energetics and Mitochondrial Function Are Impaired Following 10 Days of Bed Rest in Older Adults.

Background: Older adults exposed to periods of inactivity during hospitalization, illness, or injury lose muscle mass and strength. This, in turn, predisposes poor recovery of physical function upon reambulation and represents a significant health risk for older adults. Bed rest (BR) results in altered skeletal muscle fuel metabolism and loss of oxidative capacity that have recently been linked to the muscle atrophy program.

Loss of mitochondrial energetics is associated with poor recovery of muscle function but not mass following disuse atrophy.

Skeletal muscle atrophy is a clinically important outcome of disuse because of injury, immobilization, or bed rest. Disuse atrophy is accompanied by mitochondrial dysfunction, which likely contributes to activation of the muscle atrophy program. However, the linkage of muscle mass and mitochondrial energetics during disuse atrophy and its recovery is incompletely understood.

Developmental and transcriptional responses of maize to drought stress under field conditions.

Drought is a common abiotic stress which significantly limits global crop productivity. Maize is an important staple crop and its yield is determined by successful development of the female inflorescence, the ear. We investigated drought stress responses across several developmental stages of the maize B73 inbred line under field conditions.

tassel-less1 encodes a boron channel protein required for inflorescence development in maize.

tassel-less1 (tls1) is a classical maize (Zea mays) inflorescence mutant. Homozygous mutant plants have no tassels or very small tassels, and ear development is also impaired. Using a positional cloning approach, ZmNIP3;1 (a NOD26-like intrinsic protein) was identified as the candidate gene for tls1.

Gnom(Cmp): a quantitative approach for comparative analysis of closely related genomes of bacterial pathogens.

Comparative genome analysis is a powerful approach to understanding the biology of infectious bacterial pathogens. In this study, a quantitative approach, referred to as Gnom(Cmp), was developed to study the microevolution of bacterial pathogens. Although much more time-consuming than existing tools, this procedure provides a much higher resolution.

New implications on genomic adaptation derived from the Helicobacter pylori genome comparison.

Background: Helicobacter pylori has a reduced genome and lives in a tough environment for long-term persistence. It evolved with its particular characteristics for biological adaptation. Because several H.

GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing.

Background: Microevolution is the study of short-term changes of alleles within a population and their effects on the phenotype of organisms. The result of the below-species-level evolution is heterogeneity, where populations consist of subpopulations with a large number of structural variations. Heterogeneity analysis is thus essential to our understanding of how selective and neutral forces shape bacterial populations over a short period of time.

An exon-based comparative variant analysis pipeline to study the scale and role of frameshift and nonsense mutation in the human-chimpanzee divergence.

Chimpanzees and humans are closely related but differ in many deadly human diseases and other characteristics in physiology, anatomy, and pathology. In spite of decades of extensive research, crucial questions about the molecular mechanisms behind the differences are yet to be understood. Here I report ExonVar, a novel computational pipeline for Exon-based human-chimpanzee comparative Variant analysis.

Genome sequence of Brucella abortus vaccine strain S19 compared to virulent strains yields candidate virulence genes.

The Brucella abortus strain S19, a spontaneously attenuated strain, has been used as a vaccine strain in vaccination of cattle against brucellosis for six decades. Despite many studies, the physiological and molecular mechanisms causing the attenuation are not known. We have applied pyrosequencing technology together with conventional sequencing to rapidly and comprehensively determine the complete genome sequence of the attenuated Brucella abortus vaccine strain S19.

An SVM-based algorithm for identification of photosynthesis-specific genome features.

This paper presents a novel algorithm for identification and functional characterization of "key" genome features responsible for a particular biochemical process of interest. The central idea is that individual genome features are identified as "key" features if the discrimination accuracy between two classes of genomes with respect to a given biochemical process is sufficiently affected by the inclusion or exclusion of these features. In this paper, genome features are defined by high-resolution gene functions.

An evolution-based analysis scheme to identify CO2/O2 specificity-determining factors for ribulose 1,5-bisphosphate carboxylase/oxygenase.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo) catalyzes a rate-limiting step in photosynthetic carbon assimilation (reacting with CO2) and its competitive photo-respiratory carbon oxidation (reacting with O2). RuBisCo enzyme with an enhanced CO2/O2 specificity would boost the ability to make great progress in agricultural production and environmental management. RuBisCos in marine non-green algae, resulting from an earlier endo-symbiotic event, diverge greatly from those in green plants and cyanobacteria and, further, have the highest CO2/O2 specificity whereas RuBisCos in cyanobacteria have the lowest.

In silico discovery of enzyme-substrate specificity-determining residue clusters.

The binding between an enzyme and its substrate is highly specific, despite the fact that many different enzymes show significant sequence and structure similarity. There must be, then, substrate specificity-determining residues that enable different enzymes to recognize their unique substrates. We reason that a coordinated, not independent, action of both conserved and non-conserved residues determine enzymatic activity and specificity.

Ruleminer: a knowledge system for supporting high-throughput protein function annotations.

In this paper, we present RuleMiner, a knowledge system to facilitate a seamless integration of multi-sequence analysis tools and define profile-based rules for supporting high-throughput protein function annotations. This system consists of three essential components, Protein Function Groups (PFGs), PFG profiles and rules. The PFGs, established from an integrated analysis of current knowledge of protein functions from Swiss-Prot database and protein family-based sequence classifications, cover all possible cellular functions available in the database.