Exercise Therapy Rescues Skeletal Muscle Dysfunction and Exercise Intolerance in Cardiometabolic HFpEF.

Exercise intolerance, a hallmark of heart failure with preserved ejection fraction (HFpEF) exacerbated by obesity, involves unclear mechanisms related to skeletal muscle metabolism. In a "2-hit" model of HFpEF, we investigated the ability of exercise therapy (voluntary wheel running) to reverse skeletal muscle dysfunction and exercise intolerance. Using state-of-the-art metabolic cages and a multiomic approach, we demonstrate exercise can rescue dysfunctional skeletal muscle lipid and branched-chain amino acid oxidation and restore exercise capacity in mice with cardiometabolic HFpEF.

Pancreatic expression of CPT1A is essential for whole body glucose homeostasis by supporting glucose-stimulated insulin secretion.

Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1a) using C57BL/6J mice.

Evaluator Disagreement about the Association between Psychopathy Checklist-Revised Scores and Risk for Future Sexual Violence.

It is common for forensic evaluators to use assessment instruments in risk assessment evaluations. This study examines whether different evaluators use instrument results the same way when coming to conclusions about risk for sexual recidivism in Sexually Violent Predator (SVP) evaluations. Three evaluators who each used both the Static-99R and Psychopathy Checklist-Revised in more than 60 SVP evaluations (Total  = 338) provided data for the study.

Shortened sleep duration impairs adipose tissue adrenergic stimulation of lipolysis in postmenopausal women.

Objective: The objective of this study was to examine the changes in adipose tissue lipolytic capacity and insulin signaling in response to shortened sleep duration (SSD) in postmenopausal women.

Methods: Adipose tissue from a randomized crossover study of nine healthy postmenopausal women (mean [SD], age: 59 [4] years; BMI: 28.0 [2.

Powering down the mitochondrial LonP1 protease: a novel strategy for anticancer therapeutics.

Introduction: Mitochondrial LonP1 is an ATP-powered protease that also functions as an ATP-dependent chaperone. LonP1 plays a pivotal role in regulating mitochondrial proteostasis, metabolism and cell stress responses. Cancer cells exploit the functions of LonP1 to combat oncogenic stressors such as hypoxia, proteotoxicity, and oxidative stress, and to reprogram energy metabolism enabling cancer cell proliferation, chemoresistance, and metastasis.

Pedestrian- and bicyclist-involved crashes: Associations with spatial factors, pedestrian infrastructure, and equity impacts.

Introduction: We analyze and compare the factors that influence the fatality of pedestrian and bicyclist involved crashes in New Jersey using available police-reported crash data between 2016 and 2020. Under three percent of crashes involve non-motorists statewide, but these account for about one third of all traffic fatalities in the state.

Methods: Our analysis is broken down into five parts: we (1) analyze the relationship between minority and low-income communities and non-motorist involved crashes; (2) identify spatial differences between non-motorist involved crashes and non-motorist involved fatal crashes; (3) compare the factors affecting fatal pedestrian crashes in New Jersey and in four counties in southern New Jersey for which we have data on pedestrian infrastructure; (4) compare the factors affecting fatal pedestrian crashes and fatal cyclist crashes in New Jersey; and, (5) discuss priority areas for improving safety.

Lysosomal glucose sensing and glycophagy in metabolism.

Lysosomes are cellular organelles that function to catabolize both extra- and intracellular cargo, act as a platform for nutrient sensing, and represent a core signaling node integrating bioenergetic cues to changes in cellular metabolism. Although lysosomal amino acid and lipid sensing in metabolism has been well characterized, lysosomal glucose sensing and the role of lysosomes in glucose metabolism is unrefined. This review will highlight the role of the lysosome in glucose metabolism with a focus on lysosomal glucose and glycogen sensing, glycophagy, and lysosomal glucose transport and how these processes impact autophagy and energy metabolism.

NOD mice have distinct metabolic and immunologic profiles when compared with genetically similar MHC-matched ICR mice.

Nonobese diabetic (NOD) mice are the most commonly used rodent model to study mechanisms relevant to the autoimmunity and immunology of type 1 diabetes. Although many different strains of mice have been used as controls for studies comparing nondiabetic lines to the NOD strain, we hypothesized that the parental strain that gave rise to the NOD line might be one of the best options. Therefore, we compared female ICR and NOD mice, which are matched at key major histocompatibility complex (MHC) loci, to understand their metabolic and immunologic similarities and differences.

Child Neurology: Progressive Cerebellar Atrophy and Retinal Dystrophy: Clues to an Ultrarare -Related Neurometabolic Diagnosis.

Pathogenic biallelic variants in , which encodes the enzyme mitochondrial aconitase, are associated with the very rare diagnosis of -related infantile cerebellar retinal degeneration (OMIM 614559). We describe the diagnostic odyssey of a 4-year-old female patient with profound global developmental delays, microcephaly, severe hypotonia, retinal dystrophy, seizures, and progressive cerebellar atrophy. Whole-exome sequencing revealed 2 variants in ; c.

Pharmacological inhibition of lipolysis prevents adverse metabolic outcomes during glucocorticoid administration.

Objective: Glucocorticoids are one of the most commonly prescribed classes of anti-inflammatory drugs; however, chronic treatment promotes iatrogenic (drug-induced) diabetes. As part of their physiological role, glucocorticoids stimulate lipolysis to spare glucose. We hypothesized that persistent stimulation of lipolysis during glucocorticoid therapy plays a causative role in the development of iatrogenic diabetes.

Effect of sleep restriction on insulin sensitivity and energy metabolism in postmenopausal women: A randomized crossover trial.

Objective: The aim of this study was to investigate the effect of sleep restriction (SR) on insulin sensitivity and energy metabolism in postmenopausal women.

Methods: In a randomized crossover trial, 14 women underwent four nights of habitual sleep (HS, 100% normal sleep) and SR (60% of HS) while following a eucaloric diet. Outcomes included the following: (1) insulin sensitivity by hyperinsulinemic-euglycemic clamp, defined as the glucose infusion rate (GIR); (2) resting metabolism and substrate oxidation by indirect calorimetry; and (3) glucose, insulin, and C-peptide concentrations following a standard meal test.

Rats lacking Ucp1 present a novel translational tool for the investigation of thermogenic adaptation during cold challenge.

Aim: Valuable studies have tested the role of UCP1 on body temperature maintenance in mice, and we sought to knockout Ucp1 in rats (Ucp1 ) to provide insight into thermogenic mechanisms in larger mammals.

Methods: We used CRISPR/Cas9 technology to create Ucp1 rats. Body weight and adiposity were measured, and rats were subjected to indirect calorimetry.

Intact mitochondrial substrate efflux is essential for prevention of tubular injury in a sex-dependent manner.

The importance of healthy mitochondrial function is implicated in the prevention of chronic kidney disease (CKD) and diabetic kidney disease (DKD). Sex differences also play important roles in DKD. Our previous studies revealed that mitochondrial substrate overload (modeled by homozygous deletion of carnitine acetyl-transferase [CrAT]) in proximal tubules causes renal injury.

Bikeshare and subway ridership changes during the COVID-19 pandemic in New York City.

The COVID-19 pandemic has been unprecedented in its scale and speed, impacting the entire world, and having an impact on metropolitan transportation systems. New York City (NYC) was especially hard hit in March and April 2020. A mandatory stay-at-home order was instituted, with all but essential businesses ordered closed.

Dynamin-related protein 1 regulates substrate oxidation in skeletal muscle by stabilizing cellular and mitochondrial calcium dynamics.

Mitochondria undergo continuous cycles of fission and fusion to promote inheritance, regulate quality control, and mitigate organelle stress. More recently, this process of mitochondrial dynamics has been demonstrated to be highly sensitive to nutrient supply, ultimately conferring bioenergetic plasticity to the organelle. However, whether regulators of mitochondrial dynamics play a causative role in nutrient regulation remains unclear.

Rickettsia conorii survival in THP-1 macrophages involves host lipid droplet alterations and active rickettsial protein production.

Rickettsia conorii is a Gram-negative, cytosolic intracellular bacterium that has classically been investigated in terms of endothelial cell infection. However, R. conorii and other human pathogenic Rickettsia species have evolved mechanisms to grow in various cell types, including macrophages, during mammalian infection.

Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice.

The central integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previously, increased acute food intake following the chemical reduction of hepatic fatty acid oxidation and ATP levels was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism.

Female Mice Are Protected from Metabolic Decline Associated with Lack of Skeletal Muscle HuR.

Male mice lacking HuR in skeletal muscle (HuR) have been shown to have decreased gastrocnemius lipid oxidation and increased adiposity and insulin resistance. The same consequences have not been documented in female HuR mice. Here we examine this sexually dimorphic phenotype.

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle.

Ketogenic diets (KDs) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr).

Mobility and the effective reproduction rate of COVID-19.

Objectives: Due to the infectiousness of COVID-19, the mobility of individuals has sharply decreased, both in response to government policy and self-protection. This analysis seeks to understand how mobility reductions reduce the spread of the coronavirus (SAR-CoV-2), using readily available data sources.

Methods: Mobility data from Google is correlated with estimates of the effective reproduction rate, which is a measure of viral infectiousness (Google, 2020).

The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance.

Glucocorticoids are clinically essential drugs used routinely to control inflammation. However, a host of metabolic side effects manifests upon usage beyond a few days. In the present study, we tested the hypothesis that seven-in-absentia mammalian homolog-2 (SIAH2), a ubiquitin ligase that regulates adipogenesis, is important for controlling adipocyte size, inflammation, and the ability of adipose tissue to expand in response to a glucocorticoid challenge.

Impact of polymer type, ASD loading and polymer-drug ratio on ASD tablet disintegration and drug release.

Amorphous solid dispersion (ASD) has become an attractive strategy to enhance solubility and bioavailability of poorly water-soluble drugs. To facilitate oral administration, ASDs are commonly incorporated into tablets. Disintegration and drug release from ASD tablets are thus critical for achieving the inherent solubility advantage of amorphous drugs.

Difference in Housing Temperature-Induced Energy Expenditure Elicits Sex-Specific Diet-Induced Metabolic Adaptations in Mice.

Objective: The aim of this study was to test whether increased energy expenditure (EE), independent of physical activity, reduces acute diet-induced weight gain through tighter coupling of energy intake to energy demand and enhanced metabolic adaptations.

Methods: Indirect calorimetry and quantitative magnetic resonance imaging were used to assess energy metabolism and body composition during 7-day high-fat/high-sucrose (HFHS) feeding in male and female mice housed at divergent temperatures (20°C vs. 30°C).

Spatial associations of dockless shared e-scooter usage.

In this study, we explore the usage of e-scooter sharing services in Austin, Texas over about a six-month period. The study is based on trip records of all the shared e-scooter operators in Austin and includes trip start and end locations. We use both analysis of trip patterns and spatial regression techniques to examine how the built environment, land use, and demographics affect e-scooter trip generation.