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.

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

Background: Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control.

Methods: Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis.

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.

The RNA binding protein HuR influences skeletal muscle metabolic flexibility in rodents and humans.

Background: Metabolic flexibility can be assessed by changes in respiratory exchange ratio (RER) following feeding. Though metabolic flexibility (difference in RER between fasted and fed state) is often impaired in individuals with obesity or type 2 diabetes, the cellular processes contributing to this impairment are unclear.

Materials And Methods: From several clinical studies we identified the 16 most and 14 least metabolically flexible male and female subjects out of >100 participants based on differences between 24-hour and sleep RER measured in a whole-room indirect calorimeter.

Histopathology of Bordetella pertussis in the Baboon Model.

Pertussis is a severe respiratory disease caused by The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases.

Intraoperative Endotracheal Cuff Pressure Study: How Education and Availability of Manometers Help Guide Safer Pressures.

Introduction: Endotracheal intubation is a medical procedure that is often indicated in both the perioperative and critical care environments. Cuffed endotracheal tubes (ETT) allow for safer and more efficient delivery of positive pressure ventilation, as well as create a barrier to reduce the risk of micro-aspiration and anesthetic pollution in the operating room environment. Over-inflation of the endotracheal cuff can lead to serious and harmful sequelae.

A low fat diet ameliorates pathology but retains beneficial effects associated with CPT1b knockout in skeletal muscle.

Inhibiting fatty acid oxidation is one approach to lowering glucose levels in diabetes. Skeletal muscle specific Carnitine Palmitoyltransferase 1b knockout mice (Cpt1bm-/-) comprise a model of impaired fat oxidation; and have decreased fat mass and enhanced glucose disposal and muscle oxidative capacity compared to controls. However, unfavorable effects occur relative to controls when Cpt1bm-/- mice are fed a 25% fat diet, including decreased activity and fat free mass and increased intramuscular lipid and serum myoglobin.

Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK.

The two-component response regulator RisA, encoded by open reading frame BP3554 in the Tohama I genomic sequence, is a known activator of genes, a set of genes whose expression is increased under the same environmental conditions (known as modulation) that result in repression of the virulence regulon. Here we demonstrate that RisA is phosphorylated and that RisA phosphorylation is required for activation of genes. An adjacent histidine kinase gene, , is truncated by frameshift mutation in but not in or Neither deletion of ' or nor phenotypic modulation with MgSO affected levels of phosphorylated RisA (RisA∼P) in However, RisA phosphorylation did require the histidine kinase encoded by BP3223, here named RisK (cognate histidine kinase of RisA).

Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research.

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose tissue was a contributing factor for obesity in rats. We therefore closely examined the expression level of in adipose tissue from mice, rats, and humans.

Mitochondrial fat oxidation is essential for lipid-induced inflammation in skeletal muscle in mice.

Inflammation, lipotoxicity and mitochondrial dysfunction have been implicated in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes. However, how these factors are intertwined in the development of obesity/insulin resistance remains unclear. Here, we examine the role of mitochondrial fat oxidation on lipid-induced inflammation in skeletal muscle.

The harvestman genus Taracus Simon 1879, and the new genus Oskoron (Opiliones: Ischyropsalidoidea: Taracidae).

The ischyropsalidoid genus Taracus Simon 1879 is reviewed and all previously named species are redescribed. Taracus nigripes Goodnight & Goodnight, 1943 is synonymized with T. packardi Simon 1879, and T.

Use of a Toxin Neutralization Assay To Characterize the Serologic Response to Adenylate Cyclase Toxin after Infection with Bordetella pertussis.

Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis, and antibodies to ACT protect against B. pertussis infection in mice. The toxin is therefore a strong candidate antigen for addition to future acellular pertussis vaccines.

Lifestyle modification intervention improves glycemic control in Mongolian adults who are overweight or obese with newly diagnosed type 2 diabetes.

Objective: To evaluate the effectiveness of a weight loss intervention in Mongolian adults with newly diagnosed type 2 diabetes mellitus and with BMIs ≥ 25.0 kg/m.

Methods: Eighty participants (33 men/47 women) aged 32-56 years old received education sessions to improve nutritional habits and increase physical activity.

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle.

Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet-induced obesity.

Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis.

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge.

Pertussis vaccines and the challenge of inducing durable immunity.

Pertussis has re-emerged as an important public health concern. In the 1990s whole-cell pertussis vaccines were replaced with less reactogenic acellular vaccines consisting of purified pertussis components. However, recent data show that protection from acellular pertussis vaccines is not long-lasting.

Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism.

The correlations between intramyocellular lipid (IMCL), decreased fatty acid oxidation (FAO), and insulin resistance have led to the hypothesis that impaired FAO causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling. Using a skeletal muscle-specific carnitine palmitoyltransferase-1 KO model, we show that prolonged and severe mitochondrial FAO inhibition results in increased carbohydrate utilization, along with reduced physical activity; increased circulating nonesterified fatty acids; and increased IMCLs, diacylglycerols, and ceramides. Perhaps more importantly, inhibition of mitochondrial FAO also initiates a local, adaptive response in muscle that invokes mitochondrial biogenesis, compensatory peroxisomal fat oxidation, and amino acid catabolism.

Enhanced DNA binding affinity of RecA protein from Deinococcus radiodurans.

Deinococcus radiodurans (Dr) has a significantly more robust DNA repair response than Escherichia coli (Ec), which helps it survive extremely high doses of ionizing radiation and prolonged periods of desiccation. DrRecA protein plays an essential part in this DNA repair capability. In this study we directly compare the binding of DrRecA and EcRecA to the same set of short, defined single (ss) and double stranded (ds) DNA oligomers.

The baboon model of pertussis: effective use and lessons for pertussis vaccines.

The USA is experiencing a pertussis resurgence that resulted in a 60-year high of 48,000 cases in 2012. Our ability to counteract this resurgence is hampered by the fact that pertussis pathogenesis and immunity to pertussis infection are not well studied. Studies in humans are difficult due to the low frequency of pertussis in the population, the cyclical nature of incidence and the sporadic geographic distribution of cases.

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

Objectives: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.

Methods: Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up.

Maternal and neonatal vaccination protects newborn baboons from pertussis infection.

Background: The United States is experiencing a pertussis resurgence that resulted in a 60-year high of 48 000 cases in 2012. The majority of hospitalizations and deaths occur in infants too young to be vaccinated. Neonatal and maternal vaccination have been proposed to protect newborns until the first vaccination, currently recommended at 2 months of age.

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model.

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission.

Anthrax lethal toxin downregulates claudin-5 expression in human endothelial tight junctions.

Vascular leakage pathologies such as pleural effusion and hemorrhage are hallmarks of anthrax pathogenesis. We previously reported that anthrax lethal toxin (LT), the major virulence factor of anthrax, reduces barrier function in cultured primary human microvascular endothelial cells. Here, we show that LT-induced barrier dysfunction is accompanied by the reduced expression of the endothelial tight junction (TJ) protein claudin-5 but no change in the expression of other TJ components occludin, ZO-1, ZO-2, or the adherens junction (AJ) protein VE-cadherin.