Heat induces multiomic and phenotypic stress propagation in zebrafish embryos.

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecular signatures of this process, by integrating multiomic and phenotypic data.

Observation of exceptional points in helically structured thin films.

Exceptional points (EPs) in the polarization space were observed in reflection on helically structured thin films. These films have form anisotropy at the nanoscale introduced through dynamic control of crystalline growth geometry by changing the orientation of the substrate with respect to the impinging vapor. They are simpler alternatives to metasurfaces, because they can be produced at low cost using conventional thin-film deposition techniques.

Lack of impact of angiotensin-converting enzyme gene polymorphism and salt intake on insulin resistance and limb blood flow.

Objectives: We postulated the mechanism for the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and insulin sensitivity might relate to changes in blood flow regulation. We studied the association of this polymorphism with insulin action, and insulin-mediated changes in limb blood flow (LBF), under conditions of high and low salt intake. We also studied effects of genotype and salt loading on renin-angiotensin-aldosterone system (RAAS) activity.

Expression profiling of purified normal human luminal and myoepithelial breast cells: identification of novel prognostic markers for breast cancer.

The normal duct-lobular system of the breast is lined by two epithelial cell types, inner luminal secretory cells and outer contractile myoepithelial cells. We have generated comprehensive expression profiles of the two normal cell types, using immunomagnetic cell separation and gene expression microarray analysis. The cell-type specificity was confirmed at the protein level by immunohistochemistry in normal breast tissue.

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells.

To investigate changes in gene expression associated with ERBB2, expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs. A total of 61 significantly up- or downregulated (2.0-fold) genes were identified and further validated by RT-PCR analysis as well as microarray comparisons with a spontaneously ERBB2- overexpressing breast cancer cell line and ERBB2-positive primary breast tumors.

Investigation of potential mechanisms regulating protein expression of hepatic pyruvate dehydrogenase kinase isoforms 2 and 4 by fatty acids and thyroid hormone.

Liver contains two pyruvate dehydrogenase kinases (PDKs), namely PDK2 and PDK4, which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Starvation increases hepatic PDK2 and PDK4 protein expression, the latter occurring, in part, via a mechanism involving peroxisome proliferator-activated receptor-alpha (PPARalpha). High-fat feeding and hyperthyroidism, which increase circulating lipid supply, enhance hepatic PDK2 protein expression, but these increases are insufficient to account for observed increases in hepatic PDK activity.

Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor alpha (PPARalpha).

In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC. Signalling via peroxisome-proliferator-activated receptor alpha (PPARalpha) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression. Activation of PPARalpha in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal.

Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.

Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4. The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism. PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643.

Peroxisome-proliferator-activated receptor-alpha (PPARalpha) deficiency leads to dysregulation of hepatic lipid and carbohydrate metabolism by fatty acids and insulin.

The aim of the present study was to determine whether peroxisome-proliferator-activated receptor-alpha (PPARalpha) deficiency disrupts the normal regulation of triacylglycerol (TAG) accumulation, hepatic lipogenesis and glycogenesis by fatty acids and insulin using PPARalpha-null mice. In wild-type mice, hepatic TAG concentrations increased (P<0.01) with fasting (24 h), with substantial reversal after refeeding (6 h).

Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha: implications for glucose-stimulated insulin secretion.

The pyruvate dehydrogenase complex (PDC) has a pivotal role in islet metabolism. The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of PDC. Starvation increases islet PDK activity (Am J Physiol Endocrinol Metab 270:E988-E994, 1996).

Role of peroxisome proliferator-activated receptor-alpha in the mechanism underlying changes in renal pyruvate dehydrogenase kinase isoform 4 protein expression in starvation and after refeeding.

The pyruvate dehydrogenase complex (PDC) occupies a strategic role in renal intermediary metabolism, via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway. Inactivation of PDC via activation of pyruvate dehydrogenase kinases (PDKs), which catalyze PDC phosphorylation, occurs secondary to increased fatty acid oxidation (FAO). In kidney, inactivation of PDC after prolonged starvation is mediated by up-regulation of the protein expression of two PDK isoforms, PDK2 and PDK4.

Fuel-sensing mechanisms integrating lipid and carbohydrate utilization.

Fuel metabolism is highly regulated to ensure adequate energy for cellular function. The contribution of the major metabolic fuels--glucose, lactate and fatty acids (FAs)--often reflects their circulating levels. In addition, regulatory cross-talk and fuel-induced hormone secretion ensures appropriate and co-ordinate fuel utilization.

The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects.

Aims/hypothesis: Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent) mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial dysfunction and of acute phase activation, using both sulphonylureas and insulin.

Methods: In a randomised cross-over study we gave sulphonylureas or insulin each for a period of 16 weeks to 22 poorly controlled Type II diabetic subjects who were being treated by diet.

beta-Adrenergic regulation of proinflammatory cytokines in humans.

Objectives: To investigate the effects of beta-adrenergic stimulation on IL-6 secretion in humans, and to determine the potential contribution to this response of adipocytes and peripheral blood cells (PBC).

Design: Experimental study in 8 human volunteers, and in vitro studies on murine adipocyte cell-line, 3T3.L1 and 3T3.

Physiological relationships of uncoupling protein-2 gene expression in human adipose tissue in vivo.

The physiological significance of changes in uncoupling protein-2 (UCP-2) gene expression is controversial. In this study we investigated the biochemical and functional correlates of UCP-2 gene expression in sc abdominal adipose tissue in humans in vivo. UCP-2 messenger ribonucleic acid expression was quantified by nuclease protection in adipose tissue from lean and obese humans in both the fasting and postprandial states.

Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo.

To investigate in vivo adipose tissue production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their soluble receptors: TNF receptor type I (sTNFR-I), TNF receptor type II (sTNFR-II), and IL-6 receptor (sIL-6R), we determined arteriovenous differences in their levels across abdominal subcutaneous adipose tissue in obese subjects. Subjects had a median (interquartile range) age of 44.5 (27-51.

Lack of evidence for secretion of plasminogen activator inhibitor-1 by human subcutaneous adipose tissue in vivo.

Circulating plasminogen activator inhibitor-1 (PAI-1) levels are elevated in patients with coronary heart disease and may play an important role in atherothrombosis. Levels are also raised in obese, hypertriglyceridaemic, or insulin-resistant subjects, which predispose people to coronary heart disease. It is unclear, though, which organ is responsible for PAI-1 secretion, either in health or disease.

Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study.

Objective: To investigate the relation between decreased maternal food intake and risk factors for coronary heart disease in adult life.

Design: Cross sectional study.

Subjects: 169 subjects exposed to malnutrition in utero (intrauterine group) during the siege of Leningrad (now St Petersburg) in 1941-4; 192 subjects born in Leningrad just before rationing began, before the siege (infant group); and 188 subjects born concurrently with the first two groups but outside the area of the siege (unexposed group).

Control of acyl-CoA carboxylase activity in mycobacteria.

Acyl-CoA carboxylase activity in four pathogenic mycobacteria and Mycobacterium smegmatis was shown with both acetyl-CoA and propionyl-CoA substrates. Only very low activity was detected in mycobacteria grown in host tissues or on egg-based media rich in lecithin and avidin. This appeared to be a result of severe depression of activity, as strains which could be grown both in host tissue and egg-based media, and in the relatively simple Dubos or Sauton's media showed 8 to 120-fold higher activity in the simpler media.

Fatty acid oxidation and the beta-oxidation complex in Mycobacterium leprae and two axenically cultivable mycobacteria that are pathogens.

Intact, non-growing Mycobacterium leprae, M. avium and M. microti oxidized a wide range of 1-14C-labelled fatty acids (C8 to C24) to 14CO2.

Enzymes for biosynthesis de novo and elongation of fatty acids in mycobacteria grown in host cells: is Mycobacterium leprae competent in fatty acid biosynthesis?

Fatty acid synthetase activity in extracts of Mycobacterium leprae was equivalent to 1.7 pmol malonyl-CoA incorporated into fatty acid min-1 (mg protein)-1. This activity--if representative of living M.