Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

Shiga toxin-producing Escherichia coli in beef heifers grazing an irrigated pasture

Shiga toxin-producing Escherichia coli (STEC) produce toxins that have been associated with several human illnesses. E. coli O157:H7 is the most well-studied STEC and was first associated with consumption of improperly cooked ground beef in 1982. E. coli O157:H7 is not the only foodborne STEC because other STEC serotypes are also associated with human illnesses. The objective of this study was to assess prevalence of STEC in 23 yearling beef (Angus) heifers grazing an irrigated grass pasture in spring (April), summer (July), fall (October), and winter (December) of 1999. A total of 86 fecal samples were rectally collected and were subjected to microbiological testing for the presence of STEC. Nine E. coli isolates from five heifers (one in spring and fall and three in winter) were toxic to Vero cells. Of these isolates, four were E. coli O157:H7, two belonged to the serogroup O6, one O39:NM, one O113:H-, and the final isolate was untypable. The STEC prevalence rate in our herd ranged from 4% (spring) to 15% (winter). Based on detecting both O157:H7 and non-O157:H7 STEC in our heifers, it is clear that screening fecal samples should not be limited to E. coli O157:H7. Identification of STEC-positive cattle prior to slaughter should help in reducing the risk of beef contamination with such foodborne pathogens if pre- and/or postharvest control measures are applied to such animals.     

Effect of the drying process on the nutritive value of milk. Part 1. Biochemical composition

Five different brands of instant dry whole milk that are most commonly used, and freeze dried milk were analyzed for nitrogen, fat, ash and 4 inorganic constituents and compared with human milk. The composition of the milks differed considerably. The protein content varied widely, ranging from 11.6 to 24.5%. Fat content did not differ widely, ranging from 24.9 to 29.5%. Freeze dried milk had the highest fat content (42.6%). Three out of the five brands of dry milk studied were spray dried and the remaining two were roller dried. All milks tested contained considerably more sodium, potassium, calcium and phosphorus solid than human milk, some of them the four fold amount of calcium and phosphorus.     

A 2D numerical simulation of sub-cooled flow boiling at low-pressure and low-flow rates

The main purpose of this study is to apply a two-fluid mathematical model to numerical simulation of two-phase flow at low-pressure condition. Although models of sub-cooled boiling flow at one-dimension and high-pressure have been studied extensively, there are few equivalent studies for numerical simulation at two-dimension and low-pressure (1-2 bar) conditions. Recent literature studies on sub-cooled boiling flow at low-pressure have shown that empirical models developed for high-pressure situations are not valid at low-pressures. Since the mathematical model used in this study is accomplished at low-pressure, the transport equations for the variables of each phase are substituted in low-pressure. The governing equations of two-phase flow with an allowance to inter-phase transfer of mass, momentum and heat, are solved using a two-fluid; non-equilibrium model. The finite volume discretization scheme is used to create a linearized system of equations that are solved by SIMPLE staggered grid solution technique for a rectangular channel. Improvement of the void fraction prediction of our model for the case of low-pressure sub-cooled flow boiling conditions was achieved. It is found that the heat transfer due to evaporation and surface quenching is higher than that by convection. Good agreement is achieved with the predicted results against the experimental data’s available in the literatures for a number of test cases.     

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic Technology^TM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (−46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

Improving the direct methanol fuel cell performance with poly(vinyl alcohol)/titanium dioxide nanocomposites as a novel electrolyte additive

The present investigation deals with the fabrication of new poly(vinyl alcohol)/titanium dioxide (PVA/TiO₂) nanocomposites (NCs) with different titanium dioxide (TiO₂) loading by using ultrasound irradiation. For the improvement of nanoparticles (NPs) dispersion and increasing possible interactions between NPs and PVA, the surface of TiO₂ NPs was modified by γ-aminopropyltriethoxy silane. The as-prepared NCs were characterized by spectroscopic, thermogravimetric analysis and electron microscopy methods. The results demonstrate that NPs dispersed homogeneously within the PVA matrix on nanoscale, which could be assigned to the hydrogen and covalent bonds formed between PVA and NPs. The results indicated that heat stability of NCs was improved in the presence of modified TiO₂ NPs. The mechanisms of surface modification and a possible mechanism of ultrasonic induced interaction between polymer and NPs have been analyzed.     

Classification of image distortion based on the generalized Benford’s law

Multimedia Tools and Applications - Distortion classification is an important step in blind image quality assessment. In this paper, a new image distortion classification algorithm is presented....