Alterations of adiponectin gene expression and DNA methylation in adipose tissues and blood cells are associated with gestational diabetes and neonatal outcome

BACKGROUND: Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adipose tissue (VAT) as well as blood (cell) samples of GDM-affected (n = 25) vs. matched control (n = 30) mother-child dyads of the prospective "EaCH" cohort study, we addressed whether alterations of adiponectin plasma, mRNA, and DNA methylation levels are associated with GDM and offspring characteristics. RESULTS: Hypoadiponectinemia was present in women with GDM, even after adjustment for body mass index (BMI). This was accompanied by significantly decreased mRNA levels in both SAT and VAT (P < 0.05), independent of BMI. Maternal plasma adiponectin showed inverse relations with glucose and homeostatic model assessment of insulin resistance (both P < 0.01). In parallel to reduced mRNA expression in GDM, significant (P < 0.05) yet small alterations in locus-specific DNA methylation were observed in maternal fat (~ 2%) and blood cells (~ 1%). While newborn adiponectin levels were similar between groups, DNA methylation in GDM offspring was variously altered (~ 1-4%; P < 0.05). CONCLUSIONS: Reduced adiponectin seems to be a pathogenic co-factor in GDM, even independent of BMI, affecting materno-fetal metabolism. While altered maternal DNA methylation patterns appear rather marginally involved, functional, diagnostic, and/or predictive implications of cord blood DNA methylation should be further evaluated

Thermal Density Functional Theory in Context

This chapter introduces thermal density functional theory, starting from the ground-state theory and assuming a background in quantum mechanics and statistical mechanics. We review the foundations of density functional theory (DFT) by illustrating some of its key reformulations. The basics of DFT for thermal ensembles are explained in this context, as are tools useful for analysis and development of approximations. We close by discussing some key ideas relating thermal DFT and the ground state. This review emphasizes thermal DFT's strengths as a consistent and general framework.Comment: Submitted to Spring Verlag as chapter in "Computational Challenges in Warm Dense Matter", F. Graziani et al. ed

OmniDepth: Dense Depth Estimation for Indoors Spherical Panoramas.

Recent work on depth estimation up to now has only focused on projective images ignoring 360o content which is now increasingly and more easily produced. We show that monocular depth estimation models trained on traditional images produce sub-optimal results on omnidirectional images, showcasing the need for training directly on 360o datasets, which however, are hard to acquire. In this work, we circumvent the challenges associated with acquiring high quality 360o datasets with ground truth depth annotations, by re-using recently released large scale 3D datasets and re-purposing them to 360o via rendering. This dataset, which is considerably larger than similar projective datasets, is publicly offered to the community to enable future research in this direction. We use this dataset to learn in an end-to-end fashion the task of depth estimation from 360o images. We show promising results in our synthesized data as well as in unseen realistic images

Maternal Environmental Contribution to Adult Sensitivity and Resistance to Obesity in Long Evans Rats

The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity.On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored.During the suckling period, the pups' phenotype was almost completely determined by the strain of the mother. However, pups independently ingested food according to their genotype, regardless of their actual phenotype. At adulthood, cross fostered males of both strains and LETO females were affected in regard of their adiposity levels in the direction of the foster dam. On the other hand, OLETF females showed almost no alterations in adiposity but were affected by the strain of the dams in parameters related to the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and circulating levels of ALT, while LETO females presented a disrupted estrous cycle and increased cholesterol and triglycerides in the long term.The present study provides further support for the early postnatal environment playing a sex-divergent role in programming later life phenotype. In addition, it plays a more central role in determining the functioning of mechanisms involved in energy balance that may provide protection from or sensitivity to later life obesity and pathologies related to the metabolic syndrome

Uridine Metabolism in the Goldfish Retina During Optic Nerve Regeneration: Whole Retina Studies

Accumulation of radioactivity from [ 3 H]uridine in incubations of whole goldfish retinas is increased in the ipsilateral retina during a period of regeneration that follows unilateral optic nerve crush. Brief incubations to investigate the nature of enhanced labeling of the acid-soluble fraction showed a peak uptake 4 days following crush, with a gradual decrease to control levels by 21 days following crush. That nucleoside uptake may not mediate the effect is supported by the observation that the rate of uptake of 5′-deoxyadenosine, a nonmetabolizable nucleoside analog, is the same in post-crush (PC) and normal (N) retinal incubations. Following brief incubations of PC and N retinas with [ 3 H]uridine, there is enhanced labeling in PC retinas relative to N retinas of recovered UMP, UDP, UTP, and uridine nucleotide sugars, whereas recovery of labeled uridine itself is slightly decreased. The results suggest that the increased accumulation of radioactivity in PC retinas following incubation with uridine reflects an increase in the activities of retinal uridine kinase and uridine nucleotide kinases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65630/1/j.1471-4159.1981.tb01713.x.pd

Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate

Genetic Diversity of the ORF5 Gene of Porcine Reproductive and Respiratory Syndrome Virus Isolates in Southwest China from 2007 to 2009

To gain insight into the molecular epidemiology and possible mechanisms of genetic variation of porcine reproductive and respiratory syndrome (PRRS) in Yunnan Province of China, the ORF5 gene of 32 PRRSV isolates from clinical samples collected from 2007 to 2009 were sequenced and analyzed. Nucleotide and amino acid analyses were carried out on 32 isolates and representative strains of the North American genotype, European genotype and two representative Chinese isolates. Results revealed that these isolates share 86.9–99.0% nucleotide and 87.5–98.0% amino acid identity with VR-2332 the prototypical North American PRRSV, 61.7–62.9% and 54.3–57.8% with Lelystad virus (LV) the representative strain of European genotype, 91.2–95.4% and 90.0–94.5% with CH-1a that was isolated in mainland China in 1996, 88.1–99.3% and 85.5–99.0% with JX-A1 the representative strain of High pathogenic PRRSV in China, and 86.2–99.8% and 85.5–100.0% between isolated strains of different years, respectively. Phylogenetic analysis revealed that all 32 PRRSV isolates belonged to the North American genotype and were further divided into two different subgenotypes. Subgenotype 1 comprised twenty two Yunnan isolates which divided into two branches. Subgenotype 2 comprised ten isolates which closely related to the RespPRRS vaccine and its parent strain VR-2332. The functional domains of GP5 such as the signal peptide, ectodomain, transmembrane regions and endodomain were identified and some motifs in GP5 with known functions, such as primary neutralizing epitope (PNE) and decoy epitope were also further analyzed. Our study shown the great genetic diversity of PRRSV in southwest China, rendering the guide for control and prevention of this disease

The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner

The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP3, GP4 and GP5 envelope glycoproteins, only the M/GP5 glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP5. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines