Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. We intercrossed male and female adult control and first-generation offspring of GDM (F1-GDM) mice to obtain the second-generation (F2) offspring in four groups: C♂-C♀, C♂-GDM♀, GDM♂-C♀, and GDM♂-GDM♀. We found that birth weight significantly increased in F2 offspring through the paternal line with impaired glucose tolerance (IGT). Regardless of birth from F1-GDM with or without IGT, high risk of IGT appeared as early as 3 weeks in F2 offspring and progressed through both parental lineages, especial the paternal line. IGT in male offspring was more obvious than that in females, with parental characteristics and sex-specific transmission. In both F1 and F2 offspring of GDM, the expression of imprinted genes Igf2 and H19 was downregulated in pancreatic islets, caused by abnormal methylation status of the differentially methylated region, which may be one of the mechanisms for impaired islet ultrastructure and function. Furthermore, altered Igf2 and H19 gene expression was found in sperm of adult F1-GDM, regardless of the presence of IGT, indicating that changes of epigenetics in germ cells contributed to transgenerational transmission.

Background:Roles of SoxC genes in the development of retinal ganglion cells (RGCs) are unknown at present. Results: Targeted deletion of Sox4 and Sox11 in retina results in a complete loss of RGCs. Conclusion: Sox4 and Sox11 function redundantly to regulate RGC development. Significance: These findings highlight the essential role of SoxC genes in retinal development.

Cyano-substituted oligo (alpha-phenylenevinylene)-1,4-bis(R-cyano-4-diphenylaminostyryl)-2,5-diphenylbenzene (CNDPASDB) molecules are studied in solution and aggregate state by time-resolved fluorescence techniques. CNDPASDB exhibits a strong solvent polarity dependent characteristic of aggregation-induced emission (AIE). By time-dependent spectra, the gradual transition from local excited state to intramolecular charge transfer state with the increasing solvent polarity is clearly resolved. The transition time in high polarity solvent DMF is very fast, around 0.5 ps, resulting in a low fluorescence quantum yield. While in aggregate state, the intramolecular torsion is restricted and the local environment becomes less polar. Thus, the intramolecular charge transfer state is eliminated and efficient AIE occurs.

The role of protein dynamics in guiding multistep electron transfer is explored in the photosynthetic reaction center of Rhodobacter sphaeroides . The energetics of the charge-separated intermediates, P(+)B(A)(-) and P(+)H(A)(-) (P is the initial electron donor bacteriochlorophyll pair and B(A) and H(A) are early bacteriochlorophyll and bacteriopheophytin acceptors, respectively), were systematically varied in a series of mutants. A fast phase of P(+)H(A)(-) recombination was resolved that is very sensitive to driving force. Either increasing or decreasing the relative free energy of P(+)H(A)(-) resulted in a more prominent fast recombination component, and thus a decreased yield forward electron transfer. The fast phase apparently represents P(+)H(A)(-) charge recombination via an activated state, probably P(+)B(A)(-) (B(A) is situated between P and H(A)). In wild type, this activated state is largely inaccessible, presumably due to dynamic stabilization of P(+)H(A)(-) within the first 100 ps. In mutants that change the energetics, the rate of decay via the activated state accelerates and that pathway becomes significant. The dynamic stabilization of the protein makes it possible to achieve a nearly optimum environment of H(A) in wild type on two different time scales and for two rather different reactions. On the picosecond time scale, the energetics is nearly, though not perfectly, optimized for transfer between the excited state of P and H(A). After dynamic stabilization of the state P(+)H(A)(-), the environment is optimized to avoid rapid recombination of the charge-separated state and instead carry out forward electron transfer to the quinone with very high yield on the hundreds of picosecond time scale. Thus, by employing protein dynamics, the reaction center is able to optimize multiple reactions, on very different time scales involving the same reaction intermediate.

SummaryStanleya pinnata not only hyperaccumulates selenium (Se) to 0.5% of its dry weight, but also exhibits higher tissue Se-to-sulfur (S) ratios than other species and its surroundings.To investigate the mechanisms underlying this Se enrichment, we compared S. pinnata with the nonhyperaccumulators S. elata and Brassica juncea for selenate uptake in long-(9 d) and short-term (1 h) assays, using different concentrations of selenate and competitor sulfate. Different sulfate pre-treatments (0, 0.5, 5 mM, 3 d) were also tested for effects on selenate uptake and sulfate transporters' expression.Relative to nonhyperaccumulators, S. pinnata showed higher rates of root and shoot Se accumulation and less competitive inhibition by sulfate or by high-S pretreatment. The selenate uptake rate for S. pinnata (1 h) was three-to four-fold higher than for nonhyperaccumulators, and not significantly affected by 100-fold excess sulfate, which reduced selenate uptake by 100% in S. elata and 40% in B. juncea. Real-time reverse transcription PCR indicated constitutive upregulation in S. pinnata of sulfate transporters SULTR1;2 (root influx) and SULTR2;1 (translocation), but reduced SULTR1;1 expression (root influx).In S. pinnata, selenate uptake and translocation rates are constitutively elevated and relatively sulfate-independent. Underlying mechanisms likely include overexpression of SULTR1;2 and SULTR2;1, which may additionally have evolved enhanced specificity for selenate over sulfate.

Skeletal muscle plays a pivotal role in regulating systemic glucose homeostasis in part through the conserved cellular energy sensor AMPK. AMPK activation increases glucose uptake, lipid oxidation, and mitochondrial biogenesis, leading to enhanced muscle insulin sensitivity and whole-body energy metabolism. Here we show that the muscle-enriched H19 long noncoding RNA (lncRNA) acts to enhance muscle insulin sensitivity, at least in part, by activating AMPK. We identify the atypical dual-specificity phosphatase DUSP27/DUPD1 as a potentially important downstream effector of H19. We show that DUSP27, which is highly expressed in muscle with previously unknown physiological function, interacts with and activates AMPK in muscle cells. Consistent with decreased H19 expression in the muscle of insulin-resistant human subjects and rodents, mice with genetic H19 ablation exhibit muscle insulin resistance. Furthermore, a high-fat diet downregulates muscle H19 via both posttranscriptional and epigenetic mechanisms. Our results uncover an evolutionarily conserved, highly expressed lncRNA as an important regulator of muscle insulin sensitivity.

In plants, the posttranslational modification small ubiquitin-like modifier (SUMO) is involved in regulating several important developmental and cellular processes, including flowering time control and responses to biotic and abiotic stresses. Here, we report two proteases, SUMO PROTEASE RELATED TO FERTILITY1 (SPF1) and SPF2, that regulate male and female gamete and embryo development and remove SUMO from proteins in vitro and in vivo. mutants exhibit abnormal floral structures and embryo development, while mutants exhibit largely a wild-type phenotype. However, double mutants exhibit severe abnormalities in microgametogenesis, megagametogenesis, and embryo development, suggesting that the two genes are functionally redundant. Mutation of and genes also results in misexpression of generative- and embryo-specific genes. In vitro, SPF1 and SPF2 process SUMO1 precursors into a mature form, and as expected in vivo, and mutants accumulate SUMO conjugates. Using a yeast two-hybrid screen, we identified EMBRYO SAC DEVELOPMENT ARREST9 (EDA9) as an SPF1-interacting protein. In vivo, we demonstrate that EDA9 is sumolyated and that, in mutants, EDA9-SUMO conjugates increase in abundance, demonstrating that EDA9 is a substrate of SPF1. Together, our results demonstrate that SPF1 and SPF2 are two SUMO proteases important for plant development in Arabidopsis ().

Perfluorooctane sulfonate (PFOS), which belongs to the degradation product of many perfluorinated compounds, is on the list of persistent organic pollutants (POPs) and is currently detected in both wildlife and humans. The consequence of gestational and lactational exposure to PFOS on prediabetes effect in offspring was investigated in rats in the present study. Maternal rats were treated with vehicle, 0.5 mg/kg/day or 1.5 mg/kg/day PFOS respectively from gestation day 0 to postnatal day 21. The glucose and lipid metabolism effects were investigated on the offspring in adulthood. The gestational and lactational exposure to PFOS led to low body weight from birth to weaning, and evoked signs of a prediabetic state, with elevated fasting serum insulin and leptin level, impaired glucose tolerance, though the fasting serum glucose and glycosylated serum protein level were normal. Abnormal lipid homeostasis was also observed by the phenomenon of hepatic steatosis and increased gonadal fat pad weight. However, the circulating serum level of fasting triglyceride and cholesterol level were no different from controls. Our results suggested that developmental exposure to PFOS may contribute to glucose and lipid metabolic disorder in adulthood.