Light gravitinos, with mass in the eV to MeV range, are well motivated in particle physics, but their status as dark-matter candidates is muddled by early-Universe uncertainties. We investigate how upcoming data from colliders may clarify this picture. Light gravitinos are produced primarily in the decays of the next-to-lightest supersymmetric particle, resulting in spectacular signals, including di-photons, delayed and nonpointing photons, kinked charged tracks, and heavy metastable charged particles. We find that the Tevatron with 20fb-1 and the 7 TeV LHC with 1fb-1 may both see evidence for hundreds of light-gravitino events. Remarkably, this collider data is also well suited to distinguish between currently viable light-gravitino scenarios, with striking implications for structure formation, inflation, and other early-Universe cosmology. © 2010 The American Physical Society.

The tensile bond strength between zirconia subjected to different surface-pretreatment methods and methacryloyloxydecyl-dihydrogen-phosphate (MDP)-containing self-adhesive resin cement was evaluated herein. Eighty-eight cylindrical zirconia specimens were randomly divided into the following four groups based on the pretreatment method: (1) no treatment, (2) air abrasion, (3) HNO3/HF etching, and (4) zirconia-nanoparticle coating. The tensile bond strength of the zirconia−resin-cement complexes was investigated. One-way ANOVA and post hoc tests were performed at a 95% significance level, and the Weibull modulus was calculated. Fracture patterns were visualized by SEM. The surface roughness of the specimens without resin bonding was evaluated by AFM. The tensile bond strength of the specimens decreased as follows: Groups 3 > 4 > 2 > 1 (28.2 ± 6.6, 26.1 ± 5.7, 16.6 ± 3.3, and 13.9 ± 3.0 MPa, respectively). Groups 3 and 4 had significantly higher tensile bond strengths (p < 0.05) and lower fracture probabilities than those of Groups 1 and 2. They also showed both mixed failure and resin-cement cohesive failure, whereas Groups 1 and 2 showed mixed failure exclusively. The zirconia−resin tensile bond was stronger after HNO3/HF etching or ZrO2-nanoparticle coating than after air abrasion or no treatment. The estimated surface roughness decreased as follows: Groups 3 > 4 > 2 > 1. The combination of zirconia pretreated with HNO3/HF etching or ZrO2-nanoparticle coating and an MDP-containing self-adhesive resin cement can increase the clinical longevity of zirconia restorations by preventing their decementation.

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq^-/- ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq^-/- dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq^-/- dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq^-/- dams. Hepatic glucose and triglyceride production rates of Adipoq^-/- dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq^-/- dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq^-/- and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq^-/- dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq^-/- dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.

Background

Numerous pathologies of pregnancy originate from placental dysfunction. It is essential to understand the functions of key genes in the placenta in order to discern the etiology of placental pathologies. A paucity of animal models that allow conditional and inducible expression of a target gene in the placenta is a major limitation for studying placental development and function.

Results

To study the platelet-derived growth factor receptor alpha (PDGFRα)-directed and tamoxifen-induced Cre recombinase expression in the placenta, PDGFRα-CreER mice were crossed with mT/mG dual-fluorescent reporter mice. The expression of endogenous membrane-localized enhanced green fluorescent protein (mEGFP) and/or dTomato in the placenta was examined to identify PDGFRα promoter-directed Cre expression. Pregnant PDGFRα-CreER;mT/mG mice were treated with tamoxifen at various gestational ages. Upon tamoxifen treatment, reporter protein mEGFP was observed in the junctional zone (JZ) and chorionic plate (CP). Furthermore, a single dose of tamoxifen was sufficient to induce the recombination.

Conclusions

PDGFRα-CreER expression is restricted to the JZ and CP of mouse placentas. PDGFRα-CreER mice provide a useful tool to conditionally knock out or overexpress a target gene in these regions of the mouse placenta.

Background

Excessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity.

Methods

C57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery.

Results

We found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation.

Conclusions

These results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT.

Aims/hypothesis

The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment.

Methods

Adiponectin knockout (Adipoq (-/-) ) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth.

Results

The body weight of fetuses from Adipoq (-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect.

Conclusions/interpretation

These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

Autism spectrum disorder (ASD) is a markedly heterogeneous condition with a varied phenotypic presentation. Its high concordance among siblings, as well as its clear association with specific genetic disorders, both point to a strong genetic etiology. However, the molecular basis of ASD is still poorly understood, although recent studies point to the existence of sex-specific ASD pathophysiologies and biomarkers. Despite this, little is known about how exactly sex influences the gene expression signatures of ASD probands. In an effort to identify sex-dependent biomarkers and characterize their function, we present an analysis of a single paired-end postmortem brain RNA-Seq data set and a meta-analysis of six blood-based microarray data sets. Here, we identify several genes with sex-dependent dysregulation, and many more with sex-independent dysregulation. Moreover, through pathway analysis, we find that these sex-independent biomarkers have substantially different biological roles than the sex-dependent biomarkers, and that some of these pathways are ubiquitously dysregulated in both postmortem brain and blood. We conclude by synthesizing the discovered biomarker profiles with the extant literature, by highlighting the advantage of studying sex-specific dysregulation directly, and by making a call for new transcriptomic data that comprise large female cohorts.

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.