Parental smoking during pregnancy and risk of overweight and obesity in the daughter

Objective: Emerging evidence suggests that prenatal exposures may affect long-term health outcomes. In utero exposure to smoking is associated with an increased risk of overweight and obesity in children and adolescents. However, few studies have examined how prenatal exposure to parental smoking influences risk of obesity in adulthood and whether these associations are independent of childhood and adolescent adiposity. The aim of the current study was to investigate whether prenatal exposure to parental smoking influences body size in adulthood and whether any association may be mediated by childhood and adolescent body size. Methods: We investigated the association between parental smoking during pregnancy and risk of overweight and obesity in adulthood and at age 18, and adiposity during childhood among 35,370 participants in the Nurses’ Health Study II. Data on smoking during pregnancy and socioeconomic variables were provided by the mothers, and anthropometric data and adult risk factors were reported by participants. Results: After adjustment for socioeconomic and behavioral variables, maternal smoking during pregnancy was associated with adiposity at ages 5–10, age 18, and during adulthood. For age 18 overweight the ORs (95% CIs) for 1–14, 15–24, and 25+cigarettes/day were 1.13 (1.18–1.50), 1.40 (1.20–1.64), and 1.15 (0.79–1.69) and for obesity were 1.41 (1.14–1.75), 1.69 (1.31–2.18), and 2.36 (1.44–3.86). The corresponding ORs (95% CIs) for obesity in adulthood were 1.26 (1.16–1.37), 1.46 (1.30–1.63), and 1.43 (1.10–1.86). Risk of adiposity was not increased among daughters whose mothers stopped smoking during the first trimester (OR [95% CI] for overweight (1.03 [95% CI 0.90–1.17] and obesity (1.12 [95% CI 0.97–1.30]). Women whose fathers smoked during pregnancy were also at increased risk of overweight and obesity in adulthood with covariate-adjusted ORs (95% CIs) for obesity of 1.19 (1.11–1.29) for 1–14 cigarettes/day, 1.27 (1.18–1.37) for 15–24 cigarettes/day, and 1.40 (1.27–1.54) for 25+ cigarettes/day compared to fathers who did not smoke (ptrend<0.0001). Paternal smoking during pregnancy was also associated with an increased risk of obesity at age 18 among those whose fathers smoked 15 or more cigarettes/day but was not associated with childhood body size. Conclusions: Maternal smoking during pregnancy was associated in a dose-response manner with overweight and obesity in the daughter through adolescence and adult life. Smoking cessation during the first trimester appears to mitigate this excess risk. Paternal smoking was also associated with risk of overweight and obesity of the adult daughter and this association persisted after adjustment for maternal smoking

Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity

Autoantibodies directed against citrulline-containing proteins have an impressive specificity of nearly 100% in patients with rheumatoid arthritis and have been suggested to be involved in the disease pathogenesis. The targeted epitopes are generated by a post-translational modification catalysed by the calcium-dependent enzyme peptidyl arginine deiminase (PAD), which converts positively charged arginine to polar but uncharged citrulline. The aim of this study was to explore the effects of citrullination on the immunogenicity of autoantigens as well as on potential arthritogenicity. Thus, immune responses to citrullinated rat serum albumin (Cit-RSA) and to unmodified rat serum albumin (RSA) were examined as well as arthritis development induced by immunisation with citrullinated rat collagen type II (Cit-CII) or unmodified CII. In addition, to correlate the presence of citrullinated proteins and the enzyme PAD4 with different stages of arthritis, synovial tissues obtained at different time points from rats with collagen-induced arthritis were examined immunohistochemically. Our results demonstrate that citrullination of the endogenous antigen RSA broke immunological tolerance, as was evident by the generation of antibodies directed against the modified protein and cross-reacting with the native protein. Furthermore we could demonstrate that Cit-CII induced arthritis with higher incidence and earlier onset than did the native counterpart. Finally, this study reveals that clinical signs of arthritis precede the presence of citrullinated proteins and the enzyme PAD4. As disease progressed into a more severe and chronic state, products of citrullination appeared specifically in the joints. Citrullinated proteins were detected mainly in extracellular deposits but could also be found in infiltrating cells and on the cartilage surface. PAD4 was detected in the cytoplasm of infiltrating mononuclear cells, from day 21 after immunisation and onwards. In conclusion, our data reveal the potency of citrullination to break tolerance against the self antigen RSA and to increase the arthritogenic properties of the cartilage antigen CII. We also show that citrullinated proteins and the enzyme PAD4 are not detectable in healthy joints, and that the appearance and amounts in arthritic joints of experimental animals are correlated with the severity of inflammation

Dietary Enrichment of Fish-Oils Attenuates Diet-Induced Obesity and Hepatic Steatosis

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess hepatic fat, exceeding 5% of total liver mass. NAFLD is present in one-third of Americans and up to 90% in those who are obese. NAFLD develops largely in part to consumption of a Western diet, defined as 40-60% kcal from saturated fats; however, a diet rich in fish-oils may prevent and reverse the development of steatosis. PURPOSE: To determine the effects of fish oils on the development of NAFLD. METHODS: C57BL/6 (n=91) mice were randomly assigned to four dietary groups for 32-weeks: 10% lard (LFL), 10% fish-oil (LFFO), 41% lard (HFL), or 41% fish-oil (HFFO) diet. Significant differences (p\u3c0.05) between groups were identified by a one-way ANOVA. RESULTS: When compared to HFFO, mice in the HFL group saw an greater (Table 1) body mass and net glucose AUC by 13% (p\u3c0.001) and 24% (p=0.08), respectively. No significant difference was observed between LFL and LFFO for body mass, net glucose AUC or HOMA-IR. This is interesting given no significant difference was observed between groups for the mean weekly caloric intake. HFFO mice showed an 86% lower (p\u3c0.001) total hepatic lipid and 4.8-fold lower (p\u3c0.001) hepatic triglyceride concentration when compared to HFL. HFFO mice also saw a 32% lower (p\u3c0.001) total hepatic cholesterol when compared to HFL. There was no significant difference in total hepatic lipids between LFL and LFFO. CONCLUSION: Despite for no significant difference in caloric intake between high-fat diet groups, consumption of a high-fat diet rich in fish-oils prevented dietary induced obesity, insulin resistance and hepatic steatosis. These results suggest that a diet rich in fish-oils have preventative effects on the development of NAFLD

Fish-oils Increase BAMBI Expression to Protect Against Fibrotic Activity in LPS Stimulated Hepatic Tissue

Non-alcoholic steatohepatitis (NASH), defined as excess hepatic lipid and chronic inflammation, provides an environment prone for the development of hepatic fibrosis. Recent evidence suggests that the antifibrotic protein BAMBI (BMP-Activin membrane bound inhibitor) is downregulated in the presence of inflammation, and may be central to the development of fibrosis. Diets rich in omega-3 (w-3) fatty acids are known to provide anti-inflammatory effects; however, the effects of w-3 fatty acids on hepatic fibrosis are not well-established. PURPOSE: To determine the effects of fish-oils on the hepatic fibrosis signaling cascade, following 32-weeks of high-fat feeding in a LPS-induced model of NASH. METHODS: Male C57BL/6 mice were randomly assigned to one of four diets for 32 weeks (n=9/group): low-fat lard based (LFL, 10% kcal fat), low-fat fish-oil based (LFFO, 10% kcal fat), high-fat lard based (HFL, 41% kcal fat), or high-fat fish-oil based (HFFO, 41% kcal fat). Following in situ LPS stimulation, liver mRNA expression of CD14, TLR4, MyD88, BAMBI, and TGF-β1 was quantified using quantitative RT-PCR. Differences between diets were identified using a one-way ANOVA with statistical significance set at p\u3c0.05. RESULTS: Following LPS stimulation, CD14 was increased 2.5 fold (p=0.020) in HFFO when compared to HFL. Despite the increase in CD14, TLR4 showed no difference between groups. In contrast, MyD88 was 2.8 fold greater (p\u3c0.001) in HFL compared to HFFO. In comparison to untreated tissue, BAMBI was 1.7 fold (p=0.017) higher in the HFFO LPS-stimulated tissue, which best explained the 1-fold (p=0.004) lower expression of TGF-β1 in HFFO when compared to HFL post-LPS stimulation. CONCLUSION: Despite the increase in extracellular LPS signaling receptor CD14, the consumption of fish-oils produced a protective intracellular response as observed by an increase in BAMBI and decrease in TGF-β1. These results suggest that a diet high in w-3 fatty acids may protect against the development of hepatic fibrosi

Diet and Sex Differences Induce Unique Alterations of Markers for Blood Brain Barrier Integrity in Age-Accelerated Mice

The role of diet on brain health has received significant attention, with the Western diet (WD) contributing to cerebrovascular alterations and neurodegenerative disease. The blood-brain barrier (BBB) may play a particularly important role as it forms the interface between the peripheral circulation and the central nervous system. The WD has been shown to negatively impact the BBB. Whether there are sex specific differences with diet on BBB integrity remains unclear. PURPOSE: To determine the effect of diet and sex on the mRNA expression of markers of BBB integrity in an age-accelerated mouse model. METHODS: Male and female Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were randomly assigned to a standard diet (SD) or WD formula for a 32-week period, matched for sex, ending at 12-months of age (n=10-14/group). At 12-months of age, cortical brain tissue was evaluated for the expression of mRNA for targets associated with BBB integrity (Cldn-1, Cldn-3, Cldn-5, Cldn-12, F11r, Lsr, Msfd2a, Ocln, Tjp) using quantitative RT-PCR. A two-way ANOVA was used to identify whether mRNA expression of these targets differed with sex, diet, and their interaction. RESULTS: A significant (pCONCLUSION: Overall, female mice presented with higher expression of mRNA markers for BBB integrity, which may be a protective factor. Furthermore, mice fed the WD had lower mRNA expression of markers of BBB integrity suggesting that a Western diet may accelerate the pathogenesis of the disease state

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

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Variants in Doublecortin- and Calmodulin Kinase Like 1, a Gene Up-Regulated by BDNF, Are Associated with Memory and General Cognitive Abilities

Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation.Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system.These data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions

Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior.

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality

Growth of Long Range Forward-Backward Multiplicity Correlations with Centrality in Au+Au Collisions at sNN\sqrt{s_{NN}} = 200 GeV

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au+Au and $\textit{p+p}$ collisions at $\sqrt{s_{NN}}$ = 200 GeV. Strong short and long range correlations (LRC) are seen in central Au+Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short range correlations are observed in peripheral Au+Au collisions. Both the Dual Parton Model (DPM) and the Color Glass Condensate (CGC) predict the existence of the long range correlations. In the DPM the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC longitudinal color flux tubes generate the LRC. The data is in qualitative agreement with the predictions from the DPM and indicates the presence of multiple parton interactions.Comment: 6 pages, 3 figures The abstract has been slightly modifie