The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43.

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function.

Semen parameters are unaffected by statin use in men evaluated for infertility.

The effects of statin use on conventional semen parameters in humans are largely unknown and have not been previously studied in subfertile men. We retrospectively reviewed data from 10,140 patients seen at our fertility clinic between 2002 and 2013 to assess the effects of statin use on semen parameters. Men who used any statins for >3 months before semen sample collection were included as cases. Data were gathered on patient age, medication use and conventional semen parameters. A total of 118 patients (126 samples) used statins for at least 3 months before semen sample collection. Data from 7698 patients (8,760 samples), who were not using any medications, were used as controls. In age-adjusted regression models, statin use was not associated with statistically significant changes in semen parameters. When used in combination with other nonspermatotoxic medications, it was associated with 0.3 ml decrease in semen volume (95% confidence interval: 0.02 to 0.58 ml, p-value = .04). In conclusion, statin use was not adversely associated with semen parameters other than semen volume in subfertile patients. These findings from our large-scale retrospective study suggest that there are no clinically relevant deleterious effects from statin use on conventional semen parameters.

Risk of all-cause mortality in abdominal obesity phenotypes: Tehran Lipid and Glucose Study.

BACKGROUND AND AIM: Long-term health risks in the so-called "healthy obesity" phenotypes remain controversial. Also it is unknown if "metabolically healthy abdominal obese" (MHAO) phenotype is at increased risk of all-cause mortality compared to their non-abdominally obese counterparts. In this study we assessed the risk of all-cause mortality in different abdominal obesity phenotypes. METHODS AND RESULTS: In this large population-based cohort, 8804 participants (aged ≥ 30 years), from the Tehran Lipid and Glucose Study (TLGS) were enrolled and followed for a median of 12.0 (8.7-12.5) years. Abdominal obesity was defined using national waist circumference (WC) cut-off points of ≥89 cm for men and ≥91 cm for women. Metabolic health was defined as ≤1 components of metabolic syndrome (excluding WC), using the Joint Interim Statement (JIS) definition. Baseline prevalence of MHAO phenotype was 12.8% in the whole population and 23.4% in those with abdominal obesity. A total of 540 all-cause death occurred during the follow-up. After multivariate adjustment, all-cause mortality risk in MHAO phenotype was not significantly increased compared to "metabolically healthy non abdominal obese" (MHNAO) as the reference group (HR: 1.35, CI: 0.89-2.03). CONCLUSION: Our results indicate that MHAO individuals were not at higher risk for all-cause mortality over a median of 12 years follow-up. However, considering inadequate power of our analysis for fully adjusted model, larger studies with more follow-ups are needed.

Natural course of metabolically healthy abdominal obese adults after 10 years of follow-up: the Tehran Lipid and Glucose Study.

OBJECTIVE: This study aims to assess the natural course of metabolically healthy abdominal obese (MHAO) phenotype and determine the predictors of change in the metabolic status in this population over 10 years of follow-up. METHODS: A total of 916 MHAO subjects from the Tehran Lipid and Glucose Study were followed for changes in their metabolic health status. Anthropometric and metabolic indices were measured at baseline and were compared between subjects with healthy and unhealthy metabolic conditions at the end of follow-up. Predictors of change in metabolic health were assessed in logistic regression models. National waist circumference cutoffs were used for definition of abdominal obesity. Metabolic health was defined as ⩽1 metabolic components of metabolic syndrome according to the Joint Interim Statement criteria. RESULTS: At the end of the follow-up, nearly half of the MHAO subjects lost their metabolic health and 42.1% developed metabolic syndrome by definition. Low high-density lipoprotein cholesterol, hypertriglyceridemia and homeostasis model assessment-insulin resistance at baseline were significant predictors of change in metabolic health condition. CONCLUSION: MHAO is a relatively unstable condition and a considerable percentage of these individuals will lose their metabolic health as time passes. Baseline metabolic characteristics may be useful predictors of this change and should be considered in the care of these individuals.