A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia

About 15% of couples experience difficulty in conceiving a child, of which half of the cases are thought to be male-related. Asthenozoospermia, or low sperm motility, is one of the frequent types of male infertility. Although energy metabolism is suggested to be central to the etiology of asthenozoospermia, very few attempts have been made to identify its underlying metabolic pathways. Here, we reconstructed SpermNet, the first proteome-scale model of the sperm cell by using whole-proteome data and the mCADRE algorithm. The reconstructed model was then analyzed using the COBRA toolbox. Genes were knocked-out in the model to investigate their effect on ATP production. A total of 78 genes elevated ATP production rate considerably of which most encode components of oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, and members of the solute carrier 25 family. Among them, we identified 11 novel genes which have previously not been associated with sperm cell energy metabolism and may thus be implicated in asthenozoospermia. We further examined the reconstructed model by in silico knock out of currently known asthenozoospermia implicated-genes that were not predicted by our model. The pathways affected by knocking out these genes were also related to energy metabolism, confirming previous findings. Therefore, our model not only predicts the known pathways, it also identifies several non-glycolytic genes for deficient energy metabolism in asthenozoospermia. Finally, this model supports the notion that metabolic pathways besides glycolysis such as oxidative phosphorylation and fatty acid oxidation are essential for sperm energy metabolism and if validated, may form a basis for fertility recovery. </p

The impact of blood-borne viruses on cause-specific mortality among opioid dependent people: An Australian population-based cohort study.

BACKGROUND: Blood-borne viruses (BBV) are prevalent among people with opioid dependence but their association with cause-specific mortality has not been examined at the population-level. METHODS: We formed a population-based cohort of 29,571 opioid substitution therapy (OST) registrants in New South Wales, Australia, 1993-2007. We ascertained notifications of infection and death by record linkage between the Pharmaceutical Drugs of Addiction System (OST data), registers of hepatitis C (HCV), hepatitis B (HBV) and human immunodeficiency virus (HIV) diagnoses, and the National Death Index. We used competing risks regression to quantify associations between notification for BBV infection and causes of death. BBV status, age, year, OST status, and OST episodes were modelled as time-dependent covariates; sex was a fixed covariate. RESULTS: OST registrants notified with HCV infection were more likely to die from accidental overdose (subdistribution hazard ratio, 95% Confidence Interval: 1.7, 1.5-2.0), cancer (2.0, 1.3-3.2) and unintentional injury (1.4, 1.0-2.0). HBV notification was associated with a higher hazard of mortality due to unintentional injury (2.1, 1.1-3.9), cancer (2.8, 1.5-5.5), and liver disease (2.1, 1.0-4.3). Liver-related mortality was higher among those notified with HIV only (11, 2.5-50), HCV only (5.9, 3.2-11) and both HIV and HCV (15, 3.2-66). Registrants with an HIV notification had a higher hazard of cardiovascular-related mortality (4.0, 1.6-9.9). CONCLUSIONS: Among OST registrants, BBVs are a direct cause of death and also a marker of behaviours that can result in unintended death. Ongoing and enhanced BBV prevention strategies and treatment, together with targeted education strategies to reduce risk, are justified

HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D cohort study

BACKGROUND: Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals. METHODS: The prospective observational database of the D:A:D collaboration of 11 cohorts of HIV-infected individuals, including 212 clinics in Europe, the United States and Australia was used. Multivariate Poisson regression was used to assess the effect of HCV or HBV infection on the development of myocardial infarction after adjustment for potential confounders, including cardiovascular risk factors, diabetes mellitus and exposure to antiretroviral therapy. RESULTS: Of 33,347 individuals, 517 developed a myocardial infarction over 157,912 person-years, with an event rate of 3.3 events/1,000 person-years (95% confidence interval [CI] 3.0-3.6). Event rates (95% CIs) per 1,000 person-years in those who were HCV-seronegative and HCV-seropositive were 3.3 (3.0-3.7) and 2.7 (2.2-3.3), respectively, and for those who were HBV-seronegative, had inactive infection or had active infection were 3.2 (2.8-3.5), 4.2 (3.1-5.2) and 2.8 (1.8-3.9), respectively. After adjustment, there was no association between HCV seropositivity (rate ratio 0.86 [95% CI 0.62-1.19]), inactive HBV infection (rate ratio 1.07 [95% CI 0.79-1.43]) or active HBV infection (rate ratio 0.78 [95% CI 0.52-1.15]) and the development of myocardial infarction. CONCLUSIONS: We found no association between HBV or HCV coinfection and the development of myocardial infarction among HIV-infected individuals