Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans

Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology

The electrification-malaria nexus: the case of rural Uganda

Sub-Saharan countries are facing multiple simultaneous challenges that include the need to both increase access to electricity and combat morbidity and mortality caused by malaria. This study is the first to explore the nexus between electrification and malaria incidence using country-wide representative household-level data. The focus is on rural Uganda. Despite the fact that data used in this analysis come from a multi-topic survey and therefore do not include the ideal indicators for a malaria-related study, we do find evidence that household members having access to electricity are more likely to experience malaria. Our interpretation is that electric light attracts malaria vectors and that lifestyle changes associated with outdoor lighting increase human exposure to the vectors. Our findings suggest that the electrification process in Uganda should be complemented by anti-malaria strategies

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

This review summarizes a presentation made at the retirement Symposium of Prof. Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L‐cycloserine, the GHB receptor antagonist NCS‐382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11 C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open‐label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742