Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events

Objective We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Participants and methods Four clinical trials randomly assigned treatment-naive participants to efavirenzcontaining regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Results Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7 × 10-4). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9 × 10-27). Conclusion Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics

RV Sonne Cruise 198-2, 18 Jun-01 Aug 2008. Merak, Indonesia - Merak, Indonesia

All plate boundaries are divided into segments - pieces of fault that are distinct from one another, either separated by gaps or with different orientations. The maximum size of an earthquake on a fault system is controlled by the degree to which the propagating rupture can cross the boundaries between such segments. A large earthquake may rupture a whole segment of plate boundary, but a great earthquake usually ruptures more than one segment at once.Earthquakes offshore of Sumatra on December 26 2004 (MW=9.3) and March 28 2005 (MW=8.7) ruptured, respectively, 1200-1300 km and 300-400 km of the subduction boundary between the Indian-Australian plate and the Burman and Sumatra blocks. Rupture in the 2004 event started at the southern end of the fault segment, and propagated northwards. The observation that the slip did not propagate significantly southwards in December 2004, even though the magnitude of slip was high at the southern end of the rupture strongly suggests a barrier at that place. Maximum slip in the March 2005 earthquake occurred within ~100 km of the barrier between the 2004 and 2005 ruptures, confirming both the physical importance of the barrier, and the loading of the March 2005 rupture zone by the December 2004 earthquake. Cruise SO198-2, from Merak to Merak between 18 June and 01 August 2008 is the second of three cruises, funded by the Natural Environment Research Council (NERC), which will form a coherent set of geophysical observations in the source regions of the 2004 and 2005 great Sumatra earthquakes. This cruise collected seismic reflection (MCS) profiles at SB1 and SB2 with the following objectives:1. To image the geometry and nature of the downgoing slab from the trench to 30-40 km depth within the forearc2. To image faults within the over-riding plate responsible for the development of the accretionary wedge3. To provide a set of shots that will calibrate the array of ocean-bottom seismometers deployed on cruise SO198-1, and be recorded by the land seismometer array established by a different part of the consortium.Cruise SO198-2 also included nine days of ship time funded by the United States National Science Foundation to investigators from the University of Texas Institute for Geophysics (UTIG). This allied study targeted the subject of rupture pathways, with a focus was on how the earthquake rupture propagates updip through the accretionary prism to ultimately move the seafloor and create the tsunami.Approximately 5000km of multichannel seismic reflection data were collected during the cruise, as well as continuous recording of gravity, magnetics, Parasound and swath bathymetry data while in the permitted area

Genomics of tolerance to abiotic stress in the Triticeae

Genomics platforms offer unprecedented opportunities to identify, select and in some cases clone the genes and the quantitative trait loci (QTLs) that govern the tolerance of Triticeae to abiotic stresses and, consequently, grain yield. Transcriptome profiling and the other \u201comics\u201d platforms provide further information to unravel gene functions and validate the role of candidate genes. This review provides a synopsis of the main results on the studies that have investigated the genomics of Triticeae crops under conditions of abiotic constraints. With their rich biodiversity and high functional plasticity in response to environmental stresses, Triticeae crops provide an ideal ground for taking full advantage of the opportunities offered by genomics approaches. Ultimately, the practical impact of the knowledge and materials generated through genomics-based approaches will depend on their integration and exploitation within the extant breeding programs