Genome-Wide Identification of Alternatively Spliced mRNA Targets of Specific RNA-Binding Proteins

BACKGROUND: Alternative splicing plays an important role in generating molecular and functional diversity in multi-cellular organisms. RNA binding proteins play crucial roles in modulating splice site choice. The majority of known binding sites for regulatory proteins are short, degenerate consensus sequences that occur frequently throughout the genome. This poses an important challenge to distinguish between functionally relevant sequences and a vast array of those occurring by chance. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used a computational approach that combines a series of biological constraints to identify uridine-rich sequence motifs that are present within relevant biological contexts and thus are potential targets of the Drosophila master sex-switch protein Sex-lethal (SXL). This strategy led to the identification of one novel target. Moreover, our systematic analysis provides a starting point for the molecular and functional characterization of an additional target, which is dependent on SXL activity, either directly or indirectly, for regulation in a germline-specific manner. CONCLUSIONS/SIGNIFICANCE: This approach has successfully identified previously known, new, and potential SXL targets. Our analysis suggests that only a subset of potential SXL sites are regulated by SXL. Finally, this approach should be directly relevant to the large majority of splicing regulatory proteins for which bonafide targets are unknown

Adolescent pregnancies in the Amazon Basin of Ecuador: a rights and gender approach to adolescents' sexual and reproductive health

In the Andean region of Latin America over one million adolescent girls get pregnant every year. Adolescent pregnancy (AP) has been associated with adverse health and social outcomes, but it has also been favorably viewed as a pathway to adulthood. AP can also be conceptualized as a marker of inequity, since it disproportionately affects girls from the poorest households and those who have not been able to attend school

A New P-Wave Tomographic Model (CAP22) for North America: Implications for the Subduction and Cratonic Metasomatic Modification History of Western Canada and Alaska

Funder: Geological Survey of CanadaFunder: West Hudson Bay Architecture and Metallogeny project of the GeoNorth programOur understanding of the present‐day state and evolution of the Canadian and Alaskan mantle is hindered by a lack of absolute P‐wavespeed constraints that provide complementary sensitivity to composition in conjunction with existing S‐wavespeed models. Consequently, cratonic modification, orogenic history of western North America and complexities within the Alaskan Proto‐Pacific subduction system remain enigmatic. One challenge concerns the difficulties in extracting absolute arrival‐time measurements from often‐noisy data recorded by temporary seismograph networks required to fill gaps in continental and global databases. Using the Absolute Arrival‐time Recovery Method (AARM), we extract >180,000 new absolute arrival‐time residuals from seismograph stations across Canada and Alaska and combine these data with USArray and global arrival‐time data from the contiguous US and Alaska. We develop a new absolute P‐wavespeed tomographic model, CAP22, spanning North America that significantly improves resolution in Canada and Alaska over previous models. Slow wavespeeds below the Canadian Cordillera sharply abut fast wavespeeds of the continental interior at the Rocky Mountain Trench in southwest Canada. Slow wavespeeds below the Mackenzie Mountains continue farther inland in northwest Canada, indicating Proterozoic‐Archean metasomatism of the Slave craton. Inherited tectonic lineaments colocated with this north‐south wavespeed boundary suggest that both the crust and mantle may control Cordilleran orogenic processes. In Alaska, fast upper mantle wavespeeds below the Wrangell Volcanic Field favor a conventional subduction related mechanism for volcanism. Finally, seismic evidence for the subducted Kula and Yukon slabs indicate tectonic reconstructions of western North America may require revision

Bifurcation of the Yellowstone plume driven by subduction-induced mantle flow

The causes of volcanism in the northwestern United States over the past 20 million years are strongly contested. Three drivers have been proposed: melting associated with plate subduction; tectonic extension and magmatism resulting from rollback of a subducting slab; or the Yellowstone mantle plume. Observations of the opposing age progression of two neighbouring volcanic chains - the Snake River Plain and High Lava Plains - are often used to argue against a plume origin for the volcanism. Plumes are likely to occur near subduction zones, yet the influence of subduction on the surface expression of mantle plumes is poorly understood. Here we use experiments with a laboratory model to show that the patterns of volcanism in the northwestern United States can be explained by a plume upwelling through mantle that circulates in the wedge beneath a subduction zone. We find that the buoyant plume may be stalled, deformed and partially torn apart by mantle flow induced by the subducting plate. Using plausible model parameters, bifurcation of the plume can reproduce the primary volcanic features observed in the northwestern United States, in particular the opposite progression of two volcanic chains. Our results support the presence of the Yellowstone plume in the northwestern United States, and also highlight the power of plume-subduction interactions to modify surface geology at convergent plate margins