Distribution of Isolated Volcanoes on the Flanks of the East Pacific Rise, 15.3°-20°S

Volcanic constructions, not associated with seamount (or volcano) chains, are abundant on the flanks of the East Pacific Rise (EPR) but are rare along the axial high. The distribution of isolated volcanoes, based on multibeam bathymetric maps, is approximately symmetric about the EPR axis. This symmetry contrasts with the asymmetries in the distribution of volcano chains (more abundant on the west flank), the seafloor subsidence rates (slower on the west flank), and the distribution of plate-motion-parallel gravity lineaments (more prominento nthe west flank). Most of the isolated volcanoes complete their growth within -14 km of the axis on crust younger than 0.2 Ma, while seamount chain volcanoes continue to be active on older crust. Volcanic edifices within 6 km of the ridge axis are primarily found adjacent to axial discontinuities, suggesting a more sporadic magma supply and stronger lithosphere able to support volcanic constructions near axial discontinuities. The volume of isolated near-axis volcanoes correlates with ridge axis cross-sectional area, suggesting a link between the magma budget of the ridge and the eruption of near-axis volcanoes. Within the study area, off-axis volcanic edifices cover at least 6% of the seafloor and contribute more than 0.2% to the volume of the crust. The inferred width of the zone where isolated volcanoes initially form increases with spreading rate for the Mid-Atlantic Ridge (\u3c4 km), northern EPR (\u3c20 km), and southern EPR(\u3c28 km), so that isolated volcanoes form primarily on lithosphere younger than 0.2 Ma (\u3c 4-6 km brittle thickness), independent of spreading rate. This suggests some form of lithospheric control on the eruption of isolated off-axis volcanoes due to brittle thickness, increased normal stresses across cracks impeding dike injection, or thermal stresses within the newly forming lithosphere

The cysteine-rich domain regulates ADAM protease function in vivo

ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate “adhesive” domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases

Magmatic Subsidence of the East Pacific Rise (EPR) at 18˚14\u27S Revealed Through Fault Restoration of Ridge Crest Bathymetry

The fault restoration technique of De Chabalier and Avouac [1994] is applied to an ultra-highresolution bathymetry data set from the East Pacific Rise (EPR) at 18140S. Fault offsets are calculated and subtracted from the original seafloor bathymetry to examine the morphology of the unfaulted seafloor surface within an area encompassing the ridge axis 400 [1] 1600 m in dimension. The restored topography reveals a gently sloping seafloor 200 m wide, which slopes 5 inward toward the spreading axis. We attribute this inward sloping seafloor to subsidence within the axial trough due to subsurface magmatic deflation. The vertical deformation field extracted from the bathymetry is used to characterize the ridge axis fault population present in the area. Median fault throws (9 m for inward-facing and 8 m for outwardfacing faults) are comparable to values measured for nearby mature abyssal hill fault populations, suggesting a genetic link. However, median fault spacings (70 and 46 m) are an order of magnitude smaller, and estimated total extensional strain is 3[1]–4[1] greater than values measured for ridge flank faults. These differences indicate the axial fault population at 18140S cannot be rafted onto the ridge flanks to form abyssal hill faults without significant modification, presumably via volcanic burial. We attribute the dense faulting observed in this area to slip on axial fissures during subsidence of the crestal region. The surface subsidence of a volcanic edifice can be modeled in terms of volume change in the magma source reservoir and volume of magma withdrawn from the reservoir. Using the relationship derived for a sill-like magma body, we estimate that the axial depression at 18140S could represent magma withdrawal associated with a small number (4–22) of the frequent dike injection and eruption events required to build the upper crust during the evolution of the trough. The subsidence volumes represented by the axial topography at 18140S are a small percentage of the underlying upper crustal sections (3–4%), suggesting that only a minor mismatch between magma recharge and withdrawal from the axial melt lens during ongoing plate separation could account for this pronounced axial depression

Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS/ELSD libraries.

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E\u27 (13) and F\u27 (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship (SAR) studies. The activity patterns observed for bengamide A (6), B (7), E (8), F (9), LAF 389 (12) and 13-14 gave rise to the following observations and conclusions. Compounds 6 and 7 display potent inhibition of NF-κB (at 80 and 90 nM, respectively) without cytotoxicity to RAW264.7 macrophage immune cells. Western blot and qPCR analysis indicated that 6 and 7 reduce the phosphorylation of IκBα and the LPS-induced expression of the pro-inflammatory cytokines/chemokines TNFα, IL-6 and MCP-1 but do not effect NO production or the expression of iNOS. These results suggest that the bengamides may serve as therapeutic leads for the treatment of diseases involving inflammation, that their anti-tumor activity can in part be attributed to their ability to serve as immune modulating agents, and that their therapeutic potential against cancer merits further consideration

Brief motivational interventions for college student drinking may not be as powerful as we think: An individual participant-level data meta-analysis

Background For over two decades, brief motivational interventions (BMIs) have been implemented on college campuses to reduce heavy drinking and related negative consequences. Such interventions include in-person motivational interviews (MIs), often incorporating personalized feedback (PF), and stand-alone PF interventions delivered via mail, computer, or the Web. Both narrative and meta-analytic reviews using aggregate data from published studies suggest at least short-term efficacy of BMIs, although overall effect sizes have been small. Method The present study was an individual participant-level data (IPD) meta-analysis of 17 randomized clinical trials evaluating BMIs. Unlike typical meta-analysis based on summary data, IPD meta-analysis allows for an analysis that correctly accommodates the sampling, sample characteristics, and distributions of the pooled data. In particular, highly skewed distributions with many zeroes are typical for drinking outcomes, but have not been adequately accounted for in existing studies. Data are from Project INTEGRATE, one of the largest IPD meta-analysis projects to date in alcohol intervention research, representing 6,713 individuals each with two to five repeated measures up to 12 months post-baseline. Results We used Bayesian multilevel over-dispersed Poisson hurdle models to estimate intervention effects on drinks per week and peak drinking, and Gaussian models for alcohol problems. Estimates of overall intervention effects were very small and not statistically significant for any of the outcomes. We further conducted post hoc comparisons of three intervention types (Individual MI with PF, PF only, and Group MI) vs. control. There was a small, statistically significant reduction in alcohol problems among participants who received an individual MI with PF. Short-term and long-term results were similar. Conclusions The present study questions the efficacy and magnitude of effects of BMIs for college drinking prevention and intervention and suggests a need for the development of more effective intervention strategies

Project INTEGRATE: An Integrative Study of Brief Alcohol Interventions for College Students

This paper provides an overview of a study that synthesizes multiple, independently collected alcohol intervention studies for college students into a single, multisite longitudinal data set. This research embraced innovative analytic strategies (i.e., integrative data analysis or meta-analysis using individual participant-level data), with the overall goal of answering research questions that are difficult to address in individual studies such as moderation analysis, while providing a built-in replication for the reported efficacy of brief motivational interventions for college students. Data were pooled across 24 intervention studies, of which 21 included a comparison or control condition and all included one or more treatment conditions. This yielded a sample of 12,630 participants (42% men; 58% first-year or incoming students). The majority of the sample identified as White (74%), with 12% Asian, 7% Hispanic, 2% Black, and 5% other/mixed ethnic groups. Participants were assessed two or more times from baseline up to 12 months, with varying assessment schedules across studies. This paper describes how we combined individual participant-level data from multiple studies, and discusses the steps taken to develop commensurate measures across studies via harmonization and newly developed Markov chain Monte Carlo algorithms for two-parameter logistic item response theory models and a generalized partial credit model. This innovative approach has intriguing promises, but significant barriers exist. To lower the barriers, there is a need to increase overlap in measures and timing of follow-up assessments across studies, better define treatment and control groups, and improve transparency and documentation in future single, intervention studies

Associations between Heavy Drinking and Changes in Impulsive Behavior among Adolescent Males

Impulsive behavior in humans predicts the onset of drinking during adolescence and alcohol use disorders (AUDs) in adulthood. It is also possible, however, that heavy drinking may increase impulsive behavior by affecting the development of brain areas that support behavioral control or through other associated mechanisms. This study examined whether drinking heavily during adolescence is related to changes in impulsive behavior with a specific focus on how the association differs across individuals, contingent on the developmental course of their impulsiveness