GDNF and GFRα-1 Are Components of the Axolotl Pronephric Duct Guidance System

AbstractIn mammals, secretion of GDNF by the metanephrogenic mesenchyme is essential for branching morphogenesis of the ureteric bud and, thus, metanephric development. However, the expression pattern of GDNF and its receptor complex—the GPI-linked ligand-binding protein, GFRα-1, and the Ret tyrosine kinase signaling protein—indicates that it could operate at early steps in kidney development as well. Furthermore, the developing nephric systems of fish and amphibian embryos express components of the GDNF signaling system even though they do not make a metanephros. We provide evidence that GDNF signaling through GFRα-1 is sufficient to direct pathfinding of migrating pronephric duct cells in axolotl embryos by: (1) demonstrating that application of soluble GFRα-1 to an embryo lacking all GPI-linked proteins rescues PND migration in a dose-dependent fashion, (2) showing that application of excess soluble GFRα-1 to a normal embryo inhibits migration and that inhibition is dependent upon GDNF-binding activity, and (3) showing that the PND will migrate toward a GDNF-soaked bead in vivo, but will fail to migrate when GDNF is applied uniformly to the flank. These data suggest that PND pathfinding is accomplished by migration up a gradient of GDNF

Organogenesis: Cutting to the Chase

AbstractGonad morphogenesis in Caenorhabditis elegans requires two secreted proteases. Recent studies show that alterations of the extracellular matrix component fibulin-1 rescue gonadogenesis in the absence of these proteases. This finding is a critical step toward understanding the role of extracellular matrix in organogenesis

Seismic evidence for a slab tear at the Puerto Rico Trench

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 105 (2013): 2915-2923, doi:10.1002/jgrb.50227.The fore‐arc region of the northeast Caribbean plate north of Puerto Rico and the Virgin Islands has been the site of numerous seismic swarms since at least 1976. A 6 month deployment of five ocean bottom seismographs recorded two such tightly clustered swarms, along with additional events. Joint analyses of the ocean bottom seismographs and land‐based seismic data reveal that the swarms are located at depths of 50–150 km. Focal mechanism solutions, found by jointly fitting P wave first‐motion polarities and S/P amplitude ratios, indicate that the broadly distributed events outside the swarm generally have strike‐ and dip‐slip mechanisms at depths of 50–100 km, while events at depths of 100–150 km have oblique mechanisms. A stress inversion reveals two distinct stress regimes: The slab segment east of 65°W longitude is dominated by trench‐normal tensile stresses at shallower depths (50–100 km) and by trench‐parallel tensile stresses at deeper depths (100–150 km), whereas the slab segment west of 65°W longitude has tensile stresses that are consistently trench normal throughout the depth range at which events were observed (50–100 km). The simple stress pattern in the western segment implies relatively straightforward subduction of an unimpeded slab, while the stress pattern observed in the eastern segment, shallow trench‐normal tension and deeper trench‐normal compression, is consistent with flexure of the slab due to rollback. These results support the hypothesis that the subducting North American plate is tearing at or near these swarms. The 35 year record of seismic swarms at this location and the recent increase in seismicity suggest that the tear is still propagating

Refined model of incremental emplacement based on structural evidence from the granodioritic Newry igneous complex, Northern Ireland

Although many intrusions are now known to have been incrementally emplaced, the mechanisms through which this takes place are generally poorly understood. The Newry igneous complex was incrementally emplaced within the Southern Uplands-Down-Longford terrane of Northern Ireland during late Caledonian sinistral transtension. This study uses a variety of new and existing data and techniques to provide a fuller and firmer understanding of incremental emplacement than has previously been available, addressing both deep-crustal processes and those operating within the emplacement site. Host-rock orientations suggest that some of the accommodation space for the Newry igneous complex was generated due to pull-apart tectonics operating within the Southern Uplands-Down-Longford terrane. Local host-rock deflections, concentric igneous foliations, and concentric linear anisotropy of magnetic susceptibility (AMS)fabrics show that inflation due to magma overpressure also generated significant space. Strong AMS fabrics close to the boundaries of some magma pulses in turn suggest that inflation was accomplished by injection of individual magma pulses and was thus incremental. The dome-like orientations of mineral foliations within plutons and the truncation of steep local host-rock tracts by the Newry igneous complex imply that the complex consists of four laccolithic bodies. On a larger scale, it is suggested that the deep-seated Argyll and Newry lineaments represent faults that allowed magma generated at depth to ascend to the crustal level of the Southern Uplands-Down-Longford tract boundaries. It is also inferred that sinistral movement along the Argyll and Newry lineaments may have produced the releasing bend within the Southern Uplands-Down-Longford terrane. Higher in the crust, reduced confining pressure resulted in tectonic opening along this releasing bend. This local stress field induced horizontal magma flow and emplacement of the Newry igneous complex as laccolithic bodies. This study suggests that simplistic emplacement models should largely be abandoned in favor of holistic models incorporating the multiple interdependent processes operating during magma ascent and emplacement

Indium phosphide photonic circuits on silicon electronics

The intimate integration of photonics and electronics in transceivers facilitates energy-efficiency, bandwidth acceleration and a route to radical miniaturization. We present and implement a wafer-to-wafer integration method which combines electronic and photonic foundry technologies

Vacuum-ultraviolet photoabsorption imaging system for laser plasma plume diagnostics

We describe a recently designed and constructed system based on a 1 m normal incidence vacuum monochromator with corrected (toroidal) optics that produces a wavelength tuneable and collimated vacuum-ultraviolet (VUV) (λ=30–100 nm) beam. The VUV continuum source is a laser-generated gold plasma. The primary function of the system is the measurement of time resolved “images” or spatial distributions of photoabsorption/photoionization in expanding laser plasma plumes. This is achieved by passing the beam through the sample of interest (in our case a second synchronised plasma) and recording the “footprint” of the attenuated beam on a charge coupled device. Using this VUV photoabsorption imaging or “shadowgraphy” technique we track and extract column density distributions in expanding plasma plumes. We can also measure the plume front velocity. We have characterized the system, particularly in relation to spectral and spatial resolution and the experimental results meet very well the expectations from ray tracing done at the design phase. We present first photoabsorption images and column density distributions of laser produced Ca plumes from the system

Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa

Background: Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Methods and Findings: Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to 80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. Conclusions: The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summar

The Sources of Inflammatory Mediators in the Lung after Silica Exposure

The expression of 10 genes implicated in regulation of the inflammatory processes in the lung was studied after exposure of alveolar macrophages (AMs) to silica in vitro or in vivo. Exposure of AMs to silica in vitro up-regulated the messenger RNA (mRNA) levels of three genes [interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2)] without a concomitant increase in the protein levels. AMs isolated after intratracheal instillation of silica up-regulated mRNA levels of four additional genes [granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-1β, IL-10, and inducible nitric oxide synthase]. IL-6, MCP-1, and MIP-2 protein levels were elevated in bronchoalveolar lavage fluid. Fibroblasts under basal culture conditions express much higher levels of IL-6 and GM-CSF compared with AMs. Coculture of AMs and alveolar type II cells, or coculture of AMs and lung fibroblasts, in contact cultures or Transwell chambers, revealed no synergistic effect. Therefore, such interaction does not explain the effects seen in vivo. Identification of the intercellular communication in vivo is still unresolved. However, fibroblasts appear to be an important source of inflammatory mediators in the lung

Defining Optimal Brain Health in Adults A Presidential Advisory From the American Heart Association/American Stroke Association

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index < 25 kg/m(2)) and 3 ideal health factors (untreated blood pressure < 120/< 80 mm Hg, untreated total cholesterol < 200 mg/dL, and fasting blood glucose < 100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer's Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention