3,946 research outputs found

    Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors

    Get PDF
    The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell spreading by localizing guanine nucleotide exchange factors (GEFs) that act via the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery. In addition, if VAV2 is artificially localized to the cell edge with the subcellular targeting domain of Rap1a, it increases cell spreading independently of Rap1. These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension

    High Consequence Scenarios for North Korean Atmospheric Nuclear Tests with Policy Recommendations for the U.S. Government

    Get PDF
    The government of North Korea has declared high-altitude EMP-capability to be a “strategic goal” and has also threatened an atmospheric test of a hydrogen bomb. Atmospheric nuclear tests have the potential to cripple satellites and the undersea cable networks critical to communication, and navigation necessary for trans-Pacific trade among the U.S., China, and other nations. When a nuclear warhead is detonated at high altitude, a series of electromagnetic pulses radiate downward within the line of sight of the blast. These pulses can disable equipment with miniature electronics and long conductors. Electric grid controls and transmission systems are especially vulnerable. Intense X-rays and free electrons caused by high-altitude nuclear tests can also disable satellites over large regions of space. After the 1962 Starfish Prime test of EMP effects by the U.S, numerous satellites failed. Based on past missile tests, calculated delivery ranges, EMP coverage areas, and geography, Resilient Societies developed five scenarios for North Korean atmospheric tests. Possible sites for EMP tests include the South Pacific Ocean northeast of French Polynesia, Johnson Atoll southwest of Hawaii, and vicinity of the U.S. territory of Guam. Missile trajectories for all three of these EMP test scenarios overfly populated areas. Missile navigation or nuclear device fuzing errors could place the populations of Japan, Guam, and Hawaii are at risk. All potential EMP test locations could cause disruption to international satellite and undersea cable communications networks. North Korea should not be permitted to conduct an atmospheric nuclear tests since EMP effects on large networks necessary for electric power and international data sharing could have serious worldwide consequences due to the importance of Asia and the Pacific region to the global economy. In the regrettable event that North Korea chooses to conduct atmospheric nuclear tests, U.S. and allied monitoring of EMP effects will be helpful

    Tower and Aircraft Eddy Covariance Measurements of Water Vapor, Energy, and Carbon Dioxide Fluxes during SMACEX

    Get PDF
    Abstract A network of eddy covariance (EC) and micrometeorological flux (METFLUX) stations over corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] canopies was established as part of the Soil Moisture–Atmosphere Coupling Experiment (SMACEX) in central Iowa during the summer of 2002 to measure fluxes of heat, water vapor, and carbon dioxide (CO2) during the growing season. Additionally, EC measurements of water vapor and CO2 fluxes from an aircraft platform complemented the tower-based measurements. Sensible heat, water vapor, and CO2 fluxes showed the greatest spatial and temporal variability during the early crop growth stage. Differences in all of the energy balance components were detectable between corn and soybean as well as within similar crops throughout the study period. Tower network–averaged fluxes of sensible heat, water vapor, and CO2 were observed to be in good agreement with area-averaged aircraft flux measurements

    Effect of pH and dissolved organic matter on the photochemical fate of acetamiprid

    Get PDF
    Trabalho apresentado em 9th European Conference on Pesticides and Related Organic Micropolluants in the Environment, 4-7 de outubro 2016, Santiago de Compostela, EspanhaIn this study the effect of pH and dissolved organic matter (DOM) on the photodegradation rate of acetamiprid (ACT) was studied. Observed photodegradation rate constants in the range of 0.0010 – 0.0026 h-1 and 24 – 36 h-1 were obtained using a solar simulator (290-800 nm) and a medium pressure mercury (MP Hg) lamp, respectively. In both experiments an increase in pH from 5 to 9 did not significantly change the photodegradation rate constant of ACT. A different behaviour was found for ACT degradation in the presence of DOM. When samples were irradiated with MP Hg lamp the observed photodegradation rate constant of ACT decreased with an increase of DOM concentration.N/

    Surface Production Fuels Deep Heterotrophic Respiration in Northern Peatlands

    Get PDF
    Multiple analyses of dissolved organic carbon (DOC) from pore waters were conducted to define the processes that govern carbon balance in peatlands: (1) source, reactivity, and transport of DOC with respect to vegetation, peat, and age of carbon substrate, (2) reactivity of DOC with respect to molecular size, and (3) lability to photoxidation of surficial DOC. We found that surface organic production fuels heterotrophic respiration at depth in advection-dominated peatlands, especially in fens. Fen DOC was Δ14Cenriched relative to the surrounding fen peat, and fen respiration products were similar to this enriched DOC indicating that DOC was the main microbial substrate. Bog DOC was more variable showing either enrichment in Δ14C at depth or Δ14C values that follow peat values. This variability in bogs is probably controlled by the relative importance of vertical transport of labile carbon substrates within the peat profile versus DOC production from bog peat. These results extended our set of observations to 10 years at one bog-fen pair and add two additional bog-fen pairs to our series of observations. Anaerobic incubations of peat, rinsed free of residual DOC, produced DOC and respiration products that were strikingly similar to the peat values in a bog and two fens. This result demonstrated conclusively that downward advection is the process responsible for the presence of modern DOC found at depth in the peat column. Fen DOC has lower C/N values and up to twice as much LMW (kDa) DOC as bogs due to differences in organic inputs and greater microbial processing. Fluorescence irradiation experiments showed that fen DOC is more photolabile than bog DOC

    Relationship Between Foveal Cone Specialization and Pit Morphology in Albinism

    Get PDF
    Purpose.Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. Methods. We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. Results. We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. Conclusions. Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue

    Pattern and Outcome of Chest Injuries at Bugando Medical Centre in Northwestern Tanzania.

    Get PDF
    Chest injuries constitute a continuing challenge to the trauma or general surgeon practicing in developing countries. This study was conducted to outline the etiological spectrum, injury patterns and short term outcome of these injuries in our setting. This was a prospective study involving chest injury patients admitted to Bugando Medical Centre over a six-month period from November 2009 to April 2010 inclusive. A total of 150 chest injury patients were studied. Males outnumbered females by a ratio of 3.8:1. Their ages ranged from 1 to 80 years (mean = 32.17 years). The majority of patients (72.7%) sustained blunt injuries. Road traffic crush was the most common cause of injuries affecting 50.7% of patients. Chest wall wounds, hemothorax and rib fractures were the most common type of injuries accounting for 30.0%, 21.3% and 20.7% respectively. Associated injuries were noted in 56.0% of patients and head/neck (33.3%) and musculoskeletal regions (26.7%) were commonly affected. The majority of patients (55.3%) were treated successfully with non-operative approach. Underwater seal drainage was performed in 39 patients (19.3%). One patient (0.7%) underwent thoracotomy due to hemopericardium. Thirty nine patients (26.0%) had complications of which wound sepsis (14.7%) and complications of long bone fractures (12.0%) were the most common complications. The mean LOS was 13.17 days and mortality rate was 3.3%. Using multivariate logistic regression analysis, associated injuries, the type of injury, trauma scores (ISS, RTS and PTS) were found to be significant predictors of the LOS (P < 0.001), whereas mortality was significantly associated with pre-morbid illness, associated injuries, trauma scores (ISS, RTS and PTS), the need for ICU admission and the presence of complications (P < 0.001). Chest injuries resulting from RTCs remain a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of RTCs is necessary to reduce the incidence of chest injuries in this region

    Transient Photoreceptor Deconstruction by CNTF Enhances rAAV-Mediated Cone Functional Rescue in Late Stage CNGB3-Achromatopsia

    Get PDF
    Achromatopsia is a genetic disorder of cones, and one of the most common forms is a channelopathy caused by mutations in the β-subunit, CNGB3, of the cone cyclic nucleotide-gated (CNG) channel. Recombinant adeno-associated virus of serotype 5 (rAAV5)-mediated gene transfer of human CNGB3 cDNA to mutant dog cones results in functional and structural rescue in dogs \u3c0.5 years of age, but treatment is minimally effective in dogs \u3e1 year. We now test a new therapeutic concept by combining gene therapy with the administration of ciliary neurotrophic factor (CNTF). Intravitreal CNTF causes transient dedifferentiation of photoreceptors, a process called deconstruction, whereby visual cells become immature with short outer segments, and decreased retinal function and gene expression that subsequently return to normal. Cone function was successfully rescued in all mutant dogs treated between 14 and 42 months of age with this strategy. CNTF-mediated deconstruction and regeneration of the photoreceptor outer segments prepares the mutant cones optimally for gene augmentation therapy
    corecore