Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility

Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1). Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia. Transient overexpression of GFP–Tmod3 leads to a depolarized cell morphology and decreased cell motility. A fivefold increase in Tmod3 results in an equivalent decrease in free pointed ends in the cells. Unexpectedly, a decrease in the relative amounts of F-actin, free barbed ends, and actin-related protein 2/3 (Arp2/3) complex in lamellipodia are also observed. Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments. These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia

Instabilities in fixed bed reactors with downwards directed flow for the oligomerization of 1-butene

In this work instabilities in fixed bed reactors with downwards directed flows for the oligomerization of 1-butene were investigated. For very long residence times or very low velocities in combination with strong exothermic reactions, the buoyancy force can exceed the inertia force and the downwards directed liquid flow in the fixed bed becomes instable. These flow conditions might result in hotspots, the shift of the conversion towards unwanted by-products or even in a runaway of the reactor. Therefore, the detailed understanding of the transition between stable and instable flow conditions in fixed bed reactors is essential for a safe and reliable operation of the reactor. Various simulation methods and correlations were applied to predict instable conditions that were observed in an experimental setup. 3D CFD simulations could be used to predict instable flow conditions in fixed bed reactors

An Ecosystem-Scale Model for the Spread of a Host-Specific Forest Pathogen in the Greater Yellowstone Ecosystem

The introduction of nonnative pathogens is altering the scale, magnitude, and persistence of forest disturbance regimes in the western United States. In the high-altitude whitebark pine (Pinus albicaulis) forests of the Greater Yellowstone Ecosystem (GYE), white pine blister rust (Cronartium ribicola) is an introduced fungal pathogen that is now the principal cause of tree mortality in many locations. Although blister rust eradication has failed in the past, there is nonetheless substantial interest in monitoring the disease and its rate of progression in order to predict the future impact of forest disturbances within this critical ecosystem. This study integrates data from five different field-monitoring campaigns from 1968 to 2008 to create a blister rust infection model for sites located throughout the GYE. Our model parameterizes the past rates of blister rust spread in order to project its future impact on high-altitude whitebark pine forests. Because the process of blister rust infection and mortality of individuals occurs over the time frame of many years, the model in this paper operates on a yearly time step and defines a series of whitebark pine infection classes: susceptible, slightly infected, moderately infected, and dead. In our analysis, we evaluate four different infection models that compare local vs. global density dependence on the dynamics of blister rust infection. We compare models in which blister rust infection is: (1) independent of the density of infected trees, (2) locally density-dependent, (3) locally density-dependent with a static global infection rate among all sites, and (4) both locally and globally density-dependent. Model evaluation through the predictive loss criterion for Bayesian analysis supports the model that is both locally and globally density-dependent. Using this best-fit model, we predicted the average residence times for the four stages of blister rust infection in our model, and we found that, on average, whitebark pine trees within the GYE remain susceptible for 6.7 years, take 10.9 years to transition from slightly infected to moderately infected, and take 9.4 years to transition from moderately infected to dead. Using our best-fit model, we project the future levels of blister rust infestation in the GYE at critical sites over the next 20 years

Temporal Controls on Dissolved Organic Matter and Lignin Biogeochemistry in a Pristine Tropical River, Democratic Republic of Congo

Dissolved organic carbon (DOC), lignin biomarkers, and the optical properties of dissolved organic matter (DOM) were measured in the Epulu River (northeast Democratic Republic of Congo) with the aim of investigating temporal controls on the quantity and chemical composition of DOM in a tropical rainforest river. Three different periods defined by stages of the hydrologic regime of the region, (1) post dry flushing period, (2) intermediary period, and (3) start of the dry period/post flush, were sampled. Temporal variability in DOM quantity and quality was observed with highest DOC, lignin concentration (Σ8) and carbon‐normalized (Λ8) values during the flushing period attributed to greater surface runoff and leaching of organic‐rich horizons, with lowest values in the dry period/post flush once source materials were well leached. Chromophoric DOM (CDOM) was strongly correlated to DOC and Σ8 (r2 = 0.85 and 0.83, respectively; p \u3c 0.001), and CDOM quality measurements (SUVA254, spectral slope ratio and fluorescence index) were strongly correlated to Λ8 values (r2 = 0.77, 0.69, and 0.75, respectively; p \u3c 0.001), demonstrating the ability to derive DOC and lignin export and to track DOM quality in tropical riverine systems from simple optical measurements. This study demonstrates similar effects in the variability of DOM quantity and quality due to changing hydrologic inputs for a tropical river as has been previously reported for temperate and northern high‐latitude rivers. Therefore, flushing periods in tropical rivers warrant further study, as they are critical toward understanding ecosystem biogeochemistry as maximal export of freshly leached plant material occurs during this time period

Determination of the effective dose of a novel oral formulation of sarolaner (Simparica™) for the treatment and month-long control of fleas and ticks on dogs

AbstractThree laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.5 or 5.0mg/kg, and infested with Dermacentor reticulatus, Rhipicephalus sanguineus ticks and with Ctenocephalides felis felis (cat flea) prior to treatment and then weekly for up to 8 weeks. Fleas and ticks were counted 48h after treatment and after each subsequent infestation at 24h for fleas and 48h for ticks. The lowest dose of sarolaner (1.25mg/kg) provided 100% efficacy against fleas from treatment through Day 35 and 98.4% at Day 56. This dose of sarolaner resulted in 99.7–100% control of both species of ticks through Day 28. In Study 2, dogs were dosed orally with placebo or sarolaner suspension formulations at 0.625, 1.25 or 2.5mg/kg and infested with Ixodes scapularis prior to treatment and weekly for 6 weeks, Amblyomma americanum (pretreatment and Day 26), Dermacentor variabilis (Day 33) and A. maculatum (Day 41). Ixodes scapularis was the most susceptible; the lowest dose (0.625mg/kg) providing>95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was>95% at 1.25 and 2.5mg/kg, whereas the 0.625mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25mg/kg dose at Day 28 for A. americanum was markedly lower (88.5%) than achieved for D. reticulatus (100%) at Day 28 and also lower than for D. variabilis at Day 35 (96.2%). In Study 3, dogs were dosed orally with placebo or sarolaner in the proposed commercial tablet (Simparica™) at 1.0, 2.0 or 4.0mg/kg, and infested with A. maculatum, one of the ticks determined to be dose limiting, prior to treatment and then weekly for 5 weeks. All doses gave 100% control of the existing infestation. The two highest dosages resulted in >93% control of subsequent challenges for 5 weeks. There was no significant improvement in efficacy provided by the 4.0 mg/kg dose over the 2.0mg/kg dose (P>0.05) at any time point. The 2.0mg/kg dose was superior to the 1.0mg/kg on Day 14 (P=0.0086) and as efficacy for 1.0mg/kg declined below 90% at Day 28, a single 1mg/kg dose would not provide a full month of tick control. Thus, 2.0mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment

Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs

AbstractThe efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei. One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate® spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed.In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n=6) and those subsequently enrolled (n=14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study.In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study.Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations

The biogeochemistry of carbon across a gradient of streams and rivers within the Congo Basin

Author Posting. © American Geophysical Union, 2014. 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: Biogeosciences 119 (2014): 687–702, doi:10.1002/2013JG002442.Dissolved organic carbon (DOC) and inorganic carbon (DIC, pCO2), lignin biomarkers, and theoptical properties of dissolved organic matter (DOM) were measured in a gradient of streams and rivers within the Congo Basin, with the aim of examining how vegetation cover and hydrology influences the composition and concentration of fluvial carbon (C). Three sampling campaigns (February 2010, November 2010, and August 2011) spanning 56 sites are compared by subbasin watershed land cover type (savannah, tropical forest, and swamp) and hydrologic regime (high, intermediate, and low). Land cover properties predominately controlled the amount and quality of DOC, chromophoric DOM (CDOM) and lignin phenol concentrations (∑8) exported in streams and rivers throughout the Congo Basin. Higher DIC concentrations and changing DOM composition (lower molecular weight, less aromatic C) during periods of low hydrologic flow indicated shifting rapid overland supply pathways in wet conditions to deeper groundwater inputs during drier periods. Lower DOC concentrations in forest and swamp subbasins were apparent with increasing catchment area, indicating enhanced DOC loss with extended water residence time. Surface water pCO2 in savannah and tropical forest catchments ranged between 2,600 and 11,922 µatm, with swamp regions exhibiting extremely high pCO2 (10,598–15,802 µatm), highlighting their potential as significant pathways for water-air efflux. Our data suggest that the quantity and quality of DOM exported to streams and rivers are largely driven by terrestrial ecosystem structure and that anthropogenic land use or climate change may impact fluvial C composition and reactivity, with ramifications for regional C budgets and future climate scenarios.This work was supported by the National Science Foundation as part of the ETBC Collaborative Research: Controls on the Flux, Age, and Composition of Terrestrial Organic Carbon Exported by Rivers to the Ocean (0851101 and 0851015).2014-10-3

The pulse of the Amazon: fluxes of dissolved organic carbon, nutrients, and ions from the world's largest river

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 35(4), (2021): e2020GB006895, https://doi.org/10.1029/2020GB006895.The Amazon River drains a diverse tropical landscape greater than 6 million km2, culminating in the world's largest export of freshwater and dissolved constituents to the ocean. Here, we present dissolved organic carbon (DOC), organic and inorganic nitrogen (DON, DIN), orthophosphate (PO43−), and major and trace ion concentrations and fluxes from the Amazon River using 26 samples collected over three annual hydrographs. Concentrations and fluxes were predominantly controlled by the annual wet season flood pulse. Average DOC, DON, DIN, and PO43− fluxes (±1 s.d.) were 25.5 (±1.0), 1.14 (±0.05), 0.82 (±0.03), and 0.063 (±0.003) Tg yr−1, respectively. Chromophoric dissolved organic matter absorption (at 350 nm) was strongly correlated with DOC concentrations, resulting in a flux of 74.8 × 106 m−2 yr−1. DOC and DON concentrations positively correlated with discharge while nitrate + nitrite concentrations negatively correlated, suggesting mobilization and dilution responses, respectively. Ammonium, PO43−, and silica concentrations displayed chemostatic responses to discharge. Major and trace ion concentrations displayed clockwise hysteresis (except for chloride, sodium, and rubidium) and exhibited either dilution or chemostatic responses. The sources of weathered cations also displayed seasonality, with the highest proportion of carbonate- and silicate-derived cations occurring during peak and baseflow, respectively. Finally, our seasonally resolved weathering model resulted in an average CO2 consumption yield of (3.55 ± 0.11) × 105 mol CO2 km−2 yr−1. These results represent an updated and temporally refined quantification of dissolved fluxes that highlight the strong seasonality of export from the world's largest river and set a robust baseline against which to gauge future change.This work was supported by a grant from the Harbourton Foundation to R. G. M. Spencer and R. M. Holmes. T. W. Drake was supported by ETH Zurich core funding to J. Six. R. G. M. Spencer was additionally supported by NSF OCE-1333157.2021-09-1

Photochemical Degradation of Dissolved Organic Matter and Dissolved Lignin Phenols from the Congo River

Photochemical degradation of Congo River dissolved organic matter (DOM) was investigated to examine the fate of terrigenous DOM derived from tropical ecosystems. Tropical riverine DOM receives greater exposure to solar radiation, particularly in large river plumes discharging directly into the open ocean. Initial Congo River DOM exhibited dissolved organic carbon (DOC) concentration and compositional characteristics typical of organic rich blackwater systems. During a 57 day irradiation experiment, Congo River DOM was shown to be highly photoreactive with a decrease in DOC, chromophoric DOM (CDOM), lignin phenol concentrations (Σ8) and carbon-normalized yields (Λ8), equivalent to losses of ~45, 85–95, \u3e95 and \u3e95% of initial values, respectively, and a +3.1 % enrichment of the δ13C-DOC signature. The loss of Λ8 and enrichment of δ13C-DOC during irradiation was strongly correlated (r = 0.99, p \u3c 0.01) indicating tight coupling between these biomarkers. Furthermore, the loss of CDOM absorbance was correlated to the loss of Λ8 (e.g., a355 versus Λ8; r = 0.98, p \u3c 0.01) and δ13C-DOC (e.g., a355 versus δ13C; r = 0.97, p \u3c 0.01), highlighting the potential of CDOM absorbance measurements for delineating the photochemical degradation of lignin and thus terrigenous DOM. It is apparent that these commonly used measurements for examination of terrigenous DOM in the oceans have a higher rate of photochemical decay than the bulk DOC pool. Further process-based studies are required to determine the selective removal rates of these biomarkers for advancement of our understanding of the fate of this material in the ocean