Congress authorized creation of the Extremity Trauma and Amputation Center of Excellence (EACE) as part of the 2009 National Defense Authorization Act. The legislation mandated the Department of ...Defense (DoD) and Department of Veterans Affairs (VA) to implement a comprehensive plan and strategy for the mitigation, treatment, and rehabilitation of traumatic extremity injuries and amputation. The EACE also was tasked with conducting clinically relevant research, fostering collaborations, and building partnerships across multidisciplinary international, federal, and academic networks to optimize the quality of life of service members and veterans who have sustained extremity trauma or amputations. To fulfill the mandate to conduct research, the EACE developed a Research and Surveillance Division that complements and collaborates with outstanding DoD, VA, and academic research programs across the globe. The EACE researchers have efforts in four key research focus areas relevant to extremity trauma and amputation: (1) Novel Rehabilitation Interventions, (2) Advanced Prosthetic and Orthotic Technologies, (3) Epidemiology and Surveillance, and (4) Medical and Surgical Innovations. This overview describes the EACE efforts to innovate, discover, and translate knowledge gleaned from collaborative research partnerships into clinical practice and policy.
Blood coagulation factor XI (FXI) is an established risk factor for acute ischemic stroke (AIS) and thrombosis, but is also needed for normal hemostasis. Contact factor XII (FXII), an upstream ...activator of FXI, also contributes to experimental stroke, but is not required for hemostasis. We investigated whether selectively inhibiting FXII-mediated FXI activation, while leaving other FXI and FXII functions intact, could improve the outcome of experimental AIS in mice. Twenty-four hours before induction of AIS by placement of a filament into the internal carotid artery for 60 min, mice were anticoagulated with an antibody directed against the apple 2 domain of FXI. This antibody selectively reduces the prothrombotic activation of FXI by FXIIa but does not affect activated FXI or hemostatic activation of FXI by thrombin, thus leaving hemostasis intact in mice and primates. In this model of AIS/reperfusion injury, mice that received the antibody before AIS displayed less ischemic damage, manifested as reduced cerebral infarction and fibrin deposition (thrombosis), increased cortical reperfusion, and improved neurological behavior. Further, the antibody-anticoagulated mice had no detectable hemostasis impairment. Consistent with the neuroprotective phenotype of FXII-deficient mice, our data suggest that a single molecular event, FXII-mediated FXI activation, contributes to the development of experimental AIS.
Reported here are original data related to the article “Indigenous knowledge and stand characteristics of a threatened tree species in a highly insecure area: Chilgoza pine in Afghanistan” (Shalizi ...et al., 2018) 1. A dendrochronological summary of all known chilgoza pine tree growth increment cores collected in Afghanistan is presented in this data in brief article. Chilgoza pine trees and regeneration density profiles are reported for four provinces of eastern Afghanistan. In addition, images depicting chilgoza pine forest structure, stand conditions, and utilization impacts are presented.
In Britain, the population of native red squirrels Sciurus vulgaris has suffered population declines and local extinctions. Interspecific resource competition and disease spread by the invasive gray ...squirrel Sciurus carolinensis are the main factors behind the decline. Gray squirrels have adapted to the British landscape so efficiently that they are widely distributed. Knowledge on how gray squirrels are using the landscape matrix and being able to predict their movements will aid management. This study is the first to use global positioning system (GPS) collars on wild gray squirrels to accurately record movements and land cover use within the landscape matrix. This data were used to validate Geographical Information System (GIS) least‐cost model predictions of movements and provided much needed information on gray squirrel movement pathways and network use. Buffered least‐cost paths and least‐cost corridors provide predictions of the most probable movements through the landscape and are seen to perform better than the more expansive least‐cost networks which include all possible movements. Applying the knowledge and methodologies gained to current gray squirrel expansion areas, such as Scotland and in Italy, will aid in the prediction of potential movement areas and therefore management of the invasive gray squirrel. The methodologies presented in this study could potentially be used in any landscape and on numerous species.
Global positioning system (GPS) telemetry and least‐cost modelling were used to assess the detailed inter‐patch movements of a small mammal across the landscape. This is the first study to use GPS on grey squirrels to record highly detailed movements and landscape use.
Searching for indicator taxa representative of diverse assemblages, such as arthropods, is an important objective of many conservation studies. We evaluated the impacts of a wide gradient of ...disturbance in Gabon on a range of arthropod assemblages representing different feeding guilds. We examined 4 x 10⁵ arthropod individuals from which 21 focal taxa were separated into 1534 morphospecies. Replication included the understory of 3 sites in each of 4 different stages of forest succession and land use (i.e., habitats) after logging (old and young forests, savanna, and gardens). We used 3 complementary sampling methods to survey sites throughout the year. Overall differences in arthropod abundance and diversity were greatest between forest and open habitats, and cleared forest invaded by savanna had the lowest abundance and diversity. The magnitude of faunal differences was much smaller between old and young forests. When considered at this local scale, anthropogenic modification of habitats did not result in a monotonous decline of diversity because many herbivore pests and their associated predators and parasitoids were abundant and diverse in gardens, where plant productivity was kept artificially high year-round through watering and crop rotation. We used a variety of response variables to measure the strength of correlations across survey locations among focal taxa. These could be ranked as follows in terms of decreasing number of significant correlations: species turnover > abundance > observed species richness > estimated species richness > percentage of site-specific species. The number of significant correlations was generally low and apparently unrelated to taxonomy or guild structure. Our results emphasize the value of reporting species turnover in conservation studies, as opposed to simply measuring species richness, and that the search for indicator taxa is elusive in the tropics. One promising alternative might be to consider "predictor sets" of a small number of taxa representative of different functional groups, as identified in our study.
The fused-type S100 protein profilaggrin and its proteolytic products including filaggrin are important in the formation of a normal epidermal barrier; however, the specific function of the S100 ...calcium-binding domain in profilaggrin biology is poorly understood. To explore its molecular function, we determined a 2.2Å-resolution crystal structure of the N-terminal fused-type S100 domain of human profilaggrin with bound calcium ions. The profilaggrin S100 domain formed a stable dimer, which contained two hydrophobic pockets that provide a molecular interface for protein interactions. Biochemical and molecular approaches demonstrated that three proteins, annexin II/p36, stratifin/14-3-3 sigma, and heat shock protein 27, bind to the N-terminal domain of human profilaggrin; one protein (stratifin) co-localized with profilaggrin in the differentiating granular cell layer of human skin. Together, these findings suggest a model where the profilaggrin N-terminus uses calcium-dependent and calcium-independent protein–protein interactions to regulate its involvement in keratinocyte terminal differentiation and incorporation into the cornified cell envelope.
Abstract The contribution of voltage-gated calcium channels to excitable cell function depends, critically, upon the mechanisms that control their expression at the cell surface. While co-assembly of ...the pore forming α1 and auxiliary β subunits enhances channel surface expression, the levels are still only 30–40% of those seen with the core α1B /β1b /α2 δ calcium channel complex. To rationalize this observation, it has been suggested that the α2 /δ subunit might stabilize calcium channel expression at the cell surface. To test this notion, we have resolved the effect of the α2 /δ subunit on the rates of binding, internalization and degradation of defined N-type calcium channel surface complexes expressed in HEK293 cells, through pulse-labeling with the selective, cell impermeable, radioligand 125 I-ω-CgTx. Through detailed kinetic and sensitivity analysis we show that α1B /β1b /α2 δ complexes are internalized slowly ( kint 0.4/h), whereupon, most become degraded ( kdeg 0.02/h). In contrast, α1B /β1b complexes are internalized more rapidly ( kint 0.8/h), following which they are either quickly degraded ( kdeg 0.1/h) or are sequestered slowly ( ktra 0.1/h) to a pool that is metabolically stable within the time-frame of our experiments (24 h). In neither case did we find evidence for recycling via the cell surface. Thus, our data argue for a novel mechanism where complexes lacking an α2 /δ subunit are cleared from the cell surface and are rapidly degraded or stored, possibly for further attempts at complexation as new α2 /δ subunits become available. The slower rate of internalization of complexes containing the α2 /δ subunit rationalizes the stabilizing effect this subunit has upon calcium channel surface expression and suggests a mechanism by which α2 δ mutations may cause severe neurological deficits.
Progressive disease is common following anal sacculectomy for apocrine gland anal sac adenocarcinoma (AGASACA); additional therapy may prolong survival. Adherence to medical recommendations ...influences therapeutic success in humans. The purpose of this study was to assess the adherence to follow‐up recommendations in dogs with AGASACA. Medical records of patients that underwent anal sacculectomy for AGASACA, with or without iliosacral lymphadenectomy, between July 2015 and July 2018, were reviewed at eight referral institutions to assess post‐operative recommendations and owner adherence to recommendations. One hundred and seventy‐four dogs were included, of which 162 underwent unilateral anal sacculectomy, 12 underwent bilateral anal sacculectomy and 39 underwent concurrent iliosacral lymphadenectomy. Seventy‐six owners (44%) received recommendations for staging at the time of discharge, histopathology results or at the first follow‐up visit. One hundred and forty owners (80%) received recommendations for treatment following the initial surgery. Fifty of seventy‐six (66%) owners pursued at least one staging recommendation and 69 of 140 (49%) owners pursued some kind of adjuvant treatment recommendation. Overall, 16 of 76 (21%) were adherent to staging recommendations with 20 adherent for the first year following surgery (26%). Forty‐seven of 140 (34%) were adherent to treatment recommendations with 54 (39%) adherent for the first year. Owners that were adherent to restaging recommendations at 1 year following surgery were significantly more likely to pursue treatment for progressive disease (P = .014). Further work is required to assess owner motivation and evaluate strategies to improve adherence, given the potential impact on patient treatment.
Reaction of a digermyne with cyclooctatetraene (cot) gave two isomeric products. A Ge(II) inverse sandwich is formed as the kinetic product, which was a result of complete GeGe bond cleavage and the ...formation of a π-bound cot ring. This isomerized in solution at room temperature over a period of 5 days to give the thermodynamic product, a tetracyclic diene-digermane, in which a single-bonded GeGe moiety has inserted into a CC bond of the cot carbocycle. Kinetic studies afforded an activation enthalpy (ΔH ‡) and entropy (ΔS ‡) of 14.9 kcal mol−1 and −6.2 cal mol−1 K−1 respectively. Heating crystals of the thermodynamic product at ca. 120 °C cleanly regenerated the original inverse sandwich isomer.
We examined plasticity of the stress response among three populations of the white-crowned sparrow (Zonotrichia leucophrys). These populations breed at different elevations and latitudes and thus ...have breeding seasons that differ markedly in length. We hypothesize that in populations where birds raise only one or rarely two broods in a season, the fitness costs of abandoning a nest are substantially larger than in closely related populations that raise up to three broods per season. Thus individuals with short breeding seasons should be less responsive to stressors and therefore less likely to abandon their young. In our study, baseline and handling-induced corticosterone levels were similar among populations, but corticosteroid-binding globulins differed, leading to a direct relationship between stress-induced free corticosteroid levels and length of breeding season. There were also population-specific differences in intracellular low-affinity (glucocorticoid-like) receptors in both liver and brain tissue. Although investigations of population-based differences in glucocorticoid secretion are common, this is the first study to demonstrate population-level differences in binding globulins. These differences could lead to dramatically different physiological and behavioral responses to stress.
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