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ObjectiveThe goal of this study was to identify changes in extracellular vesicles (EV) surface proteins specific to traumatic brain injury (TBI), which could be used as a diagnostic and prognostic tool in polytrauma patients.Summary Background DataKnown serum TBI-specific biomarkers (S100B, NSE, and GFAP), which can predict the severity and outcome of isolated TBI, lose their predictive value in the presence of additional extracranial injuries. Extracellular vesicles (EVs) are released from cells in response to various stimuli and carry specific cargo/surface molecules that could be used for tracking injury-responding cells.MethodsEVs were isolated using size exclusion chromatography (SEC) from the plasma of two groups of patients (with isolated TBI, ISS≥16, AIShead≥4, n=10; and polytraumatized patients without TBI ISS≥16, AIShead=0, n=10) collected in the emergency room and 48 h after trauma. EVs’ surface epitope expression was investigated using a neurospecific multiplex flow cytometry assay and compared with healthy controls (n=10). Three enrichments of EV epitopes found to be specific to TBI were validated by western blot.ResultsThe expression of 10 EV epitopes differed significantly among the patient and control groups, and five of these epitopes (CD13, CD196, MOG, CD133, and MBP) were TBI-specific. The increased expression of CD196, CD13, and MOG-positive EVs was validated by western blot.ConclusionOur data showed that TBI is characterized by a significant increase of CD13, CD196, MOG, CD133, and MBP-positive EVs in patients’ plasma. A high level of MOG-positive EVs negatively correlated with the Glasgow Coma Scale score at admission and could be an indicator of poor neurological status.

Abstract The Popeye domain containing (POPDC) genes encode sarcolemma-localized cAMP effector proteins. Mutations in blood vessel epicardial substance (BVES) also known as POPDC1 and POPDC2 have been associated with limb-girdle muscular dystrophy and cardiac arrhythmia. Muscle biopsies of affected patients display impaired membrane trafficking of both POPDC isoforms. Biopsy material of patients carrying mutations in BVES were immunostained with POPDC antibodies. The interaction of POPDC proteins was investigated by co-precipitation, proximity ligation, bioluminescence resonance energy transfer and bimolecular fluorescence complementation. Site-directed mutagenesis was utilised to map the domains involved in protein–protein interaction. Patients carrying a novel homozygous variant, BVES (c.547G > T, p.V183F) displayed only a skeletal muscle pathology and a mild impairment of membrane trafficking of both POPDC isoforms. In contrast, variants such as BVES p.Q153X or POPDC2 p.W188X were associated with a greater impairment of membrane trafficking. Co-transfection analysis in HEK293 cells revealed that POPDC proteins interact with each other through a helix-helix interface located at the C-terminus of the Popeye domain. Site-directed mutagenesis of an array of ultra-conserved hydrophobic residues demonstrated that some of them are required for membrane trafficking of the POPDC1–POPDC2 complex. Mutations in POPDC proteins that cause an impairment in membrane localization affect POPDC complex formation while mutations which leave protein–protein interaction intact likely affect some other essential function of POPDC proteins.

Abstract Estimating absolute and relative abundance of wildlife populations is critical to addressing ecological questions and conservation needs, yet obtaining reliable estimates can be challenging because surveys are often limited spatially or temporally. Community science (i.e., citizen science) provides opportunities for semi-structured data collected by the public (e.g., eBird) to improve capacity of relative abundance estimation by complementing structured survey data collected by trained observers (e.g., North American breeding bird survey [BBS]). We developed two state-space models to estimate relative abundance and population trends: one using BBS data and the other jointly analyzing BBS and eBird data. We applied these models to seven bird species with diverse life history characteristics. Joint analysis of eBird and BBS data improved precision of mean and year-specific relative abundance estimates for all species, but the BBS-only model produced more precise trend estimates compared to the joint model for most species. The relative abundance estimates of the joint model were particularly more precise than the BBS-only estimates in areas where species detectability was low resulting from either low BBS survey effort or low abundance. These results suggest that community science data can be a valuable resource for cost-effective improvement in wildlife abundance estimation.

North American grassland birds have widely declined over the past 50 years, largely due to anthropogenic-driven loss of native prairie habitat. In response to these declines, many conservation programs have been implemented to help secure wildlife habitat on private and public lands. The Grasslands Coalition is one such initiative established to advance the conservation of grassland birds in Missouri. The Missouri Department of Conservation conducted annual point count surveys for comparison of grassland bird relative abundance between focal grassland areas and nearby paired (i.e., containing no targeted management) sites. We analyzed 17 years of point count data with a generalized linear mixed model in a Bayesian framework to estimate relative abundance and trends across focal or paired sites for nine bird species of management interest that rely on grasslands: barn swallow (Hirundo rustica), brown-headed cowbird (Molothrus ater), dickcissel (Spiza americana), eastern meadowlark (Sturnella magna), grasshopper sparrow (Ammodramus savannarum), Henslow’s sparrow (A. henslowii), horned lark (Eremophila alpestris), northern bobwhite (Colinus virginianus), and red-winged blackbird (Agelaius phoeniceus). Relative abundance of all species except eastern meadowlarks declined regionally. Relative abundance of barn swallows, brown-headed cowbirds, dickcissels, eastern meadowlarks, Henslow’s sparrows, and northern bobwhites was higher in focal than paired sites, though relative abundance trends were only improved in focal vs. paired areas for dickcissels and Henslow’s sparrows. Relative abundance increased with increasing grassland cover at the local (250-m radius) scale for all species except horned larks and red-winged blackbirds and at the landscape (2,500-m radius) scale for all species except dickcissels, eastern meadowlarks, and northern bobwhites. Our results suggest focal areas contained greater relative abundances of several grassland species of concern, likely due to increased availability of grassland habitat at local and landscape scales. Further efforts to decrease landscape-scale fragmentation and improve habitat quality may be needed to achieve conservation goals.

BackgroundTraumatic brain injury (TBI) after falls causes death and disability with immense socioeconomic impact through medical and rehabilitation costs in geriatric patients. Diagnosing TBI can be challenging due to the absence of initial clinical symptoms. Misdiagnosis is particularly dangerous in patients on permanent anticoagulation because minimal trauma might result in severe intracranial hemorrhage. The aim of this study is to evaluate the diagnostic necessity of cranial computed tomography (cCT) to rule out intracranial hemorrhage, particularly in the absence of neurologic symptoms in elderly patients on permanent anticoagulation in their premedication.Patients and methodsRetrospective cohort analysis of elderly trauma patients (≥ 65 years) admitted to the emergency department (ED) of the level-1-trauma center of the University Hospital Frankfurt from 01/2017 to 12/2019. The study included patients who suffered a ground-level fall with suspected TBI and subsequently underwent CT because of preexisting anticoagulation.ResultsA total of 227 patients met the inclusion criteria. In 17 of these patients, cCT showed intracranial hemorrhage, of which 14 were subdural hematomas (SDH). In 8 of the patients with bleeding showed no clinical symptoms, representing 5% (n = 160) of all symptom-free patients. Men and women were equally to suffer a post-traumatic hemorrhage. Patients with intracranial bleeding were hospitalized for 14.5 (±10.4) days. Acetylsalicylic acid (ASA) was the most prescribed anticoagulant in both patient cohorts—with or without intracerebral bleeding (70.6 vs. 77.1%, p = 0.539). Similarly, patients taking new oral anticoagulant (NOAC) (p = 0.748), coumarins, or other platelet inhibitors (p > 0.1) did not show an increased bleeding incidence.ConclusionAcetylsalicylic acid and NOAC use are not associated with increased bleeding risk in geriatric trauma patients (≥ 65 years) after fall-related TBI. Even in asymptomatic elderly patients on anticoagulation, intracranial hemorrhage occurs in a relevant proportion after minor trauma to the head. Therefore, cCT is an obligatory tool to rule out cerebral hemorrhage in elderly patients under anticoagulation.

Abstract Background Popeye domain-containing proteins 1 and 2 (POPDC1 and POPDC2) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction. In order to identify novel protein interaction partners, POPDC1 and 2 proteins were attached to beads and compared by proteomic analysis with control beads in the pull-down of proteins from cultured human skeletal myotubes. Results There were highly-significant interactions of both POPDC1 and POPDC2 with XIRP1 (Xin actin binding repeat-containing protein 1), actin and, to a lesser degree, annexin A5. In adult human skeletal muscle, both XIRP1 and POPDC1/2 were present at the sarcolemma and in T-tubules. The interaction of POPDC1 with XIRP1 was confirmed in adult rat heart extracts. Using new monoclonal antibodies specific for POPDC1 and POPDC2, both proteins, together with XIRP1, were found mainly at intercalated discs but also at T-tubules in adult rat and human heart. Conclusions Mutations in human POPDC1, POPDC2 and in human XIRP1, all cause pathological cardiac arrhythmias, suggesting a possible role for POPDC1/2 and XIRP1 interaction in normal cardiac conduction.

Abstract Loss and degradation of grasslands in the Great Plains region have resulted in major declines in abundance of grassland bird species. To ensure future viability of grassland bird populations, it is crucial to evaluate specific effects of environmental factors among species to determine drivers of population decline and develop effective conservation strategies. We used threshold models to quantify the effects of land cover and weather changes in "lesser prairie‐chicken" and "greater prairie‐chicken" (Tympanuchus pallidicinctus and T. cupido, respectively), northern bobwhites (Colinus virginianus), and ring‐necked pheasants (Phasianus colchicus). We demonstrated a novel approach for estimating landscape conditions needed to optimize abundance across multiple species at a variety of spatial scales. Abundance of all four species was highest following wet summers and dry winters. Prairie chicken and ring‐necked pheasant abundance was highest following cool winters, while northern bobwhite abundance was highest following warm winters. Greater prairie chicken and northern bobwhite abundance was also highest following cooler summers. Optimal abundance of each species occurred in landscapes that represented a grassland and cropland mosaic, though prairie chicken abundance was optimized in landscapes with more grassland and less edge habitat than northern bobwhites and ring‐necked pheasants. Because these effects differed among species, managing for an optimal landscape for multiple species may not be the optimal scenario for any one species.

3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.

A dramatic rise in arrest rates for girls over the past decade has led to an increasing interest in understanding gender differences in the risk factors that are associated with delinquency. Moreover, the call has been made for the implementation of gender-specific or gender-responsive interventions in order to effectively divert girls from an antisocial course. However, questions have been raised about three key assumptions underlying the gender-responsive approach to girls involved in the juvenile justice system: is there unequivocal evidence for gender-specificity in the risk factors that contribute to girls’ delinquency; is there clear evidence that existing non-gender-responsive evidence-based interventions for delinquency are less effective for girls than boys; and is there well-grounded evidence that interventions specifically tailored for girls are differentially effective? This article reviews the available research regarding each of these questions and proposes an agenda for future research into the development of effective interventions for juvenile justice-involved girls.