Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion

Objective Neurotrophin‐3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move toward the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke. Methods Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically feasible time to treatment, 24 hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for 4 weeks using implanted catheters and minipumps. Results Radiolabeled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. Functional magnetic resonance imaging during stimulation of the affected wrist showed spontaneous recovery of peri‐infarct blood oxygenation level–dependent signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways. Interpretation Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke

A multi-purpose, multi-rotor drone system for long-range and high-altitude volcanic gas plume measurements

A multi-rotor drone has been adapted for studies of volcanic gas plumes. This adaptation includes improved capacity for high-altitude and long-range, real-time SO2 concentration monitoring, long-range manual control, remotely activated bag sampling and plume speed measurement capability. The drone is capable of acting as a stable platform for various instrument configurations, including multi-component gas analysis system (MultiGAS) instruments for in situ measurements of SO2, H2S, and CO2 concentrations in the gas plume and portable differential optical absorption spectrometer (MobileDOAS) instruments for spectroscopic measurement of total SO2 emission rate, remotely controlled gas sampling in bags and sampling with gas denuders for posterior analysis on the ground of isotopic composition and halogens. The platform we present was field-tested during three campaigns in Papua New Guinea: in 2016 at Tavurvur, Bagana and Ulawun volcanoes, in 2018 at Tavurvur and Langila volcanoes and in 2019 at Tavurvur and Manam volcanoes, as well as in Mt. Etna in Italy in 2017. This paper describes the drone platform and the multiple payloads, the various measurement strategies and an algorithm to correct for different response times of MultiGAS sensors. Specifically, we emphasize the need for an adaptive flight path, together with live data transmission of a plume tracer (such as SO2 concentration) to the ground station, to ensure optimal plume interception when operating beyond the visual line of sight. We present results from a comprehensive plume characterization obtained during a field deployment at Manam volcano in May 2019. The Papua New Guinea region, and particularly Manam volcano, has not been extensively studied for volcanic gases due to its remote location, inaccessible summit region and high level of volcanic activity. We demonstrate that the combination of a multi-rotor drone with modular payloads is a versatile solution to obtain the flux and composition of volcanic plumes, even for the case of a highly active volcano with a high-altitude plume such as Manam. Drone-based measurements offer a valuable solution to volcano research and monitoring applications and provide an alternativespan idCombining double low line"page4256"/> and complementary method to ground-based and direct sampling of volcanic gases

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure

A Novel Porcine In Vitro Model of the Blood-Cerebrospinal Fluid Barrier with Strong Barrier Function

Epithelial cells of the plexus choroideus form the structural basis of the blood-cerebrospinal fluid barrier (BCSFB). In vitro models of the BCSFB presenting characteristics of a functional barrier are of significant scientific interest as tools for examination of BCSFB function. Due to a lack of suitable cell lines as in vitro models, primary porcine plexus epithelial cells were subjected to a series of selective cultivation steps until a stable continuous subcultivatable epithelial cell line (PCP-R) was established. PCP-R cells grow in a regular polygonal pattern with a doubling time of 28–36 h. At a cell number of 1.5×105 in a 24-well plate confluence is reached in 56–72 h. Cells are cytokeratin positive and chromosomal analysis revealed 56 chromosomes at peak (84th subculture). Employing reverse transcription PCR mRNA expression of several transporters and components of cell junctions could be detected. The latter includes tight junction components like Claudin-1 and -3, ZO-1, and Occludin, and the adherens junction protein E-cadherin. Cellular localization studies of ZO-1, Occludin and Claudin-1 by immunofluorescence and morphological analysis by electron microscopy demonstrated formation of a dense tight junction structure. Importantly, when grown on cell culture inserts PCP-R developed typical characteristics of a functional BCSFB including high transepithelial electrical resistance above 600 Ω×cm2 as well as low permeability for macromolecules. In summary, our data suggest the PCP-R cell line as a suitable in vitro model of the porcine BCSFB

Measurements of the Electric Form Factor of the Neutron up to Q2=3.4 GeV2 using the Reaction He3(e,e'n)pp

The electric form factor of the neutron was determined from studies of the reaction He3(e,e'n)pp in quasi-elastic kinematics in Hall A at Jefferson Lab. Longitudinally polarized electrons were scattered off a polarized target in which the nuclear polarization was oriented perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons that were registered in a large-solid-angle detector. More than doubling the Q2-range over which it is known, we find GEn = 0.0225 +/- 0.0017 (stat) +/- 0.0024 (syst), 0.0200 +/- 0.0023 +/- 0.0018, and 0.0142 +/- 0.0019 +/- 0.0013 for Q2 = 1.72, 2.48, and 3.41 GeV2, respectively.Comment: submitted to PR

Dental Microwear and Diet of the Plio-Pleistocene Hominin Paranthropus boisei

The Plio-Pleistocene hominin Paranthropus boisei had enormous, flat, thickly enameled cheek teeth, a robust cranium and mandible, and inferred massive, powerful chewing muscles. This specialized morphology, which earned P. boisei the nickname “Nutcracker Man”, suggests that this hominin could have consumed very mechanically challenging foods. It has been recently argued, however, that specialized hominin morphology may indicate adaptations for the consumption of occasional fallback foods rather than preferred resources. Dental microwear offers a potential means by which to test this hypothesis in that it reflects actual use rather than genetic adaptation. High microwear surface texture complexity and anisotropy in extant primates can be associated with the consumption of exceptionally hard and tough foods respectively. Here we present the first quantitative analysis of dental microwear for P. boisei. Seven specimens examined preserved unobscured antemortem molar microwear. These all show relatively low complexity and anisotropy values. This suggests that none of the individuals consumed especially hard or tough foods in the days before they died. The apparent discrepancy between microwear and functional anatomy is consistent with the idea that P. boisei presents a hominin example of Liem's Paradox, wherein a highly derived morphology need not reflect a specialized diet

Validation of HNO3, ClONO2, and N2O5 from the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS)

The Atmospheric Chemistry Experiment (ACE) satellite was launched on 12 August 2003. Its two instruments measure vertical profiles of over 30 atmospheric trace gases by analyzing solar occultation spectra in the ultraviolet/visible and infrared wavelength regions. The reservoir gases HNO3, ClONO2, and N2O5 are three of the key species provided by the primary instrument, the ACE Fourier Transform Spectrometer (ACE-FTS). This paper describes the ACE-FTS version 2.2 data products, including the N2O5 update, for the three species and presents validation comparisons with available observations. We have compared volume mixing ratio (VMR) profiles of HNO3, ClONO2, and N2O5 with measurements by other satellite instruments (SMR, MLS, MIPAS), aircraft measurements (ASUR), and single balloon-flights (SPIRALE, FIRS-2). Partial columns of HNO3 and ClONO2 were also compared with measurements by ground-based Fourier Transform Infrared (FTIR) spectrometers. Overall the quality of the ACE-FTS v2.2 HNO3 VMR profiles is good from 18 to 35 km. For the statistical satellite comparisons, the mean absolute differences are generally within ±1 ppbv ±20%) from 18 to 35 km. For MIPAS and MLS comparisons only, mean relative differences lie within±10% between 10 and 36 km. ACE-FTS HNO3 partial columns (~15–30 km) show a slight negative bias of −1.3% relative to the ground-based FTIRs at latitudes ranging from 77.8° S–76.5° N. Good agreement between ACE-FTS ClONO2 and MIPAS, using the Institut für Meteorologie und Klimaforschung and Instituto de Astrofísica de Andalucía (IMK-IAA) data processor is seen. Mean absolute differences are typically within ±0.01 ppbv between 16 and 27 km and less than +0.09 ppbv between 27 and 34 km. The ClONO2 partial column comparisons show varying degrees of agreement, depending on the location and the quality of the FTIR measurements. Good agreement was found for the comparisons with the midlatitude Jungfraujoch partial columns for which the mean relative difference is 4.7%. ACE-FTS N2O5 has a low bias relative to MIPAS IMK-IAA, reaching −0.25 ppbv at the altitude of the N2O5 maximum (around 30 km). Mean absolute differences at lower altitudes (16–27 km) are typically −0.05 ppbv for MIPAS nighttime and ±0.02 ppbv for MIPAS daytime measurements