SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury

Diffuse axonal injury (DAI) is a common feature of severe traumatic brain injury (TBI) and may also be a predominant pathology in mild TBI or “concussion”. The rapid deformation of white matter at the instant of trauma can lead to mechanical failure and calcium-dependent proteolysis of the axonal cytoskeleton in association with axonal transport interruption. Recently, a proteolytic fragment of alpha-II spectrin, “SNTF”, was detected in serum acutely following mild TBI in patients and was prognostic for poor clinical outcome. However, direct evidence that this fragment is a marker of DAI has yet to be demonstrated in either humans following TBI or in models of mild TBI. Here, we used immunohistochemistry (IHC) to examine for SNTF in brain tissue following both severe and mild TBI. Human severe TBI cases (survival <7d; n = 18) were compared to age-matched controls (n = 16) from the Glasgow TBI archive. We also examined brains from an established model of mild TBI at 6, 48 and 72 h post-injury versus shams. IHC specific for SNTF was compared to that of amyloid precursor protein (APP), the current standard for DAI diagnosis, and other known markers of axonal pathology including non-phosphorylated neurofilament-H (SMI-32), neurofilament-68 (NF-68) and compacted neurofilament-medium (RMO-14) using double and triple immunofluorescent labeling. Supporting its use as a biomarker of DAI, SNTF immunoreactive axons were observed at all time points following both human severe TBI and in the model of mild TBI. Interestingly, SNTF revealed a subpopulation of degenerating axons, undetected by the gold-standard marker of transport interruption, APP. While there was greater axonal co-localization between SNTF and APP after severe TBI in humans, a subset of SNTF positive axons displayed no APP accumulation. Notably, some co-localization was observed between SNTF and the less abundant neurofilament subtype markers. Other SNTF positive axons, however, did not co-localize with any other markers. Similarly, RMO-14 and NF-68 positive axonal pathology existed independent of SNTF and APP. These data demonstrate that multiple pathological axonal phenotypes exist post-TBI and provide insight into a more comprehensive approach to the neuropathological assessment of DAI

Second-Hand Stress: Neurobiological Evidence for a Human Alarm Pheromone

Alarm pheromones are airborne chemical signals, released by an individual into the environment, which transmit warning of danger to conspecifics via olfaction. Using fMRI, we provide the first neurobiological evidence for a human alarm pheromone. Individuals showed activation of the amygdala in response to sweat produced by others during emotional stress, with exercise sweat as a control; behavioral data suggest facilitated evaluation of ambiguous threat

Spitzer observations of extragalactic H II regions - III. NGC 6822 and the hot star, H II region connection

Using the short-high module of the Infrared Spectrograph on the Spitzer Space Telescope, we have measured the [S IV] 10.51, [Ne II] 12.81, [Ne III] 15.56, and [S III] 18.71-micron emission lines in nine H II regions in the dwarf irregular galaxy NGC 6822. These lines arise from the dominant ionization states of the elements neon (Ne$^{++}$, Ne$^+$) and sulphur (S$^{3+}$, S$^{++}$), thereby allowing an analysis of the neon to sulphur abundance ratio as well as the ionic abundance ratios Ne$^+$/Ne$^{++}$ and S$^{3+}$/S$^{++}$. By extending our studies of H II regions in M83 and M33 to the lower metallicity NGC 6822, we increase the reliability of the estimated Ne/S ratio. We find that the Ne/S ratio appears to be fairly universal, with not much variation about the ratio found for NGC 6822: the median (average) Ne/S ratio equals 11.6 (12.2$\pm$0.8). This value is in contrast to Asplund et al.'s currently best estimated value for the Sun: Ne/S = 6.5. In addition, we continue to test the predicted ionizing spectral energy distributions (SEDs) from various stellar atmosphere models by comparing model nebulae computed with these SEDs as inputs to our observational data, changing just the stellar atmosphere model abundances. Here we employ a new grid of SEDs computed with different metallicities: Solar, 0.4 Solar, and 0.1 Solar. As expected, these changes to the SED show similar trends to those seen upon changing just the nebular gas metallicities in our plasma simulations: lower metallicity results in higher ionization. This trend agrees with the observations.Comment: 22 pages, 13 figures. To be published in MNRAS. reference added and typos fixed. arXiv admin note: text overlap with arXiv:0804.0828, which is paper II by Rubin et al. (2008

TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver

Background The development of hepatocellular carcinoma (HCC) is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR) 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN), with HCC formation depending amongst others on interleukin (IL) 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver. The aim of this study was to investigate DEN-induced liver injury in TLR4-deficient mice with biliary fibrosis. Methods ABCB4-deficient mice on the FVB/NJ genetic background were crossed to two distinct genetic backgrounds (TLR4-sufficient C3H/HeN and TLR4-deficient C3H/HeJ) for more than 10 generations. The two congenic knockout and the two corresponding wild-type mouse lines were treated with a single dose of DEN for 48 hours. Phenotypic differences were assessed by measuring hepatic collagen contents, inflammatory markers (ALT, CRP, IL6) as well as hepatic apoptosis (TUNEL) and proliferation (Ki67) rates. Results Hepatic collagen accumulation is significantly reduced in ABCB4-/-:TLR4-/-double-deficient mice. After DEN challenge, apoptosis, proliferation and inflammatory markers are decreased in TLR4-deficient in comparison to TLR4-sufficient mice. When combining ABCB4 and TLR4 deficiency with DEN treatment, hepatic IL6 expression and proliferation rates are lowest in fibrotic livers from the double-deficient line. Consistent with these effects, selective digestive tract decontamination in ABCB4-/- mice also led to reduced tumor size and number after DEN. Conclusion This study demonstrates that liver injury upon DEN challenge depends on pre-existing fibrosis and genetic background. The generation of ABCB4-/: TLR4-/- double-deficient mice illustrates that TLR4-deficiency protects against hepatic injury in a preclinical mouse model of chronic liver disease

Musculoskeletal asymmetry in football athletes: A product of limb function over time

Purpose Asymmetrical loading patterns are commonplace in football sports. Our aim was to examine the influence of training age and limb function on lower-body musculoskeletal morphology. Methods Fifty-five elite football athletes were stratified into less experienced (≤3 yr; n = 27) and more experienced (\u3e3 yr; n = 28) groups by training age. All athletes underwent whole-body dual-energy x-ray absorptiometry scans and lower-body peripheral quantitative computed tomography tibial scans on the kicking and support limbs. Results Significant interactions between training age and limb function were evident across all skeletal parameters (F16, 91 = 0.182, P = 0.031, Wilks Λ = 0.969). Asymmetries between limbs were significantly larger in the more experienced players than the less experienced players for tibial mass (P ≤ 0.044, d ≥ 0.50), total cross-sectional area (P ≤ 0.039, d ≥ 0.53), and stress-strain indices (P ≤ 0.050, d ≥ 0.42). No significant asymmetry was evident for total volumetric density. More experienced players also exhibited greater lower-body tibial mass (P ≤ 0.001, d ≥ 1.22), volumetric density (P ≤ 0.009, d ≥ 0.79), cross-sectional area (P ≤ 0.387, d ≥ 0.21), stress-strain indices (P ≤ 0.012, d ≥ 0.69), fracture loads (P ≤ 0.018, d ≥ 0.57), and muscle mass and cross-sectional area (P ≤ 0.016, d ≥ 0.68) than less experienced players. Conclusions Asymmetries were evident in athletes as a product of limb function over time. Chronic exposure to routine high-impact gravitational loads afforded to the support limb preferentially improved bone mass and structure (cross-sectional area and cortex thickness) as potent contributors to bone strength relative to the high-magnitude muscular loads predominantly afforded to the kicking limb. Copyright © 2016 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited

Assessment of a novel algorithm to determine change-of-direction angles while running using inertial sensors

The ability to detect and quantify change-of-direction (COD) movement may offer a unique approach to load-monitoring practice. Validity and reliability of a novel algorithm to calculate COD angles for predetermined COD movements ranging from 45 to 180° in left and right directions was assessed. Five recreationally active men (age: 29.0 ± 0.5 years; height: 181.0 ± 5.6 cm; and body mass: 79.4 ± 5.3 kg) ran 5 consecutive predetermined COD trials each, at 4 different angles (45, 90, 135, and 180°), in each direction. Participants were fitted with a commercially available microtechnology unit where inertial sensor data were extracted and processed using a novel algorithm designed to calculate precise COD angles for direct comparison with a high-speed video (remotely piloted, position-locked aircraft) criterion measure. Validity was assessed using Bland-Altman 95% limits of agreement and mean bias. Reliability was assessed using typical error (expressed as a coefficient of variation [CV]). Concurrent validity was present for most angles. Left: (45° = 43.8 ± 2.0°; 90° = 88.1 ± 2.0°; 135° = 136.3 ± 2.1°; and 180° = 181.8 ± 2.5°) and Right: (45° = 46.3 ± 1.6°; 90° = 91.9 ± 2.2°; 135° = 133.4 ± 2.0°; 180° = 179.2 ± 5.9°). All angles displayed excellent reliability (CV \u3c 5%) while greater mean bias (3.6 ± 5.1°, p \u3c 0.001), weaker limits of agreement, and reduced precision were evident for 180° trials when compared with all other angles. High-level accuracy and reliability when detecting COD angles further advocates the use of inertial sensors to quantify sports-specific movement patterns

Speciated and total emission factors of particulate organics from burning western US wildland fuels and their dependence on combustion efficiency

Western US wildlands experience frequent and large-scale wildfires which are predicted to increase in the future. As a result, wildfire smoke emissions are expected to play an increasing role in atmospheric chemistry while negatively impacting regional air quality and human health. Understanding the impacts of smoke on the environment is informed by identifying and quantifying the chemical compounds that are emitted during wildfires and by providing empirical relationships that describe how the amount and composition of the emissions change based upon different fire conditions and fuels. This study examined particulate organic compounds emitted from burning common western US wildland fuels at the US Forest Service Fire Science Laboratory. Thousands of intermediate and semi-volatile organic compounds (I/SVOCs) were separated and quantified into fire-integrated emission factors (EFs) using a thermal desorption, two-dimensional gas chromatograph with online derivatization coupled to an electron ionization/vacuum ultraviolet high-resolution time-of-flight mass spectrometer (TD-GC-GC-EI/VUV-HRToFMS). Mass spectra, EFs as a function of modified combustion efficiency (MCE), fuel source, and other defining characteristics for the separated compounds are provided in the accompanying mass spectral library. Results show that EFs for total organic carbon (OC), chemical families of I/SVOCs, and most individual I/SVOCs span 2-5 orders of magnitude, with higher EFs at smoldering conditions (low MCE) than flaming. Logarithmic fits applied to the observations showed that log (EFs) for particulate organic compounds were inversely proportional to MCE. These measurements and relationships provide useful estimates of EFs for OC, elemental carbon (EC), organic chemical families, and individual I/SVOCs as a function of fire conditions

Short Term Climatological Wind Data as a Tool for Wind Forecasting

Utilizing short-term climatological wind data can enhance wind speed and wind direction forecasts. An analysis of regional or tower-based wind rose summaries can be useful forecast guides especially when synoptic-scale pressure gradients are weak. Predictive data from multiple models can be plotted against short-term climatological wind data to assess deviations from expected norms and differences between forecast models. Site-specific comparisons between predicted data and observed climatological distributions can provide further insights to the forecaster. These methods can be applied to any location where sufficient climatological data (at least two years) is available