Traumatic Axonal Injury: Mechanisms and Translational Opportunities.

Traumatic axonal injury (TAI) is an important pathoanatomical subgroup of traumatic brain injury (TBI) and a major driver of mortality and functional impairment. Experimental models have provided insights into the effects of mechanical deformation on the neuronal cytoskeleton and the subsequent processes that drive axonal injury. There is also increasing recognition that axonal or white matter loss may progress for years post-injury and represent one mechanistic framework for progressive neurodegeneration after TBI. Previous trials of novel therapies have failed to make an impact on clinical outcome, in both TBI in general and TAI in particular. Recent advances in understanding the cellular and molecular mechanisms of injury have the potential to translate into novel therapeutic targets.CSH is supported by a Wellcome Trust PhD for Clinicians. MPC is funded by the John and Lucille van Geest Foundation. DKM is supported by a Senior Investigator Award from the National Institute for Health Research, UK (NIHR), by the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, and a Framework Program 7 grant from the European Union (CENTER-TBI; Grant No: 602150)This is the final version of the article. It first appeared from Elsevier via https://doi.org/ 10.1016/j.tins.2016.03.00

An Examination of NBA MVP Voting Behavior: Does Race Matter?

The selection process of the most valuable player (MVP) in the National Basketball Association (NBA) was recently questioned as to whether African-American players were treated unfairly based on their race. Using NBA voting data from the 1995-2005 seasons, we develop two empirical models in order to examine the role that a player’s race plays in the determination of this award. Our estimates imply that after controlling for player, team, and market characteristics, there is no statistically significant effect of race on the likelihood that a player will appear on an MVP ballot or on the number of votes he will receive

Tobermorite ion-exchanger from paper recycling ash and waste glass

Å tobermorite (Ca5(Si)6O16(OH)2.4H2O) and its Al-substituted counterpart are layer-lattice cation-exchangers that are of interest with respect to their applications in nuclear and hazardous wastewater treatment [1-3]. In 2015, the European Declaration on Paper Recycling reported that 71.5% of all paper consumed in Europe was recycled, corresponding to 1.2 million tonnes more than their 70% target [4]. Waste paper recycling ash (PRA) arising from this activity contains reactive calcium aluminosilicate phases that can be used for the hydrothermal synthesis of tobermorite when stoichiometrically adjusted with additional silicate-bearing reagents [1]. Waste soda-lime-silica container glass (SCG) has also been used as a partial feedstock for the preparation tobermorite in alkaline media [2]. This research tested the feasibility of a one-step synthesis of tobermorite from a combination of PRA and SCG under alkaline hydrothermal conditions at 100 °C. Reaction products were analysed by powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). This study also evaluated the Cs+ cation-exchange capacity (CEC), selective Cs+ distribution coefficients (Kd, from Na+ and Ca2+ background solutions) and the uptake kinetics of Cd2+ and Pb2+ by the waste-derived tobermorite produc

Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster.

Traumatic brain injury is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. We demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including-improved functional outcomes, lifespan, survival of dopaminergic neurons, and retention of synaptic proteins. This data suggests that highwire represents a potential therapeutic target in traumatic injury

Characterization of Hypertension Risk Factors at the Committee on Temporary Shelter

Introduction: The health of homeless populations is at risk due to a high prevalence of undiagnosed hypertension (HTN) and cardiovascular disease (CVD). The interaction of housing and socioeconomic status with the risk factors for HTN and CVD remains unclear. Prevention of HTN through a healthy diet, exercise, adequate sleep, and avoidance of tobacco has been well described, but financial limitations and competing priorities for shelter and food make blood pressure (BP) control difficult for this population. By characterizing the risk factors and awareness of hypertension within the homeless population at the Committee on Temporary Shelter Daystation (COTS) in Burlington, Vermont, we may be able to identify promising avenues for therapeutic intervention.https://scholarworks.uvm.edu/comphp_gallery/1226/thumbnail.jp

Exotic Non-Supersymmetric Gauge Dynamics from Supersymmetric QCD

We extend Seiberg's qualitative picture of the behavior of supersymmetric QCD to nonsupersymmetric models by adding soft supersymmetry breaking terms. In this way, we recover the standard vacuum of QCD with $N_f$ flavors and $N_c$ colors when $N_f < N_c$. However, for $N_f \geq N_c$, we find new exotic states---new vacua with spontaneously broken baryon number for $N_f = N_c$, and a vacuum state with unbroken chiral symmetry for $N_f > N_c$. These exotic vacua contain massless composite fermions and, in some cases, dynamically generated gauge bosons. In particular Seiberg's electric-magnetic duality seems to persist also in the presence of (small) soft supersymmetry breaking. We argue that certain, specially tailored, lattice simulations may be able to detect the novel phenomena. Most of the exotic behavior does not survive the decoupling limit of large SUSY breaking parameters.Comment: 36 pages, latex + 2 figures (uuencoded ps

TNF Receptor-Associated Factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets.

Background: Reactive oxygen species generation is one consequence of ligand engagement of platelet glycoprotein (GP) receptors GPIb-IX-V and GPVI, which bind VWF/collagen and initiate thrombosis at arterial shear, however the precise molecular mechanism coupling redox pathway activation to engagement of these receptors is unknown. Objective: The objective of this study was to identify novel binding partners for GPIb-IX-V and GPVI that could provide a potential link between redox pathways and early platelet signalling events. Methods and Results: Using protein array analysis and affinity-binding assays, we demonstrated that the orphan TNF receptor-associated factor (TRAF) family member, TRAF4, selectively binds cytoplasmic sequences of GPIbβ and GPVI. TRAF4, p47(phox) (of the NADPH oxidase (Nox2) enzyme complex), and other redox relevant signalling proteins such as Hic-5, co-immunoprecipitate with GPIb/GPVI from human platelet lysates whilst MBP-TRAF4 or MBP-p47(phox) fusion proteins specifically pull-down GPIb/GPVI. GPIb- or GPVI-selective agonists induce phosphorylation of the TRAF4-associated proteins, Hic-5 and Pyk2, with phosphorylation attenuated by Nox2 inhibition. Conclusion: These results describe the first direct association of TRAF4 with a receptor, and identify a novel binding partner for GPIb-IX-V and GPVI, providing a potential link between these platelet receptors and downstream TRAF4/Nox2-dependent redox pathways

Phases and Faces of the Duke Lacrosse Controversy: A Conversation

This panel took place at the 2008 Annual Meeting of the Southeastern Association of Law Schools (SEALS) in July 2008 in West Palm Beach, Florida. The transcript has been edited for grammar, punctuation and writing style, as well as for limited content changes

β-Hydroxy-β-Methylbutyrate Supplementation Promotes Antitumor Immunity in an Obesity Responsive Mouse Model of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PDAC) is a deadly disease, exacerbated by obesity, which lacks effective therapeutic interventions. Most PDAC has a limited response to immune- and chemotherapy. Treating PDAC is made additionally challenging by the rapid emergence of muscle wasting and cachexia, which predict poor response to several therapies. We have found that dietary supplementation with β-hydroxy-β-methylbutyrate promotes immunosurveillance in PDAC tumors and protects muscle. This dietary supplement has the potential to be an important adjuvant in PDAC therapy, opening the doors to immunotherapy response