Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.National Institutes of Health (NIH) (R21 NS076925)University of Kansas Medical Center funds to A. B. B.NIH P20 GM104936, P30 AG035982UL1 TR000001NIH HD00252

Trabecular Bone in the Bird Knee Responds with High Sensitivity to Changes in Load Orientation

Wolff’s law of trajectorial orientation proposes that trabecular struts align with the orientation of dominant compressive loads within a joint. Although widely considered in skeletal biology, Wolff’s law has never been experimentally tested while controlling for ontogenetic stage, activity level, and species differences, all factors that may affect trabecular bone growth. Here we report an experimental test of Wolff’s law using a within-species design in age-matched subjects experiencing physiologically normal levels of bone strain. Two age-matched groups of juvenile guinea fowl Numida meleagris ran on a treadmill set at either 0° (Level group) or 20° (Incline group), for 10·min per day over a 45-day treatment period. Birds running on the 20° inclined treadmill used more-flexed knees than those in the Level group at midstance (the point of peak ground reaction force). This difference in joint posture enabled us to test the sensitivity of trabecular alignment to altered load orientation in the knee. Using a new radon transform-based method for measuring trabecular orientation, our analysis shows that the fine trabecular bone in the distal femur has a high degree of correspondence between changes in joint angle and trabecular orientation. The sensitivity of this response supports the prediction that trabecular bone adapts dynamically to the orientation of peak compressive forces.Anthropolog

Fast DNA translocation through a solid-state nanopore

We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR

Global services and support for children with developmental delays and disabilities: Bridging research and policy gaps

Summary: 1. The United Nations Sustainable Development Goals and the UN Convention on the Rights of the Child (CRC) envision an inclusive society in which health and education contribute to the well-being of all. To achieve this vision, children with developmental delays and behavioral, cognitive, mental, and neurological disabilities need greater access to health care, early childhood care and development services, and education. 2. Improved population-level detection, alongside screening, assessment, and linkage to evidence-based, intersectoral services in the first years of life, can help maximize capabilities and increase the chances of social inclusion for children with developmental delays and disabilities. 3. Educational programs for children with delays and disabilities whose service delivery structure supports the ability of parents to work should be encouraged so that parents can participate in achieving children’s educational goals while also meeting their financial needs. 4. Parents and caregivers who receive training in psychosocial interventions and ongoing support can help children with delays and disabilities thrive in family contexts. 5. Family mental health influences the developmental trajectory of children. Ensuring that parents and caregivers have access to affordable, quality mental health services helps to prevent poor outcomes for children. 6. Rigorous evaluation, continuous quality improvement, and regular monitoring of the programmatic outcomes of services and policy approaches targeting children and caregivers would inform their implementation and serve to disseminate lessons learned from successful policy and program implementation

The Apollo Medical Operations Project: Recommendations to Improve Crew Health and Performance for Future Exploration Missions and Lunar Surface Operations

Medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), advanced Extravehicular Activity (EVA) suits and Lunar habitat are currently being developed. Crews returning to the lunar surface will construct the lunar habitat and conduct scientific research. Inherent in aggressive surface activities is the potential risk of injury to crewmembers. Physiological responses and the operational environment for short forays during the Apollo lunar missions were studied and documented. Little is known about the operational environment in which crews will live and work and the hardware will be used for long-duration lunar surface operations. Additional information is needed regarding productivity and the events that affect crew function such as a compressed timeline. The Space Medicine Division at the NASA Johnson Space Center (JSC) requested a study in December 2005 to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The operationally oriented goals of this project were to develop or modify medical requirements for new exploration vehicles and habitats, create a centralized database for future access, and share relevant Apollo information with the multiple entities at NASA and abroad participating in the exploration effort

Structural, electronic, and dynamical properties of amorphous gallium arsenide: a comparison between two topological models

We present a detailed study of the effect of local chemical ordering on the structural, electronic, and dynamical properties of amorphous gallium arsenide. Using the recently-proposed ``activation-relaxation technique'' and empirical potentials, we have constructed two 216-atom tetrahedral continuous random networks with different topological properties, which were further relaxed using tight-binding molecular dynamics. The first network corresponds to the traditional, amorphous, Polk-type, network, randomly decorated with Ga and As atoms. The second is an amorphous structure with a minimum of wrong (homopolar) bonds, and therefore a minimum of odd-membered atomic rings, and thus corresponds to the Connell-Temkin model. By comparing the structural, electronic, and dynamical properties of these two models, we show that the Connell-Temkin network is energetically favored over Polk, but that most properties are little affected by the differences in topology. We conclude that most indirect experimental evidence for the presence (or absence) of wrong bonds is much weaker than previously believed and that only direct structural measurements, i.e., of such quantities as partial radial distribution functions, can provide quantitative information on these defects in a-GaAs.Comment: 10 pages, 7 ps figures with eps

Atrial Arrhythmias and Their Implications for Space Flight - Introduction

This panel will discuss the implications of atrial arrhythmias in astronauts from a variety of perspectives; including historical data, current practices, and future challenges for exploration class missions. The panelists will present case histories, outline the evolution of current NASA medical standards for atrial arrhythmias, discuss the use of predictive tools, and consider potential challenges for current and future missions

Recommendations for Exploration Space Medicine from the Apollo Medical Operations Project

Introduction: A study was requested in December, 2005 by the Space Medicine Division at the NASA-Johnson Space Center (JSC) to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The objective was to use this new information to develop medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), Lunar Habitat, and Advanced Extravehicular Activity (EVA) suits that are currently being developed within the exploration architecture. Methods: Available resources pertaining to medical operations on the Apollo 7 through 17 missions were reviewed. Ten categories of hardware, systems, or crew factors were identified in the background research, generating 655 data records in a database. A review of the records resulted in 280 questions that were then posed to surviving Apollo crewmembers by mail, face-to-face meetings, or online interaction. Response analysis to these questions formed the basis of recommendations to items in each of the categories. Results: Thirteen of 22 surviving Apollo astronauts (59%) participated in the project. Approximately 236 pages of responses to the questions were captured, resulting in 107 recommendations offered for medical consideration in the design of future vehicles and EVA suits based on the Apollo experience. Discussion: The goals of this project included: 1) Develop or modify medical requirements for new vehicles; 2) create a centralized database for future access; and 3) take this new knowledge and educate the various directorates at NASA-JSC who are participating in the exploration effort. To date, the Apollo Medical Operations recommendations are being incorporated into the exploration mission architecture at various levels and a centralized database has been developed. The Apollo crewmembers input has proved to be an invaluable resource, prompting ongoing collaboration as the requirements for the future exploration missions continue to evolve and be refined

Evidence of Counter-Streaming Ions near the Inner Pole of the HERMeS Hall Thruster

NASA is continuing the development of a 12.5-kW Hall thruster system to support a phased exploration concept to expand human presence to cis-lunar space and eventually to Mars. The development team is transitioning knowledge gained from the testing of the government-built Technology Development Unit (TDU) to the contractor-built Engineering Test Unit (ETU). A new laser-induced fluorescence diagnostic was developed to obtain data for validating the Hall thruster models and for comparing the behavior of the ETU and TDU. Analysis of TDU LIF data obtained during initial deployment of the diagnostics revealed evidence of two streams of ions moving in opposite directions near the inner front pole. These two streams of ions were found to intersect the downstream surface of the front pole at large oblique angles. This data points to a possible explanation for why the erosion rate of polished pole covers were observed to decrease over the course of several hundred hours of thruster operation