22 research outputs found

    Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

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    BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression

    Overview of the Millimeter-Wave Thermal Launch System (MTLS) Project

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    In 2012, DARPA challenged the authors to launch a small thermal rocket into the air using millimeter waves. The resulting 2-year program, the Millimeter-Wave Thermal Launch System (MTLS), has been executed by NASA Ames Research Center and involves partnerships with General Atomics DIII-D Tokamak, the Air Force Research Laboratory, and the Army High Energy Laser Systems Test Facility (HELSTF). We define the MTLS program, describe its challenges, and outline its achievement

    A Microsatellite Space Guard Force

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    The microsatellites now under development will be capable of a variety of inspection, surveillance, servicing, and propulsion services. As the military and commercial importance of space increases, a practical near-term use of this technology will be to provide the kind of services in space that the U.S. Coast Guard provides on Earth. The Coast Guard provides the U.S. coastal waters with law enforcement, search and rescue, safety inspection, and a myriad of other services. All these services are needed in the near-Earth region as well, and will become more critical as thousands of additional satellites are launched. A Space Guard constellation of micro satellites would use the technology being developed under the XSS-10, Mightysat, and other programs to provide similar services, beginning with low Earth orbit (LEO). Space Guard satellites could evaluate damaged satellites, enforce treaties by inspection, monitor traffic in key orbits, and report collision hazards, If needed, microsats could attach thrusters or tether packages to move or deorbit a disabled satellite. While an independent agency or international consortium could eventually operate the Guard, its initial deployment would most likely be under U.S. Space Command. This paper assesses the requirements and technology involved in the Space Guard proposal, along with possible operational structures and initial cost estimates. The Space Guard concept is a vital one. Microsatellites are the most affordable and effective way to put it into practice

    Liberty County Strategic Plan 2016 - 2036

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    In the fall of 2015, the County of Liberty and Texas Target Communities partnered to create a task force to represent the community. The task force was integral to the planning process, contributing the thoughts, desires, and opinions of community members—as well as their enthusiasm about Liberty’s future. This fourteen-month planning process ended in August 2016. The result of this collaboration is the County of Liberty Strategic Plan, which is the official policy guide for the community’s growth over the next twenty years.Liberty Strategic Plan 2036 provides a guide for the future growth of the county. This document was developed by Texas Target Communities in partnership with the County of Liberty

    Number of Aβ Inoculations in APP+PS1 Transgenic Mice Influences Antibody Titers, Microglial Activation, and Congophilic Plaque Levels

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    There have been several reports on the use of β-amyloid (Aβ ) vaccination in different mouse models of Alzheimer\u27s disease (AD) and its effects on pathology and cognitive function. In this report, the histopathologic findings in the APP+PS1 doubly transgenic mouse were compared after three, five, or nine Aβ inoculations. The number of inoculations influenced the effects of vaccination on Congo red levels, microglia activation, and anti-Aβ antibody titers. After three inoculations, the antibody titer of transgenic mice was substantially lower than that found in nontransgenic animals. However, after nine inoculations, the levels were considerably higher in both genotypes and no longer distinguishable statistically. The number of inoculations influenced CD45 expression, an indicator of microglial activation. There was an initial upregulation, which was significant after five inoculations, but by nine inoculations, the extent of microglial activation was equivalent to that in mice given control vaccinations. Along with this increased CD45 expression, there was a correlative reduction in staining by Congo red, which stains compact plaques. When data from the mice from all groups were combined, there was a significant correlation between activation of microglia and Congo red levels, suggesting that microglia play a role in the clearance of compact plaque

    When to use broader internalising and externalising subscales instead of the hypothesised five subscales on the Strengths and Difficulties Questionnaire (SDQ): data from British parents, teachers and children.

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    The Strengths and Difficulties Questionnaire (SDQ) is a widely used child mental health questionnaire with five hypothesised subscales. There is theoretical and preliminary empirical support for combining the SDQ's hypothesised emotional and peer subscales into an 'internalizing' subscale and the hypothesised behavioral and hyperactivity subscales into an 'externalizing' subscale (alongside the fifth prosocial subscale). We examine this using parent, teacher and youth SDQ data from a representative sample of 5-16 year olds in Britain (N = 18,222). Factor analyses generally supported second-order internalizing and externalizing factors, and the internalizing and externalizing subscales showed good convergent and discriminant validity across informants and with respect to clinical disorder. By contrast, discriminant validity was poorer between the emotional and peer subscales and between the behavioral, hyperactivity and prosocial subscales. This applied particularly to children with low scores on those subscales. We conclude that there are advantages to using the broader internalizing and externalizing SDQ subscales for analyses in low-risk samples, while retaining all five subscales when screening for disorder

    Identification of Regions in the IOTC Convention Area to Inform the Implementation of the Ecosystem Approach to Fisheries Management

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    WPEB14 recommended to convene a workshop in 2019 to provide advice on the identification of draft ecoregions to foster discussions on the operationalization of the ecosystem approach to fisheries management (EAFM) in the Indian Ocean Tuna Commission (IOTC) convention area. This workshop entitled “Identification of regions in the IOTC convention area to inform the implementation of the ecosystem approach to fisheries management” took place the 30th, 31st of August and 1st of September 2019 in La Reunion Island. The workshop gathered 17 participants with a wide range of expertise in IOTC species and fisheries and oceanography of the Indian Ocean. Prior to the workshop, a consultant was hired to prepare a baseline draft proposal of ecoregions to be presented and discussed at the workshop by all the participants. The workshop was structured into seven sessions. In the first session, the experience of developing and using ecoregions in NAFO, ICES, CCAMLR and the NPFMC in the USA were presented to the Group. The Group discussed the potential benefits and uses of ecoregions in the context of these organizations and in the context of IOTC species and fisheries. In the second session, an overview of the current existing biogeographic classifications in the Indian Ocean, which are often used to inform the delineation of ecoregion boundaries, were presented to the Group, and their relevance in the context of IOTC species and its fisheries were discussed. In the third session, a check list of evaluation criteria was presented to the Group in order to inform discussions of what factors and considerations could be used for the development of the draft ecoregions. The Group agreed that ecological factors including (i) major oceanographic patterns, (ii) main distribution of IOTC species (tunas, billfishes, neritics), in combination with (iii) the spatial distribution of IOTC fisheries (coastal and industrial fisheries) should be the primary factors to be considered in the development of initial draft ecoregions. Other considerations such as geopolitical factors were also discussed, but not considered primary factors. In the fourth session, existing data sets were revised, presented and discussed in terms of availability, quality and completeness to guide the choice of key data inputs for deriving the draft ecoregions. The data sets included (i) existing biogeographic classifications, (ii) spatial distribution and catches of IOTC species (oceanic tunas, neritics, sharks, other bycatch species), (iii) spatial distributions of IOTC fisheries (baitboats, longlines, gillnets, purse seines, etc.) and (iv) “other” potentially relevant data layers. A selection of “good” quality data sets was used as inputs in the quantitative spatial analysis to develop the baseline draft ecoregions to be discussed by the group. In the fifth session, several quantitative spatial analyses were presented and discussed by the Group. These included several spatial overlap analyses, calculations of fidelity and sensitivity indicators to examine species and fisheries composition across multiple biogeographic provinces, and clustering analyses to group biogeographic provinces according to their similarity in terms of species composition, fisheries composition and both species and fishery composition. The Group provided feedback on the technical aspects and methods used in the derivation of the baseline ecoregions. In the sixth session, three baseline ecoregions were presented and discussed by the Group. The first ecoregion classification was based on similarities of the spatial patterns in species composition, the second on the spatial patterns of fisheries, and the third on the spatial patterns of both species and fisheries. In the seventh session, the three baseline ecoregion classifications in combination with expert knowledge were used to derive draft ecoregions within the IOTC convention area, and the Group discussed conclusions and future steps. The draft ecoregions are not intended to be used for management purposes. At this stage, the benefits and potential uses (e.g. development of ecosystem report cards, ecosystem status overviews, etc.) of the draft ecoregions should be tested as a tool to facilitate the operationalization of the EAFM in IOTC. The Group requested that the WPEB reviews and comments on the delineation of the draft ecoregions and provides ongoing feedback. The Group also requested that the WPEB communicates with the rest of the WPs to solicit feedback on the draft ecoregions. The Group recommended that the WPEB endorses the draft ecoregions for further development as a tool to progress EAFM implementation (e.g. ecosystem report card, ecosystem overviews, fisheries overviews)

    An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

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    Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties
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