125,066 research outputs found
Physicists Thriving with Paperless Publishing
No full textThe Stanford Linear Accelerator Center (SLAC) and Deutsches Elektronen Synchrotron (DESY) libraries have been comprehensively cataloguing the High Energy Particle Physics (HEP) literature online since 1974. The core database, SPIRES-HEP, now indexes over 400,000 research articles, with almost 50% linked to fulltext electronic versions (this site now has over 15 000 search hits per day). This database motivated the creation of the first site in the United States for the World-Wide Web at SLAC. With this database and the invention of the Los Alamos E-print archives in 1991, the HEP community pioneered the trend to "paperless publishing" and the trend to paperless access; in other words, the "virtual library." We examine the impact this has had both on the way scientists research and on paper-based publishing. The standard of work archived at Los Alamos is very high. 70% of papers are eventually published in journals and another 20% are in conference proceedings. As a service to authors, the SPIRES-HEP collaboration has been ensuring that as much information as possible is included with each bibliographic entry for a paper. Such metadata can include tables of the experimental data that researchers can easily use to perform their own analyses as well as detailed descriptions of the experiment, citation tracking, and links to full-text documents
Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy
No full textNeurofibrillary tangles (NFTs) are associated with neuronal loss and correlate with cognitive impairment in Alzheimer disease, but how NFTs relate to neuronal death is not clear. We studied cell death in Tg4510 mice that reversibly express P301L mutant human tau and accumulate NFTs using in vivo multiphoton imaging of neurofibrillary pathology, propidium iodide (PI) incorporation into cells, caspase activation, and DNA labeling. We first observed that in live mice, a minority of neurons were labeled with the caspase probe or with PI fluorescence. These markers of cell stress were localized in the same cells and appeared specifically within NFT-bearing neurons. Contrary to expectations, the PI-stained neurons did not die during a day of observation; the presence of Hoechst-positive nuclei in them on the subsequent day indicated that the NFT-associated membrane disruption, as suggested by PI staining, and caspase activation do not lead to immediate death of neurons in this tauopathy model. This unique combination of in vivo multiphoton imaging with markers of cell death and pathological alteration is a powerful tool for investigating neuronal damage associated with neurofibrillary pathology
Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model
No full textNeurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and although they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal function. To investigate the response of cells in hippocampal circuits to complex behavioral stimuli, we used an environmental enrichment paradigm to induce expression of an immediate-early gene, Arc, in the rTg4510 mouse model of tauopathy. These mice reversibly overexpress P301L tau and exhibit substantial neurofibrillary tangle deposition, neuronal loss, and memory deficits. Using fluorescent in situ hybridization to detect Arc messenger RNA, we found that rTg4510 mice have impaired hippocampal Arc expression both without stimulation and in response to environmental enrichment; this likely reflects the combination of functional impairments of existing neurons and loss of neurons. However, tangle-bearing cells were at least as likely as non-tangle-bearing neurons to exhibit Arc expression in response to enrichment. Transgene suppression with doxycycline for 6 weeks resulted in increased percentages of Arc-positive cells in rTg4510 brains compared with untreated transgenics, restoring enrichment-induced Arc messenger RNA levels to that of wild-type controls despite the continued presence of neurofibrillary pathology. We interpret these data to indicate that soluble tau contributes to impairment of hippocampal function, although tangles do not preclude neurons from responding in a functional circuit
Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8
No full textSynapse loss correlates with cognitive decline in Alzheimer’s disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared to non-disease controls, and that proximity to amyloid-β plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation. This dataset contains the spreadsheets analysed in the study (in a zip file) and the R Notebook used for statistical analysis. The dataset relates to the upcoming M. Tzioras, M.J.D. Daniels, C. Davies, P. Baxter, D. King, S. McKay, B. Varga, K. Popovic, M. Hernandez, A.J. Stevenson, J. Barrington, E. Drinkwater, J. Borella, R.K. Holloway, J. Tulloch, J. Moss, C. Latta, J. Kandasamy, D. Sokol, C. Smith, V.E. Miron, R.T. Káradóttir, G.E. Hardingham, C.M. Henstridge, P.M. Brennan, B.W. McColl, T.L. Spires-Jones (accepted). 'Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8' https://doi.org/10.1101/795930
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Model analysis of the relationship between intracellular PO2 and energy demand in skeletal muscle
No full textOn the basis of experimental studies, the intracellular O(2) (iPo(2))-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo(2) reached a plateau at 60% of maximal WR, while another found that iPo(2) decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O(2) gradient, respectively, as alternative dominant factors for determining O(2) diffusion changes during exercise. This relationship is affected by several factors, including O(2) delivery and oxidative and glycolytic capacities of the muscle. In this study, these factors are examined using a mechanistic, mathematical model to analyze experimental data from contracting skeletal muscle and predict the effects of muscle contraction on O(2) transport, glycogenolysis, and iPo(2). The model describes convection, O(2) diffusion, and cellular metabolism, including anaerobic glycogenolysis. Consequently, the model simulates iPo(2) in response to muscle contraction under a variety of experimental conditions. The model was validated by comparison of simulations of O(2) uptake with corresponding experimental responses of electrically stimulated canine muscle under different O(2) content, blood flow, and contraction intensities. The model allows hypothetical variation of PS, glycogenolytic capacity, and blood flow and predictions of the distinctive effects of these factors on the iPo(2)-contraction intensity relationship in canine muscle. Although PS is the main factor regulating O(2) diffusion rate, model simulations indicate that PS and O(2) gradient have essential roles, depending on the specific conditions. Furthermore, the model predicts that different convection and diffusion patterns and metabolic factors may be responsible for different iPo(2)-WR relationships in humans
Human tau increases amyloid beta plaque size but not amyloid beta-mediated synapse loss in a novel mouse model of Alzheimer’s disease: Data set from Jackson et al 2016 EJN
No full textAlzheimer’s disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss.
This dataset includes data associated with this manuscript along with custom analysis macros. The raw images are too large to upload to our limited repository system, at over 300 GB total, but are available upon request [email protected]
Snowmobile Ride by Spires, Custer SD, Custer County
No full text35 mm b/w negative, two snowmobiles in a snow-covered winter landscape, there are granite spires in the backgroun
Hairpin Turn In Cathedral Spires, Custer SD, Custer County
No full text4 x 6 b/w negative, a sharp curve on a mountainous road, the granite spires of the Needles are visible in the backgroundMt. Rushmore Memorial of S.D. Black Hills, P.O. Box 1250, Rapid City, SD.Black Hills, SD. Rapid City, SD
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