143 research outputs found
The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.
Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies
Tissue phantoms in multicenter clinical trials for diffuse optical technologies
Tissue simulating phantoms are an important part of instrumentation validation, standardization/training and clinical translation. Properly used, phantoms form the backbone of sound quality control procedures. We describe the development and testing of a series of optically turbid phantoms used in a multi-center American College of Radiology Imaging Network (ACRIN) clinical trial of Diffuse Optical Spectroscopic Imaging (DOSI). The ACRIN trial is designed to measure the response of breast tumors to neoadjuvant chemotherapy. Phantom measurements are used to determine absolute instrument response functions during each measurement session and assess both long and short-term operator and instrument reliability
Detection of astrocytic tau pathology facilitates recognition of chronic traumatic encephalopathy neuropathologic change
Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer’s disease neuropathologic change (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC
Observation- and model-based estimates of particulate dry nitrogen deposition to the oceans
Anthropogenic nitrogen (N) emissions to the atmosphere have increased significantly the deposition of nitrate (NO3-) and ammonium (NH4+) to the surface waters of the open ocean, with potential impacts on marine productivity and the global carbon cycle. Global-scale understanding of the impacts of N deposition to the oceans is reliant on our ability to produce and validate models of nitrogen emission, atmospheric chemistry, transport and deposition. In this work, ~2900 observations of aerosol NO3- and NH4+ concentrations, acquired from sampling aboard ships in the period 1995 - 2012, are used to assess the performance of modelled N concentration and deposition fields over the remote ocean. Three ocean regions (the eastern tropical North Atlantic, the northern Indian Ocean and northwest Pacific) were selected, in which the density and distribution of observational data were considered sufficient to provide effective comparison to model products. All of these study regions are affected by transport and deposition of mineral dust, which alters the deposition of N, due to uptake of nitrogen oxides (NOx) on mineral surfaces. Assessment of the impacts of atmospheric N deposition on the ocean requires atmospheric chemical transport models to report deposition fluxes, however these fluxes cannot be measured over the ocean. Modelling studies such as the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), which only report deposition flux are therefore very difficult to validate for dry deposition. Here the available observational data were averaged over a 5° x 5° grid and compared to ACCMIP dry deposition fluxes (ModDep) of oxidised N (NOy) and reduced N (NHx) and to the following parameters from the TM4-ECPL (TM4) model: ModDep for NOy, NHx and particulate NO3- and NH4+, and surface-level particulate NO3- and NH4+ concentrations. As a model ensemble, ACCMIP can be expected to be more robust than TM4, while TM4 gives access to speciated parameters (NO3- and NH4+) that are more relevant to the observed parameters and which are not available in ACCMIP. Dry deposition fluxes (CalDep) were calculated from the observed concentrations using estimates of dry deposition velocities. Model – observation ratios, weighted by grid-cell area and numbers of observations, (RA,n) were used to assess the performance of the models. Comparison in the three study regions suggests that TM4 over-estimates NO3- concentrations (RA,n = 1.4 – 2.9) and under-estimates NH4+ concentrations (RA,n = 0.5 – 0.7), with spatial distributions in the tropical Atlantic and northern Indian Ocean not being reproduced by the model. In the case of NH4+ in the Indian Ocean, this discrepancy was probably due to seasonal biases in the sampling. Similar patterns were observed in the various comparisons of CalDep to ModDep (RA,n = 0.6 – 2.6 for NO3-, 0.6 – 3.1 for NH4+). Values of RA,n for NHx CalDep - ModDep comparisons were approximately double the corresponding values for NH4+ CalDep - ModDep comparisons due to the significant fraction of gas-phase NH3 deposition incorporated in the TM4 and ACCMIP NHx model products. All of the comparisons suffered due to the scarcity of observational data and the large uncertainty in dry deposition velocities used to derive deposition fluxes from concentrations. These uncertainties have been a major limitation on estimates of the flux of material to the oceans for several decades. Recommendations are made for improvements in N deposition estimation through changes in observations, modelling and model – observation comparison procedures. Validation of modelled dry deposition requires effective comparisons to observable aerosol-phase species concentrations and this cannot be achieved if model products only report dry deposition flux over the ocean
Distinct genetic architecture underlies the emergence of sleep loss and prey-seeking behavior in the Mexican cavefish
Sleep is characterized by extended periods of quiescence and reduced responsiveness to sensory stimuli. Animals ranging from insects to mammals adapt to environments with limited food by suppressing sleep and enhancing their response to food cues, yet little is known about the genetic and evolutionary relationship between these processes. The blind Mexican cavefish, Astyanax mexicanus is a powerful model for elucidating the genetic mechanisms underlying behavioral evolution. A. mexicanus comprises an extant ancestral-type surface dwelling morph and at least five independently evolved cave populations. Evolutionary convergence on sleep loss and vibration attraction behavior, which is involved in prey seeking, have been documented in cavefish raising the possibility that enhanced sensory responsiveness underlies changes in sleep. We established a system to study sleep and vibration attraction behavior in adult A. mexicanus and used high coverage quantitative trait loci (QTL) mapping to investigate the functional and evolutionary relationship between these traits. Analysis of surface-cave F2 hybrid fish and an outbred cave population indicates that independent genetic factors underlie changes in sleep/locomotor activity and vibration attraction behavior. High-coverage QTL mapping with genotyping-by-sequencing technology identify two novel QTL intervals that associate with locomotor activity and include the narcolepsy-associated tp53 regulating kinase. These QTLs represent the first genomic localization of locomotor activity in cavefish and are distinct from two QTLs previously identified as associating with vibration attraction behavior. Taken together, these results localize genomic regions underlying sleep/locomotor and sensory changes in cavefish populations and provide evidence that sleep loss evolved independently from enhanced sensory responsiveness.https://doi.org/10.1186/s12915-015-0119-
US SOLAS Science Report
The article of record may be found at https://doi.org/10.1575/1912/27821The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G).This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)
US SOLAS Science Report
The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully
designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)
First look at the Fomalhaut debris disk with the Spitzer Space Telescope
We present Spitzer Space Telescope early release observations of Fomalhaut, a nearby A-type star with dusty circumstellar debris. The disk is spatially resolved at 24, 70, and 160 � m using the Multiband Imaging Photometer for Spitzer (MIPS). While the disk orientation and outer radius are comparable to values measured in the submillimeter, the disk inner radius cannot be precisely defined: the central hole in the submillimeter ring is at least partially filled with emission from warm dust, seen inSpitzerInfrared Spectrograph (IRS) 17.5‐34 � m spectra and MIPS 24 � m images. The disk surface brightness becomes increasingly asymmetric toward shorter wavelengths, with the south-southeast ansa always brighter than the north-northwest one. This asymmetry may reflect perturbations on the disk by an unseen interior planet. Subject headingg circumstellar matter — infrared: stars — planetary systems — stars: individual (Fomalhaut
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