511 research outputs found

    The OSIRIS-REx Visible and InfraRed Spectrometer (OVIRS): Spectral Maps of the Asteroid Bennu

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    The OSIRIS-REx Visible and Infrared Spectrometer (OVIRS) is a point spectrometer covering the spectral range of 0.4 to 4.3 microns (25,000-2300 cm-1). Its primary purpose is to map the surface composition of the asteroid Bennu, the target asteroid of the OSIRIS-REx asteroid sample return mission. The information it returns will help guide the selection of the sample site. It will also provide global context for the sample and high spatial resolution spectra that can be related to spatially unresolved terrestrial observations of asteroids. It is a compact, low-mass (17.8 kg), power efficient (8.8 W average), and robust instrument with the sensitivity needed to detect a 5% spectral absorption feature on a very dark surface (3% reflectance) in the inner solar system (0.89-1.35 AU). It, in combination with the other instruments on the OSIRIS-REx Mission, will provide an unprecedented view of an asteroid's surface.Comment: 14 figures, 3 tables, Space Science Reviews, submitte

    Self-Assembling Ferritin Nanoplatform for Development of Infectious Hematopoietic Necrosis Virus (IHNV) Vaccine

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    Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold (FerritVac), we constructed a self-assembling Infectious Hematopoietic Necrosis Virus (IHNV) nanovaccine. IHNV is a WOAH-listed disease for which there are currently no therapeutic treatments and no globally available commercial vaccine. Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH and temperature conditions, mimicking the harsh gastrointestinal condition of rainbow trout, the main IHNV host. MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture incubated with different doses of up to 100 µg/mL for 14 hours. In trout head kidney macrophages, FerritVac NPs upregulated expression of innate antiviral immunity, IHNV and other fish rhabdovirus infection gene markers (mx, vig1, ifit5 and isg-15). This novel vaccine nano-self-assembly approach offers significant commercial potential for non-mammalian viruses and the control of fish viral diseases. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine

    Colour response in western flower thrips varies intraspecifically

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    Discrepancies in the published research as to the attraction of the economically important pest western flower thrips (WFT) to different colours confounds the optimisation of field traps for pest management purposes. We considered whether the different experimental conditions of independent studies could have contributed to this. Therefore, the behavioural response (i.e., landings) to different colour cues of two WFT laboratory populations from Germany (DE) and The Netherlands (NL), which had previously been independently shown to have different colour preferences, were tested in the same place, and under the same experimental conditions. Single-choice wind tunnel bioassays supported previous independent findings, with more of a NL population landing on the yellow LED lamp (588 nm) than the blue (470 nm) (p = 0.022), and a not-statistically significant trend observed in a DE population landing more on blue compared to yellow (p = 0.104). To account for potential original host rearing influences, both populations were subsequently established on bean for ~20 weeks, then yellow chrysanthemum for 4–8 and 12–14 weeks and tested in wind tunnel choice bioassays. Laboratory of origin, irrespective of the host plant rearing regime, remained a significant effect (p < 0.001), with 65% of the NL WFT landing on yellow compared to blue (35%), while 66% of the DE WFT landed on blue compared to yellow (34%). There was also a significant host plant effect (p < 0.001), with increased response to yellow independent of laboratory of origin after rearing on chrysanthemum for 12–14 weeks. Results suggest that differing responses of WFT populations to colour is, in this case, independent of the experimental situation. Long-term separate isolation from the wild cannot be excluded as a cause, and the implications of this for optimising the trap colour is discussed

    Physicochemical characteristics of soluble oligomeric A β and their pathologic role in Alzheimer's disease

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    Extracellular fibrillar amyloid deposits are prominent and universal Alzheimer's disease (AD) features, but senile plaque abundance does not always correlate directly with the degree of dementia exhibited by AD patients. The mechanism(s) and dynamics of Abeta fibril genesis and deposition remain obscure. Enhanced Abeta synthesis rates coupled with decreased degradative enzyme production and accumulating physical modifications that dampen proteolysis may all enhance amyloid deposit formation. Amyloid accumulation may indirectly exert the greatest pathologic effect on the brain vasculature by destroying smooth muscle cells and creating a cascade of negative impacts on cerebral blood flow. The most visible manifestation of amyloid dis-equilibrium could actually be a defense mechanism employed to avoid serious vascular wall degradation while the major toxic effects to the gray and white matter neurons are mediated by soluble oligomeric Abeta peptides with high beta-sheet content. The recognition that dynamic soluble oligomeric Abeta pools exist in AD and are correlated to disease severity led to neurotoxicity and physical conformation studies. It is now recognized that the most basic soluble Abeta peptides are stable dimers with hydrophobic regions sequestered from the aqueous environment and are capable of higher order aggregations. Time course experiments employing a modified ELISA method able to detect Abeta oligomers revealed dynamic intermolecular interactions and additional experiments physically confirmed the presence of stable amyloid multimers. Amyloid peptides that are rich in beta-sheet structure are capable of creating toxic membrane ion channels and a capacity to self-assemble as annular structures was confirmed in vitro using atomic force microscopy. Biochemical studies have established that soluble Abeta peptides perturb metabolic processes, provoke release of deleterious reactive compounds, reduce blood flow, induce mitochondrial apoptotic toxicity and inhibit angiogenesis. While there is no question that gross amyloid deposition does contribute to AD pathology, the destructive potential now associated with soluble Abeta suggests that treatment strategies that target these molecules may be efficacious in preventing some of the devastating effects of AD.Fil: Watson, Desiree. Pfizer Global Research and Development; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Kokjohn, Tyler A.. Midwestern University; Estados UnidosFil: Kuo, Yu Min. National Cheng Kung University; República de ChinaFil: Lyubchenko, Yuri. University of Nebrasca; Estados UnidosFil: Pinsky, David. University of Michigan; Estados UnidosFil: Connolly, E. Sander. Columbia University; Estados UnidosFil: Esh, Chera. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Stine, W. Blaine. Midwestern University; Estados UnidosFil: Rowse, Linda M.. Midwestern University; Estados UnidosFil: Emmerling, Mark R.. Midwestern University; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados Unido

    Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations

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    We describe how the James Webb Space Telescope (JWST) Near-Infrared Spectrograph's (NIRSpec's) detectors will be read out, and present a model of how noise scales with the number of multiple non-destructive reads sampling-up-the-ramp. We believe that this noise model, which is validated using real and simulated test data, is applicable to most astronomical near-infrared instruments. We describe some non-ideal behaviors that have been observed in engineering grade NIRSpec detectors, and demonstrate that they are unlikely to affect NIRSpec sensitivity, operations, or calibration. These include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real test data, we show that the reset anomaly is: (1) very nearly noiseless and (2) can be easily calibrated out. Likewise, we show that large-amplitude RTN affects only a small and fixed population of pixels. It can therefore be tracked using standard pixel operability maps.Comment: 55 pages, 10 figure

    Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

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    Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

    Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations

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    BACKGROUND: Mutations in the presenilin (PSEN) genes are associated with early-onset familial Alzheimer's disease (FAD). Biochemical characterizations and comparisons have revealed that many PSEN mutations alter gamma-secretase activity to promote accumulation of toxic Abeta42 peptides. In this study, we compared the histopathologic and biochemical profiles of ten FAD cases expressing independent PSEN mutations and determined the degradation patterns of amyloid-beta precursor protein (AbetaPP), Notch, N-cadherin and Erb-B4 by gamma-secretase. In addition, the levels of Abeta40/42 peptides were quantified by ELISA. RESULTS: We observed a wide variation in type, number and distribution of amyloid deposits and neurofibrillary tangles. Four of the ten cases examined exhibited a substantial enrichment in the relative proportions of Abeta40 over Abeta42. The AbetaPP N-terminal and C-terminal fragments and Tau species, assessed by Western blots and scanning densitometry, also demonstrated a wide variation. The Notch-1 intracellular domain was negligible by Western blotting in seven PSEN cases. There was significant N-cadherin and Erb-B4 peptide heterogeneity among the different PSEN mutations. CONCLUSION: These observations imply that missense mutations in PSEN genes can alter a range of key gamma-secretase activities to produce an array of subtly different biochemical, neuropathological and clinical manifestations. Beyond the broad common features of dementia, plaques and tangles, the various PSEN mutations resulted in a wide heterogeneity and complexity and differed from sporadic AD.Fil: Maarouf, Chera L.. Sun Health Research Institute; Estados UnidosFil: Daugs, Ian D.. Sun Health Research Institute; Estados UnidosFil: Spina, Salvatore. Universita Degli Studi Di Siena; Italia. Indiana University; Estados UnidosFil: Vidal, Ruben. Indiana University; Estados UnidosFil: Kokjohn, Tyler A.. Sun Health Research Institute; Estados Unidos. Midwestern University; Estados UnidosFil: Patton, R. Lyle. Sun Health Research Institute; Estados UnidosFil: Kalback, Walter M.. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Walker, Douglas G.. Sun Health Research Institute; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Beach, Thomas G.. Sun Health Research Institute; Estados UnidosFil: Ghetti, Bernardino. Indiana University; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados Unido

    Reduced clinical and postmortem measures of cardiac pathology in subjects with advanced Alzheimer's Disease

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    Background. Epidemiological studies indicate a statistical linkage between atherosclerotic vascular disease (ATH) and Alzheimer\u27s disease (AD). Autopsy studies of cardiac disease in AD have been few and inconclusive. In this report, clinical and gross anatomic measures of cardiac disease were compared in deceased human subjects with and without AD. Methods. Clinically documented cardiovascular conditions from AD (n = 35) and elderly non-demented control subjects (n = 22) were obtained by review of medical records. Coronary artery stenosis and other gross anatomical measures, including heart weight, ventricular wall thickness, valvular circumferences, valvular calcifications and myocardial infarct number and volume were determined at autopsy. Results. Compared to non-demented age-similar control subjects, those with AD had significantly fewer total diagnosed clinical conditions (2.91 vs 4.18), decreased coronary artery stenosis (70.8 vs 74.8%), heart weight (402 vs 489 g for males; 319 vs 412 g for females) and valvular circumferences. Carriage of the Apolipoprotein E-ε4 allele did not influence the degree of coronary stenosis. Group differences in heart weight remained significant after adjustment for age, gender, body mass index and apolipoprotein E genotype while differences in coronary artery stenosis were significantly associated with body mass index alone. Conclusions. The results are in agreement with an emerging understanding that, while midlife risk factors for ATH increase the risk for the later development of AD, once dementia begins, both risk factors and manifest disease diminish, possibly due to progressive weight loss with increasing dementia as well as disease involvement of the brain\u27s vasomotor centers. © 2011 Beach et al; licensee BioMed Central Ltd

    Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the chicken and the egg

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    In the October 2013 issue of Acta Neuropathologica there were three very interesting articles on: Amyloid or tau: the chicken or the egg? In the first article, David Mann and John Hardy argued that the deposition of aggregated amyloid β (Aβ) protein in the brain is a primary driving force behind the pathogenesis of Alzheimer’s disease with tau pathology following as a consequential or at least a secondary event. In the communication that followed, Braak and Del Tredici presented the contrary argument with accumulation of tau protein as the primary event in sporadic Alzheimer’s disease. Attems and Jellinger questioned the concept of a chicken and egg and suggested that the majority of cases of age-associated dementia are not caused by one single primary pathological mechanism

    Biofabrication of functional protein nanoparticles through simple His-tag engineering

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    Altres ajuts: Acord transformatiu CRUE-CSICWe have developed a simple, robust, and fully transversal approach for thea-la-cartefabrication of functional multimeric nanoparticles with potential biomedical applications, validated here by a set of diverse and unrelated polypeptides. The proposed concept is based on the controlled coordination between Znions and His residues in His-tagged proteins. This approach results in a spontaneous and reproducible protein assembly as nanoscale oligomers that keep the original functionalities of the protein building blocks. The assembly of these materials is not linked to particular polypeptide features, and it is based on an environmentally friendly and sustainable approach. The resulting nanoparticles, with dimensions ranging between 10 and 15 nm, are regular in size, are architecturally stable, are fully functional, and serve as intermediates in a more complex assembly process, resulting in the formation of microscale protein materials. Since most of the recombinant proteins produced by biochemical and biotechnological industries and intended for biomedical research are His-tagged, the green biofabrication procedure proposed here can be straightforwardly applied to a huge spectrum of protein species for their conversion into their respective nanostructured formats
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