The Neuropsychology of Huntington's Disease Snowden, Julie S
Archives of clinical neuropsychology,
2017-Nov-01, 2017-11-01, 20171101, Letnik:
32, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Huntington's disease is an inherited, degenerative brain disease, characterized by involuntary movements, cognitive disorder and neuropsychiatric change. Men and women are affected equally. Symptoms ...emerge at around 40 years, although there is wide variation. A rare juvenile form has onset in childhood or adolescence. The evolution of disease is insidious and structural and functional brain changes may be present more than a decade before symptoms and signs become manifest. The earliest site of pathology is the striatum and neuroimaging measures of striatal change correlate with neurological and cognitive markers of disease. Chorea and other aspects of the movement disorder are the most visible aspect of the disease. However, non-motor features have greatest affect on functional independence and quality of life, so require recognition and management. The evidence-base for non-pharmacological treatments in Huntington's disease is currently limited, but recent intervention studies are encouraging.
Background: Psychiatric symptoms are a common feature of Huntington’s disease (HD) and often precede the onset of motor and cognitive impairments. However, it remains unclear whether psychiatric ...changes in the preclinical period result from structural change, are a reaction to being at risk or simply a coincidental occurrence. Few studies have investigated the temporal course of psychiatric disorder across the preclinical period. Objectives: To compare lifetime and current prevalence of psychiatric disorder in presymptomatic gene carriers and non-carriers and to examine the relationship of psychiatric prevalence in gene carriers to temporal proximity of clinical onset. Methods: Lifetime and current psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non-carriers) were obtained using a structured clinical interview, the Composite International Diagnostic Interview. Psychiatric disorders were classified using both standardised diagnostic criteria and a more subtle symptom based approach. Follow-up of gene carriers (n = 51) enabled analysis of the role of temporal proximity to clinical onset. Results: Gene carriers and non-carriers did not differ in terms of the lifetime frequency of clinical psychiatric disorders or subclinical symptoms. However, gene carriers reported a significantly higher rate of current depressive symptoms. Moreover, the rate of depression increased as a function of proximity to clinical onset. Conclusions: Affective disorder is an important feature of the prodromal stages of HD. The findings indicate that depression cannot be accounted for by natural concerns of being at risk. There is evidence of a window of several years in which preclinical symptoms are apparent.
Investigating the Structure of Vela X Slane, P.; Lovchinsky, I.; Kolb, C. ...
The Astrophysical journal,
10/2018, Letnik:
865, Številka:
2
Journal Article
Recenzirano
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Vela X is a prototypical example of a pulsar wind nebula whose morphology and detailed structure have been affected by interaction with the reverse shock of its host supernova remnant. The resulting ...complex of filamentary structure and mixed-in ejecta embedded in a nebula that is offset from the pulsar provides the best example we have of this middle-age state that characterizes a significant fraction of composite supernova remnants (SNRs), and perhaps all of the large-diameter pulsar wind nebulae (PWNe) seen as TeV sources. Here, we report on an XMM-Newton (hereafter XMM) Large Project study of Vela X, supplemented by additional Chandra observations. Through broad spectral modeling, as well as detailed spectral investigations of discrete emission regions, we confirm previous studies that report evidence for ejecta material within Vela X, and show that equivalent-width variations of O vii and O viii are consistent with temperature maps within the PWN that show low-temperature regions where the projected SNR emission appears to dominate emission from the ejecta. We identify spectral variations in the nonthermal emission, with hard emission being concentrated near the pulsar. We carry out investigations of the Vela X "cocoon" structure, and with hydrodynamical simulations, show that its overall properties are consistent with structures formed in the late-phase evolution of a composite SNR expanding into a surrounding medium with a density gradient, with ejecta material being swept beyond the pulsar and compressed into an elongated structure in the direction opposite the high external density.
A group of 111 patients with Huntington's disease (HD) underwent a minimum of three annual neuropsychiatric assessments, using the Problem Behaviors Assessment for Huntington's Disease (PBA-HD). ...Longitudinal prevalence of neuropsychiatric symptoms was notably higher than baseline prevalence, suggesting that previous studies may have underestimated the extent of this clinical problem. Moreover, apathy, irritability, and depression were each associated with distinct longitudinal profiles. Apathy progressed over time and across disease stages. Irritability also increased significantly, but only in early stages of HD. Depression did not increase significantly at any stage of disease. The neuropsychiatric syndrome of apathy appears to be intrinsic to the evolution and progression of HD.
Far-ultraviolet (FUV) observations have revealed transition temperature gas (TTG; log T(K)~ 5), located in the lower Galactic halo and in high-velocity clouds. However, the corresponding X-ray ...absorption has so far remained mostly undetected. In order to make an improvement in this respect in Galactic X-ray absorption studies, we accumulated very deep (~3 Ms) spectra of the blazar PKS 2155-304 obtained with the spectrometers RGS1, RGS2, LETG/HRC, and LETG/ACIS-S and studied the absorption lines due to the intervening Galactic components. The very high quality of the data and coverage of important wavelengths with at least two independent instruments allowed us to reliably detect 10 Galactic lines with better than 99.75% confidence. We discovered significant absorption from blended O iv transitions 1s–2p 2S (22.571 Å), 1s–2p 2P (22.741 Å), and 1s–2p 2D (22.777 Å), and from the O v transition 1s–2p (22.370 Å) from TTG at log T(K)=5.2 ± 0.1. A joint X-ray and FUV analysis indicated that photoionisation is negligible for this component and that the gas is in a cooling transition phase. However, the temperature is high enough that the column density ratio N(O iv)/N(O v) is not significantly different from that in collisional ionisation equilibrium (CIE). Under CIE we obtained NOIV = 3.6 ± 2.0 ×1015 cm-2, corresponding to NH = 1.0 ± 0.5 ×1019(Z⊙/ZTTG) cm-2.
We have investigated the extent and pattern of immunostaining for ubiquitin protein (UBQ) in 60 patients with frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions ...(FTLD-U), 37 of whom were ascertained in Manchester UK and 23 in Newcastle-Upon-Tyne, UK. There were three distinct histological patterns according to the form and distribution of the UBQ pathology. Histological type 1 was present in 19 patients (32%) and characterised by the presence of a moderate number, or numerous, UBQ immunoreactive neurites and intraneuronal cytoplasmic inclusions within layer II of the frontal and temporal cerebral cortex, and cytoplasmic inclusions within granule cells of the dentate gyrus; neuronal intranuclear inclusions (NII) of a "cat's eye" or "lentiform" appearance were present in 17 of these patients. In histological type 2 (16 patients, 27%), UBQ neurites were predominantly, or exclusively, present with few intraneuronal cytoplasmic inclusions within layer II of the cerebral cortex, while in histological type 3 (25 patients, 42%), UBQ intraneuronal cytoplasmic inclusions either within the cortical layer II or in the granule cells of the dentate gyrus, with few or no UBQ neurites, were seen. In neither of these latter two groups were NII present. The influence of histological type on clinical phenotype was highly significant with type 1 histology being associated clinically with cases of frontotemporal dementia (FTD) or progressive non-fluent aphasia (PNFA), type 2 histology with semantic dementia (SD), and type 3 histology with FTD, or FTD and motor neurone disease (MND).
Type I fatty acid synthases (FASs) are critical metabolic enzymes which are common targets for bioengineering in the production of biofuels and other products. Serendipitously, we identified FAS as a ...contaminant in a cryoEM dataset of virus-like particles (VLPs) purified from P. pastoris, an important model organism and common expression system used in protein production. From these data, we determined the structure of P. pastoris FAS to 3.1 Å resolution. While the overall organisation of the complex was typical of type I FASs, we identified several differences in both structural and enzymatic domains through comparison with the prototypical yeast FAS from S. cerevisiae. Using focussed classification, we were also able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is key for function. Ultimately, the structure reported here will be a useful resource for further efforts to engineer yeast FAS for synthesis of alternate products.
Performance on tests of odour discrimination, naming, and matching was compared in patients with four distinct forms of neurodegenerative disease: Alzheimer's disease (AD), semantic dementia (SD), ...frontotemporal dementia (FTD), and corticobasal degeneration (CBD). The SD patients were found to have a severe impairment of identification from olfaction despite having normal discrimination, consistent with the multimodal semantic impairment characteristic of this patient group. The AD patients’ poor odour discrimination suggests that a perceptual impairment is the root of their poor odour identification. Mild impairments in odour identification observed in FTD and CBD are consistent with their generalised executive dysfunction. The findings illustrate that breakdown in olfaction can occur at a perceptual or semantic level, analogous to the distinction between apperceptive and associative forms of deficit in the visual and auditory modalities. The findings add further insights into the nature of the semantic deficit in SD by exploring a hitherto neglected modality and may have relevance in explaining the altered eating habits commonly associated with SD.
ABSTRACT The mean production factor, or broadband averaged cross-section, for solar wind charge-exchange (SWCX) with hydrogen producing emission in the ROSAT keV (R12) band is count degree−2 cm4. The ...production factor is expected to be temporally variable, and that variation is roughly 15%. These values are derived from a comparison of the long-term (background) enhancements in the ROSAT All-Sky Survey with magnetohysdrodynamic simulations of the magnetosheath. This value is 1.8-4.5 times higher than values derived from limited atomic data, suggesting that those values may be missing a large number of faint lines. This production factor is important for deriving the exact amount of keV band flux that is due to the Local Hot Bubble, for planning future observations in the keV band, and for evaluating proposals for remote sensing of the magnetosheath. The same method cannot be applied to the keV band as that band, being composed primarily of the oxygen lines, is far more sensitive to the detailed abundances and ionization balance in the solar wind. We also show, incidentally, that recent efforts to correlate XMM-Newton observing geometry with magnetosheath SWCX emission in the oxygen lines have been, quite literally, misguided. Simulations of the inner heliosphere show that broader efforts to correlate heliospheric SWCX with local solar wind parameters are unlikely to produce useful results.
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