Early Energy Deficit in Huntington Disease: Identification of a Plasma Biomarker Traceable during Disease Progression

Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD have not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance (1H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. 1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies

International audienceAbstractGastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host–pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host–pathogen interactions may help to identify novel prevention and control strategies

Control of style-of-faulting on spatial pattern of earthquake-triggered landslides

Predictive mapping of susceptibility to earthquake-triggered landslides (ETLs) commonly uses distance to fault as spatial predictor, regardless of style-of-faulting. Here, we examined the hypothesis that the spatial pattern of ETLs is influenced by style-of-faulting based on distance distribution analysis and Fry analysis. The Yingxiu–Beichuan fault (YBF) in China and a huge number of landslides that ruptured and occurred, respectively, during the 2008 Wenchuan earthquake permitted this study because the style-of-faulting along the YBF varied from its southern to northern parts (i.e. mainly thrust-slip in the southern part, oblique-slip in the central part and mainly strike-slip in the northern part). On the YBF hanging-wall, ETLs at 4.4–4.7 and 10.3–11.5 km from the YBF are likely associated with strike- and thrust-slips, respectively. On the southern and central parts of the hanging-wall, ETLs at 7.5–8 km from the YBF are likely associated with oblique-slips. These findings indicate that the spatial pattern of ETLs is influenced by style-of-faulting. Based on knowledge about the style-of-faulting and by using evidential belief functions to create a predictor map based on proximity to faults, we obtained higher landslide prediction accuracy than by using unclassified faults. When distance from unclassified parts of the YBF is used as predictor, the prediction accuracy is 80%; when distance from parts of the YBF, classified according to style-of-faulting, is used as predictor, the prediction accuracy is 93%. Therefore, mapping and classification of faults and proper spatial representation of fault control on occurrence of ETLs are important in predictive mapping of susceptibility to ETLs

A new classification of earthquake-induced landslide event sizes based on seismotectonic, topographic, climatic and geologic factors

Background This paper reviews the classical and some particular factors contributing to earthquake-triggered landslide activity. This analysis should help predict more accurately landslide event sizes, both in terms of potential numbers and affected area. It also highlights that some occurrences, especially those very far from the hypocentre/activated fault, cannot be predicted by state-of-the-art methods. Particular attention will be paid to the effects of deep focal earthquakes in Central Asia and to other extremely distant landslide activations in other regions of the world (e.g. Saguenay earthquake 1988, Canada). Results The classification of seismically induced landslides and the related ‘event sizes’ is based on five main factors: ‘Intensity’, ‘Fault factor’, ‘Topographic energy’, ‘Climatic background conditions’, ‘Lithological factor’. Most of these data were extracted from papers, but topographic inputs were checked by analyzing the affected region in Google Earth. The combination and relative weight of the factors was tested through comparison with well documented events and complemented by our studies of earthquake-triggered landslides in Central Asia. The highest relative weight (6) was attributed to the ‘Fault factor’; the other factors all received a smaller relative weight (2–4). The high weight of the ‘Fault factor’ (based on the location in/outside the mountain range, the fault type and length) is strongly constrained by the importance of the Wenchuan earthquake that, for example, triggered far more landslides in 2008 than the Nepal earthquake in 2015: the main difference is that the fault activated by the Wenchuan earthquake created an extensive surface rupture within the Longmenshan Range marked by a very high topographic energy while the one activated by the Nepal earthquake ruptured the surface in the frontal part of the Himalayas where the slopes are less steep and high. Finally, the calibrated factor combination was applied to almost 100 other earthquake events for which some landslide information was available. This comparison revealed the ability of the classification to provide a reasonable estimate of the number of triggered landslides and of the size of the affected area. According to this prediction, the most severe earthquake-triggered landslide event of the last one hundred years would actually be the Wenchuan earthquake in 2008 followed by the 1950 Assam earthquake in India – considering that the dominating role of the Wenchuan earthquake data (including the availability of a complete landslide inventory) for the weighting of the factors strongly influences and may even bias this result. The strongest landslide impacts on human life in recent history were caused by the Haiyuan-Gansu earthquake in 1920 – ranked as third most severe event according to our classification: its size is due to a combination of high shaking intensity, an important ‘Fault factor’ and the extreme susceptibility of the regional loess cover to slope failure, while the surface morphology of the affected area is much smoother than the one affected by the Wenchuan 2008 or the Nepal 2015 earthquakes. Conclusions The main goal of the classification of earthquake-triggered landslide events is to help improve total seismic hazard assessment over short and longer terms. Considering the general performance of the classification-prediction, it can be seen that the prediction either fits or overestimates the known/observed number of triggered landslides for a series of earthquakes, while it often underestimates the size of the affected area. For several events (especially the older ones), the overestimation of the number of landslides can be partly explained by the incompleteness of the published catalogues. The underestimation of the extension of the area, however, is real – as some particularities cannot be taken into account by such a general approach: notably, we used the same seismic intensity attenuation for all events, while attenuation laws are dependent on regional tectonic and geological conditions. In this regard, it is likely that the far-distant triggering of landslides, e.g., by the 1988 Saguenay earthquake (and the related extreme extension of affected area) is due to a very low attenuation of seismic energy within the North American plate. Far-distant triggering of landslides in Central Asia can be explained by the susceptibility of slopes covered by thick soft soils to failure under the effect of low-frequency shaking induced by distant earthquakes, especially by the deep focal earthquakes in the Pamir – Hindukush seismic region. Such deep focal and high magnitude (> > 7) earthquakes are also found in Europe, first of all in the Vrancea region (Romania). For this area as well as for the South Tien Shan we computed possible landslide event sizes related to some future earthquake scenarios