The role of tau in neurodegeneration

Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remain unclear, as do the mechanism(s) by which they cause neuronal death. Nonetheless, it is believed that tau-mediated neurodegeneration is likely to result from a combination of toxic gains of function as well as from the loss of normal tau function. To truly appreciate the detrimental consequences of aberrant tau function, a better understanding of all functions carried out by tau, including but not limited to the role of tau in microtubule assembly and stabilization, is required. This review will summarize what is currently known regarding the involvement of tau in the initiation and development of neurodegeneration in tauopathies, and will also highlight some of the remaining questions in need of further investigation

Temporal variations in the understory photosynthetic photon flux density of deciduous stand: the effects of canopy development, solar elevation, and sky conditions

The effects of canopy development, solar elevation, and sky conditions on temporal variation in photosynthetic photon flux density (PPFD) were examined within a 9-year-old bigleaf maple stand on Vancouver Island (Canada). PPFD was measured every second and stored as 10-min averages from 18 May to 14 October 1996, at 52 microsites characterised according to their growing season %PPFD (GSP). PPFD and %PPFD variability was examined at three different temporal levels. Specific days in May, July, and September with clear and overcast sky conditions were selected to separate the effects of canopy development and solar elevation on diurnal and seasonal light variability. \ud Diurnal light variability expressed as the mean of the difference between two consecutive 10-min averages of PPFD and %PPFD decreased with increasing GSP on clear days in May. For clear days in July and September, variability was characterised by arc-shaped relationships with high variability for microsites receiving between 20 and 80% GSP and lower variability for microsites below 20 and above 80% GSP. On overcast days, diurnal variability in PPFD increased with increasing GSP while diurnal variability in %PPFD showed an arc-shape relationship. The coefficient of variation of PPFD and %PPFD decreased with increasing GSP on clear days and sunflecks decreased with decreasing GSP and from May to September. \ud Day-to-day light variability expressed as the mean difference between consecutive daily PPFD increased with increasing GSP while the mean difference between consecutive daily %PPFD was higher for microsites receiving between 20 and 80% GSP. The coefficient of variation for the daily PPFD and %PPFD was higher for microsites receiving <20% GSP compared to other microsites. Seasonal light variability showed that microsites with <50% GSP received up to eight times more light in May than in July on both clear and overcast sky conditions because of canopy development. From July to September in clear sky conditions, decrease in light was variable for microsites receiving <40% GSP; probably because of the position of microsites in relation to the solar track. On overcast days, mean daily PPFD above canopy and in the understorey was 2 to 3 times higher in July than in September while mean daily %PPFD remained stable. The possible effects of the types of diurnal and day-to-day light variability on physiological and morphological responses of understorey plants are discussed

Comparison of various methods for estimating the mean growing season percent photosynthetic photon flux density in forests

Five methods for estimating the mean growing season percent photosynthetic photon flux density (PPFD) were compared to continuous measurements of PPFD throughout the growing season within a young bigleaf maple stand on Vancouver Island (Canada). Measured PPFD was recorded continuously as 10-min averages over the growing season (May 18-October 14, 1996) using 52 gallium arsenide phosphide photodiodes in the understory and a LI-COR quantum sensor (LI-190SA) in the open. Photodiodes were randomly located on a systematic grid of points and represented a wide range of above canopy openings which were classified into three different types of light environments: closed canopy, gaps of various sizes, and open canopy. Objectives of this study were to compare different methods for estimating the growing season %PPFD and to determine the efficiency of these methods in the three light environments. At each photodiode location, instantaneous light measurements using a Ceptometer on sunny days around noon and a LAI-2000 Plant Canopy Analyzer were made and hemispherical canopy photographs were taken. 10-min averages recorded by the photodiodes during completely overcast sky conditions were used as surrogate values for a method that uses instantaneous measurements on overcast days. Finally, a new light model (LITE) developed to estimate growing season %PPFD in a deciduous canopy was tested. All these five methods provided estimates of growing season %PPFD and are much less time consuming than continuous measurements of %PPFD using photodiodes. The three most accurate (r2>0.89) methods to estimate the growing season %PPFD were the 10 min averages on overcast days, the diffuse non-interceptance calculated using the LAI-2000, and the gap light index (GLI) calculated from the hemispherical canopy photographs. These three methods performed similarly in each type of light environment. Although the relationship between the LITE model and the growing season %PPFD was good (r2=0.79), the model systematically underestimated light transmission. The instantaneous sunny days around noon method was the least efficient method (r2=0.68) for estimating the growing season %PPFD, although replacing instantaneous measures with the mean of two 10-min averages improved r2 to 0.84. Estimates on sunny days tended to be low in low light and high in high light. Practical considerations such as equipment availability, cost, sampling and processing time, sky conditions, and the number of microsites to be sampled should be taken into account in the selection of the suitable method for a particular study

Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with indicators of disease severity. By facilitating the identification of individuals at risk of phenoconversion, and the early diagnosis of FTD, plasma NfL can aid in participant selection for prevention or early treatment trials. Moreover, its prognostic utility would improve patient care, clinical trial efficiency, and treatment outcome estimations

Predicting and managing light in the understory of boreal forests

This paper reviews current information relating to the dynamics of light in northern and boreal forests and discusses factors affecting overstory light transmission, seasonality of light, sunflecks, canopy gaps, and understory development, particularly with regard to tree regeneration. Techniques for measurement of light in forests such as radiometers, photosensitive paper or chemicals, hemispherical canopy photographs, the plant canopy analyzer, or visual estimators of canopy density are each discussed in terms of their accuracy, costs, ease of use, and conditions required during measurement. Predictive models of light transmission based on canopy architecture are also described in terms of their assumptions, accuracy, and input data costs. Lastly the paper discusses the relationship among overstory and understory densities, ground-level light, and 'windows of opportunity' for regeneration of trees in the understory following management interventions

The FALCON concept: multi-object spectroscopy combined with MCAO in near-IR

A large fraction of the present-day stellar mass was formed between z=0.5 and z~3 and our understanding of the formation mechanisms at work at these epochs requires both high spatial and high spectral resolution: one shall simultaneously} obtain images of objects with typical sizes as small as 1-2kpc(~0''.1), while achieving 20-50 km/s (R >= 5000) spectral resolution. The obvious instrumental solution to adopt in order to tackle the science goal is therefore a combination of multi-object 3D spectrograph with multi-conjugate adaptive optics in large fields. A partial, but still competitive correction shall be prefered, over a much wider field of view. This can be done by estimating the turbulent volume from sets of natural guide stars, by optimizing the correction to several and discrete small areas of few arcsec2 selected in a large field (Nasmyth field of 25 arcmin) and by correcting up to the 6th, and eventually, up to the 60th Zernike modes. Simulations on real extragalactic fields, show that for most sources (>80%), the recovered resolution could reach 0".15-0".25 in the J and H bands. Detection of point-like objects is improved by factors from 3 to >10, when compared with an instrument without adaptive correction. The proposed instrument concept, FALCON, is equiped with deployable mini-integral field units (IFUs), achieving spectral resolutions between R=5000 and 20000. Its multiplex capability, combined with high spatial and spectral resolution characteristics, is a natural ground based complement to the next generation of space telescopes.Comment: ESO Workshop Proceedings: Scientific Drivers for ESO Future VLT/VLTI Instrumentation, 10 pages and 5 figure

Magnetic and electronic properties of lithium cobalt oxide substituted by nickel

[Abstract] We measured susceptibility, electron-spin resonance, magnetization and electrical conductivity of LiCo1−yNiyO2 powders synthesized by wet-chemistry method using succinic acid as chelating agent. We found unusual properties in the nickel-rich LiCo0.2Ni0.8O2, which shows several resonance lines as a function of the temperature in the range 3.5–300 K. The signal at low magnetic field is attributed to the magnetic domains in the nanostructured sample. The two other lines correspond to the typical ferromagnetic signal observed in powdered compounds. In the temperature range 120–300 K, the unique ESR line centered at 315 mT is the paramagnetic signal with a gyromagnetic factor g=2.12, which is in good agreement with the presence of a high concentration of Ni3+ (3d7) ions. In the nickel-rich oxide, LiNi0.8Co0.2O2, the magnetic data are qualitatively well-described by the model proposed by Drillon and Panissod for a 3D ferromagnetic order.Spanish and French Foreign Office; HF 1999-0101Spanish and French Foreign Office; PAI Picasso 00717T

A fast ILP-based Heuristic for the robust design of Body Wireless Sensor Networks

We consider the problem of optimally designing a body wireless sensor network, while taking into account the uncertainty of data generation of biosensors. Since the related min-max robustness Integer Linear Programming (ILP) problem can be difficult to solve even for state-of-the-art commercial optimization solvers, we propose an original heuristic for its solution. The heuristic combines deterministic and probabilistic variable fixing strategies, guided by the information coming from strengthened linear relaxations of the ILP robust model, and includes a very large neighborhood search for reparation and improvement of generated solutions, formulated as an ILP problem solved exactly. Computational tests on realistic instances show that our heuristic finds solutions of much higher quality than a state-of-the-art solver and than an effective benchmark heuristic.Comment: This is the authors' final version of the paper published in G. Squillero and K. Sim (Eds.): EvoApplications 2017, Part I, LNCS 10199, pp. 1-17, 2017. DOI: 10.1007/978-3-319-55849-3\_16. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-55849-3_1

Biomarkers for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated With Hexanucleotide Expansion Mutations in C9orf72

Now that genetic testing can identify persons at risk for developing amyotrophic lateral sclerosis (ALS) many decades before symptoms begin, there is a critical need for biomarkers that signal the onset and progression of degeneration. The search for candidate disease biomarkers in patients with mutations in the gene C9orf72 has included imaging, physiology, and biofluid measurements. In cross-sectional imaging studies, C9+ ALS patients display diffuse reductions of gray and white matter integrity compared to ALS patients without mutations. This structural imaging signature overlaps with frontotemporal dementia (FTD), reflecting the frequent co-occurrence of cognitive impairment, even frank FTD, in C9+ ALS patients. Changes in functional connectivity occur as critical components of the networks associated with cognition and behavior degenerate. In presymptomatic C9+carriers, subtle differences in volumes of subcortical structures and functional connectivity can be detected, often decades before the typical family age of symptom onset. Dipeptide repeat proteins produced by the repeat expansion mutation are also measurable in the cerebrospinal fluid (CSF) of presymptomatic gene carriers, possibly throughout their lives. In contrast, a rise in the level of neurofilament proteins in the CSF appears to presage the onset of degeneration in presymptomatic carriers in one longitudinal study. Cross-sectional studies indicate that neurofilament protein levels may provide prognostic information for survival in C9+ ALS patients. Longitudinal studies will be needed to validate the candidate biomarkers discussed here. Understanding how these candidate biomarkers change over time is critical if they are to be used in future therapeutic decisions