Abnormal clock gene expression and locomotor activity rhythms in two month-old female APPSwe/PS1dE9 mice

In addition to cognitive decline, Alzheimer’s disease (AD) is also characterized by agitation and disruptions in activity and sleep. These symptoms typically occur in the evening or at night and have been referred to as ‘sundowning’. These symptoms are especially difficult for carers and there are no specific drug treatments. There is increasing evidence that these symptoms reflect an underlying pathology of circadian rhythm generation and transmission. We investigated whether a transgenic mouse model relevant to AD (APPswe/PS1dE9) exhibits circadian alterations in locomotor activity and expression of clock genes involved in the regulation of the circadian cycle. Female mice at 2 months of age were investigated in their home cage. Results show that the APPswe/PS1dE9 transgene alters levels and patterns in circadian rhythm of locomotor activity. Expression of the clock genes Per1, Per2, Cry1 and Cry2 was found to increase at night compared to day in wild-type control mice in the medulla/pons. This effect was blunted for Cry1 and Cry2 gene expression in APPswe/PS1dE9. In summary, this study suggests altered circadian regulation of locomotor activity is abnormal in female APPswe/PS1dE9 mice and that this alteration has biomolecular analogies in a widely available model of AD. Furthermore, the early age at which these effects are manifest suggests that these circadian effects may precede plaque development. The APPswe/PS1dE9 mouse genetic model may have potential to serve as a tool in understanding the neuropathology of circadian abnormalities in AD and as a model system to test novel therapeutic agents for these symptoms

До питання про співвідношення праворозуміння та правової думки

У статті проаналізовано структуру праворозуміння, дано визначення поняття правова думка та вказано, що праворозуміння, як осмислення правової дійсності є складовою частиною правової думки.В статье проанализировано структуру правопонимания, дано определение понятия правовая мысль иопределено, что правопонимание как осмысление правовой действительности является составляющей правовой мысли.In the article are analyzed the structure of legal understanding, given the definition of legal thought and determined that the legal comprehension as a legal interpretation of reality is a part of legal thought

A panoramic mid-infrared survey of two distant clusters

We present panoramic Spitzer MIPS 24 μm observations, covering ~9 × 9 Mpc2 (25' × 25') fields around two massive clusters, Cl 0024+16 and MS 0451-03, at z = 0.39 and z = 0.55, respectively, reaching a 5 σ flux limit of ~200 μJy. Our observations cover a very wide range of environments within these clusters, from high-density regions around the cores out to the turnaround radius. Cross-correlating the mid-infrared catalogs with deep optical and near-infrared imaging of these fields, we investigate the optical/near-infrared colors of the mid-infrared sources. We find excesses of mid-infrared sources with the optical/near-infrared colors expected of cluster members in the two clusters and test this selection using spectroscopically confirmed 24 μm members. The much more significant excess is associated with Cl 0024+16, whereas MS 0451-03 has comparatively few mid-infrared sources. The mid-infrared galaxy population in Cl 0024+16 appears to be associated with dusty star-forming galaxies (typically redder than the general cluster population by up to AV ~ 1-2 mag) rather than emission from dusty tori around active galactic nuclei in early-type hosts. We compare the star formation rates derived from the total infrared (8-1000 μm) luminosities for the mid-infrared sources in Cl 0024+16 with those estimated from a published Hα survey, finding rates 5 times those found from Hα, indicating significant obscured activity in the cluster population. Compared to previous mid-infrared surveys of clusters from z ~ 0-0.5, we find evidence for strong evolution of the level of dust-obscured star formation in dense environments to z = 0.5, analogous to the rise in the fraction of optically selected star-forming galaxies seen in clusters and the field out to similar redshifts. However, there are clearly significant cluster-to-cluster variations in the populations of mid-infrared sources, probably reflecting differences in the intracluster media and recent dynamical evolution of these systems

Spatial Structure of Stationary Nonequilibrium States in the Thermostatted Periodic Lorentz Gas

We investigate analytically and numerically the spatial structure of the non-equilibrium stationary states (NESS) of a point particle moving in a two dimensional periodic Lorentz gas (Sinai Billiard). The particle is subject to a constant external electric field E as well as a Gaussian thermostat which keeps the speed |v| constant. We show that despite the singular nature of the SRB measure its projections on the space coordinates are absolutely continuous. We further show that these projections satisfy linear response laws for small E. Some of them are computed numerically. We compare these results with those obtained from simple models in which the collisions with the obstacles are replaced by random collisions.Similarities and differences are noted.Comment: 24 pages with 9 figure

Transcriptional profiling of suberoylanilide hydroxamic acid (SAHA) regulated genes in mineralizing dental pulp cells at early and late time points

Dental pulp tissue can be damaged by a range of irritants, however, if the irritation is removed and/or the tooth is adequately restored, pulp regeneration is possible (Mjör and Tronstad, 1974 [1]). At present, dental restorative materials limit healing by impairing mineralization and repair processes and as a result new biologically-based materials are being developed (Ferracane et al., 2010 [2]). Previous studies have highlighted the benefit of epigenetic modification by histone deacetylase inhibitor (HDACi) application to dental pulp cells (DPCs), which induces changes to chromatin architecture, promoting gene expression and cellular-reparative events (Duncan et al., 2013 [3]; Paino et al., 2014 [4]). In this study a genome-wide transcription profiling in epigenetically-modified mineralizing primary DPC cultures was performed, at relatively early and late time-points, to identify differentially regulated transcripts that may provide novel therapeutic targets for use in restorative dentistry. Here we provide detailed methods and analysis on these microarray data which has been deposited in Gene Expression Omnibus (GEO): GSE67175

Statistical Theory of Spin Relaxation and Diffusion in Solids

A comprehensive theoretical description is given for the spin relaxation and diffusion in solids. The formulation is made in a general statistical-mechanical way. The method of the nonequilibrium statistical operator (NSO) developed by D. N. Zubarev is employed to analyze a relaxation dynamics of a spin subsystem. Perturbation of this subsystem in solids may produce a nonequilibrium state which is then relaxed to an equilibrium state due to the interaction between the particles or with a thermal bath (lattice). The generalized kinetic equations were derived previously for a system weakly coupled to a thermal bath to elucidate the nature of transport and relaxation processes. In this paper, these results are used to describe the relaxation and diffusion of nuclear spins in solids. The aim is to formulate a successive and coherent microscopic description of the nuclear magnetic relaxation and diffusion in solids. The nuclear spin-lattice relaxation is considered and the Gorter relation is derived. As an example, a theory of spin diffusion of the nuclear magnetic moment in dilute alloys (like Cu-Mn) is developed. It is shown that due to the dipolar interaction between host nuclear spins and impurity spins, a nonuniform distribution in the host nuclear spin system will occur and consequently the macroscopic relaxation time will be strongly determined by the spin diffusion. The explicit expressions for the relaxation time in certain physically relevant cases are given.Comment: 41 pages, 119 Refs. Corrected typos, added reference

Linking canonical microcircuits and neuronal activity: Dynamic causal modelling of laminar recordings

Neural models describe brain activity at different scales, ranging from single cells to whole brain networks. Here, we attempt to reconcile models operating at the microscopic (compartmental) and mesoscopic (neural mass) scales to analyse data from microelectrode recordings of intralaminar neural activity. Although these two classes of models operate at different scales, it is relatively straightforward to create neural mass models of ensemble activity that are equipped with priors obtained after fitting data generated by detailed microscopic models. This provides generative (forward) models of measured neuronal responses that retain construct validity in relation to compartmental models. We illustrate our approach using cross spectral responses obtained from V1 during a visual perception paradigm that involved optogenetic manipulation of the basal forebrain. We find that the resulting neural mass model can distinguish between activity in distinct cortical layers – both with and without optogenetic activation – and that cholinergic input appears to enhance (disinhibit) superficial layer activity relative to deep layers. This is particularly interesting from the perspective of predictive coding, where neuromodulators are thought to boost prediction errors that ascend the cortical hierarchy

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections : current knowledge and new perspectives

ACKNOWLEDGEMENTS: We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions. FUNDING: We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government ‘Investissement d’Avenir’ program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government ‘Investissement d’Avenir’ program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).Peer reviewedPublisher PD

Using modeling tools for implementing feasible land use and nature conservation governance systems in small islands e The Pico Island (Azores) case-study

The present study deals with the development of systematic conservation planning as management instrument in small oceanic islands, ensuring open systems of governance, and able to integrate an informed and involved participation of the stakeholders. Marxan software was used to define management areas according a set of alternative land use scenarios considering different conservation and management paradigms. Modeled conservation zones were interpreted and compared with the existing protected areas allowing more fused information for future trade-outs and stakeholder's involvement. The results, allowing the identification of Target Management Units (TMU) based on the consideration of different development scenarios proved to be consistent with a feasible development of evaluation approaches able to support sound governance systems. Moreover, the detailed geographic identification of TMU seems to be able to support participated policies towards a more sustainable management of the entire islan

Restauration morpho-dynamique et redynamisation de la section court-circuitée du Rhin en aval du barrage de Kembs (projet INTERREG / EDF)

National audienceThe Upper Rhine River has been heavily impacted by channelization for flood protection and navigation, and then by damming for hydropower generation. In normal non flooding conditions, most of the flows are diverted in a canalized section whereas the regulated “old Rhine” bypassed reach runs a minimum flow. Between Huningue and Neuf-Brisach, engineering works induced simplification and stabilization of the channel pattern from a formerly braiding sector to a single incised channel, hydrological modifications, bottom armouring due to bedload decrease, and thus ecological alterations. Two complementary and interdisciplinary projects have been initiated to restore alluvial morphodynamics: i) the international “INTERREG IV - Redynamisation of the old Rhine” project (2009-2012) coordinated by the Alsace region, France; ii) the left bank “controlled erosion” project launched by Electricité de France (EDF) within Kembs hydroelectric station relicensing process since 2003-2004. The purpose of these projects is to evaluate the feasibility of an important hydro-morphological and ecological restoration plan on a 45 km long reach, through both field testing of bank erosion techniques at favourable locations, and artificial sediments input from right bank excavations. This will help define possible long term prospective scenarios, in order to restore sustainable sediment transport, morphodynamics variability and associated ecological functions. The study will involve historical analysis, hydro-morphological / hydraulic physical and numerical modelling, physical and ecological monitoring, and sociological aspectsLe Rhin alsacien-allemand a enregistré de profondes modifications morphologiques et hydrologiques à la suite de sa correction et de sa régularisation pour la protection contre les crues et la navigation, puis après la construction de barrages hydro-électriques. Les aménagements réalisés entre Huningue et Neuf-Brisach ont engendré une simplification et une stabilisation du style fluvial. Un fleuve en tresses a cédé la place à un chenal unique incisé. Le fond de chenal est devenu pavé à cause d’une diminution des apports de charge de fond et des altérations écologiques ont été observées (simplification des habitats aquatiques et riverains). Deux projets complémentaires et interdisciplinaires ont été engagés afin de restaurer une dynamique des formes alluviales : i) le projet international INTERREG IV – Redynamisation du Vieux Rhin (2009-2012) sous l’impulsion de la région Alsace ; ii) le projet d’érosion maitrisée des berges de la rive gauche conduit par Electricité de France (EDF) dans le cadre du renouvellement de la concession de l’aménagement de Kembs. L’objectif des deux projets est de définir un plan de restauration hydro-morphologique et écologique conduisant à la redynamisation d’un tronçon de 45 km. L’étude repose sur une analyse historique, l’exploitation de modèles à la fois physiques et numériques, et les suivis morphologiques in situ d’une recharge artificielle en sédiments et d’érosions de berge contrôlées. Ces études de faisabilité sont complétées par des analyses écologique et sociologique pour apprécier l’impact socio-environnemental de ces projets