Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited disorder, which is caused by a pathological expansion of a polyglutamine (polyQ) tract in the coding region of the ATXN2 gene. Like other ataxias, SCA2 most overtly affects Purkinje cells (PCs) in the cerebellum. Using a transgenic mouse model expressing a full-length ATXN2(Q127)-complementary DNA under control of the Pcp2 promoter (a PC-specific promoter), we examined the time course of behavioral, morphologic, biochemical and physiological changes with particular attention to PC firing in the cerebellar slice. Although motor performance began to deteriorate at 8 weeks of age, reductions in PC number were not seen until after 12 weeks. Decreases in the PC firing frequency first showed at 6 weeks and paralleled deterioration of motor performance with progression of disease. Transcription changes in several PC-specific genes such as Calb1 and Pcp2 mirrored the time course of changes in PC physiology with calbindin-28 K changes showing the first small, but significant decreases at 4 weeks. These results emphasize that in this model of SCA2, physiological and behavioral phenotypes precede morphological changes by several weeks and provide a rationale for future studies examining the effects of restoration of firing frequency on motor function and prevention of future loss of PCs

An overview of Information and Communication Technology (ICT) Initiatives in rural Africa towards empowerment

Information and Communication Technology (ICT) is transforming global economy, but access to use of ICT is not distributed evenly. This research focuses on addressing major economic, political and social challenges faced by rural Africa to access Information and Communication Technology (ICT). A literature survey was conducted to see the role of ICT for rural development and how different countries developed with ICT initiatives. ICT is vital for poverty reduction and in growth of sectors like agriculture, business, health, tourism, education, governance etc. Computer illiteracy, scattered population, HIV/AIDS illnesses, lack of access to internet and telecommunication facilities and lack of good ICT policies which encourages ICT inflow, have been powerful obstacles for the social and economic growth of rural Africa. The authors present a number of successful ICT initiatives on women empowerment, e-schools, e-government, e-commerce, e-health, e-agriculture and e-business that has helped to access ICT in rural Africa. The paper also gives ideas on how rural Africa can get connected. The case studies will elaborate on ICT initiatives for rural African development. The research also focuses on various ways to close digital divide

A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2

Metabotropic glutamate receptor 1 (mGluR1) function in Purkinje neurons (PNs) is essential for cerebellar development and for motor learning and altered mGluR1 signaling causes ataxia. Downstream of mGluR1, dysregulation of calcium homeostasis has been hypothesized as a key pathological event in genetic forms of ataxia but the underlying mechanisms remain unclear. We find in a spinocerebellar ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is disturbed across a broad range of physiological conditions. At parallel fiber synapses, mGluR1-mediated excitatory postsynaptic currents (EPSCs) and associated calcium transients are increased and prolonged in SCA2 PNs. In SCA2 PNs, enhanced mGluR1 function is prevented by buffering [Ca 2+ ] at normal resting levels while in wildtype PNs mGluR1 EPSCs are enhanced by elevated [Ca 2+ ]. These findings demonstrate a deleterious positive feedback loop involving elevated intracellular calcium and enhanced mGluR1 function, a mechanism likely to contribute to PN dysfunction and loss in SCA2

Health Status and Associated factors of middle-aged and Older Adult Cancer Survivors in India : Results from the Longitudinal Ageing Study in India

Funding This study was funded by the Scottish Funding council’s Global Challenges Research Fund Pump Priming Grant (SF10206–53). The funders had no role in the data analysis or decision to publish.Peer reviewedPublisher PD

Towards a High Diffraction Efficiency of Photorefractive Multiple Quantum Wells

doi:10.1063/1.1994721 http://link.aip.org/link/?APCPCS/772/1579/1We propose a method to improve the diffraction efficiency of photorefractive multiple quantum well devices in the transverse-field geometry. Higher efficiencies have been achieved through systematic electrical modulation studies

Components of palliative care interventions addressing the needs of people with dementia living in long term care: a systematic review

© The Author(s) 2020. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background: People with dementia requiring palliative care havemultiple needs that require complex, multicomponent interventions. Thisneed is amplified in the long term care setting. The European Associationfor Palliative Care (EAPC) White Paper offers recommendations forpalliative care in dementia and highlights domains of care integral forthis population, thus providing useful guidance to developing suchinterventions. This review maps components of palliative careinterventions for people with dementia in LTCFs, with a particular focuson shared decision-making.Peer reviewe

Non-saturating magnetoresistance of inhomogeneous conductors: comparison of experiment and simulation

The silver chalcogenides provide a striking example of the benefits of imperfection. Nanothreads of excess silver cause distortions in the current flow that yield a linear and non-saturating transverse magnetoresistance (MR). Associated with the large and positive MR is a negative longitudinal MR. The longitudinal MR only occurs in the three-dimensional limit and thereby permits the determination of a characteristic length scale set by the spatial inhomogeneity. We find that this fundamental inhomogeneity length can be as large as ten microns. Systematic measurements of the diagonal and off-diagonal components of the resistivity tensor in various sample geometries show clear evidence of the distorted current paths posited in theoretical simulations. We use a random resistor network model to fit the linear MR, and expand it from two to three dimensions to depict current distortions in the third (thickness) dimension. When compared directly to experiments on Ag$_{2\pm\delta}$Se and Ag$_{2\pm\delta}$Te, in magnetic fields up to 55 T, the model identifies conductivity fluctuations due to macroscopic inhomogeneities as the underlying physical mechanism. It also accounts reasonably quantitatively for the various components of the resistivity tensor observed in the experiments.Comment: 10 pages, 7 figure

Dipolar Gases in Coupled One-Dimensional Lattices

We consider dipolar bosons in two tubes of one-dimensional lattices, where the dipoles are aligned to be maximally repulsive and the particle filling fraction is the same in each tube. In the classical limit of zero inter-site hopping, the particles arrange themselves into an ordered crystal for any rational filling fraction, forming a complete devil's staircase like in the single tube case. Turning on hopping within each tube then gives rise to a competition between the crystalline Mott phases and a liquid of defects or solitons. However, for the two-tube case, we find that solitons from different tubes can bind into pairs for certain topologies of the filling fraction. This provides an intriguing example of pairing that is purely driven by correlations close to a Mott insulator

Devil's staircases and supersolids in a one-dimensional dipolar Bose gas

We consider a single-component gas of dipolar bosons confined in a one-dimensional optical lattice, where the dipoles are aligned such that the long-ranged dipolar interactions are maximally repulsive. In the limit of zero inter-site hopping and sufficiently large on-site interaction, the phase diagram is a complete devil's staircase for filling fractions between 0 and 1, wherein every commensurate state at a rational filling is stable over a finite interval in chemical potential. We perturb away from this limit in two experimentally motivated directions involving the addition of hopping and a reduction of the onsite interaction. The addition of hopping alone yields a phase diagram, which we compute in perturbation theory in the hopping, where the commensurate Mott phases now compete with the superfluid. Further softening of the onsite interaction yields alternative commensurate states with double occupancies which can form a staircase of their own, as well as one-dimensional "supersolids" which simultaneously exhibit discrete broken symmetries and superfluidity