High-frequency peripheral vibration decreases completion time on a number of motor tasks.

A recent theoretical account of motor control proposes that modulation of afferent information plays a role in affecting how readily we can move. Increasing the estimate of uncertainty surrounding the afferent input is a necessary step in being able to move. It has been proposed that an inability to modulate the gain of this sensory information underlies the cardinal symptoms of Parkinson's disease (PD). We aimed to test this theory by modulating the uncertainty of the proprioceptive signal using high-frequency peripheral vibration, to determine the subsequent effect on motor performance. We investigated if this peripheral stimulus might modulate oscillatory activity over the sensorimotor cortex in order to understand the mechanism by which peripheral vibration can change motor performance. We found that 80 Hz peripheral vibration applied to the right wrist of a total of 54 healthy human participants reproducibly improved performance across four separate randomised experiments on a number of motor control tasks (nine-hole peg task, box and block test, reaction time task and finger tapping). Improved performance on all motor tasks (except the amplitude of finger tapping) was also seen for a sample of 18PD patients ON medication. EEG data investigating the effect of vibration on oscillatory activity revealed a significant decrease in beta power (15-30 Hz) over the contralateral sensorimotor cortex at the onset and offset of 80 Hz vibration. This finding is consistent with a novel theoretical account of motor initiation, namely that modulating uncertainty of the proprioceptive afferent signal improves motor performance potentially by gating the incoming sensory signal and allowing for top-down proprioceptive predictions

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson’s disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [123I]β-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PDT) and without tremor (PDWT) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [123I]β-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PDT than in the PDWT subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [123I]β-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset

Optimal stomatal behaviour around the world

© 2015 Macmillan Publishers Limited. All rights reserved. Stomatal conductance (g s) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of g s in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of g s that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed g s obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model and the leaf and wood economics spectrum. We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of g s across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate

Optimal stomatal behaviour around the world

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordStomatal conductance (g s) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of g s in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of g s that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed g s obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model and the leaf and wood economics spectrum. We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of g s across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.This research was supported by the Australian Research Council (ARC MIA Discovery Project 1433500-2012-14). A.R. was financially supported in part by The Next-Generation Ecosystem Experiments (NGEE-Arctic) project, which is supported by the Office of Biological and Environmental Research in the Department of Energy, Office of Science, and through the United States Department of Energy contract No. DE-AC02-98CH10886 to Brookhaven National Laboratory. M.O.d.B. acknowledges that the Brassica data were obtained within a research project financed by the Belgian Science Policy (OFFQ, contract number SD/AF/02) and coordinated by K. Vandermeiren at the Open-Top Chamber research facilities of CODA-CERVA (Tervuren, Belgium)

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.Funding for the project was provided by the Wellcome Trust for UK10K (WT091310) and DDD Study. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003] - see www.ddduk.org/access.html for full acknowledgement. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Common Fund, NIH Office of the Director. This work was supported in part by the German Ministry of Research and Education (grant nos. 01GS08160 and 01GS08167; German Mental Retardation Network) as part of the National Genome Research Network to A.R. and D.W. and by the Deutsche Forschungsgemeinschaft (AB393/2-2) to A.R. Brain expression data was provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Michael Weale, Daniah Trabzuni, Adaikalavan Ramasamy, Colin Smith and Robert Walker, affiliated with UCL Institute of Neurology (J.H., M.R., D.T.), King’s College London (M.R., M.W., A.R.) and the University of Edinburgh (C.S., R.W.)