9 research outputs found
High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington’s disease
This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.This project was supported by 1U01NS082074 (V.C. and J.T., co-principal investigators) from the National Institutes of Health, National Institute of Neurological Disorders and Stroke. The PREDICT-HD study was supported by NIH/NINDS grant 5R01NS040068 awarded to J.P.; CHDI Foundation, Inc., A3917 and 6266 awarded to J.P.; Cognitive and Functional Brain Changes in Preclinical Huntington’s Disease (HD) 5R01NS054893 awarded to J.P.; 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington’s 1U01NS082086; Functional Connectivity in Premanifest Huntington’s Disease 1U01NS082083; and Basal Ganglia Shape Analysis and Circuitry in Huntington’s Disease 1U01NS082085 awarded to Christopher A. Ross
Percolation model for a selective response of the resistance of composite semiconducting n
Normal and anomalous diffusion of non-interacting particles in linear nanopores
The diffusion of gas molecules in pores is determined by the collisions between the molecules as well as by the collisions of the molecules with the pore walls. In many applications the so-called Knudsen regime is of particular interest. In this regime the collisions of the molecules with the pore walls play the crucial role, while the inter-molecular collisions can be neglected. Here we study the influence of surface roughness on the coefficients of self (or tracer) diffusion and transport diffusion. Considering the first four iterations of a generalised fractal Koch surface, we construct pore models of different roughness. For these model pores we have performed detailed simulations of both diffusion coefficients using a cube-based algorithm. The molecular trajectories can be mapped onto L´evy walks to determine the diffusion properties. In linear two-dimensional (2d) channels we observe anomalous diffusion, which can also be induced in smooth and rough three-dimensional (3d) pores by anomalous reflection laws. Normal diffusion is found in convoluted 2d pores and in all 3d pores when a diffuse reflection law is applied.DelftChemTechApplied Science
Tourism in protected and conserved areas amid the COVID-19 pandemic
The COVID-19 pandemic has had a global impact on the tourism sector. With tourism numbers dramatically reduced, millions of jobs could be lost, and progress made in equality and sustainable economic growth could be rolled back. Widespread reports of dramatic changes to protected and conserved1 area visitation have negative consequences for conservation finances, tourism businesses and the livelihoods of people who supply labour, goods and services to tourists and tourism businesses. This paper aims to share experiences from around the world on the impacts of the COVID-19 pandemic on protected area tourism; and considers how to build resilience within protected area tourism as a regenerative conservation tool
The Sceptics' Challenge for Sustainable Tourism in the Southwest China Biodiversity Hotspot: A Choice Experiment Approach
CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion
Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a wellbehaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Copyright © 2012 by AAN Enterprises, Inc