Endoplasmic reticulum stress signalling induces casein kinase 1-dependent formation of cytosolic TDP-43 Inclusions in motor neuron-like cells

YesMotor neuron disease (MND) is a progressive neurodegenerative disease with no effective treatment. One of the principal pathological hallmarks is the deposition of TAR DNA binding protein 43 (TDP-43) in cytoplasmic inclusions. TDP-43 aggregation occurs in both familial and sporadic MND; however, the mechanism of endogenous TDP-43 aggregation in disease is incompletely understood. This study focused on the induction of cytoplasmic accumulation of endogenous TDP-43 in the motor neuronal cell line NSC-34. The endoplasmic reticulum (ER) stressor tunicamycin induced casein kinase 1 (CK1)-dependent cytoplasmic accumulation of endogenous TDP-43 in differentiated NSC-34 cells, as seen by immunocytochemistry. Immunoblotting showed that induction of ER stress had no effect on abundance of TDP-43 or phosphorylated TDP-43 in the NP-40/RIPA soluble fraction. However, there were significant increases in abundance of TDP-43 and phosphorylated TDP-43 in the NP-40/RIPA-insoluble, urea-soluble fraction, including high molecular weight species. In all cases, these increases were lowered by CK1 inhibition. Thus ER stress signalling, as induced by tunicamycin, causes CK1-dependent phosphorylation of TDP-43 and its consequent cytosolic accumulation.Funded by a biomedical research grant from the Motor Neurone Disease Association (ref Rattray/Apr15/837-791). The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome Trust and the University of Manchester Strategic Fund

United States’ neighborhood park use and physical activity over two years: The National Study of Neighborhood Parks

The United States lacks surveillance to monitor park use and conditions. The purpose of this study was to use the System for Observing Play and Recreation in Communities (SOPARC) as a surveillance tool to describe the conditions, user characteristics, and physical activity of a national sample of neighborhood parks at two time points. Using a stratified multistage sampling strategy, a representative sample of 174 neighborhood parks in 25 major United States’ cities were selected. During 2014 and 2016, park-related use, conditions, and physical activity were assessed using SOPARC in 169 parks. Overall, 74,106 park users were observed at baseline and 69,150 park users were observed two years later (p = 0.37). There were persistent disparities in park use by gender and age, with disproportionately more male than female users in each age group (child, teenager, adult, older adult). Older adults used the park less than other age groups. Almost two-thirds of park users were observed being sedentary (61.9% in 2014, 60.7% in 2016), followed by moderate (30.8%, 32.0%) and vigorous (7.3%, 7.3%) activity. Empty target areas increased over two years (75.3%, 77.6%; p = 0.01) and those that were equipped (2.6%, 1.2%; p = 0.0003), accessible (95.4%, 94.3%; p = 0.01), and organized (2.6%, 1.7%; p = 0.01) decreased. Areas that were usable (97.5%, 97.4%) or provided supervised activities (2.0%, 2.4%) did not change significantly. The findings demonstrate the value of SOPARC as a surveillance tool, identify user groups under represented at parks, and suggest an opportunity to encourage more park-based physical activity among park visitors

Digital proxemics: Designing social and collaborative interaction in virtual environments

Behaviour in virtual environments might be informed by our experiences in physical environments, but virtual environments are not constrained by the same physical, perceptual, or social cues. Instead of replicating the properties of physical spaces, one can create virtual experiences that diverge from reality by dynamically manipulating environmental, aural, and social properties. This paper explores digital proxemics, which describe how we use space in virtual environments and how the presence of others influences our behaviours, interactions, and movements. First, we frame the open challenges of digital proxemics in terms of activity, social signals, audio design, and environment. We explore a subset of these challenges through an evaluation that compares two audio designs and two displays with different social signal affordances: head-mounted display (HMD) versus desktop PC. We use quantitative methods using instrumented tracking to analyse behaviour, demonstrating how personal space, proximity, and attention compare between desktop PC and HMDs

Playground features and physical activity in U.S. neighborhood parks

All people need to engage in routine physical activity and children require it daily. Playgrounds are settings designed for children to be physically active, yet there has been little research assessing which play elements and structures are associated with more moderate-to-vigorous physical activity (MVPA) among both youth and adults. We conducted a national study of neighborhood parks with the goal of identifying factors that promote more MVPA. We selected a nationally representative sample of 162 parks between 3 and 22 acres in 25 U.S. cities with a population >100,000. We used direct observation to measure MVPA in 147 playgrounds during spring and summer of 2016, documented playground characteristics and assessed hours of use and MVPA by age group and gender. We analyzed data using descriptive statistics and generalized linear models. The most common play elements and structures were slides and ladders (92% of parks) and swings (81%); elements supporting balancing, crawling, spinning, sand and water play were in <30% of playgrounds. Each additional play element was associated with about 50% more users and 50% more MVPA. Spinning structures and splash pads were associated with more playground use and more MVPA. Playgrounds with signage advertising park programs and on-site restrooms had more person-hours of use, but only half the parks had restrooms and <30% had signage. To address insufficient physical activity, upgrades to playgrounds should include restrooms, structures that support a wide variety of movements, and elements that also encourage adults to be active

How important is perception of safety to park use? A four-city survey

Our purpose was to determine the relative importance of individual- and park-related characteristics in influencing both local park use and specific engagement in active sports, walking and sedentary pursuits. We surveyed 3815 adults living within 0.80 km of one of 24 study parks in four US metropolitan areas. Chi-square statistics and baseline-category logit models examined how perceived safety and park characteristics were related to park visitation and types of park activities, controlling for city, individual and park characteristics. Survey participants who perceived the parks as safe (88%) had 4.6 times the odds (95% CI 3.5–6.0) of reporting having visited the study park. Men and African Americans were more likely, and older individuals and those who self-reported being in fair or poor health less likely to perceive parks as safe. Parks having low incivilities scores and those with four or more different facilities, such as tennis courts, swimming pools, basketball courts, etc., were more likely than parks with fewer facilities to be perceived as safe. While park facilities had a much smaller odds ratio for predicting park visits (1.8), it affected 70% of the population. The implication is, if these associations are causal, modifying park facilities may have a greater population impact than improving perceptions of park safety. Our findings are consistent with studies suggesting that increasing the variety of park facilities and offering more organised activities may encourage physical activity among specific target groups

Use of neighbourhood parks: does socio-economic status matter? A four-city study

To determine if neighborhood socio-economic status (SES) influences park use and park-based physical activity

Resonant transmission through an open quantum dot

We have measured the low-temperature transport properties of a quantum dot formed in a one-dimensional channel. In zero magnetic field this device shows quantized ballistic conductance plateaus with resonant tunneling peaks in each transition region between plateaus. Studies of this structure as a function of applied perpendicular magnetic field and source-drain bias indicate that resonant structure deriving from tightly bound states is split by Coulomb charging at zero magnetic field.Comment: To be published in Phys. Rev. B (1997). 8 LaTex pages with 5 figure

Social VR: A new medium for remote communication and collaboration

We are facing increasingly pressure on reducing travel and working remotely. Tools that support effective remote communication and collaboration are much needed. Social Virtual Reality (VR) is an emerging medium, which invites multiple users to join a collaborative virtual environment (VE) and has the potential to support remote communication in a natural and immersive way. We successfully organized a CHI 2020 Social VR workshop virtually on Mozilla Hubs, which invited researchers and practitioners to have a fruitful discussion over user representations and ethics, evaluation methods, and interaction techniques for social VR as an emerging immersive remote communication tool. In this CHI 2021 virtual workshop, we would like to organize it again on Mozilla Hubs, continuing the discussion about proxemics, social cues and VE designs, which were identified as important aspects for social VR communication in our CHI 2020 workshop