Psychophysical correlates of global motion processing in the aging visual system: a critical review

The consequences of visual decline in aging have a fundamental and wide-reaching impact on age-related quality of life. It is of concern therefore that evidence suggests that normal aging is accompanied by impairments in the ability to effectively encode global motion. Global motion perception is a fundamentally important process. It enables us to determine the overall velocity of spatially extensive objects in the world and provides us with information about our own body movements. Here, we review what is currently known about the effects of age on performance for encoding the global motion information available in random dot kinematograms (RDKs), a class of stimuli widely used to probe the mechanisms underlying motion perception. We conclude that age-related deficits in global motion perception are not all encompassing. Rather, they appear to be specific to certain stimulus conditions. We also examine evidence for an interaction between age and gender and consider the efficacy of techniques such as visual perceptual learning that may attenuate some of the visual deficits in the older adult population

Binocular summation of second-order global motion signals in human vision

Although many studies have examined the principles governing first-order global motion perception, the mechanisms that mediate second-order global motion perception remain unresolved. This study investigated the existence, nature and extent of the binocular advantage for encoding second-order (contrast-defined) global motion. Motion coherence thresholds (79.4 % correct) were assessed for determining the direction of radial, rotational and translational second-order motion trajectories as a function of local element modulation depth (contrast) under monocular and binocular viewing conditions. We found a binocular advantage for second-order global motion processing for all motion types. This advantage was mainly one of enhanced modulation sensitivity, rather than of motion-integration. However, compared to findings for first-order motion where the binocular advantage was in the region of a factor of around 1.7 [Hess et al., 2007, Vision Research 47, 1682-1692 & the present study], the binocular advantage for second-order global 2 motion was marginal, being in the region of around 1.2. This weak enhancement in sensitivity with binocular viewing is considerably less than would be predicted by conventional models of either probability summation or neural summation

A training programme involving automatic self-transcending meditation in late-life depression: preliminary analysis of an ongoing randomised controlled trial.

: Late-life depression affects 2-6% of seniors aged 60 years and above. Patients are increasingly embracing non-pharmacological therapies, many of which have not been scientifically evaluated. This study aimed to evaluate a category of meditation, automatic self-transcending meditation (ASTM), in alleviating symptoms of depression when augmenting treatment as usual (NCT02149810). The preliminary results of an ongoing single-blind randomised controlled trial comparing a training programme involving ASTM with a wait-list control indicate that a 12-week ASTM programme may lead to significantly greater reductions in depression and anxiety severity. As such, ASTM may be an effective adjunctive therapy in the treatment of late-life depression. DECLARATION OF INTEREST: R.I.N. is Director of Research and Health Promotion for the Art of Living Foundation, Canada and supervised the staff providing ASTM training. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence

The Physiologic Benefits of Optimizing Cardiorespiratory Fitness and Physical Activity – From the Cell to Systems Level in a Post-Pandemic World

Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA

Synchronous in-field application of life-detection techniques in Icelandic Mars analogue sites

Field expeditions that simulate the operations of robotic planetary exploration missions at analogue sites on Earth can help establish best practices and are therefore a positive contribution to the planetary exploration community. There are many sites in Iceland that possess heritage as planetary exploration analogue locations and whose environmental extremes make them suitable for simulating scientific sampling and robotic operations. We conducted a planetary exploration analogue mission at two recent lava fields in Iceland, Fimmvörðuháls (2010) and Eldfell (1973), using a specially developed field laboratory. We tested the utility of in-field site sampling down selection and tiered analysis operational capabilities with three life detection and characterization techniques: fluorescence microscopy (FM), adenine-triphosphate (ATP) bioluminescence assay, and quantitative polymerase chain reaction (qPCR) assay. The study made use of multiple cycles of sample collection at multiple distance scales and field laboratory analysis using the synchronous life-detection techniques to heuristically develop the continuing sampling and analysis strategy during the expedition. Here we report the operational lessons learned and provide brief summaries of scientific data. The full scientific data report will follow separately. We found that rapid in-field analysis to determine subsequent sampling decisions is operationally feasible, and that the chosen life detection and characterization techniques are suitable for a terrestrial life-detection field mission. In-field analysis enables the rapid obtainment of scientific data and thus facilitates the collection of the most scientifically relevant samples within a single field expedition, without the need for sample relocation to external laboratories. The operational lessons learned in this study could be applied to future terrestrial field expeditions employing other analytical techniques and to future robotic planetary exploration missions

An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis

Peptides presented by HLA - E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR) - based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR - based bispecific molecule that potently and selectively binds HLA - E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA - E - expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb - infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR - based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Psychophysical correlates of age-related visual decline

Much of what we know about the physical world is afforded to us by vision. With age, our ability to perceive visual information can become compromised, affecting our autonomy and quality of life. Given the rapid aging of populations worldwide, it is imperative to develop a comprehensive understanding of the effects of age on visual function. Therefore, the aim of this thesis was to use psychophysical methods to examine the effects of 'healthy' aging on visual perception, with a particular emphasis on furthering our knowledge of age-related reductions in the perception of motion. In a series of experiments, observers ranging from 18-82 years of age were tested and compared on psychophysical tasks which measured orientation and direction sensitivity, first- and second-order global motion perception, contrast sensitivity, and visual attention as measured by the Useful Field of View. Four key findings are presented within this thesis: (1) older observers demonstrate reductions in orientation and direction sensitivity that can be attributed to increased internal noise in the aged motion pathway, (2) age related impairments in global motion perception are mediated by reductions in spatial integration, (3) older female populations may be particularly susceptible to age-related impairments in motion perception, and (4) there may be a selective impairment in the processing of second-order radial motion in the aged. The results of these experiments indicate that whilst some aspects of motion processing remain preserved with age, older observers demonstrate marked impairments on a number of motion tasks