Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

Long-Wave Forcing by the Breaking of Random Gravity Waves on a Beach

This paper presents new laboratory data on long-wave (surf-beat) forcing by the random breaking of shorter gravity water waves on a plane beach. The data include incident and outgoing wave amplitudes, together with shoreline oscillation amplitudes at long-wave frequencies, from which the correlation between forced long waves and short-wave groups is examined. A detailed analysis of the cross-shore structure of the long-wave motion is presented, and the observations are critically compared with existing theories for two-dimensional surf-beat generation. The surf beat shows a strong dependency on normalized surf-zone width, consistent with long-wave forcing by a time-varying breakpoint, with little evidence of the release and reflection of incident bound long waves for the random-wave simulations considered. The seaward-propagating long waves show a positive correlation with incident short-wave groups and are linearly dependent on short-wave amplitude. The phase relationship between the incident bound long waves and radiated free long waves is also consistent with breakpoint forcing. In combination with previous work, the present data suggest that the breakpoint variability may be the dominant forcing mechanism during conditions with steep incident short waves

Adaptive working memory strategy training in early Alzheimer's disease: randomised controlled trial.

BACKGROUND: Interventions that improve cognitive function in Alzheimer's disease are urgently required. AIMS: To assess whether a novel cognitive training paradigm based on 'chunking' improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027). METHOD: Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted. RESULTS: Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls. CONCLUSIONS: Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease

Empathy and its associations with sociodemographic and personality characteristics in a large UK population sample

Background: Empathy is fundamental to social cognition, driving prosocial behaviour and mental health. Self-reported empathy varies across cultures and there are differing reports of associations with demographic characteristics. We therefore aimed in a UK survey to characterise two main self-reported components of empathy, namely empathic concern (feeling compassion) and perspective taking (understanding others’ perspective). We hypothesised that empathy would be associated with age, gender, ethnicity, relationship status, employment, socio-economic status, education, and personality. / Methods: We asked participants in the COVID-19 Social Study - an internet-based survey of UK-dwelling adults aged ≥18 years - to complete the Interpersonal Reactivity Index subscales measuring empathic concern and perspective taking, and sociodemographic and personality questionnaires. We weighted the sample to be UK population representative and employed multivariable weighted linear regression models. Results: In 30,033 respondents, mean empathic concern score was 3.86 (95% confidence interval 3.85, 3.88) and perspective taking was 3.57 (3.56. 3.59), the correlation between these subscores was 0.45 (p < 0.001). In adjusted models, greater empathic concern was associated with female gender, non-white ethnicity, having more education, working in health, social-care, or childcare professions, and having higher neuroticism, extroversion, openness to experience and agreeableness traits. Perspective taking was associated with younger age, female gender, more education, employment in health or social-care, neuroticism, openness, and agreeableness. / Conclusions: Women and people working in caring professions have higher empathy levels. Perspective taking declines with age but empathic concern does not. Empathic compassion and understanding are distinct dimensions of empathy with differential associations with demographic factors

Empathy and its associations with age and sociodemographic characteristics in a large UK population sample

OBJECTIVES: Empathy is fundamental to social cognition, driving prosocial behaviour and mental health but associations with aging and other socio-demographic characteristics are unclear. We therefore aimed to characterise associations of these characteristics with two main self-reported components of empathy, namely empathic-concern (feeling compassion) and perspective-taking (understanding others’ perspective). METHODS: We asked participants in an internet-based survey of UK-dwelling adults aged ≥18 years to complete the Interpersonal Reactivity Index subscales measuring empathic concern and perspective taking, and sociodemographic and personality questionnaires. We weighted the sample to be UK population representative and employed multivariable weighted linear regression models. RESULTS: In 30,033 respondents, mean empathic concern score was 3.86 (95% confidence interval 3.85, 3.88) and perspective taking was 3.57 (3.56. 3.59); the correlation between these sub-scores was 0.45 (p < 0.001). Empathic concern and perspective taking followed an inverse-u shape trajectory in women with peak between 40 and 50 years whereas in men, perspective taking declines with age but empathic concern increase. In fully adjusted models, greater empathic concern was associated with female gender, non-white ethnicity, having more education, working in health, social-care, or childcare professions, and having higher neuroticism, extroversion, openness to experience and agreeableness traits. Perspective taking was associated with younger age, female gender, more education, employment in health or social-care, neuroticism, openness, and agreeableness. CONCLUSIONS: Empathic compassion and understanding are distinct dimensions of empathy with differential demographic associations. Perspective taking may decline due to cognitive inflexibility with older age whereas empathic concern increases in older men suggesting it is socially-driven

Social relationships and depression during the COVID-19 lockdown: longitudinal analysis of the COVID-19 social study

Background. The coronavirus disease 2019 (COVID-19) pandemic led to measures that reduced social contact and support. We explored whether UK residents with more frequent or supportive social contact had fewer depressive symptoms during March−August 2020, and potential factors moderating the relationship. Methods. A convenience sample of UK dwelling participants aged ⩾18 in the internet-based longitudinal COVID-19 Social Study completed up to 22 weekly questionnaires about face-toface and phone/video social contact frequency, perceived social support, and depressive symptoms using the PHQ-9. Mixed linear models examined associations between social contact and support, and depressive symptoms. We examined for interaction by empathic concern, perspective taking and pre-COVID social contact frequency. Results. In 71 117 people with mean age 49 years (standard deviation 15), those with high perceived social support scored 1.836 (1.801–1.871) points lower on PHQ-9 than those with low support. Daily face-to-face or phone/video contact was associated with lower depressive symptoms (0.258 (95% confidence interval 0.225–0.290) and 0.117 (0.080–0.154), respectively) compared to no contact. The negative association between social relationships and depressive symptoms was stronger for those with high empathic concern, perspective taking and usual sociability. Conclusions. We found during lockdown that those with higher quality or more face-to-face or phone/video contact had fewer depressive symptoms. Contact quality was more strongly associated than quantity. People who were usually more sociable or had higher empathy had more depressive symptoms during enforced reduced contact. The results have implications for COVID-19 and potential future pandemic management, and for understanding the relationship between social factors and mental health

Cross-Shelf Transport Through the Interaction among a Coastal Jet, a Topographic Wave, and Tides

Shelf break flows are often characterized by along-isobath jets with cross-shelf currents associated with tides and waves guided by variable topography. Here, we address the question: Can a superposition of such flows produce significant aperiodic cross-shelf transport? To answer this question, we use a barotropic analytic model for the jet based on a similarity solution of the shallow water equations over variable topography, a wave disturbance determined by the topography, and a diurnal tidal disturbance. We use standard Lagrangian methods to assess the cross-shelf transport, presenting the results, however, in a Eulerian frame, so as to be amenable to oceanographic observations. The relative roles of the different flow components in cross-shelf transport are assessed through an extensive parameter study. We find that a superposition of all three flow components can indeed produce consequential background aperiodic transport. An application of the model using recent observations from the Texas Shelf demonstrates that a combination of these background mechanisms can produce significant transport under realistic conditions

Potential Aboriginal-Occupation-Induced Dune Activity, Elbow Sand Hills, Northern Great Plains, Canada

Geomorphological and archeological evidence indicates potential linkages between Plains aboriginal occupation and dune activity in the Elbow Sand Hills of southern Saskatchewan, Canada. Vegetation encroachment has rapidly outpaced migration of an active dune complex over the last 65 years. Optical ages of stabilized dune remnants indicate that dune activity predates Euro-Canadian settlement (ca. AD 1900). Early Euro-Canadian explorers observed local occupation and exploitation of the sand hills by aboriginal groups for herding and impounding bison. Mapping of archeological sites in relation to physiography reveals that sand dunes, in close proximity to permanent water resources, were preferred areas of occupation. Collectively, these results support the hypothesis that aboriginal occupation disturbance may have perpetuated dune activity in the Elbow Sand Hills until the late 19th century, and that Euro-Canadian settlement and land use emphasizing conservation may have encouraged recent stabilization. We propose that similar aboriginal occupation disturbances may have been responsible for perpetuating dune activity in other dune fields in the Great Plains. To this end, climatic variability should not be considered exclusive of other drivers of dune activity in semivegetated inland dune fields of the Great Plains

Smoothing effect and delocalization of interacting Bose-Einstein condensates in random potentials

We theoretically investigate the physics of interacting Bose-Einstein condensates at equilibrium in a weak (possibly random) potential. We develop a perturbation approach to derive the condensate wavefunction for an amplitude of the potential smaller than the chemical potential of the condensate and for an arbitrary spatial variation scale of the potential. Applying this theory to disordered potentials, we find in particular that, if the healing length is smaller than the correlation length of the disorder, the condensate assumes a delocalized Thomas-Fermi profile. In the opposite situation where the correlation length is smaller than the healing length, we show that the random potential can be significantly smoothed and, in the meanfield regime, the condensate wavefunction can remain delocalized, even for very small correlation lengths of the disorder.Comment: The word "screening" has been changed to "smoothing" to avoid confusions with other effects discussed in the literature. This does not affect the content of paper, nor the results, nor the physical discussio

Influence of Strong Acid Hydrolysis Processing on the Thermal Stability and Crystallinity of Cellulose Isolated from Wheat Straw

Cellulose extractions from wheat straw via hydrochloric, nitric, and sulfuric acid hydrolysis methods were carried out. X-ray diffraction spectral analyses reveal that depending on the acid conditions used the structure of the cellulose exhibited a mixture of polymorphs (i.e., CI and CIII cellulose phases). In addition, the percent crystallinity, diameter, and length of the cellulose fibers varied tremendously as determined by X-ray diffraction and scanning electron microscopy. Thermal gravimetric analysis measurements revealed that the thermal stability of the extracted cellulose varied as a function of the acid strength and conditions used. Scanning electron microscopy analysis revealed that the aggregation of cellulose fibers during the drying process is strongly dependent upon the drying process and strength of the acids used