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

Crucible of the Modern Republic: The Yosemite Grant and Environmental Citizenship

The Yosemite Grant, which established the basis for the state, later national park in the central Sierra, initiated a powerful new force that constituted a tipping point in American environmental history, Jen A. Huntley argues. A moment in US history when the right combination of people and politics and ideas hit a nerve in the broad social psyche of a time and launched a new environmental understanding

Spin dependent potentials from SU(2) gauge theory

We present results on spin dependent potentials from lattice simulations of SU(2) gauge theory. The Coulomb like short range part of the central potential is identified as a mixed vector-scalar exchange while the linear long range part is pure scalar.Comment: Talk held at LAT 94 conference, 3 pages, latex, uses epscrc2.st

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

STR-997: INSTRUMENTATION AND LONG-TERM MONITORING OF AN INTEGRAL-ABUTMENT BRIDGE SUPERSTRUCTURE

Strain gauges were installed in the girders and deck of an integral abutment bridge to determine the behaviour of the superstructure to daily and seasonal thermal fluctuations. The two-span, 76 m-long bridge has no expansion joints; rather, the prestressed-concrete girders are cast directly into the abutments which are in turn supported by flexible pile foundations. Details of field instrumentation along with monitored data over a period of eight years are presented in this paper. Gauges measured the longitudinal strain in the girders and deck and were positioned at different elevations to provide a strain distribution across the superstructure depth. From the strain data, moments were computed at each of the installation locations. Data indicate that the superstructure responds to thermal fluctuations as expected with midspan moments smaller in magnitude when compared to the moments measured at the abutment and pier locations. Furthermore, data confirm that the level of sun exposure affects the thermally-induced moments measured in the girders

Snap-8 corrosion program quarterly progress report, period ending 28 feb. 1965

SNAP-8 corrosion program - hydrogen solubility in sodium-potassium, permeability of hydrogen and deuterum through stainless steel, and phase equilibri

Sleep Timing and Neurocognitive Networks in Youth

Sleep timing, particularly later midpoint of sleep, has been linked to emotion dysregulation and psychopathology. Prior adult studies link poor sleep (e.g., shorter duration, later midpoint), to altered resting-state functional connectivity (rs-FC) within and between key neurocognitive networks, particularly the default mode network (DMN), which is involved in internal thought and rumination. Importantly, many psychiatric disorders begin during adolescence, a period of shifted sleep schedules. We explored associations between midpoint of sleep and rs-FC of the DMN and other core neurocognitive networks in youth. Sleep timing was measured in 3,798 youth (11.9±0.6 years, 47.5% female) from the Adolescent Brain Cognitive Development study using Fitbit watches (over 13.1±6.5 days). Internalizing symptoms were measured using self-report and rs-FC was measured between the DMN and three neurocognitive networks: dorsal attention network (DAN), frontoparietal network (FPN), and salience network (SN). Associations between sleep timing and rs-FC were measured using linear regressions adjusting for age, sex, race, parental education, family income, puberty, and head motion. Average midpoint of sleep was 3:35 AM (range: 12:34 AM-11:27 PM). Later midpoint of sleep was associated with increased self-reported depressive symptoms. Later midpoint of sleep was associated with lower DMN-DAN rs-FC. There were no associations between midpoint of sleep and DMN-DMN, DMN-FPN, or DMN-SN network rs-FC. These results add to and extend prior studies in youth by incorporating objective measures of sleep timing (Fitbit data), and in a large national sample. Additionally, our findings may have implications for the consideration of sleep timing when designing behavioral-health interventions in youth

Support for midlife anxiety diagnosis as an independent risk factor for dementia: a systematic review

OBJECTIVES: Anxiety is an increasingly recognised predictor of cognitive deterioration in older adults and in those with mild cognitive impairment. Often believed to be a prodromal feature of neurodegenerative disease, anxiety may also be an independent risk factor for dementia, operationally defined here as preceding dementia diagnosis by ≥10 years. DESIGN: A systematic review of the literature on anxiety diagnosis and long-term risk for dementia was performed following published guidelines. SETTING AND PARTICIPANTS: Medline, PsycINFO and Embase were searched for peer-reviewed journals until 8 March 2017. Publications reporting HR/OR for all-cause dementia based on clinical criteria from prospective cohort or case-control studies were selected. Included studies measured clinically significant anxiety in isolation or after controlling for symptoms of depression, and reported a mean interval between anxiety assessment and dementia diagnosis of at least 10 years. Methodological quality assessments were performed using the Newcastle-Ottawa Scale. OUTCOME MEASURE: HR/OR for all-cause dementia. RESULTS: Searches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted. CONCLUSIONS: Clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom

Relict Late Wisconsinan Dune Fields of the Northern Great Plains, Canada

Late Wisconsinan dune activity is investigated within the present-day boreal forest and parkland regions of the northern Great Plains, Canada, to extend the understanding of the spatial and temporal eolian record. Optical ages from stabilized sand dunes document the timing of past activity. Eolian activity ranges from about 16 ka in west-central Alberta to 9 ka in northwestern Saskatchewan. Between about 16 and 13 ka, dune activity in central Alberta occurred in an ice-proximal tundra setting along the margins of the Laurentide and Cordilleran ice sheets. Predominant dune-forming winds were from the west and northwest. Dune activity continued in this area between about 13 and 11 ka within parkland and grassland settings as the Laurentide Ice Sheet retreated to the northeast. Winds continued to blow from the west and northwest, and the climate was likely influenced by an increasingly dominant Pacific air mass. Also beginning at about 13 ka, dune-forming winds along the margins of the retreating Laurentide Ice Sheet were influenced by anticyclonic winds from the southeast that were maintained until about 9 ka. As the Laurentide Ice Sheet retreated, these southeasterly anticyclonic winds were successively replaced by winds from the northwest associated with the Pacific air mass. Dune activity across the region terminated in a time-transgressive manner from the southwest, at about 11 ka, to the northeast, at about 9 ka, with the establishment of boreal forest vegetation and reduced wind strength.Les auteurs étudient l’activité dunaire au Wisconsinien tardif dans la forêt boréale et la prairie-parc actuelles des Grandes Plaines septentrionales du Canada, afin d’approfondir les connaissances sur l’évolution spatiotemporelle de l’activité éolienne. Les âges optiques mesurés sur des dunes de sable stabilisées permettent de reconstituer la chronologie de l’activité passée. Les âges de l’activité éolienne s’échelonnent entre 16 ka dans le centre-ouest de l’Alberta et 9 ka dans le nord-ouest de la Saskatchewan. Entre 16 et 13 ka, l’activité dunaire dans le centre de l’Alberta a eu lieu dans un environnement de toundra juxtaglaciaire le long des marges des inlandsis laurentidien et cordillérien. Les vents efficaces prédominants soufflaient de l’ouest et du nord-ouest. L’activité dunaire s’est poursuivie dans cette région entre 13 et 11 ka dans des environnements de prairie-parc et de prairie herbageuse, avec le recul de l’Inlandsis laurentidien vers le nord-est. Les vents ont continué de souffler de l’ouest et du nord-ouest, et le climat a probablement été influencé par une masse d’air du Pacifique de plus en plus dominante. Également au début de 13 ka, les vents efficaces le long des marges de l’Inlandsis laurentidien en recul ont été influencées par des vents anticycloniques du sud-ouest, qui ont duré jusqu’à 9 ka. Avec le retrait de l’Inlandsis laurentidien, ces vents ont été successivement remplacés par des vents du nord-ouest associés à la masse d’air du Pacifique. L’activité dunaire dans la région s’est terminée de façon diachrone à partir du sud-ouest, vers 11 ka, jusqu’au nord-est, vers 9 ka, par l’établissement d’une végétation forestière boréale et la diminution de la force des vents