817 research outputs found

    Wnt4 and LAP2alpha as pacemakers of Thymic Epithelial Senescence

    Get PDF
    Age-associated thymic involution has considerable physiological impact by inhibiting de novo T-cell selection. This impaired T-cell production leads to weakened immune responses. Yet the molecular mechanisms of thymic stromal adipose involution are not clear. Age-related alterations also occur in the murine thymus providing an excellent model system. In the present work structural and molecular changes of the murine thymic stroma were investigated during aging. We show that thymic epithelial senescence correlates with significant destruction of epithelial network followed by adipose involution. We also show in purified thymic epithelial cells the age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2α expression. These senescence-related changes of gene expression are strikingly similar to those observed during mesenchymal to pre-adipocyte differentiation of fibroblast cells suggesting similar molecular background in epithelial cells. For molecular level proof-of-principle stable LAP2α and Wnt4-over-expressing thymic epithelial cell lines were established. LAP2α over-expression provoked a surge of PPARγ expression, a transcription factor expressed in pre-adipocytes. In contrast, additional Wnt4 decreased the mRNA level of ADRP, a target gene of PPARγ. Murine embryonic thymic lobes have also been transfected with LAP2α- or Wnt4-encoding lentiviral vectors. As expected LAP2α over-expression increased, while additional Wnt4 secretion suppressed PPARγ expression. Based on these pioneer experiments we propose that decreased Wnt activity and increased LAP2α expression provide the molecular basis during thymic senescence. We suggest that these molecular changes trigger thymic epithelial senescence accompanied by adipose involution. This process may either occur directly where epithelium can trans-differentiate into pre-adipocytes; or indirectly where first epithelial to mesenchymal transition (EMT) occurs followed by subsequent pre-adipocyte differentiation. The latter version fits better with literature data and is supported by the observed histological and molecular level changes

    The EoR Sensitivity of the Murchison Widefield Array

    Get PDF
    Using the final 128 antenna locations of the Murchison Widefield Array (MWA), we calculate its sensitivity to the Epoch of Reionization (EoR) power spectrum of red- shifted 21 cm emission for a fiducial model and provide the tools to calculate the sensitivity for any model. Our calculation takes into account synthesis rotation, chro- matic and asymmetrical baseline effects, and excludes modes that will be contaminated by foreground subtraction. For the fiducial model, the MWA will be capable of a 14{\sigma} detection of the EoR signal with one full season of observation on two fields (900 and 700 hours).Comment: 5 pages, 4 figures, 1 table, Accepted for publication in MNRAS Letters. Supplementary material will be available in the published version, or by contacting the author

    The mechanisms and processes of connection: developing a causal chain model capturing impacts of receiving recorded mental health recovery narratives.

    Get PDF
    BACKGROUND: Mental health recovery narratives are a core component of recovery-oriented interventions such as peer support and anti-stigma campaigns. A substantial number of recorded recovery narratives are now publicly available online in different modalities and in published books. Whilst the benefits of telling one's story have been investigated, much less is known about how recorded narratives of differing modalities impact on recipients. A previous qualitative study identified connection to the narrator and/or to events in the narrative to be a core mechanism of change. The factors that influence how individuals connect with a recorded narrative are unknown. The aim of the current study was to characterise the immediate effects of receiving recovery narratives presented in a range of modalities (text, video and audio), by establishing the mechanisms of connection and the processes by which connection leads to outcomes. METHOD: A study involving 40 mental health service users in England was conducted. Participants were presented with up to 10 randomly-selected recovery narratives and were interviewed on the immediate impact of each narrative. Thematic analysis was used to identify the mechanisms of connection and how connection leads to outcome. RESULTS: Receiving a recovery narrative led participants to reflect upon their own experiences or those of others, which then led to connection through three mechanisms: comparing oneself with the narrative and narrator; learning about other's experiences; and experiencing empathy. These mechanisms led to outcomes through three processes: the identification of change (through attending to narrative structure); the interpretation of change (through attending to narrative content); and the internalisation of interpretations. CONCLUSIONS: This is the first study to identify mechanisms and processes of connection with recorded recovery narratives. The empirically-based causal chain model developed in this study describes the immediate effects on recipients. This model can inform selection of narratives for use in interventions, and be used to support peer support workers in recounting their own recovery narratives in ways which are maximally beneficial to others

    A new layout optimization technique for interferometric arrays, applied to the MWA

    Get PDF
    Antenna layout is an important design consideration for radio interferometers because it determines the quality of the snapshot point spread function (PSF, or array beam). This is particularly true for experiments targeting the 21 cm Epoch of Reionization signal as the quality of the foreground subtraction depends directly on the spatial dynamic range and thus the smoothness of the baseline distribution. Nearly all sites have constraints on where antennas can be placed---even at the remote Australian location of the MWA (Murchison Widefield Array) there are rock outcrops, flood zones, heritages areas, emergency runways and trees. These exclusion areas can introduce spatial structure into the baseline distribution that enhance the PSF sidelobes and reduce the angular dynamic range. In this paper we present a new method of constrained antenna placement that reduces the spatial structure in the baseline distribution. This method not only outperforms random placement algorithms that avoid exclusion zones, but surprisingly outperforms random placement algorithms without constraints to provide what we believe are the smoothest constrained baseline distributions developed to date. We use our new algorithm to determine antenna placements for the originally planned MWA, and present the antenna locations, baseline distribution, and snapshot PSF for this array choice.Comment: 12 pages, 6 figures, 1 table. Accepted for publication in MNRA

    Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

    Full text link
    We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uvuv-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; zz=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

    Numerical study of circulation on the inner Amazon Shelf

    Get PDF
    Author Posting. © Springer, 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ocean Dynamics 58 (2008): 187-198, doi:10.1007/s10236-008-0139-4.We studied the circulation on the coastal domain of the Amazon Shelf by applying the hydrodynamic module of the Estuarine and Coastal Ocean Model and Sediment Transport - ECOMSED. The first barotropic experiment aimed to explain the major bathymetric effects on tides and those generated by anisotropy in sediment distribution. We analyzed the continental shelf response of barotropic tides under realistic bottom stress parametrization (Cd), considering sediment granulometry obtained from a faciologic map, where river mud deposits and reworked sediments areas are well distinguished, among others classes of sediments. Very low Cd values were set in the fluid mud regions off the Amapa coast (1.0 10-4 ), in contrast to values around 3:5 10-3 for coarser sediment regions off the Para coast. Three-dimensional experiments represented the Amazon River discharge and trade winds, combined to barotropic tide influences and induced vertical mixing. The quasi-resonant response of the Amazon Shelf to the M2 tide act on the local hydrodynamics by increasing tidal admittance, along with tidal forcing at the shelf break and extensive fluid mud regions. Harmonic analysis of modeled currents agreed well with analysis of the AMASSEDS observational data set. Tidal-induced vertical shear provided strong homogenization of threshold waters, which are subject to a kind of hydraulic control due to the topographic steepness. Ahead of the hydraulic jump, the low-salinity plume is disconnected from the bottom and acquires negative vorticity, turning southeastward. Tides act as a generator mechanism and topography, via hydraulic control, as a maintainer mechanism for the low-salinity frontal zone positioning. Tidally induced southeastward plume fate is overwhelmed by northwestward trade winds so that, along with background circulation, probably play the most important role on the plume fate and variability over the Amazon Shelf

    Non-pollinator fig wasp impact on the reproductive success of an invasive fig tree: why so little?

    Get PDF
    Classical biological control agents fail to achieve an impact on their hosts for a variety of reasons and an understanding of why they fail can help shape decisions on subsequent releases. Ornamental Ficus microcarpa is a widely planted avenue fig tree that is invasive in countries where its pollinator (Eupristina verticillata) is also introduced. This tree also supports more than 20 species of non-pollinating fig wasps (NPFW) that feed in the figs and have the potential to reduce the plant’s reproduction. Odontofroggatia galili, one of the most widely introduced NPFW, has larvae that develop in galled ovules that might otherwise develop into seeds or support pollinator larvae. We examined the distribution and relative abundance of the pollinator and O. galili on F. microcarpa in China, towards the northern limit of the tree’s natural range, and in Italy where the two species have been introduced. Where they co-existed, we also recorded the impact of varying densities of O. galili on F. microcarpa seed and pollinator production. O. galili and E. verticillata displayed contrasting habitat preferences in China, with O. galili almost absent from warmer sites. O. galili abundance and sex ratios varied between the natural and introduced ranges. Figs with more O. galili contained fewer seeds and pollinator offspring, but reproduction was rarely inhibited totally. Additional species with a greater impact in the figs they occupy are needed if biocontrol of F. microcarpa is to be effective
    corecore