498 research outputs found
Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity.
Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell-cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs
Which eligible households get grants? Demographic correlates of receipt in South Africa
Since Apartheid, the South African government transformed and
expanded the social grants system to improve the well-being of
its vulnerable populations. Despite increased efforts, a sub-section
of the grant-eligible population is not reached. Too little is known
about the factors that contribute to grant receipt, especially for
the household as a whole. This article examines the household
and community characteristics associated with grant receipt
among poor households in KwaZulu-Natal. We add to previous
work by assessing grant receipt at the household level, examining
receipt of the two major grants and analysing correlates in a
multivariate framework. While associations with grant receipt are
complex and varied, we find higher grant receipt (especially the
Child Support Grant) among more disadvantaged households. We
also find that characteristics across multiple domains are needed
to best distinguish household grant receipt. We discuss theoretical
implications for models of grant receipt and practical implications
for improving grant access
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A systematic review of validity of US survey measures for assessing substance use and substance use disorders
Background: The steep rise in substance use and substance use disorder (SUD) shows an urgency to assess its prevalence using valid measures. This systematic review summarizes the validity of measures to assess the prevalence of substance use and SUD in the US estimated in population and sub-population-based surveys. Methods: A literature search was performed using nine online databases. Studies were included in the review if they were published in English and tested the validity of substance use and SUD measures among US adults at the general or sub-population level. Independent reviews were conducted by the authors to complete data synthesis and assess the risk of bias. Results: Overall, 46 studies validating substance use/SUD (n = 46) measures were included in this review, in which 63% were conducted in clinical settings and 89% assessed the validity of SUD measures. Among the studies that assessed SUD screening measures, 78% examined a generic SUD measure, and the rest screened for specific disorders. Almost every study used a different survey measure. Overall, sensitivity and specificity tests were conducted in over a third of the studies for validation, and 10 studies used receiver operating characteristics curve. Conclusion: Findings suggest a lack of standardized methods in surveys measuring and reporting prevalence of substance use/SUD among US adults. It highlights a critical need to develop short measures for assessing SUD that do not require lengthy, time-consuming data collection that would be difficult to incorporate into population-based surveys assessing a multitude of health dimensions. Systematic review registration: PROSPERO CRD42022298280.</p
Sex-Biased Gene Flow Among Elk in the Greater Yellowstone Ecosystem
We quantified patterns of population genetic structure to help understand gene flow among elk populations across the Greater Yellowstone Ecosystem. We sequenced 596 base pairs of the mitochondrial control region of 380 elk from eight populations. Analysis revealed high mitochondrial DNA variation within populations, averaging 13.0 haplotypes with high mean gene diversity (0.85). The genetic differentiation among populations for mitochondrial DNA was relatively high (FST = 0.161; P = 0.001) compared to genetic differentiation for nuclear microsatellite data (FST = 0.002; P = 0.332), which suggested relatively low female gene flow among populations. The estimated ratio of male to female gene flow (mm/mf = 46) was among the highest we have seen reported for large mammals. Genetic distance (for mitochondrial DNA pairwise FST) was not significantly correlated with geographic (Euclidean) distance between populations (Mantelās r = 0.274, P = 0.168). Large mitochondrial DNA genetic distances (e.g., FST . 0.2) between some of the geographically closest populations (,65 km) suggested behavioral factors and/or landscape features might shape female gene flow patterns. Given the strong sex-biased gene flow, future research and conservation efforts should consider the sexes separately when modeling corridors of gene flow or predicting spread of maternally transmitted diseases. The growing availability of genetic data to compare male vs. female gene flow provides many exciting opportunities to explore the magnitude, causes, and implications of sex-biased gene flow likely to occur in many species
Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis
Rationale: Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would facilitate the development of novel drugs. Although respiratory muscle weakness is a known predictor of poor prognosis, a comprehensive comparison of different tests is lacking.
Objectives: To compare the predictive power of invasive and noninvasive respiratory muscle strength assessments for survival or ventilator-free survival, up to 3 years.
Methods: From a previously published report respiratory muscle strength measurements were available for 78 patients with ALS. Time to death and/or ventilation were ascertained. Receiver operating characteristic analysis was used to determine the cutoff point of each parameter.
Measurements and Main Results: Each respiratory muscle strength assessment individually achieved statistical significance for prediction of survival or ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and maximal static expiratory mouth pressure were significant predictors of ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure for absolute survival. Although all measures had good specificity, there were differing sensitivities. All cutoff points for the VC were greater than 80% of normal, except for prediction of 3-month outcomes. Sequential data showed a linear decline for direct measures of respiratory muscle strength, whereas VC showed little to no decline until 12 months before death/ventilation.
Conclusions: The most powerful biomarker for mortality stratification was Tw Pdi, but the predictive power of sniff nasal inspiratory pressure was also excellent. A VC within normal range suggested a good prognosis at 3 months but was of little other value
Chronic Ethanol Consumption Alters Glucocorticoid Receptor Isoform Expression in Stress Neurocircuits and Mesocorticolimbic Brain Regions of Alcohol-Preferring Rats
Evidence suggests the hypothalamic-pituitary-adrenal (HPA) axis is involved in Alcohol Use Disorders (AUDs), which might be mediated by an imbalance of glucocorticoid receptor (GR), GRĪ± and GRĪ², activity. GRĪ² antagonizes the GRĪ± isoform to cause glucocorticoid (GC) resistance. In the present study, we aimed to investigate the effects of chronic continuous free-choice access to ethanol on GR isoform expression in subregions of the mesocorticolimbic reward circuit. Adult male alcohol-preferring (P) rats had concurrent access to 15% and 30% ethanol solutions, with ad lib access to lab chow and water, for six weeks. Quantitative Real-time PCR (RT-PCR) analysis showed that chronic ethanol consumption reduced GRĪ± expression in the nucleus accumbens shell (NAcsh) and hippocampus, whereas ethanol drinking reduced GRĪ² in the nucleus accumbens core (NAcc), prefrontal cortex (PFC), and hippocampus. An inhibitor of GRĪ±, microRNA-124-3p (miR124-3p) was significantly higher in the NAcsh, and GC-induced gene, GILZ, as a measure of GC-responsiveness, was significantly lower. These were not changed in the NAcc. Likewise, genes associated with HPA axis activity were not significantly changed by ethanol drinking [i.e., corticotrophin-releasing hormone (Crh), adrenocorticotrophic hormone (Acth), and proopiomelanocortin (Pomc)] in these brain regions. Serum corticosterone levels were not changed by ethanol drinking. These data indicate that the expression of GRĪ± and GRĪ² isoforms are differentially affected by ethanol drinking despite HPA-associated peptides remaining unchanged, at least at the time of tissue harvesting. Moreover, the results suggest that GR changes may stem from ethanol-induced GC-resistance in the NAcsh. These findings confirm a role for stress in high ethanol drinking, with GRĪ± and GRĪ² implicated as targets for the treatment of AUDs
The Sloan Digital Sky Survey Quasar Lens Search. II. Statistical lens sample from the third data release
We report the first results of our systematic search for strongly lensed quasars using the spectroscopically confirmed quasars in the Sloan Digital Sky Survey (SDSS). Among 46,420 quasars from the SDSS Data Release 3 (~4188 deg^2), we select a subsample of 22,683 quasars that are located at redshifts between 0.6 and 2.2 and are brighter than the Galactic extinction-corrected i-band magnitude of 19.1. We identify 220 lens candidates from the quasar subsample, for which we conduct extensive and systematic follow-up observations in optical and near-infrared wavebands, in order to construct a complete lensed quasar sample at image separations between 1" and 20" and flux ratios of faint to bright lensed images larger than 10^(ā0.5). We construct a statistical sample of 11 lensed quasars. Ten of these are galaxy-scale lenses with small image separations (~ 1"-2") and one is a large separation (15") system which is produced by a massive cluster of galaxies, representing the first statistical sample of lensed quasars including both galaxy- and cluster-scale lenses. The Data Release 3 spectroscopic quasars contain an additional 11 lensed quasars outside the statistical sample
Observations and Theoretical Implications of the Large Separation Lensed Quasar SDSS J1004+4112
We study the recently discovered gravitational lens SDSS J1004+4112, the
first quasar lensed by a cluster of galaxies. It consists of four images with a
maximum separation of 14.62''. The system has been confirmed as a lensed quasar
at z=1.734 on the basis of deep imaging and spectroscopic follow-up
observations. We present color-magnitude relations for galaxies near the lens
plus spectroscopy of three central cluster members, which unambiguously confirm
that a cluster at z=0.68 is responsible for the large image separation. We find
a wide range of lens models consistent with the data, but they suggest four
general conclusions: (1) the brightest cluster galaxy and the center of the
cluster potential well appear to be offset by several kpc; (2) the cluster mass
distribution must be elongated in the North--South direction, which is
consistent with the observed distribution of cluster galaxies; (3) the
inference of a large tidal shear (~0.2) suggests significant substructure in
the cluster; and (4) enormous uncertainty in the predicted time delays between
the images means that measuring the delays would greatly improve constraints on
the models. We also compute the probability of such large separation lensing in
the SDSS quasar sample, on the basis of the CDM model. The lack of large
separation lenses in previous surveys and the discovery of one in SDSS together
imply a mass fluctuation normalization \sigma_8=1.0^{+0.4}_{-0.2} (95% CL), if
cluster dark matter halos have an inner slope -1.5. Shallower profiles would
require higher values of \sigma_8. Although the statistical conclusion might be
somewhat dependent on the degree of the complexity of the lens potential, the
discovery is consistent with the predictions of the abundance of cluster-scale
halos in the CDM scenario. (Abridged)Comment: 21 pages, 24 figures, 5 tables, accepted for publication in Ap
Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations
Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations
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