ABSTRACT We present the discovery of nine quasars at identified in the Sloan Digital Sky Survey (SDSS) imaging data. This completes our survey of quasars in the SDSS footprint. Our final sample ...consists of 52 quasars at , including 29 quasars with mag selected from 11,240 deg2 of the SDSS single-epoch imaging survey (the main survey), 10 quasars with selected from 4223 deg2 of the SDSS overlap regions (regions with two or more imaging scans), and 13 quasars down to mag from the 277 deg2 in Stripe 82. They span a wide luminosity range of . This well-defined sample is used to derive the quasar luminosity function (QLF) at . After combining our SDSS sample with two faint ( mag) quasars from the literature, we obtain the parameters for a double power-law fit to the QLF. The bright-end slope β of the QLF is well constrained to be . Due to the small number of low-luminosity quasars, the faint-end slope and the characteristic magnitude are less well constrained, with and mag. The spatial density of luminous quasars, parametrized as , drops rapidly from to 6, with . Based on our fitted QLF and assuming an intergalactic medium (IGM) clumping factor of C = 3, we find that the observed quasar population cannot provide enough photons to ionize the IGM at ∼90% confidence. Quasars may still provide a significant fraction of the required photons, although much larger samples of faint quasars are needed for more stringent constraints on the quasar contribution to reionization.
•Almost half of cancer survivors in this survey had not communicated electronically with clinicians over the past 12 months.•Using health-related technology was a stronger predictor of ...e-communication than demographic features and patient-clinician communication.•Implications of the findings for facilitating transitions to telehealth in cancer care since the pandemic are discussed.
Because of the pandemic, electronic communication between patients and clinicians has taken on increasing significance in the delivery of cancer care. The study explored personal, clinical, and technology factors predicting cancer survivors’ electronic communication with clinicians.
Data for this investigation came from the Health Information National Trends Survey (HINTS5, Cycle 2) that included 593 respondents who previously or currently had cancer. Multivariate regression analyses were used to predict electronic communication with clinicians. Predictors included demographic variables and health status, technology use (online health information-seeking behavior, tracking of health-related data such as using a Fitbit), and quality of past communication experiences with clinicians.
In this pre COVID-19 sample, 42 % respondents (N = 252) did not engage in any type of electronic communication (e.g., emailing, texting, data sharing) with providers. In multivariate analyses, predictors of more electronic communication with clinicians included frequency of seeking health-related information online (ß = .267, p < .001) and better communication experiences with clinicians (ß = .028, p = .034), while no demographic variable showed significance. The technology use variables (online health information seeking, health tracking) were significantly higher predictors of electronic communication with clinicians (ΔR2 = .142, p < .001) than was past experiences with clinicians (ΔR2 = .029, p = .016).
Access and past experience with interactive media technologies are strong predictors of cancer patients’ electronic communication than with clinicians. Adoption of telehealth technology likely depends as much on patients’ relationships with technology as it does their relationships with clinicians.
Since Covid-19, cancer care providers have turned to telehealth provide patients with needed cancer care services. Enhancing patients’ digital competence and experience with electronic communication will help them more easily navigate telehealth care. Providers can leverage their relationship with patients to facilitate more effective use of telehealth services.
Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer ...(NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.
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•Cytoplasm of human oocytes reprograms transplanted somatic cell nuclei to pluripotency•NT-ESCs can be efficiently derived from high-quality human oocytes•Human NT-ESCs are similar to ESCs derived from fertilized embryos
For the first time, diploid human embryonic stem cells are derived from somatic cell nuclear transfer.
Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger ...epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis.
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► REG3A is abundantly expressed in psoriasis and skin wounds ► IL-17 induces REG3A in epidermal keratinocytes ► REG3A induces keratinocyte proliferation but inhibits its differentiation ► REG3A activates EXTL3-PI3K-Akt to promote wound healing
The normal microflora of the skin includes staphylococcal species that will induce inflammation when present below the dermis but are tolerated on the epidermal surface without initiating ...inflammation. Here we reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. This inhibition is mediated by staphylococcal lipoteichoic acid (LTA) and acts selectively on keratinocytes triggered through Toll-like receptor 3(TLR3). We show that TLR3 activation is required for normal inflammation after injury and that keratinocytes require TLR3 to respond to RNA from damaged cells with the release of inflammatory cytokines. Staphylococcal LTA inhibits both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a TLR2-dependent mechanism. To our knowledge, these findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora can modulate specific cutaneous inflammatory responses.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial ...flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea.
Highlights • Pfs25 is candidate for a malaria transmission blocking vaccine. • A recombinant Pfs25 protein was chemically cross-linked to ExoProtein A (EPA). • The Pfs25-EPA chemical conjugate ...appears as a 20 nm nanoparticle. • Pfs25-EPA as a nanoparticle enhanced the immunogenicity of Pfs25 in mice. • Process tech transferred for cGMP pilot-scale manufacturing of Pfs25-EPA.
Objective: This study explores how interpersonal communication environments (eg family, patient-provider, and online communication environments) affect college students' mental help-seeking during ...COVID-19. Methods: Based on Social Cognitive Theory, we conducted a cross-sectional survey assessing participants' mental help-seeking attitudes, self-stigma, self-efficacy, and readiness, as well as their communication experiences with their families, healthcare providers, and online environments. Four hundred fifty-six student participants were recruited. Structural equation modeling was used to explore relationships among the assessed variables. Results: About one-third of the participants (N = 137) had signs of mental distress, and most of them (N = 71) did not intend to seek help soon. Patient-centered communication experiences with healthcare providers were associated with reduced help-seeking stigma, whereas online and family communication predicted help-seeking readiness through changes in attitude, self-stigma, and self-efficacy. Conclusions: This study's results help identify risk factors of help-seeking reluctance. It suggests that communicative environments affect help-seeking by influencing individual predictors. This study may inform interventions targeting college students' use of mental health services during health crises like COVID-19.
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial ...tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.
Mutations in UBQLN2 cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerations. However, the mechanism by which the UBQLN2 mutations cause disease remains ...unclear. Alterations in proteins involved in autophagy are prominent in neuronal tissue of human ALS UBQLN2 patients and in a transgenic P497S UBQLN2 mouse model of ALS/FTD, suggesting a pathogenic link. Here, we show UBQLN2 functions in autophagy and that ALS/FTD mutant proteins compromise this function. Inactivation of UBQLN2 expression in HeLa cells reduced autophagic flux and autophagosome acidification. The defect in acidification was rescued by reexpression of wild type (WT) UBQLN2 but not by any of the five different UBQLN2 ALS/FTD mutants tested. Proteomic analysis and immunoblot studies revealed P497S mutant mice and UBQLN2 knockout HeLa and NSC34 cells have reduced expression of ATP6v1g1, a critical subunit of the vacuolar ATPase (V-ATPase) pump. Knockout of UBQLN2 expression in HeLa cells decreased turnover of ATP6v1g1, while overexpression of WT UBQLN2 increased biogenesis of ATP6v1g1 compared with P497S mutant UBQLN2 protein. In vitro interaction studies showed that ATP6v1g1 binds more strongly to WT UBQLN2 than to ALS/FTD mutant UBQLN2 proteins. Intriguingly, overexpression of ATP6v1g1 in UBQLN2 knockout HeLa cells increased autophagosome acidification, suggesting a therapeutic approach to overcome the acidification defect. Taken together, our findings suggest that UBQLN2 mutations drive pathogenesis through a dominant-negative loss-of-function mechanism in autophagy and that UBQLN2 functions as an important regulator of the expression and stability of ATP6v1g1. These findings may have important implications for devising therapies to treat UBQLN2-linked ALS/FTD.
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