Scholarly interest in the experience of dehumanization, the perception that one is being dehumanized, has increased significantly in recent years, yet the construct lacks a validated measurement. The ...purpose of this research is therefore to develop and validate a theoretically grounded experience of dehumanization measurement (EDHM) using item response theory. Evidence from five studies using data collected from participants in the United Kingdom (N = 2082) and Spain (N = 1427), shows that (a) a unidimensional structure replicates and fits well; (b) the measurement demonstrates high precision and reliability across a broad range of the latent trait; (c) the measurement demonstrates evidence for nomological and discriminant validity with constructs in the experience of dehumanization nomological network; (d) the measurement is invariant across gender and cultures; (e) the measurement demonstrates incremental validity in the prediction of important outcomes over and above conceptually overlapping constructs and prior measurements. Overall, our findings suggest the EDHM is a psychometrically sound measurement that can advance research relating to the experience of dehumanization.
Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body ...of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity—variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity—estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs—indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the ...interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.
Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone ...modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.
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•Modules of correlated molecular phenotypes represent inter-individual chromatin variation•Variable chromatin modules (VCMs) are embedded within chromosomal contact domains•VCMs are orchestrated by cis-acting genetic variation•VCMs rationalize chromatin state changes that are independent of local DNA sequence
Spatially defined chromosome regions, termed variable chromatin modules, exhibit coordinated chromatin state changes across cis-regulatory elements. Within these modules, genetic changes distal from the regulatory element itself can induce variation in chromatin patterns between individuals.
Area-based conservation measures, including protected areas (PA) and other effective area-based conservation measures (OECM), play an important role in biodiversity conservation. In the Brazilian ...Amazon, even though Conservation Units and Indigenous Lands have been shown to reduce deforestation, few studies have addressed Quilombola Territories, and none of the above-mentioned areas were evaluated according to their role in promoting native vegetation regrowth. Here, we used a matching analysis to show that Brazilian Amazon Indigenous Lands, Quilombola Territories, and two types of protected areas (Conservation Units of Restrict Use and Sustainable Use) contribute to reduced native vegetation conversion, when compared to their control areas. Indigenous Lands and Conservation Units of Restrict Use lost respectively 17 and five times less native vegetation cover than their unprotected control areas, between the years of 2005–2012. Similarly, Quilombola Territories had native vegetation loss rates 5.6 times lower than in matched controls. Importantly, our results demonstrate for the first time that between 2012 and 2017 Indigenous Lands and Quilombola Territories contributed two and three times more to native vegetation regrowth – a critical process for safeguarding biodiversity in many, if not all, parts of the world. Our results underscore the importance of areas beyond the formal protected areas system in conserving biodiversity and promoting forest regrowth.
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•Other effective area-based conservation measures will be an important conservation tool in the next decade.•Through matching analysis, we evaluated the effectiveness of different governances for biodiversity conservation.•Indigenous Lands, Quilombola Territories and Conservation Units are effective in curbing native vegetation conversion.•Indigenous Lands, Quilombola Territories and Conservation Units are effective in promoting regrowth.•Other non-formal protected areas can be as effective as formal ones in conserving biodiversity.
These clinical practice guidelines summarize the recommendations of the American Association of Clinical Endocrinologists for the diagnostic evaluation of hyperthyroidism and hypothyroidism and for ...treatment strategies in patients with these disorders. The sensitive thyroid-stimulating hormone (TSH or thyrotropin) assay has become the single best screening test for hyperthyroidism and hypothyroidism, and in most outpatient clinical situations, the serum TSH is the most sensitive test for detecting mild thyroid hormone excess or deficiency. Therapeutic options for patients with Graves' disease include thyroidectomy (rarely used now in the United States), antithyroid drugs (frequently associated with relapses), and radioactive iodine (currently the treatment of choice). In clinical hypothyroidism, the standard treatment is levothyroxine replacement, which must be tailored to the individual patient. Awareness of subclinical thyroid disease, which often remains undiagnosed, is emphasized, as is a system of care that incorporates regular follow-up surveillance by one physician as well as education and involvement of the patient.
Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development ...of new drugs and in the attempt of an early diagnosis that can contribute to improving people's quality of life. There are several advantages to enriching longitudinal studies in AD models with Positron Emission Tomography (PET); among these advantages, the possibility of following the principle of the 3Rs of animal welfare is fundamental. In this manuscript, good daily experimental practice focusing on animal welfare is described and commented upon, based on the experience attained from studies conducted in our Nuclear Medicine department.
Fullerenes are promising nanomaterials, due to their biological, physical, photochemical, and electrical properties. However, their negligible solubility in water represents a limit to their ...extensive use. In this work, we propose a timesaving, green and dry chemistry approach, based on O2 low pressure plasma treatment, to enhance the dispersion of C60 in water. For the first time this kind of process is investigated to modify the C60 surface with polar oxygenated moieties and to fully characterize their water dispersions. The effect of plasma power and treatment time on the chemical composition and structure of fullerene powders, as well as on their dispersibility in water was investigated. XPS analyses on powders highlighted the presence of polar groups at the surface of plasma treated C60, even in higher amount on their dried water suspensions. On the other hand, XRD evidenced, an overall preservation of C60 cages. The enhancement of C60 dispersibility in water was supported by UV–Vis spectroscopy analysis. The obtained C60 dispersions were stable at least over a period of 15 days. Particles size (∼220–250 nm), polydispersity index (∼0.15) and ζ potential (∼-40 mV) of the plasma-modified C60 dispersions were assessed via DLS and ELS confirming the stability at different pH and ionic strength. The present work expands the knowledge of fullerenes processing for the preparation of stable aqueous C60 dispersions.
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Fibrosis is a major socioeconomic burden, but effective antifibrotic therapies are not available in the clinical routine. There is growing evidence for a central role of Wnt signalling in fibrotic ...diseases such as systemic sclerosis, and we therefore evaluated the translational potential of pharmacological Wnt inhibition in experimental dermal fibrosis.
We examined the antifibrotic effects of PKF118-310 and ICG-001, two novel inhibitors of downstream canonical Wnt signalling, in the models of prevention and treatment of bleomycin-induced dermal fibrosis as well as in experimental dermal fibrosis induced by adenoviral overexpression of a constitutively active transforming growth factor (TGF)-β receptor I.
PKF118-310 and ICG-001 were well tolerated throughout all experiments. Both therapeutic approaches showed antifibrotic effects in preventing and reversing bleomycin-induced dermal fibrosis as measured by skin thickness, hydroxyproline content and myofibroblast counts. PKF118-310 and ICG-001 were effective in inhibiting TGF-β receptor I-driven fibrosis as assessed by the same outcome measures.
Blockade of canonical Wnt signalling by PKF118-310 and ICG-001 showed antifibrotic effects in different models of skin fibrosis. Both therapies were well tolerated. Although further experimental evidence for efficacy and tolerability is necessary, inhibition of canonical Wnt signalling is a promising treatment approach for fibrosis.
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