Epigenetic Effects of Resveratrol on Oncogenic Signaling in Breast Cancer.

The crosstalk between oncogenic signaling pathways plays a crucial role in driving cancer development. We previously demonstrated that dietary polyphenols, specifically resveratrol (RSV) and other stilbenoids, epigenetically target oncogenes for silencing via DNA hypermethylation in breast cancer. In the present study, we identify signal transduction regulators among RSV-hypermethylated targets and investigate the functional role of RSV-mediated DNA hypermethylation in the regulation of Hedgehog and Wnt signaling. Non-invasive ER-positive MCF-7 and highly invasive triple-negative MCF10CA1a human breast cancer cell lines were used as experimental models. Upon 9-day exposure to 15 µM RSV, pyrosequencing and qRT-PCR were performed to assess DNA methylation and expression of GLI2 and WNT4, which are upstream regulators of the Hedgehog and Wnt pathways, respectively. Our results showed that RSV led to a DNA methylation increase within GLI2 and WNT4 enhancers, which was accompanied by decreases in gene expression. Consistently, we observed the downregulation of genes downstream of the Hedgehog and Wnt signaling, including common targets shared by both pathways, CCND1 and CYR61. Further analysis using chromatin immunoprecipitation identified increased H3K27 trimethylation and decreased H3K9 and H3K27 acetylation, along with abolishing OCT1 transcription factor binding. Those changes indicate a transcriptionally silent chromatin state at GLI2 and WNT4 enhancers. The inhibition of the Wnt signal transduction was confirmed using a phospho-antibody array that demonstrated suppression of positive and stimulation of negative Wnt regulators. In conclusion, our results provide scientific evidence for dietary polyphenols as epigenetics-modulating agents that act to re-methylate and silence oncogenes, reducing the oncogenic signal transduction. Targeting such an action could be an effective strategy in breast cancer prevention and/or adjuvant therapy.

Tenascin-C promotes endochondral ossification and fracture healing through Hedgehog and Hippo signaling.

Fractures are frequent and severe musculoskeletal injuries. This study aimed to investigate the function of tenascin-C (TNC) in regulating chondrogenic during fracture healing and elucidate the underlying molecular mechanisms. A well-established femur fracture model in male C57BL/6J mice was used to transect the middle diaphysis of the femur. To identify the essential role of TNC, shTNC lentiviruses or TNC protein were administered in the animal model. Micro-CT analysis, histologic analysis, immunostaining assays, and gene expression analysis were employed to investigate the effect of TNC during fracture healing. An in vitro mesenchymal stem cell culture system was developed to investigate the role and molecular mechanism of TNC in regulating chondrogenesis. TNC expression was induced at the inflammatory phase and peaked at the cartilaginous callus phase during fracture healing. Knockdown of TNC expression in callus results in decreased callus formation and impaired fracture healing. Conversely, administration of exogenous TNC promoted chondrogenic differentiation, cartilage template formation and ultimately improved fracture healing. Both the Hedgehog and Hippo signaling pathways were found to be involved in the pro-chondrogenic function of TNC. Our observations demonstrate that TNC is a crucial factor responsible for endochondral ossification in fracture healing and provide a potential therapeutic strategy for promoting fracture healing.

Sea hedgehog-inspired surface-enhanced Raman scattering biosensor probe for ultrasensitive determination of Staphylococcus aureus in food supplements.

Staphylococcus aureus contamination in food supplements poses substantial challenges to public health and large-scale production but the sensitive detection in a timely manner remains a bottleneck. Drawing inspiration from the sea hedgehog, gold nanostars (AuNSs) were leveraged to design an ultrasensitive surface-enhanced Raman scattering (SERS) biosensor for the determination of Staphylococcus aureus in food supplements. Besides the surface enhancement furnished by the AuNSs, Raman reporter molecules and specific aptamers sequentially self-assembled onto these AuNSs to construct the "three-in-one" SERS biosensor probe for label-based quantitation of Staphylococcus aureus. Following incubation with contaminated health product samples, the gold nanostars@Raman reporter-aptamer specifically recognize and assemble around Staphylococcus aureus cells, forming a distinctive sea hedgehog structure. This unique configuration results in an amplified Raman signal at 1338 cm-1 and an enhancement factor of up to 6.71 × 107. The entire quantitative detection process can be completed within 30 min, boasting an exceptional limit of detection as low as 1.0 CFU mL-1. The method exhibits a broad working range for the determination of Staphylococcus aureus, with concentrations spanning 2.15 CFU mL-1 to 2.15 × 105 CFU mL-1. Furthermore, it demonstrates outstanding precision, with relative standard deviation values consistently below 5.0%. As a showcase to validate the practicality of the SERS method, we conducted tests on determining Staphylococcus aureus in a herbal food supplement, i.e., Ginkgo Biloba extract (GBE); the results align closely with those obtained through the conventional lysogeny broth agar plate method, pointing to the potential applicability in real-world scenarios.

The discovery of Moniliformis saudi (Acanthocephala: Moniliformidae) in the Algerian hedgehog Atelerix algirus in Malta: morphological, molecular, and metal analyses.

The acanthocephalan Moniliformis saudi Amin, Heckmann, Mohammed, Evans, 2016 was originally described from the desert hedgehog, Paraechinus aethiopicus (Ehrenberg) in central Saudi Arabia. The distribution of P. aethiopicus extends to North Africa and west to Mauritania. Moniliformis saudi was recently found in the Algerian hedgehog Atelerix algirus (Lereboullet) in Malta. The distribution of A. algirus is restricted to the North African and east Iberian Mediterranean coast and associated islands. Both host species cohabit and share the same feeding grounds in northern Algeria where common infections appear to take place. The morphology of specimens from both acanthocephalan populations was similar, with minor variations mostly related to the relatively larger Maltese specimens especially the trunk and the male reproductive system. Taxonomic features like the cone-shaped anterior trunk, size and formula of proboscis and hooks, the receptacle, size and shape of eggs, anatomy of the apical proboscis sensory pores, and the stellate body wall giant nuclei were, however, practically identical. SEM and microscope images of specimens of the Maltese population emphasize their qualitative characteristics such as the degree of the extreme spiral muscle development and the development of the posterior nucleated pouches of the proboscis receptacle. Proboscis hooks of specimens from both the Maltese and the Saudi populations had similarly high levels (percent weights) of calcium, moderate levels of phosphorus, and minimal levels of sulfur, magnesium and sodium marking the diagnostic value of the Energy Dispersive x-ray analysis in species recognition. Newly generated partial sequences of the 18S ribosomal RNA and cytochrome C oxidase subunit 1 (Cox1) of the mitochondrial gene were generated from M. saudi from Malta. Moniliformis saudi from Malta, when compared with other available sequences of the same species isolates available in the GenBank database, formed a strongly supported clade with other congeners. The comparison of the molecular profiles of specimens from populations in Malta, Spain, and Saudi Arabia shows no or low genetic variation between them. Ultimately, we provide a morphological and molecular description of a new population of M. saudi from a new host species in a new geographical location, vastly exceeding the originally described ones from Saudi Arabia. A Cox 1 haplotype network inferred with 10 sequences revealed the presence of eight haplotypes, one of which was shared between the populations of Malta and Spain of M. saudi.

The first full study of heavy metal(loid)s in western-European hedgehogs (Erinaceus europaeus) from Portugal.

The western-European hedgehog (Erinaceus europaeus) is an insectivore with a wide distribution in Portugal and a potential tool for biomonitoring relevant One Health hazards, including heavy metal(loid)s' pollution. The aim of this study was to positively contribute to the current knowledge about the metal(loid) pollution in Portugal. Forty-six hedgehogs (from rescue centres; with known provenance) were necropsied. Sex, age category and weight were determined. Spines, liver and kidney were collected, and metalloid concentrations were determined by inductively coupled plasma mass spectrophotometry (ICP-MS). In general, results did not present alarming metal(loid) concentrations, with the exception of cadmium (Cd) (in the kidneys) and copper (Cu). Hedgehogs from Viana do Castelo and Viseu showed elevated concentrations of arsenic (As) and Castelo Branco presented concerning values of cadmium (Cd). Adult and heavier hedgehogs tended to present higher levels of metal(loid)s. Sex does not seem to significantly affect the metal(loid)s' concentrations. Further analysis would be needed to prioritize areas with detail and allow the application of the necessary mitigation strategies.

Understanding the effects of per- and polyfluoroalkyl substances on early skin development: Role of ciliogenesis inhibition and altered microtubule dynamics.

Per- and polyfluoroalkyl substances (PFAS) are a class of highly stable chemicals, widely used in everyday products, and widespread in the environment, even in pregnant women. While epidemiological studies have linked prenatal exposure to PFAS with atopic dermatitis in children, little is known about their toxic effects on skin development, especially during the embryonic stage. In this study, we utilized human embryonic stem cells to generate non-neural ectoderm (NNE) cells and exposed them to six PFAS (perfluorooctanoic acid (PFOA), undecafluorohexanoic acid (PFHxA), heptafluorobutyric acid (PFBA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorobutyric acid (PFBS)) during the differentiation process to assess their toxicity to early skin development. Our results showed that PFOS altered the spindle-like morphology of NNE cells to a pebble-like morphology, and disrupted several NNE markers, including KRT16, SMYD1, and WISP1. The six PFAS had a high potential to cause hypohidrotic ectodermal dysplasia (HED) by disrupting the expression levels of HED-relevant genes. Transcriptomic analysis revealed that PFOS treatment produced the highest number (1156) of differentially expressed genes (DEGs) among the six PFAS, including the keratinocyte-related genes KRT6A, KRT17, KRT18, KRT24, KRT40, and KRT81. Additionally, we found that PFOS treatment disturbed several signaling pathways that are involved in regulating skin cell fate decisions and differentiation, including TGF-ß, NOTCH, Hedgehog, and Hippo signaling pathways. Interestingly, we discovered that PFOS inhibited, by partially interfering with the expression of cytoskeleton-related genes, the ciliogenesis of NNE cells, which is crucial for the intercellular transduction of the above-mentioned signaling pathways. Overall, our study suggests that PFAS can inhibit ciliogenesis and hamper the transduction of important signaling pathways, leading potential congenital skin diseases. It sheds light on the underlying mechanisms of early embryonic skin developmental toxicity and provides an explanation for the epidemiological data on PFAS. ENVIRONMENTAL IMPLICATION: We employed a model based on human embryonic stem cells to demonstrate that PFOS has the potential to elevate the risk of hypohidrotic ectodermal dysplasia. This is achieved by targeting cilia, inhibiting ciliogenesis, and subsequently disrupting crucial signaling pathways like TGF-ß, NOTCH, Hedgehog, and Hippo, during the early phases of embryonic skin development. Our study highlights the dangers and potential impacts of six PFAS pollutants on human skin development. Additionally, we emphasize the importance of closely considering PFHxA, PFBA, PFHxS, and PFBS, as they have shown the capacity to modify gene expression levels, albeit to a lesser degree.

Bilateral renal dysplasia with systemic fibrous osteodystrophy in a four-toed hedgehog (Atelerixalbiventris).

A 4-month-old female four-toed hedgehog (Atelerix albiventris) presented with lethargy, anorexia, dyspnoea and weight loss. Following death, post-mortem computed tomography (CT) and an autopsy were performed. CT revealed that the external surfaces of bones, including the cranial bones and vertebrae, were rough and osteolytic lesions were present multifocally in the ribs and some appendicular bones. On gross examination, both kidneys were severely enlarged and, on cut sections, a few cysts (up to 1 mm diameter) were present in the medulla. The cervical, thoracic and lumbar vertebrae were diffusely enlarged with deformation of the intervertebral discs. Histologically, there were immature glomeruli and tubules and adenomatoid/atypical epithelium in the kidneys. These changes were interpreted as renal dysplasia. In the bones evaluated, the trabeculae were thinner than normal, decreased in number and surrounded by many osteoclasts, with abundant fibrous connective tissue between atrophied trabeculae. These changes were consistent with fibrous osteodystrophy. Although kidney diseases are common in four-toed hedgehogs, there are no reports of congenital renal diseases, including renal dysplasia. To the best of our knowledge, this is the first report of the clinical and pathological features of renal dysplasia with fibrous osteodystrophy in a four-toed hedgehog.

Ectoparasites of European hedgehogs (Erinaceus europaeus) in Germany and their health impact.

BACKGROUND: The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres. METHODS: Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models. RESULTS: Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites. Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals. CONCLUSIONS: With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities.

A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren's disease.

Dupuytren's disease (DD) is a highly heritable fibrotic disorder of the hand with incompletely understood etiology. A number of genetic loci, including Wnt signaling members, have been previously identified. Our overall aim was to identify novel genetic loci, to prioritize genes within the loci for functional studies, and to assess genetic correlation with associated disorders. We performed a meta-analysis of six DD genome-wide association studies from three European countries and extensive bioinformatic follow-up analyses. Leveraging 11,320 cases and 47,023 controls, we identified 85 genome-wide significant single nucleotide polymorphisms in 56 loci, of which 11 were novel, explaining 13.3-38.1% of disease variance. Gene prioritization implicated the Hedgehog and Notch signaling pathways. We also identified a significant genetic correlation with frozen shoulder. The pathways identified highlight the potential for new therapeutic targets and provide a basis for additional mechanistic studies for a common disorder that can severely impact hand function.

Effect of urbanization on the trace element concentrations in the kidney, liver and spines of the European hedgehog (Erinaceus europaeus).

Urbanized environments may be suitable for some wild species, like the European hedgehog (Erinaceus europaeus). However, the (sub)urban areas are source of several pollutants, such as trace elements (TEs). The main objective of our study is to investigate the role of the European hedgehog as a potential bioindicator species for seven TEs (As, Cd, Cr, Cu, Ni, Pb, Zn) in a big urban agglomeration. We analyzed the kidney, liver and spines of 50 European hedgehogs. Moreover, we carried out geographic information system (GIS) with 31 individuals to examine the effects of human pressure (human density and urbanization) on TE concentrations in tissues. We detected the 7 TEs in all tissues. Trace elements, especially Pb and Zn, in the liver, kidney and spines seem to be influenced by human density and urbanization.

Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus).

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.

Verminous pneumonia in European hedgehogs (Erinaceus europaeus).

The European hedgehog (Erinaceus europaeus) is a common wildlife species in European countries. Populations are declining due to anthropogenic factors and natural diseases. Verminous pneumonia has been observed as a frequent infectious disease in hedgehogs submitted for diagnostic postmortem examination. This prompted the present in-depth investigation on the lungs of 27 necropsied hedgehogs with confirmed lungworm infections, with or without antiparasitic treatment prior to death. The histological and/or parasitic (fecal samples) examination identified Capillaria aerophila infection in most animals (82%). The parasites were found free in the airway lumen and/or within the airway epithelium, from the larynx to bronchioles. Embedded worms and eggs were associated with epithelial hyperplasia or metaplasia, and long-term inflammation. More than half of the animals (59%) carried Crenosoma striatum, and 41% had a coinfection. C striatum adults were predominantly found free in the lumen of bronchi and bronchioles, and larvae were occasionally seen in granulomas in the pulmonary interstitium, the liver, and the intestine. Independent of the parasite species, a lymphoplasmacytic peribronchitis and, less frequently, interstitial infiltration of eosinophils, neutrophils, and macrophages as well as pneumocyte type II hyperplasia was seen. Interestingly, the extent of pneumonia was not correlated with age, respiratory clinical signs, antiparasitic treatment, or single or coinfection. Verminous pneumonia appeared to be the cause of death in over 25% of the animals, indicating that these parasites not only coexist with hedgehogs but can also be a primary pathogen in this species.

African Pygmy Hedgehog Pediatrics.

African pygmy hedgehogs have become a popular pet and are commonly available through breeders and pet stores. Responsible breeding, proper husbandry, and close monitoring of the dam and pups are important for neonatal health. The risk of abandonment or cannibalism is high in this species especially in stressed dams unfamiliar to frequent handling. Hand-rearing hedgehog pups is difficult and cross-fostering is a preferable alternative for abandoned pups when possible. If intervention becomes necessary, heat support, frequent feedings, and physical stimulation to eliminate must be provided.

Efficacy of levamisole, ivermectin and moxidectin against Capillaria spp. in European hedgehogs (Erinaceus europaeus).

This randomised study aimed to assess and compare the efficacy of treatment protocols containing levamisole, ivermectin, or moxidectin against Capillaria spp. in naturally infected European hedgehogs (Erinaceus europaeus) presented to a British wildlife rehabilitation centre. Faecal analysis, consisting of wet mount and flotation, was performed for 229 hedgehogs weighing ≥200g. Animals testing positive for Capillaria spp. (81%), excluding pregnant females, were randomly allocated a treatment protocol. Initially, hedgehogs (n = 50) received one of six 'pilot' protocols, whereas the remaining animals (n = 97) received one of three 'main' protocols. Faecal analysis was repeated on day 8 and day 12 after treatment initiation. Efficacy of each treatment was assessed based on Capillaria reduction rate (CRR), weight gain, presence of respiratory clinical signs, and outcome. Pilot protocols containing only moxidectin had a significantly lower CRR (≥28.1%) compared to those with levamisole or ivermectin (≥86.6%), whereas the main protocols containing levamisole had a significantly higher CRR (≥93.0%) compared to those containing only ivermectin (≥69.3%). Clinical parameters did not differ significantly between treatments, but animals with respiratory clinical signs at the end of the trial were significantly more likely to have lower CRR and test positive for Crenosoma striatum. C. striatum often appeared refractory to treatment, and managing these infections requires additional anthelmintic therapy. Based on the formulations and dosages trialled, moxidectin is not recommended for treating capillariosis in European hedgehogs, whereas levamisole given orally for two consecutive days at 25-35 mg/kg is suggested as the treatment of choice.

Characterization of the Small Intestine in the Southern White-breasted Hedgehog (Erinaceus concolor) Using Histological, Histochemical, Immunohistochemical, and Scanning Electron Microscopic Techniques.

The present study was designed to investigate the microscopic features of the small intestine in the southern white-breasted hedgehog (Erinaceus concolor). The histochemical profile of the small intestine was investigated using periodic acid Schiff (PAS), alcian blue (AB, pH 2.5), and aldehyde fuchsin. The expression of SOX9 was also evaluated immunohistochemically, and the detailed morphology of intestinal mucosa was studied by using a scanning electron microscope. The intestinal wall was composed of the tunica mucosa, tunica submucosa, tunica muscularis, and tunica serosa. Plica circulares and muscularis mucosa were present only in the duodenum. The jejunal villi were the tallest and the ileal villi were the shortest. From the duodenum to the ileum, the population density of goblet cells decreased significantly. The goblet cells throughout the small intestine reacted positively with PAS and AB. The expression rate of SOX9 was not statistically different between the three parts of the small intestine (p > 0.05). In conclusion, despite the general characteristics of the small intestine in this species of hedgehog, there were some differences when compared with other mammalian and rodent species. These findings provide a baseline for future detailed research on the digestive system of the hedgehog species and other mammalian species.

Metal and metalloid concentrations in wild mammals from SW Europe: European hedgehog (Erinaceus europaeus) and badger (Meles meles).

In recent years, there have been increasing ecological and global concerns associated to Potentially Toxic Elements (PTEs). Thus, the relevance of wild mammals as biomonitors has been globally recognised. In the present study, Cd, Pb, Hg, Zn and As concentrations were quantified in European hedgehog and badger inhabiting SW Europe, and cumulative trends in relation to age and sex were evaluated. Liver and kidney samples were collected, mineralised and PTE content was determined by ICP-MS. Zn was the most abundant element quantified in both organs (239 and 89.8 mg kg-1 for hedgehogs and 179 and 164 mg kg-1 dw for badgers). In hedgehogs, very high Hg concentration were quantified (4.35 and 15.5 mg kg-1 dw in liver and kidney), and Cd was the most abundant for badgers (4.70 and 7.61 mg kg-1 dw in liver and kidney). Positive correlations were observed for the concentrations of PTE in the organs of both species. Age-dependence increased only Cd concentration, with levels in adult kidneys being significantly higher. In this study, European hedgehog and badger were used as biomonitors for the determination of PTEs to provide current reference values in relatively non-polluted areas of SW Europe, and to enhance the use of these species for future ecotoxicological studies.

COX2-ATP Synthase Regulates Spine Follicle Size in Hedgehogs.

Skin evolves essential appendages with adaptive patterns that synergistically insulate the body from environmental insults. How similar appendages in different animals generate diversely-sized appendages remain elusive. Here we used hedgehog spine follicles and mouse hair follicles as models to investigate how similar follicles form in different sizes postnatally. Histology and immunostaining show that the spine follicles have a significantly greater size than the hair follicles. By RNA-sequencing analysis, we found that ATP synthases are highly expressed in hedgehog skin compared to mouse skin. Inhibition of ATP synthase resulted in smaller spine follicle formation during regeneration. We also identified that the mitochondrial gene COX2 functions upstream of ATP synthase that influences energy metabolism and cell proliferation to control the size of the spine follicles. Our study identified molecules that function differently in forming diversely-sized skin appendages across different animals, allowing them to adapt to the living environment and benefit from self-protection.

Confessions of a hedgehog aspirant: Reply to Verkuyten (2023) and Jung (2023).

The potential of the disapproval-respect model as a conceptual tool and explanatory device for the analysis of tolerance phenomena as well as its value as a guideline for future tolerance research is reiterated and further explained. Also, the distinctiveness of the model is underscored as is its realism with regard to the role of tolerance in processes of social influence and social change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).