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In recent years, new media have exacerbated the complexity of online public opinion scenarios through fragmentation of information, diversification of public opinion, rapid diffusion of public opinion, and concealment of information sources, which have posed several serious challenges to the benign development of online public opinion ecosystems. Therefore, based on diversified public opinion scenarios, we study the interaction between information dissemination and the evolution of group opinions and the dissemination laws to solve the problem of imprecise grasping of the dissemination laws in complex public opinion scenarios. Facing the two-way interaction between online platforms and real society, we constructed a coupled online–offline viewpoint evolution dynamics model, which considers factors such as the user subject level and the network environment level, and combines viewpoint dynamics theory with information dissemination dynamics theory. Based on the real case of dual interaction between online and offline, we carry out the construction of a two-layer coupling network and numerical fitting comparison experiments to study the synergistic and penetration mechanism of public opinion in both online and offline multi-spaces. Based on parametric analysis experiments, the influence of different factors on communication indicators is mined, and the driving effect of the viewpoint environment of offline communication on online public opinion is studied, which reveals the objective role of multi-factors on the law of intralayer communication, cross-network communication, and viewpoint evolution, and provides strategic suggestions for the comprehensive management of public opinion in online–offline large-scale mass incidents. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD) is one of the most important and essential components within an organism. Extensive ongoing research is aimed at harnessing its potential in managing diverse diseases by supplying various forms of NAD in its oxidized state, NAD+. Ultraviolet radiation (UVR) is the most common environmental exposure factor, but also carries many risks. UVR affects the epidermis and contributes to sunburn, photo-allergy, DNA damage, and certain cancers, notably melanoma. Research has shown that NAD+ precursors, including nicotinamide riboside (NR), reduce melanogenesis in aged melanocytes. In this study, we used NR to determine whether melanin hyperpigmentation was suppressed after light stimulation. We found that melanogenesis was inhibited when B16F10 cells treated with α-melanocyte-stimulating hormone were exposed to specific doses of NR. Additionally, tyrosinase activity (a key step in melanin production) was suppressed. However, there was no difference in the expression level of melanogenic genes. Ultraviolet B light directly stimulated HaCaT cells, inducing the RNA expression of metalloproteinases. Treatment with NR suppressed the corresponding gene expression and reduced cytotoxicity. This study demonstrates the possibility of using NR as a new skin-whitening ingredient due to its inhibitory effect on hyperpigmentation and ability to maintain skin layers affected by UVR. [ABSTRACT FROM AUTHOR]

Sheep's milk is becoming increasingly popular in dairy industry technology due to its high content of bioactive substances. Owing to its high content of fat-soluble vitamins such as A, D and E, it exhibits strong antioxidant activity. It contributes to the neutralization of reactive oxygen species, which are a factor in the development of many diseases. Vitamin D supports the immune, skeletal, nervous, circulatory, and digestive systems and regulates calcium and phosphate metabolism, which is essential to normal bone development and mineralization. The purpose of the present study was to determine changes in vitamin D content in sheep milk during lactation. The study was conducted on two breeds of sheep – Polish Mountain sheep and Podhale Zackel. The sheep grazed in the Małe Pieniny Mountains, in the pasture in Jaworki. Testing of the samples was commissioned to JARS Commercial Company. A total of 550 animals were used in the study: 250 Polish Mountain ewes and 300 Podhale Zackel ewes. The study lasted from May to September and involved bulk sampling, carried out twice a month. Samples were taken from milking of 50 randomly selected animals of each breed from the entire herd. Average milk yield and vitamin D content were analysed. Analysis of the data indicated that the stage of lactation significantly affected milk yield, which decreased as it progressed, and the amount of vitamin D, which increased as it progressed. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body 's immunity and changes in intestinal flora. This study was conducted to investigate the effects of dietary Hong-bailanshen (HBLS) supplementation in horses on serum biochemical profile, antioxidant enzymes and gut microbiota. Methods: In this study, five horses were selected. On day 0, 14, 28, blood samples and feces were collected on days 0, 14, and 28 to analyse gut microbiota, serum biochemical and redox indexes. a Results: The results showed that the addition of HBLS to horse diets significantly decreased the level of alanine aminotransferase, alkaline phosphatase, creatine kinase and malondialdehyde (p < 0.05, p < 0.01) and significantly increased the activity of total antioxidant capacity, superoxide dismutase and catalase (p < 0.05, p < 0.01). Compared with day 14, the levels of alanine aminotransferase, alkaline phosphatase and creatine kinase were significantly decreased; however, the level of catalase was significantly increased in the horses continuously fed with HBLS for 28 days (p < 0.05, p < 0.01). Alpha diversity analysis was performed that chao1 (p < 0.05), observed_specicies, faith'pd and goods_coverage upregulated in the horses fed HBLS. A total of 24 differential genera were detected adding HBLS to diet increased the abundance of Bacillus, Lactobacillaceae, Leuconostocaceae, Christensenellaceae, Peptostreptococcaceae, Faecalibacterium, Erysipelotrichaceae, Pyramidobacter, Sphaerochaeta, WCHB1-25, Bacteria, Oscillospira, and Acetobacteraceae, while reduced Aerococcus, EtOH8, Syntrophomonas, Caulobacter, Bradyrhizobiaceae, W22, Succinivibrionaceae, and Desulfovibrio (p < 0.05, p < 0.01). Conclusion: Adding HBLS to the diet could be a potentially effective strategy to improve horses' health. [ABSTRACT FROM AUTHOR]

General epistemic polarization arises when the beliefs of a population grow further apart, in particular when all agents update on the same evidence. Epistemic factionalization arises when the beliefs grow further apart, but different beliefs also become correlated across the population. I present a model of how factionalization can emerge in a population of ideally rational agents. This kind of factionalization is driven by probabilistic relations between beliefs, with background beliefs shaping how the agents’ beliefs evolve in the light of new evidence. Moreover, I show that in such a model, the only possible outcomes from updating on identical evidence are general convergence or factionalization. Beliefs cannot spread out in all directions: if the beliefs overall polarize, then it must result in factionalization. [ABSTRACT FROM AUTHOR]

This paper examines the fundamental problem of testimony. Much of what we believe to know we know in good part, or even entirely, through the testimony of others. The problem with testimony is that we often have very little on which to base estimates of the accuracy of our sources. Simulations with otherwise optimal agents examine the impact of this for the accuracy of our beliefs about the world. It is demonstrated both where social networks of information dissemination help and where they hinder. Most importantly, it is shown that both social networks and a common strategy for gauging the accuracy of our sources give rise to polarisation even for entirely accuracy motivated agents. Crucially these two factors interact, amplifying one another's negative consequences, and this side effect of communication in a social network increases with network size. This suggests a new causal mechanism by which social media may have fostered the increase in polarisation currently observed in many parts of the world. [ABSTRACT FROM AUTHOR]

Computational models have shown how polarisation can rise among deliberating agents as they approximate epistemic rationality. This paper provides further support for the thesis that polarisation can rise under condition of epistemic rationality, but it does not depend on limitations that extant models rely on, such as memory restrictions or biased evaluation of other agents' testimony. Instead, deliberation is modelled through agents' purposeful introduction of arguments and their rational reactions to introductions of others. This process induces polarisation dynamics on its own. A second result is that the effect size of polarisation dynamics correlates with particular types of argumentative behaviour. Polarisation effects can be soothed when agents take into account the opinions of others as premises, and they are amplified as agents fortify their own beliefs. These results underpin the relevance of argumentation as a factor in social-epistemic processes and indicate that rising issue polarisation is not a reliable indicator of epistemic shortcomings. [ABSTRACT FROM AUTHOR]

This paper presents a case study of how agent-based modelling can be utilized to conduct a cost-benefit analysis of two differing adaptational strategies to resource insecurity. Using Inuit Nunangat (the Canadian Arctic) as the setting, models are developed to represent two adaptational strategies in response to the onset of the Little Ice Age: exchange with other communities via long-distance trade and intensification of local resource procurement. After determining the average kilograms of resources acquired through a model of local resource procurements, two models were then developed to determine under what scenarios long-distance journeys to procure perishable food goods would be more productive than hunting locally. Ultimately, the results showed that while there are scenarios where undertaking a trading journey would result in a higher average amount of resources acquired, those scenarios would not have been realistic for most Thule communities, leaving hunting locally as the more beneficial adaptational strategy on an economic basis. [ABSTRACT FROM AUTHOR]

Skin pigmentation abnormalities, ranging from aesthetic concerns to severe hyperpigmentation disease, have profound implications for individuals’ psychological and economic wellbeing. The intricate etiology of hyperpigmentation and our evolving comprehension of its underlying mechanisms underscore the need for robust animal models. Zebrafish, renowned for their transparent embryos and genetic parallels to humans, have been spotlighted as a pivotal model for skin pigmentation studies. This review offers a concise overview of zebrafish skin attributes, highlighting the shared melanin production pathways with humans. We systematically dissect the diverse strategies to craft zebrafish models of abnormal skin pigmentation, spanning physical, chemical, and genetic interventions, while critically appraising the merits and constraints of each approach. Additionally, we elucidate the metrics employed to gauge the efficacy of these models. Concluding, we cast a visionary gaze on prospective breakthroughs in the domain, aiming to steer forthcoming efforts in refined zebrafish models for skin pigmentation research. [ABSTRACT FROM AUTHOR]

Melanocytes, which originate from the neuroectoderm, are specialized cells responsible for producing pigments and possessing a dendritic morphology. These cells migrate to the epidermis and follicles, contributing to skin and hair pigmentation during embryonic development. The remarkable self-renewal capacity of melanocytes enables them to effectively restore hair and skin pigmentation. The synthesis of melanin to safeguard the skin against damage caused by ultraviolet radiation, as well as the enigmatic immune function of melanocytes, demonstrate their indispensable contributions to maintaining cutaneous homeostasis. The regulation of cutaneous pigmentation involves an intricate network influenced by intrinsic cellular signals within melanocytes and extracellular cues. Therefore, this paper provides a comprehensive review of the role of melanocytes in skin biology. This in-depth analysis could open novel avenues for research aimed at the prevention and treatment of skin disorders. [ABSTRACT FROM AUTHOR]

Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/β‐catenin signalling pathway has been of recent interest in vitiligo. Wnt/β‐catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/β‐catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. Wnt/β‐catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/β‐catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/β‐catenin signalling. Agents that can enhance the effect of Wnt/β‐catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the molecular mechanisms involved in feather color formation is important because coloration is one of the most recognizable characteristics in chickens. In this study, after transcrip-tome sequencing of the wing and neck feather follicle tissues of chickens with different plumage colors, we retrieved differentially expressed genes (DEGs) with the same trends in both the wing and neck and then identified DEGs that may be associated with melanin deposition through GO and KEGG annotation and PPI analysis. Finally, we verified that two genes in chicken melanocytes, SLC45A2 and GPNMB, promote melanocyte melanin deposition in chickens. As an essential genetic and economic trait, chicken feather color has long been an important research topic. To further understand the mechanism of melanin deposition associated with coloration in chicken feathers, we selected feather follicle tissues from the neck and wings of chickens with differently colored feathers (yellow, sub-Columbian, and silver) for transcriptome analysis. We focused on genes that were expressed in both the wings and neck and were expressed with the same trends in breeds with two different plumage colors, specifically, SLC45A2, GPNMB, MLPH, TYR, KIT, WNT11, and FZD1. GO and KEGG enrichment analyses showed the DEGs were enriched in melanin-related pathways, such as tyrosine metabolic pathway and melanogenesis, and PPI analysis highlighted the genes SLC45A2 and GPNMB as associated with melanin deposition. Verification experiments in chicken melanocytes demonstrated that these two genes promote melanocyte melanin deposition. These data enrich our knowledge of the mechanisms that regulate chicken feather color. [ABSTRACT FROM AUTHOR]

Innovations in ancient DNA (aDNA) preparation and sequencing technologies have exponentially increased the quality and quantity of aDNA data extracted from ancient biological materials. The additional temporal component from the incoming aDNA data can provide improved power to address fundamental evolutionary questions like characterizing selection processes that shape the phenotypes and genotypes of contemporary populations or species. However, utilizing aDNA to study past selection processes still involves considerable hurdles like how to eliminate the confounding factor of genetic interactions in the inference of selection. To address this issue, we extend the approach of He et al., 2023 to infer temporally variable selection from the aDNA data in the form of genotype likelihoods with the flexibility of modelling linkage and epistasis in this work. Our posterior computation is carried out by a robust adaptive version of the particle marginal Metropolis‐Hastings algorithm with a coerced acceptance rate. Our extension inherits the desirable features of He et al., 2023 such as modelling sample uncertainty resulting from the damage and fragmentation of aDNA molecules and reconstructing underlying gamete frequency trajectories of the population. We evaluate its performance through extensive simulations and show its utility with an application to the aDNA data from pigmentation loci in horses. [ABSTRACT FROM AUTHOR]

Most sociophysics opinion dynamics simulations assume that contacts between agents lead to greater similarity of opinions, and that there is a tendency for agents having similar opinions to group together. These mechanisms result, in many types of models, in significant polarization, understood as separation between groups of agents having conflicting opinions. The addition of inflexible agents (zealots) or mechanisms, which drive conflicting opinions even further apart, only exacerbates these polarizing processes. Using a universal mathematical framework, formulated in the language of utility functions, we present novel simulation results. They combine polarizing tendencies with mechanisms potentially favoring diverse, non-polarized environments. The simulations are aimed at answering the following question: How can non-polarized systems exist in stable configurations? The framework enables easy introduction, and study, of the effects of external "pro-diversity", and its contribution to the utility function. Specific examples presented in this paper include an extension of the classic square geometry Ising-like model, in which agents modify their opinions, and a dynamic scale-free network system with two different mechanisms promoting local diversity, where agents modify the structure of the connecting network while keeping their opinions stable. Despite the differences between these models, they show fundamental similarities in results in terms of the existence of low temperature, stable, locally and globally diverse states, i.e., states in which agents with differing opinions remain closely linked. While these results do not answer the socially relevant question of how to combat the growing polarization observed in many modern democratic societies, they open a path towards modeling polarization diminishing activities. These, in turn, could act as guidance for implementing actual depolarization social strategies. [ABSTRACT FROM AUTHOR]

There have been many discussions recently from philosophers, cognitive scientists, and psychologists about group polarization , with online and social media environments in particular receiving a lot of attention, both because of people's increasing reliance on such environments for receiving and exchanging information and because such environments often allow individuals to selectively interact with those who are like-minded. My goal here is to argue that the group epistemologist can facilitate understanding the kinds of factors that drive group polarization in a way that has been overlooked by the existing research. Specifically, I argue that polarization can occur in part because of the ways that members of a group treat the group itself (as opposed to an individual member within that group) as a source of information, and in doing so makes their own position, as well as that of the group, more extreme. I refer to this as a structural factor in driving polarization, and argue that such factors can contribute to explanations of polarization that occurs specifically in an important subset of groups, namely online and social media groups in which little is known about other members within the group, what I refer to as anonymous, semi-anonymous and pseudonymous (ASAP) groups. [ABSTRACT FROM AUTHOR]

Novel technologies for recovering DNA information from archaeological and historical specimens have made available an ever-increasing amount of temporally spaced genetic samples from natural populations. These genetic time series permit the direct assessment of patterns of temporal changes in allele frequencies and hold the promise of improving power for the inference of selection. Increased time resolution can further facilitate testing hypotheses regarding the drivers of past selection events such as the incidence of plant and animal domestication. However, studying past selection processes through ancient DNA (aDNA) still involves considerable obstacles such as postmortem damage, high fragmentation, low coverage, and small samples. To circumvent these challenges, we introduce a novel Bayesian framework for the inference of temporally variable selection based on genotype likelihoods instead of allele frequencies, thereby enabling us to model sample uncertainties resulting from the damage and fragmentation of aDNA molecules. Also, our approach permits the reconstruction of the underlying allele frequency trajectories of the population through time, which allows for a better understanding of the drivers of selection. We evaluate its performance through extensive simulations and demonstrate its utility with an application to the ancient horse samples genotyped at the loci for coat coloration. Our results reveal that incorporating sample uncertainties can further improve the inference of selection. [ABSTRACT FROM AUTHOR]

Simple Summary: The frequency of use of permanent hair dyes to change natural colour are associated with fibre damage and with an increased risk of serious health problems. The future of hair dyeing could be the topical modulation of the pigment production that occurs in special cells, called melanocytes, localized in the hair roots. The success of such approaches is dependent on expanding and deepening our knowledge on hair pigmentation biology. In this context, the paper aims to critically review the vast bibliography on mammalian pigmentation having in view the topical modulation of hair follicle biology to produce a desired change in the hair fibre colour. The natural colour of hair shafts is formed at the bulb of hair follicles, and it is coupled to the hair growth cycle. Three critical processes must happen for efficient pigmentation: (1) melanosome biogenesis in neural crest-derived melanocytes, (2) the biochemical synthesis of melanins (melanogenesis) inside melanosomes, and (3) the transfer of melanin granules to surrounding pre-cortical keratinocytes for their incorporation into nascent hair fibres. All these steps are under complex genetic control. The array of natural hair colour shades are ascribed to polymorphisms in several pigmentary genes. A myriad of factors acting via autocrine, paracrine, and endocrine mechanisms also contributes for hair colour diversity. Given the enormous social and cosmetic importance attributed to hair colour, hair dyeing is today a common practice. Nonetheless, the adverse effects of the long-term usage of such cosmetic procedures demand the development of new methods for colour change. In this context, case reports of hair lightening, darkening and repigmentation as a side-effect of the therapeutic usage of many drugs substantiate the possibility to tune hair colour by interfering with the biology of follicular pigmentary units. By scrutinizing mammalian pigmentation, this review pinpoints key targetable processes for the development of innovative cosmetics that can safely change the hair colour from the inside out. [ABSTRACT FROM AUTHOR]

Frizzled (FZD) proteins are receptors for the WNT family ligands. Inherited human diseases and genetic experiments using knockout mice have revealed a central role of FZDs in multiple aspects of embryonic development and tissue homeostasis. Misregulated FZD signaling has also been found in many cancers. Recent studies on three out of the ten mammalian FZDs in melanoma have shown that they promote tumor cell proliferation and invasion, via the activation of the canonical WNT/b-catenin or non-canonical PCP signaling pathway. In this concise review, we summarize our current knowledge of individual FZDs in melanoma, discuss the involvement of both the canonical and non-canonical pathways, and describe ongoing efforts to target the FZD receptors for melanoma treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite major recent therapeutic advances, melanoma remains the deadliest form of skin cancer due to the capacity of melanoma cells to adapt to drug treatment and become resistant. Improved understanding of melanoma suggests that it resists treatment not just due to DNA changing mutations but also due to changes in DNA accessibility with respect to the reading and creation of different proteins. Here, we summarize the various ways in which different DNA regions become more or less open, impacting patient response to anti-cancer therapies. For instance, targeting specific proteins governing the expression of viral-like genes can alert the immune system and enhance the effects of anti-cancer therapies. Alternatively, changes in DNA accessibility allow the activation of alternative survival signals that allow melanoma cells to escape death upon treatment. Targeting factors modulating DNA accessibility in cancer cells has recently become possible through technological developments. These novel therapies, administered alone or in combination with existing ones, represent the next frontier in the treatment of advanced melanoma. Melanoma is an aggressive skin cancer reliant on early detection for high likelihood of successful treatment. Solar UV exposure transforms melanocytes into highly mutated tumor cells that metastasize to the liver, lungs, and brain. Even upon resection of the primary tumor, almost thirty percent of patients succumb to melanoma within twenty years. Identification of key melanoma genetic drivers led to the development of pharmacological BRAFV600E and MEK inhibitors, significantly improving metastatic patient outcomes over traditional cytotoxic chemotherapy or pioneering IFN-α and IL-2 immune therapies. Checkpoint blockade inhibitors releasing the immunosuppressive effects of CTLA-4 or PD-1 proved to be even more effective and are the standard first-line treatment. Despite these major improvements, durable responses to immunotherapy and targeted therapy have been hindered by intrinsic or acquired resistance. In addition to gained or selected genetic alterations, cellular plasticity conferred by epigenetic reprogramming is emerging as a driver of therapy resistance. Epigenetic regulation of chromatin accessibility drives gene expression and establishes distinct transcriptional cell states. Here we review how aberrant chromatin, transcriptional, and epigenetic regulation contribute to therapy resistance and discuss how targeting these programs sensitizes melanoma cells to immune and targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The importance of the coat color in horses has been present since their domestication. The interactive effect of coat color-determinant genes on other traits, such as behavior, makes it a factor of importance in horse selection, as it determines the way the horse perceives and reacts to its environment. Eye temperature at rest (ETR) assessed with infrared thermography was used as a suitable non-invasive tool to assess basal reactivity. The aim of this study was to evaluate the influence of coat color on basal reactivity assessed with infrared thermography, determine their relationship with the results obtained in show jumping competitions, and to estimate the genetic parameters for ETR to test its suitability for genetic selection. Our results indicated differences in ETR due to six different factors. We also discovered a positive correlation with ranking in show jumping, indicating that less reactive horses were more likely to achieve better rankings. The genetic results indicated that part of the variability present in the basal reactivity due to coat color has an environmental origin. The heritability values indicate that ETR has a suitable genetic basis to be used in the breeding program to select for basal reactivity due to coat color. Horses have been valued for their diversity of coat color since prehistoric times. In particular, the pleiotropic effect that coat color genes have on behavior determines the way the horse perceives and reacts to its environment. The primary aim of this study was to evaluate the influence of coat color on basal reactivity assessed with infrared thermography as eye temperature at rest (ETR), determine their relation with the results obtained by these horses in Show Jumping competitions and to estimate the genetic parameters for this variable to test its suitability for genetic selection. A General Linear Model (GLM) and Duncan post-hoc analysis indicated differences in ETR due to coat color, sex, age, location, and breed-group factors. A Spearman's rank correlation of 0.11 (p < 0.05) was found with ranking, indicating that less reactive horses were more likely to achieve better rankings. Heritability values ranged from 0.17 to 0.22 and were computed with a model with genetic groups and a model with residual variance heterogeneity. Breeding values were higher with the last genetic model, thus demonstrating the pleiotropic effect of coat color. These results indicate that ETR has a suitable genetic basis to be used in the breeding program to select for basal reactivity due to coat color. [ABSTRACT FROM AUTHOR]

Bidirectional interactions between plastic tumor cells and the microenvironment critically impact tumor evolution and metastatic dissemination by enabling cancer cells to adapt to microenvironmental stresses by switching phenotype. In melanoma, a key determinant of phenotypic identity is the microphthalmia‐associated transcription factor MITF that promotes proliferation, suppresses senescence, and anticorrelates with immune infiltration and therapy resistance. What determines whether MITF can activate or repress genes associated with specific phenotypes, or how signaling regulating MITF might impact immune infiltration is poorly understood. Here, we find that MITF binding to genes associated with high MITF is via classical E/M‐box motifs, but genes downregulated when MITF is high contain FOS/JUN/AP1/ATF3 sites. Significantly, the repertoire of MITF‐interacting factors identified here includes JUN and ATF3 as well as many previously unidentified interactors. As high AP1 activity is a hallmark of MITFLow, invasive, slow‐cycling, therapy resistant cells, the ability of MITF to repress AP1‐regulated genes provides an insight into how MITF establishes and maintains a pro‐proliferative phenotype. Moreover, although β‐catenin has been linked to immune exclusion, many Hallmark β‐catenin signaling genes are associated with immune infiltration. Instead, low MITF together with Notch signaling is linked to immune infiltration in both mouse and human melanoma tumors. [ABSTRACT FROM AUTHOR]

Polarization and extremism are often viewed as the product of psychological biases or social influences, yet they still occur in the absence of any bias or irrational thinking. We show that individual decision-makers implementing optimal dynamic decision strategies will become polarized, forming extreme views relative to the true information in their environment by virtue of how they sample new information. Extreme evidence enables decision makers to stop considering new information, whereas weak or moderate evidence is unlikely to trigger a decision and is thus under-sampled. We show that this information polarization effect arises empirically across choice domains including politically-charged, affect-rich and affect-poor, and simple perceptual decisions. However, this effect can be disincentivized by asking participants to make a judgment about the difference between two options (estimation) rather than deciding. We experimentally test this intervention by manipulating participants’ inference goals (decision vs inference) in an information sampling task. We show that participants in the estimation condition collect more information, hold less extreme views, and are less polarized than those in the decision condition. Estimation goals therefore offer a theoretically-motivated intervention that could be used to alleviate polarization and extremism in situations where people traditionally intend to decide. [ABSTRACT FROM AUTHOR]

Because available depigmenting agents exhibit short efficacy and serious side effects, sericin, a waste protein from the silk industry, was hydrolyzed using Alcalase® to evaluate its anti-melanogenic activity in human melanin-producing cells. Sericin hydrolysates consisted of sericin-related peptides in differing amounts and smaller sizes compared with unhydrolyzed sericin, as respectively demonstrated by peptidomic and SDS-PAGE analysis. The lower half-maximum inhibitory concentration (9.05 ± 0.66 mg/mL) compared with unhydrolyzed sericin indicated a potent effect of sericin hydrolysates on the diminution of melanin content in human melanoma MNT1 cells. Not only inhibiting enzymatic activity but also a downregulated expression level of tyrosinase was evident in MNT1 cells incubated with 20 mg/mL sericin hydrolysates. Quantitative RT-PCR revealed the decreased mRNA level of microphthalmia-associated transcription factor (MITF), a tyrosinase transcription factor, which correlated with the reduction of pCREB/CREB, an upstream cascade, as assessed by Western blot analysis in MNT1 cells cultured with 20 mg/mL sericin hydrolysates for 12 h. Interestingly, treatment with sericin hydrolysates for 6–24 h also upregulated pERK, a molecule that triggers MITF degradation, in human melanin-producing cells. These results warrant the recycling of wastewater from the silk industry for further development as a safe and effective treatment of hyperpigmentation disorders. [ABSTRACT FROM AUTHOR]

The causal agent of the barley net blotch disease, Pyrenophora teres, is known for its high level of diversity due to sexual reproduction. Different pathotypes, defined by a virulence combination, even within the same fields are frequently found and virulence between locations can vary considerably. Evaluation of virulence patterns of a pathogen population is essential for breeding resistant cultivars suitable for specific locations. To identify virulence patterns in Icelandic Pyrenophora teres f. teres (Ptt) isolates, twenty single spore isolates of Ptt were collected from seven locations in Iceland and analysed with AFLP markers. Principle Coordinate Analysis (PCoA) revealed Icelandic Ptt isolates clustering away from reference isolates from Austria, Finland, Sweden, Switzerland, UK, and USA. Hierarchical clustering grouped the Icelandic isolates into three distinct groups. Furthermore, the virulence of these twenty isolates was tested on 16 barley differential lines and revealed high variation in their virulence. Twenty-one barley cultivars commonly used in Iceland showed high susceptibility towards inoculation with Icelandic Ptt isolates. [ABSTRACT FROM AUTHOR]

Several signaling pathways have been identified as important for developmental processes. One of such important cascades is the Wnt/β‐catenin signaling pathway, which can regulate various physiological processes such as embryonic development, tissue homeostasis, and tissue regeneration; while its dysregulation is implicated in several pathological conditions especially cancers. Interestingly, deregulation of the Wnt/β‐catenin pathway has been reported to be closely associated with initiation, progression, metastasis, maintenance of cancer stem cells, and drug resistance in human malignancies. Moreover, several genetic and experimental models support the inhibition of the Wnt/β‐catenin pathway to answer the key issues related to cancer development. The present review focuses on different regulators of Wnt pathway and how distinct mutations, deletion, and amplification in these regulators could possibly play an essential role in the development of several cancers such as colorectal, melanoma, breast, lung, and leukemia. Additionally, we also provide insights on diverse classes of inhibitors of the Wnt/β‐catenin pathway, which are currently in preclinical and clinical trial against different cancers. [ABSTRACT FROM AUTHOR]

Domesticated animals have been widely used for transport labor in many societies throughout the Holocene. Domestic dogs (Canis familiaris) used in transporting goods with packs or simple drag-sleds called travois feature prominently in ethnographic and historic accounts of Native American communities in the Intermountain West and Great Plains. Dogs were used to transport shelter and household belongings, firewood, trade goods, and bison meat by Intermountain and Plains foragers. Forager mobility and investment in technology are strongly correlated with environmental unpredictability. The Field Processing Model reveals that travois transport was tenable for food only when processing costs were relatively low and many trips were necessary. These data indicate that dogs were not adapted for use as draft animals in the daily acquisition of food, but rather to facilitate the transport of shelter, equipment, and food reserves that could be used to offset the risk of resource shortfall. [ABSTRACT FROM AUTHOR]

Cereal production in important growing regions is negatively influenced by climate change. This can be countered by expanding cereal production northwards in Scandinavia and Iceland, where today, barley (Hordeum vulgare L.) is primarily used as feed, as it rarely reaches malting quality. This study explores genetic factors underlying the ability of barley to mature fully in low temperature and long photoperiod. A panel of 84 spring barley lines were grown in controlled environments with different day lengths and temperatures, partially mimicking the target environment. The panel was screened for accumulated heat sum to heading, maturity, and height, all traits of importance for adaptation to the northern periphery. Subgroups with different stability and heat sum requirements were found, and day‐length‐neutral lines were identified. Height was temperature controlled, with lower temperature resulting in taller plants. The results were coupled to a genome‐wide association study (GWAS). Despite the small panel size, the Mat‐a locus was identified to have the strongest association with heat sum to heading; Ppd‐H1, Mat‐a, FT1, and DHAR2 with heat sum to maturity; and GA20ox1 with height. Early maturing lines with height stability have successfully been developed in Iceland, and this study confirms their performance in controlled environments for the first time. It provides insight to the mechanisms behind early maturity that will increase our ability to further adapt barley and other cereals to the northern climate. This will facilitate breeding work toward combining early maturity and height stability with traits such as quality, further enabling the northward expansion of grain production. Core Ideas: Early maturity and height stability are key traits in adaptation of cereals to high latitudes.We investigated effect of day length and temperature on a panel of Nordic spring barley.Temperature had effect on plant height with few lines showing height stability.Heat sum requirement to maturity varied among the panel according to day length.Key MTAs found in a GWAS included GA20ox1, Mat‐a, Ppd‐H1, and FT1. [ABSTRACT FROM AUTHOR]

Over the past years, Human Amnion Epithelial Cells (hAECs), a placental stem cell, are gaining higher attention from the scientific community as they showed several advantages over other types of stem cells, including availability, easy accessibility, reduced rejection rate, non-tumorigenicity, and minimal legal constraint. Recently, natural compounds are used to stimulate stem cell differentiation and proliferation and to enhance their disease-treating potential. A polyphenolic compound 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) has been previously reported to induce human neural stem cell differentiation and may affect melanocyte stem cell differentiation as well. In this study, TCQA was tested on 3D cultured hAECs after seven days of treatment, and then, microarray gene expression profiling was conducted of TCQA-treated and untreated control cells on day 0 and day 7. Analyses revealed that TCQA treatment significantly enriched pigment and neural cells sets; besides, genes linked with neurogenesis, oxidation–reduction process, epidermal development, and metabolism were positively regulated. Interestingly, TCQA stimulated cell cycle arrest-related pathways and differentiation signaling. On the other hand, TCQA decreased interleukins and cytokines expression and this due to its anti-inflammatory properties as a polyphenolic compound. Results were validated to highlight the main activities of TCQA on hAECs, including differentiation, cell cycle arrest, and anti-inflammatory. This study highlights the important role of hAECs in regenerative medicine and the use of natural compounds to regulate their fate. 4ntr2z8GsC-Lz3nsa9SfYx Video abstract [ABSTRACT FROM AUTHOR]

Melanin, a pigment synthesized by melanocytes in the skin, resists the damage caused by ultraviolet rays to cells. Citric acid, a well-known food additive, is commonly used as an antioxidant and is an important part of the tricarboxylic acid (TCA) cycle for energy production during cellular metabolism. Here, we aimed to investigate whether the addition of excess citric acid regulates melanin synthesis, and to delineate the underlying mechanism. First, we observed that citric acid exerts opposite redox effects on mouse and human cells. Interestingly, treatment with excess citric acid increased the melanin content in mouse cells but decreased it in human cells. Furthermore, the expression of factors important for melanin synthesis, such as microphthalmia-associated transcription factor (MITF), was also regulated by citric acid treatment—it was promoted in mouse cells and suppressed in human cells. Citric acid also impacted the upstream regulators of MITF, glycogen synthase kinase 3β (GSK3β), and β-catenin. Second, we determined the importance of GSK3β in the citric acid-mediated regulation of melanin synthesis, using a GSK3β inhibitor (BIO). To the best of our knowledge, this is the first study to show that citric acid regulates melanin synthesis via the GSK3β/β-catenin signaling pathway, and that equal amounts of exogenous citric acid exert opposing effects on mouse and human cells. [ABSTRACT FROM AUTHOR]

The clinical benefit of immune checkpoint inhibitory therapy (ICT) in advanced melanomas is limited by primary and acquired resistance. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. As such, a paradigm shift in melanoma treatment, to surmount the therapeutic impasses linked to the resistance, is an important ongoing challenge. This review outlines the multifaceted interplay between microphthalmia-associated transcription factor (MITF), a major determinant of the biology of melanoma cells, and the immune system. In melanomas, MITF functions downstream oncogenic pathways and microenvironment stimuli that restrain the immune responses. We highlight how MITF, by controlling differentiation and genome integrity, may regulate melanoma-specific antigen expression by interfering with the endolysosomal pathway, KARS1, and antigen processing and presentation. MITF also modulates the expression of coinhibitory receptors, i.e., PD-L1 and HVEM, and the production of an inflammatory secretome, which directly affects the infiltration and/or activation of the immune cells. Furthermore, MITF is also a key determinant of melanoma cell plasticity and tumor heterogeneity, which are undoubtedly one of the major hurdles for an effective immunotherapy. Finally, we briefly discuss the role of MITF in kidney cancer, where it also plays a key role, and in immune cells, establishing MITF as a central mediator in the regulation of immune responses in melanoma and other cancers. We propose that a better understanding of MITF and immune system intersections could help in the tailoring of current ICT in melanomas and pave the way for clinical benefits and long-lasting responses. [ABSTRACT FROM AUTHOR]

Retinal development and maturation are orchestrated by a series of interacting signalling networks that drive the morphogenetic transformation of the anterior developing brain. Studies in model organisms continue to elucidate these complex series of events. However, the human retina shows many differences from that of other organisms and the investigation of human eye development nowbenefits from stem cell-derived organoids. Retinal differentiation methods have progressed from simple 2D adherent cultures to self-organising micro-physiological systems. As models of development, these have collectively offered new insights into the previously unexplored early development of the human retina and informed our knowledge of the key cell fate decisions that govern the specification of light-sensitive photoreceptors. Although the developmental trajectories of other retinal cell types remain more elusive, the collation of omics datasets, combined with advanced culture methodology, will enable modelling of the intricate process of human retinogenesis and retinal disease in vitro. [ABSTRACT FROM AUTHOR]

Defining markers of different phenotypic states in melanoma is important for understanding disease progression, determining the response to therapy, and defining the molecular mechanisms underpinning phenotype‐switching driven by the changing intratumor microenvironment. The ABCB5 transporter is implicated in drug‐resistance and has been identified as a marker of melanoma‐initiating cells. Indeed ongoing studies are using ABCB5 to define stem cell populations. However, we show here that the ABCB5 is a direct target for the microphthalmia‐associated transcription factor MITF and its expression can be induced by β‐catenin, a key activator and co‐factor for MITF. Consequently, ABCB5 mRNA expression is primarily associated with melanoma cells exhibiting differentiation markers. The results suggest first that ABCB5 is unlikely to represent a marker of de‐differentiated melanoma stem cells, and second that ABCB5 may contribute to the non‐genetic drug‐resistance associated with highly differentiated melanoma cells. To reconcile the apparently conflicting observations in the field, we propose a model in which ABCB5 may mark a slow‐cycling differentiated population of melanoma cells. [ABSTRACT FROM AUTHOR]

There are currently eight native horse populations in Japan, namely, Hokkaido, Kiso, Noma, Taishu, Misaki, Tokara, Miyako, and Yonaguni horses. Since locomotion traits, including gaitedness, are important for riding and packing horses, the genetic properties associated with these traits could be informative for understanding the characteristics and history of these horses. In this study, we investigated the distribution of the mutant allele of DMRT3 gene (DMRT3:p.Ser301Ter) associated with ambling gaits in the Japanese native horse. We also examined haplotypes of SNPs in the 83-kb region including DMRT3 gene by genotyping four SNPs in this region. The results revealed the presence of DMRT3:p.Ser301Ter in the Hokkaido and Yonaguni populations at allele frequencies of 0.18 and 0.02, respectively, and the observed haplotype associated with DMRT3:p.Ser301Ter was estimated as the most common haplotype in the horses in the world. Since DMRT3:p.Ser301Ter has been hypothesized to spread across Eurasian continent from Medieval England after 850 to 900 CE, our findings of the presence of DMRT3:p.Ser301Ter with the common haplotype in the Japanese native horses will provide a new insight into the history of the Japanese native horse, such as considerable level of gene flow from Eurasian continent after 850 to 900 CE. [ABSTRACT FROM AUTHOR]

Recently, it has been described that programmed cell death protein 1 (PD-1) overexpressing melanoma cells are highly aggressive. However, until now it has not been defined which factors lead to the generation of PD-1 overexpressing subpopulations. Here, we present that melanoma-derived exosomes, conveying oncogenic molecular reprogramming, induce the formation of a melanoma-like, PD-1 overexpressing cell population (mMSCPD-1+) from naïve mesenchymal stem cells (MSCs). Exosomes and mMSCPD-1+ cells induce tumor progression and expression of oncogenic factors in vivo. Finally, we revealed a characteristic, tumorigenic signaling network combining the upregulated molecules (e.g., PD-1, MET, RAF1, BCL2, MTOR) and their upstream exosomal regulating proteins and miRNAs. Our study highlights the complexity of exosomal communication during tumor progression and contributes to the detailed understanding of metastatic processes. [ABSTRACT FROM AUTHOR]

β-Catenin is essential for embryonic development and required for cell renewal/regeneration in adult life. Cellular β-catenin exists in three different pools: membranous, cytoplasmic and nuclear. In this review, we focus on functions of the nuclear pool in relation to tumorigenesis. In the nucleus, β-catenin functions as both activator and repressor of transcription in a context-dependent manner. It promotes cell proliferation and supports tumour growth by enhancing angiogenesis. β-Catenin-mediated signalling regulates cancer cell metabolism and is associated with tumour-initiating cells in multiple malignancies. In addition, it functions as both pro- and anti-apoptotic factor besides acting to inhibit recruitment of inflammatory anti-tumour T-cells. Thus, β-catenin appears to possess a multifaceted nuclear function that may significantly impact tumour initiation and progression. [ABSTRACT FROM AUTHOR]

The growing interest in skin lightening has recently renewed attention on the esthetic applications of Chinese herbal medicine. Although Scutellaria baicalensis Georgi is used for antipyretic and antiinflammatory purposes, its whitening effect remains unclear. This study reports three major findings: (1) S. baicalensis has a potent inhibitory effect on melanogenesis; (2) wogonin and its glycoside are the active components of S. baicalensis; and (3) O-methylated flavones from S. baicalensis, such as wogonin, inhibit intracellular melanosome transport. Using a melanin quantification assay, we showed that S. baicalensis potently inhibits melanogenesis in B16F10 cells. Componential analyses revealed that the main components of S. baicalensis are baicalin, wogonoside, baicalein, wogonin, and oroxylin A. Among these five flavones, wogonin and wogonoside consistently inhibited melanogenesis in both B16F10 melanoma cells and primary melanocytes. Wogonin exhibited the strongest inhibition of melanin production and markedly lightened the color of skin equivalents. We identified microphthalmia-associated transcription factor and tyrosinase-related proteins as potential targets of wogonin- and wogonoside-induced melanogenesis suppression. In culture, we found that the melanosomes in wogonin-treated B16F10 cells were localized to the perinuclear region. Immunoblotting analyses revealed that wogonin significantly reduced in melanophilin protein, which is required for actin-based melanosome transport. Other actin-based melanosome transport-related molecules, i.e., Rab27A and myosin Va, were not affected by wogonin. Cotreatment with MG132 blocked the wogonin-induced decrease in melanophilin, suggesting that wogonin promotes the proteolytic degradation of melanophilin via the calpain/proteasomal pathway. We determined that the structural specificities of the mono-O-methyl group in the flavone A-ring and the aglycone form were responsible for reducing melanosome transport. Furthermore, wogonin and two wogonin analogs, mono-O-methyl flavones, strongly suppressed melanosome transport. Our findings suggest the applicability of S. baicalensis in the esthetic field. Thus, we propose a novel pharmacologic approach for the treatment of hyperpigmentation. [ABSTRACT FROM AUTHOR]

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Microphthalmia-associated transcription factor (Mitf) is a key regulator for differentiation of melanoblasts, precursors to melanocytes. The mouse homozygous for the black-eyed white (Mitfmi-bw) allele is characterized by the white-coat color and deafness with black eyes due to the lack of melanocytes. The Mitfmi-bw allele carries LINE-1, a retrotransposable element, which results in the Mitf deficiency. Here, we have established the black spotting mouse that was spontaneously arisen from the homozygous Mitfmi-bw mouse lacking melanocytes. The black spotting mouse shows multiple black patches on the white coat, with age-related graying. Importantly, each black patch also contains hair follicles lacking melanocytes, whereas the white-coat area completely lacks melanocytes. RT-PCR analyses of the pigmented patches confirmed that the LINE-1 insertion is retained in the Mitf gene of the black spotting mouse, thereby excluding the possibility of the somatic reversion of the Mitfmi-bw allele. The immunohistochemical analysis revealed that the staining intensity for beta-catenin was noticeably lower in hair follicles lacking melanocytes of the homozygous Mitfmi-bw mouse and the black spotting mouse, compared to the control mouse. In contrast, the staining intensity for beta-catenin and cyclin D1 was higher in keratinocytes of the black spotting mouse, compared to keratinocytes of the control mouse and the Mitfmi-bw mouse. Moreover, the keratinocyte layer appears thicker in the Mitfmi-bw mouse, with the overexpression of Ki-67, a marker for cell proliferation. We also show that the presumptive black spots are formed by embryonic day 15.5. Thus, the black spotting mouse provides the unique model to explore the molecular basis for the survival and death of developing melanoblasts and melanocyte stem cells in the epidermis. These results indicate that follicular melanocytes are responsible for maintaining the epidermal homeostasis; namely, the present study has provided evidence for the link between melanocyte development and the epidermal microenvironment. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) play important roles in many biological processes by regulating gene expression at the post-transcriptional level. However, the mechanism by which specific mi RNAs may regulate plumage pigmentation has remained largely elusive. In this study, we sequenced mi RNAs using Solexa sequencing and then performed a detailed analysis of their expression profiles between the black and white feather bulbs of ducks from Cui Hei, Kaiya, Liancheng pure breeds and a Kaiya- Liancheng F2 population. mirdeep2 software identified 121 conserved and eight novel mi RNAs. Five differentially expressed mi RNAs between the two tissues types were also identified by degseq software. Notably, mi R-204 was predominantly expressed in black feather bulbs. To further validate the sequencing data, we applied stem-loop quantitative PCR of ten known mi RNAs based on the identified sequences. Furthermore, in exploring the temporal expression pattern of mi R-204, we performed profiling in nine duck tissues. The targets of these mi RNAs were predicted using a PITA algorithm and were later grouped based on Gene Ontology and KEGG pathway analysis using the DAVID website. The melanogenesis pathway was among the identified signalling pathways, implying key roles of these mi RNAs in plumage pigmentation. Expression analysis of the target genes in the melanogenesis pathways was also performed. This study provides the foundation for subsequent studies on the prospective practical role for such mi RNAs in post-transcriptional gene regulation linked to plumage pigmentation. [ABSTRACT FROM AUTHOR]

Malignant melanoma is a neoplasm of melanocytes, and the microphthalmia-associated transcription factor ( MITF) is essential for the existence of melanocytes. MITF's relevance for this cell lineage is maintained in melanoma, where it is an important regulator of survival and balances melanoma cell proliferation with terminal differentiation (pigmentation). The MITF gene is amplified in ~20% of melanomas and MITF mutation can predispose to melanoma development. Furthermore, the regulation of MITF expression and function is strongly linked to the BRAF/ MEK/ ERK/ MAP-kinase ( MAPK) pathway, which is deregulated in >90% of melanomas and central target of current therapies. MITF expression in melanoma is heterogeneous, and recent findings highlight the relevance of this heterogeneity for the response of melanoma to MAPK pathway targeting drugs, as well as for MITF's role in melanoma progression. This review aims to provide an updated overview on the regulation of MITF function and plasticity in melanoma with a focus on its link to MAPK signaling. [ABSTRACT FROM AUTHOR]