The skin we live in: pigmentation traits and tanning behaviour in British young adults, an observational and genetically-informed study.

Background: Skin cancer incidence has been increasing worldwide, representing a particularly high burden for populations of European ancestry. Outdoor and indoor tanning using ultraviolet radiation (UVR) devices are major risk factors for skin cancer. While tanning behaviours can be modified by targeted interventions to reduce skin cancer rates, there is insufficient evidence on the motivations for tanning preferences and their relationship with pigmentation phenotypes. The present observational and genetically-informed study investigates motives for tanning and the role that pigmentation phenotypes play on outdoor and indoor tanning behaviour in British young adults. Methods: This study included 3722 participants from the Avon Longitudinal Study of Parents and Children in South West England. Skin, hair and eye colour features, and tanning ability and preferences were collected using a questionnaire applied when participants were ~25 years of age. Genotypes for 41 single nucleotide polymorphisms (SNPs) associated with pigmentation were obtained from a subset of participants who provided a biological sample, and used to estimate the probability of having particular pigmentation traits with the HIrisPlex-S system. Results: Liking to tan and outdoor tanning were strongly influenced by skin, hair and eye pigmentation, and tanning ability. However, the association of these traits with UV indoor tanning was weaker. Conversely, females, participants of lower socioeconomic position, individuals who were unhappy with their pigmentation phenotype during adolescence, and participants who believed that tanning helps prevent sunburn were more likely to have used UVR-based tanning devices. Conclusion: Our results provide evidence to support the implementation of skin cancer preventative interventions that consider individual biological characteristics and motives for undergoing outdoor and indoor tanning.

Identifying the genetic and non-genetic factors associated with accelerated eye aging by using deep learning to predict age from fundus and optical coherence tomography images

With age, eyesight declines and the vulnerability to age-related eye diseases such as glaucoma, cataract, macular degeneration and diabetic retinopathy increases. With the aging of the global population, the prevalence of these diseases is projected to increase, leading to reduced quality of life and increased healthcare cost. In the following, we built an eye age predictor by training convolutional neural networks to predict age from 175,000 eye fundus and optical coherence tomography images (R-Squared=83.6+/-0.6%; root mean squared error=3.34+/-0.07 years). We used attention maps to identify the features driving the eye age prediction. We defined accelerated eye aging as the difference between eye age and chronological age and performed a genome wide association study [GWAS] on this phenotype. Accelerated eye aging is 28.2+-1.2% GWAS-heritable, and is associated with 255 single nucleotide polymorphisms in 122 genes (e.g HERC2, associated with eye pigmentation). Similarly, we identified biomarkers (e.g blood pressure), clinical phenotypes (e.g chest pain), diseases (e.g cataract), environmental variables (e.g sleep deprivation) and socioeconomic variables (e.g income) associated with our newly defined phenotype. Our predictor could be used to detect premature eye aging in patients, and to evaluate the effect of emerging rejuvenation therapies on eye health.

Ocular pigmentation in humans, great apes, and gibbons is not suggestive of communicative functions

Pigmentation patterns of the visible part of the eyeball, encompassing the iris and portions of the sclera, have been discussed to be linked to social cognition in primates. The cooperative eye hypothesis suggests the white sclera of humans to be a derived adaptive trait that enhances eye-mediated communication. Here, we provide a comparative analysis of ocular pigmentation patterns in 15 species of hominoids (humans, great apes & gibbons) that show marked differences in social cognition and quantify scleral exposure at the genus level. Our data reveals a continuum of eye pigmentation traits in hominoids which does not align with the complexity of gaze-mediated communication in the studied taxa. Gibbons display darker eyes than great apes and expose less sclera. Iridoscleral contrasts in orangutans and gorillas approach the human condition but differ between congeneric species. Contrary to recent discussions, we found chimpanzee eyes to exhibit a cryptic coloration scheme that resembles gibbons more than other apes. We reevaluate the evidence for links between social cognition and eye pigmentation in primates, concluding that the cooperative eye hypothesis cannot explain the patterns observed. Differences in scleral pigmentation between great apes and humans are gradual and might have arisen via genetic drift and sexual selection.

Ocular pigmentation in humans, great apes, and gibbons is not suggestive of communicative functions - having an eye on the ‘cooperative eye hypothesis’

Pigmentation patterns of the visible part of the eyeball, encompassing the iris and portions of the sclera, have been discussed to be linked to social cognition in primates. In the context of the cooperative eye hypothesis, the white sclera of humans has been viewed as a derived adaptive trait, enhancing communication via glance cueing. Here, we provide a comparative analysis of ocular pigmentation patterns in 15 species of hominoids (humans, great apes & gibbons) representing all extant ape genera, based on photographs and literature data. Additionally, we quantify hominoid scleral exposure on the genus level during different glancing situations. Our data reveals a continuum of eye pigmentation traits among the studied taxa. Gibbons display darker, more uniformly colored eyes than great apes and expose less sclera, particularly during averted glancing. Iridoscleral contrasts in orangutans and gorillas approach the human condition but differ between congeneric species. Contrary to recent discussions, we found chimpanzee eyes to exhibit a cryptic coloration scheme that resembles gibbons more than other great apes and that does not enhance glance cueing or gaze following. We critically evaluate the evidence for links between social cognition and eye pigmentation in primates, concluding that the cooperative eye hypothesis cannot convincingly explain the patterns observed. Although the human eye exhibits unique traits that are likely linked to social communication, high iridoscleral contrast is not one of them. Differences in scleral pigmentation between great apes and humans are gradual and might have arisen via genetic drift and sexual selection.

Teratogenic and developmental toxic effects of etridiazole on zebrafish (Danio rerio) embryos

Etridiazole (EDZ), a thiadiazole-containing toxic chemical, is widely used as a fungicide. Regular usage of EDZ may reach and contaminate water bodies, but its adverse effects on aquatic vertebrates have not been well studied. Therefore, the present study aimed to evaluate the harmful effects of EDZ using zebrafish (ZF) (Danio rerio) embryos. ZF embryos were treated with 3.75, 7.5, 15, 30, and 60 mg/L of EDZ. Subsequently, mortality and developmental toxicities were quantified at 24, 48, 72, and 96 h post fertilization (hpf). The results showed that embryo mortality was concentration- and time-dependent. The median lethal concentration (LC50) of EDZ at 96-h was 25.58 ± 1.49 mg/L. Besides, EDZ induced a series of morphological deformities, including abnormal somite formation, abnormal eye pigmentation, abnormal tail morphology, tail kinks, skeletal malformations (lordosis, kyphosis, and scoliosis), and yolk sac edema in a concentration-dependent manner. Among the deformities, the most significant were reduced heartbeat and increased incidence of pericardial edema. The median effective concentration (EC50) of EDZ at 96-h was 17.93 ± 2.22 mg/L and the 96-h teratogenic index (TI) value was 1.52. Taken together, these results indicate that EDZ is a teratogen, and primarily affects the cardiovascular system of ZF.

The Almond plumage color pattern is associated with eye pigmentation defects in the domestic pigeon (Columba livia)

Changes in epidermal pigmentation are associated with eye defects in humans and other vertebrates. In the rock pigeon (Columba livia), the sex-linked Almond color pattern is characterized by hypopigmentation of epidermal structures. The trait is controlled by the classical Stipper (St) locus, and homozygous (ZStZSt) Almond males often have severe eye defects. Heterozygous (ZStZ+) and hemizygous (ZStW) pigeons do not typically have obvious eye defects, suggesting that higher dosage of the mutant allele is deleterious. Because Almond pigeons have pronounced hypopigmentation in epidermal structures, we hypothesized that they might also have reduced eye pigmentation. Here, we examined pigmentation in the iris, ciliary body, anterior retinal pigmented epithelium (RPE), and posterior RPE in pigeons with and without Almond alleles. We found that pigmentation of anterior segment structures was reduced in birds with at least one Almond allele. However, posterior eye pigmentation was substantially reduced only in homozygous Almond birds. We postulate that the gradient of effects on eye pigmentation is due to the different embryological origins of anterior and posterior eye pigment-producing cells.

Ommochrome pathway genes kynurenine 3-hydroxylase and cardinal participate in eye pigmentation in Plutella xylostella

Background Eye pigmentation genes have been utilized as visible markers for constructing genetic control prototypes in several insect vectors of human disease. Here, orthologs of two ommochrome pathway genes, kynurenine 3-hydroxylase (kmo) and cardinal, were investigated in Plutella xylostella, a globally distributed, economically important pest of Brassica crops. Results Both somatic mosaic and germline mutations were efficiently created using the CRISPR/Cas9 system, and null mutant strains of Pxkmo and Pxcardinal were obtained. A frame-shift mutation in Pxkmo caused yellow compound eyes at adult stage while an in-frame mutation lacking two amino acids resulted in a hypomorphic red eye phenotypes. In contrast, Pxcardinal-deficient moths with a frame-shift mutation exhibited yellow eye pigmentation in newly emerged adults which turned to red as the adults aged. Additionally, differences were observed in the coloration of larval ocelli, brains and testes in Pxkmo and Pxcardinal yellow-eye mutant lines. Conclusions Our work identifies the important roles of Pxkmo and Pxcardinal in P. xylostella eye pigmentation and provides tools for future genetic manipulation of this important crop pest.

Melanin and Melanin-Like Hybrid Materials in Regenerative Medicine

Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed.