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Aims The Gα subunit is a major component of heterotrimeric G proteins, which play a crucial role in the development and pathogenicity of several model fungi. However, its detailed function in the causal agent of pear black spot (Alternaria alternata) is unclear. Our aim was to understand the characteristics and functions of AaGA1 in A. alternata. Methods and results AaGA1 was cloned from A. alternata in this study, which encodes 353 amino acids and has a "G-alpha" domain. Mutant ΔAaGA1 resulted in reduced vegetative growth, conidiation, and spore germination. Especially, mutant ΔAaGA1 produced only fewer conidia on the V8A medium, and spore formation-related genes AbaA, BrlA , and WetA were significantly downregulated. More tolerance against cell wall-inhibiting agents was observed after the deletion of AaGA1. Moreover, AaGA1 deletion led to a significant reduction in melanin and toxin production. Interestingly, deletion of AaGA1 resulted in defective appressorium-like formations, complete loss of the ability to penetrate cellophane, and decreased infection on non-wound inoculated tobacco leaves. Cell wall-degrading enzyme-related genes PME, CL, Cut2 , and LC were significantly downregulated in mutant ΔAaGA1 mutant, significantly reducing virulence on wound-inoculated pear fruits. Conclusions The G protein alpha subunit AaGA1 is indispensable for fungal development, appressorium-like formations, and pathogenicity in A. alternata. [ABSTRACT FROM AUTHOR]

Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen. [ABSTRACT FROM AUTHOR]

How and why certain groups become speciose is a key question in evolutionary biology. Novel traits that enable diversification by opening new ecological niches are likely important mechanisms. However, ornamental traits can also promote diversification by opening up novel sensory niches and thereby creating novel inter-specific interactions. More specifically, ornamental colors may enable more precise and/or easier species recognition and may act as key innovations by increasing the number of species-specific patterns and promoting diversification. While the influence of coloration on diversification is well-studied, the influence of the mechanisms that produce those colors (e.g. pigmentary, nanostructural) is less so, even though the ontogeny and evolution of these mechanisms differ. We estimated a new phylogenetic tree for 121 sunbird species and combined color data of 106 species with a range of phylogenetic tools to test the hypothesis that the evolution of novel color mechanisms increases diversification in sunbirds, one of the most colorful bird clades. Results suggest that: (1) the evolution of novel color mechanisms expands the visual sensory niche, increasing the number of achievable colors, (2) structural coloration diverges more readily across the body than pigment-based coloration, enabling an increase in color complexity, (3) novel color mechanisms might minimize trade-offs between natural and sexual selection such that color can function both as camouflage and conspicuous signal, and (4) despite structural colors being more colorful and mobile, only melanin-based coloration is positively correlated with net diversification. Together, these findings explain why color distances increase with an increasing number of sympatric species, even though packing of color space predicts otherwise. [ABSTRACT FROM AUTHOR]

Bird plumage coloration is a complex and multifactorial process that involves both genetic and environmental factors. Diverse pigment groups contribute to plumage variation in different birds. In parrots, the predominant green color results from the combination of 2 different primary colors: yellow and blue. Psittacofulvin, a pigment uniquely found in parrots, is responsible for the yellow coloration, while blue is suggested to be the result of light scattering by feather nanostructures and melanin granules. So far, genetic control of melanin-mediated blue coloration has been elusive. In this study, we demonstrated that feather from the yellow mutant rose-ringed parakeet displays loss of melanosome granules in spongy layer of feather barb. Using whole genome sequencing, we found that mutation in SLC45A2, an important solute carrier protein in melanin synthetic pathway, is responsible for the sex-linked yellow phenotype in rose-ringed parakeet. Intriguingly, one of the mutations, P53L found in yellow Psittacula krameri is already reported as P58A/S in the human albinism database, known to be associated with human OCA4. We further showed that mutations in SLC45A2 gene affect melanin production also in other members of Psittaculidae family such as alexandrine and plum-headed parakeets. Additionally, we demonstrate that the mutations associated with the sex-linked yellow phenotype, localized within the transmembrane domains of the SLC45A2 protein, affect the protein localization pattern. This is the first evidence of plumage color variation involving SLC45A2 in parrots and confirmation of associated mutations in the transmembrane domains of the protein that affects its localization. [ABSTRACT FROM AUTHOR]

Understanding the evolution of adaptive plasticity is fundamental to our knowledge of how organisms interact with their environments and cope with environmental change. Plasticity in melanin pigmentation is common in response to variable environments, especially thermal environments. Yet, the adaptive significance of melanin plasticity in thermally variable environments is often assumed, but rarely explicitly tested. Furthermore, understanding the role of plasticity when a trait is responsive to multiple environmental stimuli and plays many functional roles remains poorly understood. We test the hypothesis that melanin plasticity is an adaptation for thermally variable environments using Hyles lineata, the white‐lined sphinx moth, which shows plasticity in melanin pigmentation during the larval stage. Melanin pigmentation influences thermal traits in H. lineata, as melanic individuals had higher heating rates and reached higher body temperatures than non‐melanic individuals. Importantly, melanin pigmentation has temperature specific fitness consequences. While melanic individuals had an advantage in cold temperatures, neither phenotype had a clear fitness advantage at warm temperatures. Thus, the costs associated with melanin production may be unrelated to thermal context. Our results highlight the importance of explicitly testing the adaptive role of plasticity and considering all the factors that influence costs and benefits of plastic phenotypes across environments. [ABSTRACT FROM AUTHOR]

Melanosis, the aberrant deposition of melanin pigment in the absence of melanocytes, is very rare in the genitourinary tract. We report a case of a 74-year-old male with symptomatic benign prostatic hyperplasia. Diagnostic cystourethroscopy demonstrated bladder mucosa remarkable for numerous flat, velvety, and brown–black lesions. The patient underwent cystolitholapaxy, transurethral resection of the prostate, and bladder biopsy. Microscopic examination of the bladder biopsy demonstrated urothelium with granular, black pigmentation within the mucosa and histiocytes in the lamina propria; a Fontana Masson stain was positive for melanin. Microscopic examination of the transurethral resection of the prostate demonstrated nodular hyperplasia with focal, black pigmentation of the stroma. The rarity of bladder and prostate melanosis highlights the need for further investigation to elucidate its clinical significance and provide assurance of its benignity. Despite its rarity, melanosis should be kept in the differential diagnosis when melanotic lesions are encountered during cystoscopy. [ABSTRACT FROM AUTHOR]

The sphinx moth genus Hyles comprises 29 described species inhabiting all continents except Antarctica. The genus diverged relatively recently (40-25 MYA), arising in the Americas and rapidly establishing a cosmopolitan distribution. The whitelined sphinx moth, Hyles lineata, represents the oldest extant lineage of this group and is one of the most widespread and abundant sphinx moths in North America. Hyles lineata exhibits the large body size and adept flight control characteristic of the sphinx moth family (Sphingidae), but it is unique in displaying extreme larval color variation and broad host plant use. These traits, in combination with its broad distribution and high relative abundance within its range, have made H. lineata a model organism for studying phenotypic plasticity, plant-herbivore interactions, physiological ecology, and flight control. Despite being one of the most well-studied sphinx moths, little data exist on genetic variation or regulation of gene expression. Here, we report a high-quality genome showing high contiguity (N50 of 14.2 Mb) and completeness (98.2% of Lepidoptera BUSCO genes), an important first characterization to facilitate such studies. We also annotate the core melanin synthesis pathway genes and confirm that they have high sequence conservation with other moths and are most similar to those of another, well-characterized sphinx moth, the tobacco hornworm (Manduca sexta). [ABSTRACT FROM AUTHOR]

The tobacco BY-2 cell line is one of the most utilized plant cell lines. After long-term culture, the cells turn brown to black, but the causal pigment is unknown. We successfully isolated a blackish-brown pigment from BY-2 cells cultured for 3 weeks. Morphological and spectroscopic analyses indicated that the pigment had similar features to a melanin-like substance reported previously. Furthermore, physicochemical analyses revealed that this pigment possessed most of the properties of melanin-like pigments. In addition, the high nitrogen content suggested that it differed from common plant melanins classified as allomelanins, suggesting a novel eumelanin-like pigment: "BY2-melanin". This is the first example showing that eumelanin-like pigments are produced in the cultures of plant cells for which the accumulation of melanin has not been reported. This tobacco BY-2 cell culture technique may represent a customizable and sustainable alternative to conventional melanin production platforms, with significant potential for industrial and pharmacological applications. [ABSTRACT FROM AUTHOR]

Aims To investigate the relationship between microbial community profiles and gill pathology during a production cycle of Atlantic salmon in two commercial hatcheries. Methods and Results Relationships between gill histology, environmental conditions, and microbiome were determined using high-throughput data, including 16S rDNA amplicon sequencing data, histopathology data, and water quality parameters. Hatchery A used riverine water and operated a mixed system of recirculation aquaculture system (RAS) and flowthrough. Hatchery B was used bore water and operated a RAS. Melanin deposits, hyperplastic, and inflammatory lesions were observed histologically in the gills. A higher prevalence of melanin deposits was detected and correlated to a change in beta diversity of bacterial communities in early time points (fingerling and parr stages). High abundance of Sphaerotilus sp. Pseudomonas sp. Nitrospira sp. Exiguobacterium sp. Deinococcus sp. and Comamonas sp. was correlated with a high prevalence of melanin in filaments. Bacterial diversity increased as the fish cohort transitioned from RAS to flowthrough in hatchery A. Conclusions Under commercial conditions, the commensal community of gill bacteria was related to melanin prevalence. [ABSTRACT FROM AUTHOR]

Hermansky--Pudlak syndrome is an autosomal recessive disease characterized by albinism, visual impairment, and blood platelet dysfunction. One of the genes responsible for Hermansky--Pudlak syndrome, hps1, regulates organelle biogenesis and thus plays important roles in melanin production, blood clotting, and the other organelle-related functions in humans and mice. However, the function of hps1 in other species remains poorly understood. In this study, we discovered albino medaka fish during the maintenance of a wild-derived population and identified hps1 as the responsible gene using positional cloning. In addition to the specific absence of melanophore pigmentation, the hps1 mutant showed reduced blood coagulation, suggesting that hps1 is involved in clotting caused by both mammalian platelets and fish thrombocytes. Together, the findings of our study demonstrate that hps1 has an evolutionarily conserved role in melanin production and blood coagulation. In addition, our study presents a useful vertebrate model for understanding the molecular mechanisms of Hermansky-- Pudlak syndrome. [ABSTRACT FROM AUTHOR]

Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes bean anthracnose and it is rated among the top 10 important diseases infecting beans. Currently our knowledge on molecular mechanisms underlying C. lindemuthianum pathogenesis is limited. About five pathogenicity genes have been identified in C. lindemuthianum using Restricted Enzyme Mediated Integration and the transformation using Agroinfection has not been optimized. In this study, a series of experiments were conducted to optimize the key parameters affecting the Agrobacterium tumefaciens‐mediated transformation for C. lindemuthianum. The transformation efficiency increased with increase in spore concentration and co‐cultivation time. However, the optimum conditions that yielded significant number of transformants were 106 ml−1 spore concentration, co‐cultivation time of 72 h, incubation at 25°C and using a cellulose membrane filter for the co‐cultivation. The optimized protocol resulted in establishment of large mutant library (2400). A few mutants were melanin deficient and a few were unable to produce conidia. To determine the altered pathogenicity, two new approaches such as detached leaf and twig techniques proved reliable and require fewer resources to screen the large mutant libraries in a short time. Among the 1200 transformants tested for virulence, 90% transformants were pathogenically similar to wild type (race 2047), 96 and 24 were reduced and impaired, respectively. The altered avirulent transformants can prove vital for understanding the missing link between growth and developmental stages of pathogen with virulence. This platform will help to develop strategies to determine the potential pathogenicity genes and to decipher molecular mechanisms of host–pathogen interactions in more detail. [ABSTRACT FROM AUTHOR]

Background In the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors. Materials and Methods Our case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel). Results Of the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp , CDKN2A , TP53 , and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1 , APC , PRKAR1A , and KIT was identified in the HPMel cohort compared with LPMel. Conclusions In this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression. [ABSTRACT FROM AUTHOR]

Pyomelanin is a brown-black phenolic polymer and results from the oxidation of homogentisic acid (HGA) in the L-tyrosine pathway. As part of the research for natural and active ingredients issued from realistic bioprocesses, this work re-evaluates the HGA pigment and makes an updated inventory of its syntheses, microbial pathways, and properties, with tracks and recent advances for its large-scale production. The mechanism of the HGA polymerization is also well documented. In alkaptonuria, pyomelanin formation leads to connective tissue damage and arthritis, most probably due to the ROS issued from HGA oxidation. While UV radiation on human melanin may generate degradation products, pyomelanin is not photodegradable, is hyperthermostable, and has other properties better than L-Dopa melanin. This review aims to raise awareness about the potential of this pigment for various applications, not only for skin coloring and protection but also for other cells, materials, and as a promising (semi)conductor for bioelectronics and energy. [ABSTRACT FROM AUTHOR]

Pigmentation in insects has been linked to mate selection and predator evasion, thus representing an important aspect for natural selection. Insect body color is classically associated to the activity of tyrosine pathway enzymes, and eye color to pigment synthesis through the tryptophan and guanine pathways, and their transport by ATP-binding cassette proteins. Among the hemiptera, the genetic basis for pigmentation in kissing bugs such as Rhodnius prolixus, that transmit Chagas disease to humans, has not been addressed. Here, we report the functional analysis of R. prolixus eye and cuticle pigmentation genes. Consistent with data for most insect clades, we show that knockdown for yellow results in a yellow cuticle, while scarlet and cinnabar knockdowns display red eyes as well as cuticle phenotypes. In addition, tyrosine pathway aaNATpreto knockdown resulted in a striking dark cuticle that displays no color pattern or UV reflectance. In contrast, knockdown of ebony and tan, that encode N-beta-alanyl dopamine hydroxylase branch tyrosine pathway enzymes, did not generate the expected dark and light brown phenotypes, respectively, as reported for other insects. We hypothesize that R. prolixus, which requires tyrosine pathway enzymes for detoxification from the blood diet, evolved an unusual strategy for cuticle pigmentation based on the preferential use of a color erasing function of the aaNATpreto tyrosine pathway branch. We also show that genes classically involved in the generation and transport of eye pigments regulate red body color in R. prolixus. This is the first systematic approach to identify the genes responsible for the generation of color in a blood-feeding hemiptera, providing potential visible markers for future transgenesis. [ABSTRACT FROM AUTHOR]

Summary: Skin bleaching, also known as skin lightening, is the deliberate lightening of an individual's skin tone without medical supervision. The causes are complex, multifactorial and often intertwined, although the unifying themes centre around a belief that lighter skin denotes an individual of higher status, socioeconomic background or physical beauty, than their darker‐skinned counterpart. Skin lightening is achieved using agents that block the production of melanin and often contain drugs such as hydroquinone, superpotent topical steroids or mercury. These drugs can cause serious local and systemic complication. Skin‐lightening compounds are illegal in most countries throughout the world; however the industry is worth billions of dollars annually, and the agents can be easily obtained by individuals seeking to lighten their skin. Dermatologists are in a unique position to identify those at risk of using skin‐bleaching agents, manage complications and give advice on the physiological variation in pigmentation and how to avoid using skin‐lightening agents to treat dermatological conditions. To manage the belief that lighter skin is better, societal level change is required to ensure that people of all skin tones are represented in the media. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. Summary: There is an increasing recognition of ethnic dermatology to reflect the increase in skin of colour (SOC) populations in the UK. Hyperpigmentary disorder is one of the commonest skin concerns in SOC but there has been limited training available in this field of dermatology. Variations in skin colour are genetically determined by the amount of melanin content, the eumelanin/pheomelanin ratio and the size of melanosomes, but is also influenced by other factors such as hormones and extrinsic factors such as ultraviolet radiation. Hyperpigmentation is a broad term to describe increased pigmentation in the skin, and making a correct diagnosis is an important first step in the successful management of hyperpigmentary disorders. A systematic approach based on the disease pathogenesis (e.g. reactive vs. nonreactive, increased melanin vs. increased number of cells or epidermal vs. dermal pigmentation) aided by a detailed history and clinical examination is the best way to diagnose a hyperpigmentary disorder. Based on its pathogenesis, management can be planned. For epidermal hyperpigmentation caused by increased melanin, topical skin‐lightening agents targeting inhibition of tyrosinase or melanosome transfer and promotion of keratinocyte turnover can be used. Hydroquinone‐containing cream is the gold‐standard treatment for epidermal hyperpigmentation. Alternative treatments include laser toning or chemical peels. However, increased dermal pigmentation is more challenging to target with topical treatments. If hyperpigmentation is due to increased numbers of melanocytes or keratinocytes, high‐fluence laser is the most appropriate treatment method. [ABSTRACT FROM AUTHOR]

For ectothermic insects, their colour and size are important determinants of body temperature: larger bodies require more heat to reach a certain temperature, and dark colours absorb heat more efficiently. These dark colours are expressed using melanin, which has been intimately linked with the thermoregulatory capabilities of insects. Melanin is also linked with immune defence and is often used as a secondary sexual character in insects. There is a potential trade-off situation between thermoregulatory capabilities, immune defence and secondary sexual characters, all of which use melanin. Some Calopteryx damselflies, such as Calopteryx splendens , have melanin-based wing pigmentation that is sexually selected and drives intra- and interspecific territorial aggression. Our goal was to study experimentally how the wing pigmentation and body size of C. splendens males affect their thermoregulation and, especially, their ability to become active (hereafter, 'activate') after being cooled down. Our results were in line with our hypotheses, showing that individuals with larger wing spots had significantly faster activation times than those with smaller wing spots, and that individuals with larger body size had significantly slower activation times than those with smaller body size. Both variables showed an interaction and are therefore important in damselfly warm-up and activation. We discuss the role of wing pigmentation and thermoregulation in the behavioural patterns observed in Calopteryx species. [ABSTRACT FROM AUTHOR]

In Parkinson's disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson's disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson's disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson's disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson's disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content. [ABSTRACT FROM AUTHOR]

Human skin and hair pigmentation play important roles in social behavior but also in photoprotection from the harmful effects of ultraviolet light. The main pigments in mammalian skin, the melanins, are synthesized within specialized organelles called melanosomes in melanocytes, which sit at the basal layer of the epidermis and the hair bulb. The melanins are then transferred from melanocytes to keratinocytes, where they accumulate perinuclearly in membrane-bound organelles as a "cap" above the nucleus. The mechanism of transfer, the nature of the pigmented organelles within keratinocytes, and the mechanism governing their intracellular positioning are all debated and poorly understood, but likely play an important role in the photoprotective properties of melanin in the skin. Here, we detail our current understanding of these processes and present a guideline for future experimentation in this area. [ABSTRACT FROM AUTHOR]

Melanins, the main pigments of the skin and hair in mammals, are synthesized within membrane-bound organelles of melanocytes called melanosomes. Melanosome structure and function are determined by a cohort of resident transmembrane proteins, many of which are expressed only in pigment cells and localize specifically to melanosomes. Defects in the genes that encode melanosome-specific proteins or components of the machinery required for their transport in and out of melanosomes underlie various forms of ocular or oculocutaneous albinism, characterized by hypopigmentation of the hair, skin, and eyes and by visual impairment. We review major components of melanosomes, including the enzymes that catalyze steps in melanin synthesis from tyrosine precursors, solute transporters that allow these enzymes to function, and structural proteins that underlie melanosome shape and melanin deposition. We then review the molecular mechanisms by which these components are biosynthetically delivered to newly forming melanosomes—many of which are shared by other cell types that generate cell type-specific lysosome-related organelles. We also highlight unanswered questions that need to be addressed by future investigation. [ABSTRACT FROM AUTHOR]

Aims: Bacterial melanins are UV‐absorber biopolymers with potential applications in cosmetics and pharmaceutical industries. However, the cost concern of these pigments remains a limiting factor for their commercial production. Hence, the present study was aimed to isolate a bacterium with high yield of melanin by optimization of an inexpensive waste sources. Methods and Results: Pseudomonas koreensis UIS 19 (accession number: MG548583), which displayed significant bioproduction of melanin along with high tyrosinase enzyme activity was isolated from soil and introduced as a melanin‐producing bacterium. Scanning and transmission electron microscope studies revealed that melanin pigments accumulated inside as well as the extracellular space of the cells. Melanin was extracted from the isolated strain and its detection was investigated using NMR and HPLC analyses. Here, we showed that the DPPH radical scavenging activity of 20 mg ml−1 melanin extracted from the isolated strain was >92·42% and its sun protection factor (SPF) value was 61·55. Melanin production by the UIS 19 in molasses medium showed sugar consumption (32 g l−1) for biomass production (5·4 g dry wt) and melanin yield of 0·44 g dry wt g−1 biomass from l‐tyrosine. Some critical intermediated such tyramine, l‐dopa, dopamine and dopaquinone related to the melanin Raper Mason pathway were detected by H‐NMR. Furthermore, to achieve high bioproduction of melanin in inexpensive media include 5% molasses 5 Brix as an industrial waste, nutritional and environmental parameters were screened using response surface methodology by Box‐Behnken design in which, maximum melanin yield of 5·5 g dry wt l−1 was obtained. Conclusions: The bioproduction of melanin as valuable compound from P. koreensis was performed using an optimized waste medium. The purified melanin showed high radical scavenging activity and high SPF value. Significance and Impact of the Study: Pseudomonaskoreensis UIS 19 is a promising candidate for industrial production of melanin as cosmetic skin‐care product. [ABSTRACT FROM AUTHOR]

A recent study published in the British Journal of Dermatology has identified loss-of-function variants in the GLMN gene as a cause of generalized skin hyperpigmentation. The study used whole-exome and Sanger sequencing to identify these genetic variants in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. The discovery of these variants expands our understanding of the genetic basis of skin hyperpigmentation disorders and opens up new possibilities for targeted therapies. However, the study also highlights the complexity of genetic interactions and suggests that additional factors may influence the manifestation of the disease. Further research is needed to elucidate these factors and their contributions to the disease. [Extracted from the article]

Introduction and aims Melanin is a photoprotective pigment that effectively absorbs and scatters solar ultraviolet radiation (UVR) affording protection against nuclear DNA photodamage. In lightly pigmented skin, UVR-mediated damage of cellular DNA is not limited to nuclear DNA; mitochondrial DNA (mtDNA) is also susceptible to UVR-induced damage leading to an increased frequency of deletions and mutations. However, the protective role of melanin against UVR-induced mtDNA damage is unknown. Therefore, we sought to determine whether melanin affords protection against UVR-induced mtDNA damage. Methods Using Genome Analysis Toolkit best practices, mtDNA was extracted from photoexposed forearm and photoprotected buttock of Black African (n = 3) and White Northern European (n = 3) volunteers and sequenced to identify somatic mutations. Results Comparison of photoexposed forearm with photoprotected buttock identified a total of 21 somatic mutations, including single-nucleotide transitions, deletions and additions. Of these, three somatic mutations were observed in Black skin, whereas 18 were identified in White skin (P < 0.01). Analysis of single-nucleotide transitions revealed a total of 13 variations and of these, two were identified in Black skin and 11 in White skin. Interestingly, of the somatic mutations observed in White skin, there was enrichment of the cytosine to thymine (C>T) transitions in all volunteers. In contrast, photoexposed Black skin had a thymine to guanine transition at position 414 (T414G) identified for two of the three Black volunteers. Conclusions Here we identified that Black skin exhibited fewer mtDNA mutations compared with White skin; enrichment of C>T transitions in White skin is consistent with a previously reported UVR-signature of mtDNA damage, whereas the T414G transition identified in Black photoexposed skin has previously been suggested as a mitochondrial biomarker of photoageing. Our study suggests that melanin confers protection against UVR-mediated mtDNA damage and that the mtDNA damage signature differs between skin types. [ABSTRACT FROM AUTHOR]

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomized crossover design, 19 patients with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7 T imaging of the locus coeruleus using a neuromelanin-sensitive magnetization transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in patients with Parkinson's disease. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Metal mining causes serious ecological disturbance, due partly to heavy metal (HM) pollution that can accumulate at mining sites themselves and be dispersed downstream as runoff. Plumage coloration is important in birds' social and ecological interactions and sensitive to environmental stressors, and several local-scale studies have found decreased carotenoid-based plumage and/or increased melanin-based plumage in wild birds exposed to HM pollution. We investigated regional-scale effects of proximity to mines and their downstream rivers as a proxy of exposure to HM-contaminated mining waste on plumage coloration in Streak-backed Orioles (Icterus pustulatus) in south-central Mexico. We measured the plumage color of museum skins using reflectance spectrometry and digital photography, then used geographic information systems to estimate each specimen's distance from the nearest mining concession and river and determine whether that river's watershed contained mines. Proximity to mines and their downstream rivers was related to ventral (but not dorsal) carotenoid-based coloration; birds collected farther from mines had more vivid yellow-orange breast plumage, and belly plumage was more vivid and redder with increasing distance from rivers with upstream mines. Breast background reflectance unexpectedly decreased with mine distance and was higher among birds whose nearest river had mines upstream. The area (but not reflectance) of melanin-based plumage was also related to mines. The area of dark back streaks decreased with mine distance, while the bib patch was smaller among birds presumably more exposed to mining waste. While some of these results are consistent with predicted effects of HM pollution on plumage, most were not straightforward, and effects differed among plumage patches and variables. Further investigation is needed to understand the direct (e.g., toxicity, oxidative stress) and/or indirect (e.g., decreased availability of carotenoid-rich food) mechanisms responsible and their individual-, population-, and community-level implications. [ABSTRACT FROM AUTHOR]

Melanins are pigments used by fungi to withstand various stresses and to strengthen vegetative and reproductive structures. In Sordariales fungi, their biosynthesis starts with a condensation step catalyzed by an evolutionary-conserved polyketide synthase. Here we show that complete inactivation of this enzyme in the model ascomycete Podospora anserina through targeted deletion of the PaPks1 gene results in reduced female fertility, in contrast to a previously analyzed nonsense mutation in the same gene that retains full fertility. We also show the utility of PaPks1 mutants for detecting rare genetic events in P. anserina, such as parasexuality and possible fertilization and/or apomixis of nuclei devoid of mating-type gene. [ABSTRACT FROM AUTHOR]

Color and color pattern are critical for animal camouflage, reproduction, and defense. Few studies, however, have attempted to identify candidate genes for color and color pattern in squamate reptiles, a colorful group with over 10,000 species. We used comparative transcriptomic analyses between white, orange, and yellow skin in a color-polymorphic species of anole lizard to 1) identify candidate color and color-pattern genes in squamates and 2) assess if squamates share an underlying genetic basis for color and color pattern variation with other vertebrates. Squamates have three types of chromatophores that determine color pattern: guanine-filled iridophores, carotenoid- or pteridine-filled xanthophores/erythrophores, and melanin-filled melanophores. We identified 13 best candidate squamate color and color-pattern genes shared with other vertebrates: six genes linked to pigment synthesis pathways, and seven genes linked to chromatophore development and maintenance. In comparisons of expression profiles between pigment-rich and white skin, pigment-rich skin upregulated the pteridine pathway as well as xanthophore/erythrophore development and maintenance genes; in comparisons between orange and yellow skin, orange skin upregulated the pteridine and carotenoid pathways as well as melanophore maintenance genes. Our results corroborate the predictions that squamates can produce similar colors using distinct color-reflecting molecules, and that both color and color-pattern genes are likely conserved across vertebrates. Furthermore, this study provides a concise list of candidate genes for future functional verification, representing a first step in determining the genetic basis of color and color pattern in anoles. [ABSTRACT FROM AUTHOR]

Iridescence is widespread in the living world, occurring in organisms as diverse as bacteria, plants, and animals. Yet, compared to pigment-based forms of coloration, we know surprisingly little about the developmental and molecular bases of the structural colors that give rise to iridescence. Birds display a rich diversity of iridescent structural colors that are produced in feathers by the arrangement of melanin-containing organelles called melanosomes into nanoscale configurations, but how these often unusually shaped melanosomes form, or how they are arranged into highly organized nanostructures, remains largely unknown. Here, we use functional genomics to explore the developmental basis of iridescent plumage using superb starlings (Lamprotornis superbus), which produce both iridescent blue and non-iridescent red feathers. Through morphological and chemical analyses, we confirm that hollow, flattened melanosomes in iridescent feathers are eumelanin-based, whereas melanosomes in non-iridescent feathers are solid and amorphous, suggesting that high pheomelanin content underlies red coloration. Intriguingly, the nanoscale arrangement of melanosomes within the barbules was surprisingly similar between feather types. After creating a new genome assembly, we use transcriptomics to show that non-iridescent feather development is associated with genes related to pigmentation, metabolism, and mitochondrial function, suggesting non-iridescent feathers are more energetically expensive to produce than iridescent feathers. However, iridescent feather development is associated with genes related to structural and cellular organization, suggesting that, while nanostructures themselves may passively assemble, barbules and melanosomes may require active organization to give them their shape. Together, our analyses suggest that iridescent feathers form through a combination of passive self-assembly and active processes. [ABSTRACT FROM AUTHOR]

A major goal of evolutionary genetics and evo-devo is to understand how changes in genotype manifest as changes in phenotype. Bumble bees display remarkable color pattern diversity while converging onto numerous regional Müllerian mimicry patterns, thus enabling exploration of the genetic mechanisms underlying convergent phenotypic evolution. In western North America, multiple bumble bee species converge onto local mimicry patterns through parallel shifts of midabdominal segments from red to black. It was previously demonstrated that a Hox gene, Abd-B , is the key regulator of the phenotypic switch in one of these species, Bombus melanopygus , however, the mechanism by which Abd-B regulates color differentiation remains unclear. Using tissue/stage-specific transcriptomic analysis followed by qRT–PCR validation, this study reveals a suite of genes potentially involved downstream of Abd-B during color pattern differentiation. The data support differential genes expression of not only the first switch gene Abd-B , but also an intermediate developmental gene nubbin , and a whole suite of downstream melanin and redox genes that together reinforce the observed eumelanin (black)-pheomelanin (red) ratios. These include potential genes involved in the production of insect pheomelanins, a pigment until recently not thought to occur in insects and thus lacking known regulatory enzymes. The results enhance understanding of pigmentation gene networks involved in bumble bee color pattern development and diversification, while providing insights into how upstream regulators such as Hox genes interact with downstream morphogenic players to facilitate this adaptive phenotypic radiation. [ABSTRACT FROM AUTHOR]

Hagfishes are an ancient group of benthic marine craniates that are found in deep or cold waters around the world. Among the 83 valid species, four are described from the Galapagos Islands: Eptatretus bobwisneri , E. grouseri , E. mccoskeri and Rubicundus lakeside. During a recent expedition to the archipelago, six species of hagfishes were collected, including four undescribed species of the genera Eptatretus (Eptatretus goslinei sp. nov.) and Myxine (Myxine greggi sp. nov. , M. martinii sp. nov. and M. phantasma sp. nov.). In this paper, we provide a review of the eight species of hagfishes from the Galapagos Islands, including new diagnoses and an identification key for all species. Myxine phantasma is remarkable in that it is the only species of Myxine known to completely lack melanin-based pigments. Our species delineations were based on both morphological and molecular analyses. A phylogenetic hypothesis based on molecular data suggests that Galapagos hagfishes arose from multiple independent colonisations of the islands from as many as five different ancestral lineages. The large number of endemic hagfishes in the geologically young Galapagos Islands suggests that there is much global hagfish diversity yet to be discovered. [ABSTRACT FROM AUTHOR]

Cationic biocides are widely utilized for surface disinfection. Photosensitizers such as toluidine blue O (TBO) produce reactive oxygen species following light excitation and are being investigated as novel biocides for similar applications. Aspergillus brasiliensis conidia contain melanin which protects against environmental stressors. The negative charge and antioxidant properties of melanin may confer resistance to photosensitizers and other biocides. In this study, the yeasticidal and fungicidal activity benzalkonium chloride (BZC), sodium dichloroisocyanurate (NaDCC) and TBO with red light were examined using quantitative suspension tests. All three biocides were highly effective against Candida albicans and > 5·0 log10 reductions in viability were attainable within 5 minutes. Wild‐type A. brasiliensis conidia were highly tolerant to treatment and 0·4 log10 reductions in viability were observed within the same time frame when treated with TBO or BZC. NaDCC was markedly more effective. Inhibition of melanin biosynthesis by culturing with 100 μg ml−1 kojic acid resulted in a hypopigmented phenotype with significantly increased sensitivity to all three biocides. These observations indicate that melanin is a significant contributor towards A. brasiliensis tolerance of biocides and photosensitizers and demonstrate that cationic biocides are poorly suited to applications where the control of A. brasiliensis is required. [ABSTRACT FROM AUTHOR]

Senile lentigo or age spots are hyperpigmented macules of skin that commonly develop following long-term exposure to ultraviolet radiation. This condition is caused by accumulation of large numbers of melanosomes (melanin granules) produced by melanocytes within neighboring keratinocytes. However, there is still no consensus regarding the melanosome transfer mechanism in senile lentigo. To date, most pathohistological studies of skin have been two-dimensional and do not provide detailed data on the complex interactions of the melanocyte–keratinocyte network involved in melanosome transfer. We performed a three-dimensional reconstruction of the epidermal microstructure in senile lentigo using three different microscopic modalities to visualize the topological melanocyte–keratinocyte relationship and melanosome distribution. Confocal laser microscopy images showed that melanocyte dendritic processes are more frequently branched and elongated in senile lentigo skin than in normal skin. Serial transmission electron micrographs showed that dendritic processes extend into intercellular spaces between keratinocytes. Focused ion beam-scanning electron micrographs showed that dendritic processes in senile lentigo encircle adjacent keratinocytes and accumulate large numbers of melanosomes. Moreover, melanosomes transferred to keratinocytes are present not only in the supranuclear area but throughout the perinuclear area except on the basal side. The use of these different microscopic methods helped to elucidate the three-dimensional morphology and topology of melanocytes and keratinocytes in senile lentigo. We show that the localization of melanosomes in dendritic processes to the region encircling recipient keratinocytes contributes to efficient melanosome transfer in senile lentigo. [ABSTRACT FROM AUTHOR]

Over the years, several studies have shown that many factors are likely to affect the results of forensic hair analyses and complicate their interpretation. Among these factors, one of the major drawbacks in hair analysis is the affectability of deposited xenobiotics by cosmetic treatments, which could be eventually used to adulterate the sample. It is well known that some cosmetic treatments containing hydrogen peroxide, such as permanent dyeing or bleaching, lead to the formation of 1-H‐pyrrole‐2,3,5‐tricarboxylic acid (PTCA), a melanin degradation product. Considering that PTCA is also an endogenous compound, spontaneously formed by natural oxidation of melanin, its only detection in hair is not enough to confirm a cosmetic oxidative treatment. For this reason, the aim of the present work was to develop and validate a reliable liquid–liquid extraction method in ultra-high-performance liquid chromatographic–tandem mass spectrometry for the determination of endogenous PTCA in hair from a wide multi-ethnic population (African, Arab, Asian-Pacific, Caucasian, Hispanic and Indian). According to previous studies, untreated hair samples showed a PTCA content of 8.54 ± 5.72 ng/mg (mean ± standard deviation [SD]), ranging between 0.44 and 23.7 ng/mg; after in vitro cosmetic bleaching, PTCA increased to 16.8 ± 6.95 ng/mg (range: 4.16–32.3 ng/mg). Comparing baseline PTCA levels of each subgroup with the others, we could not observe any statistically significant difference, except for Caucasians (P  < 0.05), wherein the concentrations were lower. Further studies and a wider sampling are necessary to elucidate the role of PTCA as diagnostic marker of cosmetic hair treatment in forensic field. [ABSTRACT FROM AUTHOR]

Background Eumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative agents of black-grain mycetoma are unknown and unravelling them could identify potential new therapeutic targets. Method Melanin biosynthetic pathways in the causative fungi were identified by the use of specific melanin inhibitors. Results In Trematosphaeria grisea and Falciformispora tompkinsii , 1,8-dihydroxynaphthalene (DHN)-melanin synthesis was inhibited, while DHN-, 3,4-dihydroxyphenylalanine (DOPA)- and pyo-melanin were inhibited in Medicopsis romeroi and Falciformispora senegalensis. Conclusion Our data suggest that Me. romeroi and F. senegalensis synthesise DHN-, DOPA- and pyo-melanin, while T. grisea and F. tompkinsii only synthesise DHN-melanin. [ABSTRACT FROM AUTHOR]

Vitamin D synthesis by exposure of skin to solar ultraviolet radiation (UVR) provides the majority of this hormone that is essential for bone development and maintenance but may be important for many other health outcomes. This process, which is the only well‐established benefit of solar UVR exposure, depends on many factors including genetics, age, health, and behavior. However, the most important factor is the quantity and quality of UVR reaching the skin. Vitamin D synthesis specifically requires ultraviolet B (UVB) radiation that is the minority component (<5%) of solar UVR. This waveband is also the most important for the adverse effects of solar exposure. The most obvious of which is sunburn (erythema), but UVB is also the main cause of DNA damage to the skin that is a prerequisite for most skin cancers. UVB at the Earth's surface depends on many physical and temporal factors such as latitude, altitude, season, and weather. Personal, cultural, and behavioral factors are also important. These include skin melanin, clothing, body surface area exposed, holiday habits, and sunscreen use. There is considerable disagreement in the literature about the role of some of these factors, possibly because some studies have been done by researchers with little understanding of photobiology. It can be argued that vitamin D supplementation obviates the need for solar exposure, but many studies have shown little benefit from this approach for a wide range of health outcomes. There is also increasing evidence that such exposure offers health benefits independently of vitamin D: the most important of which is blood‐pressure reduction. In any case, public health advice must optimize risk versus benefit for solar exposure. It is fortunate that the individual UVB doses necessary for maintaining optimal vitamin D status are lower than those for sunburn, irrespective of skin melanin. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Identification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world's highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai–Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies. [ABSTRACT FROM AUTHOR]

Pear juice concentrate prepared by boiling Japanese pear (Pyrus pyrifolia Nakai cv. Nijisseiki) juice can significantly inhibit the activity of tyrosinase, a key enzyme in melanin synthesis in human skin. Using the ethanol extract of pear juice concentrate, we homogeneously purified an active compound that was identified as 5-hydroxymethyl-2-furaldehyde (5-HMF) through 1H- and 13C-NMR and mass spectroscopy. We observed that 5-HMF inhibited the monophenolase and diphenolase activities of mushroom tyrosinase as a mixed-type inhibitor (Ki values of 3.81 and 3.70 mmol/L, respectively). In B16 mouse melanoma cells, treatment with 170 µmol/L of 5-HMF significantly reduced α-melanocyte-stimulated melanin synthesis by suppressing the cyclic adenosine monophosphate-dependent signaling pathway involved in melanogenesis. The results of our study indicated that 5-HMF can be potentially used as a skin-lightening agent in the cosmetic industry. Abbreviations: AC: adenylate cyclase; CREB: cAMP response element-binding protein; dhFAME: S-(−)-10,11-Dihydroxyfarnesoic acid methyl ester; DMEM: dulbecco′s modified eagle medium; l-DOPA: 3-(3,4-Dihydroxyphenyl)- l-alanine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HEPES: 4-(2-Hydroxyethyl)-1-piperazine ethane sulfonic acid; 5-HMF: 5-Hydroxymethyl-2-furaldehyde; MITF: microphthalmia-associated transcription factor; α-MSH: α-Melanocyte-stimulating hormone; PKA: protein kinase A; PVDF: polyvinylidene difluoride; SDS: sodium dodecyl sulfate; TRP1: tyrosinase-related protein 1; TRP2: tyrosinase-related protein 2 5-Hydroxymethyl-2-furaldehyde can act as a tyrosinase and/or melanogenesis inhibitor, which can be used as a skin-lightening agent in the cosmetic industry. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification. [ABSTRACT FROM AUTHOR]

The pigmentation mutation speck is a commonly used recombination marker characterized by a darkly pigmented region at the wing hinge. Identified in 1910 by Thomas Hunt Morgan, speck was characterized by Sturtevant as the most “workable” mutant in the rightmost region of the second chromosome and eventually localized to 2-107.0 and 60C1-2. Though the first speck mutation was isolated over 110 years ago, speck is still not associated with any gene. Here, as part of an undergraduate-led research effort, we show that speck is encoded by the Arylalkylamine N-acetyltransferase 1 (AANAT1) gene. Both alleles from the Morgan lab contain a retrotransposon in exon 1 of the RB transcript of the AANAT1 gene. We have also identified a new insertion allele and generated multiple deletion alleles in AANAT1 that all give a strong speck phenotype. In addition, expression of AANAT1 RNAi constructs either ubiquitously or in the dorsal portion of the developing wing generates a similar speck phenotype. We find that speck alleles have additional phenotypes, including ectopic pigmentation in the posterior pupal case, leg joints, cuticular sutures and overall body color. We propose that the acetylated dopamine generated by AANAT1 decreases the dopamine pool available for melanin production. When AANAT1 function is decreased, the excess dopamine enters the melanin pathway to generate the speck phenotype. [ABSTRACT FROM AUTHOR]

Melanin metabolism disorders may cause severe impacts on the psychological and social activities of patients. Different from the other two steps of melanin metabolism, namely synthesis and transport, little has been known about the mechanism of melanin degradation. Isoimperatorin (ISO) suppressed the activity of tyrosinase, an essential enzyme in melanin biosynthesis, hence, we investigated the effects and mechanism of ISO in melanin reduction. ISO stimulation significantly reduces the melanin contents and PMEL 17 protein levels; meanwhile, the activity and the protein levels of two critical lysosomal enzymes, Cathepsin B and Cathepsin D, can be significantly increased by ISO treatment. MiR-3619 inhibited the expression of CSTB and CSTD, therefore affecting ISO-induced degradation of melanin. In summary, ISO reduces the melanin content via miR-3619/CSTB and miR-3619/CSTD axes. ISO could be a potent skin-whitening agent, which needs further in vivo and clinical investigation. ISO reduces the melanin content and increase lysosomal enzye activity via miR-3619/CSTB and miR-3619/CSTD axes. [ABSTRACT FROM AUTHOR]

Intralesional corticosteroid (triamcinolone acetonide [TAC]) injections have become one of the cornerstone treatments of hypertrophic scar (HSc). However, the evidence is of limited-quality, and published investigations have almost exclusively been performed in linear scars rather than hypertrophic burn scars. Thus, the aim of this study was to perform an appropriately powered, single-blinded, randomized controlled trial to evaluate the impact of TAC injections on burn HSc compared with patient-matched usual care control scars. Fifty burn survivors with two scars (separated by nonscarred skin preferably on the contralateral side or an anatomically similar site) were selected based on high-frequency ultrasound thickness (>2.034 mm to ensure that the site was outside of the range of normal scar). Pretreatment thickness measurements of the two sites were within 0.5 mm of each other, to ensure homogeneity and an erythema index >300 to establish they were immature HSc. The sites were randomly assigned to treatment or control. The treatment HSc received a 10 mg/ml TAC. When necessary, the injection was repeated after 6 weeks and a third final injection 6 weeks later. Objective evaluation of thickness, elasticity, erythema, and melanin was obtained at the treatment and control sites at pretreatment, posttreatment, and follow-up 6 weeks after the last injection. Thirty participants completed the study, reaching the required number for an adequately powered sample based on pilot study data analyses. Ten participants received only one injection, 27 received only two injections, and 13 received three injections of TAC. Analysis of covariance comparing the treatment vs control HSc posttreatment, controlling for pretreatment values and Fitzpatrick skin type, revealed a significant decrease in thickness and increase in elasticity of the treated compared with control HSc (P = .0003), but no significant difference in erythema or melanin. Pretreatment to posttreatment comparisons using paired t-tests revealed a significant decrease in thickness of both the treated and control HSc, an increase in elasticity of the treated HSc during the treatment period, but no significant change in the control HSc elasticity or erythema of either site, and a significant increase in melanin of both the treated (P < .001) and control (P = .02) HSc. A regression model for repeated measures, controlling for pretreatment values and skin type, revealed no significant change in thickness, elasticity, erythema, or melanin during the 6-week follow-up. Although thickness decreased at both the treated and control HSc across time, there was a significantly greater reduction at the TAC injected HSc and a significantly greater increase in elasticity. Melanin significantly increased at both the treatment and control site. There was no significant change during the follow-up period of any of the HSc characteristics. [ABSTRACT FROM AUTHOR]

Summary: Deleterious mutations within the SLC45A2 gene, encoding membrane‐associated transporter protein (MATP), are responsible for type 4 oculocutaneous albinism. The cytogenetic location of SLC45A2 is 5p13.2 and it comprises seven exons located over around 40 kb. Its encoded protein, MATP, is 530 amino acids long and has 12 putative transmembrane domains. MATP is synthesized within melanocytes. It is in these cells that melanogenesis takes place and the melanin is contained within specialized organelles called melanosomes. Previous studies have shown that when MATP expression was reduced using small interfering RNA in MNT‐1 melanoma cells, pH was lowered within melanosomes, they became poorly melanized and tyrosinase activity within melanocytes was also reduced. This type of albinism produces a broad spectrum of phenotypes, ranging from complete absence of melanin to brown hair and brown irides. In the current study, blood was collected from a family in which four members had oculocutaneous albinism, showing a complete absence of melanin in skin, hair and eyes. Screening of the TYR gene using the extracted DNA showed no mutation and therefore whole exome sequencing analysis was performed. A novel deletion mutation c.579delG [p.(Gly194Valfs*7)] in the SLC45A2 gene, predicted to be pathogenic and to result in both frameshift and premature termination of the MATP chain, was identified. These data add to the information pertaining to the mutation spectrum of OCA4. [ABSTRACT FROM AUTHOR]

Melanin‐ and carotenoid‐based ornaments often signal different aspects of individual quality or similar components of quality under different environmental conditions and, thus, they may become evolutionarily integrated into a composite sexual trait. On the other hand, functionally and developmentally different characters (e.g. coloration characters of different developmental origin) are more likely to evolve independently from each other than more similar traits. Here, we examined evolutionary correlations between the occurrence of a conspicuous melanin‐based ornament (hood) and carotenoid‐based bare‐part ornaments within gull family. We also aimed to identify major ecological, life‐history and biogeographical predictors of hood occurrence and reconstruct evolutionary history of this ornament. We found that hood occurrence was associated with red or dark coloration of unfeathered traits (bill and legs), whereas combinations of hood with yellow carotenoid‐based coloration of integument were evolutionarily avoided. Also, hood occurrence correlated negatively with the occurrence of other melanin‐based plumage character (mantle). Breeding latitude and habitat were identified as major predictors of hood occurrence in gulls, as hoods were recorded more frequently in low‐latitude and inland (rather than marine) species. Finally, our analysis provided support for evolutionary lability in hood occurrence, with a dominance of transitions towards hood loss in the evolutionary history of gulls. The results of our study provide one of the first evidence for a correlated evolution of melanin‐ and carotenoid‐based ornaments in an avian lineage, which supports evolutionary modularity of developmentally and functionally different coloration traits. [ABSTRACT FROM AUTHOR]

We compared temporal changes in the concentration of photoprotective compounds (PCs) in zooplankton of two adjacent (600 m apart) tropical high mountain lakes, El Sol and La Luna. The lakes have the same geological origin, age and drainage basin. However, they differ in underwater light and UV penetration and in the presence of Oncorhynchus mykiss , only found in El Sol. Whereas Daphnia ambigua from the clear La Luna had carotenoids and melanin, in El Sol, the same species lacked pigmentation. The copepod Leptodiaptomus cuauhtemoci was only found in El Sol and relied on accumulation of MAAs and carotenoids. The maximum concentration of PCs was found over the period with highest incident ultraviolet radiation (UVR). Our data suggest that tropical species of zooplankton respond to UVR by accumulating PCs that are too different in relation to exposure to UVR. However, we cannot discard the possibility that the presence of fish in Lake El Sol influences also their phenotypical and behavioral responses. Overall, zooplankton exhibited an ample phenotypic plasticity in the type and concentrations of PCs in response to the high and variable doses of UVR prevailing in low-latitude lakes, similar to the zooplankton of their high-latitude counterparts. [ABSTRACT FROM AUTHOR]

Kuji amber is fossilized tree resin of the Late Cretaceous in Japan. In this study, new biological activities of ethanol extract of Kuji amber (EtOH ext.) and supercritical carbon dioxide fluid extract of Kuji amber (scCO2 ext.) were examined. Both EtOH ext. and scCO2 ext. inhibited melanin production in B16 mouse melanoma cells and promoted collagen production in human skin fibroblast SF-TY cells. The scCO2 ext. had more potent activity than that of EtOH ext. and may depend on the efficiency of the extraction. The main new biologically active compound in Kuji amber, kujigamberol had no activities against melanin production, however, it promoted collagen production at low concentrations. A biologically active compound having a different structure, spirolactone norditerpenoid, showed both the inhibition activity against melanin production and the promotion activity of collagen production in a dose dependent manner. EtOH ext. and scCO2 ext., which include both kujigamberol and spirolactone norditerpenoid, have not only anti-allergy activity, but also inhibit melanin production and promote collagen production. The extracts of Kuji amber had inhibition activity of melanin production and promotion activity of collagen activity, with almost the same activity as β-arbutin and L-ascorbic acid. Biologically active compounds were idetified as spirolactone norditerpenoid and kujigamberol. [ABSTRACT FROM AUTHOR]

Heterocyclic aromatic amines (HAAs) are mutagens and potential human carcinogens. Our group and others have demonstrated that HAAs may also produce selective dopaminergic neurotoxicity, potentially relevant to Parkinson's disease (PD). The goal of this study was to elucidate mechanisms of HAA-induced neurotoxicity through examining a translational biochemical weakness of common PD models. Neuromelanin is a pigmented byproduct of dopamine metabolism that has been debated as being both neurotoxic and neuroprotective in PD. Importantly, neuromelanin is known to bind and potentially release dopaminergic neurotoxicants, including HAAs (eg, β-carbolines such as harmane). Binding of other HAA subclasses (ie, aminoimidazoaazarenes) to neuromelanin has not been investigated, nor has a specific role for neuromelanin in mediating HAA-induced neurotoxicity been examined. Thus, we investigated the role of neuromelanin in modulating HAA-induced neurotoxicity. We characterized melanin from Sepia officinalis and synthetic dopamine melanin, proposed neuromelanin analogs with similar biophysical properties. Using a cell-free assay, we demonstrated strong binding of harmane and 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP) to neuromelanin analogs. To increase cellular neuromelanin, we transfected SH-SY5Y neuroblastoma cells with tyrosinase. Relative to controls, tyrosinase-expressing cells exhibited increased neuromelanin levels, cellular HAA uptake, cell toxicity, and oxidative damage. Given that typical cellular and rodent PD models form far lower neuromelanin levels than humans, there is a critical translational weakness in assessing HAA-neurotoxicity. The primary impacts of these results are identification of a potential mechanism by which HAAs accumulate in catecholaminergic neurons and support for the need to conduct neurotoxicity studies in systems forming neuromelanin. [ABSTRACT FROM AUTHOR]

Background Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the melanin concentrating hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association. Methods We analyzed MCHR1 and pro-melanin concentrating hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the melanin concentrating hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of melanin concentrating hormone expressing neurons using a Cre-inducible diphtheria toxin system. Results MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P  < .05, CommonMind and PsychEncode combined datasets, n = 901) while pro-melanin concentrating hormone is below the detection threshold. MCHR1 expression decreased with aging (P  = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of pro-melanin concentrating hormone neurons increased repetitive behavior and produced a deficit in sensorimotor gating. Conclusions Our study indicates that early disruption of the melanin concentrating hormone system interferes with neurodevelopmental processes, which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by melanin concentrating hormone may lead to a therapeutic target for early prevention of schizophrenia. [ABSTRACT FROM AUTHOR]

Human activities cause rapid eutrophication and increased water turbidity in aquatic ecosystems, but their effects on fish communication and colour signals remain of debate. In particular, melanin-based coloration in fish has been understudied, because it was believed to be less costly to display than carotenoid-based colours. Here, we measured the phenotypic divergence of melanin-based coloration in 17 populations of gudgeon (Gobio occitaniae) along a turbidity gradient. We also tested the short-term plasticity of coloration using a reciprocal transplant experiment. We found strong variability in melanin-based coloration along the turbidity gradient: interpopulation divergence in coloration was higher than predicted by genetic drift, and fish were paler with increasing levels of turbidity. Finally, a reciprocal transplant experiment revealed that fish transplanted into more turbid habitats expressed a paler melanin-based coloration, suggesting that melanin-based coloration was highly plastic in the short term. Overall, our results suggest that eutrophication in human-altered rivers can rapidly alter melanin-based coloration, with potential consequences for fish visual communication and sexual selection. [ABSTRACT FROM AUTHOR]

This is the first report of a fully annotated genomic sequence of Streptomyces spectabilis NRRL-2792, isolated and identified by The Upjohn Company in 1961. The genome was assembled into a single scaffold for annotation and analysis. The chromosome is linear, 9.5 Mb in size which is one of the largest Streptomyces genomes yet described, has a G+C content of 72%, and encodes for approximately 7943 genes. Antibiotic Secondary Metabolite Analysis Shell (antiSMASH) and Basic Local Alignment Search Tool (BLAST) bioinformatics analyses identified six complete secondary metabolite biosynthetic gene clusters for ectoine, melanin, albaflavenone, spectinomycin, 2-methylisoborneol and coelichelin. Additionally, biosynthetic clusters were identified that shared ≥ 90% gene content with complestatin, hopene, neoaureothin, or undecylprodigiosin. Thirty-one other likely secondary metabolite gene clusters were identified by antiSMASH. BLAST identified two subsets of undecylprodigiosin biosynthetic genes at polar opposites of the chromosome; their duplication was subsequently confirmed by primer walking. [ABSTRACT FROM AUTHOR]