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Lanmei Wang, Wenbin Zhu, Zaijie Dong, Feibiao Song, Juanjuan Dong, Jianjun Fu
Differentiation and variation in body color has been a growing limitation to the commercial value of red tilapia. Limited microRNA (miRNA) information is available on skin color differentiation and variation in fish so far. In this study, a high-throughput Illumina sequencing of sRNAs was conducted on three color varieties of red tilapia and 81,394,491 raw reads were generated. A total of 158 differentially expressed miRNAs (|log₂(fold change)| ≥ 1 and q -value ≤ 0.001) were identified. Target prediction and functional analysis of color-related miRNAs showed that a variety of putative target genes—including slc7a11 , mc1r and asip —played potential roles in pigmentation...
April 16, 2018: International Journal of Molecular Sciences
Feng Gao, Wiebke Sihver, Ralf Bergmann, Birgit Belter, Cristina Bolzati, Nicola Salvarese, Jörg Steinbach, Jens Pietzsch, Hans-Jürgen Pietzsch
α-Melanocyte stimulating hormone (α-MSH) derivatives target the melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the α-MSH derived peptide NAP-NS1 (Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2) with and without linkers was conjugated with 5-(bis(pyridin-2-yl)methyl)amino)pentanoic acid (DPA-COOH) and labeled with [99mTc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pots method, however obtaining similarly high yields. Negligible transchelation and high stability in physiological solutions was determined for the [99mTc]Tc-tricarbonyl-peptide conjugates...
April 16, 2018: ChemMedChem
Po-Yuan Wu, Ya-Jhen You, Yi-Jung Liu, Chien-Wei Hou, Chin-Sheng Wu, Kuo-Ching Wen, Chien-Yih Lin, Hsiu-Mei Chiang
Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation...
April 7, 2018: International Journal of Molecular Sciences
María Castejón-Griñán, Cecilia Herraiz, Conchi Olivares, Celia Jiménez-Cervantes, Jose Carlos García-Borrón
The melanocortin 1 receptor gene (MC1R), a well-established melanoma susceptibility gene, regulates the amount and type of melanin pigments formed within epidermal melanocytes. MC1R variants associated with increased melanoma risk promote the production of photosensitizing pheomelanins as opposed to photoprotective eumelanins. Wild-type (WT) MC1R activates DNA repair and antioxidant defenses in a cAMP-dependent fashion. Since melanoma-associated MC1R variants are hypomorphic in cAMP signaling, these non-pigmentary actions are thought to be defective in MC1R-variant human melanoma cells and epidermal melanocytes, consistent with a higher mutation load in MC1R-variant melanomas...
April 6, 2018: Oncogene
Thomas Durek, Philipp M Cromm, Andrew M White, Christina I Schroeder, Quentin Kaas, Joachim Weidmann, Abdullah Ahmad Fuaad, Olivier Cheneval, Peta J Harvey, Norelle L Daly, Yang Zhou, Anita Dellsén, Torben Österlund, Niklas Larsson, Laurent Knerr, Udo Bauer, Horst Kessler, Minying Cai, Victor J Hruby, Alleyn T Plowright, David J Craik
Ultra-stable cyclic peptide frameworks offer great potential for drug design due to their improved bioavailability compared to their linear analogues. Using the sunflower trypsin inhibitor-1 (SFTI-1) peptide scaffold in combination with systematic N-methylation of the grafted pharmacophore led to the identification of novel subtype selective melanocortin receptor (MCR) agonists. Multiple bicyclic peptides were synthesized and tested towards their activity at MC1R and MC3-5R. Double N-methylated compound 18 showed a pKi of 8...
March 31, 2018: Journal of Medicinal Chemistry
Alejandro Martin-Gorgojo, Celia Requena, Zaida Garcia-Casado, Victor Traves, Rajiv Kumar, Eduardo Nagore
The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM) and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants...
February 13, 2018: Acta Dermato-venereologica
Huirong Li, Ling Hou
Somatic stem cells are regulated by their niches to maintain tissue homeostasis and repair throughout the lifetime of an organism. An excellent example to study stem cell/niche interactions is provided by the regeneration of melanocytes during the hair cycle and in response to various types of injury. These processes are regulated by neighboring stem cells and multiple signaling pathways, including WNT/β-catenin, KITL/KIT, EDNs/EDNRB, TGFβ/TGFβR, α-MSH/MC1R, and Notch signaling. In this review, we highlight recent studies that have advanced our understanding of the molecular crosstalk between melanocyte stem cells and their neighboring cells, which collectively form the niche microenvironment, and we focus on the question of how McSCs/niche interactions shape the responses to genotoxic damages and mechanical injury...
March 26, 2018: Pigment Cell & Melanoma Research
Nao Matsuda, Satoshi Kasagi, Toru Nakamaru, Reiji Masuda, Akiyoshi Takahashi, Masatomo Tagawa
Body coloration in flatfish is one of the most distinctive asymmetries in the animal kingdom, although the fundamental molecular mechanism of the pigmentation is unclear. In the dorso-ventral coloration (countershading) of other teleost fishes, ventral-specific expression of agouti signaling protein 1 (ASIP1), an endogenous antagonist of melanocortin 1 receptor (MC1R), has been reported to play a pivotal role. Contribution of ASIP1 is also suggested in the asymmetrical pigmentation of flatfish. In order to confirm the contribution of ASIP1 and further examine receptor function in the body coloration of Japanese flounder, expression levels of asip1, mc1r, melanocortin 5 receptor (mc5r), and melanin-concentrating hormone receptor 2 (mchr2) were measured in the normally pigmented area of the left side, the normally non-pigmented area of the right side, and the abnormally pigmented (exhibiting hypermelanosis) area of the right side...
March 21, 2018: General and Comparative Endocrinology
Yinuo Liu, Elke Albrecht, Lisa Schering, Christa Kuehn, Runjun Yang, Zhihui Zhao, Steffen Maak
Transcriptome analyses of bovine muscle tissue differing in intramuscular fat (IMF) content identified agouti signaling protein (ASIP) as a promising candidate gene for fat deposition. The protein is secreted from adipocytes and may serve as a signaling molecule in cross-talk between adipocytes and muscle fibers or other cells. Known receptors for ASIP are the melanocortin receptors (e.g., MC4R) and attractin (ATRN). The present study was conducted to determine relationships between the expression of ASIP and its receptors in different bovine tissues with fat deposition...
2018: Frontiers in Physiology
Robert M Dores, Michelle Scuba-Gray, Bridgette McNally, Perry Davis, Akiyoshi Takahashi
Previous studies on bony vertebrate MC2R orthologs (i.e., ray finned fishes, amphibians, reptiles, birds, and mammals) have shown that these MC2R orthologs have an obligatory requirement for interaction with bony vertebrate MRAP1 orthologs to a) allow for the trafficking of the MC2R ortholog to the plasma membrane; and b) to allow activation by ACTH, but not by any MSH-sized ligand. In addition, previous studies have found that co-expression of teleost and mammalian MC4R orthologs with corresponding MRAP2 has positive effects on sensitivity to stimulation by αMSH or ACTH...
March 7, 2018: General and Comparative Endocrinology
Visalini Nair-Shalliker, Sam Egger, Agata Chrzanowska, Rebecca Mason, Louise Waite, David Le Couteur, Markus J Seibel, David J Handelsman, Robert Cumming, David P Smith, Bruce K Armstrong
BACKGROUND: Melanoma and prostate cancer may share risk factors. This study examined the association between serum PSA levels, which is a risk factor for prostate cancer, and variants in some melanoma-associated pigmentary genes. METHODS: We studied participants, all aged 70+ years, in the Concord Health and Ageing in Men Project who had no history of prostatitis or received treatment for prostate disease (n = 1033). We genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174)...
2018: PloS One
Bruno William, Martinuzzi Claudia, Dalmasso Bruna, Andreotti Virginia, Pastorino Lorenza, Cabiddu Francesco, Gualco Marina, Spagnolo Francesco, Ballestrero Alberto, Queirolo Paola, Grillo Federica, Mastracci Luca, Ghiorzo Paola
Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants...
January 19, 2018: Oncotarget
Jonathan L Whitney, Brian W Bowen, Stephen A Karl
One of the primary challenges of evolutionary research is to identify ecological factors that favor reproductive isolation. Therefore, studying partially isolated taxa has the potential to provide novel insight into the mechanisms of evolutionary divergence. Our study utilizes an adaptive color polymorphism in the arc-eye hawkfish (Paracirrhites arcatus) to explore the evolution of reproductive barriers in the absence of geographic isolation. Dark and light morphs are ecologically partitioned into basaltic and coral microhabitats a few meters apart...
February 8, 2018: Molecular Ecology
Claudia Huerta, Zaida Garcia-Casado, José Bañuls, Manuel Moragon, Vicente Oliver, Blanca Unamuno, Celia Requena, Rajiv Kumar, Eduardo Nagore
Melanoma results from a complex interplay between environmental factors and individual genetic susceptibility. Familial melanoma is attributable to predisposition genes with variable penetrance. The aim of this study was to identify differences between familial melanoma and sporadic cases in our population, based on the presence of CDKN2A mutations and MC1R variants. Comparing 107 patients with familial melanoma from 87 families (17% CDKN2A mutated) with 1,390 cases of sporadic melanomas, the former were younger and exhibited an increased prevalence of atypical naevi and squamous cell carcinoma (SCC)...
February 6, 2018: Acta Dermato-venereologica
Jae Ok Seo, Silvia Yumnam, Kwang Won Jeong, Sun Yeou Kim
Finasteride is a well-known 5α-reductase inhibitor used for treatment of alopecia and prostate cancer. But the effect of finasteride in regulating melanogenesis is still unclear. In the present study the role of finasteride on melanogenesis was investigated. Finasteride decrease melanin level in melanocyte melan-a cells and B16F10 melanoma cells without inducing cytotoxicity. MC1R (melanocortin 1 receptor) protein expression was also inhibited by finasteride thereby decreasing the expression of adenylate cyclase, MITF (Melanogenesis associated transcription factor), tyrosinases, TRP (tyrosinase-related protein) -1 and -2...
February 3, 2018: Archives of Pharmacal Research
Christina Marie Rochus, Flavie Tortereau, Florence Plisson-Petit, Gwendal Restoux, Carole Moreno-Romieux, Gwenola Tosser-Klopp, Bertrand Servin
BACKGROUND: One of the approaches to detect genetics variants affecting fitness traits is to identify their surrounding genomic signatures of past selection. With established methods for detecting selection signatures and the current and future availability of large datasets, such studies should have the power to not only detect these signatures but also to infer their selective histories. Domesticated animals offer a powerful model for these approaches as they adapted rapidly to environmental and human-mediated constraints in a relatively short time...
January 23, 2018: BMC Genomics
Yao Yu, Hao Hu, Jiun-Sheng Chen, Fulan Hu, Jerry Fowler, Paul Scheet, Hua Zhao, Chad D Huff
While a number of genes have been implicated in melanoma susceptibility, the role of protein-coding variation in melanoma development and progression remains underexplored. To better characterize the role of germline coding variation in melanoma, we conducted a whole-exome case-control and somatic-germline interaction study involving 322 skin cutaneous melanoma cases from The Cancer Genome Atlas and 3607 controls of European ancestry. We controlled for cross-platform technological stratification using XPAT and conducted gene-based association tests using VAAST 2...
January 6, 2018: Biochimica et Biophysica Acta
Anna C Thomas, Pauline Heux, Chloe Santos, Wisenave Arulvasan, Nita Solanky, Magalie E Carey, Dianne Gerrelli, Veronica A Kinsler, Heather C Etchevers
BACKGROUND: MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk. MC1R mutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentation in utero alter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight...
March 15, 2018: Birth Defects Research
M U Anu Prathap, Carlos Iván Rodríguez, Omer Sadak, Jiehao Guan, Vijayasaradhi Setaluri, Sundaram Gunasekaran
We report the development of an antibody (anti-MC1R antibody)-functionalized polyaniline nanofibers modified screen-printed electrode capable of efficient electrochemical detection of melanoma cells at levels (1 cell per mL) not readily achieved by other methods. This immunosensor is highly selective in its detection of melanoma cells over normal human cells.
January 18, 2018: Chemical Communications: Chem Comm
Peter A Kanetsky, Jennifer L Hay
Melanoma rates have been increasing in the United States, and neither primary (sun protection and avoidance) nor secondary (skin examination) prevention is practiced consistently, even by those with melanoma risk factors. Inherited variation at MC1R is a robust marker for increased risk of melanoma, even among individuals with "sun-resistant" phenotypes. Although MC1R conveys important information about inherited melanoma risk for a broad spectrum of individuals, concerns that MC1R feedback could have negative consequences, including increased distress about melanoma, inappropriate use of health services, and development of a false sense of security, are valid and require empirical examination...
March 2018: Cancer Prevention Research
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