Melanin Deposition Research Articles

Genome-Wide Association Study for Screening and Identifying Potential Shin Color Loci in Ducks.

Shin color diversity is a widespread phenomenon in birds. In this study, ducks were assessed to identify candidate genes for yellow, black, and spotted tibiae. For this purpose, we performed whole-genome resequencing of an F2 population consisting of 275 ducks crossed between Runzhou crested-white ducks and Cherry Valley ducks. We obtained 12.6 Mb of single nucleotide polymorphism (SNP) data, and the three shin colors were subsequently genotyped. Genome-wide association studies (GWASs) were performed to identify candidate and potential SNPs for the three shin colors. According to the results, 2947 and 3451 significant SNPs were associated with black and yellow shins, respectively, and six potential SNPs were associated with spotted shins. Based on the SNP annotations, the MITF, EDNRB2, POU family members, and the SLC superfamily were the candidate genes regulating pigmentation. In addition, the isoforms of EDNRB2, TYR, TYRP1, and MITF-M were significantly different between the black and yellow tibiae. MITF and EDNRB2 may have synergistic roles in the regulation of melanin synthesis, and their mutations may lead to phenotypic differences in the melanin deposition between individuals. This study provides new insights into the genetic factors that may influence tibia color diversity in birds.

Hematopoietic plasticity mapped in Drosophila and other insects.

Hemocytes, similar to vertebrate blood cells, play important roles in insect development and immunity, but it is not well understood how they perform their tasks. New technology, in particular single-cell transcriptomic analysis in combination with Drosophila genetics, may now change this picture. This review aims to make sense of recently published data, focusing on Drosophila melanogaster and comparing to data from other drosophilids, the malaria mosquito, Anopheles gambiae, and the silkworm, Bombyx mori. Basically, the new data support the presence of a few major classes of hemocytes: (1) a highly heterogenous and plastic class of professional phagocytes with many functions, called plasmatocytes in Drosophila and granular cells in other insects. (2) A conserved class of cells that control melanin deposition around parasites and wounds, called crystal cells in D. melanogaster, and oenocytoids in other insects. (3) A new class of cells, the primocytes, so far only identified in D. melanogaster. They are related to cells of the so-called posterior signaling center of the larval hematopoietic organ, which controls the hematopoiesis of other hemocytes. (4) Different kinds of specialized cells, like the lamellocytes in D. melanogaster, for the encapsulation of parasites. These cells undergo rapid evolution, and the homology relationships between such cells in different insects are uncertain. Lists of genes expressed in the different hemocyte classes now provide a solid ground for further investigation of function.

Genome-Wide Analysis Identifies Candidate Genes Encoding Beak Color of Duck.

Beak color diversity is a broadly occurring phenomenon in birds. Here, we used ducks to identify candidate genes for yellow, black, and spotted beaks. For this, an F2 population consisting of 275 ducks was genotyped using whole genome resequencing containing 12.6 M single-nucleotide polymorphisms (SNPs) and three beak colors. Genome-wide association studies (GWAS) was used to identify the candidate and potential SNPs for three beak colors in ducks (yellow, spotted, and black). The results showed that 2753 significant SNPs were associated with black beaks, 7462 with yellow, and 17 potential SNPs with spotted beaks. Based on SNP annotation, MITF, EDNRB2, members of the POU family, and the SLC superfamily were the candidate genes regulating pigmentation. Meanwhile, isoforms MITF-M and EDNRB2 were significantly different between black and yellow beaks. MITF and EDNRB2 likely play a synergistic role in the regulation of melanin synthesis, and their mutations contribute to phenotypic differences in beak melanin deposition among individuals. This study provides new insights into genetic factors that may influence the diversity of beak color.

Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS-mutant neurocutaneous melanosis.

Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS-mutant neurocutaneous melanosis.

Analysis of the Effects of Melanin Depigmentation on Immunohistochemical Staining.

Heavily pigmented lesions are difficult to evaluate histologically, as melanin obscures cellular details. Several classic laboratory techniques aim to clear melanin and allow evaluation. Most of them are old and appeared before immunohistochemistry (IHC) use. Many laboratories perform IHC with aminoethylcarbazole instead of diaminobenzidine (DAB) in heavily pigmented lesions, as red-stained is easy to interpret despite pigmentation. Nevertheless, many laboratories lack alternatives to DAB. The aim of this study is to compare 6 different tissue bleaching techniques and evaluate which is the best for immunohistochemical staining with DAB. In the present study we have selected a case with gross pigmentation because of the high grade of melanin deposition. We have performed 6 different bleaching techniques and subsequently performed 2 different IHC stains, frequently used in melanoma: SOX10 (nuclear) and Melan-A (cytoplasmic). Five different pathologists, 2 of them with expertise in dermatopathology, have blindly reviewed and scored the staining quality. Our results indicate a high grade of interobserver concordance in the evaluation of IHC results between pathologists. All the bleaching techniques that included a sulfuric acid led to tissue detachment from the slide. The best method for SOX10 was that based in potassium permanganate, with a high quality of staining (4 over 5), while the best method for Melan-A was the 1 based in peroxide hydrogen (4 over 5). We consider this study can be quite useful for those laboratories lacking aminoethylcarbazole for IHC techniques, allowing the use of DAB for IHC of heavily pigmented lesions.

The C2H2 Transcription Factor SsZFH1 Regulates the Size, Number, and Development of Apothecia in Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a notorious phytopathogenic Ascomycota fungus with a host range of >600 plant species worldwide. This homothallic Leotiomycetes species reproduces sexually through a multicellular apothecium that produces and releases ascospores. These ascospores serve as the primary inoculum source for disease initiation in the majority of S. sclerotiorum disease cycles. The regulation of apothecium development for this pathogen and other apothecium-producing fungi remains largely unknown. Here, we report that a C2H2 transcription factor, SsZFH1 (zinc finger homologous protein), is necessary for the proper development and maturation of sclerotia and apothecia in S. sclerotiorum and is required for the normal growth rate of hyphae. Furthermore, ΔSszfh1 strains exhibit decreased H2O2 accumulation in hyphae, increased melanin deposition, and enhanced tolerance to H2O2 in the process of vegetative growth and sclerotia formation. Infection assays on common bean leaves, with thin cuticles, and soybean and tomato leaves, with thick cuticles, suggest that the deletion of Sszfh1 slows the mycelial growth rate, which in turn affects the expansion of leaf lesions. Collectively, our results provide novel insights into a major fungal factor mediating maturation of apothecia with additional effects on hyphae and sclerotia development.

INDEPENDENT OBSERVATIONS OF PHAEOMELANIC MALES OF THE VARIABLE SEEDEATER (SPOROPHILA CORVINA) WITH COMMENTS ABOUT ITS POTENTIAL FOR EVOLUTIONARY DIVERGENCE

Plumage coloration largely depends on the type and concentration of pigments present in feathers. Therefore, changes in pigment deposition may result in aberrant colorations, which, in turn, will likely interfere with the plumage color’s function (e.g., signaling, protection). Published records of aberrant plumage colors underestimate the type and frequency of these phenotypes, especially in the tropics. Here, we report five independent observations of phaeomelanic males of the Variable Seedeater (Sporophila corvina), in which typically white feathers were instead chestnut-red, likely due to the deposition of phaeomelanin. Our observations add to previous reports of aberrant melanin-based coloration in this species, suggesting that genomic region(s) influencing the expression of phaeomelanin are a biased target for mutations. Because mutations affecting the regulation of melanin deposition result in novel plumage phenotypes, we discuss aberrant phenotypes as an important source of variation fueling rapid divergence among populations of this avian clade.

Frenectomy and Gingival Depigmentation as a Preliminary Preparation for Orthodontic Treatment: A Case Report

Background: High attachment of labial frenulum causes central diastema and obstructs the movement of orthodontic devices. A surgical approach is needed in the form of frenectomy to improve the attachment of the frenulum. The presence of gingival hyperpigmentation due to excessive deposition of melanin is also an aesthetic problem. This hyperpigmented and uneven appearance of gum color can be corrected by ablation procedures, one of which is by using a scalpel scraping technique.
 Objective: To discuss the procedure for frenectomy and gingival depigmentation in preparation for further orthodontic treatment.
 Case Report: An 18-year-old woman was referred from the Department of Orthodontics to the Department of Periodontia, Hasanuddin University Dental and Oral Hospital, with the chief complaint of central diastema and hyperpigmented gum. The patient was planned to receive orthodontic treatment and was also disturbed by the darker color of her gums. The patient had no family history of hyperpigmented gums, smoking or consuming drugs. There was a high attachment of the frenulum, categorized as papillapenetrating type, and gingival hyperpigmentation was caused by intrinsic factor, which based on DOPI was classified as grade 3. The surgery was done in two steps. Gingival depigmentation was done one week after the frenectomy procedure.
 Results: The results of the treatment showed improved adhesion of the frenulum and eliminated gingival hyperpigmentation.
 Conclusion: Frenectomy and gingival depigmentation improved the patient’s appearance and frenectomy allowed preparation for further orthodontic treatment.
 Keywords: gingival hyperpigmentation, central diastema, frenectomy, orthodontic treatment

Biological characterization of the melanin biosynthesis gene Bcscd1 in the plant pathogenic fungus Botrytis cinerea

The gray mold fungus Botrytis cinerea produces dark-colored conidia and sclerotia due to deposition of melanin on the cell wall of these structures. However, the role of melanin biosynthesis on development and function of conidia and sclerotia have not been well elucidated in this fungus. This study disrupted the melanin biosynthesis gene Bcscd1 (for scytalone dehydratase) in the wild type B05.10, and the resulting mutants were compared with B05.10 and complementary mutants (COM) for growth and development, virulence and response to biotic/abiotic stresses. Three disruption mutants were obtained, and they did not differ from B05.10 and COM in mycelial growth rate on potato dextrose agar, however, they formed brownish conidia and scleotia deficient in melanogenesis, whereas B05.10 and COM formed grayish conidia and black sclerotia with normal melanogenesis. The disruption mutants were as aggressive as B05.10 and COM in infection of tobacco leaves. TEM observation showed that the disruption mutant ΔScd1-85 formed numerous tiny grooves in the conidial cell wall, thereby causing uneven thickness in the cell wall. In contrast, B05.10 and COM rarely formed tiny grooves in their conidial cell wall with even thickness. Moreover, the sclerotial cortex cell wall of ΔScd1-85 lost rigidity and the cells became collapsed, whereas the sclerotial cortex cell wall of B05.10 and COM appeared rigid, and the cells appeared plump in shape. The disruption mutants were more sensitive than B05.10 and COM in response to chemical stresses (H2O2, NaCl, SDS, sorbitol) for conidial germination and sclerotial survival. The sclerotia of the disruption mutants were more susceptible than the sclerotia of B05.10 and COM to infection by the mycoparasite Trichoderma koningiopsis. These results confirmed previous studies about the effect of melanin production on pathogenicity of B. cinerea, and expanded our knowledge about the role of Bcscd1 in cell wall integrity and in response to biotic and abiotic stresses.

Genome-wide association analysis reveal the genetic reasons affect melanin spot accumulation in beak skin of ducks

BackgroundSkin pigmentation is a broadly appearing phenomenon of most animals and humans in nature. Here we used a bird model to investigate why melanin spot deposits on the skin.ResultsOur result showed that growth age and the sunlight might induce melanin deposition in bird beak skin which was determined by genetic factors. GWAS helped us to identify two major loci affecting melanin deposition, located on chromosomes 13 and 25, respectively. The fine mapping works narrowed the candidate regions to 0.98 Mb and 1.0 Mb on chromosomes 13 and 25. The MITF and POU2F3 may be the causative genes and synergistically affect melanin deposition during duck beak skin. Furthermore, our data strongly demonstrated that the pathway of melanin metabolism contributes to melanin deposition on the skin.ConclusionsWe demonstrated that age and sunlight induce melanin deposition in bird beak skin, while heredity is fundamental. The MITF and POU2F3 likely played a synergistic effect on the regulation of melanin synthesis, and their mutations contribute to phenotypic differences in beak melanin deposition among individuals. It is pointed out that melanin deposition in the skin is related to the pathway of melanin metabolism, which provided insights into the molecular regulatory mechanisms and the genetic improvement of the melanin deposition in duck beak.

Population Genomic Sequencing Delineates Global Landscape of Copy Number Variations that Drive Domestication and Breed Formation of in Chicken.

Copy number variation (CNV) is an important genetic mechanism that drives evolution and generates new phenotypic variations. To explore the impact of CNV on chicken domestication and breed shaping, the whole-genome CNVs were detected via multiple methods. Using the whole-genome sequencing data from 51 individuals, corresponding to six domestic breeds and wild red jungle fowl (RJF), we determined 19,329 duplications and 98,736 deletions, which covered 11,123 copy number variation regions (CNVRs) and 2,636 protein-coding genes. The principal component analysis (PCA) showed that these individuals could be divided into four populations according to their domestication and selection purpose. Seventy-two highly duplicated CNVRs were detected across all individuals, revealing pivotal roles of nervous system (NRG3, NCAM2), sensory (OR), and follicle development (VTG2) in chicken genome. When contrasting the CNVs of domestic breeds to those of RJFs, 235 CNVRs harboring 255 protein-coding genes, which were predominantly involved in pathways of nervous, immunity, and reproductive system development, were discovered. In breed-specific CNVRs, some valuable genes were identified, including HOXB7 for beard trait in Beijing You chicken; EDN3, SLMO2, TUBB1, and GFPT1 for melanin deposition in Silkie chicken; and SORCS2 for aggressiveness in Luxi Game fowl. Moreover, CSMD1 and NTRK3 with high duplications found exclusively in White Leghorn chicken, and POLR3H, MCM9, DOCK3, and AKR1B1L found in Recessive White Rock chicken may contribute to high egg production and fast-growing traits, respectively. The candidate genes of breed characteristics are valuable resources for further studies on phenotypic variation and the artificial breeding of chickens.

Management of gingival hyperpigmentation using three different techniques: A case series

Although the colour of the gingiva plays a vital part in overall aesthetics, the ideas and strategies for treating problems caused by gingival melanin pigmentation are still being worked out. Clinicians are confronted with obtaining acceptable gingival aesthetics as well as resolving biologic and functional difficulties as aesthetics has become an important element of dentistry. This case report discusses three different de-epithelization treatments that have been effectively utilised to treat gingival hyperpigmentation caused by excessive melanin deposition, as well as the importance of having an aesthetically pleasant smile, especially for smile aware people. Creating esthetic awareness among dental practitioners about various treatment modalitites for the management of gingival hyperpigmentation.

Bladder Melanosis

This case report describes a rare cystoscopic finding in an octogenarian, presenting initially with nonspecific lower urinary tract symptoms. Physical examination did not reveal any abnormal skin or mucoepidermoid pigmentation. Routine ultrasound identified cystic changes in the bladder prompting cystoscopic investigation. Flexible cystoscopy identified melanin deposits within the bladder mucosa, and biopsy subsequently confirmed a diagnosis of bladder melanosis. The authors of this report wish to add to the available literature on this extremely rare finding in the hope a more robust evidence base would allow a protocol to be established for follow-up. The ultrasound findings reported in this study have not been previously reported and may benefit future guidelines on diagnosis.

Many faces of malignant melanoma: Histopathological evaluation of liver biopsies.

Malignant melanoma (MM) is an aggressive tumor characterized by high metastatical potential and is sometimes diagnosed by distant organ metastasis such as liver. Morphologically it may mimic many other tumors and cause diagnostic challenges. In this paper, eleven MM cases metastasized to the liver with different morphologic patterns were analyzed in the light of literature. Histopathological and immunohistochemical findings of the cases diagnosed as MM metastasis in liver were reevaluated in the light of clinical data. We obtained 11 MM cases with hepatic metastasis. In slides of the first four cases, morphologic features similar to epithelioid variant of MM with different amounts of melanin deposition were observed. In the fifth and sixth cases, fascicular patterned tumoral lesion composed of spindled cells were detected; and in the seventh and eighth cases, nested and sheet-like patterned tumoral lesion consist of giant bizarre and spindled cells with hyperchromatic nuclei were observed. The last three cases consisted of plasmacytoid cells with eccentric nuclei in pseudoalveolar pattern; and the exact diagnosis was possible with the help of immunohistochemistry. MM should always be kept in mind in differential diagnosis of metastatic hepatic tumors with unknown primary because of its various morphological characteristics.

Radiofrequency Irradiation Mitigated UV-B-Induced Skin Pigmentation by Increasing Lymphangiogenesis.

Dermal macrophages containing melanin increase skin pigmentation since dermal melanin removal is slower than epidermal melanin removal. Lymphatic vessels are also involved in melanin clearance. We evaluated whether radiofrequency (RF) irradiation induced an increase in HSP90, which promotes lymphangiogenesis by activating the BRAF/MEK/ERK pathway and decreasing tyrosinase activity, in the UV-B exposed animal model. The HSP90/BRAF/MEK/ERK pathway was upregulated by RF. Tyrosinase activity and the VEGF-C/VEGFR 3/PI3K/pAKT1/2/pERK1/2 pathway, which increase lymphangiogenesis, as well as the expression of the lymphatic endothelial marker LYVE-1, were increased by RF. Additionally, the number of melanin-containing dermal macrophages, the melanin content in the lymph nodes, and melanin deposition in the skin were decreased by RF. In conclusion, RF increased HSP90/BRAF/MEK/ERK expression, which decreased tyrosinase activity and increased lymphangiogenesis to eventually promote the clearance of dermal melanin-containing macrophages, thereby decreasing skin pigmentation.

How melanism affects the sensitivity of lizards to climate change

Abstract The impact of climate change on global biodiversity is firmly established, but the differential effect of climate change on populations within the same species is rarely considered. In ectotherms, melanism (i.e. darker integument due to heavier deposition of melanin) can significantly influence thermoregulation, as dark individuals generally heat more and faster than bright ones. Therefore, darker ectotherms might be more susceptible to climate change. Using the colour‐polyphenic lizard Karusasaurus polyzonus (Squamata: Cordylidae), we hypothesized that, under future climatic projections, darker populations will decrease their activity time more than brighter ones due to their greater potential for overheating. To test this, we mechanistically modelled the body temperatures of 56 individuals from five differently coloured populations under present and future climate conditions. We first measured morphological traits and integumentary reflectance from live animals, and then collected physiological data from the literature. We used a biophysical model to compute activity time of individual lizards as proxy for their viability, and thereby predict how different populations will cope with future climate conditions. Contrary to our expectations, we found that all populations will increase activity time and, specifically, that darker populations will become relatively more active than bright ones. This suggests that darker populations of K. polyzonus may benefit from global warming. Our study emphasizes the importance of accounting for variation between populations when studying responses to climate change, as we must consider these variations to develop efficient and specific conservation strategies. A free Plain Language Summary can be found within the Supporting Information of this article.

SOX9 in Keratinocytes Regulates Claudin 2 Transcription during Skin Aging.

In order to prove that SOX9 in keratinocytes regulates claudin 2 transcription during skin aging, the skin of 8-week-old and 24-month-old mice is sequenced to obtain a differentially expressed gene SOX9. The gene is mainly expressed in keratinocytes, and it increases first and then decreases from newborn to aging. Six core sequences of SOX9 and claudin 2 are predicted from Jaspar. The double Luciferase Report shows that overexpression of SOX9 induces the full-length promoter of claudin 2 significantly and has no effect on the mutation and cleavage plasmid without SOX9 response. Claudin 2 is consistent with SOX9 in the skin of mice of different ages, and SOX9 is strongly positively correlated with claudin 2. Finally, overexpression of SOX9 and claudin 2 will delay PM2.5-induced keratinocyte senescence. The silencing of claudin 2 leads to the loss of SOX9 function. It is clearly evident that SOX9 can affect the transcription of claudin 2, which increases first and then decreases in the process of mice from newborn to aging. SOX9 inhibits proinflammatory mediators, increases antioxidant capacity, and restores keratin differentiation. It can effectively prevent melanin deposition and delay aging.

Yellow nail syndrome

Yellow nail syndrome is an extremely rare syndrome, mainly in people over 50 years of age, occurring both systemically and in isolation and requiring the most careful collection of anamnesis, since this condition has a close relationship with respiratory diseases, malignant neoplasms of internal organs and rheumatoid arthritis. Moreover, this rare disease is not sufficiently studied to fully understand its pathogenesis and effective treatment. Patients pay attention to the yellow color of the nails, associated with the deposition of melanin, bile pigments and hemosiderin in the submarginal space, slowing down the growth and thickening of the nail. It should be noted that the change in the nail plates can be observed long before the other clinical manifestations of this syndrome are detected, and probably this can in some cases serve as a harbinger of incipient changes in the lung tissue, neoplasms and changes in the lymphatic vessels. In this regard, it is extremely important to clearly differentiate this condition and refer patients to related specialists for verification of the diagnosis and further treatment.

Comparative Study of Hematological and Histopathological Alterations in Oreochromis niloticus and Clarias gariepinus Exposed to Industrial Waste Effluents

In recent decades the level of foreign compounds in aquatic ecosystems such as heavy metals, pesticides and other persistent organic pollutants has increased alarmingly as a result of domestic, industrial and agricultural effluent. This research therefore examined the histopathological and haematological effects of industrial effluent on Orechromis niloticus and Clarias gariepinus. The histopathology and haematology parameters of the fishes exposed to graded doses of the effluent were assessed using conventional techniques. The results of the haematological assessment of the fishes shows a steady and significant (P < 0.05) reduction in the PCV of the tilapia from 23% (control) to 10% and 25% (control) to 18% in catfish exposed to 6.25 ml/L of the effluent, the RBC count reduced with increase in the concentration of the effluent from 2.60 x 106/L (control) to 1.15 x 106/L (tilapia) and from 2.80 to 1.72 x 106/L (catfish) in the sample exposed to 6.25 ml/L of the effluent. Also, the values of Hb concentration reduced from 7.73 g/dL to 3.10 g/dL (tilapia) and from 8.33 to 5.17 g/dL (catfish). However, the WBC count increased from 4800.33 x 103/L to 9500.30 x 103/L (tilapia) and from 5300.30 x 103/L to 7800.50 x 103/L (catfish) in those exposed to 6.25 ml/L of the effluent. In the histological assessment of the gills of the fishes, the tilapia fish exposed to 6.25ml/L of the effluent recorded an extensive damage, distortion and thickening of the tilapia fish gill lamellae. Also, there was loss of secondary lamellae and loss of gill raker filaments of the catfish. The liver cells of tilapia had many monocytes (kuppfer cells) while there were mild increase in the number of kuppfer cells of the catfish. The kidney artery of tilapia was filled with leucocytes while there were cellular proliferation (hyperplasia) and less of melanin deposits in the kiney cells of catfish. These are indications that the industrial effluent contain toxicants that are dangerous to the fish health.

Biomolecular interactions and binding dynamics of inhibitor arachidonic acid, with tyrosinase enzyme

Hyperpigmentation is a disorder caused by increased melanin deposition and changes in skin pigmentation. Inhibition of tyrosinase activity contributes to the control of food browning and skin pigmentation diseases. The effects of arachidonic acid (AA) on tyrosinase activity were examined using different spectroscopy methods including UV-VIS spectrophotometry, fluorescence spectroscopy, circular dichroism (CD) differential scanning calorimetry, and molecular dynamics (MD) simulations. Based on the kinetic results, arachidonic acid showed mixed-type of inhibition with Ki = 4.7 µM. Fluorescence and CD studies showed changes of secondary and tertiary structures of enzyme and a reduction of α-helix* amino acids after its incubation with different concentrations of AA, which is also confirmed by DSSP analysis. In addition, differential scanning calorimetry (DSC) studies showed a decrease in thermodynamic stability of enzyme from Tm = 338.65k for sole enzyme after incubation with AA in comparison with complex enzyme with Tm= 334.26k, ΔH =7.52 kJ/mol, and ΔS = 0.15 kJ/mol k. Based on the theoretical methods, it was found that the interaction between enzyme and AA follows an electrostatic manner with ΔG = −8.314 kJ/mol and ΔH = −12.9 kJ/mol. The MD results showed the lowest flexibility in the complex amino acids and minimal fluctuations in AA interaction with tyrosinase in Residue 240 to 260 and 66 to 80. Thus, AA inhibitory and structural and thermodynamic instability of tyrosinase supported advantages of this fatty acid for prevention of medical hyperpigmentation. Therefore, it is a good candidate for cosmetic applications. Communicated by Ramaswamy H. Sarma