RESUMEN
Fossilized eyes permit inferences of the visual capacity of extinct arthropods1-3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes of 54-million-year-old crane-flies, which together provide a proxy for the interpretation of optical systems in some other ancient arthropods. These well-preserved visual organs comprise calcified corneal lenses that are separated by intervening spaces containing eumelanin pigment. We also show that eumelanin is present in the facet walls of living crane-flies, in which it forms the outermost ommatidial pigment shield in compound eyes incorporating a chitinous cornea. To our knowledge, this is the first record of melanic screening pigments in arthropods, and reveals a fossilization mode in insect eyes that involves a decay-resistant biochrome coupled with early diagenetic mineralization of the ommatidial lenses. The demonstrable secondary calcification of lens cuticle that was initially chitinous has implications for the proposed calcitic corneas of trilobites, which we posit are artefacts of preservation rather than a product of in vivo biomineralization4-7. Although trilobite eyes might have been partly mineralized for mechanical strength, a (more likely) organic composition would have enhanced function via gradient-index optics and increased control of lens shape.
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Artrópodos/anatomía & histología , Artrópodos/química , Dípteros/anatomía & histología , Dípteros/química , Fósiles , Pigmentos Biológicos/análisis , Pigmentos Biológicos/química , Animales , Biomarcadores/análisis , Biomarcadores/química , Femenino , Pinzones , Masculino , Melaninas/análisis , Melaninas/química , Óptica y FotónicaRESUMEN
Abnormal metal distribution in vulnerable brain regions is involved in the pathogenesis of most neurodegenerative diseases, suggesting common molecular mechanisms of metal dyshomeostasis. This study aimed to compare the intra- and extra-neuronal metal content and the expression of proteins related to metal homeostasis in the substantia nigra (SN) from patients with Parkinson's disease (PD), multiple sclerosis (MS), and control subjects. Metal quantification was performed via ion-beam micro-analysis in neuromelanin-positive neurons and the surrounding tissue. For proteomic analysis, SN tissue lysates were analyzed on a nanoflow chromatography system hyphenated to a hybrid triple-quadrupole time-of-flight mass spectrometer. We found increased amounts of iron in neuromelanin-positive neurons and surrounding tissue in patients with PD and MS compared to controls (4- to 5-fold higher) that, however, also showed large inter-individual variations. Copper content was systematically lower (-2.4-fold) in neuromelanin-positive neurons of PD patients compared with controls, whereas it remained unchanged in MS. Protein-protein interaction (PPI) network analyses revealed clusters related to Fe and Cu homeostasis among PD-deregulated proteins. An enrichment for the term "metal homeostasis" was observed for MS-deregulated proteins. Important deregulated hub proteins included hemopexin and transferrin in PD, and calreticulin and ferredoxin reductase in MS. Our findings show that PD and MS share commonalities in terms of iron accumulation in the SN. Concomitant proteomics experiments revealed PPI networks related to metal homeostasis, substantiating the results of metal quantification.
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Esclerosis Múltiple , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Proteómica , Esclerosis Múltiple/metabolismo , Sustancia Negra/patología , Metales/metabolismo , Hierro/metabolismo , Melaninas/análisis , Melaninas/metabolismoRESUMEN
Ex vivo physiological experiments using small insect models such as Drosophila larvae have become increasingly useful to address fundamental biological questions. To perform such experiments, various artificial saline solutions have been developed, but their osmolality varies significantly from one to the next. Such a variation of osmolality stems, in part, from the difficulty of determining the true value of haemolymph osmolality in Drosophila larvae. Thus, there is a pressing need to refine protocols for collecting and measuring the osmolality of the larval haemolymph. Two major obstacles are thought to impede the accurate analysis of haemolymph collected from small insects: melanin formation and gut-derived contamination. Here, we greatly refined existing haemolymph collection methods, evaluated the purity of the collected haemolymph under melanin-free conditions, and concluded that the true value of haemolymph osmolality is close to 306.0â mOsmâ kg-1 in Drosophila larvae.
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Hemolinfa , Larva , Animales , Hemolinfa/química , Hemolinfa/metabolismo , Concentración Osmolar , Larva/crecimiento & desarrollo , Larva/química , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Melaninas/metabolismo , Melaninas/análisisRESUMEN
Ichthyosaurs are extinct marine reptiles that display a notable external similarity to modern toothed whales. Here we show that this resemblance is more than skin deep. We apply a multidisciplinary experimental approach to characterize the cellular and molecular composition of integumental tissues in an exceptionally preserved specimen of the Early Jurassic ichthyosaur Stenopterygius. Our analyses recovered still-flexible remnants of the original scaleless skin, which comprises morphologically distinct epidermal and dermal layers. These are underlain by insulating blubber that would have augmented streamlining, buoyancy and homeothermy. Additionally, we identify endogenous proteinaceous and lipid constituents, together with keratinocytes and branched melanophores that contain eumelanin pigment. Distributional variation of melanophores across the body suggests countershading, possibly enhanced by physiological adjustments of colour to enable photoprotection, concealment and/or thermoregulation. Convergence of ichthyosaurs with extant marine amniotes thus extends to the ultrastructural and molecular levels, reflecting the omnipresent constraints of their shared adaptation to pelagic life.
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Evolución Biológica , Regulación de la Temperatura Corporal , Dinosaurios/anatomía & histología , Dinosaurios/fisiología , Fósiles , Homeostasis , Adaptación Fisiológica , Tejido Adiposo/anatomía & histología , Tejido Adiposo/química , Animales , Dermis/anatomía & histología , Dermis/química , Delfines , Epidermis/anatomía & histología , Epidermis/química , Femenino , Queratinocitos/química , Lípidos/análisis , Masculino , Melaninas/análisis , Melanóforos/química , Marsopas , Proteínas/análisisRESUMEN
BACKGROUND: Vascular structure, blood oxygen saturation, and melanin status of the epidermis are chromophore factors related to light absorption. Therefore, they are likely to be related to skin appearance. Thus, it is important to measure these internal skin features and understand their characteristics. Thus, we aimed to analyze the individual differences and aging changes in the skin by measuring the internal skin characteristics, such as vascular structure, oxygen saturation, and the 3D distribution of melanin in the epidermis, using a noninvasive photoacoustic (PA) measurement method. MATERIALS AND METHODS: A PA measurement device was used as a noninvasive measurement method. Eighty Japanese women aged between 20 and 60 years were enrolled. The target area was the buccal region of the face. RESULTS: The blood vessel structure showed a decrease in fine vessels with age, with a stronger tendency observed in the dermis layer, and the volume of blood vessels was larger in the dermis layer than in the dermal-subcutaneous fat boundary layer. Oxygen saturation showed a similar decreasing trend with age in all depths examined. Melanin condition as the torus-like pattern structure tended to increase with age. CONCLUSION: PA measurements revealed the characteristics of several chromophores, providing a new skin aging mechanism.
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Melaninas , Saturación de Oxígeno , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Melaninas/análisis , Epidermis/diagnóstico por imagen , Epidermis/metabolismo , Piel/irrigación sanguínea , Análisis Espectral , OxígenoRESUMEN
The fingerprint of Vernonia anthelmintica effective part (VAEP) from 15 different producing areas was established, followed by cluster analysis and principal component analysis. The relationship between the fingerprint and the melanogenesis-promoting activity of VAEP was then analyzed using the grey correlation degree and the orthogonal partial least square method. The characteristic peaks reflecting the pharmacodynamic effect of VAEP were identified as vernodalin, 3,5-O-dicaffeoyl quinic acid (3,5-diCQA), and butin. Based on the distribution characteristics of these components in plants from different habitats and the verification of results from the spectrum-effect relationship, vernodalin and 3,5-diCQA can be used as characteristic components for quality control and pharmacodynamic assessment of V. anthelmintica products. This research establishes a theoretical foundation for planting areas and provides a scientific evaluation of the melanogenesis-promoting effect of V. anthelmintica.
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Melaninas , Vernonia , Vernonia/química , Cromatografía Líquida de Alta Presión/métodos , Melaninas/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/química , Animales , Análisis de Componente Principal , RatonesRESUMEN
A novel water-soluble Amygdalus persica L. flowers polysaccharide (APL) was successfully isolated and purified from Amygdalus persica L. flowers by hot water extraction. Its chemical components and structure were analyzed by IR, GC-MS, and HPLC. APL consisted of rhamnose, arabinose, mannose and glucose in a molar ratio of 0.17:0.034:1.0:0.17 with an average molecular weight of approximately 208.53 kDa and 15.19 kDa. The antioxidant activity of APL was evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 3-ethylbenzthiazoline-6-sulfonic acid (ABTS), Hydroxyl radical scavenging, Superoxide radical scavenging, and the reducing power activity was also determined in vitro. Besides, in vivo antioxidant experiment, zebrafish (Danio rerio) embryos were treated with different concentrations of APL and then exposed to LPS to induce oxidative stress. Treatment with APL at 50 or 100 µg/mL significantly reduced LPS-induced oxidative stress in the zebrafish, demonstrating the strong antioxidant activity of APL. Moreover, the effect of APL on zebrafish depigmentation was tested by analyzing the tyrosinase activity and melanin content of zebrafish embryos. APL showed a potential reduction in the total melanin content and tyrosinase activity after treatment. This work provided important information for developing a potential natural antioxidant in the field of cosmetics and food.
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Antioxidantes , Pez Cebra , Animales , Antioxidantes/química , Monofenol Monooxigenasa , Lipopolisacáridos , Melaninas/análisis , Flores/química , Agua/análisisRESUMEN
In neurodegenerative diseases, particularly in Parkinson's disease (PD), antinociceptive centers are often implicated in neurodegeneration, leading to persistent pain unresponsive to narcotic substances. This study investigated the periaqueductal gray matter (PAG) and the nucleus raphe magnus (NRM), components of the brain's antinociceptive system. In conditions of rotenone intoxication (an experimental PD model), morphological changes in intracellular structures were observed in PAG and NRM neurons, indicating metabolic disorders characteristic of PD (alterations in the shape and size of neuronal bodies and processes, disruption of acid phosphatase activity in neuron cytoplasm). Under the influence of bacterial melanin and in combination with synoestrol, positive changes in structural properties were observed in PAG and NRM neurons compared to the rotenone model of PD. This included the preservation of the morphological characteristics typical of these brain regions, with cells exhibiting shapes and sizes close to normal. Furthermore, under the influence of these therapeutic agents, an increase in phosphatase activity in cell cytoplasm was detected, indicating an acceleration of metabolic processes (metabolic activation) disrupted by rotenone intoxication. The data obtained suggests that bacterial melanin and synoestrol may act as potential neuroprotective agents against PAG and NRM neurons in the rat brain in the rotenone model of PD. Further research is needed to elucidate the mechanisms of action of therapeutic doses and propose their use in the treatment of PD, either in isolation or combination therapy.
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Enfermedad de Parkinson , Núcleos del Rafe , Animales , Núcleos del Rafe/fisiología , Enfermedad de Parkinson/tratamiento farmacológico , Rotenona/farmacología , Rotenona/análisis , Melaninas/análisis , AnalgésicosRESUMEN
BACKGROUND: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. OBJECTIVES: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. METHODS: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. RESULTS: In bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. CONCLUSIONS: Changes in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores. This trial was registered at clinicaltrials.gov as NCT04056624.
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Dieta , Verduras , Humanos , Carotenoides , Frutas/química , Hemoglobinas/análisis , Melaninas/análisis , PielRESUMEN
BACKGROUND: Skin tone and pigmented regions, associated with melanin and hemoglobin, are critical indicators of skin condition. While most prior research focuses on pigment analysis, the capability to simulate diverse pigmentation conditions could greatly broaden the range of applications. However, current methodologies have limitations in terms of numerical control and versatility. METHODS: We introduce a hybrid technique that integrates optical methods with deep learning to produce skin tone and pigmented region-modified images with numerical control. The pigment discrimination model produces melanin, hemoglobin, and shading maps from skin images. The outputs are reconstructed into skin images using a forward problem-solving approach, with model training aimed at minimizing the discrepancy between the reconstructed and input images. By adjusting the melanin and hemoglobin maps, we create pigment-modified images, allowing precise control over changes in melanin and hemoglobin levels. Changes in pigmentation are quantified using the individual typology angle (ITA) for skin tone and melanin and erythema indices for pigmented regions, validating the intended modifications. RESULTS: The pigment discrimination model achieved correlation coefficients with clinical equipment of 0.915 for melanin and 0.931 for hemoglobin. The alterations in the melanin and hemoglobin maps exhibit a proportional correlation with the ITA and pigment indices in both quantitative and qualitative assessments. Additionally, regions overlaying melanin and hemoglobin are demonstrated to verify independent adjustments. CONCLUSION: The proposed method offers an approach to generate modified images of skin tone and pigmented regions. Potential applications include visualizing alterations for clinical assessments, simulating the effects of skincare products, and generating datasets for deep learning.
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Trastornos de la Pigmentación , Pigmentación de la Piel , Humanos , Melaninas/análisis , Piel/diagnóstico por imagen , Piel/química , Eritema , Hemoglobinas/análisisRESUMEN
BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.
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Melaninas , Melanosis , Humanos , Melaninas/análisis , Melanocitos/química , Melanocitos/patología , Piel/patología , Epidermis/patología , Rayos UltravioletaRESUMEN
The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates. They are produced in melanocytes in the epidermis, hair follicles, the choroid, the iris, the inner ear, and other tissues. The diversity of colors in animals is mainly caused by the quantity and quality of their melanin, such as by the ratios of EM versus PM. We have developed micro-analytical methods to simultaneously measure EM and PM and used these to study the biochemical and genetic fundamentals of pigmentation. The photoreactivity of melanin has become a major focus of research because of the postulated relevance of EM and PM for the risk of UVA-induced melanoma. Our biochemical methods have found application in many clinical studies on genetic conditions associated with alterations in pigmentation. Recently, besides chemical degradative methods, other methods have been developed for the characterization of melanin, and these are also discussed here.
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Melaninas , Melanoma , Animales , Melaninas/análisis , Melanocitos , Pigmentación , Epidermis , Melanoma/químicaRESUMEN
In Parkinson's disease, the depletion of iron-rich dopaminergic neurons in nigrosome 1 of the substantia nigra precedes motor symptoms by two decades. Methods capable of monitoring this neuronal depletion, at an early disease stage, are needed for early diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue microstructure and in particular, to iron. However, the exact mechanisms of MRI contrast in the substantia nigra are not well understood, hindering the development of powerful biomarkers. In the present report, we illuminate the contrast mechanisms in gradient and spin echo MR images in human nigrosome 1 by combining quantitative 3D iron histology and biophysical modeling with quantitative MRI on post mortem human brain tissue. We show that the dominant contribution to the effective transverse relaxation rate (R2*) in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. This contribution is appropriately described by a static dephasing approximation of the MRI signal. We demonstrate that the R2* contribution from dopaminergic neurons reflects the product of cell density and cellular iron concentration. These results demonstrate that the in vivo monitoring of neuronal density and iron in nigrosome 1 may be feasible with MRI and provide directions for the development of biomarkers for an early detection of dopaminergic neuron depletion in Parkinson's disease.
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Neuronas Dopaminérgicas/química , Hierro/análisis , Imagen por Resonancia Magnética/métodos , Sustancia Negra/citología , Anciano de 80 o más Años , Biofisica , Ferritinas/análisis , Humanos , Masculino , Melaninas/análisis , Persona de Mediana Edad , Modelos Neurológicos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Programas Informáticos , Sustancia Negra/químicaRESUMEN
Melanoma is a common, highly fatal skin cancer. Photoacoustic imaging can achieve highly sensitive and high-contrast detection of melanin molecules in tissues, also inheriting the high penetration depth and high spatial resolution characteristics of ultrasound imaging, thus it is a very promising non-invasive diagnostic tool for early melanoma. In this work, we built an acoustic-resolution-based photoacoustic microscopy system, using 1064 nm/532 nm pulsed light to observe melanoma in the back of a mouse with simultaneous photoacoustic/ultrasound imaging. Through the fusion of multi-modal images, accurate positioning of melanoma and its surrounding normal tissues were realized. This work will further promote the application of photoacoustic imaging in the clinical diagnosis of early melanoma.
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Melanoma/diagnóstico por imagen , Imagen Multimodal/métodos , Técnicas Fotoacústicas/métodos , Neoplasias Cutáneas/diagnóstico por imagen , Ultrasonografía/métodos , Animales , Detección Precoz del Cáncer/métodos , Melaninas/análisis , Melanoma/química , Melanoma/patología , Metales , Ratones , Ratones Endogámicos C57BL , Fantasmas de Imagen , Neoplasias Cutáneas/química , Neoplasias Cutáneas/patologíaRESUMEN
Melanins are a diverse group of dark pigments with similar properties. In fungi, the most studied is the dihydroxynaphtalene (DHN)-melanin, present in several species including all the chromoblastomycosis agents, a chronic, disabling, and recalcitrant subcutaneous mycosis. It is synthesized in a pathway known as the pentaketide pathway, which has the agrochemical tricyclazole as an inhibitor, widely used in in vitro studies because it does not prevent the growth of fungi. There are different methodologies for qualitative and quantitative analyses of DHN-melanin, which made it possible to discover its important structural and antioxidant functions, with melanin acting as a protective factor against the host's immune system. Also, it can interact with some of the main antifungals of medical interest, reducing its activity and the susceptibility of fungi to these agents. This review aims to discuss the aspects of DHN-melanin, focusing on chromoblastomycosis, bringing the main findings of the published scientific studies, and highlighting the need for further research to understand this important fungal pathogenicity and a virulence factor.
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Antifúngicos/farmacología , Antioxidantes/farmacología , Ascomicetos/efectos de los fármacos , Cromoblastomicosis/tratamiento farmacológico , Melaninas/farmacología , Naftoles/farmacología , Ascomicetos/patogenicidad , Humanos , Melaninas/análisis , Naftoles/análisisRESUMEN
The melanin fluorescence emitted by pigment cells of the human skin has been a central research topic for decades, because melanin, on the one hand, protects against (solar) radiation in the near-UV range, whereas on the other hand, melanocytes are the starting point for the malignant transformation into melanoma. Until recently, however, melanin fluorescence was not accessible in the context of conventional spectroscopy, because it is ultraweak and is overshadowed by the more intense so-called autofluorescence of endogenous fluorophores. The advent of a new method of laser spectroscopy has made this melanin fluorescence measurable in vivo. A stepwise two-photon absorption with 800 nm photons is used, which more selectively excites melanin (dermatofluoroscopy). Our review summarizes the experimental results on melanin fluorescence of the four types of cutaneous pigment cells from healthy and malignant tissues. Outstanding is the finding that different types of melanocytes (i.e., melanocytes of common nevi, versus dysplastic nevi or versus melanoma cells) show characteristically different fluorescence spectra. The possibilities of using this melanin fluorescence for melanoma diagnosis are shown. Moreover, the uniform fluorescence spectra emitted by different melanoma subtypes are essential. Conclusions are drawn about the molecular processes in the melanosomes that determine fluorescence. Finally, experimental suggestions for further investigations are given.
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Melaninas/metabolismo , Melanocitos/metabolismo , Melanoma/metabolismo , Transformación Celular Neoplásica/patología , Fluorescencia , Humanos , Melaninas/análisis , Melanoma/clasificación , Melanoma/fisiopatología , Piel/patología , Neoplasias Cutáneas/patología , Análisis Espectral/métodosRESUMEN
Ommochromes are one of the least studied groups of natural pigments, frequently confused with melanin and, so far, exclusively found in invertebrates such as cephalopods and butterflies. In this study focused on the purple color of the shells of a mollusk, Crassostrea gigas, the first evidence of a metabolite of ommochromes, xanthurenic acid (XA), was obtained by liquid chromatography combined with mass spectrometry (UPLC-MS). In addition to XA and various porphyrins previously identified, a second group of high molecular weight acid-soluble pigments (HMASP) has been identified with physicochemical and structural characteristics similar to those of ommochromes. In addition, fragmentation of HMASP by tandem mass spectrometry (MS/MS) has revealed a substructure common to XA and ommochromes of the ommatin type. Furthermore, the presence of melanins was excluded by the absence of characteristic by-products among the oxidation residues of HMASP. Altogether, these results show that the purple color of the shells of Crassostrea gigas is a complex association of porphyrins and ommochromes of potentially ommatin or ommin type.
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Exoesqueleto/química , Crassostrea/química , Metaboloma , Fenotiazinas/metabolismo , Pigmentación , Xanturenatos/análisis , Ácidos/química , Animales , Melaninas/análisis , Melaninas/química , Oxidación-Reducción , SolubilidadRESUMEN
Melanins are synthesized macromolecules that are found in all biological kingdoms. These pigments have a myriad of roles that range from microbial virulence to key components of the innate immune response in invertebrates. Melanins also exhibit unique properties with potential applications in physics and material sciences, ranging from electrical batteries to novel therapeutics. In the fungi, melanins, such as eumelanins, are components of the cell wall that provide protection against biotic and abiotic elements. Elucidation of the smallest fungal cell wall-associated melanin unit that serves as a building block is critical to understand the architecture of these polymers, its interaction with surrounding components, and their functional versatility. In this study, we used isopycnic gradient sedimentation, NMR, EPR, high-resolution microscopy, and proteomics to analyze the melanin in the cell wall of the human pathogenic fungus Cryptococcus neoformans We observed that melanin is assembled into the cryptococcal cell wall in spherical structures â¼200 nm in diameter, termed melanin granules, which are in turn composed of nanospheres â¼30 nm in diameter, termed fungal melanosomes. We noted that melanin granules are closely associated with proteins that may play critical roles in the fungal melanogenesis and the supramolecular structure of this polymer. Using this structural information, we propose a model for C. neoformans' melanization that is similar to the process used in animal melanization and is consistent with the phylogenetic relatedness of the fungal and animal kingdoms.
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Pared Celular/metabolismo , Cryptococcus neoformans/metabolismo , Melaninas/química , Cryptococcus neoformans/clasificación , Levodopa/química , Espectroscopía de Resonancia Magnética , Melaninas/análisis , Melaninas/metabolismo , Microscopía Electrónica de Transmisión , Nanopartículas/química , Tamaño de la Partícula , Filogenia , ProteómicaRESUMEN
Higher cutaneous melanin reduces vitamin D3 production. This may increase fracture risk. We found that cutaneous melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. Melanin density either acts as a surrogate marker or its relationship with fracture changes with time. INTRODUCTION: Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, prevalent and incident fractures in a cohort of exclusively older Caucasian adults. METHODS: 1072 community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Participants were followed up at 2.5 (n = 879), 5 (n = 767), and 10 (n = 571) years after the baseline assessment. Prevalence and number of symptomatic fractures were assessed by questionnaire. RESULTS: Higher melanin density was independently associated with greater prevalence of any fracture (RR 1.08, p = 0.03), vertebral fracture (RR 1.41, p = 0.04) and major fracture (RR 1.12, p = 0.04) and the number of fractures (RR 1.09, p = 0.04) and vertebral fractures (RR 1.47, p = 0.04) in cross-sectional analysis. At the 2.5-year follow-up, higher melanin density was associated with incident fractures (RR 1.42, p = 0.01) and major fractures (RR 1.81, p = 0.01) and the number of incident fractures (RR 1.39, p = 0.02) and major fractures (RR 2.14, p = 0.01). The relationship between melanin density and incident fracture attenuated as the duration of follow-up increased and was not significant at the 5- or 10-year follow-up. CONCLUSIONS: Constitutive melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. This suggests melanin density either acts as a surrogate marker for an unmeasured fracture risk factor or the relationship between melanin density and fracture changes with time.
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Fracturas Óseas , Melaninas , Fracturas de la Columna Vertebral , Adulto , Anciano , Anciano de 80 o más Años , Densidad Ósea , Estudios Transversales , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Humanos , Melaninas/análisis , Persona de Mediana Edad , Factores de Riesgo , Fracturas de la Columna Vertebral/epidemiologíaRESUMEN
Environmental stress often causes phenotypic changes among pathogenic cryptococci, such as altered antifungal susceptibility, changes in capsule and melanin formation, as well as altered levels of the membrane sterol and antifungal target, ergosterol. We therefore hypothesised that nitrogen limitation, a prevalent environmental stress in the natural habitat of these yeasts, might affect virulence and antifungal susceptibility. We tested the effect of different nitrogen concentrations on capsule, melanin and ergosterol biosynthesis, as well as amphotericin B (AmB) and fluconazole (FLU) susceptibility. This was achieved by culturing cryptococcal strains representing Cryptococcus neoformans and Cryptococcus gattii in media with high (0.53 g/l), control (0.42 g/l) and low (0.21 g/l) NH4Cl concentrations. India ink staining was used to determine capsule thickness microscopically, while melanin and ergosterol content were determined spectrophotometrically. We found that lower nitrogen concentrations enhanced both ergosterol and capsule biosynthesis, while a variable effect was observed on melanisation. Evaluation of drug tolerance using time-kill methodology, as well as tests for FLU heteroresistance, revealed that the low nitrogen cultures had the highest survival percentages in the presence of both AmB and FLU, and showed the highest frequency of FLU heteroresistance, suggesting that nitrogen concentration may indeed influence drug tolerance.