Red Hair Research Articles

Diagnosis of a suspicious Spitzoid nevus

The mortality rate of cutaneous melanoma in the United States continues to increase year over year. Research supports that the development of melanoma is determined by genetics, the environment, and an individual’s behavior with certain phenotypic features, such as fair skin, red hair, multiple moles, and a prior history of sunburns, placing some individuals at greater risk of developing melanoma. New treatments have improved the survival rate of individuals with melanoma; however, the proper diagnosis of this deadly cancer is imperative. Histopathology remains the gold standard for diagnosing melanoma, sometimes with the help of immunohistochemistry staining. When a clear diagnosis cannot be made, genomic testing can be a helpful tool to differentiate between a benign and malignant lesion. Here, we present the case of a 27-year-old male patient with Fitzpatrick skin type III who presented to the dermatology clinic with a growing pink bump on his left upper arm. After a shave biopsy, the dermatopathologist reported that the lesion was a suspicious-looking Spitzoid nevus, for which a wide excision by surgical oncology was recommended. The immunohistochemistry staining did not secure a diagnosis of benign or malignant. As the diagnosis was inconclusive, the specimen was sent for a gene expression profile test, which came back positive, indicating malignant melanoma. This case illustrates how diagnostic and prognostic genomic testing can be used to identify a malignant melanoma and determine the likelihood of metastasis, thus guiding the patient's follow-up plan. It also illustrates how genomic testing might help the patient avoid unnecessary and costly medical procedures with potential side effects.

The Glorious Return of the Supernatural to the Novel: An Analysis of the New Conception of Reality in the Stories of Efrasiyab and the Red-Haired Woman

Realism lingered quite long in Turkish literature. From the 1900s onwards, realism and naturalism were prominent movements. If the often-despised detective novels are put aside, there was hardly any room for the extraordinary in fiction. During the socialist realism era, realism almost became the sole movement and was strong until the 1950s. Despite the appearance of the first modern literature from that time on, it kept its prominent position until the 1970s. What realism skillfully pushed outside the literature were the supernatural, the magic, the extraordinary, the mythical, and the fairy-tale-inspired narration. However, these elements made a comeback in the 1980s and quickly spread in the 2000s. Today, almost all fiction comprises these elements, and this time not in the form of the despised "B-literature," but in a very mainstream way. Today, the fantastic, detective novels, historical/biographical fiction and science fiction of all sorts are living their golden age. Often fused with myths, fairy-tales, epics, and such, this new type of fiction is like a scene where the supernatural has made its glorious comeback. In this paper, I will show the different ways and forms of this comeback in two novels: The Stories of Efrasiyab by İhsan Oktay Anar and The Red Haired Woman by Orhan Pamuk. Analyzing these novels based on their approach to the supernatural, I will try to show how myths and reality mix, what type of novel universe they create, and what this new reality stands for in the postmodern times we live in.

Uncovering molecular mechanisms for amelanotic/hypopigmented primary cutaneous melanoma.

A portion of approximately 2-20% of cutaneous melanoma (CM) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. Since the degree to which somatic mutations and copy number aberrations (CNA) in genes associated with skin-lightening or albinism may contribute to the loss of tumour pigmentation in AHM samples has not yet been addressed, we have investigated loss of function mutations of key pigmentation genes in matched germline and AHM as well as pigmented melanoma (PM) tumour DNA samples. An analysis of clinical and histopathological characteristics together with whole exome sequencing data of 34 fresh frozen primary CM, graded according to the amount of pigmentation present was performed. Together with germline and somatic variant analysis, 30 samples were previously analysed for CNA changes. This study focussed on germline and somatic variants in the coding region of 16 genes known to be associated with albinism/hypopigmentation or variation in human pigmentation in all samples. Chromosomal regions encompassing these 16 genes were examined for DNA copy loss or gain. The finding that red hair related MC1R and TYR R402Q loss of activity gene variant alleles and genotypes are associated with AHM was validated in this study. Germline AHM-related gene variants were enriched in 70% (n=7 of 10) of AHM patients vs 8.3% (n=2 of 24) of PM patients. This surprisingly high frequency of rare germline variants in AHM patients constitutes the "first hit" and confirms that AHM patients are more likely to be albinism allele carriers than patients with PM. Next, in CNA analysis of each tumour sample, 50% (n=4 of 8) AHM samples with a pigmentation gene variant had LOH in the region containing the corresponding gene, and 25% (=2 of 8) had loss-of-heterozygosity (LOH) in chromosomal regions of two AHM-related genes. This study proposes that the likely molecular mechanism for development of amelanogenesis in AHM is carriage of an albinism/hypopigmentation allele followed by LOH of the corresponding gene in the tumour.

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

Association Between Natural Hair Color, Race, and Alopecia.

Limited epidemiologic data has suggested direct associations between hair pigment, race, and incidence of alopecia areata (AA). Here, we examine the relationship between natural hair color, race, and the lifetime risk alopecia. In this case-control study, we included UK Biobank patients of all races and self-reported hair color with diagnoses of AA, androgenetic alopecia (AGA), or scarring alopecia (SA). Multivariable logistic regression was used to detect differences in lifetime risk. Findings reveal a significantly increased risk of AA among individuals with black hair compared to dark brown hair (OR 1.71 [95% CI 1.22-2.38], p < 0.001). Those with red or blonde hair showed a decreased risk of AA (0.74 [0.56-0.97]; 0.62 [0.41-0.95], p < 0.05). No racial differences in AA prevalence were observed among individuals with black hair. Darker hair colors may be associated with a higher risk of AA, lighter hair colors with a lower risk, and differences in hair color could contribute to previously noted racial variations in AA incidence, potentially influencing dermatologists' perspectives on the disease's epidemiology.

Journey through the spectacular landscape of melanocortin 1 receptor.

The physiological role of α-melanocyte stimulating hormone in regulating integumental pigmentation of many vertebrate species has been recognized since the 1960's. However, its physiological significance for human pigmentation remained enigmatic until the 1990's. α-Melanocyte stimulating hormone and related melanocortins are synthesized locally in the skin, primarily by keratinocytes, in addition to the pituitary gland, and therefore act as paracrine factors for melanocytes. Human melanocytes express the melanocortin 1 receptor, which recognizes α-melanocyte stimulating hormone and the related adrenocorticotropic hormone as agonists. This review summarizes the current knowledge of the pleotropic effects of the activated melanocortin 1 receptor that maintain human melanocyte homeostasis by regulating melanogenesis and the response to environmental stressors, mainly solar radiation. Certain allelic variants of the melanocortin 1 receptor gene are associated with specific pigmentary phenotypes in various human populations. Variants associated with red hair phenotype compromise the function of the encoded receptor. Activation of the human melanocortin 1 receptor regulates eumelanin synthesis and enhances DNA damage response of melanocytes to solar radiation and oxidative stressors. We describe how synthetic selective melanocortin 1 receptor agonists can be efficacious as sunless tanning agents, for treatment of vitiligo and photosensitivity disorders, and for prevention of skin cancer, including melanoma.

Exploring tolerance mechanisms and root morphological development of New Zealand spinach and quinoa across salinity levels

Soil salinity, root sodium concentration, and transpiration rate are important environmental factors impacting plant growth and productivity. This study investigates the salt-coping strategies of two plant species under varying salinity levels: New Zealand spinach species grown at three salinity levels (i.e., 0, 100, and 200 mM NaCl) and three varieties of quinoa, i.e., “Vikinga”, “Dave 407” and “Red Head”, grown with or without salt (i.e., 0 and 100 mM NaCl). The plants were grown on glass fiber sheets (rhizoslides) under controlled laboratory conditions. The relationship between transpiration rate, salinity, and root architecture was analyzed for each species. The root apparatus of New Zealand spinach was significantly more developed in plants grown at 100 mM NaCl compared to both 200 mM NaCl and control. The quinoa varieties responded differently to the increasing salt concentrations, with salt-treated “Red Head” plants significantly reducing their total root length and salt-treated “Vikinga” significantly reducing its lateral roots compared to the controls. Salt concentration near New Zealand spinach roots was lower compared to areas without roots, suggesting active salt uptake. In contrast, quinoa rhizoslides exhibited higher salt concentration in proximity to the roots, indicative of salt exclusion. The study provides insights into the adaptation and tolerance mechanisms of these two species to salinity, elucidating the mechanisms by which plants regulate their sodium uptake and root growth. The obtained results suggest that not only the selection of appropriate plant species (halophytes), but also varieties, plays a crucial role in improving crop productivity in salt-affected areas. Elucidating the salt-coping mechanisms of halophytes in relation to soil and climatic conditions is important to better predict their behavior in various saline environments.

The Body of the Antagonist in Current Spanish Novels for Children and Young Adults

This article examines the bodies of antagonists in Spanish award-winning children’s and young adult novels between 2018 and 2020. Qualitative analysis using software was used to categorise antagonists’ physical descriptions and identify common types and characteristics. There are attractive antagonists with pleasant physical appearances that conceal an inner malevolence, while others adhere more closely to the traditional prototype with physically unattractive features beyond normative standards of beauty. The predominance of male bodies as antagonists is highlighted, reflecting cultural stereotypes of violence and aggression associated with masculinity. In addition, common features such as reddish hair, facial hair, a penetrating gaze, and a smile that anticipates malice are observed. Although expected features such as androidisation are not evident, the analysis shows how cultural processes of physical normalisation are either reinforced or challenged.

Происхождение и лексико-семантическая характеристика цветообозначения ерән ‘рыжий’ в башкирском языке

The article examines the origin, historical development and semantics of the word yeran ‘red’ in the Bashkir language. The relevance of the study lies in the fact that for the first time in Bashkir linguistics, this color designation is subjected to a comprehensive etymological, comparative historical, and lexico-semantic analysis. During the scientific analysis, it was revealed that the yeran ‘red’ lexeme is characterized by an ancient origin: scientists have restored its proto-Turkic (*jẹgre-n ‘red (about the color of a horse); deer, gazelle, antelope’), proto-Altai (*negre ‘type of deer’) forms. It is established that the first fixation of the word falls on the ancient Turkic period. The word is found in almost all Turkic languages in the meaning of ‘red color of a horse or other animals’, in Kipchak – in the designation of red hair, mustache, beard, in some Turkic languages – as the names of animals ‘roe deer, gazelle, antelope’ (‘roe deer’, ‘gazelle’, ‘antelope’). It is assumed that jagren ‘chestnut’ in the Turkic languages originally meant the color of the horse’s skin, over time the semantics of the word expanded – it began to be applied to the color of human hair, then gradually to all objects of reddish color, reddish hue. In Bashkir, eran, like the reflexes *jẹgre-n in many Turkic languages, functions in the meanings of ‘red (about the suit, about the hair, mustache, beard)’. Related lexemes are found in other Altaic languages: in Korean and Tungusic-Manchurian languages, they are used in the meanings of ‘roe deer’, ‘vazhenka (female reindeer)’. In the Mongolian and Tungusic-Manchu languages, the meaning of the word ‘red horse color’ is a Turkic loan. The Turkic word entered the Russian language as well: Igreny ‘light red (about horse color)’.

Red-Haired People's Altered Responsiveness to Pain, Analgesics, and Hypnotics: Myth or Fact?-A Narrative Review.

Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.

Infertility in POMC-deficient mice

The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and its product is cleaved into several peptides including the melanocyte stimulating hormones (α, β, or γ-MSH), adrenocorticotropic hormone (ACTH), and beta-endorphin. Alpha-MSH is involved in regulating appetite, sexual behavior, and melanin, while ACTH regulates secretion of glucocorticoids from the adrenal cortex. Humans who have a POMC mutation either produce an abnormally short version of POMC or are missing the protein completely and therefore lack these hormones. This has biological consequences including red hair and fair skin, early-onset obesity (due to severe hyperphagia), and potentially hypothyroidism, hypogonadism, and infertility. Many of these same effects are seen with mice containing this deficiency. We are interested in studying infertility through a mouse model of hypothalamic-specific POMC-deficiency. These mice also experience early-onset obesity and infertility. Estradiol is a key reproductive hormone that is essential for fertility. POMC deficiency may lead to hypogonadism, which can cause low levels of estrogen so we hypothesize that POMC-deficient mice have reduced estrogen levels, which may contribute to their infertility. To test this hypothesis, we will measure estrogen levels in POMC-deficient mice at different stages of the estrus cycle using an estradiol ELISA kit. We expect the POMC-deficient mice to have lower estrogen levels than control mice. We also plan to use liquid chromatography mass spectrometry (LC-MS) to measure estrogen levels. Before collecting the blood samples, vaginal cell samples are obtained and viewed under a microscope to analyze the ratio of cells and determine which stage the females were in—proestrus, estrus, metestrus, or diestrus. Blood samples are then collected into 1.5 mL microcentrifuge tubes with 10 microliters of 0.5 M EDTA to prevent blood clotting. After blood is collected, it is centrifuged at 2,000 g for 20 minutes at 4 degrees Celsius. The plasma is then stored at -80 degrees Celsius until analysis. Based on preliminary results we expect the POMC deficient mice to have reduced estrogen and/or altered levels throughout the cycle. So far, our results have indicated that POMC-deficient female mice have abnormal estrus cycles and also reduced uterine weights. The conclusions from this study will help us understand more about the causes of infertility in POMC-deficient mice, which may also lead to greater understanding on how to treat humans with infertility due to a POMC mutation. Support for this research was provided by IRACDA grant NIHK12GM111725 to Z.T. and UVU Scholarly Activities Grant to A.G. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Learning epistatic polygenic phenotypes with Boolean interactions.

Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surrounding MC1R and novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surrounding HLA-DRB1, a variant previously associated with MS in several populations. Taken together, these results highlight the potential for epiTree rankings to help reduce the design space for follow up experiments.

Kelayakan Hair Tonic Jahe Pada Jenis Rambut Rontok

This study aims to analyze a ginger-based hair tonic product in preventing hair loss. The hair tonic is made from natural ginger, which has been known for its potential in improving hair health and preventing hair loss. The study was conducted using a quantitative experimental method involving 12 female participants with hair loss issues. The participants were divided into a treatment group that used ginger hair tonic and a control group that used other commercial products proven effective in preventing hair loss. The results showed that the use of ginger hair tonic significantly reduced the hair loss rate in the participants of the treatment group. During the 2-week usage period, the participants reported increased hair thickness, significant reduction in hair loss, as well as improved shine and softness of their hair. Hedonic testing was also conducted to evaluate the users' preference for the ginger hair tonic. The results of the hedonic test showed that the majority of respondents liked the aroma and absorption power of the ginger hair tonic, but there were some uncertainties regarding the texture and color of the product. Nevertheless, the ginger hair tonic still showed potential as a preferred product among the majority of respondents. In further development, it is important to consider the feedback from the hedonic test to improve the formulation of the ginger hair tonic. This study provides promising preliminary evidence on the feasibility of using ginger hair tonic in naturally preventing hair loss.

Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.

To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function. Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells. Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC50 of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively. It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.

Epigenetic regulatory differentiation of hematopoietic stem cells to the red lineage Running head: Epigenetics of erythropoiesis

The differentiation process from hematopoietic (HSCs) to mature red blood cells (RBCs) is characterized by remarkable precision and is tightly controlled from the initial lineage commitment to eventual terminal differentiation. Erythropoiesis is the dynamic journey of HSCs through various functional and phenotypic stages. The physiological course of erythrogenesis is intricately linked to significant changes in chromatin accessibility, necessitating precise coordination of transcription factors and epigenetic elements. This review presents a comprehensive overview of recent investigations into the molecular-level epigenetic regulatory factors that influence differentiation of the erythroid lineage. This encompasses the exploration of transcriptional, post-transcriptional, and post-translational regulatory processes. The intricate interplay of epigenetic and transcriptional regulatory networks in erythroid differentiation not only enhances our understanding of this fundamental biological process, but also provides valuable insights into the underlying mechanisms contributing to the pathogenesis of disorders associated with abnormal erythroid development. These findings hold significant promise for the development of novel therapeutic strategies to address these diseases and improve patient outcomes.

Boudica, the Warrior Queen, as seen through DevianArt: Why pop culture proves to be so informative

The paper aims to investigate the image of the Warrior Queen Boudica (Boudicca, Boadicea) in contemporary pop culture through the lens of the website DeviantArt (®), providing valuable information about the countries and the gender of the creators, along with the possibility of studying the creative scene in real-time by artists who are most often not professionals but young creators and even more importantly, young female creators. From a general point of view, Boudica-the-Warrior is winning the battle in the other representations of Boudica and certainly over Boudica-the-Mother. But while there is hardly any difference when it comes to carrying weapons, this is not the case for the portrayal of aggression. Here, the rate is twice as high among male contributors. The difference is even greater for the sexualization of Boudica’s body. Several general trends observed for Boudica are also true for Cleopatra. Each is represented more often standing alone. Each is more often described as a powerful embodiment of strong women: in arms for Boudica, with felines for Cleopatra. And in each case, their images have been simplified in order to be understood by large audiences. A sexualized Egyptian (i.e. pharaonic) woman is now necessarily Cleopatra. The same holds true for Boudica: a warrior woman with red hair and blue paint on her visage seems only to refer to her.

THE IMAGE OF ANNA YAROSLAVNA IN FINE ARTS: PAST AND PRESENT

The article focuses on the iconography of Anna Yaroslavna (around 1032-between 1075 and 1089), the daughter of Yaroslav Mudry (983/98-1054), who was married to Henry I (1027-1060) and acquired the status of Queen of France. The study is based on the most famous portraits created by artists from the Middle Ages to the present day in various types of visual arts - sculpture, painting, graphics, numismatics. It is not known for certain what the princess looked like – rather insignificant evidence about her appearance has been preserved. In historical chronicles, the red hair color of the young wife of Henry I is primarily noted. More often, character traits are emphasized – kindness, generosity, humility, self-sacrifice. Portraits of the daughter of Yaroslav Mudry during his lifetime cause heated discussions in scientific circles. It is hypothesized that the sons and not daughters of Yaroslav the Wise are depicted in St. Sophia Cathedral (11th century). And on the copy of the 18th century from a drawing by the Dutch artist A. van Westerfeld in 1651, another couple is represented – Volodymyr Svyatoslavych and his wife Anna (baptizers of Rus) accompanied by eight princes and princesses. Engraved and sculptural portraits of the 17th century, despite the fashionable image of the era, reveal certain characteristic features of Anna Yaroslavna – thinness, general elegance, elongated face oval. Modern Ukrainian artists (V. Znoba, M. Znoba, G. Sevruk, V. Stelmakh), recreating the image of Anna Yaroslavna, are guided by the well-known engraved image of the Flemish artist Jacobus de Bie in 1643. At the same time, each portrait is distinguished by the author's decision and virtuoso mastery of the material. The presented article is not only the first intelligence covering pictorial and historical sources. The collected material testifies to the significant contribution of national history to the development of the European political and cultural space, is a demonstration of unity and friendly relations between Ukraine and France.

Myth and Modernity: Feminism and Identity in Orhan Pamuk’s The Red Haired Woman

Myth and Modernity: Feminism and Identity in Orhan Pamuk’s The Red Haired Woman

Peripheral MC1R Activation Modulates Immune Responses and is Neuroprotective in a Mouse Model of Parkinson’s Disease

BackgroundMelanocortin 1 receptor (MC1R) is a key pigmentation gene, and loss-of-function of MC1R variants that produce red hair may be associated with Parkinson’s disease (PD). We previously reported compromised dopaminergic neuron survival in Mc1r mutant mice and dopaminergic neuroprotective effects of local injection of a MC1R agonist to the brain or a systemically administered MC1R agonist with appreciable central nervous system (CNS) permeability. Beyond melanocytes and dopaminergic neurons, MC1R is expressed in other peripheral tissues and cell types, including immune cells. The present study investigates the impact of NDP-MSH, a synthetic melanocortin receptor (MCR) agonist that does not cross BBB, on the immune system and the nigrostriatal dopaminergic system in mouse model of PD.MethodsC57BL/6 mice were treated systemically with MPTP.HCl (20 mg/kg) and LPS (1 mg/kg) from day 1 to day 4 and NDP-MSH (400 µg/kg) or vehicle from day 1 to day 12 following which the mice were sacrificed. Peripheral and CNS immune cells were phenotyped and inflammatory markers were measured. The nigrostriatal dopaminergic system was assessed behaviorally, chemically, immunologically, and pathologically. To understand the role of regulatory T cells (Tregs) in this model, CD25 monoclonal antibody was used to deplete CD25 + Tregs.ResultsSystemic NDP-MSH administration significantly attenuated striatal dopamine depletion and nigral dopaminergic neuron loss induced by MPTP + LPS. It improved the behavioral outcomes in the pole test. Mc1r mutant mice injected with NDP-MSH in the MPTP and LPS paradigm showed no changes in striatal dopamine levels suggesting that the NDP-MSH acts through the MC1R pathway. Although no NDP-MSH was detected in the brain, peripheral, NDP-MSH attenuated neuroinflammation as observed by diminished microglial activation in the nigral region, along with reduced TNF-α and IL1β levels in the ventral midbrain. Depletion of Tregs was associated with diminished neuroprotective effects of NDP-MSH.ConclusionsOur study demonstrates that peripherally acting NDP-MSH confers protection on dopaminergic nigrostriatal neurons and reduces hyperactivated microglia. NDP-MSH modulates peripheral immune responses, and Tregs may be involved in the neuroprotective effect of NDP-MSH.

『원사(元史)』에 기록된 궁정악대(宮廷樂隊) 연구

The purpose of this study was to consider court musical bands (宫廷樂隊) in the Mongol(Yuan)empire. It is what interpreted a piece of music that is accompanied with Muscal performance procedures in Akeumwangdae (樂音王隊), Suseongdae (壽星隊), Yeakdae (禮樂隊), Seolbeopdae (說法隊), which are four court ‘musical bands’ (宮廷樂隊) of having been recorded in 『Yuan-shi(元史)』 ｢Liyuezhi(禮樂志)｣.&#x0D; In terms of 4 musical bands in the Mongol (Yuan) empire, first, Muscal performance procedures seems to having succeeded in the archetype of the previous generation, but has a difference in which a variety of mask dances appear such as ‘Mask dance with red hair and blue face (紅發青面具舞).’ Second, it is composed of Gochwiakgi (鼓吹樂器, wind and percussion instruments) in percussion instruments and wind instruments. There are diverse percussion instruments, which have been unable to be seen in the last period, such as Chalgo (札鼓) or Hwago (和鼓). Third, a musical piece has the mainstream as Sanqu (散曲), which appeared in the Yuan dynasty(元代) of being interrelated even with Yuanqu (元曲). There are also a few musical pieces that were accepted from abroad along with Buddhist culture.&#x0D; Considering the record in 『Yuan-shi (元史)』 ｢Liyuezhi (禮樂志)｣, four musical bands in the Mongol (Yuan) empire have new court music in the Mongol (Yuan) empire by which Buddhist music in Western Xia (西夏) or Xiyu (西域) was absorbed in the music culture of Mongolia race.