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https://www.readbyqxmd.com/read/28738163/a-local-duplication-of-the-i-melanocortin-receptor-1-i-locus-in-i-astyanax-i
#1
Joshua B Gross, James Weagley, Bethany A Stahl, Li Ma, Luis Espinasa, Suzanne E McGaugh
In this study, we report evidence of a novel duplication of <i>Melanocortin receptor 1 (Mc1r)</i> in the cavefish genome. This locus was discovered following the observation of excessive allelic diversity in a ~820 bp fragment of <i>Mc1r</i> amplified via degenerate PCR from a natural population of <i>Astyanax aeneus</i> fish from Guerrero, Mexico. The cavefish genome reveals the presence of two closely related <i>Mc1r</i> open reading frames separated by a 1...
July 24, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28735903/genetics-of-non-syndromic-childhood-obesity-and-the-use-of-high-throughput-dna-sequencing-technologies
#2
REVIEW
Ana Carolina Proença da Fonseca, Claudio Mastronardi, Angad Johar, Mauricio Arcos-Burgos, Gilberto Paz-Filho
BACKGROUND: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. OBJECTIVES: To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function...
June 16, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28727208/differential-expression-of-appetite-regulating-genes-in-avian-models-of-anorexia-and-obesity
#3
Jiaqing Yi, Jingwei Yuan, Elizabeth R Gilbert, Paul B Siegel, Mark A Cline
Chickens from lines that have been selected for low (LWS) or high (HWS) juvenile body weight for more than 57 generations provide a unique model to research appetite regulation. The LWS display different severities of anorexia while all HWS become obese. Herein we measured mRNA abundance of various factors in appetite-associated nuclei in the hypothalamus. The lateral hypothalamus (LHA), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), dorsomedial nucleus (DMN), and arcuate nucleus (ARC) were collected from 5 day-old chicks that were fasted for 180 minutes or provided continuous access to food...
July 20, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28720755/functional-variants-of-the-melanocortin-4-receptor-associated-with-the-odontoceti-and-mysticeti-suborders-of-cetaceans
#4
Liyuan Zhao, Xiaofan Zhou, Antonis Rokas, Roger D Cone
Cetaceans, a group of mammals adapted to the aquatic environment that descended from terrestrial artiodactyls, exhibit tremendous interspecific differences in a number of phenotypes, including feeding behavior, such as filter feeding in the Mysticeti vs prey-hunting Odontoceti, and size, with the smallest cetacean, the vaquita, at 1.4 meters and the largest, the blue whale, reaching 33 meters. The Melanocortin-4 receptor (MC4R) regulates food intake, energy balance, and somatic growth in both mammals and teleosts...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715181/structural-insights-into-selective-ligand-receptor-interactions-leading-to-receptor-inactivation-utilizing-selective-melanocortin-3-receptor-antagonists
#5
Minying Cai, Udaya Kiran Marelli, Blake Mertz, Johannes G Beck, Florian Opperer, Florian Rechenmacher, Horst Kessler, Victor J Hruby
Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to mul-tiple binding and functional selectivity towards melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conforma-tional studies in solution of two selective antagonists of the third isoform of the melanocortin re-ceptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His6-D-Nal(2')7-NMe-Arg8-Trp9-Lys]-NH2 (15) and Ac-Nle-c[Asp-His6-D-Nal(2')7-NMe-Arg8-NMe-Trp9-NMe-Lys]-NH2 (17)...
July 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28714883/nmr-insights-into-the-structure-function-relationships-in-the-binding-of-melanocortin-analogues-to-the-mc1r-receptor
#6
Maurício Morais, Héctor Zamora-Carreras, Paula D Raposinho, Maria Cristina Oliveira, David Pantoja-Uceda, João D G Correia, M Angeles Jiménez
Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ (CycN-K6) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ (CycN-K7)...
July 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28699792/novel-approaches-to-the-design-of-bioavailable-melanotropins
#7
Yang Zhou, Minying Cai
The melanocortin system is a primordial and critical system for survival, involved in a wide variety of physiological functions. It includes melanocortin receptors (MCRs) and melanotropin ligands (MCLs). MCRs are important drug targets that can regulate several key physiological processes. Extensive efforts have been made to develop peptide and peptidomimetics targeting melanocortin receptors including MC1R, MC3R, MC4R and MC5R. Most research is focused on developing potent and selective melanotropins. However, developing bioavailable melanotropins remains challenging...
July 12, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28690493/emerging-signaling-pathway-in-arcuate-feeding-related-neurons-role-of-the-acbd7
#8
REVIEW
Damien Lanfray, Denis Richard
The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28685029/does-gastric-bypass-surgery-change-body-weight-set-point
#9
REVIEW
Z Hao, M B Mumphrey, C D Morrison, H Münzberg, J Ye, H R Berthoud
The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28677151/getting-a-tan-without-getting-sik
#10
John D'Orazio
It has been more than a decade since the Fisher lab reported that epidermal eumelanin could be robustly up-regulated by topical application of forskolin, an adenylyl cyclase activator that bypassed a defective melanocortin 1 receptor (Mc1r) to promote melanin synthesis. Eumelanin induction protected fair-skinned mice from UV damage using an animal model that recapitulates many of the features of pigmented human epidermis. Through constitutive production of stem cell factor (Kit ligand) in the basal epidermis, the K14-Scf transgenic mouse retains interfollicular melanocytes in the skin and therefore accumulates melanin pigments in the epidermis...
July 5, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28676423/functional-interplay-between-secreted-ligands-and-receptors-in-melanoma
#11
REVIEW
Cecilia Herraiz, Celia Jiménez-Cervantes, Berta Sánchez-Laorden, José C García-Borrón
Melanoma, the most aggressive form of skin cancer, results from the malignant transformation of melanocytes located in the basement membrane separating the epidermal and dermal skin compartments. Cutaneous melanoma is often initiated by solar ultraviolet radiation (UVR)-induced mutations. Melanocytes intimately interact with keratinocytes, which provide growth factors and melanocortin peptides acting as paracrine regulators of proliferation and differentiation. Keratinocyte-derived melanocortins activate melanocortin-1 receptor (MC1R) to protect melanocytes from the carcinogenic effect of UVR...
July 1, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28660550/clinical-and-economic-evaluation-of-repository-corticotropin-injection-a-narrative-literature-review-of-treatment-efficacy-and-healthcare-resource-utilization-for-seven-key-indications
#12
REVIEW
Michael Philbin, John Niewoehner, George J Wan
INTRODUCTION: Repository corticotropin injection (RCI; H.P. Acthar(®) Gel; Mallinckrodt Pharmaceuticals Inc., Hampton, NJ) is a highly purified, prolonged-release porcine preparation of adrenocorticotropic hormone (ACTH) analogue that is FDA-approved for treatment of 19 autoimmune and inflammatory disorders. The diverse physiological actions of RCI at the melanocortin receptors (MCRs) affect processes involved in inflammation, pigmentation, steroidogenesis, and immunomodulation. Although RCI has been approved to treat inflammatory and autoimmune diseases for more than 60 years, recent progress in understanding both MCRs and the effects of RCI in modulating immune responses has led to increased interest in RCI as a therapeutic choice...
June 28, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28651519/analysis-of-the-genetic-variation-in-mitochondrial-dna-y-chromosome-sequences-and-mc1r-sheds-light-on-the-ancestry-of-nigerian-indigenous-pigs
#13
Adeniyi C Adeola, Olufunke O Oluwole, Bukola M Oladele, Temilola O Olorungbounmi, Bamidele Boladuro, Sunday C Olaogun, Lotanna M Nneji, Oscar J Sanke, Philip M Dawuda, Ofelia G Omitogun, Laurent Frantz, Robert W Murphy, Hai-Bing Xie, Min-Sheng Peng, Ya-Ping Zhang
BACKGROUND: The history of pig populations in Africa remains controversial due to insufficient evidence from archaeological and genetic data. Previously, a Western ancestry for West African pigs was reported based on loci that are involved in the determination of coat color. We investigated the genetic diversity of Nigerian indigenous pigs (NIP) by simultaneously analyzing variation in mitochondrial DNA (mtDNA), Y-chromosome sequence and the melanocortin receptor 1 (MC1R) gene. RESULTS: Median-joining network analysis of mtDNA D-loop sequences from 201 NIP and previously characterized loci clustered NIP with populations from the West (Europe/North Africa) and East/Southeast Asia...
June 26, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28642375/acquired-resistance-to-corticotropin-therapy-in-nephrotic-syndrome-role-of-de-novo-neutralizing-antibody
#14
Pei Wang, Yan Zhang, Yu Wang, Andrew S Brem, Zhangsuo Liu, Rujun Gong
There is increasing evidence supporting the use of corticotropin as an alternative treatment of refractory proteinuric glomerulopathies. The efficacy of short-acting corticotropin, however, remains unknown and was tested here in an adolescent with steroid-dependent nephrotic syndrome caused by minimal change disease. After developing Cushing syndrome and recently being afflicted with severe cellulitis, the patient was weaned off all immunosuppressants, including corticosteroids. This resulted in a relapse of generalized anasarca, associated with massive proteinuria and hypoalbuminemia...
June 22, 2017: Pediatrics
https://www.readbyqxmd.com/read/28641771/fatigue-in-multiple-sclerosis-is-it-related-to-cytokines-and-hypothalamic-pituitary-adrenal-axis
#15
Aylin Akcali, Fatma Zengin, Sefika Nur Aksoy, Orhan Zengin
BACKGROUND: Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores...
July 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28627277/anti-acne-drugs-in-phase-1-and-2-clinical-trials
#16
REVIEW
Christos C Zouboulis, Clio Dessinioti, Fragkiski Tsatsou, Harald P M Gollnick
Despite the impressive increase of knowledge on acne etiology accumulated during the last 20 years, few efforts have been overtaken to introduce new therapeutic regiments targeting the ideal treatment of acne. The increasing emergence of microbial resistance associated with antibiotics, teratogenicity, particularly associated with systemic isotretinoin, and the need for an adverse drug profile, which can be tolerated by the patient, make the need of new pathogenesis relevant anti-acne agents an emerging issue...
July 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28625749/preclinical-evaluation-of-melanocortin-1-receptor-mc1-r-specific-68-ga-and-44-sc-labeled-dota-napamide-in-melanoma-imaging
#17
Gábor Nagy, Noémi Dénes, Adrienn Kis, Judit P Szabó, Ervin Berényi, Ildikó Garai, Péter Bai, István Hajdu, Dezső Szikra, György Trencsényi
PURPOSE: Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors...
August 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28619748/pore-polarity-and-charge-determine-differential-block-of-kir1-1-and-kir7-1-potassium-channels-by-the-small-molecule-inhibitor-vu590
#18
Sujay Kharade, Jonathan Sheehan, Eric Figueroa, Jens Meiler, Jerod Denton
VU590 was the first publicly disclosed, sub-micromolar-affinity (IC50=0.2 µM), small-molecule inhibitor of the inward rectifier potassium (Kir) channel, Kir1.1, an emerging diuretic target for the treatment of hypertension. VU590 also inhibits Kir7.1, albeit with 40-fold lower potency (IC50~8 µM), and has been used as a Kir7.1 tool compound to uncover new roles of the channel in regulation of myometrial contractility and melanocortin signaling in the brain. Here, we employed molecular modeling, site-directed mutagenesis, and patch clamp electrophysiology to elucidate the molecular mechanisms underlying inhibition of Kir1...
June 15, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28614768/melanocortin-4-receptor-agonist-ro27-3225-ameliorates-soleus-but-not-gastrocnemius-atrophy-in-arthritic-rats
#19
A B Gomez-Sanmiguel, M P Nieto-Bona, C Fernandez-Galaz, T Priego, A I Martin, A Lopez-Calderon
Adjuvant-induced arthritis in rats decreases body weight and muscle mass. Melanocyte stimulating hormone administration to arthritic rats decreases inflammation and skeletal muscle wasting. In this study, we investigate whether activation of melanocortin-4 receptor by RO27-3225 administration is able to prevent the effect of arthritis on the expression of muscle-specific E3 ubiquitin ligases and MyoD in two different muscles, gastrocnemius (a mainly fast type muscle) and soleus (slow type). Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28599948/fish-pigmentation-and-the-melanocortin-system
#20
REVIEW
Laura Cal, Paula Suarez-Bregua, José Miguel Cerdá-Reverter, Ingo Braasch, Josep Rotllant
The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes...
June 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
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