Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model?

Evolution of Nuclear Receptors and Ligand Signaling: Toward a Soft Key-Lock Model? Curr Top Dev Biol. 2017;125:1-38 Authors: Holzer G, Markov GV, Laudet V Abstract Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that modulate a wide variety of physiological functions in a ligand-dependent manner. The first NRs were discovered as receptors of well-known hormones such as 17β-estradiol, corticosteroids, or thyroid hormones. In these cases a direct activation of the receptor transcriptional activity by a very specific ligand, with nanomolar affinity, was demonstrated, providing a strong conceptual framework to understand the mechanism of action of these hormones. However, the discovery that some NRs are able to bind different ligands with micromolar affinity was a first sign that the univocal relationship between a specific receptor (e.g., TR) and a specific ligand (e.g., thyroid hormone) should not be generalized to the whole family. These discussions about the nature of NR ligands have been reinforced by the study of the hormone/receptor couple evolution. Indeed when the ligand is not a protein but a small molecule derived from a biochemical pathway, a simple coevolution mechanism between the ligand and the receptor cannot operate. We and others have recently shown that the ligands acting for a given NR early on during evolution were often different from the classical mammalian ligands. This suggests that the NR/ligand e...
Source: Current Topics in Developmental Biology - Category: Biology Authors: Tags: Curr Top Dev Biol Source Type: research

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Authors: Yang HJ Abstract Mycoplasma pneumoniae pneumonia (MPP) has been generally susceptible to macrolides, however emergence of macrolide-resistant Mycoplasma pneumoniae pneumonia (MRMP) has made the treatment of MPP challenging. MRMP rapidly spread after 2000s, especially in the Eastern Asia. MRMPs are more common in children and adolescents than in adults, which is likely related to the frequent use of macrolides for treatments of MP infections in children. The MRMP is unlikely to be related with clinical, laboratory, or radiological- severity, although it is likely to cause longer persistence of symptoms and ...
Source: Korean Journal of Pediatrics - Category: Pediatrics Tags: Korean J Pediatr Source Type: research
Authors: Kang J, Cho YS, Choi DK, Lee JS, Oh YM, Lee SD, Lee SW Abstract Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma ...
Source: Journal of Korean Medical Science - Category: Biomedical Science Tags: J Korean Med Sci Source Type: research
CONCLUSION: A trend toward increasing use of intravitreal anti-VEGF injections for DME treatment was observed in Korea. However, the frequency of dosing and monitoring was lower in clinical practice versus major clinical trials, which may have led to the less-than-favorable improvements in visual outcomes. PMID: 31001935 [PubMed - in process]
Source: Journal of Korean Medical Science - Category: Biomedical Science Tags: J Korean Med Sci Source Type: research
Publication date: May 2019Source: American Journal of Kidney Diseases, Volume 73, Issue 5Author(s):
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
CONCLUSIONS: Re-excision of skin cancer, below-knee excisions, and intraoperative hemorrhagic complications were predictive for infection in more than one study. More high-quality studies are required to accurately identify risk factors so they can be reliably used in clinical guidelines.
Source: Advances in Skin and Wound Care - Category: Dermatology Tags: FEATURES: LITERATURE REVIEW Source Type: research
Authors: Ramachandran V, Cline A, Feldman SR, Strowd LC Abstract INTRODUCTION: Atopic dermatitis (AD) is a chronic and recurrent disease presenting with eczematous lesions and pruritus. It impacts patient and family quality of life, increases morbidity, and accounts for large health-care expenditures. Although nonpharmacologic, topical, and systemic treatments exist, management of AD remains challenging due to limited treatment options. Crisaborole is a topical small molecule inhibitor of phosphodiesterase 4 (PDE4), recently approved for the treatment of AD in the United States. Areas covered: The authors review cr...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Authors: Sano A, Inoue J, Kakazu E, Ninomiya M, Iwata T, Morosawa T, Takai S, Nakamura T, Masamune A Abstract Selective immunoglobulin M deficiency (SIGMD) is an uncommon primary immunodeficiency disorder. We herein report an SIGMD patient with autoimmune hepatitis. A 21-year-old Japanese man was transferred to our hospital because of acute liver dysfunction. His serum IgM level was low, whereas those of IgG and IgA were normal, indicating that he had SIGMD. We diagnosed him with acute-onset autoimmune hepatitis, and his liver function test findings gradually recovered with corticosteroid administration. Although S...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
We report a 36-year-old man with chronic cough, hemoptysis, significant weight loss, and orogenital ulcers from one year before referral. Initial assessments revealed multiple parahillar nodules in chest X-ray, chronic inflammatory anemia, erythrocyte sedimentation rate more than 100, and positive Human Leukocyte Antigen B5 and B51. Evaluation for infection and malignancies was unremarkable. Open exploratory lung study showed multiple pulsatile nodules in both lungs. AMIGO computed tomogram confirmed multiple right and left pulmonary artery aneurysms and impending to rupture aneurysm at subdivision of inferior mesenteric a...
Source: Oman Medical Journal - Category: Middle East Health Tags: Oman Med J Source Type: research
Publication date: Available online 18 April 2019Source: Actas Dermo-Sifiliográficas (English Edition)Author(s): F.J. Navarro-Triviño, S. Arias-Santiago, Y. Gilaberte-CalzadaAbstractIn recent years, the growing interest in the role played by vitamin D in skin disease has given rise to the publication of many studies of the relationship between this vitamin and certain skin conditions. As dermatologists, we need to understand, among other aspects, how vitamin D is synthesized and the main sources in humans, as well as plasma levels and the factors that can modify them. Of particular interest are the latest disc...
Source: Actas Dermo-Sifiliograficas - Category: Dermatology Source Type: research
Allergic contact dermatitis (ACD) is a T-cell-mediated immune response to repeated contact with allergens (e.g. nickel or poison ivy). Current treatments involve topical corticosteroids, which non-specifically and transiently suppress inflammation without addressing the underlying immune dysfunction. Here we present a novel approach to induce systemic allergen-specific tolerance by delivering both allergen and a tolerance-favoring immune modifier into the same cutaneous microenvironment. Dissolvable microneedle arrays (MNAs) simultaneously deliver hapten or protein allergens with vitamin D3 analog MC903 to induce a tolerog...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
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