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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We describe a middle-aged woman with chronic GVHD after allo-HCT who presented with a rapidly progressive cerebellar syndrome. Thorough investigation revealed only cerebellar atrophy on brain imaging and positive anti-GAD65 antibodies in serum and cerebrospinal fluid suggesting the diagnosis of anti-GAD antibody-associated cerebellar ataxia. Despite prompt treatment with high-dose corticosteroids, intravenous immunoglobulins, and rituximab, the patient ’s condition rapidly deteriorated, and she died 4 months later. This case suggests that anti-GAD antibody-associated cerebellar ataxia may be a rare manifestation of c...
Source: Acta Haematologica - Category: Hematology Source Type: research
CONCLUSION: This well-documented case highlighted FCE as the preferential location for CNV development in PIC with multimodal imaging emphasizing a chorioretinal entity. SUMMARY: This case report demonstrated the clinical course of focal choroidal excavation in a patient initially diagnosed with punctate inner choroidopathy complicated by choroidal neovascularization and its treatment response, well documented by multimodal imaging including optical coherence tomography angiography. PMID: 30422049 [PubMed - as supplied by publisher]
Source: Ocular Immunology and Inflammation - Category: Allergy & Immunology Tags: Ocul Immunol Inflamm Source Type: research
AbstractPurposePlantar fasciitis is a very common (lifetime incidence ~  10%) and long-lasting injury with major impact on daily function. Combining corticosteroid injection and physical training (strength training and stretching) was hypothesized to result in a superior effect compared to each treatment separately.MethodsA single blinded randomized controlled superiority trial conducted in 2013 –2014 with a 2-year follow-up (end Sept 2016). 123 consecutive patients (20–65 years) referred to two study centers in Denmark: Institute of Sports Medicine, Bispebjerg Hospital, University of Copenhagen and...
Source: Knee Surgery, Sports Traumatology, Arthroscopy - Category: Orthopaedics Source Type: research
This study characterizes the extent and cost of the use of corticosteroid-eluting sinus stents between 2012 and 2017.
Source: JAMA Otolaryngology - Head and Neck Surgery - Category: ENT & OMF Source Type: research
Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelin...
Source: Blood - Category: Hematology Authors: Tags: Special Reports, Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research
ConclusionsOur results suggest that the difference in ethnicity and age of the study population play an important role in the AH PK profiles of topical ophthalmic corticosteroid suspensions. Considering the subject-specific covariate effects in designing bioequivalence studies with AH PK endpoints could reduce bias from covariate imbalance and help identify true effects of formulation differences.
Source: Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research
Conclusions: Lesions at the PD catheter exit site are usually treated for infections. However, for ulcers that are painful, rapidly expanding, nonhealing, and unresponsive to antibiotics, PG should be considered as a differential diagnosis. This is the first reported case of PG occurring at the exit site of a PD catheter.Case Rep Nephrol Dial 2018;8:239 –245
Source: Case Reports in Nephrology and Dialysis - Category: Urology & Nephrology Source Type: research
Publication date: Available online 14 November 2018Source: Journal of the Formosan Medical AssociationAuthor(s): Chun-Pin Chiang, Julia Yu-Fong Chang, Yi-Ping Wang, Yu-Hsueh Wu, Yang-Che Wu, Andy SunRecurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases characterized by recurrent and painful ulcerations on the movable or nonkeratinized oral mucosae. Clinically, three types of RAS, namely minor, major, and herpetiform types, can be identified. RAS more commonly affects labial mucosa, buccal mucosa, and tongue. Previous studies indicate that RAS is a multifactorial T cell-mediated immune-dysregul...
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
Publication date: Available online 13 November 2018Source: The Journal of Allergy and Clinical Immunology: In PracticeAuthor(s): Elissa M. Abrams, Stanley J. Szefler, Allan B. BeckerThe treatment of “yellow zone,” or worsening, asthma in children remains controversial. The 2018 Global Initiative for Asthma strategy recommends increasing the dose of inhaled corticosteroid (ICS) for the short (1-2 weeks) or longer (3 months) term in children older than 5 years with worsening asthma. In contrast, the National Heart, Lung, and Blood Institute's Expert Panel Report 3 guideline for the diagnosis and management of ast...
Source: The Journal of Allergy and Clinical Immunology: In Practice - Category: Allergy & Immunology Source Type: research
We describe the 18F-FDG PET/CT findings in a rare case of mesenteric panniculitis caused by systemic lupus. A previous CT had raised suspicion of a space-occupying lesion in the left hypochondrium in a context of aspecific constitutional symptoms and inflammatory parameters. The diagnosis of panniculitis was confirmed at laparoscopic biopsy directed by the PET findings. Follow-up 18F-FDG PET/CT after 1 month of corticosteroid therapy showed complete disappearance of the abdominal hypermetabolic foci.
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
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