scholarly journals Commentary: The Year in Orphan Nuclear Receptors and Their Coregulators

2011 ◽  
Vol 25 (12) ◽  
pp. 1983-1988
Author(s):  
David D. Moore
Keyword(s):  
Nuclear Receptors ◽  
Orphan Nuclear Receptors ◽  
Orphan Receptors ◽  
Wide Range ◽  
Basic Studies ◽  
Shed Light

Abstract We are beginning to integrate the functions of individual orphan receptors into larger networks. It is particularly exciting that these basic studies are beginning to shed light on important diseases. We are now able to address not just physiological but also pathological functions of these proteins and their potential as targets for treating a surprisingly wide range of diseases.

scholarly journals The orphan nuclear receptors at their 25-year reunion

2013 ◽  
Vol 51 (3) ◽  
pp. T115-T140 ◽  
Author(s):  
Shannon E Mullican ◽  
Joanna R DiSpirito ◽  
Mitchell A Lazar
Keyword(s):  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Biological Processes ◽  
Orphan Nuclear Receptors ◽  
Orphan Receptors ◽  
Critical Insight ◽  
Genomic Regions ◽  
Insight Into

The nuclear receptor superfamily includes many receptors, identified based on their similarity to steroid hormone receptors but without a known ligand. The study of how these receptors are diversely regulated to interact with genomic regions to control a plethora of biological processes has provided critical insight into development, physiology, and the molecular pathology of disease. Here we provide a compendium of these so-called orphan receptors and focus on what has been learned about their modes of action, physiological functions, and therapeutic promise.

scholarly journals Minireview: Genomics Versus Orphan Nuclear Receptors—A Half-Time Report

2002 ◽  
Vol 16 (6) ◽  
pp. 1135-1144
Author(s):  
Timothy M. Willson ◽  
John T. Moore
Keyword(s):  
Nuclear Receptors ◽  
Drug Targets ◽  
Hormone Receptors ◽  
Receptor Gene ◽  
Orphan Nuclear Receptors ◽  
Orphan Receptors ◽  
Genomic Technologies ◽  
Full Complement ◽  
And Function ◽  
The Impact

Abstract Following the successful cloning of the orphan nuclear receptors during the 1990s we entered the 21st century with knowledge of the full complement of human nuclear receptors. Many of these proteins are ligand-activated transcription factors that act as the cognate receptors for steroid, retinoid, and thyroid hormones. In addition to these well characterized endocrine hormone receptors, there are a large number of orphan receptors of which less is known about the nature and function of their ligands. The task of deciphering the physiological function of these orphan receptors has been aided by a new generation of genomic technologies. Through application of chemical, structural, and functional genomics, several orphan nuclear receptors have emerged as pharmaceutical drug targets for the treatment of important human diseases. The significant progress that has been made in the functional analysis of more than half of the nuclear receptor gene family provides an opportunity to review the impact of genomics in this endeavor.

scholarly journals Orphan nuclear receptors in angiogenesis and follicular development

Reproduction ◽  
2021 ◽  
Author(s):  
Adrian Guzmán ◽  
Camilla H.k. Hughes ◽  
Bruce D. Murphy
Keyword(s):  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Antral Follicle ◽  
Follicle Development ◽  
Orphan Nuclear Receptors ◽  
Ovarian Follicle Development ◽  
Wide Range

Orphan nuclear receptors (ONRs) are a subset of the nuclear receptor family that lack known endogenous ligands. Among 48 nuclear receptors identified in humans, 25 are classified as ONRs. They function as transcription factors and control expression of a wide range of genes to regulate metabolism, fertility, immunity, angiogenesis, and many other functions. Angiogenic factors are essential during ovarian follicle development, including follicle growth and ovulation,. Correct development of blood vessels contributes to preantral and antral follicular development, selection of the dominant follicle or follicles, follicular atresia, and ovulation. Although progress has been made in understanding the molecular mechanisms that regulate follicular angiogenesis, the role of ONRs as regulators is not clear. Based on their functions in other tissues, the ONRs NR1D1 (REV-ERBß), NR2C2 (TR4), NR2F2 (COUP-TF-II) and NR3B1, 2, and 3 (ERRα, ERRß and ERRγ) may modulate angiogenesis during antral follicle development. We hypothesize that this is achieved by effects on the expression and function of VEGFA, ANGPT1, THBS1, and soluble VEGFR1. Further, angiogenesis during ovulation is expected to be influenced by ONRs. NR5A2 (LRH-1), which is required for ovulation, regulates angiogenic genes in the ovary, including VEGFA and the upstream regulator of angiogenesis, PGE2. These angiogenic molecules may also be regulated by NR5A1 (SF-1). Evidence from outside the reproductive tract suggests that NR2F2 and NR4A1(NUR77) promote VEGFC and PGF respectively and NR4As (ΝUR77, NOR1) seem to be necessary for the angiogenic effects of VEGFA and PGE2. Together, the data suggest that ONRs are important regulators of follicular angiogenesis.

Sentence-Based Experience Logging in New Hearing Aid Users

2020 ◽  
Vol 29 (3S) ◽  
pp. 631-637
Author(s):  
Katja Lund ◽  
Rodrigo Ordoñez ◽  
Jens Bo Nielsen ◽  
Dorte Hammershøi
Keyword(s):  
Hearing Aid ◽  
Patient Experiences ◽  
Online Tool ◽  
Rehabilitation Process ◽  
Hearing Rehabilitation ◽  
Clinical Observations ◽  
Hearing Aid Use ◽  
Wide Range ◽  
Insight Into ◽  
Shed Light

Purpose The aim of this study was to develop a tool to gain insight into the daily experiences of new hearing aid users and to shed light on aspects of aided performance that may not be unveiled through standard questionnaires. Method The tool is developed based on clinical observations, patient experiences, expert involvement, and existing validated hearing rehabilitation questionnaires. Results An online tool for collecting data related to hearing aid use was developed. The tool is based on 453 prefabricated sentences representing experiences within 13 categories related to hearing aid use. Conclusions The tool has the potential to reflect a wide range of individual experiences with hearing aid use, including auditory and nonauditory aspects. These experiences may hold important knowledge for both the patient and the professional in the hearing rehabilitation process.

scholarly journals Biosynthesis of Nature-Inspired Unnatural Cannabinoids

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2914
Author(s):  
Kevin J. H. Lim ◽  
Yan Ping Lim ◽  
Yossa D. Hartono ◽  
Maybelle K. Go ◽  
Hao Fan ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Cannabis Sativa ◽  
Genetic Manipulation ◽  
Therapeutic Agents ◽  
Orphan Receptors ◽  
Complex Chemical ◽  
Biological Targets ◽  
Chemical Structures ◽  
Commercial Use ◽  
Wide Range

Natural products make up a large proportion of medicine available today. Cannabinoids from the plant Cannabis sativa is one unique class of meroterpenoids that have shown a wide range of bioactivities and recently seen significant developments in their status as therapeutic agents for various indications. Their complex chemical structures make it difficult to chemically synthesize them in efficient yields. Synthetic biology has presented a solution to this through metabolic engineering in heterologous hosts. Through genetic manipulation, rare phytocannabinoids that are produced in low yields in the plant can now be synthesized in larger quantities for therapeutic and commercial use. Additionally, an exciting avenue of exploring new chemical spaces is made available as novel derivatized compounds can be produced and investigated for their bioactivities. In this review, we summarized the biosynthetic pathways of phytocannabinoids and synthetic biology efforts in producing them in heterologous hosts. Detailed mechanistic insights are discussed in each part of the pathway in order to explore strategies for creating novel cannabinoids. Lastly, we discussed studies conducted on biological targets such as CB1, CB2 and orphan receptors along with their affinities to these cannabinoid ligands with a view to inform upstream diversification efforts.

Local Regulation of Adrenal Steroidogenesis: Subtle in vitro Effects of IL-1β on the Human Cell Line NCI-H295R Steroid Production along with Changes in MicroRNA Profile and Orphan Nuclear Receptors NR4As

2021 ◽  
pp. 1-11
Author(s):  
Natalia Santucci ◽  
Rocío Stampone ◽  
Eduardo Brandão Ferreira da Silva ◽  
Silvina Villar ◽  
Silvana Spinelli ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cell Line ◽  
Nuclear Receptors ◽  
Human Cell ◽  
Human Cell Line ◽  
Mirna Profile ◽  
Orphan Nuclear Receptors ◽  
Steroid Production ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis

<b><i>Introduction:</i></b> IL-1β, a cytokine from the innate immune response, is well known for its proinflammatory effects and stimulating activity on the hypothalamus-pituitary-adrenal axis, leading to the pituitary synthesis of adrenocorticotropic hormone followed by cortisol (and dehydroepiandrosterone – DHEA) release by the adrenal gland. While IL-1β modulates the adrenal steroidogenesis at the central level, it is unclear whether it also exerts an effect on the adrenal gland. <b><i>Method:</i></b> We studied the effect of IL-1β on adrenal steroid production and steroidogenic enzyme RNA expression in the human cell line NCI-H295R. We also explored eventual changes in the microRNA (miRNA) profile from IL-1β-treated NCI-H295R cells. <b><i>Results:</i></b> Transcripts encoding IL-1β receptors 1 and 2 were noticeable in the cell line, with cortisol and DHEA production showing a subtle increase after cytokine treatment. Transcripts from key enzymes in the steroidogenic pathway were analyzed, with no noticeable changes on them. The miRNA profile was modified by IL-1β treatment to an extent which bears some relationship with the regulatory mechanisms underlying adrenal steroid production. Since orphan nuclear receptors NR4As have emerged as potential key factors for coordinating inflammatory and metabolic responses, cell expression studies were also carried out to show an NR4As transcript augmentation following IL-1β treatment. <b><i>Discussion/Conclusions:</i></b> The subtle increase in adrenal steroid production in response to IL-1β stimulation without any modification in the transcription of the steroidogenic enzymes analyzed suggests an additional inflammatory/anti-inflammatory loop, wherein NR4As receptors may participate. Besides its physiological role, this process might be implied in pathological states accompanied by an unbalanced immune-endocrine relationship.

scholarly journals Beyond cultural and geographical proximity: delving into the factors that influence the dynamics of academic relationships between students in higher education

2021 ◽  
Author(s):  
José-Vicente Tomás-Miquel ◽  
Jordi Capó-Vicedo
Keyword(s):  
University Students ◽  
Academic Research ◽  
Past Research ◽  
Academic Networks ◽  
Level Data ◽  
Wide Range ◽  
Specific Stage ◽  
The University ◽  
Proximity Dimensions ◽  
Shed Light

AbstractScholars have widely recognised the importance of academic relationships between students at the university. While much of the past research has focused on studying their influence on different aspects such as the students’ academic performance or their emotional stability, less is known about their dynamics and the factors that influence the formation and dissolution of linkages between university students in academic networks. In this paper, we try to shed light on this issue by exploring through stochastic actor-oriented models and student-level data the influence that a set of proximity factors may have on formation of these relationships over the entire period in which students are enrolled at the university. Our findings confirm that the establishment of academic relationships is derived, in part, from a wide range of proximity dimensions of a social, personal, geographical, cultural and academic nature. Furthermore, and unlike previous studies, this research also empirically confirms that the specific stage in which the student is at the university determines the influence of these proximity factors on the dynamics of academic relationships. In this regard, beyond cultural and geographic proximities that only influence the first years at the university, students shape their relationships as they progress in their studies from similarities in more strategic aspects such as academic and personal closeness. These results may have significant implications for both academic research and university policies.

scholarly journals Messianism, rationalism and inter-Asian connections: The Majalis-i Jahangiri (1608–11) and the socio-intellectual history of the Mughal ‘ulama

2017 ◽  
Vol 54 (3) ◽  
pp. 317-338 ◽  
Author(s):  
Corinne Lefèvre
Keyword(s):  
Central Asia ◽  
Intellectual History ◽  
State Building ◽  
Specific Role ◽  
Wide Range ◽  
History Of ◽  
Muslim Intellectuals ◽  
Shed Light

Relying on the Majalis-i Jahangiri (1608–11) by ʿAbd al-Sattar b. Qasim Lahauri, this essay explores some of the discussions the Mughal Emperor Jahangir (r. 1605–27) conducted with a wide range of scholars, from Brahmans and ʿulama to Jesuit padres and Jewish savants. By far the most numerous, the debates bearing on Islam and involving Muslim intellectuals are especially significant on several accounts. First, because they illuminate how, following in the steps of his father Akbar (r. 1556–605), Jahangir was able to conciliate his messianic claims with a strong engagement with reason and to turn this combination into a formidable instrument for confession and state building. These conversations also provide promising avenues to think afresh the socio-intellectual history of the Mughal ʿulama inasmuch as they capture the challenges and adjustments attendant on imperial patronage, depict the jockeying for influence and positions among intellectuals (particularly between Indo-Muslim and Iranian lettrés), and shed light on relatively little known figures or on unexplored facets of more prominent individuals. In addition, the specific role played by scholars hailing from Iran—and, to a lesser extent, from Central Asia—in the juridical-religious disputes of the Indian court shows how crucial inter-Asian connections and networks were in the fashioning of Mughal ideology but also the ways in which the ongoing flow of émigré ʿulama was disciplined before being incorporated into the empire.

The NR4A family of orphan nuclear receptors are not required for adipogenesis

2007 ◽  
Vol 32 (2) ◽  
pp. 388-392 ◽  
Author(s):  
W-S Au ◽  
V A Payne ◽  
S O'Rahilly ◽  
J J Rochford
Keyword(s):  
Nuclear Receptors ◽  
Orphan Nuclear Receptors
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