scholarly journals The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

2011 ◽  
Vol 211 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Gavin P Vinson
Keyword(s):  
Receptor Activation ◽  
Structure And Function ◽  
Rational Drug Design ◽  
Hydroxyl Group ◽  
Making Sense ◽  
Rational Drug ◽  
Wide Range ◽  
Clear Insight ◽  
Systematic Understanding ◽  
And Function

Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor activation, and, in particular, the relationship between steroid hormone structure and function remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak mineralocorticoid, while the addition of an 11β-hydroxyl group produces glucocorticoid activity, yet further hydroxylation at C18 leads to the most potent mineralocorticoid, aldosterone? This review aims to show that the field has been confused by the misreading of the earlier literature and that DOC, far from being relatively inactive, in fact has a wide range of activities not shared by the other corticoids. In contrast to the accepted view, the presence of an 11β-hydroxyl group yields, in corticosterone or cortisol, hormones with more limited functions, and also more readily regulated, by 11β-hydroxysteroid dehydrogenase. This interpretation leads to a more systematic understanding of structure–function relationships in the corticosteroids and may assist more rational drug design.

Relationships between hydrogen bonds and halogen bonds in biological systems

2017 ◽  
Vol 73 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Rhianon K. Rowe ◽  
P. Shing Ho
Keyword(s):  
Biological Systems ◽  
Halogen Bonding ◽  
Structure And Function ◽  
Rational Drug Design ◽  
Biological Molecules ◽  
Halogen Bonds ◽  
Rational Drug ◽  
Complex Relationships ◽  
And Function ◽  
The Relationship

The recent recognition that halogen bonding (XB) plays important roles in the recognition and assembly of biological molecules has led to new approaches in medicinal chemistry and biomolecular engineering. When designing XBs into strategies for rational drug design or into a biomolecule to affect its structure and function, we must consider the relationship between this interaction and the more ubiquitous hydrogen bond (HB). In this review, we explore these relationships by asking whether and how XBs can replace, compete against or behave independently of HBs in various biological systems. The complex relationships between the two interactions inform us of the challenges we face in fully utilizing XBs to control the affinity and recognition of inhibitors against their therapeutic targets, and to control the structure and function of proteins, nucleic acids and other biomolecular scaffolds.

scholarly journals TOWARDS FUNCTIONAL ARCHITECTURAL DECOMPOSITION OF CONSTRAINED LAYER INFLATABLE SYSTEMS

2021 ◽  
Vol 1 ◽  
pp. 3219-3228
Author(s):  
Koray Benli ◽  
Jonathan Luntz ◽  
Diann Brei ◽  
Wonhee Kim ◽  
Paul Alexander ◽  
...  
Keyword(s):  
Conceptual Design ◽  
Form And Function ◽  
New Concepts ◽  
Wide Range ◽  
Systematic Understanding ◽  
And Function

AbstractPneumatically activated systems enable myriad types of highly functional inflatables employing a wide range of architectural approaches affecting their form and function, making systematic conceptual design difficult. A new architectural class of pneumatically activated systems, constrained layer inflatable systems, consists of hierarchically architected flat layers of thin airtight bladders that are internally and/or externally constrained to generate a variety of functionalities. The highly hierarchical architectural structure of constrained layer inflatable systems coincides with the hierarchy of produced functions, providing an opportunity for the development of a functional architectural decomposition, capturing the inherent relationship between architectural and functional hierarchies. The basis of the approach is conveyed through the design of an example constrained layer inflatable system. This approach empowers the systematic understanding of the interrelated architectural and functional breakdown of constrained layer inflatable systems, enabling designers to iteratively analyze, synthesize, and re-synthesize the components of the system improving existing designs and exploring new concepts.

scholarly journals Changes in the structure and function of the human thrombin receptor during receptor activation, internalization, and recycling.

1994 ◽  
Vol 269 (4) ◽  
pp. 2943-2952
Author(s):  
L.F. Brass ◽  
S. Pizarro ◽  
M. Ahuja ◽  
E. Belmonte ◽  
N. Blanchard ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Structure And Function ◽  
Thrombin Receptor ◽  
Human Thrombin ◽  
And Function

scholarly journals Visual Disfunction due to the Selective Effect of Glutamate Agonists on Retinal Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6245
Author(s):  
Santiago Milla-Navarro ◽  
Ariadna Diaz-Tahoces ◽  
Isabel Ortuño-Lizarán ◽  
Eduardo Fernández ◽  
Nicolás Cuenca ◽  
...  
Keyword(s):  
Harmful Effect ◽  
Receptor Activation ◽  
Structure And Function ◽  
Retinal Cell ◽  
Retinal Ganglion ◽  
Retinal Cells ◽  
Great Loss ◽  
Intraocular Injection ◽  
Glutamate Agonists ◽  
And Function

One of the causes of nervous system degeneration is an excess of glutamate released upon several diseases. Glutamate analogs, like N-methyl-DL-aspartate (NMDA) and kainic acid (KA), have been shown to induce experimental retinal neurotoxicity. Previous results have shown that NMDA/KA neurotoxicity induces significant changes in the full field electroretinogram response, a thinning on the inner retinal layers, and retinal ganglion cell death. However, not all types of retinal neurons experience the same degree of injury in response to the excitotoxic stimulus. The goal of the present work is to address the effect of intraocular injection of different doses of NMDA/KA on the structure and function of several types of retinal cells and their functionality. To globally analyze the effect of glutamate receptor activation in the retina after the intraocular injection of excitotoxic agents, a combination of histological, electrophysiological, and functional tools has been employed to assess the changes in the retinal structure and function. Retinal excitotoxicity caused by the intraocular injection of a mixture of NMDA/KA causes a harmful effect characterized by a great loss of bipolar, amacrine, and retinal ganglion cells, as well as the degeneration of the inner retina. This process leads to a loss of retinal cell functionality characterized by an impairment of light sensitivity and visual acuity, with a strong effect on the retinal OFF pathway. The structural and functional injury suffered by the retina suggests the importance of the glutamate receptors expressed by different types of retinal cells. The effect of glutamate agonists on the OFF pathway represents one of the main findings of the study, as the evaluation of the retinal lesions caused by excitotoxicity could be specifically explored using tests that evaluate the OFF pathway.

scholarly journals Regulation of OmpA Translation and Shigella dysenteriae Virulence by an RNA Thermometer

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Erin R. Murphy ◽  
Johanna Roßmanith ◽  
Jacob Sieg ◽  
Megan E. Fris ◽  
Hebaallaha Hussein ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Species ◽  
Regulation Of Gene Expression ◽  
Structure And Function ◽  
Shigella Dysenteriae ◽  
Content Type ◽  
Bacterial Physiology ◽  
Wide Range ◽  
Rna Thermometer ◽  
And Function

ABSTRACT RNA thermometers are cis-acting riboregulators that mediate the posttranscriptional regulation of gene expression in response to environmental temperature. Such regulation is conferred by temperature-responsive structural changes within the RNA thermometer that directly result in differential ribosomal binding to the regulated transcript. The significance of RNA thermometers in controlling bacterial physiology and pathogenesis is becoming increasingly clear. This study combines in silico, molecular genetics, and biochemical analyses to characterize both the structure and function of a newly identified RNA thermometer within the ompA transcript of Shigella dysenteriae. First identified by in silico structural predictions, genetic analyses have demonstrated that the ompA RNA thermometer is a functional riboregulator sufficient to confer posttranscriptional temperature-dependent regulation, with optimal expression observed at the host-associated temperature of 37°C. Structural studies and ribosomal binding analyses have revealed both increased exposure of the ribosomal binding site and increased ribosomal binding to the ompA transcript at permissive temperatures. The introduction of site-specific mutations predicted to alter the temperature responsiveness of the ompA RNA thermometer has predictable consequences for both the structure and function of the regulatory element. Finally, in vitro tissue culture-based analyses implicate the ompA RNA thermometer as a bona fide S. dysenteriae virulence factor in this bacterial pathogen. Given that ompA is highly conserved among Gram-negative pathogens, these studies not only provide insight into the significance of riboregulation in controlling Shigella virulence, but they also have the potential to facilitate further understanding of the physiology and/or pathogenesis of a wide range of bacterial species.

Commentary on “Reflections on culture, structure and function of an intensive support service centred on positive behavioural support”

2016 ◽  
Vol 21 (4) ◽  
pp. 212-219 ◽  
Author(s):  
Sandy Toogood
Keyword(s):  
Support Service ◽  
Structure And Function ◽  
Content Type ◽  
Behavioural Support ◽  
Wide Range ◽  
Service Models ◽  
History Of ◽  
Positive Behaviour Support ◽  
The Uk ◽  
And Function

Purpose The purpose of this paper is to provide a commentary on Patterson and Berry’s paper “Reflections on culture, structure and function of an intensive support service centred on positive behavioural support”. Design/methodology/approach This paper reviews key ideas presented in Patterson and Berry’s article relative to the recent history of service delivery in the UK and the growing interest being shown in positive behaviour support. Findings Patterson and Berry’s article adds to a modest literature on specialist support services and should stimulate further descriptions of service models and the concepts underpinning them. Originality/value The literature on specialist support service models is limited and this addition should be relevant to a wide range of clinicians, consumers and commissioners.

scholarly journals Structure and biogenesis of small nucleolar RNAs acting as guides for ribosomal RNA modification.

1999 ◽  
Vol 46 (2) ◽  
pp. 377-389 ◽  
Author(s):  
W Filipowicz ◽  
P Pelczar ◽  
V Pogacic ◽  
F Dragon
Keyword(s):  
Ribosomal Rna ◽  
Structure And Function ◽  
Hydroxyl Group ◽  
Rna Modification ◽  
Small Nucleolar Rnas ◽  
Yeast Saccharomyces Cerevisiae ◽  
Site Specific ◽  
Alternative Pathways ◽  
And Function ◽  
Nucleolar Rnas

Maturation of pre-ribosomal RNA (pre-rRNA) in eukaryotic cells takes place in the nucleolus and involves a large number of cleavage events, which frequently follow alternative pathways. In addition, rRNAs are extensively modified, with the methylation of the 2'-hydroxyl group of sugar residues and conversion of uridines to pseudouridines being the most frequent modifications. Both cleavage and modification reactions of pre-rRNAs are assisted by a variety of small nucleolar RNAs (snoRNAs), which function in the form of ribonucleoprotein particles (snoRNPs). The majority of snoRNAs acts as guides directing site-specific 2'-O-ribose methylation or pseudouridine formation. Over one hundred RNAs of this type have been identified to date in vertebrates and the yeast Saccharomyces cerevisiae. This number is readily explained by the findings that one snoRNA acts as a guide usually for one or at most two modifications, and human rRNAs contain 91 pseudouridines and 106 2'-O-methyl residues. In this article we review information about the biogenesis, structure and function of guide snoRNAs.

scholarly journals Structure and function of the immune system in the spleen

2019 ◽  
Vol 4 (33) ◽  
pp. eaau6085 ◽  
Author(s):  
Steven M. Lewis ◽  
Adam Williams ◽  
Stephanie C. Eisenbarth
Keyword(s):  
Cell Types ◽  
Structure And Function ◽  
Lymphoid Organ ◽  
The Body ◽  
Human Spleen ◽  
Cell Clearance ◽  
Wide Range ◽  
Abnormal Cells ◽  
Cell Organization ◽  
And Function

The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red blood cell clearance. The physical organization of the spleen allows it to filter blood of pathogens and abnormal cells and facilitate low-probability interactions between antigen-presenting cells (APCs) and cognate lymphocytes. APCs specific to the spleen regulate the T and B cell response to these antigenic targets in the blood. This review will focus on cell types, cell organization, and immunologic functions specific to the spleen and how these affect initiation of adaptive immunity to systemic blood-borne antigens. Potential differences in structure and function between mouse and human spleen will also be discussed.

scholarly journals Biosynthesis of Polyketides in Streptomyces

2019 ◽  
Vol 7 (5) ◽  
pp. 124 ◽  
Author(s):  
Chandra Risdian ◽  
Tjandrawati Mozef ◽  
Joachim Wink
Keyword(s):  
Secondary Metabolites ◽  
Structure And Function ◽  
Polyketide Synthases ◽  
Type I ◽  
Type Ii ◽  
Filamentous Form ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Different Types ◽  
And Function

Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.

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