Expanding the horizons of G protein-coupled receptor structure-based ligand discovery and optimization using homology models

2015 ◽  
Vol 51 (71) ◽  
pp. 13576-13594 ◽  
Author(s):  
Claudio N. Cavasotto ◽  
Damián Palomba

We show the key role of structural homology models in GPCR structure-based lead discovery and optimization, highlighting methodological aspects, recent progress and future directions.

Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.


2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.


2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.


Author(s):  
Igor Ponomarev

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.


Author(s):  
Bruno and

Multisensory interactions in perception are pervasive and fundamental, as we have documented throughout this book. In this final chapter, we propose that contemporary work on multisensory processing is a paradigm shift in perception science, calling for a radical reconsideration of empirical and theoretical questions within an entirely new perspective. In making our case, we emphasize that multisensory perception is the norm, not the exception, and we remark that multisensory interactions can occur early in sensory processing. We reiterate the key notions that multisensory interactions come in different kinds and that principles of multisensory processing must be considered when tackling multisensory daily-life problems. We discuss the role of unisensory processing in a multisensory world, and we conclude by suggesting future directions for the multisensory field.


Author(s):  
Adrián Yoris ◽  
Adolfo M. García ◽  
Paula Celeste Salamone ◽  
Lucas Sedeño ◽  
Indira García-Cordero ◽  
...  

Dimensional and transdiagnostic approaches have revealed multiple cognitive/emotional alterations shared by several neuropsychiatric conditions. While this has been shown for externally triggered neurocognitive processes, the disruption of interoception across neurological disorders remains poorly understood. This chapter aims to fill this gap while proposing cardiac interoception as a potential common biomarker across disorders. It focuses on key aspects of interoception, such as the mechanisms underlying different interoceptive dimensions; the relationship among interoception, emotion, and social cognition; and the roles of different interoceptive pathways. It considers behavioral and brain evidence in the context of an experimental and clinical agenda to evaluate the potential role of interoception as a predictor of clinical outcomes, a marker of neurocognitive deficits across diseases, and a general source of insights for breakthroughs in the treatment and prevention of multiple disorders. Finally, future directions to improve the dimensional and transdiagnostic assessment of interoception are outlined.


Author(s):  
Amanda Denes ◽  
Anuraj Dhillon ◽  
Ambyre L. P. Ponivas ◽  
Kara L. Winkler

Sexual communication is a pivotal part of interpersonal relationships; recent research reveals associations between sexual communication and various relational outcomes. Within the broad domain of sexual communication, current scholarship specifically addresses the role of postsex communication in relationships and its links to physiological and genetic markers. Given these advancements, the present chapter offers an overview of research linking physiology, hormones, and genes to communication after sexual activity. The chapter first presents reviews of two key hormones in sexual communication research: testosterone (T) and oxytocin (O). The oxytocin receptor gene and its link to social behavior broadly, and sexual behavior specifically, is also explored. The chapter then offers a review of several theories relevant to understanding the hormonal underpinnings of sexual communication, as well as future directions for research exploring sexual communication and physiology.


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