scholarly journals Tapping into 5-HT3 Receptors to Modify Metabolic and Immune Responses

2021 ◽  
Vol 22 (21) ◽  
pp. 11910
Author(s):  
Helen Irving ◽  
Ilona Turek ◽  
Christine Kettle ◽  
Nor Yaakob
Keyword(s):  
Immune Responses ◽  
Structural Biology ◽  
Serotonin Receptors ◽  
Recent Progress ◽  
The Other ◽  
Current Status ◽  
Genes Encoding ◽  
Metabolic Conditions ◽  
Type 3 ◽  
G Protein Coupled

5-hydroxytryptamine type 3 (5-HT3) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT3 subunits and increasing understanding of their implications in patient’s predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.

scholarly journals An Overview of Live Attenuated Recombinant Pseudorabies Viruses for Use as Novel Vaccines

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Bo Dong ◽  
Dante S. Zarlenga ◽  
Xiaofeng Ren
Keyword(s):  
Immune Responses ◽  
Pseudorabies Virus ◽  
Viral Infections ◽  
Current Status ◽  
Virus Propagation ◽  
Swine Virus ◽  
Double Stranded Dna ◽  
A Genome ◽  
Genes Encoding ◽  
Heterologous Antigens

Pseudorabies virus (PRV) is a double-stranded, DNA-based swine virus with a genome approximating 150 kb in size. PRV has many nonessential genes which can be replaced with genes encoding heterologous antigens but without deleterious effects on virus propagation. Recombinant PRVs expressing both native and foreign antigens are able to stimulate immune responses. In this paper, we review the current status of live attenuated recombinant PRVs and live PRV-based vector vaccines with potential for controlling viral infections in animals.

Current Status in the Design and Development of Agonists and Antagonists of Adenosine A3 Receptor as Potential Therapeutic Agents

2019 ◽  
Vol 25 (25) ◽  
pp. 2772-2787 ◽  
Author(s):  
Raghu P. Mailavaram ◽  
Omar H.A. Al-Attraqchi ◽  
Supratik Kar ◽  
Shinjita Ghosh
Keyword(s):  
Drug Target ◽  
Therapeutic Agents ◽  
G Protein Coupled Receptors ◽  
Current Status ◽  
Renal Diseases ◽  
Adenosine A3 Receptor ◽  
Drug Candidates ◽  
Novel Drugs ◽  
The Family ◽  
G Protein Coupled

Adenosine receptors (ARs) belongs to the family of G-protein coupled receptors (GPCR) that are responsible for the modulation of a wide variety of physiological functions. The ARs are also implicated in many diseases such as cancer, arthritis, cardiovascular and renal diseases. The adenosine A3 receptor (A3AR) has emerged as a potential drug target for the progress of new and effective therapeutic agents for the treatment of various pathological conditions. This receptor’s involvement in many diseases and its validity as a target has been established by many studies. Both agonists and antagonists of A3AR have been extensively investigated in the last decade with the goal of developing novel drugs for treating diseases related to immune disorders, inflammation, cancer, and others. In this review, we shall focus on the medicinal chemistry of A3AR ligands, exploring the diverse chemical classes that have been projected as future leading drug candidates. Also, the recent advances in the therapeuetic applications of A3AR ligands are highlighted.

scholarly journals Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Dark Phase ◽  
Light Phase ◽  
Dark Cycle ◽  
Simultaneous Activation ◽  
Type 3 ◽  
G Protein Coupled

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

scholarly journals The assembled and annotated genome of the pigeon louse Columbicola columbae, a model ectoparasite

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
James G Baldwin-Brown ◽  
Scott M Villa ◽  
Anna I Vickrey ◽  
Kevin P Johnson ◽  
Sarah E Bush ◽  
...  
Keyword(s):  
Low Cost ◽  
Single Copy ◽  
Odorant Receptors ◽  
Rna Seq ◽  
Pediculus Humanus ◽  
Final Assembly ◽  
Oxford Nanopore ◽  
Genes Encoding ◽  
Host Parasite ◽  
G Protein Coupled

Abstract The pigeon louse Columbicola columbae is a longstanding and important model for studies of ectoparasitism and host-parasite coevolution. However, a deeper understanding of its evolution and capacity for rapid adaptation is limited by a lack of genomic resources. Here, we present a high-quality draft assembly of the C. columbae genome, produced using a combination of Oxford Nanopore, Illumina, and Hi-C technologies. The final assembly is 208 Mb in length, with 12 chromosome-size scaffolds representing 98.1% of the assembly. For gene model prediction, we used a novel clustering method (wavy_choose) for Oxford Nanopore RNA-seq reads to feed into the MAKER annotation pipeline. High recovery of conserved single-copy orthologs (BUSCOs) suggests that our assembly and annotation are both highly complete and highly accurate. Consistent with the results of the only other assembled louse genome, Pediculus humanus, we find that C. columbae has a relatively low density of repetitive elements, the majority of which are DNA transposons. Also similar to P. humanus, we find a reduced number of genes encoding opsins, G protein-coupled receptors, odorant receptors, insulin signaling pathway components, and detoxification proteins in the C. columbae genome, relative to other insects. We propose that such losses might characterize the genomes of obligate, permanent ectoparasites with predictable habitats, limited foraging complexity, and simple dietary regimes. The sequencing and analysis for this genome were relatively low cost, and took advantage of a new clustering technique for Oxford Nanopore RNAseq reads that will be useful to future genome projects.

scholarly journals Recent progress in materials development for CO2 conversion: issues and challenges

2021 ◽  
Author(s):  
Sourav Ghosh ◽  
Arindam Modak ◽  
Arnab Samanta ◽  
Kanika Kole ◽  
Subhra Jana
Keyword(s):  
Recent Progress ◽  
Value Added ◽  
Advanced Materials ◽  
Current Status ◽  
Co2 Conversion ◽  
Technical Feasibility ◽  
Materials Development

A comprehensive and critical in-depth discussion on the development and prospect of several advanced materials for conversion of CO2 to value added chemicals is provided, together with their current status, technical feasibility and future opportunities.

scholarly journals Exposure to low doses of pesticides induces an immune response and the production of nitric oxide in honeybees

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merle T. Bartling ◽  
Susanne Thümecke ◽  
José Herrera Russert ◽  
Andreas Vilcinskas ◽  
Kwang-Zin Lee
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Bacterial Pathogen ◽  
Wild Plants ◽  
P450 Monooxygenase ◽  
Abiotic Stressors ◽  
Genes Encoding ◽  
Pesticides Exposure ◽  
Colony Survival ◽  
Oxide Synthase

AbstractHoneybees are essential pollinators of many agricultural crops and wild plants. However, the number of managed bee colonies has declined in some regions of the world over the last few decades, probably caused by a combination of factors including parasites, pathogens and pesticides. Exposure to these diverse biotic and abiotic stressors is likely to trigger immune responses and stress pathways that affect the health of individual honeybees and hence their contribution to colony survival. We therefore investigated the effects of an orally administered bacterial pathogen (Pseudomonas entomophila) and low-dose xenobiotic pesticides on honeybee survival and intestinal immune responses. We observed stressor-dependent effects on the mean lifespan, along with the induction of genes encoding the antimicrobial peptide abaecin and the detoxification factor cytochrome P450 monooxygenase CYP9E2. The pesticides also triggered the immediate induction of a nitric oxide synthase gene followed by the delayed upregulation of catalase, which was not observed in response to the pathogen. Honeybees therefore appear to produce nitric oxide as a specific defense response when exposed to xenobiotic stimuli. The immunity-related and stress-response genes we tested may provide useful stressor-dependent markers for ecotoxicological assessment in honeybee colonies.

scholarly journals Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1294
Author(s):  
Yogesh R. Suryawanshi ◽  
Autumn J. Schulze
Keyword(s):  
Immune Responses ◽  
Malignant Glioma ◽  
Blood Brain Barrier ◽  
Tumor Heterogeneity ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Brain Barrier ◽  
Current Status ◽  
Blood Brain ◽  
Federal Authority

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood–brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood–brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

Cloning of Human Genes Encoding Novel G Protein-Coupled Receptors

Genomics ◽  
1994 ◽  
Vol 23 (3) ◽  
pp. 609-618 ◽  
Author(s):  
Adriano Marchese ◽  
John M. Docherty ◽  
Tuan Nguyen ◽  
Michael Heiber ◽  
Regina Cheng ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Human Genes ◽  
Genes Encoding ◽  
G Protein Coupled

scholarly journals act Operon Control of Developmental Gene Expression in Myxococcus xanthus

2002 ◽  
Vol 184 (4) ◽  
pp. 1172-1179 ◽  
Author(s):  
Thomas M. A. Gronewold ◽  
Dale Kaiser
Keyword(s):  
Fruiting Body ◽  
Myxococcus Xanthus ◽  
The Other ◽  
Loss Of Function ◽  
Wild Type ◽  
Developmental Gene ◽  
Developmental Gene Expression ◽  
Mutant Strains ◽  
Genes Encoding ◽  
Signal Production

ABSTRACT Cell-bound C-signal guides the building of a fruiting body and triggers the differentiation of myxospores. Earlier work has shown that transcription of the csgA gene, which encodes the C-signal, is directed by four genes of the act operon. To see how expression of the genes encoding components of the aggregation and sporulation processes depends on C-signaling, mutants with loss-of-function mutations in each of the act genes were investigated. These mutations were found to have no effect on genes that are normally expressed up to 3 h into development and are C-signal independent. Neither the time of first expression nor the rate of expression increase was changed in actA, actB, actC, or actD mutant strains. Also, there was no effect on A-signal production, which normally starts before 3 h. By contrast, the null act mutants have striking defects in C-signal production. These mutations changed the expression of four gene reporters that are related to aggregation and sporulation and are expressed at 6 h or later in development. The actA and actB null mutations substantially decreased the expression of all these reporters. The other act null mutations caused either premature expression to wild-type levels (actC) or delayed expression (actD), which ultimately rose to wild-type levels. The pattern of effects on these reporters shows how the C-signal differentially regulates the steps that together build a fruiting body and differentiate spores within it.

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