Evolution and Potential Function in Molluscs of Neuropeptide and Receptor Homologues of the Insect Allatostatins

The allatostatins (ASTs), AST-A, AST-B and AST-C, have mainly been investigated in insects. They are a large group of small pleotropic alloregulatory neuropeptides that are unrelated in sequence and activate receptors of the rhodopsin G-protein coupled receptor family (GPCRs). The characteristics and functions of the homologue systems in the molluscs (Buccalin, MIP and AST-C-like), the second most diverse group of protostomes after the arthropods, and of high interest for evolutionary studies due to their less rearranged genomes remains to be explored. In the present study their evolution is deciphered in molluscs and putative functions assigned in bivalves through meta-analysis of transcriptomes and experiments. Homologues of the three arthropod AST-type peptide precursors were identified in molluscs and produce a larger number of mature peptides than in insects. The number of putative receptors were also distinct across mollusc species due to lineage and species-specific duplications. Our evolutionary analysis of the receptors identified for the first time in a mollusc, the cephalopod, GALR-like genes, which challenges the accepted paradigm that AST-AR/buccalin-Rs are the orthologues of vertebrate GALRs in protostomes. Tissue transcriptomes revealed the peptides, and their putative receptors have a widespread distribution in bivalves and in the bivalve Mytilus galloprovincialis, elements of the three peptide-receptor systems are highly abundant in the mantle an innate immune barrier tissue. Exposure of M. galloprovincialis to lipopolysaccharide or a marine pathogenic bacterium, Vibrio harveyi, provoked significant modifications in the expression of genes of the peptide precursor and receptors of the AST-C-like system in the mantle suggesting involvement in the immune response. Overall, our study reveals that homologues of the arthropod AST-systems in molluscs are potentially more complex due to the greater number of putative mature peptides and receptor genes. In bivalves they have a broad and varying tissue distribution and abundance, and the elements of the AST-C-like family may have a putative function in the immune response.

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Signaling and regulation of G-protein coupled receptors encoded by cytomegaloviruses

Biochemistry and Cell Biology ◽

10.1139/o04-115 ◽

2004 ◽

Vol 82 (6) ◽

pp. 636-642 ◽

Cited By ~ 8

Author(s):

Melissa P. M Stropes ◽

William E Miller

Keyword(s):

Immune Response ◽

Host Cell ◽

G Protein ◽

Host Immune Response ◽

G Protein Coupled Receptors ◽

Molecular Regulation ◽

Virally Encoded ◽

Species Specific ◽

G Protein Coupled ◽

Insight Into

Cytomegaloviruses (CMVs) are species-specific β-herpesviruses whose replicative success is largely due to establishment of novel mechanisms for altering the host immune response. CMV encodes 3 families of putative G-protein coupled receptors (GPCRs) likely pirated from the host cell. While the functions of these virally encoded GPCRs remain unclear, the receptors possess potent signaling abilities. Understanding the molecular regulation of these GPCRs will provide important insight into CMV pathogenesis.Key words: GPCRs, HCMV, GRKs, β-arrestin, US28.

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Effect of Demethylating Agents (5-Azacytidine/5-AzaC) On the Immune Response

Blood ◽

10.1182/blood.v116.21.2771.2771 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2771-2771

Author(s):

Silvia Gutiérrez Cosío ◽

Esteban Ballestar ◽

Carlos Santamaría ◽

Belén Blanco ◽

Luis Ignacio Sánchez Abarca ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Board Of Directors ◽

Methylation Status ◽

Allogeneic Transplantation ◽

Advisory Committees ◽

Graft Versus Host ◽

Expression Of Genes ◽

Before And After ◽

First Time

Abstract Abstract 2771 Introduction: We have previously shown that 5-azaC inhibits T-cells proliferation and favours the development of Tregs which decreases the risk of GVHD after allogeneic transplantation. This is at least in part due to the effect of the drug on the expression of genes such as FOXP3. Nevertheless, considering the unspecific effect of 5-azaC, it could also favour the overexpression of other genes related to the regulation of the immune response such as TBET, GATA3, IFNg or IL-2, which in turn would favour the development of a Th1, Th2 or Th17 polarization instead of a Treg expansion. In the current study we have evaluated the effect of 5-azaC on these genes in order to know the mechanisms involved in the effect of the drug on the immune response. Methods: We analyzed TBET, GATA3, FOXP3, IFNg and IL-2 mRNA expression of T lymphocytes by RT-PCR after exposure to 1mM 5-azaC during eleven days of culture. These T cells were cultured in medium alone or stimulated with plate-bound anti-CD3 (5 mg/ml) plus soluble anti-CD28 (2.5 mg/ml). Furthermore, we analyzed the methylation status of the promoters of these genes before and after 5-azaC treatment. Results: The expression of TBET, GATA3 and RORγ is not significantly affected by the exposure to the drug whereas the expression of FOXP3 significantly increases along the culture. Regarding IFNg and IL-2 expression no increased expression was observed after exposure to the drug at different time-points along the 11 days of culture. Upon analyzing the mathylation status of the promoter of these genes, we observed that in steady state the promoter of TBET and GATA is demethylated, which is in contrast to FOXP3 promoter. For this reason, the exposure to the drug decreases the methylation status of the promoter of FOXP3 while there is no effect on the promoters of TBET or RORg, thus justifying the absence of effect on the expression of these genes. By contrat, the promoter of both IFNg and IL-2 is methylated prior to the exposure to 5-azaC and it is demethylated after exposure to the drug, which is in contrast to the absence of increased expression of these genes. Accordingly, other mechanisms in addition to the epigenetic regulation of the promoter of IFNg and IL-2 are responsible for their expression in this model. Conclusions: In the current study we show by the first time the effect of 5-azaC on the promoters of genes which regulate the immune response. While no effect was observed for TBET, and GATA3 5-azaC induces a strong demethylation in the promoter of IFN or IL-2. In spite of this effect there is no increase in their expression which could be due to the overexpression of FOXP3 or to additional mechanisms involved in their regulation which are currently being evaluated. Disclosures: Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees. San Miguel:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jangssen-cilag: Membership on an entity's Board of Directors or advisory committees; millennium: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The drug used in this study is the demethylating agent 5-azacytidine (5-azaC) and the purpose is the inhibition of graft versus host disease.

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Bats, Primates, and the Evolutionary Origins and Diversification of Mammalian Gammaherpesviruses

mBio ◽

10.1128/mbio.01425-16 ◽

2016 ◽

Vol 7 (6) ◽

Cited By ~ 16

Author(s):

Marina Escalera-Zamudio ◽

Edith Rojas-Anaya ◽

Sergios-Orestis Kolokotronis ◽

Blanca Taboada ◽

Elizabeth Loza-Rubio ◽

...

Keyword(s):

Current View ◽

Host Switching ◽

Evolutionary Analysis ◽

Evolutionary Origins ◽

Public Repositories ◽

Species Specific ◽

Scenario Testing ◽

First Time ◽

Viral Sequences ◽

Vampire Bat

ABSTRACTGammaherpesviruses (γHVs) are generally considered host specific and to have codiverged with their hosts over millions of years. This tenet is challenged here by broad-scale phylogenetic analysis of two viral genes using the largest sample of mammalian γHVs to date, integrating for the first time bat γHV sequences available from public repositories and newly generated viral sequences from two vampire bat species (Desmodus rotundusandDiphylla ecaudata). Bat and primate viruses frequently represented deep branches within the supported phylogenies and clustered among viruses from distantly related mammalian taxa. Following evolutionary scenario testing, we determined the number of host-switching and cospeciation events. Cross-species transmissions have occurred much more frequently than previously estimated, and most of the transmissions were attributable to bats and primates. We conclude that the evolution of theGammaherpesvirinaesubfamily has been driven by both cross-species transmissions and subsequent cospeciation within specific viral lineages and that the bat and primate orders may have potentially acted as superspreaders to other mammalian taxa throughout evolutionary history.IMPORTANCEIt has long been believed that herpesviruses have coevolved with their hosts and are species specific. Nevertheless, a global evolutionary analysis of bat viruses in the context of other mammalian viruses, which could put this widely accepted view to the test, had not been undertaken until now. We present two main findings that may challenge the current view of γHV evolution: multiple host-switching events were observed at a higher rate than previously appreciated, and bats and primates harbor a large diversity of γHVs which may have led to increased cross-species transmissions from these taxa to other mammals.

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An Epistemological Criticism of Social Entrepreneurship: Is Social Entrepreneurship a Sound Scientific Field of Research

10.31124/advance.7091927.v1 ◽

2018 ◽

Author(s):

Amir Forouharfar

Keyword(s):

Social Entrepreneurship ◽

Social Constructivism ◽

Social Epistemology ◽

American English ◽

Meta Analysis ◽

Research Question ◽

Knowledge Structure ◽

Scientific Field ◽

The Other ◽

First Time

The paper was shaped around the pivotal question: Is SE a sound and scientific field of research? The question has given a critical tone to the paper and has also helped to bring out some of the controversial debates in the realm of SE. The paper was organized under five main discussions to be able to provide a scientific answer to the research question: (1) is “social entrepreneurship” an oxymoron?, (2) the characteristics of SE knowledge, (3) sources of social entrepreneurship knowledge, (4) SE knowledge: structure and limitations and (5) contributing epistemology-making concepts for SE. Based on the sections, the study relied on the relevant philosophical schools of thought in Epistemology (e.g. Empiricism, Rationalism, Skepticism, Internalism vs. Externalism, Essentialism, Social Constructivism, Social Epistemology, etc.) to discuss these controversies around SE and proposes some solutions by reviewing SE literature. Also, to determine the governing linguistic discourse in the realm of SE, which was necessary for our discussion, Corpus of Contemporary American English (COCA) for the first time in SE studies was used. Further, through the study, SE buzzwords which constitute SE terminology were derived and introduced to help us narrowing down and converging the thoughts in this field and demarking the epistemological boundaries of SE. The originality of the paper on one hand lies in its pioneering discussions on SE epistemology and on the other hand in paving the way for a construction of sound epistemology for SE; therefore in many cases after preparing the philosophical ground for the discussions, it went beyond the prevalent SE literature through meta-analysis to discuss the cases which were raised. The results of the study verified previously claimed embryonic pre-paradigmatic phase in SE which was far from a sound and scientific knowledge, although the scholarly endeavors are the harbingers of such a possibility in the future which calls for further mature academic discussion and development of SE knowledge by the SE academia.

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Mapping the Heart

Microscopy Today ◽

10.1017/s155192951000043x ◽

2010 ◽

Vol 18 (4) ◽

pp. 6-8

Author(s):

Stephen W. Carmichael

Keyword(s):

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

G Protein Coupled Receptors ◽

Receptor Subtypes ◽

Cardiac Muscle Cells ◽

Guanine Nucleotide Binding Protein ◽

The Common ◽

Guanine Nucleotide Binding ◽

First Time ◽

G Protein Coupled

Some of the receptors on the surface of cardiac muscle cells (cardiomyocytes) mediate the response of these cells to catecholamines by causing the production of the common second messenger cyclic adenosine monophosphate (cAMP). An example of such receptors are the β1- and β2-adrenergic receptors (βARs) that are heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Selective stimulation of these two receptor subtypes leads to distinct physiological and pathophysiological responses, but their precise location on the surface of cardiomyocytes has not been correlated with these responses. In an ingenious combination of techniques, Viacheslav Nikolaev, Alexey Moshkov, Alexander Lyon, Michele Miragoli, Pavel Novak, Helen Paur, Martin Lohse, Yuri Korchev, Sian Harding, and Julia Gorelik have mapped the function of these receptors for the first time.

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Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351

Scientific Reports ◽

10.1038/s41598-021-87225-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jee-Yun Park ◽

Hee-Young Sohn ◽

Young Ho Koh ◽

Chulman Jo

Keyword(s):

Oxidative Stress ◽

Crucial Role ◽

Curcuma Longa ◽

Expression Plasmid ◽

Expression Of Genes ◽

Nrf2 Activation ◽

First Time ◽

Nrf2 Protein ◽

Endogenous Defense ◽

In Cells

AbstractCurcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.

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Effect of six weeks 1000 mg/day vitamin C supplementation and healthy training in elderly women on genes expression associated with the immune response - a randomized controlled trial

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00416-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Małgorzata Żychowska ◽

Agata Grzybkowska ◽

Mariusz Zasada ◽

Anna Piotrowska ◽

Danuta Dworakowska ◽

...

Keyword(s):

Immune Response ◽

Vitamin C ◽

Body Mass ◽

Elderly Women ◽

Controlled Trial ◽

Expression Of Genes ◽

Genes Expression ◽

Vitamin C Supplementation ◽

Group A ◽

Adaptation To Training

Abstract Background In this study, we investigated the effects of supplementation and exercise on the expression of genes associated with inflammation like CCL2, CRP, IL1, IL6, IL10 mRNA in elderly women. Methods Twenty four participants divided randomly into two groups were subjected to 6 weeks of the same health training program (three times per week). SUP group (supplemented, n = 12, mean age 72.8 ± 5.26 years and mean body mass 68.1 ± 8.3 kg) received 1000 mg of Vitamin C/day during the training period, while CON group (control, n = 12, mean age 72.4 ± 5.5 years and body mass 67.7 ± 7.5 kg) received placebo. Results No significant changes in IL-1, IL-6, IL-10 and CRP mRNA were observed within and between groups. However, there was a clear tendency of a decrease in IL-6 (two-way ANOVA, significant between investigated time points) and an increase in IL-10 mRNA noted in the supplemented group. A significant decrease in CCL2 mRNA was observed only in the CON group (from 2^0.2 to 2^0.1, p = 0.01). Conclusions It can be concluded, that 6 weeks of supplementation and exercise was too short to obtain significant changes in gene expression in leukocytes, but supplementation of 1000 mg vitamin C positively affected IL-6 and IL-10 expression – which are key changes in the adaptation to training. However, changes in body mass, IL1 and CCL2 were positive in CON group. It is possible that Vitamin C during 6 weeks of supplementation could have different effects on the expression of individual genes involved in the immune response. Trial registration Retrospectively registered.

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The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

Journal of Clinical Medicine ◽

10.3390/jcm10143058 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3058

Author(s):

Aleksandra Mielczarek-Palacz ◽

Celina Kruszniewska-Rajs ◽

Marta Smycz-Kubańska ◽

Jarosław Strzelczyk ◽

Wojciech Szanecki ◽

...

Keyword(s):

Ovarian Cancer ◽

Peritoneal Fluid ◽

Tumor Tissue ◽

Mrna Level ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Expression Of Genes ◽

Genes Encoding ◽

First Time ◽

Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

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Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

Scientific Reports ◽

10.1038/s41598-021-85872-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

L. Criado-Mesas ◽

N. Abdelli ◽

A. Noce ◽

M. Farré ◽

J. F. Pérez ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Barrier Function ◽

Nutrient Transport ◽

Gene Expression Pattern ◽

Vaccine Dose ◽

Special Focus ◽

Intestinal Health ◽

Barrier Failure ◽

Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

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