scholarly journals Functional conservation in genes and pathways linking ageing and immunity

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel K. Fabian ◽  
Matías Fuentealba ◽  
Handan Melike Dönertaş ◽  
Linda Partridge ◽  
Janet M. Thornton
Keyword(s):  
Immune System ◽  
Fruit Fly ◽  
Model Organisms ◽  
Current Evidence ◽  
Future Research ◽  
Functional Conservation ◽  
Human Orthologs ◽  
Evolutionarily Conserved ◽  
Nematode Worm ◽  
Pathogenic Infection

AbstractAt first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the house mouse Mus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.

scholarly journals Characterizing novel olfactory receptors expressed in the murine renal cortex

2019 ◽  
Vol 317 (1) ◽  
pp. F172-F186 ◽  
Author(s):  
Victoria L. Halperin Kuhns ◽  
Jason Sanchez ◽  
Dylan C. Sarver ◽  
Zoya Khalil ◽  
Premraj Rajkumar ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Olfactory Receptors ◽  
Future Research ◽  
Orphan Receptors ◽  
Functional Roles ◽  
Human Orthologs ◽  
Evolutionarily Conserved ◽  
Human Ortholog ◽  
G Protein Coupled

The kidney uses specialized G protein-coupled receptors, including olfactory receptors (ORs), to act as sensors of molecules and metabolites. In the present study, we cloned and studied seven renal ORs, which we previously found to be expressed in the murine renal cortex. As most ORs are orphan receptors, our goal was to identify ligands for these ORs in the hope that this will guide future research into their functional roles. We identified novel ligands for two ORs: Olfr558 and Olfr90. For Olfr558, we confirmed activation by previously reported ligands and identified 16 additional carboxylic acids that activated this OR. The strongest activation of Olfr558 was produced by butyric, cyclobutanecarboxylic, isovaleric, 2-methylvaleric, 3-methylvaleric, 4-methylvaleric, and valeric acids. The primary in vivo source of both butyric and isovaleric acids is gut microbial metabolism. We also identified 14 novel ligands that activated Olfr90, the strongest of which were 2-methyl-4-propyl-1,3-oxathiane, 1-octen-3-ol, 2-octanol, and 3-octanol. Interestingly, 8 of these 14 ligands are of fungal origin. We also investigated the tissue distribution of these receptors and found that they are each found in a subset of “nonsensory” tissues. Finally, we examined the putative human orthologs of Olfr558 and Olfr90 and found that the human ortholog of Olfr558 (OR51E1) has a similar ligand profile, indicating that the role of this OR is likely evolutionarily conserved. In summary, we examined seven novel renal ORs and identified new ligands for Olfr558 and Olfr90, which imply that both of these receptors serve to detect metabolites produced by microorganisms.

scholarly journals Gut Microbiome and Its Interaction with Immune System in Spondyloarthritis

2020 ◽  
Vol 8 (11) ◽  
pp. 1727
Author(s):  
Jacqueline So ◽  
Lai-Shan Tam
Keyword(s):  
Immune System ◽  
Gut Microbiome ◽  
Current Evidence ◽  
Future Research ◽  
Hla B27 ◽  
Human Immune System ◽  
Gut Inflammation ◽  
Germ Free ◽  
Gut Microorganisms

Emerging evidence suggests there is a gut-joint axis in spondyloarthritis (SpA). In a study, subclinical gut inflammation occurred in nearly 50% of SpA. Chronic gut inflammation also correlated with disease activity in SpA. Trillions of microorganisms reside in the human gut and interact with the human immune system. Dysbiosis affects gut immune homeostasis and triggers different autoimmune diseases including SpA. The absence of arthritis in HLA-B27 germ-free mice and the development of arthritis after the introduction of commensal bacteria to HLA-B27 germ-free mice proved to be the important role of gut bacteria in shaping SpA, other than the genetic factor. The recent advance in gene sequencing technology promotes the identification of microorganisms. In this review, we highlighted current evidence supporting the link between gut and axial SpA (axSpA). We also summarized available findings of gut microbiota and its interaction with the immune system in axSpA. Future research may explore the way to modulate gut microorganisms in axSpA and bring gut microbiome discoveries towards application.

scholarly journals Conserved meiotic mechanisms in the cnidarian Clytia hemisphaerica revealed by Spo11 knockout

2022 ◽  
Author(s):  
Catriona Munro ◽  
Hugo Cadis ◽  
Evelyn Houliston ◽  
Jean-Ren&eacute Huynh
Keyword(s):  
Classical Model ◽  
Fruit Fly ◽  
Model Organisms ◽  
Oocyte Growth ◽  
Alternative Pathways ◽  
Functional Studies ◽  
Evolutionarily Conserved ◽  
Synaptonemal Complex Formation ◽  
Chromosome Movements

During meiosis, each duplicated chromosome pairs and recombines with its unique homolog to ensure the shuffling of genetic information across generations. Functional studies in classical model organisms have revealed a surprising diversity in the chronology and interdependency of the earliest meiotic steps such as chromosome movements, pairing, association via Synaptonemal Complex formation (synapsis), recombination and the formation of chiasmata. A key player is Spo11, an evolutionarily conserved topoisomerase-related transesterase that initiates meiotic recombination via the catalysis of programmed DNA double stranded breaks (DSBs). While DSBs are required for pairing and synapsis in budding yeast and mouse, alternative pathways are employed during female meiosis of the fruit fly and nematode Caenorhabditis elegans. Here, to provide a comparative perspective on meiotic regulation from a distinct animal clade, we chart gametogenesis in Clytia hemisphaerica jellyfish and examine the role of Spo11 using CRISPR-Cas9 mutants, generated clonally from F0 polyp colonies. Spo11 mutant females fail to assemble synaptonemal complexes and chiasmata, such that homologous chromosome pairs disperse during oocyte growth. Subsequent meiotic divisions are abnormal but produce viable progeny. Clytia thus shares an ancient eukaryotic dependence of synapsis and chromosome segregation on Spo11-generated DSBs. It provides a valuable additional experimental model for dissecting meiotic mechanisms during animal gametogenesis, and for building a comparative framework for distinguishing evolutionarily conserved versus flexible features of meiosis.

Epithelial cell polarity: what flies can teach us about cancer

2012 ◽  
Vol 53 ◽  
pp. 129-140 ◽  
Author(s):  
Daniel T. Bergstralh ◽  
Daniel St Johnston
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Human Cancer ◽  
Fruit Fly ◽  
Model Organisms ◽  
Epithelial Cell Polarity ◽  
Energetic Stress ◽  
Evolutionarily Conserved ◽  
Cellular Machinery

Epithelial cells are polarized along their apical–basal axis. Much of the cellular machinery that goes into establishing and maintaining epithelial cell polarity is evolutionarily conserved. Model organisms, including the fruit fly, Drosophila melanogaster, are thus particularly useful for the study of cell polarity. Work in Drosophila has identified several important components of the polarity machinery and has also established the surprising existence of a secondary cell polarity pathway required only under conditions of energetic stress. This work has important implications for the understanding of human cancer. Most cancers are epithelial in origin, and the loss of cell polarity is a critical step towards malignancy. Thus a better understanding of how polarity is established and maintained in epithelial cells will help us to understand the process of malignant transformation and may lead to improved therapies. In the present chapter we discuss the current understanding of how epithelial cell polarity is regulated and the known associations between polarity factors and cancer.

scholarly journals Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2429
Author(s):  
Sajjad Muhammad ◽  
Shafqat Rasul Chaudhry ◽  
Ulf Dietrich Kahlert ◽  
Mika Niemelä ◽  
Daniel Hänggi
Keyword(s):  
Ischemic Stroke ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Time Window ◽  
Critical Role ◽  
Current Evidence ◽  
Future Research ◽  
Mortality And Morbidity ◽  
Molecular Patterns ◽  
The Brain

Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.

scholarly journals InterMOD: integrated data and tools for the unification of model organism research

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Julie Sullivan ◽  
Kalpana Karra ◽  
Sierra A. T. Moxon ◽  
Andrew Vallejos ◽  
Howie Motenko ◽  
...  
Keyword(s):  
Comparative Research ◽  
Model Organism ◽  
Genomic Analysis ◽  
Fruit Fly ◽  
Model Organisms ◽  
Basic Biology ◽  
Set Up ◽  
And Function ◽  
Model Organism Databases ◽  
Nematode Worm

Abstract Model organisms are widely used for understanding basic biology and have significantly contributed to the study of human disease. In recent years, genomic analysis has provided extensive evidence of widespread conservation of gene sequence and function amongst eukaryotes, allowing insights from model organisms to help decipher gene function in a wider range of species. The InterMOD consortium is developing an infrastructure based around the InterMine data warehouse system to integrate genomic and functional data from a number of key model organisms, leading the way to improved cross-species research. So far including budding yeast, nematode worm, fruit fly, zebrafish, rat and mouse, the project has set up data warehouses, synchronized data models and created analysis tools and links between data from different species. The project unites a number of major model organism databases, improving both the consistency and accessibility of comparative research, to the benefit of the wider scientific community.

scholarly journals Probióticos en enfermedad celíaca: ¿estamos listos para su aplicación en la práctica clínica?

2021 ◽  
Vol 51 (4) ◽  
Author(s):  
Gastón H Rueda ◽  
M Inés Pinto-Sánchez
Keyword(s):  
Celiac Disease ◽  
Immune System ◽  
Gastrointestinal Symptoms ◽  
Mechanisms Of Action ◽  
Current Evidence ◽  
Future Research ◽  
Preclinical Studies ◽  
Gluten Free ◽  
Review Of The Literature ◽  
Areas Of Interest

Probiotics, live microorganisms that produce a beneficial effect on health, are a possible supplement to a gluten-free diet in the treatment of celiac disease. Several clinical studies have shown that celiac patients treated with probiotics improved their gastrointestinal symptoms. Although the mechanisms of probiotics in celiac disease are unclear, preclinical studies in mice suggest different mechanisms, such as the modulation of the intestinal microbiota and the immune system, or through the production of proteases. We conducted a review of the literature to address the current evidence on the efficacy of probiotics in the treatment of celiac disease, possible mechanisms of action, and areas of interest for future research studies.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

Recognition of Fungal Components by the Host Immune System

2020 ◽  
Vol 21 (3) ◽  
pp. 245-264 ◽  
Author(s):  
Laura C. García-Carnero ◽  
José A. Martínez-Álvarez ◽  
Luis M. Salazar-García ◽  
Nancy E. Lozoya-Pérez ◽  
Sandra E. González-Hernández ◽  
...  
Keyword(s):  
Immune System ◽  
Histoplasma Capsulatum ◽  
Paracoccidioides Brasiliensis ◽  
Sporothrix Schenckii ◽  
Clinical Importance ◽  
Pathogenic Fungi ◽  
Diagnostic Tools ◽  
Future Research ◽  
Host Immune System ◽  
Fungal Antigens

: By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.

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