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142 results for “Toll-like receptor”
Toll-like receptor polymorphism in fan mussels
<p><span>The fan mussel <em>Pinna</em> <em>nobilis</em> is currently on the brink of extinction due to a multifactorial disease mainly caused to the highly pathogenic parasite <em>Haplosporidium</em> <em>pinnae</em>, meaning that the selection pressure outweighs the adaptive potential of the species. Hopefully, rare specimens have been observed somehow resistant to the parasite, stretching the need to identify the traits underlying this better fitness. Among the candidate to explore at first intention are fast-evolving immune genes, of which toll-like receptor (TLR). In this study, we examined the genetic diversity at 14 TLR loci across <em>Pinna</em> <em>nobilis</em>, <em>Pinna</em> <em>rudis</em> and <em>Pinna</em> <em>nobilis</em> x <em>Pinna</em> <em>rudis</em> hybrid genomes, collected at four physically distant regions, that were found to be either resistant or sensitive to the parasite <em>H</em>. <em>pinnae</em>. We report a high genetic diversity, mainly observed at cell surface TLRs compared to that of endosomal TLRs. However, the endosomal TLR-7 exhibited unexpected level of diversity and haplotype phylogeny. The lack of population structure, associated with a high genetic diversity and elevated dN/dS ratio, was interpreted as balancing selection, though both directional and purifying selection were detected. Interestingly, roughly 40% of the <em>P. nobilis</em> identified as resistant to <em>H. pinnae</em> were introgressed with <em>P. rudis </em>TLR. Specifically, all these <em>P. nobilis</em> carried a TLR-7 of <em>P. rudis</em> origin. On the contrary, sensitive <em>P. nobilis</em> were not introgressed, at least at TLR loci, highlighting that TLR-7 might be a potent effector of resistance. Small contributions of TLR-6 and TLR-4 single nucleotide polymorphism to the cluster of resistant and sensitive groups could be detected, but their specific role in the resistance remains highly speculative. This study brings additional knowledge on the molecular processes of resistance to <em>H. pinnae</em> and will likely contribute to the conservation efforts carried out to prevent from extinction this Mediterranean endemic species. </span></p>
A Phase I, 2-part (Part 1 Being a Single Dose Escalation and Part 2, a Parallel Group) Study of Toll-like Receptor (TLR4) Agonist (GSK1795091) in Healthy Subjects
ClinicalTrials.gov study NCT02798978. IPD Sharing: YES. Countries: 1. Publications: 1.
Toll-like Receptor (TLR) 7 Agonist, Cyclophosphamide, and Radiotherapy for Breast Cancer With Skin Metastases
ClinicalTrials.gov study NCT01421017. IPD Sharing: Not stated. Countries: 1. Publications: 3.
Dermal fibroblast cultures recapitulate differences between deermice and mice in responses to a Toll-like receptor agonist
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Toll-like receptor polymorphism in fan mussels
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Data from: Contracting patterns of diversity and population differentiation at the innate immunity gene Toll-like receptor 2 (TLR2) in two sympatric rodent species
Comparing patterns of diversity and divergence between populations at immune genes and neutral markers can give insights into the nature and geographic scale of parasite-mediated selection. To date, studies investigating such patterns of selection in vertebrates have primarily focused on the acquired branch of the immune system, whereas it remains largely unknown how parasite-mediated selection shapes innate immune genes both within and across vertebrate populations. Here, we present a study on the diversity and population differentiation at the innate immune gene Toll-like receptor 2 (TLR2) across nine populations of yellow-necked mice (Apodemus flavicollis) and bank voles (Myodes glareolus) in southern Sweden. In yellow-necked mice, TLR2 diversity was very low, as was TLR2 population differentiation compared to neutral loci. In contrast, several TLR2 haplotypes co-occurred at intermediate frequencies within and across bank vole populations, and pronounced isolation by distance between populations was observed. The diversity and differentiation at neutral loci was similar in the two species. These results indicate that parasite-mediated selection has been acting in dramatically different ways on a given immune gene in ecologically similar and sympatric species. Furthermore, the finding of TLR2 population differentiation at a small geographical scale in bank voles highlights that vertebrate innate immune defence may be evolutionarily more dynamic than has previously been appreciated.
Data from: Drift, not selection, shapes toll-like receptor variation among oceanic island populations
Understanding the relative role of different evolutionary forces in shaping the level and distribution of functional genetic diversity among natural populations is a key issue in evolutionary and conservation biology. To do so accurately genetic data must be analyzed in conjunction with an unambiguous understanding of the historical processes that have acted upon the populations. Here we focused on diversity at toll-like receptor (TLR) loci, which play a key role in the vertebrate innate immune system and, therefore, are expected to be under pathogen-mediated selection. We assessed TLR variation within and among 13 island populations (grouped into three archipelagos) of Berthelot's pipit, Anthus berthelotii, for which detailed population history has previously been ascertained. We also compared the variation observed with that found in its widespread sister species, the tawny pipit, Anthus campestris. We found strong evidence for positive selection at specific codons in TLR1LA, TLR3 and TLR4. Despite this, we found that at the allele frequency level, demographic history has played the major role in shaping patterns of TLR variation in Berthelot's pipit. Levels of diversity and differentiation within and across archipelagos at all TLR loci corresponded very closely with neutral microsatellite variation, and with the severity of the bottlenecks that occurred during colonization. Our study shows that despite the importance of TLRs in combating pathogens, demography can be the main driver of immune gene variation within and across populations, resulting in patterns of functional variation that can persist over evolutionary timescales.
Study of the Activation of Proinflammatory Pathways of Toll-like Receptors in Schizophrenia Patients
ClinicalTrials.gov study NCT02897167. IPD Sharing: NO. Countries: 1. Publications: 1.
Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection
ClinicalTrials.gov study NCT02443935. IPD Sharing: Not stated. Countries: 1. Publications: 2.
ENABLE-1 (Engaging Toll-like Receptor Signalling for B-cell Lymphoma Chimeric Antigen Receptor Therapy)
ClinicalTrials.gov study NCT04049513. IPD Sharing: YES. Countries: 1. Publications: 4.
Expression of Toll-Like Receptors 2 and 4 in Asthmatic Patients.
ClinicalTrials.gov study NCT02028637. IPD Sharing: Not stated. Countries: 1. Publications: 7.
Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults
ClinicalTrials.gov study NCT00562939. IPD Sharing: Not stated. Countries: 1. Publications: 2.
A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients
ClinicalTrials.gov study NCT01585350. IPD Sharing: Not stated. Countries: 1. Publications: 2.
Data from: Contracting patterns of diversity and population differentiation at the innate immunity gene Toll-like receptor 2 (TLR2) in two sympatric rodent species
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Data from: Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
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Data from: Drift, not selection, shapes toll-like receptor variation among oceanic island populations
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Data from: Genetic drift outweighs natural selection at toll-like receptor (TLR) immunity loci in a reintroduced population of a threatened species
During population establishment, genetic drift can be the key driver of changes in genetic diversity, particularly while the population is small. However, natural selection can also play a role in shaping diversity at functionally important loci. We used a well-studied, re-introduced population of the threatened Stewart Island robin (N = 722 pedigreed individuals) to determine whether selection shaped genetic diversity at innate immunity toll-like receptor (TLR) genes, over a 9-year period of population growth following establishment with 12 genetic founders. We found no evidence for selection operating with respect to TLR diversity on first-year overwinter survival for the majority of loci, genotypes and alleles studied. However, survival of individuals with TLR4BE genotype was significantly improved: these birds were less than half as likely to die prior to maturity compared with all other TLR4 genotypes. Furthermore, the population frequency of this genotype, at a two-fold excess over Hardy–Weinberg expectation, was increased by nonrandom mating. Near-complete sampling and full pedigree and reproductive data enabled us to eliminate other potential causes of these patterns including inbreeding, year effects, density dependence, selection on animals at earlier life history stages or genome-level association of the TLR4E allele with 'good genes'. However, comparison of observed levels of gene diversity to predictions under simulated genetic drift revealed results consistent with neutral expectations for all loci, including TLR4. Although selection favoured TLR4BE heterozygotes in this population, these effects were insufficient to outweigh genetic drift. This is the first empirical study to show that genetic drift can overwhelm natural selection in a wild population immediately following establishment.
Data from: Repurposed transcriptomic data facilitate discovery of innate immunity Toll-Like Receptor (TLR) genes across Lophotrochozoa
The growing volume of genomic data from across life represents opportunities for deriving valuable biological information from data that were initially collected for another purpose. Here, we use transcriptomes collected for phylogenomic studies to search for toll-like receptor (TLR) genes in poorly sampled lophotrochozoan clades (Annelida, Mollusca, Brachiopoda, Phoronida, and Entoprocta) and one ecdysozoan clade (Priapulida). TLR genes are involved in innate immunity across animals by recognizing potential microbial infection. They have an extracellular leucine-rich repeat (LRR) domain connected to a transmembrane domain and an intracellular toll/interleukin-1 receptor (TIR) domain. Consequently, these genes are important in initiating a signaling pathway to trigger defense. We found at least one TLR ortholog in all but two taxa examined, suggesting that a broad array of lophotrochozoans may have innate immune systems similar to those observed in vertebrates and arthropods. Comparison to the SMART database confirmed the presence of both the LRR and the TIR protein motifs characteristic of TLR genes. Because we looked at only one transcriptome per species, discovery of TLR genes was limited for most taxa. However, several TRL-like genes that vary in the number and placement of LRR domains were found in phoronids. Additionally, several contigs contained LRR domains but lacked TIR domains, suggesting they were not TLRs. Many of these LRR-containing contigs had other domains (e.g., immunoglobin) and are likely involved in innate immunity.
Discovery of Novel small-molecule dual inhibitor targeting toll-like receptors 7 and 9
<p>The data sets contained the MD simulation of TLR7-TIC10g and TLR9-TIC10g complexes.</p>
Expression of Toll-like Receptors 3 , 7 and 9 in Peripheral Blood Mononuclear Cells of COVID-19 Patients
ClinicalTrials.gov study NCT05089110. IPD Sharing: Not stated. Countries: 0. Publications: 2.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.