Academic literature on the topic 'TLR Genes'
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Journal articles on the topic "TLR Genes"
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Bergman, Ingrid-Maria, Amelie Johansson, Caroline Fossum, Leif Andersson, and Inger Edfors-Lilja. "Genetic analysis of porcine TLR genes." Veterinary Immunology and Immunopathology 128, no. 1-3 (March 2009): 218–19. http://dx.doi.org/10.1016/j.vetimm.2008.10.022.
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Liu, Long, Yu-Shan Wei, and Dun Wang. "Identification of Core Genes of Toll-like Receptor Pathway from Lymantria dispar and Induced Expression upon Immune Stimulant." Insects 12, no. 9 (September 14, 2021): 827. http://dx.doi.org/10.3390/insects12090827.
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The gypsy moth, Lymantria dispar, is a polyphagous forest pest worldwide. The baculovirus, Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) is a natural pathogen of L. dispar. The Toll-like receptors (TLR) pathway plays a crucial role in both innate and adaptive immunity in animals. However, The TLR pathway and its underlying immune mechanism against baculovirus in L. dispar have not been explored. In this study, eleven TLRs and five downstream TLR pathway components were identified and characterized from L. dispar. Structural analysis indicated that intracellular Toll/interleukin-1 receptor (TIR) domains of LdTLRs and LdMyD88 contained three conserved motifs, and the 3D structures of TIR domains of LdTLRs possessed similar patterns in components arrangement and spatial conformation. The TLR proteins of L. dispar were placed into five monophyletic groups based on the phylogenetic analysis. LdTLR1, 2, 5, 6, 7, 8 and all identified downstream TLR pathway factors were highly induced upon LdMNPV infection, indicating that the TLR pathway of L. dispar was activated and might play a role in the immune response to LdMNPV infection. Collectively, these results help elucidate the crucial role of the TLR pathway in the immune response of L. dispar against LdMNPV, and offer a foundation for further understanding of innate immunity of the pest.
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Pryimenko, Nataliia O., Tetiana M. Kotelevska, Tetiana I. Koval, Vadym A. Bodnar, Liudmyla M. Syzova, and Stanislav S. Rudenko. "EFFICACY OF SPECIFIC PREVENTION OF INFLUENZA IN INDIVIDUALS WITH POLYMORPHISMS ARG753GLN OF TLR-2, LEU412PHE OF TLR-3, ASP299GLY OF TLR-4 GENES." Wiadomości Lekarskie 73, no. 9 (2020): 1944–49. http://dx.doi.org/10.36740/wlek202009209.
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The aim: Is to study the efficacy of influenza vaccination for individuals with polymorphism Arg753Gln of TLR-2 gene, Leu412Phe of TLR-3 gene, and Asp299Gly of TLR-4 gene. Materials and methods: 66 people with mutant genotypes and normal distribution of alleles of TLR-2, TLR-3, TLR-4 genes, aged 18-63, were inoculated with anti-influenza vaccine. The genotyping of Arg753Gln polymorphic site of TLR-2, Asp299Gly of TLR-4, and Leu412Phe of TLR-3 gene was carried out by polymerase chain reaction with oligonucleotide primers usage. The immunological efficacy of vaccination was evaluated by seroconversion, seroprotection, and dynamics of mean geometric titers of antibodies. Results: It has been established that individuals with mutant genotypes Arg/Gln of TLR-2, Leu/Phe, Phe/Phe of TLR-3, Asp/Gly of TLR-4 genes have a vaccinal response to administering anti-influenza vaccine at the level of subjects with normal distribution of TLR alleles, as evidenced by the growth in dynamics of mean geometric titers of antibodies to vaccine strains, the level of seroprotection and seroconversion. Clinical and epidemiological efficacy of vaccination in this category of people is characterized by: reduction of ARI cases in the postvaccinal period by 2,0-3,0 times; prevention of pneumonia in all vaccinated subjects; decrease in the frequency of bronchitis by 2,5-3,8 times. Conclusions: Effectiveness of influenza vaccination in individuals with Arg573Gln polymorphism of TLR-2, Leu412Phe of TLR-3, Asp299Gly of TLR-4 genes by immune and clinical epidemiological parameters is determined at the level of vaccinated subjects with normal distribution of TLR-2, TLR-3, TLR-4 alleles. Specific influenza immunization of people with polymorphic modified genotypes of TLR-2, TLR-3, TLR-4 genes can prevent the development of pneumonia and reduce the incidence of bronchitis.
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Cui, Jian, Greta J. Frankham, Rebecca N. Johnson, Adam Polkinghorne, Peter Timms, Denis O’Meally, Yuanyuan Cheng, and Katherine Belov. "SNP Marker Discovery in Koala TLR Genes." PLOS ONE 10, no. 3 (March 23, 2015): e0121068. http://dx.doi.org/10.1371/journal.pone.0121068.
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Ramos Aguila, Luis Carlos, Hafiza Javaira Ashraf, Jessica Paola Sánchez Moreano, Komivi Senyo Akutse, Bamisope Steve Bamisile, Liuyang Lu, Xiaofang Li, Jingyi Lin, Qing Wu, and Liande Wang. "Genome-Wide Identification and Characterization of Toll-like Receptors (TLRs) in Diaphorina citri and Their Expression Patterns Induced by the Endophyte Beauveria bassiana." Journal of Fungi 8, no. 8 (August 22, 2022): 888. http://dx.doi.org/10.3390/jof8080888.
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Toll-like receptors (TLRs) are pathogen recognition receptors (PRRs), which play key roles in helping the host immune system fight pathogen invasions. Systematic information on TLRs at the genome-wide level and expression profiling in response to endophytic colonization is very important to understand their functions but is currently lacking in this field. Here, a total of two TLR genes were identified and characterized in Diaphorina citri. The TLR genes of D. citri were clustered into five families according to the phylogenetic analysis of different species’ TLRs. The domain organization analyses suggested that the TLRs were constituted of three important parts: a leucine-rich repeat (LRR) domain, a transmembrane region (TR) and a Toll/interleukin-1 receptor (TIR) domain. The mRNA expression levels of the two TLR genes (DcTOLL and DcTLR7) were highly regulated in both nymphs and adults of D. citri. These results elucidated the potentiated TLR gene expression in response to endophytically colonized plants. Furthermore, the 3D structures of the TIR domain were highly conserved during evolution. Collectively, these findings elucidate the crucial roles of TLRs in the immune response of D. citri to entomopathogens systematically established as endophytes, and provide fundamental knowledge for further understanding of the innate immunity of D. citri.
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Fajar, Jonny Karunia. "H1 antihistamines in allergic rhinitis: The molecular pathways of interleukin and toll - like receptor systems." Journal of Health Sciences 6, no. 1 (March 25, 2016): 1. http://dx.doi.org/10.17532/jhsci.2016.272.
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The complex interaction between inflammatory mediators in allergic rhinitis (AR) is determined by the role of genetic polymorphisms, including interleukin (IL) and toll-like receptor (TLR) genes. This study aimed to discuss the effects of H1-antihistamines on IL and TLR systems. Several ILs involved in AR pathogenesis are: IL-4 (rs2243250, rs1800925, rs1801275, rs2227284, rs2070874), IL-6 (rs1800795, rs1800797), IL-10 (rs1800871, rs1800872), IL-12R (rs438421), IL-13 (rs1800925, rs20541), IL-17 (rs3819024), IL-18 (rs360721, rs360718, rs360717, rs187238), IL-23R (rs7517847), and IL-27 (rs153109, rs17855750). In the IL system, histamines stimulate the IL production in Type 2 helper T (Th2) cells through protein kinase A (PKA), janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, and the activation of H1-histamine receptor and histidine decarboxylase (HDC) genes. On contrary, antihistamines down-regulate the H1-histamine receptor gene expression through the transcription suppression of HDC and IL genes and suppress histamine basal signaling through the inverse agonistic activity. TLRs involved in AR pathogenesis are TLR2 (rs4696480, rs3804099, rs5743708), TLR4 (rs4986790), TLR6 (rs2381289), TLR7 (rs179008, rs5935438), TRL8 (rs2407992, rs5741883, rs17256081, rs4830805, rs3788935, rs178998), and TLR10 (rs11466651). In the TLR system, histamines trigger the TLR expression by stimulating interferon-γ (IFN-γ) to up-regulate mast cells and by stimulating receptor-interacting protein (RIP) to activate IκB kinase-β. Contrastingly, antihistamines suppress TIR-domain-containing adaptor protein inducing IFN-β (TRIF) and RIP protein and thus inhibit the expression of TLR. In addition, several studies indicated that H1-antihistamines inhibit the IL and TLR systems indirectly.
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Tantia, M. S., Bina Mishra, P. Banerjee, J. Joshi, S. Upasna, and R. K. Vijh. "Phylogenetic and sequence analysis of toll like receptor genes (TLR-2 and TLR-4) in buffaloes." Indian Journal of Animal Sciences 82, no. 8 (August 14, 2012): 875–78. http://dx.doi.org/10.56093/ijans.v82i8.23016.
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The toll like receptors play a significant role in innate immune response with TLR2 and TLR4 genes being associated with mastitis in cattle. The sequences of these genes were not known in buffaloes and in the present study we sequenced these 2 genes in buffaloes using 24 samples belonging to 6 diverse buffalo breeds of India. Primers were designed from the cattle data base and the buffalo genomic DNA was amplified. The gene sequences obtained after alignment were submitted to NCBI. The TLR2 gene was 3590 bases with 2 exons and coding for 784 amino acids. The TLR4 gene was 4256 nucleotide bases and consisted of 3 exons and coded for 841 amino acids. Eight SNPs were detected in TLR2 gene out of which 3 were non-synonymous. 25 SNPs were detected in TLR4 gene and out of which 10 were non-synonymous leading to change in amino acids. The 2 genes were found to be highly conserved across all mammalian species, and the phylogenetic relationship revealed the closeness of buffalo species with other ruminants, viz. cattle, sheep and goat compared to mono-gastric animals, viz. pigs and man.
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Sharbafi, Mohammad Hossein, Sara Assadiasl, Fatemeh Pour‐reza‐gholi, Saeed Barzegari, Peyman Mohammadi Torbati, Shiva Samavat, Mohammad Hossein Nicknam, and Aliakbar Amirzargar. "TLR‐2, TLR‐4 and MyD88 genes expression in renal transplant acute and chronic rejections." International Journal of Immunogenetics 46, no. 6 (July 9, 2019): 427–36. http://dx.doi.org/10.1111/iji.12446.
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Shaik-Dasthagirisaheb, Yazdani, Steve Shen, Caroline Genco, and Frank Gibson III. "Ageing and expression of TLR pathway associated genes in macrophages to Porphyromonas gingivalis challenge. (55.26)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 55.26. http://dx.doi.org/10.4049/jimmunol.188.supp.55.26.
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Abstract Background: Periodontal disease is a chronic inflammatory disease that leads to progressive loss of soft and hard tissues supporting the teeth. Porphyromonas gingivalis (Pg) is a bacterium closely associated with periodontal disease. Toll-like receptors (TLR) and their intracellular signaling pathways play roles in host response to Pg. The focus of the current study was to define the expression profile of TLR pathway associated genes in macrophages (MØ) cultured with Pg, and to define changes in expression of these genes as a consequence of ageing. Methods: Bone marrow MØ from 2 months and1 year old wild type (WT), TLR2 knockout (KO), TLR4KO, MyD88KO and LPS2 mice were cultured with Pg. RNA was harvested from unchallenged and Pg challenged cells and expression of TLR pathway associated genes was measured by qPCR microarrays. Results: Pg challenge of WT MØ induced expression of a large set of TLR pathway associated genes. MØ gene expression data revealed 19, 48, 45 and 56 genes differentially regulated in TLR2KO, TLR4KO, MyD88KO and LPS2 mice respectively as compared with WT in response to Pg. We identified 19 genes that are commonly regulated in all four mutant genotypes. Age had little effect on the differential regulation of these genes by mutant MØ as compared with WT. Conclusions: Regulation of TLR pathway associated genes by MØ was highly responsive to Pg challenge. Pg challenge and mouse genotype had the strongest effects on gene expression in this model.
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Melnichuk, Nataliia, Vladimir Kashuba, Svitlana Rybalko, and Zenoviy Tkachuk. "Complexes of Oligoribonucleotides with d-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo." Pharmaceuticals 11, no. 3 (July 22, 2018): 73. http://dx.doi.org/10.3390/ph11030073.
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Rapid replication of the influenza A virus and lung tissue damage caused by exaggerated pro-inflammatory host immune responses lead to numerous deaths. Therefore, novel therapeutic agents that have anti-influenza activities and attenuate excessive pro-inflammatory responses that are induced by an influenza virus infection are needed. Oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess both antiviral and anti-inflammatory activities. The current research was aimed at studying the ORNs-d-M effects on expression of innate immune genes in mice lungs during an influenza virus infection. Expression of genes was determined by RT-qPCR and Western blot assays. In the present studies, we found that the ORNs-d-M reduced the influenza-induced up-expression of Toll-like receptors (TLRs) (tlr3, tlr7, tlr8), nuclear factor NF-kB (nfkbia, nfnb1), cytokines (ifnε, ifnk, ifna2, ifnb1, ifnγ, il6, il1b, il12a, tnf), chemokines (ccl3, ccl4, сcl5, cxcl9, cxcl10, cxcl11), interferon-stimulated genes (ISGs) (oas1a, oas2, oas3, mx1), and pro-oxidation (nos2, xdh) genes. The ORNs-d-M inhibited the mRNA overexpression of tlr3, tlr7, and tlr8 induced by the influenza virus, which suggests that they impair the upregulation of NF-kB, cytokines, chemokines, ISGs, and pro-oxidation genes induced by the influenza virus by inhibiting activation of the TLR-3, TLR-7, and TLR-8 signaling pathways. By impairing activation of the TLR-3, TLR-7, and TLR-8 signaling pathways, the ORNs-d-M can modulate the innate immune response to an influenza virus infection.
Dissertations / Theses on the topic "TLR Genes"
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Wlasiuk, Battagliotti Gabriela. "THE MOLECULAR EVOLUTION OF INNATE IMMUNITY GENES." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/195184.
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It is not clear whether genes of the innate immune system of vertebrates are subject to the same selective pressures as genes of the adaptive immune system, despite the fact that innate immunity genes lie directly at the interface between host and pathogens. The lack of consensus about the incidence, type, and strength of selection acting on vertebrate innate immunity genes motivated this study. The goal of this work was to elucidate the general principles of innate immune receptor evolution within and between species. A phylogenetic analysis of the Toll-like receptor 5 (TLR5) in primates showed an excess of nonsynonymous substitutions at certain codons, a pattern that is consistent with recurrent positive selection. The putative sites under selection often displayed radical substitutions, independent parallel changes, and were located in functionally important regions of the protein. In contrast with this interspecific pattern, population genetic analysis of this gene in humans and chimpanzees did not provide conclusive evidence of recent selection. The frequency and distribution of a TLR5 null mutation in human populations further suggested that TLR5 function might be partially redundant in the human immune system (Appendix A). Comparable analyses of the remaining nine human TLRs produced similar results and further pointed to a biologically meaningful difference in the pattern of molecular evolution between TLRs specialized in the recognition of viral nucleic acids and the other TLRs (Appendix B). The general picture that emerges from these studies challenges the conventional idea that pattern recognition receptors are subject to an extreme degree of functional constraint dictated by the recognition of molecules that are essential for microbial fitness. Instead, TLRs display patterns of substitution between species that reflect an old history of positive selection in primates. A common theme, however, is that only a restricted proportion of sites is under positive selection, indicating an equally important role for purifying selection as a conservative force in the evolution of this gene family. A comparative analysis of evolutionary rates at fifteen loci involved in innate, intrinsic and adaptive immunity, and mating systems revealed that more promiscuous species are on average under stronger selection at defense genes (Appendix C). Although the effect is weak, this suggests that sexual promiscuity plays some role in the evolution of immune loci by affecting the risk of contracting infectious diseases.
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Maughan, Willard. "The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1844.
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AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased African-American population. Additionally, this is the first study to assess the role of TLR-9 polymorphism in periodontitis patients. METHODS: A total of 130 subjects were involved in the study. The chronic periodontitis (CP) group contained 73 subjects, and the healthy control (NP) group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 (C260T) genes by TaqMan® allelic discrimination using Assay-by-DesignSM SNP Genotyping Assays (Applied Biosystems). Accuracy of genotyping was confirmed by known DNA samples of each genotype and by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses on selected samples. Fisher’s exact test and chi-square analyses were performed to compare genotype and allele frequencies. Within disease groups, we investigated whether SNPs were related to disease severity by step-wise logistic regression adjusted for age, gender, and smoking status. RESULTS: There was a significant difference in the distribution of specific TLR9 (T1486C) genotypes between the periodontally diseased group versus the control group. Expression of TT genotype was more prevelant in periodontally-diseased individuals compared to periodontally-healthy subjects (p<0.0001) whereas individuals expressing C allele of the TLR9 SNP (CC&CT) were more frequently found in the control group after adjusting for age, gender, and smoking status (p<0.0001) There was no statistically significant difference in the distribution of genotypes between groups for any other TLRs or CD14 polymorphism. CONCLUSION: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to chronic periodontal disease susceptibility in African Americans. Additionally, presence of the C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD14 genes are not related to periodontitis in African Americans.
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Franchim, Camila Sommerauer [UNIFESP]. "Mediadores de inflamação e pré-eclâmpsia: análise de polimorfismos de genes codificadores de IL1-R1, IL-12, IL-18, TLR-2 e TLR-4." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9805.
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Previous issue date: 2009-04-29Objetivo: avaliar a possível relação entre polimorfismos dos genes codificadores de receptor 1 de interleucina (IL) 1 (IL-1R1) (PstI, rs2234650), IL-12 (+1188, rs3212227), IL-18 (-137, rs187238), IL-18 (-607, rs1946519), receptor tipo Toll (TLR) 2 (TLR-2) (+2258, rs5743708) e TLR-4 (+896, rs4986790) e a pré-eclâmpsia (PE). Pacientes e métodos: Este estudo de caráter caso-controle incluiu 109 pacientes com PE e 174 gestantes sem patologia sistêmica ou obstétrica, e com história de duas ou mais gestações sem intercorrências, como controles. O DNA genômico foi extraído de sangue periférico por método de DTAB/CTAB, e os polimorfismos foram genotipados por técnicas de PCR-RFLP ou PCR-ARMS. Para a análise dos resultados, foram utilizados os testes t de Student e exato de Fischer, tendo sido adotado o nível de significância de p<0,05. Resultados: As freqüências genotípicas do polimorfismo do gene IL-1R1 foram 20,9% CC, 59% CT e 20,1% TT em casos de PE; e 24,7% CC, 56,2% CT e 19,1% TT em controles (p=0,82). As freqüências do polimorfismo do gene IL-12 foram 54,7% AA, 32,9% AC e 12,4% CC em casos de PE; e 55,4% AA, 33,8% AC e 10,8% CC em controles (p=0,93). As freqüências genotípicas de IL-18 (-137) foram 5,2% CC, 42,7% CG e 52,1% GG em casos de PE; e 7,6% CC, 43% CG e 49,4% GG em controles (p=0,74). As freqüências genotípicas de IL-18 (-607) foram 41% CC, 52,7% CA e 6,3% AA em pacientes com PE; e 32,2% CC, 56,2% CA e 11,6% AA no grupo controle (p=0,22). As freqüências do polimorfismo do gene TLR-2 foram 84,6% GG e 15,4% GA em casos de PE; e 84,8% GG e 15,2% GA em controles (p=0,97). As freqüências do polimorfismo do gene TLR-4 foram 93,6% AA e 6,4% AG em casos de PE; e 87,6% AA, 11,7% AG e 0,7% GG em controles (p=0,23). Não houve diferenças significantes entre os grupos, quanto às freqüências genotípicas e alélicas. Conclusões: Não foi observada associação entre polimorfismos de genes codificadores de IL- 1R1, IL-12, IL-18, TLR-2 e TLR-4 e a ocorrência de pré-eclâmpsia.
Problem: Intense maternal inflammatory response is a central event in the pathogenesis of preeclampsia (PE) Our aim was to assess a possible relation between pro-inflammatory mediators: IL-1R1, IL-12, IL-18, IL-18, TLR-2 and TLR-4 gene polymorphisms and PE. Method of Study: This case-control study included 109 patients with PE and 174 healthy women (controls). Genotyping were performed by PCR-ARMS or PCR-RFLP techniques. Data were analyzed by Student´s t or Fischer´s exact tests, and significance was set at p<0.05. Results: Genotypic and allelic distribution for all six polymorphisms was similar between the study and control groups (p=0.82 for IL-1R1, p=0.93 for IL-12, p=0.74 for IL-18 -137, p=0.22 for IL-18 -607, p=0.97 for TLR-2 and p=0.23 for TLR-4 gene polymorphisms). Conclusions: Our findings suggest that the analyzed pro-inflammatory gene polymorphisms are not associated with the occurrence of PE. Further studies have to be done to confirm these results.
TEDE
BV UNIFESP: Teses e dissertações
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Morale, Mirian Galliote. "Efeito da infecção por HPV nas vias de sinalização por toll like receptors." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-30112016-100636/.
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As oncoproteínas E6 e E7 do Papilomavírus Humano (HPV) estão envolvidas na desregulação do sistema imune inato, provocando alterações na expressão dos receptores do tipo Toll (TLR). Considerando-se a função da via de sinalização iniciada por TLR, haveria uma vantagem para o vírus capaz de manipular a resposta desta via de modo que possa persistir nas células sem ser detectado pelo sistema imune ou ainda modulando essa resposta e criando um ambiente mais propício à manutenção da infecção. No entanto, muitos dos mecanismos que levam à eliminação da infecção ou persistência do HPV ainda são pouco conhecidos. O objetivo principal desse trabalho é investigar o papel das vias de TLR no processo de carcinogênese mediado por HPV. Inicialmente, foi analisada a expressão de genes da via de TLR em linhagens de tumores cervicais e em células expressando as oncoproteínas virais. Foram identificados vários genes diferencialmente expressos entre linhagens de células tumorais e queratinócitos normais, incluindo moléculas adaptadoras da via de TLR e genes associados à via da MAP quinase, ativação de NFkappaB e resposta imune antiviral. Cerca de 90% destes genes foram regulados negativamente. Entre eles, destacamos HMGB1, que apesar de possuir menos RNAm nas células tumorais possui um nível proteico muito maior, além de ter-se mostrado de grande importância para a viabilidade e proliferação das células tumorais, conforme demonstrado através de experimentos de supressão gênica. Em conjunto, os nossos dados indicam que E6 e E7 de HPVs de alto risco inibem proteínas da via de sinalização de TLRPrevious studies have shown that E6 and E7 HPV oncoproteins are involved in innate immune system dysregulation, causing alterations on Toll-like receptors (TLR) expression. Considering TLR pathway function, it would be advantageous for a virus to manipulate the response of this pathway so it can persist in cells without being detected by the immune system or to modulate this response to create a better environment for persistence of infection. However, many of the mechanisms leading to HPV infection clearance or persistence are still unknown and matter of active investigation. We analyzed in cervical cancer cell lines expression of genes from TLR pathway; several were differentially expressed between tumor cells lines and normal keratinocytes, including TLR adaptors molecules and genes associated with MAP kinase pathway, NFkappaB activation and antiviral immune response. About 90% of these genes were down regulated. Among them, we selected HMGB1 for further characterization due to its interference with tumor cell viability and proliferation. Altogether, our data indicate that high risk HPV E6 and E7 can inhibit TLR signaling pathway
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Das, Avishek. "Frequency and distribution of TLR genes in some human populations of North Bengal and their association with rheumatoid arthritis." Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2827.
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Belo, Vanessa de Almeida. "Expressão de genes da resposta imune em bovinos infestados com carrapatos (Boophilus microplus)." Universidade Federal de Juiz de Fora (UFJF), 2008. https://repositorio.ufjf.br/jspui/handle/ufjf/2841.
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Nos países tropicais, as perdas causadas pela infestação de carrapatos em bovinos acarretam um grande impacto no sistema de produção animal. Recentes estudos têm mostrado a importância de fatores genéticos ligados a resistência a carrapato em Bos taurus indicus e Bos taurus taurus e que as citocinas têm um papel crítico na prevenção ou progressão de doenças. O objetivo desse trabalho foi avaliar os níveis de expressão dos genes IL-10 e IL-4 relacionados ao perfil imunológico Th2 associado à susceptibilidade ao carrapato e os genes IL-2 e IFN- relacionados ao perfil imunológico Th1 associado à resistência ao parasito. Além destes genes, analisou-se o perfil de expressão do gene TLR-2, importante no processo de reconhecimento de patógenos e os genes IL-8 e TNF-α importantes no processo inflamatório inicial. Seis animais mais resistentes e seis animais mais susceptíveis de uma população F2 de 332 animais, originária do cruzamento de animais F1(½ Holandês: ½ Gir), foram selecionados baseado na contagem de carrapatos e valor genético. Amostras de tecido foram coletadas de pele no 5° e 12° dias após a infestação para extração de RNA total. As PCRs em tempo real foram realizadas usando o gene GAPDH como controle endógeno. Os animais resistentes e susceptíveis apresentaram aumento de expressão do gene IL-10 no 5° (p<0,01) e 12 ° dias após a infestação (p<0,05). O gene IL-2, nos animais resistentes e susceptíveis, no 5° dia após a infestação não apresentou alteração da expressão sendo que 12° dia, em ambos os grupos de animais, este gene passou a ser mais expresso em relação ao animal controle sugerindo um perfil de resposta imunológica do tipo de Th2 nos animais resistentes e susceptíveis nos primeiros dias após a infestação. O gene IL-4 apresentou uma tendência ao aumento de expressão nos animais resistentes e susceptíveis em relação ao controle, sendo o perfil Th2 sugerido atribuído a IL-10 produzida por linfócitos T regulatórios (p>0,05). O gene TNF- apresentou aumento de expressão nos animais susceptíveis no 5° dia após a infestação com posterior diminuição no 12° dia após a infestação (p<0,05). Nos animais resistentes não foi observada alteração da expressão deste gene, isto sugere que ele possa estar mais atuante no início do processo inflamatório, logo após a fixação do carrapato. A mesma observação estende-se para o gene IL-8, em que não foi verificada alteração de expressão nos animais resistentes, embora nos animais susceptíveis este gene apresentou diminuição da expressão no 12° dia após a infestação (p<0,05). Quanto ao gene IFN-, não houve diferença de expressão entre os animais resistentes e susceptíveis, sendo que este gene parece não estar relacionado ao mecanismo de resistência. O gene TLR-2 apresentou diminuição da expressão em ambos os grupos de animais. Estes resultados sugerem que a resposta imune adquirida avaliada neste trabalho não apresenta papel preponderante no mecanismo de resistência e que resposta imune inata poderia está envolvida no mecanismo de resistência ao carrapato. Portanto, avaliação da resposta imunológica horas após a fixação do carrapato poderia nos fornecer resultados mais conclusivos.
In tropical countries losses caused by tick infestation in cattle lead to a major impact on animal production systems. Recent studies have shown the importance of genetic factors linked to tick resistance in Bos indicus and Bos taurus as well as the critical role in the prevention or progression of diseases mediated by cytokines. The aim of this work was to evaluate gene expression of IL-10 and IL-4 in relation to tick susceptibility associated with the Th2 profile and gene expression of IL-2 and IFN- in relation to tick resistance associated with the Th1 profile. In addition, the expression of TLR-2, important in the process the recognition of pathogens, and TNF-α and IL-8 genes, important in the initial inflammatory process, were evaluated. Six tick-resistant and six tick-susceptible animals from a F2 population of 332 animals, originated from the cross of F1 animals (½ Holstein: ½ Gir), were selected based on tick count and breeding value for tick resistance. Skin biopsies were collected in the 5th and 12th days after tick infestation. The GAPDH was used as endogenous control to normalize the amount of starting cDNA target in the real-time PCR assay. Both resistant and susceptible animals showed increased gene expression of IL-10 in the 5th and 12th days after infestation in relation to control animal (p<0.05). The IL-2 gene showed no change of expression in the 5th day after infestation for the resistant and susceptible animals. In the 12th post infestation, both resistant and susceptible animals showed increased gene expression in relation to control animal. These results suggest an enhancement of Th2 profile through the increase of IL-10 mRNA levels and a possible inhibition of the Th1 pattern in both groups (resistant and susceptible) starting 5 days after infestation and return to normal by day 12. Despite our results suggest the occurrence of the Th2 profile, the susceptible and resistant animals did not show variation on gene expression for IL-4 in relation to control animal. The susceptible animals showed increased expression of TNF-α in the 5th day after infestation. However, in the 12th day post infestation it was noted a decrease in the gene expression level. The resistant animals showed no change in the expression of this gene in relation to control animals suggesting that TNF-α could be more actively expressed in the early steps of the inflammatory process. Similarly, the resistant animals showed no variation in the expression of IL-8 while the susceptible animals showed increased expression in the 12th day post infestation. There were no differences of expression between resistant and susceptible animals in relation to IFN-γ what suggests that this gene might not be involved in the resistance mechanism. The TLR-2 gene showed decreased expression in both resistant and susceptible animals (p<0.05). Finally, there was no difference in expression between susceptible and resistant animals in relation to all selected genes in the 5th and 12th days after infestation. These results suggest that the acquired immunity evaluated in this work might not have preponderant role in the resistance mechanism. The innate immunity might be playing a major role in the bovine tick resistance/susceptibility mechanism in early hours after infestation.
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Brito, Sara Alves Paiva de. "Produção de prostaglandinas pelo endométrio canino ao longo do ciclo éstrico e a sua relação com a transcrição de genes dos toll-like receptors." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2011. http://hdl.handle.net/10400.5/3131.
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Dissertação de Mestrado Integrado em Medicina VeterináriaO endométrio canino constitui a primeira linha de defesa contra infecções bacterianas ascendentes, sendo os toll-like receptors (TLRs) elementos chave no reconhecimento de agentes patogénicos por parte do sistema imunitário inato. Um dos objectivos deste trabalho consistiu na avaliação da expressão de mRNA dos TLRs no endométrio da cadela ao longo do ciclo éstrico. Detectou-se a expressão de mRNA dos TLRs 1-7 e 9 por RT-PCR, o que demonstra a sua capacidade de reconhecimento de uma grande variedade de ligandos através da activação via TLRs. Verificou-se ainda que a transcrição dos TLRs 2 e 4 se encontra significativamente diminuída no início de diestro, o que pode justificar a maior susceptibilidade do útero à infecção por E. coli nesta fase. Pelo contrário, no final de diestro, a transcrição de genes destes receptores demonstrou estar bastante aumentada. O outro objectivo consistiu na determinação da produção de PGE2 e de PGF2α por explantes do endométrio de diferentes fases do ciclo éstrico, na ausência e na presença de estímulos como o lipopolissacarídeo (LPS) e o ácido lipoteicóico (LTA). A estimulação com LPS e LTA levou a um aumento da produção de ambas as prostaglandinas em relação ao tecido não estimulado. No entanto, este aumento foi significativamente superior nos explantes de final de diestro, quando comparado com os de fase folicular, diestro e anestro. Estes resultados sugerem, em suma, a capacidade de activação dos TLRs 2 e 4 em modelos de cultura de explantes de endométrio de cadela, resultando na produção de mediadores capazes de regular a resposta inflamatória local.
ABSTRACT - PROSTAGLANDINS PRODUCTION BY CANINE ENDOMETRIUM THROUGH THE OESTRUS CYCLE AND ITS RELATIONSHIP WITH TOLL-LIKE RECEPTORS GENES TRANSCRIPTION - The canine endometrium is the first line of defense against ascending bacterial infections and the toll-like receptors (TLRs) are key elements in pathogen recognition by innate immune system. The first aim of this study was to evaluate the mRNA expression of TLRs in the endometrium of the bitch throughout the oestrus cycle. Gene transcription of TLRs 1-7 and 9 was detected by RT-PCR, which demonstrates its ability to recognize a wide range of ligands through TLR activation. It was also found that gene transcription of TLRs 2 and 4 are downregulated in early diestrus, which might explain the higher susceptibility to uterine infection, induced by Escherichia coli, in this stage. On the other hand, in late diestrus the mRNA expression of these receptors has proven to be greatly increased. The other objective was to assess the production of PGE2 and PGF2α by endometrial explants in different stages of the oestrus cycle, in the absence and presence of stimuli like lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Stimulation with LPS and LTA led to an increased production of both prostaglandins compared with that observed in unstimulated tissues. However, this increase was significantly higher in explants from late diestrus, when compared with those in follicular phase, diestrus and anestrus. These results suggest, briefly, the activation of TLRs 2 and 4 in canine endometrial explants culture models, which result in the mediators production that may further regulate local inflammatory response.
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Fornuskova, Alena. "Genes of innate immunity and their significance in evolutionary ecology of free livings rodents." Phd thesis, Université Montpellier II - Sciences et Techniques du Languedoc, 2013. http://tel.archives-ouvertes.fr/tel-01021258.
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Appropriate recognition of parasites is crucial for effective immune response, ensuring activation of adequate defence mechanisms. In vertebrates, it has frequently been demonstrated that genes encoding proteins involved in pathogen recognition by an adaptive immune system are often subject to intense selection pressures. On the contrary, much less information has been provided on the evolution of recognition mechanisms of innate immunity. The aim of this thesis is to describe the pattern of natural variation of innate immunity genes involved in pathogen recognition in rodents and to analyze the mechanisms of their evolution. We used murine rodents (subfamily Murinae) as a principal model group because they are potential reservoirs of various pathogens dangerous to humans. First, we studied the intraspecific variability of five bacterial sensing Toll-like receptors (TLR1, TLR2, TLR4, TLR5, and TLR6) in inbred strains derived from two subspecies of the house mouse (M. m. musculus, hereafter abbreviated as Mmm and Mus musculus domesticus, Mmd). Wild-derived inbred strains are suitable tools for studying variation of immunity genes because they provide information about alleles that occur in natural populations, and at the same time they occur at homozygous state. The most significant results include the findings of a stop codon in exon 2 of the Tlr5 gene in one Mmm strain and no variability in Tlr4 of Mmd. Following these results we decided to check whether the absence of Tlr4 polymorphism in Mmd reflects the pattern found in natural populations, or whether it is a consequence of insufficient sampling or subsequent breeding. We therefore sequenced Tlr4 in both subspecies across a large part of the Western Palearctic region (in total 39 Mmm and 62 Mmd individuals), then we compared these results with variability on mitochondrial DNA (cytochrome b). The result confirmed our prediction that observed variability in Mmd is strongly reduced also in free-living populations (compared to Mmm), probably due to strong purifying selection by pathogens with which they met during the westward colonization. However, the influence of random evolutionary processes (e.g. drift during bottlenecks) cannot be excluded based on our data. At the intraspecific level, we could not find any sign of positive selection. The last part of my dissertation is devoted to interspecific comparison of two receptors, TLR4 and TLR7. These two TLRs differ in the exposure and the ligands detection. TLR4 is an extracellular receptor detecting mainly bacterial ligands (especially lipopolysaccharides), while TLR7 is located inside the cell and detects ssRNA viruses. The aim of this part of the thesis was to describe variability of both receptors at the interspecific level and to reveal selection forces acting on TLRs in longer evolutionary time scale. In total we analyzed 23 rodent species of the subfamily Murinae in Europe, Asia and Africa. Our results suggest that purifying selection has been a dominant force in evolution of the Tlr4 and Tlr7 genes, but we also demonstrated that episodic diversifying selection has shaped the present species-specific variation in rodent Tlrs. Sites under positive selection were concentrated mainly in the extracellular domain of both receptors, which is responsible for ligand binding. The comparison between two TLRs lead us to the conclusion that the intracellular TLR7 is under much stronger negative selection pressure, presumably due to its interaction with viral nucleic acids.
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Бевз, Т., Г. Мартинюк, С. Куляс, О. Попович, and Л. Медведєва. "Особливості клінічного перебігу та прогнозу хронічного гепатиту С при поліморфізмі гену TLR4." Thesis, Сумський державний університет, 2017. http://essuir.sumdu.edu.ua/handle/123456789/65455.
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Згідно офіційної статистики, в Україні станом
на 1 січня 2014 р. близько 3% наслення хворі на ВГС.
Приблизно у 85% всіх інфікованих розвивається хронічний
гепатит С, що призводить до розвитку цирозу печінки у 20%
(протягом 20 років) і гепатоцелюлярної карциноми у 7%
пацієнтів. Відсутність специфічної імунопрофілактики; побічні
ефекти та стійкість до лікування, яке є високовартісним – все це
диктує необхідність пошуку нових шляхів оптимізації
діагностики та лікування хворих на хронічний вірусний гепатит
С.The clinical investigation discusses the connection between TLR4-polymorphysm and the liver fibrosis progression degree, HCV viral load among patients with chronic HCV-hepatitis for diagnostics and treatment improvement in such individuals.
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Neto, Lídio Gonçalves Lima. "Polimorfismo dos genes CD14, TLR2, TLR4, IL6 e sua associação com o infarto do miocárdio em adultos jovens." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-18022014-101606/.
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O objetivo deste estudo foi avaliar a possível associação entre os polimorfismos -260C/T do gene CD14, Arg753Gln do gene TLR2, Asp299Gli e Thr39911e do gene TLR4 e -174G/C do gene IL6 com o infarto do miocárdio em adultos jovens. Para isso, foi realizado um estudo caso controle, sendo o grupo de estudo constituído por 102 pacientes que tiveram de infarto do miocárdio (34,5 ± 5 anos) e o grupo controle (35,1±8,7 anos) por 108 indivíduos sem histórico de doenças cardiovasculares. A genotipagem foi realizada pela PCRRFLP. Houve ausência de associação entre a distribuição dos genótipos dos SNPs -260C/T do gene CD14, Arg753Gln do gene TLR2, Asp299Gli e Thr39911e do gene TLR4 e -174G/C do gene IL6 entre os dois grupos estudados (p<0,05). O perfil sérico inflamatório e hematológico relacionou-se com polimorfismo -174G/C IL-6 do grupo IAM. O genótipo GG relacionou com elevação nas concentrações de PAI-1 (p<0,0001), o genótipo GC com maiores quantidades de hemácias (p=0,02) e o genótipo CC com concentrações elevadas de fibrinogênio (p<0,01) e quantidade aumentada de leucócitos (p<0,05). O genótipo CC do polimorfismo -260C/T CD14 também mostrou relação com a elevação nas concentrações de PAI-1 (0,0001) e o genótipo CT com o de fibrinogênio (p<0,01). O genótipo GG do polimorfismo -174G/C IL-6 relacionou com elevação nas concentrações de glicose (p<0,05) e o genótipo CC com diminuição nas concentrações de apoA (p<0,01), HDL (p<0,001) e elevação nas de LDL (p<0,05), colesterol total (p<0,05). O genótipo CT do polimorfismo -260C/T CD14 também relacionou com concentrações elevadas de colesterol total (p<0,0001). Em conclusão, os polimorfismos não estão relacionados com o infarto do miocárdio em jovens, porém os SNPs -260CT CD14 e -174 IL-6 parecem estar relacionados com o perfil sérico inflamatório, hematológico e bioquímico de pacientes enfartados.The objective of this study was to assess the possible association between the polymorphism - 260C/T of the gene CD14, Arg7S3Gln TLR2, Asp299Gli and Thr399lle TLR4 and - 174G/C of the gene IL6 with myocardial infarction in young adults. For that a case control study was conducted and the case group was formed by 102 patients who had myocardial infarction, and the control group by 108 individuals without history of cardiovascular disease. The genotyping was performed by PCR-RFLP. There was no association between the distribution of genotypes of SNPs - 260C/T of the gene CD14, Arg7S3Gln TLR2, Asp299Gli and Thr399lle TLR4 and -174G/C of the gene IL6 between the two groups studied (p<0.05). The serum inflammatory blood profile was related with polymorphism - 174G/C IL-6 in the group IAM. The GG genotype was linked with elevated PAI-1 concentrations (p<0.0001), the genotype GC with larger quantities of red blood cells (p=0.02) and CC genotype with high concentrations of fibrinogênio (p<0.01) and leucocytes increased quantity (p<0.05). The CC genotype of polymorphism of -260C/T CD14 also showed associated with the elevation in PAI-1 concentrations (p<0.0001) and the CT genotype with elevated fibrinogênio concentrations (p<0.01). The GG genotype of the -174G/C IL-6 polymorphism was related with elevated glucose concentrations (p<0.05) and CC genotype with decrease in the apoA (p <0.01) and HDL (p<0001) concentrations and elevation of the LDL (p <0.05), total cholesterol (p <0.05) concentrations. The CT genotype of -260C / T CD14 polymorphism also was Iinked with high total cholesterol concentrations (p <0.0001). In conclusion, the polymorphism is not associated with myocardial infarction in young patients, but the -260CT CD14 and -174 IL-6 SNPs appear to be related to the serum biochemical, hematological and inflammatory blood profile in patients that had myocardial infarction.
Books on the topic "TLR Genes"
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Berkel, Klaas van. Spiegelbeeld der wetenschap: Het Genootschap ter Bevordering van Natuur-, Genees- en Heelkunde, 1790-1990. Rotterdam: Erasmus Publishing, 1991.
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Brent, Jonathan Robert. The ALS Genes TDP-43 and FUS/TLS Regulate a Common Pathway in the Nervous System of Drosophila Melanogaster. [New York, N.Y.?]: [publisher not identified], 2012.
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Bilański, Piotr. Trypodendron laeve Eggers w Polsce na tle wybranych aspektów morfologicznych i genetycznych drwalników (Trypodendron spp., Coleoptera, Curculionidae, Scolytinae). Publishing House of the University of Agriculture in Krakow, 2019. http://dx.doi.org/10.15576/978-83-66602-38-0.
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In Poland, there are 4 species of the liypodendron genus: T lineaium Oliv., T domestkum L., T signature Fakir. and 7: laeve Egg. Trypodendron laeve is the leastknown of this group. Many factors had influence on the state of research on this species, including taxonomic aspects. Taking into account the unsatisfactory state of knowledge regarding the prevalence of T iaeve in Poland, as well as scarce information on the morphology of this species, research was undertaken to I) document the presence, including new sites, of T laeve in Poland and define, if possible, the habitat and trophic conditions that may affect its occurrence, as well as II) determinate suitability of biometric and genetic methods for correct identification of t laeve against the background of other ambrosia beetle species. Research on the occurrence of T laeve in Poland, was carried out on 143 areas located throughout the country, representing various environmental conditions, primarily such as species composition of tree stands, terrain, altitude (from 16 to 929 meters above sea level) and their location in relation to zoogeographic regions. The research material was obtained mainly using various types of traps for catching ambrosia beetles baited with pheromone. Only in a few cases when attacking the wood of trees, the imagines of ambrosia beetles were obtained without luring agents. The research was conducted in 2007-2016. From the insect individuals identified on the grounds of morphological traits as T lineatum, T laeve, T domesticum and T signatum, originating from selected locations in Poland, 3-11 specimens were collected, for which genetic analyses were performed based on the COI gene fragments obtained by PCR. The research included tests for following paramcter: s sequence similarity, phylogenetic, evolutionary divergence and genetic. structure. As a result of research on the occurrence of ambrosia beetles in Poland, a total of 44207 individuals belonging to four species were collected: T lineatutn, 7: laeve, T domesticum and T signatum, whose share was respectively: 49.2%, 31.4%; 19.1% and 0.3%. In Poland, 1: laeve's imagines were found in 124 out of 143 examined sites. The presence of L reeve has been documented for the first time in 14 zoogeographic regions. This species was commonly found on study areas located from 118 to 929 m above sea level. In Poland the tree species attacked by T Mate include Pinus sylvestris L. and Picea abies (L) H. Karst. In Poland, T laeve as a host plant prefers sylvestris and reaches the highest population densities in the stands of this species. The work presents the exact morphological characteristics of T laeve and indicates the most important features that distinguish it from the other Trypodendrun spp. occurring in Poland. It has also been shown that the best results in the determination of species of the liypodendron genus, regardless of their sex, can be obtained using phylogenetic analysis based on a fragment of the COI gene.
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Geri, Guillaume, and Jean-Paul Mira. Host–pathogen interactions in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0306.
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Infection by a pathogenic micro-organism triggers a coordinated activation of both innate and adaptive immune responses. The innate immune response quickly triggers an antimicrobial response that will initiate development of a pathogen-specific, long-lasting adaptive immune response. Accurate recognition of microbial-associated molecular patterns by pattern-recognition receptors (PRRs) is the cornerstone of this immediate response. Most studied PRRs are Toll-like receptors (TLRs) and their kinase signalling cascades that activate nuclear transcription factors, and induce gene expression and cytokine production. Deficiencies or genetic variability in these different signalling pathways may lead to recurrent pyogenic infections and severe invasive diseases. After initial contact between the host and pathogen, numerous factors mediate the inflammatory response, as pro-inflammatory cytokines and chemokines. Apart from host genetic variability, pathogen diversity also influences the phenotypic features of various infectious diseases. Genomic analysis may assist in the development of targeted therapies or new therapeutic strategies based on both patient and microorganism genotype.
Book chapters on the topic "TLR Genes"
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Pecman, Mojca, and Natalie Kübler. "Chapter 12. Text genres and Terminology." In Theoretical Perspectives on Terminology, 263–90. Amsterdam: John Benjamins Publishing Company, 2022. http://dx.doi.org/10.1075/tlrp.23.12pec.
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Rhein, Simone, and Neşe Çakmak-Görür. "TCR Gene Therapy for Cancer." In Methods in Molecular Biology, 95–128. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2441-8_6.
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Duarte, Isabel Margarida, and Maria Aldina Marques. "Chapter 11. Vós and other pronominal forms of address ( tu, você, vocês )." In It's different with you, 272–93. Amsterdam: John Benjamins Publishing Company, 2023. http://dx.doi.org/10.1075/tar.5.11dua.
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This chapter aims to highlight some uses of pronominal address forms (tu, você, vocês and vós [‘you’ sg+pl]) in European Portuguese and compare them to Brazilian Portuguese, based on speakers’ perceptions which express their pragmatic awareness. The data were collected on the internet, from Facebook posts. An online linguistic survey on this matter was conducted to complement the data. Some examples were also collected from public speeches covering various discourse genres. Our findings show that (i) the speakers have highly varied metalinguistic and metapragmatic knowledge regarding the uses of the pronominal address systems in both varieties, (ii) knowledge of the language is supported by opinions and beliefs that value the central notion of social prestige related to a standard variety.
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Lefferts, Juliet W., Vera Boersma, Marne C. Hagemeijer, Karima Hajo, Jeffrey M. Beekman, and Erik Splinter. "Targeted Locus Amplification and Haplotyping." In Methods in Molecular Biology, 31–48. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2819-5_2.
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AbstractTargeted locus amplification (TLA) allows for the detection of all genetic variation (including structural variation) in a genomic region of interest. As TLA is based on proximity ligation, variants can be linked to each other, thereby enabling allelic phasing and the generation of haplotypes. This allows for the study of genetic variants in an allele-specific manner. Here, we provide a step-by-step protocol for TLA sample preparation and a complete bioinformatics pipeline for the allelic phasing of TLA data. Additionally, to illustrate the protocol, we show the ability of TLA to re-sequence and haplotype the complete cystic fibrosis transmembrane (CFTR) gene (> 200 kb in size) from patient-derived intestinal organoids.
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Kutikhin, Anton G., and Arseniy E. Yuzhalin. "Structural Genomic Variation in TLR4 Gene and Cancer." In Genomics of Pattern Recognition Receptors, 33–55. Basel: Springer Basel, 2013. http://dx.doi.org/10.1007/978-3-0348-0688-6_3.
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Larionov, Vladimir. "Direct Isolation of Specific Chromosomal Regions and Entire Genes by TAR Cloning." In Genetic Engineering, 37–55. Boston, MA: Springer US, 1999. http://dx.doi.org/10.1007/978-1-4615-4707-5_3.
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Gaynor, Richard. "Role of the TAR Element in Regulating HIV Gene Expression." In Advances in Molecular Biology and Targeted Treatment for AIDS, 79–91. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4684-5928-9_8.
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Hens, Kristien. "7. Een procesontologie voor de bio-ethiek." In Toevallige ontmoetingen, 89–100. Cambridge, UK: Open Book Publishers, 2023. http://dx.doi.org/10.11647/obp.0370.07.
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Ik ga verder op het pad van een ontwikkelingsgerichte kijk op het leven. Ik beargumenteer dat een dergelijke kijk impliceert dat bio-ethiek zich minder richt op wat we kunnen controleren, bijvoorbeeld wat we kunnen weten van onze genen, en meer op het omgaan met toeval en onzekerheden. Ik gebruik ideeën van Alfred North Whitehead en procesfilosofie om een representationele benadering van bio-ethiek ter discussie te stellen.
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Sapkota, Sunil, and Michael P. Gantier. "Selecting Therapeutic Antisense Oligonucleotides with Gene Targeting and TLR8 Potentiating Bifunctionality." In Methods in Molecular Biology, 225–34. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3331-1_17.
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Zorina, Anna A., Galina V. Novikova, and Dmitry A. Los. "Participation of Ser-Thr Protein Kinases in Regulation of Heat Stress Responses inSynechocystis." In Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria, 766–80. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2016. http://dx.doi.org/10.1002/9781119004813.ch74.
Full textConference papers on the topic "TLR Genes"
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Liu-Mares, Wen, Jennifer J. Hu, Ioanna Konidari, Glenn O. Allen, Peter E. Clark, M. Craig Hall, Chuanhui Dong, J. Sunil Rao, and William K. Scott. "Abstract 2771: Genetic variation in interleukin, TLR, TNF and TRAF genes of NF-κB activation pathway and risk of prostate cancer." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2771.
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Paniagua, N. Díaz, EG Tranquilino Batres, AP Lόpez Flores, A. Lozano Cardenas, E. Vallarino Reyes, AL Alvarez Grijalva, L. Sanchez Chapul, C. Díaz Hernández, L. Ríos Ventura, and A. Lopez Macay. "AB0861 Expression control by methylation of the TLR1, TLR2, TLR4, IL1B, ALPK1 SLC2A9 and SLC22A12 genes in monocytes of patients with gout." In Annual European Congress of Rheumatology, 14–17 June, 2017. BMJ Publishing Group Ltd and European League Against Rheumatism, 2017. http://dx.doi.org/10.1136/annrheumdis-2017-eular.3594.
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Souza, Sabrina Pires Maciel de, JULIANA ECHEVARRIA LIMA, and RENATA MEIRELLES PEREIRA. "LINFÓCITOS INFECTADOS PELO HTLV-1 INDUZEM A DIFERENCIAÇÃO DE MONÓCITOS EM MACRÓFAGOS \"M1-LIKE\" IN VITRO." In II Congresso Brasileiro de Imunologia On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/ii-conbrai/5788.
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Introdução: O vírus linfotrópico para células T humanas do tipo 1 (HTLV-1) é um retrovírus associado à leucemia/linfoma de células T e à mielopatia/paraparesia espástica tropical (MAH/PET). A MAH/PET é uma doença inflamatória crônica, caracterizada pela infiltração de leucócitos na medula espinhal e neurodegeneração. Embora os linfócitos T sejam o principal alvo do HTLV-1, células como monócitos também podem ser infectadas. Monócitos de indivíduos infectados pelo HTLV-1 apresentam importantes alterações funcionais quando comparados com células de doadores não infectados. O presente estudo caracterizou o perfil de monócitos durante a infecção pelo HTLV-1 utilizando células de linhagem THP-1 como modelo. Metodologia: Co-cultivamos células THP-1 com linhagens de linfócitos transformados pelo HTLV-1 (MT2) afim de elucidar a relação do contato célula-célula e/ou fatores secretados pelas células infectadas na resposta e diferenciação de monócitos. Resultados: Observamos que as células THP-1 adquiriram características similares a macrófagos baseado na morfologia e expressão de CD68, além da expressão das moléculas de superfície HLA-DR, CD80 e CD86, bem como de genes pró-inflamatórios (TNF, IL6 e IL1B) e secreção de citocinas (TNF-α and IL-6) após o co-cultivo com a MT2. Entretanto, não houve aumento da expressão de ARG (gene codificante para Arginase) e TGFB1, característicos de macrófagos M2. A presença da MT2 na cultura também induziu a expressão de TLR4, TLR2 e MD2, relacionados com ativação celular. Além disso, observamos aumento na regulação de genes estimulados pelo Interferon (IFNB1, OASL e ISG15), corroborando com o estado de infecção viral. Esses resultados, em conjunto com a detecção do gene viral Tax, sugere a infecção das células THP-1 pelo HTLV-1 após o co-cultivo. Tais efeitos ocorreram independente de contato, conforme observado nos ensaios utilizando sistema transwell. Conclusão: Nossos resultados sugerem que após o co-cultivo com células infectadas pelo HTLV-1, monócitos THP-1 foram capazes de se diferenciar em um fenótipo compatível com o perfil de macrófagos M1 in vitro e induziu a expressão de genes associados à resposta inflamatória e anti-viral em um sistema independente do contato célula-célula. Esses achados podem auxiliar no entendimento da resposta protetora e patológica mediada por monócitos e macrófagos durante a infecção pelo HTLV-1.
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ELIZA DE JESUS BARROS DOS, SANTOS, LIMA ALINE MEDEIROS, SANTOS ADRYANA TRAVASSOS DOS, and PAIVA RAFAEL DA SILVA. "A IDENTIFICAÇÃO E CARACTERIZAÇÃO DA FAMILIA DE GENE 1,3-BETAGLUCOSIDASE DE MANIHOT ESCULENTA CRANTZ." In III Congresso Brasileiro de Ciências Biológicas On-line. Revista Multidisciplinar de Educação e Meio Ambiente, 2022. http://dx.doi.org/10.51189/iii-conbracib/6420.
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Introdução: A mandioca (Manihot esculenta, Crantz) é uma planta dicotiledônea, arbustiva, de crescimento perene e pertencente à família Euphorbiaceae, na qual tem uma característica de consumo familiar na região norte, e estão distribuídas em várias áreas do meio ambiente, fazendo que os mesmos fiquem expostas a vários fatores, como os estresses bióticos e abióticos. O presente trabalho vem retratar sobre a identificação de caracterização da família de gene 1,3-beta-glucosidase de Manihot Esculenta Crantz. Diante disso, a família de genes glucosidase vem ser importante para retardar o crescimento de fungos patogênicos e diminuir a deterioração dos fungos nos frutos causados pelos mesmo, além disso, a aplicação das glucosidases em controle biológico ocorre devido à composição da parede celular, no qual vem ser a localização subcelular das 1,3-beta-glucosidase nos micro-organismos que são patogênicos. Objetivo: Atrelado a isso, este estudo visa identificar e caracterizar in silico a família de genes 1,3 –beta-glucosidase de Manihot esculenta crantz, através de aspectos evolutivos possibilitando análises de suas atividades enzimáticas e biológicas. Material e métodos: As sequências genômicas dos genes da família de 1,3-beta-glucosidase da mandioca foram obtidas por meio das ferramentas de busca disponível no Phytozome, no qual mostrou 30 sequências genômica que compõe a família glucosidase, onde foram nomeadas de Mesidae1, Mesidae2 .... Mesidae30, entretanto, as 30 sequências estão dispostas em 19 cromossomos. Resultados: Através do programa InterProScan, foi possível analisar que os genes Mesidae2; Mesidae3 e Mesidae10 ambos apresentam 496pb. Já o Mesidae17; Messidae25 e Mesidae30, também irão apresentar uma à similaridade no número de pb, pois vão conter 658. Entretanto, o Mesidae21 e Mesidae28 vão ter 458pb. O Mesidae22 e Mesidae26, irão ter 528pb. Já os Mesidae23 e Mesidae27 vão ter 553 pb, respectivamente todas as sequências vão ter uma variação de 2 a 10 introns na sequência. Através do programa SWISS-MODEL, foi constatado observar o arranjo tridimensional das proteínas. Conclusão: Os resultados obtidos neste trabalho permitem concluir que a família 1,3-beta-glucosidase da Manihot esculenta crantz possui 30 isoformas, onde estas têm as características necessárias para serem consideradas famílias.
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Liu, Tao, Qiu-Ling Xu, Zhao-Xin Yang, and Yan Zhao. "Emodin Protects NAFLD Rats via Regulating the Genes Expression of Hepatic TLR4 Genes." In 2015 International Conference on Medicine and Biopharmaceutical. WORLD SCIENTIFIC, 2016. http://dx.doi.org/10.1142/9789814719810_0069.
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Stuchi, Amanda Maria, Leonardo Paroche de Matos, Allan Luis Barboza Atum, and José Antônio Silva Júnior. "EXPOSIÇÃO PRÉ-NATAL AO ÁLCOOL E A EXPRESSÃO DE GENES RELACIONADOS À HIPERTROFIA CARDÍACA EM CAMUNDONGOS." In Congresso Médico Acadêmico da Universidade Nove de Julho. Universidade Nove de Julho, 2022. http://dx.doi.org/10.5585/comamedvg.2022.9.
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Introdução: A exposição pré-natal ao álcool (E.P.A.) é considerada uma das principais responsáveis pelas alterações congênitas humanas teratogênicas. Estima-se que 20% das gestantes consumam álcool durante toda a gestação, além de 35% das gestantes relataram ter consumido álcool, mesmo que em pequenas doses. O impacto potencial da E.P.A. varia consideravelmente entre os indivíduos, podendo levar a alterações morfológicas e genéticas sistêmicas. Entretanto, muitas dessas alterações ocorrem a nível celular, podendo, ao longo da vida, predispor o indivíduo às doenças crônicas. No sistema cardiovascular, a E.P.A. pode levar a alterações, como hipertrofia cardíaca e defeitos valvares, bem como alterações na expressão de genes relacionados à homeostase cardiovascular. Objetivo: Analisar o impacto da E.P.A. na ativação de hipertrofia cardíaca, analisando a expressão de RNA mensageiro de componentes da via de transdução de sinais hipertróficos. Materiais e métodos: O estudo foi aprovado pelo Comitê de Ética no Uso de Animais (CEUA = 9355120319 ID 000115). Foram utilizados camundongos isogênicos da linhagem C57Bl/6. As fêmeas progenitoras foram separadas e randomizadas no grupo controle (n=4) e no grupo de exposição ao álcool (n=11). O protocolo do grupo E.P.A. durante a gestação, foi a exposição do álcool na proporção de 10% (v/v) diluídos em água de consumo. Após 45 dias, 10 filhotes de cada grupo (n=20) foram anestesiados com isoflurano (<20 segs.) e decapitados. O ventrículo esquerdo (VE) foi coletado e tratado. A expressão relativa foi obtida pela técnica RT-qPCR utilizando placas customizadas TaqMan®, sendo utilizado como controle endógeno o gene rRNA 18S. A estatística foi calculada com a aplicação IBM SPSS Statistics for Windows, Version 25.0.; a normalidade foi testada através do teste de Shapiro-Wilk e os dados representados por média ± EPM ou Md + intervalos interquartis (25-75%). Comparação entre grupos: Teste T para amostras independentes ou Test U de Mann Whitney sendo considerado o valor de significância p ≤0,05 em ambos os testes. Resultados: Além de leve hipertrofia do coração e VE, observamos a presença de deposição de colágeno perivascular confirmadas por técnica de Tricrômico de Masson. Observamos, também, alterações na transcrição de 18 dos 20 genes analisados, sendo o maior aumento apresentado pelo gene codificador do Peptídeo Natriurético B (405,92%). Discussão e conclusão: As alterações na expressão dos genes Col1a1, Myh6, Myh7 e Tgfb1 em conjunto com uma maior deposição de colágeno, sugerem a ocorrência de leve hipertrofia do VE nos animais do grupo E.P.A.. Em nosso modelo experimental, portanto, a E.P.A. induziu alterações morfométricas e hipertrofia cardíaca, bem como, modulou a transcrição de genes relacionados a esta condição cardiovascular. Além disso, nossos dados sugerem que estas alterações são comparáveis às observadas em animais com disfunções cardíacas experimentais, como o infarto do miocárdio. Palavras-chave: coração; expressão gênica; hipertrofia cardíaca; transdução de sinal.
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Almeida, Jamile Aislin Silva de, and Carla Yasmym De Carvalho Lima. "NUTRIGENÔMICA E AS DOENÇAS CRÔNICAS NÃO TRANSMISSÍVEIS: UMA REVISÃO BIBLIOGRÁFICA ENTRE OS POLIFORMISMOS E COMPOSTOS BIOATIVOS." In II Congresso Brasileiro de Biologia Molecular On-line. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/2323.
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Introdução: A presença de poliformismos associados ao risco de Doenças Crônicas Não Transmissíveis (DCNTs) se tornou um despertar de interesse para a genômica nutricional, que tem como foco o estudo da relação gene-nutriente, uma vez que vários nutrientes e compostos bioativos podem ter um papel importante na diminuição de tais doenças nos indivíduos. Objetivo: Analisar a contribuição da nutrigenômica para precaver os casos de DCNT, como obesidade, Diabetes Mellitus II, câncer, doenças inflamatórias intestinais e outras complicações, durante os últimos 3 anos. Material e Métodos: A pesquisa foi realizada a partir de 7 estudos retirados nas bases de dados SciElo, Web of, Science e Scopus. Publicados no período de 2018 e 2020, utilizando as palavras-chaves: “doenças crônicas não transmissíveis”, “nutrição”, “nutrigenômica” e “poliformismo”. Resultados: Estudos demonstraram que existem em nosso genoma diversos tipos de poliformismos, associados a incidência de DCNTs. Dentre eles temos os Poliformismos de Nucleotídeo Único (SNps) nos genes FTO; FADS1, ADRB2, LEPR, IL-6, LPIN1, AdipoR1, PPARγ, ZnT8, TCF7L2, BRCA1, PPM1K, RVD, DIO1-2, GPX-1,3, SEPHS1, SEPSECS e TXNRD2 e FOXO3. Com relação aos alimentos, temos aqueles à base de plantas, especialmente as frutas e hortaliças, que são fontes de uma variedade de compostos bioativos, como terpenóides, polifenóis, compostos de enxofre, alcalóides e poliaminas, em que a ingestão está ligado à proteção contra doenças crônicas. Compostos polifenóis, por exemplo, quando entram na via do fator nuclear κB (NF-κB) exercem a função de transcrição de vários genes, incluindo os que se relacionam com a produção de citocinas pró-inflamatórias, quimiocinas e moléculas essenciais para a resposta inflamatória, que irão exerce importante ação no retardo de DCNTs. Conclusão: Os resultados nutrigenômicos servem como parâmetro para a análise das DCNTs no período de três anos. Mas, é necessário corroborar que elas são resultado de uma rede de fatores, não apenas genéticos e nutricionais, mas também, ambientais, como a prática de atividade física, uso de álcool e tabaco e fatores individuais. Sendo de grande relevância entender melhor a interação gene-nutriente e seu papel para a saúde da população portadora de DCNTs ou em processo de tratamento.
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Ginting, Ronistra, Mohammad Basyuni, and Yuntha Bimantara. "Bioinformatics Identification of TLR4 Genes in Brahma Chicken (Gallus gallus domesticus)." In 2019 3rd International Conference on Electrical, Telecommunication and Computer Engineering (ELTICOM). IEEE, 2019. http://dx.doi.org/10.1109/elticom47379.2019.8943920.
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Pannekok, H., A. J. Van Zonneveid, C. J. M. de vries, M. E. MacDonald, H. Veerman, and F. Blasi. "FUNCTIONAL PROPERTIES OF DELETION-MUTANTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643724.
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Over the past twenty-five years, genetic methods have generated a wealth of information on the regulation and the structure-function relationship of bacterial genes.These methods are based on the introduction of random mutations in a gene to alter its function. Subsequently, genetic techniques cure applied to localize the mutation, while the nature of the impairedfunction could be determined using biochemical methods. Classic examples of this approach is now considered to be the elucidation of the structure and function of genes, constituting the Escherichia coli lactose (lac) and tryptophan (trp) operons,and the detailed establishment of the structure and function of the repressor (lacl) of the lac operon. Recombinant DNA techniques and the development of appropriate expression systems have provided the means both to study structure and functionof eukaryotic (glyco-) proteins and to create defined mutations with a predestinedposition. The rationale for the construction of mutant genes should preferentiallyrely on detailed knowledge of the three-dimensional structure of the gene product.Elegant examples are the application of in vitro mutagenesis techniques to substitute amino-acid residues near the catalytic centre of subtilisin, a serine proteasefrom Bacillus species and to substituteanamino acid in the reactive site (i.e. Pi residue; methionine) of α-antitrypsin, a serine protease inhibitor. Such substitutions have resulted into mutant proteins which are less susceptible to oxidation and, in some cases, into mutant proteins with a higher specific activity than the wild-type protein.If no data are available on the ternary structure of a protein, other strategies have to be developed to construct intelligent mutants to study the relation between the structure and the function of a eukaryotic protein. At least for a number of gene families, the gene structure is thought to be created by "exon shuffling", an evolutionary recombinational process to insert an exon or a set of exons which specify an additional structural and/or functional domain into a pre-existing gene. Both the structure of the tissue-type plasminogen activator protein(t-PA) and the t-PA gene suggest that this gene has evolved as a result of exon shuffling. As put forward by Gilbert (Science 228 (1985) 823), the "acid test"to prove the validity of the exon shuffling theory is either to delete, insert or to substitute exon(s) (i.e. in the corresponding cDNA) and toassay the properties of the mutant proteins to demonstrate that an exon or a set of adjacent exons encode (s) an autonomousfunction. Indeed, by the construction of specific deletions in full-length t-PA cDNA and expression of mutant proteins intissue-culture cells, we have shown by this approach that exon 2 of thet-PA gene encodes the function required forsecretion, exon 4 encodes the "finger" domain involved in fibrin binding(presumably on undegraded fibrin) and the set of exons 8 and 9 specifies kringle 2, containing a lysine-binding sit(LBS) which interacts with carboxy-terminal lysines, generated in fibrin after plasmic digestion. Exons 10 through 14 encode the carboxy-ter-minal light chain of t-PA and harbor the catalytic centre of the molecule and represents the predominant "target site" for the fast-acting endothelial plasminogen activator inhibitor (PAI-1).As a follow-up of this genetic approach to construct deletion mutants of t-PA, we also created substitution mutants of t-PA. Different mutants were constructed to substitute cDNA encoding thelight chain of t-PA by cDNA encoding the B-chain of urokinase (u-PA), in order to demonstrate that autonomous structural and functional domains of eitherone of the separate molecules are able toexert their intrinsic properties in a different context (C.J.M. de Vries et al., this volume). The possibilities and the limitations of this approach to study the structure and the function of t-PA and of other components of the fibrinolytic process will be outlined.
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Carvalho, Gabriel Leal, Isadora Ghilardi, Allan Alcará, Felipe Rodrigues, Ângela Zanatta, Giovani Zocche, Giulia Pinzetta, et al. "Gene expression of calcium channel CACNA1H in epileptogenesis can be modulated by mesenchymal stem cells." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.593.
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Introduction: Temporal Lobe Epilepsy (TLE) is the most common refractory epilepsy, and it is characterized by abnormal firing of a population of neurons in the brain, and by cognitive deficit1 . This abnormal intrinsic phenomenon can cause deregulation of the T-type calcium channels, increasing neuronal excitability, leading to structural changes in the Central Nervous System2 . Mesenchymal Stem Cells (MSCs) are a therapeutic alternative for the TLE for they can modulate neurotransmitters liberation, reducing neuronal death and increasing neurogenesis3,4,5. The present study analyzed MSCs effects on gene expression of T-type calcium channel CACNA1H in the brain of pilocarpine-induced TLE animal models. Methods: The MSCs were obtained from the bone marrow of Wistar rats, cultured, and transplanted intravenously and intranasally. The animals were separated into the following groups: control and pilocarpine-induced status epilepticus, then they were euthanized 1- and 7-days post-transplant for gene expression analysis. Results: The results show that 1-day post-transplant there was no difference in the CACNA1H gene expression between the MSC-treated pilocarpine groups and the control and untreated pilocarpine groups. Subsequently 7-days posttransplant, the treated groups showed greater expression of the gene in both means of administration. Moreover, there was an increase in CACNA1H gene expression in the prefrontal cortex of the treated pilocarpine group, which makes us conjecture a mechanism of greater need for its transcription in this area. Conclusion: Thus, MSCs were able to modulate the expression of the CACNA1H gene in the brain, increasing its importance as a target for future studies on epilepsy therapies involving cells.
Reports on the topic "TLR Genes"
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Fluhr, Robert, and Maor Bar-Peled. Novel Lectin Controls Wound-responses in Arabidopsis. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7697123.bard.
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Innate immune responses in animals and plants involve receptors that recognize microbe-associated molecules. In plants, one set of this defense system is characterized by large families of TIR–nucleotide binding site–leucine-rich repeat (TIR-NBS-LRR) resistance genes. The direct interaction between plant proteins harboring the TIR domain with proteins that transmit and facilitate a signaling pathway has yet to be shown. The Arabidopsis genome encodes TIR-domain containing genes that lack NBS and LRR whose functions are unknown. Here we investigated the functional role of such protein, TLW1 (TIR LECTIN WOUNDRESPONSIVE1). The TLW1 gene encodes a protein with two domains: a TIR domain linked to a lectin-containing domain. Our specific aim in this proposal was to examine the ramifications of the TL1-glycan interaction by; A) The functional characterization of TL1 activity in the context of plant wound response and B) Examine the hypothesis that wounding induced specific polysaccharides and examine them as candidates for TL-1 interactive glycan compounds. The Weizmann group showed TLW1 transcripts are rapidly induced by wounding in a JA-independent pathway and T-DNA-tagged tlw1 mutants that lack TLW1 transcripts, fail to initiate the full systemic wound response. Transcriptome methodology analysis was set up and transcriptome analyses indicates a two-fold reduced level of JA-responsive but not JA-independent transcripts. The TIR domain of TLW1 was found to interact directly with the KAT2/PED1 gene product responsible for the final b-oxidation steps in peroxisomal-basedJA biosynthesis. To identify potential binding target(s) of TL1 in plant wound response, the CCRC group first expressed recombinant TL1 in bacterial cells and optimized conditions for the protein expression. TL1 was most highly expressed in ArcticExpress cell line. Different types of extraction buffers and extraction methods were used to prepare plant extracts for TL1 binding assay. Optimized condition for glycan labeling was determined, and 2-aminobenzamide was used to label plant extracts. Sensitivity of MALDI and LC-MS using standard glycans. THAP (2,4,6- Trihydroxyacetophenone) showed minimal background peaks at positive mode of MALDI, however, it was insensitive with a minimum detection level of 100 ng. Using LC-MS, sensitivity was highly increased enough to detect 30 pmol concentration. However, patterns of total glycans displayed no significant difference between different extraction conditions when samples were separated with Dionex ICS-2000 ion chromatography system. Transgenic plants over-expressing lectin domains were generated to obtain active lectin domain in plant cells. Insertion of the overexpression construct into the plant genome was confirmed by antibiotic selection and genomic DNA PCR. However, RT-PCR analysis was not able to detect increased level of the transcripts. Binding ability of azelaic acid to recombinant TL1. Azelaic acid was detected in GST-TL1 elution fraction, however, DHB matrix has the same mass in background signals, which needs to be further tested on other matrices. The major findings showed the importance of TLW1 in regulating wound response. The findings demonstrate completely novel and unexpected TIR domain interactions and reveal a control nexus and mechanism that contributes to the propagation of wound responses in Arabidopsis. The implications are to our understanding of the function of TIR domains and to the notion that early molecular events occur systemically within minutes of a plant sustaining a wound. A WEB site (http://genome.weizmann.ac.il/hormonometer/) was set up that enables scientists to interact with a collated plant hormone database.
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Liang, Yuting, Liyou Wu, Ian Clark, Kai Xue, Joy D. Van Nostrand, Ye Deng, Zhili He, Penny Hirsch, Steve Mcgrath, and Jizhong Zhou. Taxa-area Relationship (TAR) of Microbial Functional Genes with Long-TGerm Fertilization. Office of Scientific and Technical Information (OSTI), May 2010. http://dx.doi.org/10.2172/985942.
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Dickman, Martin B., and Oded Yarden. Role of Phosphorylation in Fungal Spore Germination. United States Department of Agriculture, August 1993. http://dx.doi.org/10.32747/1993.7568761.bard.
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Spore germination is a common and fundamental event in fungal development and in many instances an essential phase of fungal infection and dissemination. Spore germination is also critical for hyperparasites to function as biocontrol agents as well as in fermentation proceses. Our common objective is to understand the mechanisms which regulated spore germination and identify factors involved in pathogenicity related prepenetration development. Our approach is to exploit the overall similarity among filamentous fungi using both a plant pathogen (Colletotricum trifolii) and a model system that is genetically sophisticated (Neurospora crassa). The simulataneous use of two organisms has the advantage of the available tools in Neurospora to rapidly advance the functional analysis of genes involved in spore germination and development of an economically important fungal phytopathogen. Towards this we have isolated a protein kinase gene from C. trifolii (TB3) that is maximally expressed during the first hour of conidial germination and prior to any visible gene tube formation. Based on sequence similarities with other organisms, this gene is likely to be involved in the proliferative response in the fungus. In addition, TB3 was able to functionally complement a N. crassa mutant (COT-1). Pharmacological studies indicated the importance of calmodulin in both germination and appressorium differentiation. Using an antisense vector from N. crassa, direct inhibition of calmodulin results in prevention of differentiation as well as pathogenicity. Both cAMP dependent protein kinase (PKA) and protein kinase C (PKC) like genes have been cloned from C. trifolii. Biochemical inhibition of PKA prevents germination; biochemical inhibitors of PKC prevents appressorium differentiation. In order to analyze reversible phosphorylation as a regulatory mechanism, some ser.thr dephosphorylative events have also been analyzed. Type 2A and Type 2B (calcineurin) phosphatases have been identified and structurally and functionally analyzed in N. crassa during this project. Both phosphatases are essential for hyphal growth and maintenance of proper hyphal architecture. In addition, a first novel-type (PPT/PP5-like) ser/thr phosphatase has been identified in a filamentous fungus. The highly collaborative project has improved our understanding of a fundamental process in fungi, and has identified targets which can be used to develop new approaches for control of fungal plant pathogens as well as improve the performance of beneficial fungi in the field and in industry. In addition, the feasibility of molecular technology transfer in comparative mycology has been demonstrated.
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David, Lior, Yaniv Palti, Moshe Kotler, Gideon Hulata, and Eric M. Hallerman. Genetic Basis of Cyprinid Herpes Virus-3 Resistance in Common Carp. United States Department of Agriculture, January 2011. http://dx.doi.org/10.32747/2011.7592645.bard.
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The goal of this project was to provide scientific and technical basis for initiating the development of breeding protocols using marker assisted selection for viral disease resistance in common carp. The specific objectives were: 1) Establishing families and characterizing the phenotypic and genetic variation of viral resistance; 2) Measuring the dynamics of immune response and developing a method to measure the long term immune memory; 3) Developing markers and generating a new genetic linkage map, which will enable initial QTL mapping; and, 4) Identifying genetic linkage of markers and candidate genes (like MHC and TLRs) with resistance to CyHV-3. The common carp is an important farmed freshwater fish species in the world. Edible carp is second only to tilapia in Israeli aquaculture production and ornamental carp (koi) is an important product in both the US and Israel. Carp industries worldwide have recently suffered enormous economic damage due to a viral disease caused by Cyprinid herpes virus 3 (CyHV-3). Aside from preventative measures, a sustainable solution to this problem will be to establish a genetic improvement program of the resistance of fish to the pathogen. The aims of the project was to take the necessary first steps towards that. The differences in survival rates after infection with CyHV-3 virus among 20 families from six types of crosses between three carp lines (two commercial lines and one wild-type carp) revealed that the wild-type carp and its crosses had a much-improved survival over the crosses of the commercial lines themselves. These crosses set the starting point for breeding of commercial strains with improved resistance. Resistant fish had lower antibody titer against the virus suggesting that resistance might depend more on the innate immunity. A set of 500 microsateliite markers was developed and the markers are currently being used for generating a genetic linkage map for carp and for identifying disease resistance QTL. Fourteen candidate immune genes, some of which were duplicated, were cloned from the carp and SNP markers were identified in them. The expression of these genes varied between tissues and suggested functional divergence of some duplicated genes. Initial association between CyHV-3 resistance and one of the genes was found when SNP alleles in these genes were tested for their segregation between susceptible and resistant progeny. The results of this project have implications to the development of viral resistant commercial carp strains and effective immunization against this aggressive disease. The genetic and immunological knowledge accumulated in this project will not only promote carp and koi production but will also contribute to a broader understanding of fish immunogenetics.
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Weiss, David, and Neil Olszewski. Manipulation of GA Levels and GA Signal Transduction in Anthers to Generate Male Sterility. United States Department of Agriculture, 2000. http://dx.doi.org/10.32747/2000.7580678.bard.
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The original objectives of the research were: i. To study the role of GA in anther development, ii. To manipulate GA and/or GA signal transduction levels in the anthers in order to generate male sterility. iii. To characterize the GA signal transduction repressor, SPY. Previous studies have suggested that gibberellins (GAs) are required for normal anther development. In this work, we studied the role of GA in the regulation of anther development in petunia. When plants were treated with the GA-biosynthesis inhibitor paclobutrazol, anther development was arrested. Microscopic analysis of these anthers revealed that paclobutrazol inhibits post-meiotic developmental processes. The treated anthers contained pollen grains but the connective tissue and tapetum cells were degenerated. The expression of the GA-induced gene, GIP, can be used in petunia as a molecular marker to: study GA responses. Analyses of GIP expression during anther development revealed that the gene is induced only after microsporogenesis. This observation further suggests a role for GA in the regulation of post-meiotic processes during petunia anther development. Spy acts as a negative regulator of gibberellin (GA) action in Arabidopsis. We cloned the petunia Spy homologue, PhSPY, and showed that it can complement the spy-3 mutation in Arabidopsis. Overexpression of Spy in transgenic petunia plants affected various GA-regulated processes, including seed germination, shoot elongation, flower initiation, flower development and the expression of a GA- induced gene, GIP. In addition, anther development was inhibited in the transgenic plants following microsporogenesis. The N-terminus of Spy contains tetratricopeptide repeats (TPR). TPR motifs participate in protein-protein interactions, suggesting that Spy is part of a multiprotein complex. To test this hypothesis, we over-expressed the SPY's TPR region without the catalytic domain in transgenic petunia and generated a dominant- negative Spy mutant. The transgenic seeds were able to germinate on paclobutrazol, suggesting an enhanced GA signal. Overexpression of PhSPY in wild type Arabidopsis did not affect plant stature, morphology or flowering time. Consistent with Spy being an O-GlcNAc transferase (OGT), Spy expressed in insect cells was shown to O-GlcNAc modify itself. Consistent with O-GlcNAc modification playing a role in GA signaling, spy mutants had a reduction in the GlcNAc modification of several proteins. After treatment of the GA deficient, gal mutant, with GA3 the GlcNAc modification of proteins of the same size as those affected in spy mutants exhibited a reduction in GlcNAcylation. GA-induced GlcNAcase may be responsible for this de-GlcNAcylation because, treatment of gal with GA rapidly induced an increase in GlcNAcase activity. Several Arabidopsis proteins that interact with the TPR domain of Spy were identified using yeast two-hybrids screens. One of these proteins was GIGANTEA (GI). Consistent with GI and Spy functioning as a complex in the plant the spy-4 was epistatic to gi. These experiments also demonstrated that, in addition to its role in GA signaling, Spy functions in the light signaling pathways controlling hypocotyl elongation and photoperiodic induction of flowering. A second Arabidopsis OGT, SECRET AGENT (SCA), was discovered. Like SPY, SCA O-GlcNAc modifies itself. Although sca mutants do not exhibit dramatic phenotypes, spy/sca double mutants exhibit male and female gamete and embryo lethality, indicating that Spy and SCA have overlapping functions. These results suggest that O-GlcNAc modification is an essential modification in plants that has a role in multiple signaling pathways.
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Splitter, Gary, and Menachem Banai. Microarray Analysis of Brucella melitensis Pathogenesis. United States Department of Agriculture, 2006. http://dx.doi.org/10.32747/2006.7709884.bard.
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Original Objectives 1. To determine the Brucella genes that lead to chronic macrophage infection. 2. To identify Brucella genes that contribute to infection. 3. To confirm the importance of Brucella genes in macrophages and placental cells by mutational analysis. Background Brucella spp. is a Gram-negative facultative intracellular bacterium that infects ruminants causing abortion or birth of severely debilitated animals. Brucellosis continues in Israel, caused by B. melitensis despite an intensive eradication campaign. Problems with the Rev1 vaccine emphasize the need for a greater understanding of Brucella pathogenesis that could improve vaccine designs. Virulent Brucella has developed a successful strategy for survival in its host and transmission to other hosts. To invade the host, virulent Brucella establishes an intracellular niche within macrophages avoiding macrophage killing, ensuring its long-term survival. Then, to exit the host, Brucella uses placenta where it replicates to high numbers resulting in abortion. Also, Brucella traffics to the mammary gland where it is secreted in milk. Missing from our understanding of brucellosis is the surprisingly lillie basic information detailing the mechanisms that permit bacterial persistence in infected macrophages (chronic infection) and dissemination to other animals from infected placental cells and milk (acute infection). Microarray analysis is a powerful approach to determine global gene expression in bacteria. The close genomic similarities of Brucella species and our recent comparative genomic studies of Brucella species using our B. melitensis microarray, suqqests that the data obtained from studying B. melitensis 16M would enable understanding the pathogenicity of other Brucella organisms, particularly the diverse B. melitensis variants that confound Brucella eradication in Israel. Conclusions Results from our BARD studies have identified previously unknown mechanisms of Brucella melitensis pathogenesis- i.e., response to blue light, quorum sensing, second messenger signaling by cyclic di-GMP, the importance of genomic island 2 for lipopolysaccharide in the outer bacterial membrane, and the role of a TIR domain containing protein that mimics a host intracellular signaling molecule. Each one of these pathogenic mechanisms offers major steps in our understanding of Brucella pathogenesis. Strikingly, our molecular results have correlated well to the pathognomonic profile of the disease. We have shown that infected cattle do not elicit antibodies to the organisms at the onset of infection, in correlation to the stealth pathogenesis shown by a molecular approach. Moreover, our field studies have shown that Brucella exploit this time frame to transmit in nature by synchronizing their life cycle to the gestation cycle of their host succumbing to abortion in the last trimester of pregnancy that spreads massive numbers of organisms in the environment. Knowing the bacterial mechanisms that contribute to the virulence of Brucella in its host has initiated the agricultural opportunities for developing new vaccines and diagnostic assays as well as improving control and eradication campaigns based on herd management and linking diagnosis to the pregnancy status of the animals. Scientific and Agricultural Implications Our BARD funded studies have revealed important Brucella virulence mechanisms of pathogenesis. Our publication in Science has identified a highly novel concept where Brucella utilizes blue light to increase its virulence similar to some plant bacterial pathogens. Further, our studies have revealed bacterial second messengers that regulate virulence, quorum sensing mechanisms permitting bacteria to evaluate their environment, and a genomic island that controls synthesis of its lipopolysaccharide surface. Discussions are ongoing with a vaccine company for application of this genomic island knowledge in a Brucella vaccine by the U.S. lab. Also, our new technology of bioengineering bioluminescent Brucella has resulted in a spin-off application for diagnosis of Brucella infected animals by the Israeli lab by prioritizing bacterial diagnosis over serological diagnosis.
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Dickman, Martin B., and Oded Yarden. Involvement of the PKA and MAPK signal transduction pathways in sclerotial morphogenesis in Sclerotinia sclerotiorum. United States Department of Agriculture, September 2007. http://dx.doi.org/10.32747/2007.7695861.bard.
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The long-term goals of our research are to understand the regulation of sclerotial development and pathogenicity in S. sclerotiorum. The focus in this project is on the elucidation of the signaling events and environmental cues involved in the regulation of these processes, utilizing and continuously developing tools our research groups have established and/or adapted for analysis of S. sclerotiorum. Our stated specific objectives were to: 1. Follow activities and function of S. sclerotiorumPKA. 2. Identify and functionally evaluate effectors of the S. sclerotiorumERK-likeMAPK signaling pathway. 3. Perform structural and functional analysis of genes whose expression is altered under conditions affecting either PKA and/or MAPK. As can be seen below, we have not only met most of the listed goals, but have also expanded our research. We have been working both together and in parallel in order to advance our goals. We have jointly shown how an ERK-likeMAPK is required sclerotia formation. We have analyzed, in parallel, the involvement of PKA in sclerotiogenesis and, interestingly, have reached some overlapping results but each group has provided a slightly different interpretation to the picture obtained. It will be interesting to see how this aspect of the analysis progresses, as we jointly tackle the yet unresloved issues. We have also made progress on the analysis of ser/thr phosphatases (specifically – calcineurin, which has been reported to interact with PKA) and PP2A in S. sclerotiorum as well as the S. sclerotiorum rasgene, which we have cloned and shown induces SMK1, the ERK-like kinase responsible for sclerotia formation. In addition to the time and efforts invested towards reaching the specific goals mentioned, both PIs are actively involved in a major international effort to sequence and annotate the entire S. sclerotiorum genome. Though time consuming (and perhaps requiring divergence of some time and resources from the original workplan), we have given this topic a very high priority to this effort as the long term implications of the success of this venture are enormous.
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Dickman, Martin B., and Oded Yarden. Regulation of Early Events in Hyphal Elongation, Branching and Differentiation of Filamentous Fungi. United States Department of Agriculture, 2000. http://dx.doi.org/10.32747/2000.7580674.bard.
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In filamentous fungi, hyphal elongation, branching and morphogenesis are in many cases the key to successful saprophytic and pathogenic fungal proliferation. The understanding of the fungal morphogenetic response to environmental cues is in its infancy. Studies concerning the regulation of fungal growth and development (some of which have been obtained by the participating collaborators in this project) point to the fact that ser/thr protein kinases and phosphatases are (i) involved in the regulation of such processes and (ii) share common structural and functional features between saprophytes and pathogens. It is our objective to combine a pharmaceutical and a genetic approach in order to identify, characterize and functionally dissect some of the regulatory factors involved in hyphal growth, branching and differentiation. Using an immunohistochemical approach, a ser/thr protein kinase involved in hyphal elongation in both Neurospora crassa and Colletotrichum trifolii has been localized in order to identify the physical arena of regulation of hyphal elongation. The analysis of additional kinases and phosphatases (e.g. Protein kinase C, cAMP-dependent kinase, lipid-activated protein kinase, components of the type 2A protein phosphatase) as well as a RAS-related gene (an additional key participant in signal transduction) has been performed. In order to succeed in advancing the goals of this project, we have taken advantage of available elongation/branching mutants in N. crassa and continuously combined the accumulated information obtained while studying the two systems in order to dissect the elements involved in these processes. The various inhibitors/effectors analyzed can serve as a basis for modification to be used as anti-fungal compounds. Understanding the regulation of hyphal proliferation is a key requirement for identifying novel target points for either curbing fungal growth (as in the case of pathogenesis) or affecting growth patterns in various biotechnological processes. The major objective of our joint project was to advance our understanding of regulation of hyphal growth, especially during early events of fungal germination. Towards achieving this goal, we have coupled the analysis of a genetically tractable organism (N. crassa) with a plant pathogen o economic importance (C. trifolii). As the project progressed we believe that the results obtained have provided a reinforcement to our basic approach which called for combining the two fungal systems for a joint research project. On the one hand, we feel that much of the advance made was possible due to the amenability of N. crassa to genetic manipulations. The relevance of some of the initial findings obtained in Neurospora have been proven to be relevant to the plant pathogen while unique features of the pathogen have been identified in Colletotrichum. Most of the results obtained from this research project have been published. Thus, the main volume of this report is comprised of the relevant publications describing the research and results obtained.
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Galili, Gad, Harry J. Klee, and Asaph Aharoni. Elucidating the impact of enhanced conversion of primary to secondary metabolism on phenylpropanoids secondary metabolites associated with flavor, aroma and health in tomato fruits. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7597920.bard.
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• Targeted manipulating Phenylalanine (Phe) synthesis is one of the most powerful strategies to boost the biologically and economically important secondary metabolites, including phenylpropaniods, aromatic volatiles and specialized secondary metabolites. • Over-expression of the petunia MYB transcript factor, ODORANT1 (ODO1), results in significant alterations of the levels of specific phenylpropanoid compounds in plants. • Our previous studies indicated that ectopic expression of the feedback-insensitive AroG could break the bottleneck between primary and secondary metabolisms in tomato, thereby aiding in producing new tomato composition and identifying the unknown roles of multiple key regulators in specialized metabolism. Therefore, combining the AroG and ODO1 is of particular interest for elucidating the combined regulatory role of both of these genes in the Phe metabolic pathway, as well as generating tomato fruits that contain higher levels of secondary metabolites. • Here, we performed the LC-MS and GC-MS analyses on fruits of four tomato genotypes, namely, wild type tomato fruits as well as tomato fruits expressing the AroG, ODO1 and the combination of AroG plus ODO1 (AO) genotypes. Our results elaborated that the levels of many of the Phe-derived metabolites were predominately altered in fruits of the AO genotype, compared to tomato fruits expressing either AroG or ODO1 individually. The levels of most of these metabolites were significantly stimulated, such as Tyrosine (Tyr), coumaric acid and ferulic acid derived metabolites, but the levels of some important secondary metabolites were reduced in the AO transgenic genotypes as compared to either AroG or ODO1 lines. Nevertheless, our results also revealed that the levels of aromatic volatiles were obviously down regulated in the AO, compared to that in AroG transgenic fruits, but were boosted while compared to the wild type and ODO1 transgenic fruits. • Our results suggest that ODO1 expression may also have a negative effect on the production of some of the aromatic volatiles in tomato fruits, indicating that ODO1 acts as an important regulator of the shikimate pathway, which leads to the production of the aromatic amino acids and secondary metabolites derived from them. Key words: AroG, ODO1, tomato, metabolism, shikimate pathway
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Barash, Itamar, and Robert Rhoads. Translational Mechanisms Governing Milk Protein Levels and Composition. United States Department of Agriculture, 2006. http://dx.doi.org/10.32747/2006.7696526.bard.
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Original objectives: The long-term goal of the research is to achieve higher protein content in the milk of ruminants by modulating the translational apparatus of the mammary gland genetically, nutritionally, or pharmacologically. The short-term objectives are to obtain a better understanding of 1) the role of amino acids (AA) as regulators of translation in bovine and mouse mammary epithelial cells and 2) the mechanism responsible for the synergistic enhancement of milk-protein mRNA polyadenylation by insulin and prolactin. Background of the topic: In many cell types and tissues, individual AA affect a signaling pathway which parallels the insulin pathway to modulate rates and levels of protein synthesis. Diverse nutritional and hormonal conditions are funneled to mTOR, a multidomain serine/threonine kinase that regulates a number of components in the initiation and elongation stages of translation. The mechanism by which AA signal mTOR is largely unknown. During the current grant period, we have studied the effect of essential AA on mechanisms involved in protein synthesis in differentiated mammary epithelial cells cultured under lactogenic conditions. We also studied lactogenic hormone regulation of milk protein synthesis in differentiated mammary epithelial cells. In the first BARD grant (2000-03), we discovered a novel mechanism for mRNA-specific hormone-regulated translation, namely, that the combination of insulin plus prolactin causes cytoplasmic polyadenylation of milk protein mRNAs, which leads to their efficient translation. In the current BARD grant, we have pursued the signaling pathways of this novel hormone action. Major conclusions/solutions/achievements: The positive and negative signaling from AA to the mTOR pathway, combined with modulation of insulin sensitization, mediates the synthesis rates of total and specific milk proteins in mammary epithelial cells. The current in vitro study revealed cryptic negative effects of Lys, His, and Thr on cellular mechanisms regulating translation initiation and protein synthesis in mammary epithelial cells that could not be detected by conventional in vivo analyses. We also showed that a signaling pathway involving Jak2 and Stat5, previously shown to lead from the prolactin receptor to transcription of milk protein genes, is also used for cytoplasmic polyadenylation of milk protein mRNAs, thereby stabilizing these mRNAs and activating them for translation. Implications: In vivo, plasma AA levels are affected by nutritional and hormonal effects as well as by conditions of exercise and stress. The amplitude in plasma AA levels resembles that applied in the current in vitro study. Thus, by changing plasma AA levels in the epithelial cell microenvironment or by sensitizing the mTOR pathway to their presence, it should be possible to modulate the rate of milk protein synthesis. Furthermore, knowledge that phosphorylation of Stat5 is required for enhanced milk protein synthesis in response to lactogenic opens the possibility for pharmacologic approaches to increase the phosphorylation of Stat5 and, thereby, milk protein production.