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effector evolution

Julia E Rood, Thomas N Burn, Vanessa Neal, Niansheng Chu, Edward M Behrens
Danger signals mediated through ST2, the interleukin-33 (IL-33) receptor, amplify CD8+ T cell-mediated inflammation in the murine model of familial hemophagocytic lymphohistiocytosis type 2 (FHL2), and blockade of ST2 provides a potential therapeutic strategy in this disease. However, the long-term effects of disrupting IL-33/ST2 signaling on the CD8+ T cell compartment are unknown. Here, we examined the evolution of the T cell response in murine FHL type 2 in the absence of ST2 signaling and found that CD8+ T cells gradually undergo exhaustion, similar to a related nonfatal FHL model...
2018: Frontiers in Immunology
Adriana Egui, Darién Ledesma, Elena Pérez-Antón, Andrés Montoya, Inmaculada Gómez, Sara María Robledo, Juan José Infante, Ivan Darío Vélez, Manuel C López, M Carmen Thomas
The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4+ and CD8+ T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD)...
2018: Frontiers in Cellular and Infection Microbiology
Prasenjit Paria, Hirak Jyoti Chakraborty, Bijay Kumar Behera, Pradeep Kumar Das Mahapatra, Basanta Kumar Das
Vibrio parahaemolyticus is a major seafood-borne pathogen that causes life-threatening gastroenteric diseases in humans through the consumption of contaminated seafoods. V. parahaemolyticus produces different kinds of toxins, including thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), and some effector proteins belonging to the Type 3 Secretion System, out of which TDH and TRH are considered to be the major factors for virulence. Although TRH is one of the major virulent proteins, there is a dearth of understanding about the structural and functional properties of this protein...
November 29, 2018: Microbial Pathogenesis
Morgan E Carter, Matthew Helm, Antony Chapman, Emily Wan, Ana M Restrepo Sierra, Roger Innes, Adam J Bogdanove, Roger Philip Wise
The Pseudomonas syringae cysteine protease AvrPphB activates the Arabidopsis resistance protein RPS5 by cleaving a second host protein, PBS1. AvrPphB induces defense responses in other plant species, but the genes and mechanisms mediating AvrPphB recognition in those species have not been defined. Here, we show that AvrPphB induces defense responses in diverse barley cultivars. We show also that barley contains two PBS1 orthologs, that their products are cleaved by AvrPphB, and that the barley AvrPphB response maps to a single locus containing a nucleotide-binding leucine-rich repeat (NLR) gene, which we termed AvrPphB Resistance 1 (Pbr1)...
November 27, 2018: Molecular Plant-microbe Interactions: MPMI
Musa A Hassan, Aude-Anais Olijnik, Eva-Maria Frickel, Jeroen P Saeij
The severe virulence of Toxoplasma gondii in classical laboratory inbred mouse strains contradicts the hypothesis that house mice (Mus musculus) are the most important intermediate hosts for its transmission and evolution because death of the mouse before parasite transmission equals death of the parasite. However, the classical laboratory inbred mouse strains (Mus musculus domesticus), commonly used to test Toxoplasma strain differences in virulence, do not capture the genetic diversity within Mus musculus...
November 21, 2018: International Journal for Parasitology
Henry M Kariithi, Drion G Boucias, Edwin K Murungi, Irene K Meki, Güler Demirbaş-Uzel, Monique M van Oers, Marc J B Vreysen, Adly M M Abd-Alla, Just M Vlak
BACKGROUND: Hytrosaviruses (SGHVs; Hytrosaviridae family) are double-stranded DNA (dsDNA) viruses that cause salivary gland hypertrophy (SGH) syndrome in flies. Two structurally and functionally distinct SGHVs are recognized; Glossina pallidipes SGHV (GpSGHV) and Musca domestica SGHV (MdSGHV), that infect the hematophagous tsetse fly and the filth-feeding housefly, respectively. Genome sizes and gene contents of GpSGHV (~ 190 kb; 160-174 genes) and MdSGHV (~ 124 kb; 108 genes) may reflect an evolution with the SGHV-hosts resulting in differences in pathobiology...
November 23, 2018: BMC Microbiology
Rachel Young, Stephen J Bush, Lucas Lefevre, Mary E B McCulloch, Zofia M Lisowski, Charity Muriuki, Lindsey A Waddell, Kristin A Sauter, Clare Pridans, Emily L Clark, David A Hume
Activated mouse macrophages metabolize arginine via NO synthase (NOS2) to produce NO as an antimicrobial effector. Published gene expression datasets provide little support for the activation of this pathway in human macrophages. Generation of NO requires the coordinated regulation of multiple genes. We have generated RNA-sequencing data from bone marrow-derived macrophages from representative rodent (rat), monogastric (pig and horse), and ruminant (sheep, goat, cattle, and water buffalo) species, and analyzed the expression of genes involved in arginine metabolism in response to stimulation with LPS...
January 1, 2018: ImmunoHorizons
Cordelia Manickam, Haiying Li, Spandan V Shah, Kyle Kroll, R Keith Reeves
Natural killer cells are primary immune effector cells with both innate and potentially adaptive functions against viral infections, but commonly become exhausted or dysfunctional during chronic diseases such as HIV. Chimpanzees are the closest genetic relatives of humans and have been previously used in immunology, behavior, and disease models. Due to their similarities to humans, a better understanding of chimpanzee immunology, particularly innate immune cells, can lend insight into the evolution of human immunology, as well as response to disease...
November 12, 2018: International Immunology
Yi-Ping Wang, Qun-Ying Lei
Metabolite sensing is one of the most fundamental biological processes. During evolution, multilayered mechanisms developed to sense fluctuations in a wide spectrum of metabolites, including nutrients, to coordinate cellular metabolism and biological networks. To date, AMPK and mTOR signaling are among the best-understood metabolite-sensing and signaling pathways. Here, we propose a sensor-transducer-effector model to describe known mechanisms of metabolite sensing and signaling. We define a metabolite sensor by its specificity, dynamicity, and functionality...
2018: Signal Transduction and Targeted Therapy
Juan J Mariman, Pablo Burgos, Pedro E Maldonado
During the control of reaching movements, a key contribution of the visual system is the localization of relevant environmental targets. In motor adaptation processes, the visual evaluation of effector motor behavior enables learning from errors, which demands continuous visual attentional focus. However, most current adaptation paradigms include static targets; therefore, when a learning situation develops in a highly variable environment and there is a double demand for visual resources (environment and motor performance), the evolution of learning processes is unknown...
November 7, 2018: European Journal of Neuroscience
Joana DE Fátima Ferreira Borges DA Costa, Carla DE Castro Sant' Anna, José Augusto Pereira Carneiro Muniz, Carlos Alberto Machado DA Rocha, Letícia Martins Lamarão, Caroline DE Fátima Aquino Moreira Nunes, Paulo Pimentel DE Assumpção, Rommel Rodriguez Burbano
BACKGROUND/AIM: The evolution of gastric carcinogenesis remains largely unknown, as the regulatory mechanisms involved in the aggressiveness of gastric cancer are still poorly understood. Kinases are downstream modulators and effectors of various cell signaling cascades and play key roles in the development of neoplastic diseases. The objective of this study was to evaluate the expression of genes and proteins of the SRC family, including FYN, YES, BLK, FGR, LYN and SRC, in a model of intestinal gastric carcinogenesis generated by treating Cebus apella, a New World non-human primate, with N-methyl nitrosourea (MNU)...
November 2018: Anticancer Research
Frank E Marino
The relationship between performance, heat load and the ability to withstand serious thermal insult is a key factor in understanding how endurance is regulated. The capacity to withstand high thermal loads is not unique to humans and is typical to all mammals. Thermoregulation is an evolutionary adaptation which is species specific and should be regarded as a survival strategy rather than purely a physiological response. The fact that mammals have selected ~37°C as a set point could be a key factor in understanding our endurance capabilities and strategy...
2018: Progress in Brain Research
Marion C Müller, Coraline R Praz, Alexandros G Sotiropoulos, Fabrizio Menardo, Lukas Kunz, Seraina Schudel, Simone Oberhänsli, Manuel Poretti, Andreas Wehrli, Salim Bourras, Beat Keller, Thomas Wicker
Blumeria graminis f. sp. tritici (B.g. tritici) is the causal agent of the wheat powdery mildew disease. The highly fragmented B.g. tritici genome available so far has prevented a systematic analysis of effector genes that are known to be involved in host adaptation. To study the diversity and evolution of effector genes we produced a chromosome-scale assembly of the B.g. tritici genome. The genome assembly and annotation was achieved by combining long-read sequencing with high-density genetic mapping, bacterial artificial chromosome fingerprinting and transcriptomics...
November 2, 2018: New Phytologist
Lucy C Young, Nicole Hartig, Isabel Boned Del Río, Sibel Sari, Benjamin Ringham-Terry, Joshua R Wainwright, Greg G Jones, Frank McCormick, Pablo Rodriguez-Viciana
Dephosphorylation of the inhibitory "S259" site on RAF kinases (S259 on CRAF, S365 on BRAF) plays a key role in RAF activation. The MRAS GTPase, a close relative of RAS oncoproteins, interacts with SHOC2 and protein phosphatase 1 (PP1) to form a heterotrimeric holoenzyme that dephosphorylates this S259 RAF site. MRAS and SHOC2 function as PP1 regulatory subunits providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kanika Bansal, Sanjeet Kumar, Prabhu B Patil
Xanthomonas, a complex group of pathogens, infects more than 400 plants, which is expanding to new hosts causing serious diseases. Genome-based studies are transforming our understanding on diversity and relationship of host-specific members, known as pathovars. In this study, we report complete genome sequence of a novel pathovar Xanthomonas axonopodis pv. commiphorae (Xcom) from India. It causes gumming disease of Commiphora wightii, a medicinally important plant. Genome-based phylogenetic and taxonomic investigation revealed that the pathovar belongs to Xanthomonas euvesicatoria and not X...
November 1, 2018: Genome Biology and Evolution
Soumya Rao, Saphy Sharda, Vineesha Oddi, Madhusudan R Nandineni
The ascomycete fungus Colletotrichum truncatum is a major phytopathogen with a broad host range which causes anthracnose disease of chilli. The genome sequencing of this fungus led to the discovery of functional categories of genes that may play important roles in fungal pathogenicity. However, the presence of gaps in C. truncatum draft assembly prevented the accurate prediction of repetitive elements, which are the key players to determine the genome architecture and drive evolution and host adaptation. We re-sequenced its genome using single-molecule real-time (SMRT) sequencing technology to obtain a refined assembly with lesser and smaller gaps and ambiguities...
2018: Frontiers in Microbiology
Aijun Wang, Linxiu Pang, Na Wang, Peng Ai, Desuo Yin, Shuangcheng Li, Qiming Deng, Jun Zhu, Yueyang Liang, Jianqing Zhu, Ping Li, Aiping Zheng
Tilletia horrida is a soil-borne, mononucleate basidiomycete fungus with a biotrophic lifestyle that causes rice kernel smut, a disease that is distributed throughout hybrid rice growing areas worldwide. Here we report on the high-quality genome sequence of T. horrida; it is composed of 23.2 Mb that encode 7,729 predicted genes and 6,973 genes supported by RNA-seq. The genome contains few repetitive elements that account for 8.45% of the total. Evolutionarily, T. horrida lies close to the Ustilago fungi, suggesting grass species as potential hosts, but co-linearity was not observed between T...
October 18, 2018: Scientific Reports
Olga Makarova, Paul Johnston, Alexandro Rodriguez-Rojas, Baydaa El Shazely, Javier Moreno Morales, Jens Rolff
Antimicrobial peptides (AMP) are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetle Tenebrio molitor, a defensin and a coleoptericin are highly expressed in vivo after inoculation with S. aureus. The defensin displays strong in vitro activity but no survival benefit in vivo. The coleoptericin provides a survival benefit in vivo, but no activity in vitro. This suggests a potentiating effect in vivo, and here we wanted to investigate the effects of this combination on resistance evolution using a bottom-approach in vitro starting with a combination of two abundant AMPs only...
October 18, 2018: Scientific Reports
Ashley L Fink, Sabra L Klein
Males and females differ in their effector and memory immune responses to foreign and self-antigens. The difference in antibody responses (i.e., humoral immunity), in particular, is one of the most well conserved sex differences in immunology. Certain sex differences in humoral immunity are present throughout life, whereas others are only apparent after puberty and prior to reproductive senescence, suggesting that both genes and hormones are involved. Importantly, these sex-based differences in humoral immunity contribute to variation in the responses to vaccines and may explain some disparities in vaccine efficacy between the sexes...
December 2018: Current Opinion in Physiology
Xiaoyang Li, Haitao Tu, Shen Q Pan
Agrobacterium tumefaciens transfers oncogenic DNA (T-DNA) and effector proteins into various host plants. T-DNA is generated inside the bacteria and subsequently delivered into plant cells along with the companion effectors VirD2, VirE2, and VirE3. However, it is not clear how the T-complex consisting of VirD2 and VirE2 is assembled inside plant cells. Here, we report that the effector protein VirE3 localized to plant plasma membranes as an anchorage through a conserved α-helical-bundle domain. VirE3 interacted with itself and enabled VirE2 accumulation at host entry sites through direct interactions...
October 9, 2018: Cell Reports
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