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effector evolution

Josef P Rauschecker
At first glance, the monkey brain looks like a smaller version of the human brain. Indeed, the anatomical and functional architecture of the cortical auditory system in monkeys is very similar to that of humans, with dual pathways segregated into a ventral and a dorsal processing stream. Yet, monkeys do not speak. Repeated attempts to pin this inability on one particular cause have failed. A closer look at the necessary components of language, according to Darwin, reveals that all of them got a significant boost during evolution from nonhuman to human primates...
June 2018: Current Opinion in Behavioral Sciences
Charles Bou-Nader, Jackson M Gordon, Frances E Henderson, Jinwei Zhang
The interferon-inducible protein kinase R (PKR) is a key component of host innate immunity that restricts viral replication and propagation. As one of the four eIF2alpha kinases that sense diverse stresses and direct the integrated stress response (ISR) crucial for cell survival and proliferation, PKR's versatile roles extend well beyond antiviral defense. Targeted by numerous host and viral regulators made of RNA and proteins, PKR is subject to multiple layers of endogenous control and external manipulation, driving its rapid evolution...
February 15, 2019: RNA
Yohey Ogawa, Tomoya Shiraki, Yoshimasa Asano, Akira Muto, Koichi Kawakami, Yutaka Suzuki, Daisuke Kojima, Yoshitaka Fukada
Color discrimination in the vertebrate retina is mediated by a combination of spectrally distinct cone photoreceptors, each expressing one of multiple cone opsins. The opsin genes diverged early in vertebrate evolution into four classes maximally sensitive to varying wavelengths of light: UV (SWS1), blue (SWS2), green (RH2), and red (LWS) opsins. Although the tetrachromatic cone system is retained in most nonmammalian vertebrate lineages, the transcriptional mechanism underlying gene expression of the cone opsins remains elusive, particularly for SWS2 and RH2 opsins, both of which have been lost in the mammalian lineage...
February 14, 2019: Proceedings of the National Academy of Sciences of the United States of America
Sunil Singhal, Jason Stadanlick, Michael J Annunziata, Abhishek S Rao, Pratik S Bhojnagarwala, Shaun O'Brien, Edmund K Moon, Edward Cantu, Gwenn Danet-Desnoyers, Hyun-Jeong Ra, Leslie Litzky, Tatiana Akimova, Ulf H Beier, Wayne W Hancock, Steven M Albelda, Evgeniy B Eruslanov
Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs)...
February 13, 2019: Science Translational Medicine
Stylianos Bournazos
Immunoglobulins (Ig), a critical component of the adaptive immune system, are present in all jawed vertebrates and through sophisticated diversification mechanisms are able to recognize antigens of almost infinite diversity. During mammalian evolution, IgG has emerged as the predominant Ig isotype that is elicited upon antigenic challenge, representing the most abundant isotype present in circulation. Along with the IgG molecule, a family of specialized receptors has evolved in mammalian species that specifically recognize the Fc domain of IgG...
February 10, 2019: Current Topics in Microbiology and Immunology
Rick Masonbrink, Tom R Maier, Usha Muppirala, Arun S Seetharam, Etienne Lord, Parijat S Juvale, Jeremy Schmutz, Nathan T Johnson, Dmitry Korkin, Melissa G Mitchum, Benjamin Mimee, Sebastian Eves-van den Akker, Matthew Hudson, Andrew J Severin, Thomas J Baum
BACKGROUND: Heterodera glycines, commonly referred to as the soybean cyst nematode (SCN), is an obligatory and sedentary plant parasite that causes over a billion-dollar yield loss to soybean production annually. Although there are genetic determinants that render soybean plants resistant to certain nematode genotypes, resistant soybean cultivars are increasingly ineffective because their multi-year usage has selected for virulent H. glycines populations. The parasitic success of H. glycines relies on the comprehensive re-engineering of an infection site into a syncytium, as well as the long-term suppression of host defense to ensure syncytial viability...
February 7, 2019: BMC Genomics
Anna-Kristin Ludwig, Malwina Michalak, Qi Xiao, Ulrich Gilles, Francisco J Medrano, Hanyue Ma, Forrest G FitzGerald, William D Hasley, Adriel Melendez-Davila, Matthew Liu, Khosrow Rahimi, Nina Yu Kostina, Cesar Rodriguez-Emmenegger, Martin Möller, Ingo Lindner, Herbert Kaltner, Mare Cudic, Dietmar Reusch, Jürgen Kopitz, Antonio Romero, Stefan Oscarson, Michael L Klein, Hans-Joachim Gabius, Virgil Percec
Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface...
February 4, 2019: Proceedings of the National Academy of Sciences of the United States of America
Jose Pedro Fonseca, Kirankumar S Mysore
Most potential pathogens fail to establish virulence for a plethora of plants found in nature. This intrinsic property to resist pathogen virulence displayed by organisms without triggering canonical resistance (R) genes has been termed nonhost resistance (NHR). While host resistance involves recognition of pathogen elicitors such as avirulence factors by bona fide R proteins, mechanism of NHR seems less obvious, often involving more than one gene. We can generally describe NHR in two steps: 1) pre-invasive resistance, either passive or active, which can restrict the pathogen from entering the host, and 2) post-invasive resistance, an active defense response that often results in hypersensitive response like programmed cell death and reactive oxygen species accumulation...
February 2019: Plant Science: An International Journal of Experimental Plant Biology
Janine Haueisen, Mareike Möller, Christoph J Eschenbrenner, Jonathan Grandaubert, Heike Seybold, Holger Adamiak, Eva H Stukenbrock
Many filamentous plant pathogens exhibit high levels of genomic variability, yet the impact of this variation on host-pathogen interactions is largely unknown. We have addressed host specialization in the wheat pathogen Zymoseptoria tritici . Our study builds on comparative analyses of infection and gene expression phenotypes of three isolates and reveals the extent to which genomic variation translates into phenotypic variation. The isolates exhibit genetic and genomic variation but are similarly virulent...
January 2019: Ecology and Evolution
Laura Gomez-Valero, Christophe Rusniok, Danielle Carson, Sonia Mondino, Ana Elena Pérez-Cobas, Monica Rolando, Shivani Pasricha, Sandra Reuter, Jasmin Demirtas, Johannes Crumbach, Stephane Descorps-Declere, Elizabeth L Hartland, Sophie Jarraud, Gordon Dougan, Gunnar N Schroeder, Gad Frankel, Carmen Buchrieser
The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 Legionella genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and Legionella Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates...
January 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
Sandro Goruppi, Andrea Clocchiatti, G Paolo Dotto
In the tumor stroma, cancer-associated fibroblasts (CAFs) affect all aspects of tumor evolution. Whereas several programs leading to CAF activation have been elucidated, little is known about the impact of the microenvironment on the turnover of key CAF regulators. RBPJ/CSL is a transcriptional repressor that mediates NOTCH signaling and its down-modulation activates the gene expression program(s) leading to stromal senescence and CAF activation. We overview our evidence that conditions increasing macroautophagy/autophagy, as often found in the stroma of tumors, cause the down-modulation of the RBPJ protein...
January 17, 2019: Autophagy
Rongzhi Zhang, Fengya Zheng, Shugen Wei, Shujuan Zhang, Genying Li, Peijian Cao, Shancen Zhao
Biotic stresses do damage to the growth and development of plants, and yield losses for some crops. Confronted with microbial infections, plants have evolved multiple defense mechanisms, which play important roles in the never-ending molecular arms race of plant⁻pathogen interactions. The complicated defense systems include pathogen-associated molecular patterns (PAMP) triggered immunity (PTI), effector triggered immunity (ETI), and the exosome-mediated cross-kingdom RNA interference (CKRI) system. Furthermore, plants have evolved a classical regulation system mediated by miRNAs to regulate these defense genes...
January 15, 2019: International Journal of Molecular Sciences
Alexander Wagner, Christoph Dehio
The α-proteobacterial genus Bartonella comprises a large number of facultative intracellular pathogens that share a common life-style hallmarked by hemotrophic infection and arthropod transmission. Speciation in the four deep-branching lineages (L1-L4) occurred by host adaptation facilitating the establishment of long-lasting bacteremia in specific mammalian reservoir host(s). Two distinct type-IV-secretion systems (T4SSs) acquired horizontally by different Bartonella lineages mediate essential host interactions during infection and represent key innovations for host adaptation...
January 15, 2019: Cellular Microbiology
John M McDowell
Plants perceive a variety of molecules produced by microbes, insects, and nematodes. These pathogen-derived components include so-called microbe-associated molecular patterns, or MAMPs, as well as effector proteins that are secreted to the exterior or interior of plant cells and these molecules can be recognized by receptor protein complexes on the exterior or interior of plant cells, thereby activating MAMP- or effector-triggered immunity (MTI or ETI, respectively). Because these processes are key components of plant disease resistance, they have been studied intensively...
January 2019: Molecular Plant-microbe Interactions: MPMI
Franciane Paul, Guillaume Cartron
Rituximab, an anti-CD20 monoclonal antibody (mAb), is indicated in the treatment of B-cell non Hodgkin lymphomas, chronic lymphoid leukemia and rheumatoid arthritis. The occurrence of infusion related reactions (IRR), especially during the first infusion, is one of the main concerns of rituximab, otherwise well tolerated. Although IRR are usually mild to moderate, fatal evolutions have been reported. These reactions are not specific to rituximab and also observed with other compounds, including those recruiting effectors cells...
December 24, 2018: Expert Review of Clinical Immunology
Ly-Binh-An Tran, Thanh-Trang Cao-Pham, Bénédicte F Jordan, Sofie Deschoemaeker, Arne Heyerick, Bernard Gallez
Tumour hypoxia is a well-established factor of resistance in radiation therapy (RT). Myo-inositol trispyrophosphate (ITPP) is an allosteric effector that reduces the oxygen-binding affinity of haemoglobin and facilitates the release of oxygen by red blood cells. We investigated herein the oxygenation effect of ITPP in six tumour models and its radiosensitizing effect in two of these models. The evolution of tumour pO2 upon ITPP administration was monitored on six models using 1.2 GHz Electron Paramagnetic Resonance (EPR) oximetry...
December 21, 2018: Journal of Cellular and Molecular Medicine
Harmeet Kaur, Neetu Sain, Debasisa Mohanty, Dinakar M Salunke
BACKGROUND: Antibody, the primary effector molecule of the immune system, evolves after initial encounter with the antigen from a precursor form to a mature one to effectively deal with the antigen. Antibodies of a lineage diverge through antigen-directed isolated pathways of maturation to exhibit distinct recognition potential. In the context of evolution in immune recognition, diversity of antigen cannot be ignored. While there are reports on antibody lineage, structural perspective with respect to diverse recognition potential in a lineage has never been studied...
December 19, 2018: BMC Structural Biology
Pellegrino Crafa, Michele Russo, Chiara Miraglia, Alberto Barchi, Florenzo Moccia, Antonio Nouvenne, Gioacchino Leandro, Tiziana Meschi, Gian Luigi De' Angelis, Francesco Di Mario
Chronic gastritis is a long-lasting disease that can lead to a loss of appropriate gastric glands. Gastritis, as term, apply to an inflammation of the stomach, histologically proven, sometimes with structural mucosal changes. Worldwide Helicobacter pylori's infection play a pivotal role as the main etiological effector of chronic active gastritis. H. p. is a bacterium with a selective tropism for the gastric mucosa, able to survive in a hostile environment for colonization of organisms other than itself, able to develop strategies for survival and for avoidance of the defence mechanisms, causing inflammatory changes, that vary from asymptomatic mild gastritis to more severe injury such as peptic ulcer as well as premalignant lesions and malignant tumours...
December 17, 2018: Acta Bio-medica: Atenei Parmensis
Bennett Davenport, Jens Eberlein, Verena van der Heide, Kevin Jhun, Tom T Nguyen, Francisco Victorino, Andrew Trotta, Jerry Chipuk, Zhengzi Yi, Weijia Zhang, Eric T Clambey, Donald K Scott, Dirk Homann
Aging of established antiviral T cell memory can foster a series of progressive adaptations that paradoxically improve rather than compromise protective CD8+ T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8+ memory T cell (TM ) homeostasis. Over time, CD8+ TM generated in the wake of an acute infection with the natural murine pathogen lymphocytic choriomeningitis virus become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8+ TM quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8+ TM from blood and nonlymphoid tissues to lymphatic organs results in CD8+ TM accumulations in bone marrow, splenic white pulp, and, particularly, lymph nodes...
December 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Winston X Yan, Pratyusha Hunnewell, Lauren E Alfonse, Jason M Carte, Elise Keston-Smith, Shanmugapriya Sothiselvam, Anthony J Garrity, Shaorong Chong, Kira S Makarova, Eugene V Koonin, David R Cheng, David A Scott
Type V CRISPR-Cas systems are distinguished by a single RNA-guided RuvC domain-containing effector, Cas12. Although effectors of subtypes V-A (Cas12a) and V-B (Cas12b) have been studied in detail, the distinct domain architectures and diverged RuvC sequences of uncharacterized Cas12 proteins suggest unexplored functional diversity. Here, we identify and characterize Cas12c, g, h, and i. Cas12c, h, and i demonstrate RNA-guided double-stranded (ds) DNA interference activity. Cas12i exhibits markedly different efficiencies of crRNA spacer complementary and non-complementary strand cleavage resulting in predominant dsDNA nicking...
December 6, 2018: Science
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