Letteratura scientifica selezionata sul tema "Host dependency factors"
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Articoli di riviste sul tema "Host dependency factors"
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Hamm, Joshua N., Susanne Erdmann, Emiley A. Eloe-Fadrosh, Allegra Angeloni, Ling Zhong, Christopher Brownlee, Timothy J. Williams et al. "Unexpected host dependency of Antarctic Nanohaloarchaeota". Proceedings of the National Academy of Sciences 116, n. 29 (28 giugno 2019): 14661–70. http://dx.doi.org/10.1073/pnas.1905179116.
Testo completoAbstract (sommario):
In hypersaline environments, Nanohaloarchaeota (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaeota [DPANN] superphylum) are thought to be free-living microorganisms. We report cultivation of 2 strains of Antarctic Nanohaloarchaeota and show that they require the haloarchaeon Halorubrum lacusprofundi for growth. By performing growth using enrichments and fluorescence-activated cell sorting, we demonstrated successful cultivation of Candidatus Nanohaloarchaeum antarcticus, purification of Ca. Nha. antarcticus away from other species, and growth and verification of Ca. Nha. antarcticus with Hrr. lacusprofundi; these findings are analogous to those required for fulfilling Koch’s postulates. We use fluorescent in situ hybridization and transmission electron microscopy to assess cell structures and interactions; metagenomics to characterize enrichment taxa, generate metagenome assembled genomes, and interrogate Antarctic communities; and proteomics to assess metabolic pathways and speculate about the roles of certain proteins. Metagenome analysis indicates the presence of a single species, which is endemic to Antarctic hypersaline systems that support the growth of haloarchaea. The presence of unusually large proteins predicted to function in attachment and invasion of hosts plus the absence of key biosynthetic pathways (e.g., lipids) in metagenome assembled genomes of globally distributed Nanohaloarchaeota indicate that all members of the lineage have evolved as symbionts. Our work expands the range of archaeal symbiotic lifestyles and provides a genetically tractable model system for advancing understanding of the factors controlling microbial symbiotic relationships.
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Verrier, Eloi R., Amélie Weiss, Charlotte Bach, Laura Heydmann, Vincent Turon-Lagot, Arnaud Kopp, Houssein El Saghire et al. "Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets". Gut 69, n. 1 (4 marzo 2019): 158–67. http://dx.doi.org/10.1136/gutjnl-2018-317065.
Testo completoAbstract (sommario):
ObjectiveHepatitis D virus (HDV) is a circular RNA virus coinfecting hepatocytes with hepatitis B virus. Chronic hepatitis D results in severe liver disease and an increased risk of liver cancer. Efficient therapeutic approaches against HDV are absent.DesignHere, we combined an RNAi loss-of-function and small molecule screen to uncover host-dependency factors for HDV infection.ResultsFunctional screening unravelled the hypoxia-inducible factor (HIF)-signalling and insulin-resistance pathways, RNA polymerase II, glycosaminoglycan biosynthesis and the pyrimidine metabolism as virus-hepatocyte dependency networks. Validation studies in primary human hepatocytes identified the carbamoyl-phosphatesynthetase 2, aspartate transcarbamylase and dihydroorotase (CAD) enzyme and estrogen receptor alpha (encoded by ESR1) as key host factors for HDV life cycle. Mechanistic studies revealed that the two host factors are required for viral replication. Inhibition studies using N-(phosphonoacetyl)-L-aspartic acid and fulvestrant, specific CAD and ESR1 inhibitors, respectively, uncovered their impact as antiviral targets.ConclusionThe discovery of HDV host-dependency factors elucidates the pathogenesis of viral disease biology and opens therapeutic strategies for HDV cure.
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Kanojia, Aditi, Mansi Sharma, Rishad Shiraz e Shashank Tripathi. "Flavivirus–Host Interaction Landscape Visualized through Genome-Wide CRISPR Screens". Viruses 14, n. 10 (30 settembre 2022): 2164. http://dx.doi.org/10.3390/v14102164.
Testo completoAbstract (sommario):
Flaviviruses comprise several important human pathogens which cause significant morbidity and mortality worldwide. Like any other virus, they are obligate intracellular parasites. Therefore, studying the host cellular factors that promote or restrict their replication and pathogenesis becomes vital. Since inhibiting the host dependency factors or activating the host restriction factors can suppress the viral replication and propagation in the cell, identifying them reveals potential targets for antiviral therapeutics. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has provided an effective means of producing customizable genetic modifications and performing forward genetic screens in a broad spectrum of cell types and organisms. The ease, rapidity, and high reproducibility of CRISPR technology have made it an excellent tool for carrying out genome-wide screens to identify and characterize viral host dependency factors systematically. Here, we review the insights from various Genome-wide CRISPR screens that have advanced our understanding of Flavivirus-Host interactions.
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Becker, Tanja, Vu Le-Trilling e Mirko Trilling. "Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses". International Journal of Molecular Sciences 20, n. 7 (2 aprile 2019): 1636. http://dx.doi.org/10.3390/ijms20071636.
Testo completoAbstract (sommario):
Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that frequently causes morbidity and mortality in individuals with insufficient immunity, such as transplant recipients, AIDS patients, and congenitally infected newborns. Several antiviral drugs are approved to treat HCMV infections. However, resistant HCMV mutants can arise in patients receiving long-term therapy. Additionally, side effects and the risk to cause birth defects limit the use of currently approved antivirals against HCMV. Therefore, the identification of new drug targets is of clinical relevance. Recent work identified DNA-damage binding protein 1 (DDB1) and the family of the cellular cullin (Cul) RING ubiquitin (Ub) ligases (CRLs) as host-derived factors that are relevant for the replication of human and mouse cytomegaloviruses. The first-in-class CRL inhibitory compound Pevonedistat (also called MLN4924) is currently under investigation as an anti-tumor drug in several clinical trials. Cytomegaloviruses exploit CRLs to regulate the abundance of viral proteins, and to induce the proteasomal degradation of host restriction factors involved in innate and intrinsic immunity. Accordingly, pharmacological blockade of CRL activity diminishes viral replication in cell culture. In this review, we summarize the current knowledge concerning the relevance of DDB1 and CRLs during cytomegalovirus replication and discuss chances and drawbacks of CRL inhibitory drugs as potential antiviral treatment against HCMV.
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Aromolaran, Olufemi, Thomas Beder, Eunice Adedeji, Yvonne Ajamma, Jelili Oyelade, Ezekiel Adebiyi e Rainer Koenig. "Predicting host dependency factors of pathogens in Drosophila melanogaster using machine learning". Computational and Structural Biotechnology Journal 19 (2021): 4581–92. http://dx.doi.org/10.1016/j.csbj.2021.08.010.
Testo completo
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Petrova, Evgeniya, Ségolène Gracias, Guillaume Beauclair, Frédéric Tangy e Nolwenn Jouvenet. "Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen". Viruses 11, n. 1 (15 gennaio 2019): 68. http://dx.doi.org/10.3390/v11010068.
Testo completoAbstract (sommario):
Flaviviruses, such as dengue (DENV), West Nile (WNV), yellow fever (YFV) and Zika (ZIKV) viruses, are mosquito-borne pathogens that present a major risk to global public health. To identify host factors that promote flavivirus replication, we performed a genome-wide gain-of-function cDNA screen for human genes that enhance the replication of flavivirus reporter particles in human cells. The screen recovered seventeen potential host proteins that promote viral replication, including the previously known dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit (DDOST). Using silencing approaches, we validated the role of four candidates in YFV and WNV replication: ribosomal protein L19 (RPL19), ribosomal protein S3 (RPS3), DDOST and importin 9 (IPO9). Applying a panel of virological, biochemical and microscopic methods, we validated further the role of RPL19 and DDOST as host factors required for optimal replication of YFV, WNV and ZIKV. The genome-wide gain-of-function screen is thus a valid approach to advance our understanding of flavivirus replication.
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Syarifuddin, Ferry. "The Dynamics of Foreign Portfolio Investment and Exchange Rates: An Interconnection Approach in ASEAN". Journal of Eurasian Economies 1, n. 2 (22 luglio 2022): 1–12. http://dx.doi.org/10.36880/j01.2.0113.
Testo completoAbstract (sommario):
This paper examines the spatial dependence of foreign portfolio investment (FPI) inflows among ASEAN countries in 2002Q1-2018Q4 utilizing the spatial econometric approach. This paper adds clarity to the identification of the true nature of portfolio investment performances. I show a competitive relationship among ASEAN countries, indicating crowding out of FPI in the host country is most likely to occur when the neighboring country is experiencing a crowding out. I also show that exchange rate volatility and changes, both in the host country and neighboring country, do not significantly affect FPI in the host country. Furthermore, I find that, aside from macroeconomic factors of the host country, foreign investors also consider the macroeconomic conditions in the neighboring country, suggesting the existence of spatial dependency. Robustness checks are conducted to confirm the main findings of this study.
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Rother, Marion, Christiane Dimmler, Friderike Weege, Hans-Joachim Mollenkopf, Thomas F. Meyer e Michael Naumann. "Discovery of Zika virus host dependency factors in trophoblasts using CRISPR/Cas9 screening". Journal of Virological Methods 290 (aprile 2021): 114085. http://dx.doi.org/10.1016/j.jviromet.2021.114085.
Testo completo
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King, Cason R., e Andrew Mehle. "The later stages of viral infection: An undiscovered country of host dependency factors". PLOS Pathogens 16, n. 8 (25 agosto 2020): e1008777. http://dx.doi.org/10.1371/journal.ppat.1008777.
Testo completo
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Ma, Yijie, Michael J. Walsh, Katharina Bernhardt, Camille W. Ashbaugh, Stephen J. Trudeau, Isabelle Y. Ashbaugh, Sizun Jiang et al. "CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors". Cell Host & Microbe 21, n. 5 (maggio 2017): 580–91. http://dx.doi.org/10.1016/j.chom.2017.04.005.
Testo completoTesi sul tema "Host dependency factors"
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Couderc, Élodie. "Discovery of mosquito molecular factors modulating arbovirus infection in Aedes aegypti". Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS199.
Testo completoAbstract (sommario):
Les virus transmis par les arthropodes (arbovirus) impactent significativement la santé humaine à l'échelle mondiale, causant des maladies avec une morbidité et une mortalité élevées. Les flavivirus transmis par les moustiques, notamment les virus de la dengue (DENV) et Zika (ZIKV), sont particulièrement préoccupants. Ces virus sont principalement transmis par le moustique Aedes aegypti, dont la répartition géographique s'étend en raison des changements globaux. Actuellement, il n'existe pas de vaccins approuvés à grande échelle ni d'antiviraux spécifiques pour ces virus, et les méthodes traditionnelles de contrôle des vecteurs sont entravées par la résistance aux insecticides. Face à ces défis, des stratégies alternatives ont été développées pour manipuler la biologie des vecteurs afin de réduire leur compétence vectorielle, c'est-à-dire leur aptitude à être infectés et à transmettre des pathogènes. Une stratégie potentielle est de relâcher de moustiques modifiés incapables de transmettre des agents pathogènes. Il est donc crucial d'identifier des cibles optimales pour ces modifications, et les facteurs moléculaires des moustiques qui modulent la transmission des arbovirus sont des candidats prometteurs. Cependant, une grande partie des connaissances actuelles sur la compétence vectorielle des moustiques provient d'études sur l'insecte modèle Drosophila melanogaster, qui ne reproduit pas entièrement les réponses des moustiques. Des approches spécifiques aux moustiques sont donc essentielles pour étudier les facteurs intrinsèques de leur compétence vectorielle.Cette thèse de doctorat présente trois approches in vivo pour étudier les facteurs moléculaires influençant l'infection, la dissémination et la transmission des flavivirus chez Aedes aegypti. Le premier chapitre traite de la caractérisation fonctionnelle in vivo d'un gène Vago-like, VLG-1, chez Ae. aegypti dans le contexte de l'infection par les flavivirus. De façon surprenante, une lignée mutante de VLG-1 générée par CRISPR/Cas9 a montré que chez Ae. aegypti, VLG-1 favorise la dissémination de DENV et ZIKV dans le moustique, remettant en question le dogme affirmant que les gènes Vago-like sont des facteurs antiviraux conservés chez les arthropodes. Une analyse transcriptomique organe-spécifique a révélé que VLG-1 affecte des processus biologiques potentiellement liés à la réplication virale, tels que la réponse au stress oxydatif. Le deuxième chapitre rapporte la découverte d'un nouveau facteur antiviral non canonique, le cytochrome P450 4g15, associé à une résistance naturelle à DENV dans une population d'Ae. aegypti. L'induction de ce gène dans le tube digestif après un repas sanguin entrave l'infection par DENV. Des polymorphismes dans la séquence promotrice de ce gène contrôlent son expression et la probabilité d'infection par DENV. Cette étude est la première à démontrer l'impact de variants naturels d'un gène sur la résistance d'Ae. aegypti à DENV. Le troisième chapitre décrit la caractérisation in vivo de potentiels récepteurs de DENV chez Ae. aegypti, en particulier prohibitin-2. Malgré un effet proviral de prohibitin-2 sur la réplication de DENV dans le corps du moustique, ce gène n'a pas montré de rôle significatif dans l'entrée de DENV dans le tube digestif du moustique in vivo. Ces résultats indiquent que l'identification in vitro de récepteurs viraux ne garantit pas la confirmation in vivo de leur rôle dans l'entrée virale. En résumé, cette thèse de doctorat contribue à faire avancer notre compréhension des interactions moustiques-virus, à identifier de nouvelles cibles pour le contrôle des vecteurs et à mettre en lumière la complexité des mécanismes moléculaires de la compétence vectorielle. Elle met en avant la nécessité de la recherche in vivo et l'importance d'exploiter la diversité génétique naturelle des populations de moustiques pour développer des stratégies innovantes de contrôle des maladies transmises par les moustiquesArthropod-borne viruses (arboviruses) significantly impact global health, causing diseases with high morbidity and mortality. Mosquito-borne flaviviruses, notably dengue (DENV) and Zika (ZIKV) viruses, are of particular concern. These viruses are primarily transmitted by the Aedes aegypti mosquito, which is expanding its range due to global changes. Currently, there are no globally approved vaccines or specific antivirals for these viruses, and traditional vector control methods are hindered by insecticide resistance. Concerns about the future of vector control have led to alternative strategies aimed at manipulating the biology of vectors to reduce their vector competence, i.e., the ability of mosquitoes to become infected and transmit pathogens. The release of modified mosquitoes that cannot transmit pathogens is a potential strategy to reduce the incidence of human disease. Thus, there is a growing need to identify optimal targets for modification, and mosquito molecular factors that modulate arbovirus transmission are promising candidates.However, much of the knowledge on mosquito vector competence derives from studies in the insect model Drosophila melanogaster and does not fully recapitulate mosquito responses. Therefore, implementation of mosquito-specific approaches is essential to investigate intrinsic factors underlying vector competence. In this context, this PhD thesis presents three in vivo approaches to investigate molecular factors that influence flavivirus infection, dissemination, and transmission in Aedes aegypti.The first chapter is dedicated to the functional characterization of a Vago-like gene, VLG-1, in Ae. aegypti in the context of flavivirus infection. Arthropod Vago genes are often described as analogs of mammalian cytokines with antiviral functions. Strikingly, a VLG-1 mutant line generated by CRISPR/Cas9-mediated gene editing revealed that in Ae. aegypti, VLG-1 promotes DENV and ZIKV dissemination within the mosquito, challenging the idea that Vago-like genes are conserved antiviral factors. Tissue-specific transcriptome analysis indicated that VLG-1 affects biological processes potentially linked to viral replication, such as oxidative stress response. The second chapter focuses on the discovery of a novel non-canonical antiviral factor, cytochrome P450 4g15, associated with a natural DENV resistance phenotype in a field-derived Ae. aegypti population. Induction of cytochrome P450 4g15 in the midgut after bloodmeal ingestion hinders DENV infection. Polymorphisms in this gene's promoter sequence control its expression level and the probability of successful DENV infection, marking the first report of natural gene variants impacting DENV resistance in Ae. aegypti.The third chapter examines candidate DENV receptors in Ae. aegypti, with a specific emphasis on prohibitin-2. This study demonstrated a proviral effect of prohibitin-2 on DENV replication in mosquito bodies. Nevertheless, despite employing a range of experimental techniques, prohibitin-2 did not exhibit a substantial role in DENV entry into mosquito midguts in vivo. These findings indicate that in vitro identification of viral receptors may not necessarily translate to in vivo confirmation of their role in viral entry.Overall, this PhD thesis contributes to advancing our understanding of mosquito-virus interactions, identifying new targets for vector control strategies, and highlighting the complexity of the molecular mechanisms underlying vector competence. This work emphasizes the necessity for in vivo research and underscores the value of exploiting the natural genetic diversity of field-derived mosquito populations to gain insights into the complex mechanisms governing mosquito vector competence for flaviviruses and to develop innovative strategies for controlling mosquito-borne diseases
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Shapka, Natalia. "IDENTIFICATION OF VIRAL AND HOST FACTORS INVOLVED IN TOMBUSVIRUS REPLICATION AND RECOMBINATION". UKnowledge, 2006. http://uknowledge.uky.edu/gradschool_diss/449.
Testo completoAbstract (sommario):
Rapid evolution of RNA viruses with mRNA-sense genomes is a major concern to health and economic welfare due to the devastating diseases these viruses inflict on humans, animals and plants. Rapid viral RNA evolution is frequently due to RNA recombination, which can be facilitated by recombination signals present in viral RNAs. Among such signals are short sequences with high AU contents that constitute recombination hot spots in Brome mosaic virus (BMV) and retroviruses. We have demonstrated that a defective interfering (DI) RNA, a model template associated with Tomato bushy stunt virus (TBSV), a tombusvirus, undergoes frequent recombination in plants and protoplast cells when it carries the AU-rich hot spot sequence from BMV. Similar to the situation with BMV, most of the recombination junction sites in the DI RNA recombinants were found within the AU-rich region. Our results support the idea that common AU-rich recombination signals might promote interviral recombination between unrelated viruses. To test if host genes can affect the evolution of RNA viruses, we used a Saccharomyces cerevisiae single-gene deletion library, which includes ~80% of yeast genes, in RNA recombination studies based on a small viral replicon RNA derived from TBSV. The genome-wide screen led to the identification of five host genes, whose absence resulted in rapid generation of novel viral RNA recombinants. Thus, these genes normally suppress viral RNA recombination, but in their absence hosts become viral recombination hotbeds. Four of the five recombination suppressor genes are likely involved in RNA degradation, suggesting that RNA degradation could play a role in viral RNA recombination. Overall, our results demonstrate for the first time that a set of host genes have major effect on RNA virus recombination and evolution. Replication of the non-segmented, plus-stranded RNA genome of Cucumber necrosis tombusvirus (CNV) requires two essential overlapping viral-coded replication proteins, the p33 replication co-factor and the p92 RNA-dependent RNA polymerase. We have demonstrated that p33 is phosphorylated in vivo and in vitro by a membrane-bound plant kinase. Based on in vitro studies with purified recombinant p33, we show evidence for phosphorylation of threonine and serine residues adjacent to the essential RNA-binding site in p33. Our findings suggest that phosphorylation of threonine/serine residues adjacent to the essential RNA-binding site in the auxiliary p33 protein likely plays a role in viral RNA replication and subgenomic RNA synthesis during tombusvirus infections.
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Pérez, Vilaró Gemma 1985. "Cellular processing bodies and the hepatitis C virus life cycle : characterization of their dynamic interplay". Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/97092.
Testo completoAbstract (sommario):
Els cossos de processament (cossos-P) són grànuls discrets i dinàmics que contenen mRNAs represos en la traducció així com proteïnes involucrades en la degradació dels mRNAs i de la maquinària dels miRNAs. Alguns components dels cossos-P, com els repressors de la traducció PatL1, LSm1 i DDX6, promouen la traducció i la replicació del virus de la hepatitis C (VHC) i d’altres virus RNA de polaritat positiva [RNA(+)]. A més a més, un genome wide screening en llevat va determinar que l’exonucleasa Xrn1, que també es localitza als cossos-P, pot afectar la taxa de recombinació d’un virus RNA(+) de plantes Així doncs, els components dels cossos-P estan estretament relacionats amb els cicles vitals dels virus RNA(+).
En l’estudi que aquí es presenta hem explorat la relació del VHC amb els cossos-P, demostrant que la infecció pel VHC promou canvis en la composició dels cossos-P a través de l’alteració de la localització d’aquells components que són necessaris per a la replicació viral. A més a més, hem demostrat que els components dels cossos-P però no els grànuls per se són necessaris per a la replicació del VHC. Addicionalment, hem posat a punt un sistema de detecció de recombinació en cultiu cel•lular basat en replicons del VHC que permet analitzar successos de recombinació i caracteritzar la possible participació dels components dels cossos-P en aquest mecanisme d’evolució. Amb aquest sistema s’han establert les primeres estimacions en la freqüència de recombinació del VHC indicant que la recombinació en aquest virus no és gaire comú. A més a més, la reducció del nivell d’expressió de Xrn1 no va alterar la taxa de recombinació del VHC indicant que la utilització de l’exonucleasa no és una característica general en la recombinació dels virus RNA(+). En conjunt, aquests resultats incrementen el nostre coneixement sobre els aspectes bàsics de la biologia del VHC així com de l’estreta relació que aquest virus estableix amb l’hoste.
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Prakhar, Praveen. "Wnt/β-Catenin-dependent Epigenetic Factors Shape Host Immune Responses During Mycobacterial Infection". Thesis, 2017. http://etd.iisc.ac.in/handle/2005/4226.
Testo completoAbstract (sommario):
The genus mycobacterium has more than 120 species of bacteria; one being M. tuberculosis (Mtb), the etiological agent of tuberculosis (TB). During infection, the host mounts a heightened immune response to contain the spread of the pathogen. Facilitating the response mediated by the host, PRRs (Pattern Recognition Receptors), upon their interaction with cognate ligands set forth a plethora of signaling cascades that effectuate responses like inflammation, apoptosis or autophagy to eradicate mycobacteria from the system. The early responses against Mtb are brought about by macrophages, dendritic cells (DCs) and neutrophils whereas the effector function of CD4+ and CD8+ T cells are critical for suppression of mycobacterial infection. Tumor necrosis factor (TNF)-alpha, Cytokines like interleukin (IL)-23, IL-12 and interferon (IFN)-gamma are secreted by type I T helper (Th1) subset of CD4+ T cells that provides protective immunity against pathogenic mycobacteria. Inspite of these extreme measures taken by the host to contain the infection, afflicted individuals are unable to eliminate the pathogen. Over one-third of the world’s population is infected with Mtb, which is a testimony of its success as a pathogen. This can be attributed to the various immune evasion strategies it employs like inhibition of phagosome-lysosome fusion, inhibition of antigen processing and presentation, suppression of pro-inflammatory cytokines, shifting the immune response towards Th2 type suppression of RNI and ROS, inhibition of apoptosis/autophagy and induction of regulatory T cells (Tregs) etc. Further, the emergence of MDR/XDR strains and co-infections has compounded the graveness of the disease. Understanding the mechanism underlying such immune evasion strategies will provide effective check on pathogenesis of mycobacteria.
In this regard, evaluation of the host-pathogen interactions during Mtb infection in terms of key the signaling pathway would provide us a critical insight into details of immune responses and its regulation. The present study addresses the role of WNT/ β-CATENIN pathway-dependent factors in modulating the host immune responses during Mtb infection. WNT/ β-CATENIN pathway-dependent G9a (histone methyltransferase) and Sirtuin6 (SIRT6; histone deacetylase) regulate cholesterol metabolism/homeostasis and mycobacterial survival (Chapter 3); AMPK-WNT/ β-CATENIN pathway-dependent COP1, an E3 ubiquitin ligase, skews the macrophage towards M2 phenotype hence aiding mycobacterial survival (Chapter 4) and finally the ability of mycobacterial surface antigen Ac2PIM in selectively suppressing NOD2-induced immunomodulators COX2, SOCS3 and MMP9 (Chapter 5).
Formation of highly structured aggregate of immune cells, called granulomas, is a hallmark of mycobacterial infection. One of the characteristic cells constituting the granulomas is the lipid-laden foamy macrophages (FM). These FMs serve as a source of nutrients as well as immune-modulators that aid in the survival of the pathogen. Amongst other lipids, cholesterol and cholesterol esters are significantly accumulated in the FMs. Further, it has been reported that cholesterol is one of the major carbon source for mycobacteria and helps in its persistence within the host. However, the molecular mechanisms that regulate intracellular cholesterol accumulation during the course of infection are not clear. Here, we analyzed the role of two histone modifiers G9a (histone methyltransferase; H3K9me1) and SIRT6 (histone deacetylase; H3K9Ac), which have been implicated in regulating immune responses. Mtb infection augments the levels of G9a and SIRT6 in macrophages as well as in the lungs of infected mice. Further, genes involved in cholesterol biosynthesis, uptake and efflux are differentially regulated upon mycobacterial infection. G9a was found to regulate genes involved in uptake (Lrp2) and biosynthesis (Aacs, Hmgcs1, Mvd, Dhcr24) of cholesterol by recruiting at the respective promoters and bringing about H3K9me1leading to their enhanced expression. On the contrary, cholesterol efflux genes (Abca1, Abcag1) promoters were found to be enriched with SIRT6 with loss of H3K9Ac upon infection indicating their repression. Corroborating these observation mouse aerosol infection model of TB was utilized to ascertain the role of G9a and SIRT6 in mycobacterial survival wherein mice treated with G9a inhibitor or Sirt6-/+ mice showed significant decrease in mycobacterial burden in organs such as spleen and lung. Immunofluorescence and transcript level analyses of the target genes in infected and uninfected lungs further substantiated our in vitro findings. Also, G9a and SIRT6 were found to be under the tight regulation of Mtb activated WNT/ β-CATENIN pathway. Thus our study unveiled the role of WNT/ β-CATENIN dependent G9a and SIRT6 in regulating cholesterol levels and consequently pathogen survival during mycobacterial infection.
The host induces the production of pro-inflammatory cytokines to counter any bacterial infection, including that by mycobacteria. However, mycobacteria skews the immune cells towards eliciting anti-inflammatory cytokine response, which prove more conducive for their survival. In this context, we investigated the role of AMPK, a crucial energy-sensing molecule that has been reported to play critical role in polarizing macrophage towards M2 phenotype and an E3 ubiquitin ligase COP1 in modulating immune responses during mycobacterial infection. AMPK is activated upon mycobacterial infection in macrophages through the action of upstream kinase PKCζand LKB1. Activated AMPK cross-talk with WNT/ β-CATENIN signaling that leads to the expression of COP1, an E3 ubiquitin ligase. Chromatin immunoprecipitation analysis confirms the recruitment of β-CATENIN at the promoter of COP1. Further, knockdown studies show that AMPK and COP1 are important for the expression of M2 cytokines/chemokines like IL-10, IL-4, CCL-4, CCL-17 and ARGINASE-1 that could aid the survival of mycobacteria in the host. Thus, our study highlights the activation of PKCζ-LKB1-AMPK-WNT/ β-CATENIN-COP1 pathway upon mycobacterial infection and postulates the essential role of the axis in modulating cytokine levels, thereby aiding in mycobacterial survival.
Specific and coordinated regulation of innate immune receptor-driven signaling networks often determines the net outcome of the immune responses. Here, we investigated the cross-regulation of toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)2 pathways mediated by Ac2PIM, a tetra-acylated form of mycobacterial cell wall component and muramyl dipeptide (MDP), a peptidoglycan derivative respectively. While Ac2PIM treatment of macrophages compromised their ability to induce NOD2-dependent immunomodulators like cyclooxygenase (COX)-2, suppressor of cytokine signaling (SOCS)-3 and matrix metalloproteinase (MMP)-9, no change in the NOD2-responsive NO, TNF-α, VEGF-A and IL-12 levels was observed. Further, genome-wide microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1 respectively. Interestingly, Ac2PIM was found to activate the SRC-FAK-PYK2-CREB cascade via TLR2 to recruit CBP/P300 at the promoters of miR-150 and miR-143 and epigenetically induce their expression. Loss-of-function studies utilizing specific miRNA inhibitors establish that Ac2PIM, via the miRNAs, abrogate NOD2-induced PI3K-PKCδ-MAPK pathway to suppress β-CATENIN-mediated expression of COX-2, SOCS-3 and MMP-9. Our investigation has thus underscored the negative regulatory role of Ac2PIM-TLR2 signaling on NOD2 pathway, which could broaden our understanding of cross-regulation between two PRRs upon activation.
Altogether, we have established an implication of novel molecular players in the pathogenesis of TB. We have found that an intricately woven network of signaling pathways and epigenetic factors fine tune the execution of mycobacterial survival strategies such as accumulation of cholesterol and swerving of the inflammatory milieu. Further, we gained insights into the extensive implication of cross-talk between PRRs in coining the outcome of conditions where they are simultaneously stimulated. Such detailed investigations would confer a holistic perspective of host-pathogen interactions and would bear potential in effective disease control by aiding the search for efficacious therapeutics.
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Su, Yu-Siang, e 蘇煜翔. "Characterization of DDX3 and HSC70 as the host factors for IRES-dependent translation under EV71 infected condition". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/16944212096929126887.
Testo completo
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Wu, HuiChuan, e 吳慧娟. "Identification of Host Factors Using the Hydrophilic Region and RNA-Dependent RNA Polymerase of Bamboo Mosaic Virus Replicase as Bait in Yeast Two-Hybrid Screen". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/97157053554241335344.
Testo completoAbstract (sommario):
碩士國立中興大學
生物科技學研究所
91
Bamboo mosaic virus (BaMV), a member of the potexvirus group, contains a single-stranded, positive sense RNA genome with five open reading frames (ORFs) and infects primarily members of the Bambusoideae, few other monocotyledonous plants and Nicotiana benthamiana. ORF1 encodes a 155-kDa replicase divided into capping enzyme, RNA helicase-like domain, and RNA-dependent RNA polymerase (RdRp) on the order of from N to C termini. Between the first two domains is a highly hydrophilic region (HR) with approximate 110 amino acids, while a proline-rich stretch sits between the latter two domains. To investigate the potential role of the hydrophilic region and search for cellular proteins involved in the viral replication, yeast two-hybrid screening against a leaf cDNA library of N. benthamiana is being employed by using the hydrophilic region and RdRp as bait. At first, the bait plasmids were constructed. RdRp was a well-behaved bait, but the hydrophilic region itself can transactivate the reporter genes (HIS3 lacZ). To avoid the nonspecific activation activity, the hydrophilic region was variously truncated, and finally the one with 33 amino acids deleted at N terminus (HRΔN) was used as bait in yeast two-hybrid screen. In the meanwhile, a leaf cDNA library containing 3.5×104 clones of N. benthamiana was constructed. Using HRΔN as bait to screen the leaf cDNA library, 26 colonies could grow up on minimal medium that lacked histidine (His+) and showed β-galactosidase activity (LacZ+). However, when putative interactors were retrieved and retested the ability of the two-hybrid proteins to interact specifically by retransforming to yeast, both of HIS3 and LacZ reporter genes could not be activated. It meant that all of 26 clones were false positive. This may result from the deletion of the N terminus of HR. On the other hand, 582 double-positive colonies (His+ LacZ+) were obtained when RdRp was used as bait. Using quantitative assay of β-galactosidase activity, 47 clones showed stronger interaction. By retrieving these putative interactors and retransforming to yeast to test the specific interaction, 25 clones can specifically interact with RdRp. Then the nucleotide sequences of these clones were determined and their deduced amino acid were searched in database. As a result, their encoded proteins have homology with four class proteins including photosynthesis related proteins, stress induced proteins, ubiquitin-proteasome pathway related proteins and unknown function proteins. In the future, biochemical assay will have to be performed to confirm these interactions. And how these proteins interacted with RdRp to affect the growth of the host plant or regulate virus replication? They also have to be further investigated.
Libri sul tema "Host dependency factors"
1
Koehler, Philipp, e Oliver A. Cornely. Fungal infections in haemato-oncology. A cura di Christopher C. Kibbler, Richard Barton, Neil A. R. Gow, Susan Howell, Donna M. MacCallum e Rohini J. Manuel. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755388.003.0032.
Testo completoAbstract (sommario):
Invasive fungal infections on haemato-oncology wards present a major challenge. Patients at risk for invasive fungal infection usually have a compromised immune system due to bone marrow failure caused by underlying disease, prolonged neutropenia after intensive chemotherapy, or immunosuppression after haematopoietic stem cell transplantation to avoid graft-versus-host disease. Three major entities—invasive candidiasis, invasive aspergillosis, and mucormycosis—account for the majority of fungal infections. Here, we describe specific host and therapeutic factors predisposing to invasive fungal infection in the haemato-oncology setting. Clinical presentation is highly variable and dependent on the underlying pathogen, organ involvement, and site of infection. Diagnosis is mainly based on radiographic imaging combined with microbiological and histopathological work-up. Various prophylaxis and treatment strategies have been developed, and the evidence for these is discussed.
2
Mason, Owen. The Old Bering Sea Florescence about Bering Strait. A cura di Max Friesen e Owen Mason. Oxford University Press, 2016. http://dx.doi.org/10.1093/oxfordhb/9780199766956.013.24.
Testo completoAbstract (sommario):
Dependent on whaling, a series of complex, sedentary societies termed Old Bering Sea arose around Bering Strait at proximity to resource hot spots, ca. 250 B.C. to A.D. 400, thrived between A.D. 600 and 800 and with influences as late as A.D. 1300. Old Bering Sea developed adjacent to walrus haul-outs and was associated with the most elaborate aesthetic system known in the Arctic. Virtually every artifact was overlain with formalized motifs, as figural representations were crafted, of both animals and humans. This breakthrough was due either to internal societal dynamics or, alternatively, was an artifact of taphonomic factors, such as fortuitous site preservation. The origins of the culture remain obscure, as does its fate; its technology is related to subsequent Punuk and Thule cultures.
3
Solomon, M. Scott. Labor Migrations and the Global Political Economy. Oxford University Press, 2017. http://dx.doi.org/10.1093/acrefore/9780190846626.013.251.
Testo completoAbstract (sommario):
Cross-border migration of people from one country to another has become an increasingly important feature of the globalizing world and it raises many important economic, social, and political issues. Migration is overwhelmingly from less developed to more developed countries and regions. Some of the factors affecting migration include: differences between wages for equivalent jobs; access to the benefits system of host countries plus state education, housing, and health care; and a desire to travel, build new skills and qualifications, and develop networks. On a more economic standpoint, studies show that labor migration provides various advantages. Migrants can provide complementary skills to domestic workers, which can raise the productivity of both. Migration can also be a driver of technological change and a fresh source of entrepreneurs. Much innovation comes from the work of teams of people who have different perspectives and experiences. Furthermore, a convenient way to accommodate individual actors in the global economy is to view them as economically dependent workers rather than as citizens capable of bringing about social change. The economic globalization process has modified this perspective to some extent, with greater recognition of the integration of a diverse, but nationally based, workforce into production patterns that can span several sovereign jurisdictions and world regions.
Capitoli di libri sul tema "Host dependency factors"
1
Meertens, Laurent, Laurine Couture e Ali Amara. "Genome-Wide CRISPR-Cas9 Screening for the Identification of Host Dependency Factors of Emerging Viruses". In Methods in Molecular Biology, 203–19. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3926-9_14.
Testo completo
2
McAnally, Heath B. "Addressing Host Factors: Overview of Dependence and Addiction". In Opioid Dependence, 207–32. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-47497-7_9.
Testo completo
3
McAnally, Heath B. "Addressing Host Factors: Primary, Secondary, and Tertiary Prevention of Opioid Dependence". In Opioid Dependence, 265–90. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-47497-7_11.
Testo completo
4
Boyd, James D., e Martha E. Grady. "Effect of Host Surface Factors on Biocompatible Adhesion Index". In Challenges in Mechanics of Time Dependent Materials, Mechanics of Biological Systems and Materials & Micro-and Nanomechanics, Volume 2, 85–88. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-86737-9_12.
Testo completo
5
Shah, Rahul, Bipin N. Savani e Shruti Chaturvedi. "Bleeding and Thrombotic Complications". In The EBMT Handbook, 355–63. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-44080-9_40.
Testo completoAbstract (sommario):
AbstractBleeding and thrombotic complications are an important cause of morbidity and mortality in patients undergoing hematopoietic cell transplantation (HCT). The major thrombotic complications include venous thromboembolism (VTE) including catheter-related thrombosis (CRT), sinusoidal obstruction syndrome (SOS), and transplant-associated thrombotic microangiopathy (TA-TMA), while bleeding commonly involves the gastrointestinal or respiratory tracts and is most common in thrombocytopenic patients or those with graft-versus-host disease (GVHD). HCT is associated with multiple risk factors for both thrombosis and bleeding including the underlying malignancy, thrombocytopenia, high-dose myeloablative chemotherapy (MAC) and immune-modulatory drugs, GVHD, infections, indwelling vascular catheters, and prolonged immobilization (Chiu and Lazo-Langner 2023; Gerber et al. 2008; Chaturvedi et al. 2016; Nadir and Brenner 2007). In addition, HCT is also associated with alterations in the coagulation system with activation of endothelium-dependent coagulation factors, increase in von Willebrand factor (vWF) and platelet adhesion, increased thrombin generation, decreased antithrombin levels, and decreased levels of anticoagulant proteins such as protein C (Vannucchi et al. 1994). Collectively, major patient-, disease-, and therapy-related factors contribute to hemostatic complications in HCT patients. Thrombotic and bleeding complications in HCT are discussed separately in the following section.
6
Wassem, R., F. O. Pedrosa, M. Buck, M. G. Yates, L. U. Rigo e E. M. Souza. "Dual Role for the Integration Host Factor at an Enhancer-Dependent nifA Promoter". In Nitrogen Fixation: From Molecules to Crop Productivity, 135. Dordrecht: Springer Netherlands, 2002. http://dx.doi.org/10.1007/0-306-47615-0_68.
Testo completo
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Drash, Allan L. "Does Beta Cell Death Result Exclusively from Genetically-Mediated Autoimmune Mechanisms? A Polemic — The Case for Environmental Factors in the Etiology of Insulin-dependent Diabetes Mellitus". In Standardization of Epidemiologic Studies of Host Susceptibility, 145–64. Boston, MA: Springer US, 1994. http://dx.doi.org/10.1007/978-1-4899-1213-8_20.
Testo completo
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Dalmo, Roy Ambli, e Jarl Bøgwald. "Innate Immunity". In Principles of Fish Immunology, 31–103. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-85420-1_2.
Testo completoAbstract (sommario):
AbstractResearch on the innate immunity has accelerated over the last decades. The main reason for this has been the discovery of receptors recognizing danger molecules from pathogens. This has been facilitated through genome and transcriptome sequencing of different fish species. Also, endogenous host molecules from sterile physiological insults may also bind to certain receptors and induce immunological processes. The magnitude and quality of adaptive immunity are known to be dependent on the instructions the innate response gives. This chapter gives an overview of selected innate immune organs/tissues, factors, and processes that have been suggested to possess important roles during innate immune response in fish.
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Mortellaro, Alessandra, Matteo Urbano, Stefania Citterio, Maria Foti, Francesca Granucci e Paola Ricciardi-Castagnoli. "Generation of Murine Growth Factor-Dependent Long-Term Dendritic Cell Lines to Investigate Host-Parasite Interactions". In Macrophages and Dendritic Cells, 17–27. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-59745-396-7_2.
Testo completo
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Takabe, Hideaki. "Physical of Warm Dense Matters". In Springer Series in Plasma Science and Technology, 397–450. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-45473-8_9.
Testo completoAbstract (sommario):
AbstractContinuous progress of compute capability, DFT has been used to study complicated physics of warm-dense matter (WDM) to compared to a variety of experimental results in laboratories obtained by compression and heating of solids with intense lasers. The phase transition of insulator-metal of hydrogen is now hot topics in high-pressure physics (HPP). Advancement of laser technology and diagnostics have made such challenging subjects as precision science.In twenty-first century, x-ray free electron laser (XFEL) facilities have been constructed as users’ facility. XFEL is new method to precision diagnostics of dense matters via x-ray Thomson scattering (XRTS). For bridging the experiment and theory to analyze XRTS data, Chihara formulated scattering spectra by decomposing three dynamical structure factors (DSF). Now, time-dependent DFT (TDDFT) is also solved with supercomputer to apply laser-matter interaction in quantum world.In this chapter, whole stories and models are explained and some examples are explained regarding the application to analyze experimental data obtained with intense lasers and XFEL.
Atti di convegni sul tema "Host dependency factors"
1
Poirier, John T., Boerries Brandenburg, Eileen Sun, Xiaowei Zhuang e Charles M. Rudin. "Abstract 2592: Host dependency factors for binding and internalization of oncolytic Seneca Valley Virus". In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2592.
Testo completo
2
Peyvandi, Soodeh, Rohiza Ahmad e M. Nordin Zakaria. "Association among independent and dependent factors of host in volunteer computing". In 2014 International Conference on Computer and Information Sciences (ICCOINS). IEEE, 2014. http://dx.doi.org/10.1109/iccoins.2014.6868834.
Testo completo
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Soares, Renan F., e Kevin P. Garry. "The Introduction of MultiWake - An Adaptable Bluff-Body Wake Emulator for Ground Vehicle Studies". In WCX SAE World Congress Experience. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, 2023. http://dx.doi.org/10.4271/2023-01-0953.
Testo completoAbstract (sommario):
<div class="section abstract"><div class="htmlview paragraph">The rise of autonomous technologies may reflect on new vehicle traffic characteristics, likely reducing vehicle-to-vehicle proximity and emerging platooning formations. Energy consumption, stability, and surface contamination are relevant factors that are sensitive to aerodynamic interference while platooning. From the experimental perspective, most wind tunnels were originally designed to host isolated models, and these constraints often limit the investigation of multiple full-body vehicle formations (e.g. test section length, moving ground dimensions, standard testing points).</div><div class="htmlview paragraph">This paper introduces the ‘MultiWake’ model - a parametric bluff-body device based on a morphing concept, which can emulate the aerodynamic wake characteristics of different vehicle classes. The goal is the enhancement of experimental facilities to investigate vehicle-to-vehicle interference by (i) expanding the effective test section length, and (ii) improving time efficiency since the model morphology can be automated; therefore, allowing a given vehicle model to be exposed to multiple wakes during the same wind tunnel run. The design development pursued, with a focus on parametric simplicity and efficiency, the emulation of three wake types based on the experimental dataset of four full-body DrivAer models: Fastback, Notchback, Estateback, and high-performance Fastback.</div><div class="htmlview paragraph">An experimental campaign was conducted to characterise the recommended MultiWake configurations, where each wake is characterised on multiple downstream planes as a function of total pressure. The ‘Fastback’ and ‘Notchback’ modes are classified as Wake Type 1: a small wake with minor downwash; with attenuated downwash and increasing total pressure loss on the ‘Notchback’ mode. Wake Type 2 achieved in ‘Estateback’ mode provides a full detached flow and wake size proportional to the rear base, with lateral inwash. Wake Type 3 resembles motorsport applications, where the wake features a strong upwash linked with a coherent counter-rotating vortex pair. A Reynolds number dependency study and confidence interval mappings of the measurement approach complement the experimental validation.</div></div>
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Kowarsch, Dandan, e Jingyu Wang. "The Impact of Refugees on Economic Growth in Latin America and the Caribbean". In 13th International Conference on Applied Human Factors and Ergonomics (AHFE 2022). AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1002294.
Testo completoAbstract (sommario):
The aim of this article is to explore the relationship between refugees and the host country’s economic growth in Latin America and the Caribbean using a simulation modeling approach. There is a large body of work on the topic using statistics. However, one big challenge of conducting econometrics methods to unveil any correlation is that regressions are data dependent. Since the current available refugee data doesn’t truly represent the reality as there has been a quite substantial number of unregistered Venezuelan refugees in Latin America and Caribbean region since 2015. Using agent-based simulation modeling approach overcomes the challenges of data issue and passes by strict assumptions for an OLS regression to produce BLUE outcomes. In our ABM model, agents represent labors, defined as age between 16 and 65, and Venezuelan refugees. To evaluate the impact on gender inequality on employment in the host country, despite of age, agents also carry the attributes of gender, work capability, average education years, birth (matured female only), and death. Three countries Venezuela, Colombia, and Chile are modeled as patches in Netlogo . Countries own the attributes of GDP and GDP per capita at macro level. The simulated result based on the initial values suggests that in Latin America and the Caribbean, refugee growth and host country’s economy are positively correlated. In contrast, the simulated results suggest that the higher fertility rate negatively affects the labor value added outcomes. It could imply the more female refugees in the host country, the lower GDP will be. We also found that the life expectancy is correlated to economic growth, labor’s work capacity, and education years. Life expectancy could be an indicator of the overall quality of human capital. In brief, the findings might imply labor value added output or labor capacity is the driver of economic growth.
5
Horie, Kazuyuki, Norio Murase e Makoto Ikemoto. "Wavelength Dependence of Photochemical Hole-Burning Efficiency and Vibronic Structure in an Absorption Band". In Spectral Hole-Burning and Luminescence Line Narrowing: Science and Applications. Washington, D.C.: Optica Publishing Group, 1992. http://dx.doi.org/10.1364/shbl.1992.fa2.
Testo completoAbstract (sommario):
Photochemical hole-burning(PHB) is a good tool for understanding the dynamics of host polymers as well as for realizing a high performance optical storage. The quantum efficiency for persistent hole formation, ϕ, is one of the essential parameters for the PHB phenomenon. If one is aware of some kinds of application, its value is preferable to be large. This is why the quantum efficiencies for several series of substances are measured and the efforts to find out the dominant factor for controlling these values are continued.1) As ever, these values are measured near the peaks of the lowest energy absorption bands. However, we noticed recently very large difference in quantum efficiencies of hole formation, ϕ, between the cases when the hole is burnt on the higher frequency slope or on the lower frequency slope of the lowest energy inhomogeneous absorption peak in the Q band of free base tetraphenylporphin derivatives.2) We also found out the wavelength dependences of the formation rate of satellite holes, which originate from the vibronic excitations of the dye molecules accompanied by the electronic excitation. These facts suggest that the lowest energy inhomogeneous absorption band is actually composed of several kinds of vibronic dye transitions, and the 0-0 absorption component is one of the portion of this absorption band.
6
Chukwu, Engr Emeke, e Chinyere Offor. "Sustainable Host Community Development – An Enabler for Energy security & Economic development in Nigeria". In SPE Nigeria Annual International Conference and Exhibition. SPE, 2023. http://dx.doi.org/10.2118/217142-ms.
Testo completoAbstract (sommario):
Abstract Till date, Nigeria is heavily dependent on revenue generated from oil and gas to finance its annual budget to provide public goods and services beneficial to its citizenry. The 2022 budget reflects that 31% of Federal government earnings will be result from oil and gas. Despite the push to diversify her economy, the stark reality remains that oil and gas sales is an influential factor to enabling economic development in Nigeria. More so, countries such as Saudi Arabia and Norway have utilized oil and gas wealth as the basis to invest in other sectors and promote diversification. However, Nigeria's goal of Energy security and economic development is likely not to be achieved as she battles with crude theft plaguing her ability to evacuate crude to her customers. Nigeria National Petroleum Company Limited (NNPCL) reported a loss of 470,000 bpd of crude amounting to an estimated 0.4 trillion naira monthly due to oil theft. The annualized estimate of 5.2 trillion-naira loss represents a staggering 30% of Nigeria's 2022 budget expenditure of 16 trillion naira. With other associated impacts to Nigeria, there is an imperative to deal and ultimately put an end to this looming menace. This study focused on addressing the crude oil theft through sustainable Host community engagement and development. A review of the factors promoting crude oil theft in Nigeria was performed. The study analyzed the production loss data over a decade and positively correlated it with economic development indicators such as poverty index, inflation, per capita income. The impact on the host community was studied. The results showed that the disenchantment of host communities (despite being key stakeholders in the oil and gas value chain) necessitated their little to no responsibility for protecting oil & gas assets and preventing the perpetration of crude oil theft. The study developed and proposed a "Host community development plan" which if administered with provisions already existing in the Petroleum Industry Act could revolutionize the Oil & gas industry by promoting increased ownership & fostering collaboration towards achieving Energy security & Economic development in Nigeria.
7
Twynstra, M. G., K. J. Daun, E. Caron, N. Adam e D. Womack. "Modelling and Optimization of a Batch Furnace for Hot Stamping". In ASME 2013 Heat Transfer Summer Conference collocated with the ASME 2013 7th International Conference on Energy Sustainability and the ASME 2013 11th International Conference on Fuel Cell Science, Engineering and Technology. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/ht2013-17248.
Testo completoAbstract (sommario):
Non-uniform heating during the austenization stage of hot-stamping can lead to inhomogeneous mechanical properties, coating thickness variations, and residual stresses in the stamped components. This paper presents a heat transfer model of an electrically-powered batch austenization furnace, with the objective of diagnosing and correcting factors that cause non-uniform blank heating. Radiation view factors are calculated with the Monte Carlo method. Convection with the furnace air and conduction through the blank and furnace door is also incorporated into a transient global domain energy balance. The model incorporates temperature- and phase-dependent radiative and thermophysical properties of the steel blanks and ceramic insulation of the furnace walls. The heat transfer model is validated with data obtained from instrumented blanks in an actual production cycle. The model is then used to optimize heater settings for the existing furnace using simulated annealing.
8
Wu, Xin, Omar M. Ramahi, Gary A. Brist e Donald P. Cullen. "Surface Finish Effects on High-Speed Interconnects". In ASME 2003 International Electronic Packaging Technical Conference and Exhibition. ASMEDC, 2003. http://dx.doi.org/10.1115/ipack2003-35332.
Testo completoAbstract (sommario):
In printed circuit boards (PCB), the selection of surface finish is a balance of cost, performance and material compatibility consideration. When the operating frequency is in gigahertz range, the signal loss in interconnects has stronger dependence on the material composition of traces, surface finishes, substrates, and geometry of the traces. Skin effects, frequency dependent dielectric properties and the electrical functioning mechanism are important factors that affect signal integrity. In this work, both measurements and finite element method (FEM) based full wave simulation are used to investigate the effects of hot air solder leveling (HASL) and its alternatives on signal degradation of high-speed interconnect structures. For the microstrip line structure, the loss due to surface finishes is negligible. For the differential mode coupled microstrip lines, the loss increment resulted from surface finish can be up to 50%∼200% at 10 GHz. Surface finish caused signal loss must be carefully considered for differential mode interconnects.
9
Lin, J. W.-I., T. Tada, S. Saikan, T. Kushida e T. Tani. "The study of weak linear electron-phonon coupling in iron-free hemeproteins". In Persistent Spectral Hole Burning: Science and Applications. Washington, D.C.: Optica Publishing Group, 1991. http://dx.doi.org/10.1364/pshb.1991.fd3.
Testo completoAbstract (sommario):
The present interest in the PHB optical memories has motivated research into finding materials which have weak electron-phonon coupling between the guest impurity and the host system. The magnitude of the linear electron-phonon coupling strength can be obtained from the Debye- Waller factor, the relative strength of the zero-phonon line and phonon sideband of the homogeneous spectrum. The Debye-Waller factor can be determined readily in crystals; in amorphous solids, however, the large inhomogeneous spectral broadening masks the individual homogeneous spectrum. Out of the many nonlinear spectroscopic techniques, our group utilized the femtosecond accumulated photon echo technique with phase modulation1 to examine the polymer dependence of the electron-phonon coupling in amorphous dye-doped polymer systems.
10
Takahashi, K., K. Akagi, S. Nishimura, Y. Fukuizumi e V. Kallianpur. "Factors for Improving Reliability in Large Industrial Gas Turbines". In ASME Turbo Expo 2004: Power for Land, Sea, and Air. ASMEDC, 2004. http://dx.doi.org/10.1115/gt2004-54196.
Testo completoAbstract (sommario):
The use of aero engine design methods and experience including higher temperature materials and protective coatings have significantly increased thermal efficiency, and output capability of large industrial gas turbines such as the F, G and H class. As a result the gas path components operate at much higher gas temperatures over significantly longer maintenance intervals, as compared to aero engine experience. Therefore, it is essential that the hardware durability can effectively endure longer periods of attack by oxidation, creep and fatigue because of longer operating intervals between scheduled maintenance periods. Another factor that has become increasingly important is the need for greater flexibility in power plant operation. Specifically, the power plants must operate reliably under more frequent cyclic operation, including partial load cycling. This is in addition to the normal dispatch cycle of the power plant (i.e. daily-start-stop, weekly-start-stop, etc). Gas Turbine reliability is directly dependent on hardware performance and durability. Therefore, the gas turbine must have sufficient design margin to sustain the synergistic effect of higher firing temperature, and the operational challenges associated with greater partial load cycling. This paper discusses Mitsubishi’s approach for achieving the above mentioned objectives so that the overarching goals of higher reliability and durability of hot components are achieved in large advanced gas turbines.
Rapporti di organizzazioni sul tema "Host dependency factors"
1
Prusky, Dov, e Jeffrey Rollins. Modulation of pathogenicity of postharvest pathogens by environmental pH. United States Department of Agriculture, dicembre 2006. http://dx.doi.org/10.32747/2006.7587237.bard.
Testo completoAbstract (sommario):
Until recently, environmental pH was not considered a factor in determining pathogen compatibility. Our hypothesis was that the environmental pH at the infection site, which is dynamically controlled by activities of both the host and the pathogen, regulates the expression of genes necessary for disease development in Colletotrichum gloeosporioides and Sclerotinia sclerotiorum. This form of regulation ensures that genes are expressed at optimal conditions for their encoded activities.Pectate lyase encoded by pelB, has been demonstrated to play a key role in virulence of C. gloeosporioides in avocado fruit. Polyglacturonase synergism with oxalic acid production is considered to be an essential pathogenicity determinant in the interactions of S. sclerotiorum with its numerous hosts. A common regulatory feature of these virulence and pathogenicity factors is their dependence upon environmental pH conditions within the host niche to create optimal conditions for expression and secretion. In this proposal we have examined, 1) the mechanisms employed by these fungi to establish a suitable pH environment, 2) the molecular levels at which genes and gene products are regulated in response to environmental pH, and 3) the molecular basis and functional importance of pH-responsive gene regulation during pathogenicity. The specific objectives of the proposal were: 1. Characterize the mechanism of local pH modulation and the effect of ambient pH on the expression and secretion of virulence factors. 2. Provide evidence that a conserved molecular pathway for pH-responsive gene expression exists in C. gloeosporioides by cloning a pacC gene homologue. 3. Determine the role of pacC in pathogenicity by gene disruption and activating mutations. Major conclusions 1. We determined the importance of nitrogen source and external pH in the secretion of the virulence factor pectate lyase with respect to the ambient pH transcriptional regulator pacC. It was concluded that nitrogen source availability and ambient pH are two independent signals for the transcriptional regulation of genes required for the disease process of C. gloeosporioides and possibly of other pathogens. 2. We also determined that availability of ammonia regulate independently the alkalinization process and pelB expression, pecate lyase secretion and virulence of C. gloeosporioides. 3. Gene disruption of pacC reduced virulence of C. gloeosporioides however did not reduced fully pelB expression. It was concluded that pelB expression is regulated by several factors including pH, nitrogen and carbon sources. 4. Gene disruption of pacC reduced virulence of S. slcerotiourum Creation of a dominant activating
2
Matthew, Gray. Data from "Winter is Coming – Temperature Affects Immune Defenses and Susceptibility to Batrachochytrium salamandrivorans". University of Tennessee, Knoxville Libraries, gennaio 2021. http://dx.doi.org/10.7290/t7sallfxxe.
Testo completoAbstract (sommario):
Environmental temperature is a key factor driving various biological processes, including immune defenses and host-pathogen interactions. Here, we evaluated the effects of environmental temperature on the pathogenicity of the emerging fungus, Batrachochytrium salamandrivorans (Bsal), using controlled laboratory experiments, and measured components of host immune defense to identify regulating mechanisms. We found that adult and juvenile Notophthalmus viridescens died faster due to Bsal chytridiomycosis at 14 ºC than at 6 and 22 ºC. Pathogen replication rates, total available proteins on the skin, and microbiome composition likely drove these relationships. Temperature-dependent skin microbiome composition in our laboratory experiments matched seasonal trends in wild N. viridescens, adding validity to these results. We also found that hydrophobic peptide production after two months post-exposure to Bsal was reduced in infected animals compared to controls, perhaps due to peptide release earlier in infection or impaired granular gland function in diseased animals. Using our temperature-dependent infection results, we performed a geographic analysis that suggested that N. viridescens populations in the northeastern United States and southeastern Canada are at greatest risk for Bsal invasion. Our results indicate that environmental temperature will play a key role in the epidemiology of Bsal and provide evidence that temperature manipulations may be a viable Bsal management strategy.
3
Ostersetzer-Biran, Oren, e Alice Barkan. Nuclear Encoded RNA Splicing Factors in Plant Mitochondria. United States Department of Agriculture, febbraio 2009. http://dx.doi.org/10.32747/2009.7592111.bard.
Testo completoAbstract (sommario):
Mitochondria are the site of respiration and numerous other metabolic processes required for plant growth and development. Increased demands for metabolic energy are observed during different stages in the plants life cycle, but are particularly ample during germination and reproductive organ development. These activities are dependent upon the tight regulation of the expression and accumulation of various organellar proteins. Plant mitochondria contain their own genomes (mtDNA), which encode for a small number of genes required in organellar genome expression and respiration. Yet, the vast majority of the organellar proteins are encoded by nuclear genes, thus necessitating complex mechanisms to coordinate the expression and accumulation of proteins encoded by the two remote genomes. Many organellar genes are interrupted by intervening sequences (introns), which are removed from the primary presequences via splicing. According to conserved features of their sequences these introns are all classified as “group-II”. Their splicing is necessary for organellar activity and is dependent upon nuclear-encoded RNA-binding cofactors. However, to-date, only a tiny fraction of the proteins expected to be involved in these activities have been identified. Accordingly, this project aimed to identify nuclear-encoded proteins required for mitochondrial RNA splicing in plants, and to analyze their specific roles in the splicing of group-II intron RNAs. In non-plant systems, group-II intron splicing is mediated by proteins encoded within the introns themselves, known as maturases, which act specifically in the splicing of the introns in which they are encoded. Only one mitochondrial intron in plants has retained its maturaseORF (matR), but its roles in organellar intron splicing are unknown. Clues to other proteins required for organellar intron splicing are scarce, but these are likely encoded in the nucleus as there are no other obvious candidates among the remaining ORFs within the mtDNA. Through genetic screens in maize, the Barkan lab identified numerous nuclear genes that are required for the splicing of many of the introns within the plastid genome. Several of these genes are related to one another (i.e. crs1, caf1, caf2, and cfm2) in that they share a previously uncharacterized domain of archaeal origin, the CRM domain. The Arabidopsis genome contains 16 CRM-related genes, which contain between one and four repeats of the domain. Several of these are predicted to the mitochondria and are thus postulated to act in the splicing of group-II introns in the organelle(s) to which they are localized. In addition, plant genomes also harbor several genes that are closely related to group-II intron-encoded maturases (nMats), which exist in the nucleus as 'self-standing' ORFs, out of the context of their cognate "host" group-II introns and are predicted to reside within the mitochondria. The similarity with known group-II intron splicing factors identified in other systems and their predicted localization to mitochondria in plants suggest that nuclear-encoded CRM and nMat related proteins may function in the splicing of mitochondrial-encoded introns. In this proposal we proposed to (i) establish the intracellular locations of several CRM and nMat proteins; (ii) to test whether mutations in their genes impairs the splicing of mitochondrial introns; and to (iii) determine whether these proteins are bound to the mitochondrial introns in vivo.
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Grumet, Rebecca, e Benjamin Raccah. Identification of Potyviral Domains Controlling Systemic Infection, Host Range and Aphid Transmission. United States Department of Agriculture, luglio 2000. http://dx.doi.org/10.32747/2000.7695842.bard.
Testo completoAbstract (sommario):
Potyviruses form one of the largest and most economically important groups of plant viruses. Individual potyviruses and their isolates vary in symptom expression, host range, and ability to overcome host resistance genes. Understanding factors influencing these biological characteristics is of agricultural importance for epidemiology and deployment of resistance strategies. Cucurbit crops are subject to severe losses by several potyviruses including the highly aggressive and variable zucchini yellow mosaic virus (ZYMV). In this project we sought to investigate protein domains in ZYMV that influence systemic infection and host range. Particular emphasis was on coat protein (CP), because of known functions in both cell to cell and long distance movement, and helper component-protease (HC-Pro), which has been implicated to play a role in symptom development and long distance movement. These two genes are also essential for aphid mediated transmission, and domains that influence disease development may also influence transmissibility. The objectives of the approved BARD project were to test roles of specific domains in the CP and HC-Pro by making sequence alterations or switches between different isolates and viruses, and testing for infectivity, host range, and aphid transmissibility. These objectives were largely achieved as described below. Finally, we also initiated new research to identify host factors interacting with potyviral proteins and demonstrated interaction between the ZYMV RNA dependent RNA polymerase and host poly-(A)-binding protein (Wang et al., in press). The focus of the CP studies (MSU) was to investigate the role of the highly variable amino terminus (NT) in host range determination and systemic infection. Hybrid ZYMV infectious clones were produced by substituting the CP-NT of ZYMV with either the CP-NT from watermelon mosaic virus (overlapping, but broader host range) or tobacco etch virus (TEV) (non- overlapping host range) (Grumet et al., 2000; Ullah ct al., in prep). Although both hybrid viruses initially established systemic infection, indicating that even the non-cucurbit adapted TEV CP-NT could facilitate long distance transport in cucurbits, after approximately 4-6, the plants inoculated with the TEV-CPNT hybrid exhibited a distinct recovery of reduced symptoms, virus titer, and virus specific protection against secondary infection. These results suggest that the plant recognizes the presence of the TEV CP-NT, which has not been adapted to infection of cucurbits, and initiates defense responses. The CP-NT also appears to play a role in naturally occurring resistance conferred by the zym locus in the cucumber line 'Dina-1'. Patterns of virus accumulation indicated that expression of resistance is developmentally controlled and is due to a block in virus movement. Switches between the core and NT domains of ZYMV-NAA (does not cause veinal chlorosis on 'Dina-1'), and ZYMV-Ct (causes veinal chlorosis), indicated that the resistance response likely involves interaction with the CP-NT (Ullah and Grumet, submitted). At the Volcani Center the main thrust was to identify domains in the HC-Pro that affect symptom expression or aphid transmissibility. From the data reported in the first and second year report and in the attached publications (Peng et al. 1998; Kadouri et al. 1998; Raccah et al. 2000: it was shown that: 1. The mutation from PTK to PAK resulted in milder symptoms of the virus on squash, 2. Two mutations, PAK and ATK, resulted in total loss of helper activity, 3. It was established for the first time that the PTK domain is involved in binding of the HC-Pro to the potyvirus particle, and 4. Some of these experiments required greater amount of HC-Pro, therefore a simpler and more efficient purification method was developed based on Ni2+ resin.
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Whitham, Steven A., Amit Gal-On e Victor Gaba. Post-transcriptional Regulation of Host Genes Involved with Symptom Expression in Potyviral Infections. United States Department of Agriculture, giugno 2012. http://dx.doi.org/10.32747/2012.7593391.bard.
Testo completoAbstract (sommario):
Understanding how RNA viruses cause disease symptoms in their hosts is expected to provide information that can be exploited to enhance modern agriculture. The helper component-proteinase (HC-Pro) protein of potyviruses has been implicated in symptom development. Previously, we demonstrated that symptom expression is associated with binding of duplex small-interfering-RNA (duplex-siRNA) to a highly conserved FRNK amino acid motif in the HC-Pro of Zucchini yellow mosaic virus (ZYMV). This binding activity also alters host microRNA (miRNA) profiles. In Turnip mosaic virus (TuMV), which infects the model plant Arabidopsis, mutation of the FRNK motif to FINK was lethal providing further indication of the importance of this motif to HC-Pro function. In this continuation project, our goal was to further investigate how ZYMV and TuMV cause the mis-expression of genes in cucurbits and Arabidopsis, respectively, and to correlate altered gene expression with disease symptoms. Objective 1 was to examine the roles of aromatic and positively charged residues F164RNH and K215RLF adjacent to FR180NK in small RNA binding. Objective 2 was to determine the target genes of the miRNAs which change during HC-Pro expression in infected tissues and transgenic cucumber. Objective 3 was to characterize RNA silencing mechanisms underlying differential expression of host genes. Objective 4 was to analyze the function of miRNA target genes and differentially expressed genes in potyvirus-infected tissues. We found that the charged K/R amino acid residues in the FKNH and KRLF motifs are essential for virus viability. Replacement of K to I in FKNH disrupted duplex-siRNA binding and virus infectivity, while in KRLF mutants duplex-siRNA binding was maintained and virus infectivity was limited: symptomless following a recovery phenomenon. These findings expanded the duplex-siRNA binding activity of HC-Pro to include the adjacent FRNK and FRNH sites. ZYMV causes many squash miRNAs to hyper-accumulate such as miR166, miR390, mir168, and many others. Screening of mir target genes showed that only INCURVATA-4 and PHAVOLUTA were significantly upregulated following ZYMVFRNK infection. Supporting this finding, we found similar developmental symptoms in transgenic Arabidopsis overexpressing P1-HC-Pro of a range of potyviruses to those observed in miR166 mutants. We characterized increased transcription of AGO1 in response to infection with both ZYMV strains. Differences in viral siRNA profiles and accumulation between mild and severe virus infections were characterized by Illumina sequencing, probably due to the differences in HC-Pro binding activity. We determined that the TuMV FINK mutant could accumulate and cause symptoms in dcl2 dcl4 or dcl2 dcl3 dcl4 mutants similar to TuMV FRNK in wild type Arabidopsis plants. These dcl mutant plants are defective in antiviral defenses, and the results show that factors other than HC-ProFRNK motif can induce symptoms in virus-infected plants. As a result of this work, we have a better understanding of the FRNK and FKNH amino acid motifs of HC-Pro and their contributions to the duplex-siRNA binding functions. We have identified plant genes that potentially contribute to infectivity and symptoms of virus infected plants when they are mis-expressed during potyviral infections. The results establish that there are multiple underlying molecular mechanisms that lead viral pathogenicity, some dependent on HC-Pro. The potential benefits include the development of novel strategies for controlling diseases caused by viruses, methods to ensure stable expression of transgenes in genetically improved crops, and improved potyvirus vectors for expression of proteins or peptides in plants.
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Coplin, David, Isaac Barash e Shulamit Manulis. Role of Proteins Secreted by the Hrp-Pathways of Erwinia stewartii and E. herbicola pv. gypsophilae in Eliciting Water-Soaking Symptoms and Initiating Galls. United States Department of Agriculture, giugno 2001. http://dx.doi.org/10.32747/2001.7580675.bard.
Testo completoAbstract (sommario):
Many bacterial pathogens of plants can inject pathogenicity proteins into host cells using a specialized type III secretion system encoded by hrpgenes. This system deliver effector proteins, into plant cells that function in both susceptible and resistant interactions. We have found that the virulence of Erwinia stewartii(Es; syn. Pantoea stewartii) and Erwinia herbicola pv. gypsophilae (Ehg, syn. Pantoea agglomerans), which cause Stewart's wilt of corn and galls on Gypsophila, respectively, depends on hrpgenes. The major objectives of this project were: To increase expression of hrpgenes in order to identify secreted proteins; to identify genes for proteins secreted by the type-III systems and determine if they are required for pathogenicity; and to determine if the secreted proteins can function within eukaryotic cells. We found that transcription of the hrp and effector genes in Es and Ehg is controlled by at least four genes that constitute a regulatory cascade. Environmental and/or physiological signaling appears to be mediated by the HrpX/HrpY two component system, with HrpX functioning as a sensor-kinase and HrpY as a response regulator. HrpYupregulateshrpS, which encodes a transcriptional enhancer. HrpS then activates hrpL, which encodes an alternate sigma factor that recognizes "hrp boxes". All of the regulatory genes are essential for pathogenicity, except HrpX, which appears only to be required for induction of the HR in tobacco by Es. In elucidating this regulatory pathway in both species, we made a number of significant new discoveries. HrpX is unusual for a sensor-kinase because it is cytoplasmic and contains PAS domains, which may sense the redox state of the bacterium. In Es, a novel methyl-accepting protein may function upstream of hrpY and repress hrp gene expression in planta. The esaIR quorum sensing system in Es represses hrp gene expression in Es in response to cell-density. We have discovered six new type III effector proteins in these species, one of which (DspE in Ehg and WtsE in Es) is common to both pathogens. In addition, Es wtsG, which is a homolog of an avrPpiB from P. syringae pv. pisi, and an Ehg ORF, which is a homolog of P. syringae pv. phaseolicola AvrPphD, were both demonstrated to encode virulence proteins. Two plasmidborne, Ehg Hop proteins, HsvG and PthG, are required for infection of gypsophilia, but interestingly, PthG also acts as an Avr elicitor in beets. Using a calmodulin-dependent adenylate cyclase (cyaA) reporter gene, we were successful in demonstrating that an HsvG-CyaA fusion protein can be transferred into human HeLa cells by the type-III system of enteropathogenic E. coli. This is a highly significant accomplishment because it is the first direct demonstration that an effector protein from a plant pathogenic bacterium is capable of being translocated into a eukaryotic cell by a type-III secretion system. Ehg is considered a limiting factor in Gypsophila production in Israel and Stewart’s Wilt is a serious disease in the Eastern and North Central USA, especially on sweet corn in epidemic years. We believe that our basic research on the characterization of type III virulence effectors should enable future identification of their receptors in plant cells. This may lead to novel approaches for genetically engineering resistant plants by modifying their receptors or inactivating effectors and thus blocking the induction of the susceptible response. Alternatively, hrp gene regulation might also provide a target for plant produced compounds that interfere with recognition of the host by the pathogen. Such strategies would be broadly applicable to a wide range of serious bacterial diseases on many crops throughout the USA and Israel.
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Miller, Gad, e Jeffrey F. Harper. Pollen fertility and the role of ROS and Ca signaling in heat stress tolerance. United States Department of Agriculture, gennaio 2013. http://dx.doi.org/10.32747/2013.7598150.bard.
Testo completoAbstract (sommario):
The long-term goal of this research is to understand how pollen cope with stress, and identify genes that can be manipulated in crop plants to improve reproductive success during heat stress. The specific aims were to: 1) Compare heat stress dependent changes in gene expression between wild type pollen, and mutants in which pollen are heat sensitive (cngc16) or heat tolerant (apx2-1). 2) Compare cngc16 and apx2 mutants for differences in heat-stress triggered changes in ROS, cNMP, and Ca²⁺ transients. 3) Expand a mutant screen for pollen with increased or decreased thermo-tolerance. These aims were designed to provide novel and fundamental advances to our understanding of stress tolerance in pollen reproductive development, and enable research aimed at improving crop plants to be more productive under conditions of heat stress. Background: Each year crop yields are severely impacted by a variety of stress conditions, including heat, cold, drought, hypoxia, and salt. Reproductive development in flowering plants is highly sensitive to hot or cold temperatures, with even a single hot day or cold night sometimes being fatal to reproductive success. In many plants, pollen tube development and fertilization is often the weakest link. Current speculation about global climate change is that most agricultural regions will experience more extreme environmental fluctuations. With the human food supply largely dependent on seeds, it is critical that we consider ways to improve stress tolerance during fertilization. The heat stress response (HSR) has been intensively studied in vegetative tissues, but is poorly understood during reproductive development. A general paradigm is that HS is accompanied by increased production of reactive oxygen species (ROS) and induction of ROS-scavenging enzymes to protect cells from excess oxidative damage. The activation of the HSR has been linked to cytosolic Ca²⁺ signals, and transcriptional and translational responses, including the increased expression of heat shock proteins (HSPs) and antioxidative pathways. The focus of the proposed research was on two mutations, which have been discovered in a collaboration between the Harper and Miller labs, that either increase or decrease reproductive stress tolerance in a model plant, Arabidopsis thaliana (i.e., cngc16--cyclic nucleotide gated channel 16, apx2-1--ascorbate peroxidase 2,). Major conclusions, solutions, achievements. Using RNA-seq technology, the expression profiles of cngc16 and apx2 pollen grains were independently compared to wild type under favourable conditions and following HS. In comparison to a wild type HSR, there were 2,776 differences in the transcriptome response in cngc16 pollen, consistent with a model in which this heat-sensitive mutant fails to enact or maintain a normal wild-type HSR. In a comparison with apx2 pollen, there were 900 differences in the HSR. Some portion of these 900 differences might contribute to an improved HSR in apx2 pollen. Twenty-seven and 42 transcription factor changes, in cngc16 and apx2-1, respectively, were identified that could provide unique contributions to a pollen HSR. While we found that the functional HS-dependent reprogramming of the pollen transcriptome requires specific activity of CNGC16, we identified in apx2 specific activation of flavonol-biosynthesis pathway and auxin signalling that support a role in pollen thermotolerance. Results from this study have identified metabolic pathways and candidate genes of potential use in improving HS tolerance in pollen. Additionally, we developed new FACS-based methodology that can quantify the stress response for individual pollen in a high-throughput fashion. This technology is being adapted for biological screening of crop plant’s pollen to identify novel thermotolerance traits. Implications, both scientific and agricultural. This study has provided a reference data on the pollen HSR from a model plant, and supports a model that the HSR in pollen has many differences compared to vegetative cells. This provides an important foundation for understanding and improving the pollen HSR, and therefor contributes to the long-term goal of improving productivity in crop plants subjected to temperature stress conditions. A specific hypothesis that has emerged from this study is that pollen thermotolerance can be improved by increasing flavonol accumulation before or during a stress response. Efforts to test this hypothesis have been initiated, and if successful have the potential for application with major seed crops such as maize and rice.