Relevant bibliographies by topics / Host-directed

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  2. Dissertations / Theses
  3. Books
  4. Book chapters
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Academic literature on the topic 'Host-directed'

Author: Grafiati
Published: 6 September 2023

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Journal articles on the topic "Host-directed"

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Wilkinson, Robert John. "Host-directed therapies against tuberculosis." Lancet Respiratory Medicine 2, no. 2 (February 2014): 85–87. http://dx.doi.org/10.1016/s2213-2600(13)70295-9.

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Stricker, Raphael B. "Host-Directed Therapy for AIDS." Annals of Internal Medicine 123, no. 6 (September 15, 1995): 471. http://dx.doi.org/10.7326/0003-4819-123-6-199509150-00019.

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Lederman, Michael M. "Host-Directed Therapy for AIDS." Annals of Internal Medicine 123, no. 6 (September 15, 1995): 472. http://dx.doi.org/10.7326/0003-4819-123-6-199509150-00020.

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Jeong, Eui-Kwon, Hyo-Ji Lee, and Yu-Jin Jung. "Host-Directed Therapies for Tuberculosis." Pathogens 11, no. 11 (November 3, 2022): 1291. http://dx.doi.org/10.3390/pathogens11111291.

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Tuberculosis (TB) is one of the leading causes of death worldwide, consistently threatening public health. Conventional tuberculosis treatment requires a long-term treatment regimen and is associated with side effects. The efficacy of antitubercular drugs has decreased with the emergence of drug-resistant TB; therefore, the development of new TB treatment strategies is urgently needed. In this context, we present host-directed therapy (HDT) as an alternative to current tuberculosis therapy. Unlike antitubercular drugs that directly target Mycobacterium tuberculosis (Mtb), the causative agent of TB, HDT is an approach for treating TB that appropriately modulates host immune responses. HDT primarily aims to enhance the antimicrobial activity of the host in order to control Mtb infection and attenuate excessive inflammation in order to minimize tissue damage. Recently, research based on the repositioning of drugs for use in HDT has been in progress. Based on the overall immune responses against Mtb infection and the immune-evasion mechanisms of Mtb, this review examines the repositioned drugs available for HDT and their mechanisms of action.
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Maeurer, Markus, Renata Ramalho, Fu-Sheng Wang, and Alimuddin Zumla. "Host-directed therapies for COVID-19." Current Opinion in Pulmonary Medicine 27, no. 3 (February 2, 2021): 205–9. http://dx.doi.org/10.1097/mcp.0000000000000769.

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Davis, Angharad G., Joseph Donovan, Marise Bremer, Ronald Van Toorn, Johan Schoeman, Ariba Dadabhoy, Rachel P. J. Lai, et al. "Host Directed Therapies for Tuberculous Meningitis." Wellcome Open Research 5 (July 1, 2021): 292. http://dx.doi.org/10.12688/wellcomeopenres.16474.2.

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A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.
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Singh, Bhawana, Sanjay Varikuti, Gregory Halsey, Greta Volpedo, Omar M. Hamza, and Abhay R. Satoskar. "Host-directed therapies for parasitic diseases." Future Medicinal Chemistry 11, no. 15 (August 2019): 1999–2018. http://dx.doi.org/10.4155/fmc-2018-0439.

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Parasitic infections are responsible for significant morbidity and mortality throughout the world. Management strategies rely primarily on antiparasitic drugs that have side effects and risk of drug resistance. Therefore, novel strategies are needed for treatment of parasitic infections. Host-directed therapy (HDT) is a viable alternative, which targets host pathways responsible for parasite invasion/survival/pathogenicity. Recent innovative combinations of genomics, proteomics and computational biology approaches have led to discovery of several host pathways that could be promising targets for HDT for treating parasitic infections. Herein, we review major advances in HDT for parasitic disease with regard to core regulatory pathways and their interactions.
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Davis, Angharad G., Joseph Donovan, Marise Bremer, Ronald Van Toorn, Johan Schoeman, Ariba Dadabhoy, Rachel PJ Lai, et al. "Host Directed Therapies for Tuberculous Meningitis." Wellcome Open Research 5 (December 23, 2020): 292. http://dx.doi.org/10.12688/wellcomeopenres.16474.1.

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A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.
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Guler, Reto, and Frank Brombacher. "Host-directed drug therapy for tuberculosis." Nature Chemical Biology 11, no. 10 (September 17, 2015): 748–51. http://dx.doi.org/10.1038/nchembio.1917.

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Zumla, Alimuddin, Jeremiah Chakaya, Michael Hoelscher, Francine Ntoumi, Roxana Rustomjee, Cristina Vilaplana, Dorothy Yeboah-Manu, et al. "Towards host-directed therapies for tuberculosis." Nature Reviews Drug Discovery 14, no. 8 (July 17, 2015): 511–12. http://dx.doi.org/10.1038/nrd4696.

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Dissertations / Theses on the topic "Host-directed"

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Jordan, Brian J. "Directed assembly host-guest chemistry, nanowires, and polymeric templates /." Amherst, Mass. : University of Massachusetts Amherst, 2009. http://scholarworks.umass.edu/dissertations/AAI3359899/.

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Süss, Heike Ingrid. "Property directed inclusion formation by channel forming host compounds /." [S.l.] : [s.n.], 2004. http://www.zb.unibe.ch/download/eldiss/04suess_hi.pdf.

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Paudyal, Bhesh Raj [Verfasser]. "Small lipid mediators in experimental tuberculosis as target for host-directed therapy / Bhesh Raj Paudyal." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2017. http://d-nb.info/1147619638/34.

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Pathi, Krishna [Verfasser]. "Establishment of maize resistance to fungal diseases by host-induced gene silencing and site-directed mutagenesis / Krishna Pathi." Hannover : Gottfried Wilhelm Leibniz Universität, 2021. http://d-nb.info/1235138437/34.

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Laughery, Zachary. "Synthesis of Molecular Baskets and Introduction of Inward Facing Functionality." ScholarWorks@UNO, 2006. http://scholarworks.uno.edu/td/328.

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As a first step to producing a shape selective catalysts or enzyme mimic, two preorganized host molecules were synthesized. Binding studies of the two hosts with a variety of guests in three solvents demonstrated that an important driving force in the association was the formation of C-H???X-R hydrogen bonds (X = halogen). A deuterated host was utilized to further examine the formation of the C-H???X-R hydrogen bonds. In an effort to place functionality in the hydrophobic pocket of these hosts, two methods were developed. The first utilized directed ortho metallation to place electrophiles above and/or directed into the cavity. Perlithiation of the host could lead to sixty-nine products but reaction conditions and host rigidity limited product formation. This reaction technique led to the placement of carboxylic acid groups onto the host and the isolation of twelve products. Two different positions of the carboxylic acids (endoand exo-) direct the orientation of the guest. 1D- and 2D-NMR were utilized to examine how the was orientated inside the host. The second method employed to place functionality on the host, sited a tripodal zinc binding ligand on the side of the hydrophobic pocket of the host. The synthesized host was able to bind zinc strongly and in a 1:1 manner.
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Smyth, Robin. "Role of Protein Kinase R in the Immune Response to Tuberculosis." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41842.

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Tuberculosis (TB) is a deadly infectious lung disease caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb). The identification of macrophage signaling proteins exploited by Mtb during infection will enable the development of alternative host-directed therapies (HDT) for TB. HDT strategies will boost host immunity to restrict the intracellular replication of Mtb and therefore hold promise to overcome antimicrobial resistance, a growing crisis in TB therapy. Protein Kinase R (PKR) is a key host sensor that functions in the cellular antiviral response. However, its role in defense against intracellular bacterial pathogens is not clearly defined. Herein, we demonstrate that expression and activation of PKR is upregulated in macrophages infected with Mtb. Immunological profiling of human THP-1 macrophages that overexpress PKR (THP-PKR) showed increased production of IP-10 and reduced production of IL-6, two cytokines that are reported to activate and inhibit IFNy-dependent autophagy, respectively. Indeed, sustained expression and activation of PKR reduced the intracellular survival of Mtb, an effect that could be enhanced by IFNy treatment. We further demonstrate that the enhanced anti-mycobacterial activity of THP-PKR macrophages is mediated by a mechanism dependent on selective autophagy as indicated by increased levels of LC3-II that colocalize with intracellular Mtb. Consistent with this mechanism, inhibition of autophagolysosome maturation with bafilomycin A1 abrogated the ability of THP-PKR macrophages to limit replication of Mtb, whereas pharmacological activation of autophagy enhanced the anti-mycobacterial effect of PKR overexpression. As such, PKR represents a novel and attractive host target for development of HDT for TB, and our data suggest value in the design of more specific and potent activators of PKR.
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Hlaka, Lerato. "Investigation of minor groove binders (MGB), non-ionic surfactant vesicles (NIV) delivery systems and IL-4i1 as novel pathogen- and host-directed drug therapy for tuberculosis." Doctoral thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31054.

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Tuberculosis (TB), caused by Mycobacterium tuberculosis is the leading infectious disease epidemic that claims over 1.6 million lives, while 10 million fell ill in 2017. South Africa is burdened with the third highest global incidences following India and China with high rates of co-infections with HIV and highest numbers of multi-drug resistant (MDR) and extremely resistant (XDR) TB per capita. The current treatment regimen is decades old and requires a prolonged period of 6 months. The lack of efficient TB therapy and the emergence of MDR and XDR TB, there is an urgent need to find new drug targets for TB therapy through understanding the complex host-pathogen interactions. This may then lead to pathogen, host-directed therapies (HDT) or adjunct therapies as well as the development of effective drugs and drug formulations for the treatment of TB. Here we aimed to investigate potential targets for pathogen-and host-directed therapies for TB. We screened the anti-mycobacterial activity of 172 minor groove binder (MGB) compounds that selectively bind to AT-rich regions of the minor groove of bacterial DNA with the helical structure matching that of DNA in Mtb culture. Of the 172 total compounds screened 17 hits were identified, of which 2, MGB 362 and MGB 364 displayed intracellular mycobactericidal activity against Mtb HN878 at an MIC50 of 4.09 and 4.19 μM, respectively, whilst being non-toxic. Encapsulation of MGBs into non- ionic surfactant vesicles (NIVs) demonstrated a 1.6- and 2.1-fold increased intracellular mycobacterial activity, similar to that of rifampicin when compared with MGB alone. Treatment with MGB 364 or MGB 364 formulation did not cause DNA damage in murine infected macrophages as displayed by low expression of γ-H2Ax compared to H2O2 and DMSO. Intranasal administration of MGB 364 and MGB-NIV 364 formulation showed one log reduction in bacterial burden with improved pathology and immune cytokine production when in formulation. However, intranasal administration of 10 mg/kg MGB 362 together with rifampicin had no effect on bacterial loads. In summary, the data demonstrate the potential of MGB as a novel class of drug/chemical entity in anti-TB therapy and NIVs as an effective delivery system in a novel anti-TB formulation. Using deep CAGE and small RNA (CHIP-seq) technologies, International Center for Genetic Engineering and Biotechnology’s Cytokines and Diseases lab in collaboration with the RIKEN Center for Integrative Medical Sciences (Yokohama, Japan) performed a novel transcriptomics study approach by conducting a genome-wide transcriptional analyses of RNA transcripts from classically activated macrophages (caMph) and alternatively activated macrophages (aaMph) during Mtb infection. We identified host target genes that may play a role in host immune subverting mechanism by Mtb to hide away from host effector functions providing a possible target for host-directed therapy for tuberculosis. It is postulated that Mtb modulates the transcriptional landscape of IL-4/IL13 alternatively activated macrophages (aaMph) to escape killing by reactive nitrogen intermediates (NO) and reactive oxygen species (ROS) functions by IFN-γ stimulated classically activated macrophages (caMph). Here we report on the immunoregulatory role of IL-4i1, a candidate gene that was upregulated in aaMph during Mtb infection. IL-4i1 is a secreted L-amino oxidase with antibacterial properties. The enzyme converts Phenylalanine (Phe) into phenylpyruvate releasing toxic products ammonia and hydrogen peroxide (H2O2) which in-turn cause immunosuppression of effector T-cells by directly inhibiting polarization, proliferation and function or by promoting the generation of Foxp3 T-regulatory cells. Thus suggesting that IL-4i1 is involved in immune-regulatory mechanisms and may be implicated in immune evasion mechanisms by the pathogen. Here we report on the role of IL-4i1 on tissue localized T-cell activation and proliferative status thus maintaining immune local immune homeostasis. Thus showing that the absence of IL-4i1 could cause autoimmunity. To determine the functional role of IL-4i1 during Mtb infection, IL-4i1 deficient mice and wild-type littermate controls were infected with H37Rv and hypervirulent HN878 Mtb strain. IL-4i1 deficient mice were highly resistant to both strains of Mtb at 12- and 21-days post-infection as denoted by significant reduction in bacterial loads, reduced inflammation, reduced tissue iNOS expression reduced recruitment of interstitial macrophages, pro-inflammatory cytokines showed a trend for reduction. Interestingly there was a significant increase in NO production in infected tissues. There was an increase in M1-like macrophages that correlated with increased pro-inflammatory cytokines and chemokines. These data suggested that IL-4i1 regulates macrophage-mediated inflammatory responses during acute Mtb infection thus showing potential as an immunomodulatory target for TB HDT therapy. The study thus provides a framework for new drug targets for the development of new effective drugs and vaccines for TB therapy.
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Marzo, Escartín Elena. "Tuberculosi pulmonar: com evitar el pas de granuloma a cavitat. Estudi de la inflamació en la patogènesi de la malaltia tuberculosa i desenvolupament de noves estratègies terapèutiques." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/285649.

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La tuberculosi (TB) és una epidèmia global causada per Mycobacterium tuberculosis (Mtb) amb 8,6 milions de malalts i 1,3 milions de morts cada any. El tractament actual amb antibiòtics és molt llarg, car, i presenta efectes adversos. Quan una persona s’infecta amb Mtb pot controlar la infecció en el 90% dels casos (infecció latent), desenvolupant només lesions microscòpiques al pulmó: granulomes de 0,5mm de diàmetre, invisibles en una radiografia. En el 10% restant la infecció no es controla i es desenvolupen lesions més grans, típicament cavitats d’uns 20mm en adults immunocompetents. La clau per comprendre la patogènesi de la TB activa és la formació de grans cavitats a partir de granulomes de 0,5mm. En aquesta tesi s’ha desenvolupat un model murí, mitjançant la infecció endovenosa de ratolins C3HeB/FeJ amb la soca virulenta de Mtb H37Rv, que desenvolupa lesions amb necrosi granulomatosa central i liqüefacció molt similars a les lesions prèvies a la cavitació en humans. Les lesions creixen de forma exponencial en part degut a la infiltració neutrofílica massiva, i en part degut a la coalescència de les lesions properes. Els estudis comparatius amb la soca resistent C3H/HeN i l’ús d’antiinflamatoris no esteroideus (AINEs) en el model han confirmat que la inflamació és un factor clau en el desenvolupament de la TB activa, i també que els AINEs podrien utilitzar-se com a tractament coadjuvant en la TB pulmonar en adults immunocompetents, ja que en frenar la inflamació ajuden a controlar la malaltia. D’altra banda s’ha desenvolupat un mètode profilàctic que mitjançant l’administració oral de dosis baixes de micobacteris inactivats indueix tolerància al Mtb, i en conseqüència una resposta immunitària més equilibrada, amb contenció de la resposta Th17, resultant en una millora de la supervivència, la càrrega bacil·lar i la histopatologia dels ratolins. Conclusions: S’ha desenvolupat un model murí de TB activa, s’ha caracteritzat el paper que té la inflamació en el desenvolupament de cavitats, concretament la infiltració massiva de neutròfils, s’ha proposat l’ús d’AINEs com a tractament coadjuvant de la tuberculosi activa en adults immunocompetents, i s’ha desenvolupat un nou mètode profilàctic que podria evitar la malaltia mitjançant la inducció de tolerància oral al Mtb que s’aconsegueix amb l’administració oral de dosis baixes de micobactèries inactivades.
La tuberculosis (TB) es una epidemia global causada por Mycobacterium tuberculosis (Mtb) con 8,6 millones de enfermos y 1,3 millones de muertes cada año. El tratamiento actual con antibióticos es muy largo, caro i presenta efectos adversos. Cuando una persona se infecta con Mtb puede controlar la infección en el 90% de los casos (infección latente), desarrollando solamente lesiones microscópicas en el pulmón: granulomas de 0,5mm de diámetro invisibles en una radiografía. En el 10% restante la infección no se controla y se desarrollan lesiones mayores, típicamente cavidades de unos 20mm en adultos inmunocompetentes. La clave para comprender la patogénesis de la TB activa es el paso de granulomas de 0,5mm a cavidades de gran tamaño. En esta tesis se ha desarrollado un modelo murino mediante la infección endovenosa de ratones C3HeB/FeJ con la cepa virulenta H37Rv de Mtb, que desarrolla lesiones con necrosis granulomatosa central y licuefacción, muy similares a las lesiones previas a la cavitación en humanos. Las lesiones crecen de forma exponencial debido en parte a la infiltración neutrofílica masiva, y en parte a la coalescencia de las lesiones vecinas. Los estudios comparativos con la cepa resistente C3H/HeN y el uso de antiinflamatorios no esteroideos (AINEs) en el modelo han confirmado que la inflamación es un factor clave en el desarrollo de la TB activa, y también que los AINE podrían utilizarse como tratamiento coadyuvante en la TB pulmonar en adultos inmunocompetentes, dado que en frenar la inflamación ayudan a controlar la enfermedad. Por otro lado se ha desarrollado un método profiláctico que mediante la administración oral de dosis bajas de micobacterias inactivadas induce tolerancia al Mtb, y en consecuencia una respuesta inmunitaria más equilibrada, conteniendo la respuesta Th17, resultando en una mejora de la supervivencia, la carga bacilar y la histopatología de los ratones. Conclusiones: Se ha desarrollado un modelo murino de TB activa, se ha caracterizado el papel de la inflamación en el desarrollo de cavidades, concretamente de la infiltración masiva de neutrófilos, se ha propuesto el uso de AINEs como tratamiento coadyuvante para la tuberculosis activa en adultos inmunocompetentes, y se ha desarrollado un nuevo método profiláctico que podría evitar la enfermedad mediante la inducción de tolerancia oral al Mtb que se consigue con la administración oral de bajas dosis de micobacterias inactivadas.
Tuberculosis (TB) is a global epidemic caused by Mycobacterium tuberculosis (Mtb). In 2012 an estimated 8,6 million of people developed TB and 1,3 million died from the disease. The current treatment with antibiotics is expensive, long-lasting and presents adverse effects. When people are infected with Mtb the infection is controlled in the 90% of the cases, developing microscopic lesions in the lungs, 0,5mm of size granulomas, invisibles to the X-rays. In the other 10% the infection is not controlled and bigger lesions are developed: in immunocompetent adults the most characteristic lesion is a cavity sized about 20mm of diameter. The clue to understand active TB pathogenesis must be the development of 20mm cavities from 0,5mm granulomas. In this work a murine model has been developed through the endovenous infection of C3HeB/FeJ mice with H37Rv virulent strain of Mtb, which develops lesions presenting central granulomatous necrosis and further liquefaction, very similarly to the lesions previous to cavity formation in human patients. The lesions grow exponentially due to massive neutrophilic infiltration and coalescence of neighbour lesions. The comparative studies with the resistant mice strain C3H/HeN and the use of non-steroidal anti-iflammatory drugs (NSAIDs) in the model confirmed that inflammation is clue in the active TB development, and also that NSAIDs could be use as adjunctive therapy in the treatment of pulmonary TB in immunocompetent adults, through control of excessive inflammation. On the other hand, a prophylactic method has been developed consisting on induction of tolerance to Mtb through oral administration of low doses of heat-killed mycobacteria, driving to a more balanced immune response, limiting Th17 development and resulting in a better outcome of mice in terms of survival, histopathology and bacillary load in lungs. Conclusions: A murine active TB model has been developed, and the role of inflammation in cavity formation characterized, namely the role of massive neutrophilic infiltration. The use of NSAIDs has been proposed as an adjuvant treatment of active TB in immunocompetent adults, and a new prophylactic method has been developed that could avoid the disease by induction of oral tolerance to Mtb through the administration of heat killed micobacteria at low doses.
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Matsui, Yusuke. "Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis." Kyoto University, 2015. http://hdl.handle.net/2433/199190.

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Chiu, Chia-I., and 邱嘉儀. "Evaluation of Host-Directed Anti-Bacterial Agents Against Intracellular Salmonella Typhimurium." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/w39y38.

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碩士
國立臺灣大學
醫學檢驗暨生物技術學研究所
106
Some bacteria pathogens that can reside in host cells, for example: Salmonella spp. and will lead to chronic infection. These pathogens will invade host cells to evade external antibiotics’ attack and continue to survive in the cell, thus they are difficult to completely eradicated with antibiotics and often lead to drug resistance. Host-directed therapies have been proposed in many studies for the treatment of intracellular bacterial infections. AR-12 (a.k.a. OSU-03012), was originally used as an anti-cancer drug and have been showed in our previous studies that AR-12 combined with aminoglycoside antibiotics can significantly clear intracellular bacteria, making AR-12 as a potential drug for the treatment of intracellular bacterial infections. As the half-lethal dose (IC50) of AR-12 is close to half-effective concentration, we decided to conduct AR-12 structure optimization. In addition, we previously found that an antipsychotic drug - loxapine in combined with aminoglycoside antibiotics showed antimicrobial efficacy and significantly cleared intracellular bacteria with a high half-lethal dose (IC50), however, loxapine cannot prolong the survival of mice. Therefore, we hope to obtain potential drugs by synthesis of loxapine derivatives. In this study, we obtained 167 AR-12 derivatives and 5 loxapine derivatives. We tested the anti-bacterial activity against intracellular Salmonella Typhimurium of all compounds and simultaneously tested toxicity towards host cells to identify more effective and low toxicity drugs. At the same time, we used loxapine as the representative to explore its antibacterial mechanism. First, we performed AR-12 derivative screening. We found that seven compounds have lower toxicity and equal antibacterial activity to AR-12. Another seven compounds showed better antibacterial activity but equal toxicity to AR-12. We further evaluated the efficacy of these 14 compounds in combination with aminoglycoside antibiotics for the treatment of intracellular S. Typhimurium. The results of the cell infection experiments showed that 4 of 14 compounds had no significant antibacterial activity. Subsequent test of the three compounds with highest selectivity for antibacterial activity against multidrug-resistant strains also demonstrated the same effect. In the cell infection test and toxicity test of loxapine, three compounds showed better antibacterial ability than loxapine, but with high toxicity, thus there was no high selectivity. At present, the synthesis and test of AR-12 derivatives and loxapine derivatives are ongoing. The above findings demonstrated that the antibacterial activity of AR-12 can be dissociated from its antiproliferative activity via structure optimization and that hit compounds are potential to be served as antibiotic adjuvants for MDR Salmonella Typhimurium infection.
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Books on the topic "Host-directed"

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Karakousis, Petros C., Richard Hafner, and Maria Laura Gennaro, eds. Advances in Host-Directed Therapies Against Tuberculosis. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-56905-1.

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Host-Directed Therapies for Tuberculosis. MDPI, 2020. http://dx.doi.org/10.3390/books978-3-03943-502-9.

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Karakousis, Petros C., Richard Hafner, and Maria Laura Gennaro. Advances in Host-Directed Therapies Against Tuberculosis. Springer International Publishing AG, 2021.

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Karakousis, Petros C., Richard Hafner, and Maria Laura Gennaro. Advances in Host-Directed Therapies Against Tuberculosis. Springer International Publishing AG, 2020.

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Wilkinson, Robert, Anna Kathleen Coussens, and Thomas Richard Hawn, eds. Natural Resistance to and Host-Directed Prevention of Tuberculosis. Frontiers Media SA, 2020. http://dx.doi.org/10.3389/978-2-88963-799-7.

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Brombacher, Frank, Abhay Satoskar, and Alessandro Marcello, eds. Towards Host-Directed Drug Therapies for Infectious and Non-Communicable Diseases. Frontiers Media SA, 2019. http://dx.doi.org/10.3389/978-2-88963-102-5.

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Fraziano, Maurizio, Roberto Nisini, Gian Maria Rossolini, and Marco Rinaldo Oggioni, eds. Exploiting Novel Combined Host- and Pathogen-Directed Therapies for Combating Bacterial Multidrug Resistance. Frontiers Media SA, 2020. http://dx.doi.org/10.3389/978-2-88966-307-1.

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Katia, Yannaca-Small. Part III Guide to Key Jurisdictional Issues, 16 The Umbrella Clause: Is the Umbrella Closing? Oxford University Press, 2018. http://dx.doi.org/10.1093/law/9780198758082.003.0016.

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‘Umbrella clauses’ are inserted in treaties to provide additional protection to investors and are directed at covering investment agreements that host countries frequently conclude with foreign investors. Inclusion of umbrella clauses in investment treaties provides a mechanism to make host States’ promises ‘enforceable’ and comes as an additional protection of investor-state contracts, which raises the controversial issue of whether the umbrella clause seeks to elevate contractual breaches to treaty breaches. For a better understanding of the clause, this chapter (i) gives an overview of its history; (ii) briefly discusses the significance of the language included in a number of bilateral investment treaties; and (iii) looks at the effect, scope and conditions of application of the umbrella clause as interpreted by arbitral tribunals.
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Thompson, Evan. Looping Effects and the Cognitive Science of Mindfulness Meditation. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190495794.003.0003.

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Cognitive neuroscience tends to conceptualize mindfulness meditation as inner observation of a private mental realm of thoughts, feelings, and body sensations, and tries to model mindfulness as instantiated in neural networks visible through brain imaging tools such as EEG and fMRI. This approach confuses the biological conditions for mindfulness with mindfulness itself, which, as classically described, consists in the integrated exercise of a whole host of cognitive and bodily skills in situated and ethically directed action. From an enactive perspective, mindfulness depends on internalized social cognition and is a mode of skillful, embodied cognition that depends directly not only on the brain, but also on the rest of the body and the physical, social, and cultural environment.
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Wise, Matt, and Paul Frost. Nutritional support in the critically ill. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0334.

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Major injury evokes a constellation of reproducible hormonal, metabolic, and haemodynamic responses which are collectively termed ‘the adaptive stress response’. The purpose of the adaptive stress response is to facilitate tissue repair and restore normal homeostasis. If critical illness is prolonged, the adaptive stress response may become maladaptive, in essence exerting a parasitic effect leaching away structural proteins and impairing host immunity. Primarily therapy should be directed towards the underlying illness, as nutritional support per se will not reverse the stress response and its sequelae. Nonetheless, adequate nutritional support in the early stages of critical illness may attenuate protein catabolism and its adverse effects. This chapter covers nutritional assessment; detection of malnutrition; energy and protein requirements; monitoring the effectiveness of nutritional replacements; nutritional delivery; complications; and refeeding syndrome.
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Book chapters on the topic "Host-directed"

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Weintraub, Zachary, and Katherine Menson. "Host-Directed Therapy." In Bronchiectasis, 191–98. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-12926-1_8.

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Dutta, Noton K., and Petros C. Karakousis. "Statins as Host-Directed Therapy for Tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 109–19. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_8.

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Jo, Eun-Kyeong. "Nuclear Receptors in Host-Directed Therapies against Tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 61–67. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_5.

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Smulan, Lorissa, Hardy Kornfeld, and Amit Singhal. "Sirtuin Deacetylases: Linking Mycobacterial Infection and Host Metabolism." In Advances in Host-Directed Therapies Against Tuberculosis, 15–26. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_2.

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Frank, Daniel J., and Robert N. Mahon. "Introduction: An Overview of Host-Directed Therapies for Tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 3–12. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_1.

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Ruibal, Paula, Tom H. M. Ottenhoff, and Simone A. Joosten. "Conventional and Unconventional Lymphocytes in Immunity Against Mycobacterium tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 133–68. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_10.

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Parveen, Sadiya, John R. Murphy, and William R. Bishai. "Targeting Inhibitory Cells Such as Tregs and MDSCs in the Tuberculous Granuloma." In Advances in Host-Directed Therapies Against Tuberculosis, 169–203. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_11.

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Kleynhans, Léanie, and Gerhard Walzl. "Targeting Suppressor T Cells." In Advances in Host-Directed Therapies Against Tuberculosis, 205–10. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_12.

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Dallenga, Tobias K., and Ulrich E. Schaible. "Neutrophil-Mediated Mechanisms as Targets for Host-Directed Therapies Against Tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 211–17. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_13.

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Mayer-Barber, Katrin D., and Christopher M. Sassetti. "Type I Interferon and Interleukin-1 Driven Inflammatory Pathways as Targets for HDT in Tuberculosis." In Advances in Host-Directed Therapies Against Tuberculosis, 219–32. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56905-1_14.

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Conference papers on the topic "Host-directed"

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Dey, Nidhi Sharma. "Immunopathology pipeline to study potential host directed therapy targets in cutaneous leishmaniasis." In Microscience Microscopy Congress 2021 incorporating EMAG 2021. Royal Microscopical Society, 2021. http://dx.doi.org/10.22443/rms.mmc2021.296.

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FELCIANO, RAMON M., SINA BAVARI, DANIEL R. RICHARDS, JEAN-NOEL BILLAUD, TRAVIS WARREN, REKHA PANCHAL, and ANDREAS KRÄMER. "PREDICTIVE SYSTEMS BIOLOGY APPROACH TO BROAD-SPECTRUM, HOST-DIRECTED DRUG TARGET DISCOVERY IN INFECTIOUS DISEASES." In Proceedings of the Pacific Symposium. WORLD SCIENTIFIC, 2012. http://dx.doi.org/10.1142/9789814447973_0003.

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Jakobs, Nikolas, Kerstin Walter, Johanna Volz, Alexandra Hölscher, Torsten Goldmann, Sebastian Marwitz, Markus Weckmann, Folke Brinkmann, and Christoph Hölscher. "Multiplex Immunofluorescence and Multispectral Imaging as a tool to evaluate host directed therapy against tuberculosis." In 44. Jahrestagung der Gesellschaft für Pädiatrische Pneumologie. Georg Thieme Verlag, 2023. http://dx.doi.org/10.1055/s-0043-1761549.

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Guy, M. J., A. Boskovic, D. U. Noske, and J. R. Taylor. "Femtosecond Pulse Generation At 1.3 μm From A Praseodymium Fibre Laser." In International Conference on Ultrafast Phenomena. Washington, D.C.: Optica Publishing Group, 1994. http://dx.doi.org/10.1364/up.1994.wc.3.

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Femtosecond pulses have been generated in erbium doped fibre lasers using a number of different cavity designs and mode-locking techniques. These have proven capable of directly generating pulses as short as 98 fs at 1.55 μm1, the lowest loss "window" in optical fibre used for telecommunications. A second low loss window exists at 1.3 μm and recently considerable interest has been directed towards Praseodymium (Pr3+) doped fluoride fibre as an amplifier providing gain at this wavelength. Pr3+ doped into a fluoride glass host high gain over a range of ~50 nm and this broad bandwidth has the potential to support femtosecond pulses.
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Ermer, Susan, Doris S. Leung, Steven M. Lovejoy, John F. Valley, and Marc Stiller. "Photobleachable Donor-Acceptor-Donor Chromophores with Enhanced Thermal Stability." In Organic Thin Films for Photonic Applications. Washington, D.C.: Optica Publishing Group, 1993. http://dx.doi.org/10.1364/otfa.1993.wc.2.

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An important step in the realization of active optical interconnects is the development of poled electro-optic (EO) polymer materials stable to both manufacturing and end-use environments. These environments vary according to process and ultimate application, but many require longterm thermal stability to 125 °C and short excursions to 250 °C or higher.1 Our efforts with EO polymers have been directed toward thermally stable waveguide devices2 and polyimide-based guest-host material systems.3 We recently demonstrated a proof-of-principle all-polyimide triple stack Mach-Zehnder based on DCM (4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran) as the active chromophore in the core waveguide layer.4 The structure of DCM is shown in Figure 1(a). Advantages of DCM include low absorbance at device wavelengths, photobleachability, compatibility with polyimides and their polyamic acid precursors, and commercial ability at high purity. DCM is less than optimum in its thermal characteristics, however. It out-diffuses when heated above 220 °C for significant periods of time and it plasticizes the host material. This plasticization depresses the glass transition temperature Tg, and is detrimental to long-term stability of the poled state.
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Wallis, R. S., S. Ginindza, T. Beattie, N. Arjun, M. Likoti, V. Edward, M. Rassool, et al. "Preliminary Results of an Experimental Medicine Trial of Adjunctive Host-Directed Therapy in Adults with Moderately or Far-Advanced Rifampin-Susceptible Pulmonary Tuberculosis." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7388.

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Williams, Alicia, Ashok Sinha, Pavlos Vlachos, and Ishwar K. Puri. "Magnetic Targeting of Particle Transport Under Pulsatile Flow." In ASME 2006 2nd Joint U.S.-European Fluids Engineering Summer Meeting Collocated With the 14th International Conference on Nuclear Engineering. ASMEDC, 2006. http://dx.doi.org/10.1115/fedsm2006-98124.

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Magnetic Drug Targeting (MDT) has been shown to be a promising technique to effectively deliver medicinal drugs via functionalized [1] magnetic particles to target sites during the treatment of cancer and other diseases [2,3,4]. In this paper, we investigate the interaction of steady and pulsatile flows injected with a ferrofluid, which is a colloidal suspension of superparamagnetic nanoparticles in a glass tube under the influence of a magnetic field. Ferrofluids are colloidal suspensions of single domain magnetic nanoparticles that are of the order of 10 nm in diameter. In this experiment, the ferrofluid particles were directed to a particular region of interest within a 10 mm diameter glass vessel by means of an applied localized magnetic field that originated outside of the vessel. The magnetic field was generated using a rare earth sintered permanent magnet which produced the magnetic field gradient required for inducing a body force on the volume of the ferrofluid. The experimental results reveal flows with rich dynamical phenomena. The aggregation of the ferrofluid produces a self-assembled hemispherical structure which dynamically interacts with the host flow. The aggregation generates an occlusion creating a flow field that is similar to that past an obstruction. However, since the structure itself is of a fluidic nature, it is subject to shear forces caused by the host fluid. In addition, the wake of the flow behind the aggregation creates vortices which are critical to study the stability of the ferrofluid aggregate. This paper presents a detailed investigation of the dynamics of the flow using Time-Resolved Digital Particle Image Velocimetry. To the best of the authors’ knowledge, these are the first quantitative, spatiotemporally resolved measurements documenting the interaction of a host fluid with a ferrofluid aggregate under steady or pulsatile flow conditions.
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Wouters, Katinka, Hugo Moors, and Natalie Leys. "Boom Clay Borehole Water, Home of a Diverse Bacterial Community." In ASME 2013 15th International Conference on Environmental Remediation and Radioactive Waste Management. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/icem2013-96222.

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For over two decades, Boom Clay has been studied in the framework of geological disposal of nuclear waste thereby mainly addressing its geochemical properties. Today, also the microbiological properties and the possibility of microbes interacting with radionuclides or repository components including the waste form, in a host formation like Boom Clay are considered [2,3]. In the past, a reference composition for synthetic Boom Clay pore water (BCPW) was derived, based on interstitial water sampled from different layers within the Boom clay [1]. Similarly, the primary aim of this microbiological study was to determine the core BCPW bacterial community and identify representative water samples for future microbial directed lab experiments. In this respect, BCPW was sampled from different Boom Clay layers using the Morpheus piezometer (Fig. 1) and subsequently analysed by microscopy and molecular techniques, in search for overall shared and abundant micro-organisms.
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Thomas, Wendy E., Evgeni V. Sokurenko, and Viola Vogel. "How Bacteria Bind More Strongly Under Mechanical Force: The Catch-Bond FimH." In ASME 2003 International Mechanical Engineering Congress and Exposition. ASMEDC, 2003. http://dx.doi.org/10.1115/imece2003-43680.

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We study a protein that responds to mechanical force in most striking manner. We demonstrate that Escherichia coli bacteria need shear stress to bind to certain tissues and model surfaces; they bind strongest precisely when the body tries to wash them off. We have determined that the protein responsible for this behavior is FimH, a ubiquitous adhesion protein in intestinal bacteria that mediates adhesion to host cells via the carbohydrate mannose. Although mechanical force noramlly decreases bond lifetimes, we have shown that the bond betweeen FimH and simple mono-mannose receptors is s “catch-bond” that lasts longer under shear stress. In contrast, structural variations in either FimH or the receptor cause a stronger mode of adhesion in static conditions with little or no activation under force. We derive a structural for how mechanical force switches FimH to a strong binding mode by using steered molecular dynamics simulations, and validate the predictions with subsequent site-directed mutagenesis. The physiological consequences as well as the engineering principles suggested by the structural model will be discussed.
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Marchant, David, Gurpreet Singerha, John H. Boyd, Delbert Dorscheid, Bruce M. McManus, and Richard Hegele. "P38 Mitogen Activated Protein Kinase Is Activated By Toll Like Receptor 4 Via MyD88 During Pulmonary Virus Entry To Activate Virus Internalization And Replication: A New Host-directed Antiviral." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1046.

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Reports on the topic "Host-directed"

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Gutnick, David, and David L. Coplin. Role of Exopolysaccharides in the Survival and Pathogenesis of the Fire Blight Bacterium, Erwinia amylovora. United States Department of Agriculture, September 1994. http://dx.doi.org/10.32747/1994.7568788.bard.

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Fireblight, a disease of apples and pears, is caused by Erwinia amylovora. Mutants of E. amylovora that do not produce the extreacellular polysaccharide (EPS), amylovoran, are avirulent. A similar EPS, stewartan, is produced by E. stewartii, which caused Stewart's wilt of corn, and which has also been implicated in the virulence of this strain. Both stewartan and amylovoran are type 1 capsular polysaccharides, typified by the colanic acid slime produced by Escherichia coli. Extracellular polysaccharide slime and capsules are important for the virulence of bacterial pathogens of plants and animals and to enhance their survival and dissemination outside of the host. The goals of this project were to examine the importance of polysaccharide structure on the pathogenicity and survival properties of three pathogenic bacteria: Erwinia amylovora, Erwinia stewartii and Escherichia coli. The project was a collaboration between the laboratories of Dr. Gutnick (PI, E. coli genetics and biochemistry), Dr. Coplin (co-PI, E. stewartii genetics) and Dr. Geider (unfunded collaborator, E. amylovora genetics and EPS analysis). Structural analysis of the EPSs, sequence analysis of the biosynthetic gene clusters and site-directed mutagenesis of individual cps and ams genes revealed that the three gene clusters shared common features for polysaccharide polymerization, translocation, and precursor synthesis as well as in the modes of transcriptional regulation. Early EPS production resulted in decreased virulence, indicating that EPS, although required for pathogenicity, is anot always advantageous and pathogens must regulate its production carefully.
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Gal-On, Amit, Shou-Wei Ding, Victor P. Gaba, and Harry S. Paris. role of RNA-dependent RNA polymerase 1 in plant virus defense. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7597919.bard.

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Objectives: Our BARD proposal on the impact of RNA-dependent RNA polymerase 1 (RDR1) in plant defense against viruses was divided into four original objectives. 1. To examine whether a high level of dsRNA expression can stimulate RDR1 transcription independent of salicylic acid (SA) concentration. 2. To determine whether the high or low level of RDR1 transcript accumulation observed in virus resistant and susceptible cultivars is associated with viral resistance and susceptibility. 3. To define the biogenesis and function of RDR1-dependent endogenous siRNAs. 4. To understand why Cucumber mosaic virus (CMV) can overcome RDR1-dependent resistance. The objectives were slightly changed due to the unique finding that cucumber has four different RDR1 genes. Background to the topic: RDR1 is a key plant defense against viruses. RDR1 is induced by virus infection and produces viral and plant dsRNAs which are processed by DICERs to siRNAs. siRNAs guide specific viral and plant RNA cleavage or serve as primers for secondary amplification of viral-dsRNA by RDR. The proposal is based on our preliminary results that a. the association of siRNA and RDR1 accumulation with multiple virus resistance, and b. that virus infection induced the RDR1-dependent production of a new class of endogenous siRNAs. However, the precise mechanisms underlying RDR1 induction and siRNA biogenesis due to virus infection remain to be discovered in plants. Major conclusions, solutions and achievements: We found that in the cucurbit family (cucumber, melon, squash, watermelon) there are 3-4 RDR1 genes not documented in other plant families. This important finding required a change in the emphasis of our objectives. We characterized 4 RDR1s in cucumber and 3 in melon. We demonstrated that in cucumber RDR1b is apparently a new broad spectrum virus resistance gene, independent of SA. In melon RDR1b is truncated, and therefore is assumed to be the reason that melon is highly susceptible to many viruses. RDR1c is dramatically induced due to DNA and RNA virus infection, and inhibition of RDR1c expression led to increased virus accumulation which suggested its important on gene silencing/defense mechanism. We show that induction of antiviral RNAi in Arabidopsis is associated with production of a genetically distinct class of virus-activated siRNAs (vasiRNAs) by RNA dependent RNA polymerase-1 targeting hundreds of host genes for RNA silencing by Argonaute-2. Production of vasiRNAs is induced by viruses from two different super groups of RNA virus families, targeted for inhibition by CMV, and correlated with virus resistance independently of viral siRNAs. We propose that antiviral RNAi activate broad-spectrum antiviral activity via widespread silencing of host genes directed by vasiRNAs, in addition to specific antiviral defense Implications both scientific and agricultural: The RDR1b (resistance) gene can now be used as a transcription marker for broad virus resistance. The discovery of vasiRNAs expands the repertoire of siRNAs and suggests that the siRNA-processing activity of Dicer proteins may play a more important role in the regulation of plant and animal gene expression than is currently known. We assume that precise screening of the vasiRNA host targets will lead in the near future for identification of plant genes associate with virus diseases and perhaps other pathogens.
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McClure, Michael A., Yitzhak Spiegel, David M. Bird, R. Salomon, and R. H. C. Curtis. Functional Analysis of Root-Knot Nematode Surface Coat Proteins to Develop Rational Targets for Plantibodies. United States Department of Agriculture, October 2001. http://dx.doi.org/10.32747/2001.7575284.bard.

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The goal of this research was to provide a better understanding of the interface between root-knot nematodes, Meloidogyne spp., and their host in order to develop rational targets for plantibodies and other novel methods of nematode control directed against the nematode surface coat (SC). Specific objectives were: 1. To produce additional monoclonal SC antibodies for use in Objectives 2, 3, and 4 and as candidates for development of plantibodies. 2. To determine the production and distribution of SC proteins during the infection process. 3. To use biochemical and immunological methods to perturbate the root-knot nematode SC in order to identify SC components that will serve as targets for rationally designed plantibodies. 4. To develop SC-mutant nematodes as additional tools for defining the role of the SC during infection. The external cuticular layer of nematodes is the epicuticle. In many nematodes, it is covered by a fuzzy material termed "surface coat" (SC). Since the SC is the outermost layer, it may playa role in the interaction between the nematode and its surroundings during all life stages in soil and during pathogenesis. The SC is composed mainly of proteins, carbohydrates (which can be part of glycoproteins), and lipids. SC proteins and glycoproteins have been labeled and extracted from preparasitic second-stage juveniles and adult females of Meloidogyne and specific antibodies have been raised against surface antigens. Antibodies can be used to gain more information about surface function and to isolate genes encoding for surface antigens. Characterization of surface antigens and their roles in different life-stages may be an important step towards the development of alternative control. Nevertheless, the role of the plant- parasitic nematode's surface in plant-nematode interaction is still not understood. Carbohydrates or carbohydrate-recognition domains (CROs) on the nematode surface may interact with CROs or carbohydrate molecules, on root surfaces or exudates, or be active after the nematode has penetrated into the root. Surface antigens undoubtedly play an important role in interactions with microorganisms that adhere to the nematodes. Polyclonal (PC) and monoclonal (MC) antibodies raised against Meloidogyne javanica, M. incognita and other plant-parasitic nematodes, were used to characterize the surface coat and secreted-excreted products of M. javanica and M. incognita. Some of the MC and PC antibodies raised against M. incognita showed cross-reactivity with the surface coat of M. javanica. Further characterization, in planta, of the epitopes recognized by the antibodies, showed that they were present in the parasitic juvenile stages and that the surface coat is shed during root penetration by the nematode and its migration between root cells. At the molecular level, we have followed two lines of experimentation. The first has been to identify genes encoding surface coat (SC) molecules, and we have isolated and characterized a small family of mucin genes from M. incognita. Our second approach has been to study host genes that respond to the nematode, and in particular, to the SC. Our previous work has identified a large suite of genes expressed in Lycopersicon esculentum giant cells, including the partial cDNA clone DB#131, which encodes a serine/threonine protein kinase. Isolation and predicted translation of the mature cDNA revealed a frame shift mutation in the translated region of nematode sensitive plants. By using primers homologous to conserved region of DB#131 we have identified the orthologues from three (nematode-resistant) Lycopersicon peruvianum strains and found that these plants lacked the mutation.
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