24 results on '"Humann J"'
Search Results
2. Effects of Postharvest Onion Curing Parameters on the Development of Sour Skin and Slippery Skin in Storage.
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Schroeder, B. K., Humann, J. L., and du Toit, L. J.
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ONION storage , *COLD storage , *HARVESTING , *BULBS (Plants) , *PLANT inoculation , *POSTHARVEST technology of crops , *ONION varieties - Abstract
The influence of postharvest curing temperature and duration on devel-opment of slippery skin (caused by Burkholderia gladioli pv. alliicola) and sour skin (caused by B. cepacia) in onion (Allium cepa) bulbs during storage was evaluated by inoculating bulbs of the storage culti-vars 'Redwing' and 'Vaquero' with each of the pathogens after harvest, curing the bulbs at 25, 30, 35, or 40°C for 2 or 14 days, and storing the bulbs at 5°C for 1, 2, or 3 months. Noninoculated bulbs and bulbs injected with sterile water served as control treatments. The onion bulbs were from drip-irrigated, commercial onion crops grown in the semiarid Columbia Basin of central Washington in 2009 and 2010. Each bulb was cut through the point of inoculation from the neck to the basal plate to assess severity of bulb rot (percentage of cut bulb surface area with bacterial rot symptoms) after 1, 2, or 3 months of storage. Bulb rot severity in the 2009-10 and 2010-11 trials was negligible for noninoculated bulbs (mean of 4.0 and 4.5%, respectively) and bulbs injected with water (6.2 and 10.1%, respectively) compared with bulbs inoculated with B. cepacia (34.6 and 39.8%, respectively) and B. gladioli pv. alliicola (20.7 and 27.4%, respectively). Bulbs inoculated with B. cepacia developed significantly more severe rot than those inoculated with B. gladioli pv. alliicola, even though a 10-fold greater inoculum concentration was used for B. gladioli pv. alliicola, demonstrating the more aggressive nature of B. cepacia compared with B. gladioli pv. alliicola. Severity of bulb decay caused by B. cepacia or B. gladioli pv. alliicola was affected significantly (P < 0.05) by season (trial), cultivar, curing temperature, curing duration, and storage duration, with significant interactions among these factors. In both trials and for both pathogens, bulb rot was significantly more severe the greater the curing temperature and the severity of bulb rot was significantly greater when bulbs were cured for 14 versus 2 days prior to cold storage. Overall, the severity of bulb rot was greater with a longer duration of storage after curing. This increase in bulb rot sever-ity, which resulted from an increase in curing temperature and dura-tion, was significantly greater for Vaquero than Redwing and signifi-cantly greater for bulbs inoculated with B. cepacia than B. gladioli pv. alliicola. The results suggest that postharvest curing at temperatures <35°C for a limited duration can significantly reduce the severity of sour skin or slippery skin in storage. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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3. Chances of pregnancy and live birth among women undergoing conservative management of early-stage endometrial cancer: a systematic review and meta-analysis.
- Author
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Herrera Cappelletti E, Humann J, Torrejón R, and Gambadauro P
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- Adult, Female, Humans, Pregnancy, Conservative Treatment, Pregnancy Rate, Progestins therapeutic use, Young Adult, Endometrial Neoplasms pathology, Endometrial Neoplasms therapy, Live Birth
- Abstract
Background: Endometrial cancer is common and usually occurs after menopause, but the number of women diagnosed during reproductive age is increasing. The standard treatment including hysterectomy is effective but causes absolute uterine factor infertility. In order to avoid or postpone surgery, conservative management of endometrial cancer (CMEC) has been proposed for younger women who want to retain their fertility., Objective and Rationale: The main objective of this study was to estimate the chances of pregnancy and live birth for women with early-stage endometrial cancer (EEC) who are managed conservatively for fertility preservation., Search Methods: The PRISMA recommendations for systematic reviews and meta-analyses were followed. Structured searches were performed in PubMed, Embase and the Cochrane Library, from inception until 13 June 2021. Inclusion was based on the following criteria: group or subgroup of women with Clinical Stage IA, well-differentiated, endometrioid endometrial cancer (from now on, EEC); CMEC for fertility preservation; and reported frequencies of women achieving pregnancy and/or live birth after CMEC. The following exclusion criteria applied: impossibility to isolate/extract outcome data of interest; second-line CMEC for persistent/recurrent disease; CMEC in the presence of synchronous tumours; case reports; non-original or duplicated data; and articles not in English. Qualitative synthesis was performed by means of tabulation and narrative review of the study characteristics. Study quality was assessed with an ad hoc instrument and several moderator and sensitivity analyses were performed., Outcomes: Out of 1275 unique records, 133 were assessed in full-text and 46 studies were included in the review. Data from 861 women with EEC undergoing CMEC were available. Progestin-based treatment was reported in all but three studies (93.5%; 836 women). Complete response to treatment was achieved in 79.7% of women, with 35.3% of them having a disease recurrence during follow-up. Of 286 pregnancies obtained after CMEC; 69.4% led to live birth (9% of them multiple births) and 66.7% were achieved through fertility treatment. Based on random-effects meta-analyses, women treated with progestin-based CMEC have a 26.7% chance of achieving pregnancy (95% CI 21.3-32.3; I2 = 53.7%; 42 studies, 826 women) and a 20.5% chance to achieve a live birth (95% CI 15.7-25.8; I2 = 40.2%; 39 studies, 650 women). Sample size, average age, publication year, study design and quality score were not associated with the outcomes of progestin-based CMEC in moderator analyses with meta-regression. However, mean follow-up length (in months) was positively associated with the chances of pregnancy (regression coefficient [B] = 0.003; 95% CI 0.001-0.005; P = 0.006) and live birth (B = 0.005; 95% CI 0.003-0.007; P < 0.001). In sensitivity analyses, the highest chances of live birth were estimated in subsets of studies including only women of age 35 or younger (30.7%), the combination of progestins with hysteroscopic resection (30.7%), or at least 3 years of follow-up (42.4%)., Wider Implications: Progestin-based CMEC is viable for women with well-differentiated, Clinical Stage 1A, endometrioid endometrial cancer who want to preserve their fertility, but there is room for improvement as only one-fifth of them are estimated to achieve live birth according to this meta-analysis. Further investigations on prognosis-driven selection, hysteroscopic resection and long-term surveillance are arguably needed to improve the reproductive outcomes of CMEC., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
- Published
- 2022
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4. CottonGen: The Community Database for Cotton Genomics, Genetics, and Breeding Research.
- Author
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Yu J, Jung S, Cheng CH, Lee T, Zheng P, Buble K, Crabb J, Humann J, Hough H, Jones D, Campbell JT, Udall J, and Main D
- Abstract
Over the last eight years, the volume of whole genome, gene expression, SNP genotyping, and phenotype data generated by the cotton research community has exponentially increased. The efficient utilization/re-utilization of these complex and large datasets for knowledge discovery, translation, and application in crop improvement requires them to be curated, integrated with other types of data, and made available for access and analysis through efficient online search tools. Initiated in 2012, CottonGen is an online community database providing access to integrated peer-reviewed cotton genomic, genetic, and breeding data, and analysis tools. Used by cotton researchers worldwide, and managed by experts with crop-specific knowledge, it continuous to be the logical choice to integrate new data and provide necessary interfaces for information retrieval. The repository in CottonGen contains colleague, gene, genome, genotype, germplasm, map, marker, metabolite, phenotype, publication, QTL, species, transcriptome, and trait data curated by the CottonGen team. The number of data entries housed in CottonGen has increased dramatically, for example, since 2014 there has been an 18-fold increase in genes/mRNAs, a 23-fold increase in whole genomes, and a 372-fold increase in genotype data. New tools include a genetic map viewer, a genome browser, a synteny viewer, a metabolite pathways browser, sequence retrieval, BLAST, and a breeding information management system (BIMS), as well as various search pages for new data types. CottonGen serves as the home to the International Cotton Genome Initiative, managing its elections and serving as a communication and coordination hub for the community. With its extensive curation and integration of data and online tools, CottonGen will continue to facilitate utilization of its critical resources to empower research for cotton crop improvement.
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- 2021
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5. The Breeding Information Management System (BIMS): an online resource for crop breeding.
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Jung S, Lee T, Gasic K, Campbell BT, Yu J, Humann J, Ru S, Edge-Garza D, Hough H, and Main D
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- Genomics, Information Management, Software, Databases, Genetic, Plant Breeding
- Abstract
In this era of big data, breeding programs are producing ever larger amounts of data. This necessitates access to efficient management systems to keep track of cross, performance, pedigree, geographical and image-based data, as well as genotyping data. In this article, we report the progress on the Breeding Information Management System (BIMS), a free, secure and online breeding management system that allows breeders to store, manage, archive and analyze their private breeding data. BIMS is the first publicly available database system that enables individual breeders to integrate their private phenotypic and genotypic data with public data and, at the same time, have complete control of their own breeding data along with access to tools such as data import/export, data analysis and data archiving. The integration of breeding data with publicly available genomic and genetic data enhances genetic understanding of important traits and maximizes the marker-assisted breeding utility for breeders and allied scientists. BIMS incorporates the use of the Android App Field Book, open-source phenotype data collection software for phones and tablets that allows breeders to replace hard copy field books, thus alleviating the possibility of transcription errors while providing faster access to the collected data. BIMS comes with training materials and support for individual or small group training and is currently implemented in the Genome Database for Rosaceae, CottonGEN, the Citrus Genome Database, the Pulse Crop Database, and the Genome Database for Vaccinium. Database URLs: (https://www.rosaceae.org/), (https://www.cottongen.org/), (https://www.citrusgenomedb.org/), (https://www.pulsedb.org/) and (https://www.vaccinium.org/)., (© The Author(s) 2021. Published by Oxford University Press.)
- Published
- 2021
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6. Neural and behavioral traces of error awareness.
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Kirschner H, Humann J, Derrfuss J, Danielmeier C, and Ullsperger M
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- Awareness, Humans, Mental Processes, Psychomotor Performance, Reaction Time, Electroencephalography, Evoked Potentials
- Abstract
Monitoring for errors and behavioral adjustments after errors are essential for daily life. A question that has not been addressed systematically yet, is whether consciously perceived errors lead to different behavioral adjustments compared to unperceived errors. Our goal was to develop a task that would enable us to study different commonly observed neural correlates of error processing and post-error adjustments in their relation to error awareness and accuracy confidence in a single experiment. We assessed performance in a new number judgement error awareness task in 70 participants. We used multiple, robust, single-trial EEG regressions to investigate the link between neural correlates of error processing (e.g., error-related negativity (ERN) and error positivity (Pe)) and error awareness. We found that only aware errors had a slowing effect on reaction times in consecutive trials, but this slowing was not accompanied by post-error increases in accuracy. On a neural level, error awareness and confidence had a modulating effect on both the ERN and Pe, whereby the Pe was most predictive of participants' error awareness. Additionally, we found partial support for a mediating role of error awareness on the coupling between the ERN and behavioral adjustments in the following trial. Our results corroborate previous findings that show both an ERN/Pe and a post-error behavioral adaptation modulation by error awareness. This suggests that conscious error perception can support meta-control processes balancing the recruitment of proactive and reactive control. Furthermore, this study strengthens the role of the Pe as a robust neural index of error awareness.
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- 2021
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7. Tripal MegaSearch: a tool for interactive and customizable query and download of big data.
- Author
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Jung S, Cheng CH, Buble K, Lee T, Humann J, Yu J, Crabb J, Hough H, and Main D
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- Big Data, Genotype, Information Storage and Retrieval, Internet, Software, User-Computer Interface, Databases, Genetic, Genomics
- Abstract
Tripal MegaSearch is a Tripal module for querying and downloading biological data stored in Chado. This module allows site users to select data types, restrict the dataset by applying various filters and then customizing fields to view and download through a single interface. Set by site administrators, example data types include gene, germplasm, marker, map, QTL, genotype, phenotype and expression data. When querying for genes, users can restrict the gene dataset using various filters such as name, chromosome position and functional annotation. They can then customize fields to download, such as name, organism, type, chromosome position, various functional annotations such as BLAST, KEGG, InterPro and GO term. FASTA files can also be downloaded for the sequence data. Site administrators can choose from two different data sources to serve data: Tripal MegaSearch materialized views or Chado tables. If neither data source is desired, administrators may also create their own materialized views and serve them through the flexible dynamic Tripal MegaSearch query form. Tripal MegaSearch is currently implemented in several databases including the Genome Database for Rosaceae www.rosaceae.org and TreeGenes www.https://treegenesdb.org/., (© The Author(s) 2021. Published by Oxford University Press.)
- Published
- 2021
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8. Testosterone modulation of ethanol effects on the µ-opioid receptor kinetics in castrated rats.
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Khalil R and Humann J
- Abstract
The present investigation was conducted to evaluate the effects of testosterone on ethanol-induced alterations of µ-opioid receptor binding kinetics in specific brain regions of castrated rats. Male Sprague Dawley rats (100-124 g) adapted to a 12-h light/dark cycle were used. Animals were castrated under pentobarbital anesthesia. After a recovery period of 14 days, ethanol [3 g/kg as 22.5% solution in saline via intraperitoneal injection (i.p.)], testosterone [2.5 mg in 0.2 ml of olive oil via subcutaneous injection (s.c.) in the dorsal neck region] or the combination of ethanol and testosterone were administered to rats at 9:00 a.m. The control group was injected i.p. with 2 ml saline and s.c. with 0.2 ml olive oil for 7 days. Animals were sacrificed by decapitation at 2 h after the final injection. The brains were immediately removed, and the cortex, hippocampus, hypothalamus and midbrain were dissected. In an attempt to elucidate the mechanism involved in the hormonal modulation of the effects of ethanol and testosterone on the endogenous opioid system, the binding kinetics of the µ-opioid receptors were determined. The results obtained in the present study assisted in identifying the regulatory role of testosterone on ethanol-induced changes on µ-opioid receptor binding kinetics.
- Published
- 2019
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9. 15 years of GDR: New data and functionality in the Genome Database for Rosaceae.
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Jung S, Lee T, Cheng CH, Buble K, Zheng P, Yu J, Humann J, Ficklin SP, Gasic K, Scott K, Frank M, Ru S, Hough H, Evans K, Peace C, Olmstead M, DeVetter LW, McFerson J, Coe M, Wegrzyn JL, Staton ME, Abbott AG, and Main D
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- Computational Biology statistics & numerical data, Gene Expression Profiling methods, Genes, Plant genetics, Information Storage and Retrieval methods, Internet, Plant Breeding methods, Quantitative Trait Loci genetics, Rosaceae classification, Species Specificity, Synteny, Time Factors, User-Computer Interface, Computational Biology methods, Databases, Genetic, Genome, Plant genetics, Genomics methods, Rosaceae genetics
- Abstract
The Genome Database for Rosaceae (GDR, https://www.rosaceae.org) is an integrated web-based community database resource providing access to publicly available genomics, genetics and breeding data and data-mining tools to facilitate basic, translational and applied research in Rosaceae. The volume of data in GDR has increased greatly over the last 5 years. The GDR now houses multiple versions of whole genome assembly and annotation data from 14 species, made available by recent advances in sequencing technology. Annotated and searchable reference transcriptomes, RefTrans, combining peer-reviewed published RNA-Seq as well as EST datasets, are newly available for major crop species. Significantly more quantitative trait loci, genetic maps and markers are available in MapViewer, a new visualization tool that better integrates with other pages in GDR. Pathways can be accessed through the new GDR Cyc Pathways databases, and synteny among the newest genome assemblies from eight species can be viewed through the new synteny browser, SynView. Collated single-nucleotide polymorphism diversity data and phenotypic data from publicly available breeding datasets are integrated with other relevant data. Also, the new Breeding Information Management System allows breeders to upload, manage and analyze their private breeding data within the secure GDR server with an option to release data publicly.
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- 2019
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10. AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture.
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Harper L, Campbell J, Cannon EKS, Jung S, Poelchau M, Walls R, Andorf C, Arnaud E, Berardini TZ, Birkett C, Cannon S, Carson J, Condon B, Cooper L, Dunn N, Elsik CG, Farmer A, Ficklin SP, Grant D, Grau E, Herndon N, Hu ZL, Humann J, Jaiswal P, Jonquet C, Laporte MA, Larmande P, Lazo G, McCarthy F, Menda N, Mungall CJ, Munoz-Torres MC, Naithani S, Nelson R, Nesdill D, Park C, Reecy J, Reiser L, Sanderson LA, Sen TZ, Staton M, Subramaniam S, Tello-Ruiz MK, Unda V, Unni D, Wang L, Ware D, Wegrzyn J, Williams J, Woodhouse M, Yu J, and Main D
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- Breeding, Gene Ontology, Metadata, Surveys and Questionnaires, Agriculture, Databases, Genetic, Genomics
- Abstract
The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require data management plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices.
- Published
- 2018
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11. Extension modules for storage, visualization and querying of genomic, genetic and breeding data in Tripal databases.
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Jung S, Lee T, Cheng CH, Ficklin S, Yu J, Humann J, and Main D
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Tripal is an open-source database platform primarily used for development of genomic, genetic and breeding databases. We report here on the release of the Chado Loader, Chado Data Display and Chado Search modules to extend the functionality of the core Tripal modules. These new extension modules provide additional tools for (1) data loading, (2) customized visualization and (3) advanced search functions for supported data types such as organism, marker, QTL/Mendelian Trait Loci, germplasm, map, project, phenotype, genotype and their respective metadata. The Chado Loader module provides data collection templates in Excel with defined metadata and data loaders with front end forms. The Chado Data Display module contains tools to visualize each data type and the metadata which can be used as is or customized as desired. The Chado Search module provides search and download functionality for the supported data types. Also included are the tools to visualize map and species summary. The use of materialized views in the Chado Search module enables better performance as well as flexibility of data modeling in Chado, allowing existing Tripal databases with different metadata types to utilize the module. These Tripal Extension modules are implemented in the Genome Database for Rosaceae (rosaceae.org), CottonGen (cottongen.org), Citrus Genome Database (citrusgenomedb.org), Genome Database for Vaccinium (vaccinium.org) and the Cool Season Food Legume Database (coolseasonfoodlegume.org). Database URL: https://www.citrusgenomedb.org/, https://www.coolseasonfoodlegume.org/, https://www.cottongen.org/, https://www.rosaceae.org/, https://www.vaccinium.org/., (© The Author(s) 2017. Published by Oxford University Press.)
- Published
- 2017
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12. Soft tissue volume alterations after connective tissue grafting at teeth: the subepithelial autologous connective tissue graft versus a porcine collagen matrix - a pre-clinical volumetric analysis.
- Author
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Schmitt CM, Matta RE, Moest T, Humann J, Gammel L, Neukam FW, and Schlegel KA
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- Animals, Collagen, Dogs, Gingiva, Gingival Recession, Swine, Tooth Root, Connective Tissue
- Abstract
Aim: This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG)., Material and Methods: In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm)., Results: 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3) ± 35.16 mm(3) ) than in the SCTG group (47.65 mm(3) ± 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3) ± 9.26 mm(3) ; CM: 8.67 mm(3) ± 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm ± 0.29 mm (SCTG) and 0.79 mm ± 0.37 mm (CM) with no significant difference., Conclusions: Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
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13. Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior.
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Humann J, Mann B, Gao G, Moresco P, Ramahi J, Loh LN, Farr A, Hu Y, Durick-Eder K, Fillon SA, Smeyne RJ, and Tuomanen EI
- Published
- 2016
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14. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.
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Brown AO, Mann B, Gao G, Hankins JS, Humann J, Giardina J, Faverio P, Restrepo MI, Halade GV, Mortensen EM, Lindsey ML, Hanes M, Happel KI, Nelson S, Bagby GJ, Lorent JA, Cardinal P, Granados R, Esteban A, LeSaux CJ, Tuomanen EI, and Orihuela CJ
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- Adhesins, Bacterial metabolism, Animals, Bacterial Proteins metabolism, Female, Immunization, Interleukin-1beta metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Myocardium immunology, Platelet Membrane Glycoproteins metabolism, Pneumococcal Infections metabolism, Receptors, G-Protein-Coupled metabolism, Receptors, Laminin metabolism, Streptolysins metabolism, Macaca microbiology, Myocardium pathology, Pneumococcal Infections immunology, Pneumococcal Infections microbiology, Streptococcus pneumoniae pathogenicity
- Abstract
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.
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- 2014
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15. A live-attenuated pneumococcal vaccine elicits CD4+ T-cell dependent class switching and provides serotype independent protection against acute otitis media.
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Rosch JW, Iverson AR, Humann J, Mann B, Gao G, Vogel P, Mina M, Murrah KA, Perez AC, Edward Swords W, Tuomanen EI, and McCullers JA
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- Acute Disease, Animals, CD4-Positive T-Lymphocytes cytology, Chinchilla, Disease Models, Animal, Immunoglobulin Class Switching, Immunoglobulin G blood, Mice, Mice, Inbred BALB C, Otitis Media mortality, Otitis Media pathology, Serotyping, Sinusitis microbiology, Sinusitis mortality, Sinusitis prevention & control, Streptococcus pneumoniae metabolism, Survival Rate, Vaccines, Attenuated immunology, Virulence Factors immunology, CD4-Positive T-Lymphocytes immunology, Otitis Media prevention & control, Pneumococcal Vaccines immunology
- Abstract
Acute otitis media (AOM) caused by Streptococcus pneumoniae remains one of the most common infectious diseases worldwide despite widespread vaccination. A major limitation of the currently licensed pneumococcal vaccines is the lack of efficacy against mucosal disease manifestations such as AOM, acute bacterial sinusitis and pneumonia. We sought to generate a novel class of live vaccines that (1) retain all major antigenic virulence proteins yet are fully attenuated and (2) protect against otitis media. A live vaccine candidate based on deletion of the signal recognition pathway component ftsY induced potent, serotype-independent protection against otitis media, sinusitis, pneumonia and invasive pneumococcal disease. Protection was maintained in animals coinfected with influenza virus, but was lost if mice were depleted of CD4(+) T cells at the time of vaccination. The live vaccine induced a strong serum IgG2a and IgG2b response that correlated with CD4(+) T-cell mediated class switching. Deletion of genes required for microbial adaptation to the host environment is a novel live attenuated vaccine strategy yielding the first experimental vaccine effective against pneumococcal otitis media.
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- 2014
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16. First Report of Tomato Pith Necrosis (Pseudomonas corrugata) on Tomato (Solanum lycopersicum) in Washington.
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Powell M, Gundersen B, Miles CA, Humann JL, Schroeder BK, and Inglis DA
- Abstract
Tomato pith necrosis was observed on 2.7% of tomatoes grown in rows covered with black polyethylene, various biodegradable plastics, and an experimental spunbond poly(lactic) acid agricultural mulch in high tunnel and open field experimental plots, in western Washington in 2011. Symptoms developed on 3-month-old plants and progressed acropetally until night temperatures dropped to 10°C. Affected plants had chlorotic leaves, produced adventitious roots, and pith tissue was brown and either corrugated or rotted. Similar symptoms were observed again in 2012 on 2.0% of plants, but only in experimental plots with black polyethylene mulch. Diseased stem tissue was homogenized with a mortar and pestle in sterile water and the extract was streaked onto King's medium B (KMB) agar. Colonies were white and smooth initially, and after 5 days had an irregular surface and margin and produced a tan diffuse pigment. One isolate, Pc.Sl.2011, was gram-negative, grew at 37°C on nutrient broth yeast (NBY) agar, did not fluoresce on KMB (3), and was arginine dihydrolase positive. A partial 16S fragment, 1,387 bp, was obtained via PCR with universal 27f and 1492f primers. The resulting sequence exhibited 99% identity to Pseudomonas corrugata Roberts & Scarlett, and has been assigned GenBank Accession KC812729. Pathogenicity of Pc.Sl.2011 was tested in two greenhouse trials with five replications of one tomato plant per treatment. Seeds of 'Celebrity' were surface sterilized by soaking in 70% EtOH for 30 s and then 10% NaOCl for 30 s, then rinsed with sterile water and sown into 14 cm diameter pots filled with non-sterile Sunshine Mix #1 (SunGro Horticulture Distribution Inc., Bellevue, WA). Seedlings were inoculated at the four leaf stage using 5 ml NBY broth cultures of Pc.Sl.2011 grown at 28°C for 12 h with agitation. A sterile needle was used to inject 10 μl of either sterile water or a bacterial suspension of 1.0 × 10
10 CFU/ml into the axil of the second true leaf. Inoculum concentration was confirmed by NBY dilution plate counts. The plants were incubated in clear polyethylene bags for 4 days and placed in a greenhouse at 21.1 ± 1.2°C with a 14-h photoperiod. The first and second trials were sampled at 8 and 9 weeks after inoculation, respectively. Plants inoculated with sterile water had green pith tissue. However, 60 and 40% of inoculated plants had brown pith tissue around the inoculation site in the first and second trial, respectively, but wilting and adventitious roots were not observed. Stem tissue from the inoculation site of symptomatic plants was homogenized as above, and the extract streaked onto NBY agar plates. Three isolates recovered from inoculated plants from both trials had the same characteristics as the original isolate, including similar colony morphology, ability to grow on NBY at 37°C, and lack of fluorescence on KMB. To our knowledge, this is the first documented report of tomato pith necrosis in Washington. Pith necrosis has been reported previously in high tunnel tomato production (4), where excess nitrogen fertilization occurs with cool evening temperatures (3), and when plastic mulch is utilized (2). In the cool climate of western Washington, successful tomato production requires the use of agricultural mulches and covers that trap heat. Since P. corrugata has been isolated from soil and the tomato seeds of inoculated plants (1), local growers attempting to manage pith necrosis need to select tomato seed lots carefully and avoid applying excess nitrogen, especially when using plastic mulch. References: (1) V. Catara. Mol. Plant Pathol. 8:233, 2007. (2) E. J. Sikora and W. S. Gazaway. Online. ACES.edu ANR-0797, 2009. (3) C. M. Scarlett and J. T. Fletcher. Ann. Appl. Biol. 88:105, 1978. (4) X. Xu et al. Plant Dis. 97:988, 2013.- Published
- 2013
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17. Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogenes.
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Knowles H, Heizer JW, Li Y, Chapman K, Ogden CA, Andreasen K, Shapland E, Kucera G, Mogan J, Humann J, Lenz LL, Morrison AD, and Perraud AL
- Subjects
- Adjuvants, Immunologic pharmacology, Animals, Cytokines biosynthesis, Female, Immunity, Innate drug effects, Immunity, Innate genetics, Interferon-gamma pharmacology, Interleukin-12 deficiency, Interleukin-12 genetics, Interleukin-12 immunology, Interleukin-12 Receptor beta 2 Subunit deficiency, Interleukin-12 Receptor beta 2 Subunit genetics, Interleukin-12 Receptor beta 2 Subunit immunology, Listeria monocytogenes pathogenicity, Listeriosis immunology, Listeriosis prevention & control, Macrophages immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils immunology, Receptors, Interferon deficiency, Receptors, Interferon genetics, Receptors, Interferon immunology, Recombinant Proteins, TRPM Cation Channels deficiency, TRPM Cation Channels genetics, Interferon gamma Receptor, Immunity, Innate physiology, Listeria monocytogenes immunology, TRPM Cation Channels immunology
- Abstract
The generation of reactive oxygen species (ROS) is inherent to immune responses. ROS are crucially involved in host defense against pathogens by promoting bacterial killing, but also as signaling agents coordinating the production of cytokines. Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable channel gated via binding of ADP-ribose, a metabolite formed under conditions of cellular exposure to ROS. Here, we show that TRPM2-deficient mice are extremely susceptible to infection with Listeria monocytogenes (Lm), exhibiting an inefficient innate immune response. In a comparison with IFNγR-deficient mice, TRPM2(-/-) mice shared similar features of uncontrolled bacterial replication and reduced levels of inducible (i)NOS-expressing monocytes, but had intact IFNγ responsiveness. In contrast, we found that levels of cytokines IL-12 and IFNγ were diminished in TRPM2(-/-) mice following Lm infection, which correlated with their reduced innate activation. Moreover, TRPM2(-/-) mice displayed a higher degree of susceptibility than IL-12-unresponsive mice, and supplementation with recombinant IFNγ was sufficient to reverse the unrestrained bacterial growth and ultimately the lethal phenotype of Lm-infected TRPM2(-/-) mice. The severity of listeriosis we observed in TRPM2(-/-) mice has not been reported for any other ion channel. These findings establish an unsuspected role for ADP-ribose and ROS-mediated cation flux for innate immunity, opening up unique possibilities for immunomodulatory intervention through TRPM2.
- Published
- 2011
- Full Text
- View/download PDF
18. Antagonistic crosstalk between type I and II interferons and increased host susceptibility to bacterial infections.
- Author
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Rayamajhi M, Humann J, Kearney S, Hill KK, and Lenz LL
- Subjects
- Animals, Dendritic Cells immunology, Gene Expression Profiling, Histocompatibility Antigens Class II biosynthesis, Macrophages immunology, Mice, Phosphorylation, Receptors, Interferon biosynthesis, STAT1 Transcription Factor metabolism, Interferon gamma Receptor, Interferon-alpha immunology, Interferon-beta immunology, Interferon-gamma immunology, Listeria monocytogenes immunology, Macrophages microbiology
- Abstract
Type I and II interferons (IFNs αβ and γ) have opposing effects on immune resistance to certain pathogenic bacteria. While IFNγ generally plays a protective role, IFNαβ exacerbates Listeria monocytogenes and Mycobacterium tuberculosis infections. Our findings provided evidence that this increased susceptibility reflects a novel antagonistic cross talk between IFNαβ and IFNγ. Macrophages infected with L. monocytogenes strains that induce IFNαβ production responded poorly to IFNγ, as measured by reduced phosphorylation of STAT1 and reduced IFNγ-dependent gene expression. The impaired responsiveness to IFNγ correlated with reduced expression of its receptor, IFNGR, by both infected and bystander macrophages. Down regulation of IFNGR was dependent on responsiveness to IFNγ and mimicked by recombinant IFNβ. Mice lacking responsiveness to IFNαβ (IFNAR1 (-/-)) retained high IFNGR expression, developed higher expression of MHC-II on macrophages and DCs, and were more resistant to systemic L. monocytogenes infection--but only in the presence of IFNγ. Thus, the ability of IFNαβ to down regulate IFNGR provides an explanation for its ability to reduce responsiveness to IFNγ and to increase host susceptibility to bacterial infection. It remains to be determined whether and how such antagonistic interferon crosstalk benefits the host.
- Published
- 2010
- Full Text
- View/download PDF
19. Activation of naive NK cells in response to Listeria monocytogenes requires IL-18 and contact with infected dendritic cells.
- Author
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Humann J and Lenz LL
- Subjects
- Animals, Bone Marrow Cells immunology, Bone Marrow Cells microbiology, Cells, Cultured, Coculture Techniques, Dendritic Cells microbiology, Female, Interferon-gamma biosynthesis, Killer Cells, Natural metabolism, Killer Cells, Natural microbiology, Listeriosis immunology, Listeriosis microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88 biosynthesis, Myeloid Differentiation Factor 88 deficiency, Myeloid Differentiation Factor 88 physiology, Cell Communication immunology, Dendritic Cells immunology, Interleukin-18 physiology, Killer Cells, Natural immunology, Listeria monocytogenes immunology, Lymphocyte Activation immunology
- Abstract
The mechanisms for NK cell activation during infection by intracellular bacterial pathogens are not clearly defined. To dissect how Listeria monocytogenes infection elicits NK cell activation, we evaluated the requirements for activation of naive splenic NK cells by infected bone marrow-derived dendritic cells (BMDCs). We found that NK cell activation in this setting required infection of BMDCs by live wild type bacteria. NK cells were not activated when BMDCs were infected with a live hemolysin deficient (Deltahly) strain. Neutralization of IL-12, TNF-alpha, or caspase-1 each dramatically reduced NK cell IFN-gamma production in response to live wt L. monocytogenes infection. Addition of recombinant IL-18, but not IL-1beta, reversed the effects of caspase-1 inhibition. Recombinant IL-18 also restored NK cell activation by BMDCs infected with Deltahly L. monocytogenes, which produced IL-12 but not IL-18. IL-18 acted on NK cells because MyD88 expression was required in responding NK cells, but not infected BMDC. However, secreted cytokines were not sufficient for activation of naive NK cells by infected BMDCs. Rather, NK cell activation additionally required contact between infected BMDCs and NK cells. These data suggest that the activation of NK cells during L. monocytogenes infection requires both secreted cytokines and ligation of NK activating receptors during direct contact with infected DCs.
- Published
- 2010
- Full Text
- View/download PDF
20. Induction of IFN-alphabeta enables Listeria monocytogenes to suppress macrophage activation by IFN-gamma.
- Author
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Rayamajhi M, Humann J, Penheiter K, Andreasen K, and Lenz LL
- Subjects
- Animals, Cells, Cultured, Dendritic Cells immunology, Down-Regulation, Female, Immunity, Innate, Interferon Type I immunology, Interferon-gamma immunology, Interferon-gamma pharmacology, Macrophages metabolism, Mice, Receptors, Interferon antagonists & inhibitors, Receptors, Interferon metabolism, Interferon gamma Receptor, Interferon Type I metabolism, Interferon-gamma metabolism, Listeria monocytogenes, Listeriosis immunology, Macrophage Activation drug effects, Macrophages immunology, Macrophages microbiology
- Abstract
Production of type I interferon (IFN; IFN-alphabeta) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-gamma) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-alphabeta and IFN-gamma occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-gamma treatment as a result of down-regulation of the IFN-gamma receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-alphabeta. Accordingly, macrophages and dendritic cells (DCs) showed reduced IFNGR1 expression and reduced responsiveness to IFN-gamma during systemic infection of IFN-alphabeta-responsive mice. Furthermore, the increased resistance of mice lacking the IFN-alphabeta receptor (IFNAR(-/-)) to L. monocytogenes correlated with increased expression of IFN-gamma-dependent activation markers by macrophages and DCs and was reversed by depletion of IFN-gamma. Thus, IFN-alphabeta produced in response to bacterial infection and other stimuli antagonizes the host response to IFN-gamma by down-regulating the IFNGR. Such cross talk permits prioritization of IFN-alphabeta-type immune responses and may contribute to the beneficial effects of IFN-beta in treatment of inflammatory diseases such as multiple sclerosis.
- Published
- 2010
- Full Text
- View/download PDF
21. Bacterial peptidoglycan degrading enzymes and their impact on host muropeptide detection.
- Author
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Humann J and Lenz LL
- Subjects
- Amino Acid Sequence, Animals, Bacteria pathogenicity, Bacterial Infections immunology, Humans, Immunity, Innate, Mice, N-Acetylmuramoyl-L-alanine Amidase chemistry, N-Acetylmuramoyl-L-alanine Amidase immunology, Peptidoglycan metabolism, Protein Structure, Tertiary, Bacteria enzymology, Host-Pathogen Interactions immunology, N-Acetylmuramoyl-L-alanine Amidase metabolism, Peptidoglycan immunology
- Abstract
Peptidoglycan (PGN) is a major component of the bacterial cell envelope in both Gram-positive and Gram-negative bacteria. These muropeptides can be produced or modified by the activity of bacterial glycolytic and peptidolytic enzymes referred to as PGN hydrolases and autolysins. Some of these bacterial enzymes are crucial for bacterial pathogenicity and have been shown to modulate muropeptide release and/or host innate immune responses. The ability of muropeptides to modulate host responses is due to the fact that eukaryotes do not produce PGN and have instead evolved numerous strategies to detect intact PGN and PGN fragments (muropeptides). Here we review the structure of PGN and introduce the various bacterial enzymes known to degrade or modify bacterial PGN. Host factors involved in PGN and muropeptide detection are also briefly discussed, as are examples of how specific bacterial pathogens use PGN degradation and modification to subvert host innate immunity.
- Published
- 2009
- Full Text
- View/download PDF
22. Expression of the p60 autolysin enhances NK cell activation and is required for listeria monocytogenes expansion in IFN-gamma-responsive mice.
- Author
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Humann J, Bjordahl R, Andreasen K, and Lenz LL
- Subjects
- Animals, Bacterial Proteins biosynthesis, Bacterial Proteins genetics, Bone Marrow Cells immunology, Bone Marrow Cells metabolism, Bone Marrow Cells microbiology, Bystander Effect immunology, Gene Expression Regulation, Bacterial immunology, Immunity, Innate genetics, Interferon-gamma biosynthesis, Interleukin-12 biosynthesis, Interleukin-12 immunology, Interleukin-6 biosynthesis, Interleukin-6 immunology, Killer Cells, Natural metabolism, Listeria monocytogenes genetics, Listeria monocytogenes metabolism, Listeria monocytogenes pathogenicity, Listeriosis genetics, Macrophages immunology, Macrophages metabolism, Macrophages microbiology, Mice, Mice, Inbred BALB C, Mice, Knockout, Mutation, N-Acetylmuramoyl-L-alanine Amidase biosynthesis, N-Acetylmuramoyl-L-alanine Amidase genetics, Receptors, Interferon deficiency, Receptors, Interferon immunology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Bacterial Proteins immunology, Interferon-gamma immunology, Killer Cells, Natural immunology, Listeria monocytogenes immunology, Listeriosis immunology, Lymphocyte Activation immunology, N-Acetylmuramoyl-L-alanine Amidase immunology
- Abstract
Both peptidoglycan and muropeptides potently modulate inflammatory and innate immune responses. The secreted Listeria monocytogenes p60 autolysin digests peptidoglycan and promotes bacterial infection in vivo. Here, we report that p60 contributes to bacterial subversion of NK cell activation and innate IFN-gamma production. L. monocytogenes deficient for p60 (Deltap60) competed well for expansion in mice doubly deficient for IFNAR1 and IFN-gammaR1 or singly deficient for IFN-gammaR1, but not in wild-type, IFNAR1(-/-), or TLR2(-/-) mice. The restored competitiveness of p60-deficient bacteria suggested a specific role for p60 in bacterial subversion of IFN-gamma-mediated immune responses, since in vivo expansion of three other mutant L. monocytogenes strains (DeltaActA, DeltaNamA, and DeltaPlcB) was not complemented in IFN-gammaR1(-/-) mice. Bacterial expression of p60 was not required to induce socs1, socs3, and il10 expression in infected mouse bone marrow macrophages but did correlate with enhanced production of IL-6, IL-12p70, and most strikingly IFN-gamma. The primary source of p60-dependent innate IFN-gamma was NK cells, whereas bacterial p60 expression did not significantly alter innate IFN-gamma production by T cells. The mechanism for p60-dependent NK cell stimulation was also indirect, given that treatment with purified p60 protein failed to directly activate NK cells for IFN-gamma production. These data suggest that p60 may act on infected cells to indirectly enhance NK cell activation and increase innate IFN-gamma production, which presumably promotes early bacterial expansion through its immunoregulatory effects on bystander cells. Thus, the simultaneous induction of IFN-gamma production and factors that inhibit IFN-gamma signaling may be a common strategy for misdirection of early antibacterial immunity.
- Published
- 2007
- Full Text
- View/download PDF
23. VirE1-Mediated Resistance to Crown Gall in Transgenic Arabidopsis thaliana.
- Author
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Humann J, Andrews S, and Ream W
- Abstract
ABSTRACT Crown gall disease, caused by Agrobacterium tumefaciens, remains a serious agricultural problem despite current biocontrol methods. Agrobacterium tumefaciens transfers single-stranded DNA (T-strands) into plant cells along with several virulence proteins, including a single-stranded DNA-binding protein (VirE2). In plant cells, T-strands are protected from nucleases and targeted to the nucleus by VirE2, which is essential for efficient transmission (transfer and integration) of T-strands. VirE1 is the secretory chaperone for VirE2; it prevents VirE2 from forming aggregates and from binding the T-strands in bacterial cells. Therefore, we hypothesized that sufficient quantities of VirE1 expressed in plant cells might block T-DNA transmission by preventing VirE2 from binding T-strands. Here we show that root explants from Arabidopsis thaliana plants that expressed virE1 formed 3.5-fold fewer tumors than roots from plants without virE1. Also, this resistance was specific for VirE2-mediated Agrobacterium transformation. Plants that have been genetically altered to resist crown gall may prove more effective than biological control.
- Published
- 2006
- Full Text
- View/download PDF
24. Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens.
- Author
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Liu S, Velez MG, Humann J, Rowland S, Conrad FJ, Halverson R, Torres RM, and Pelanda R
- Subjects
- Age Factors, Alleles, Animals, B-Lymphocytes cytology, B-Lymphocytes metabolism, Binding Sites, Antibody genetics, Cell Differentiation genetics, Cells, Cultured, Hybridomas, Immune Tolerance immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Phosphorylation, Receptors, Antigen, B-Cell metabolism, src-Family Kinases physiology, Autoantibodies physiology, Autoantigens immunology, Autoantigens metabolism, B-Lymphocytes immunology, Cell Differentiation immunology, Gene Rearrangement, B-Lymphocyte immunology, RNA Editing immunology, Receptors, Antigen, B-Cell genetics
- Abstract
Receptor editing is a major B cell tolerance mechanism that operates by secondary Ig gene rearrangements to change the specificity of autoreactive developing B cells. In the 3-83Igi mouse model, receptor editing operates in every autoreactive anti-H-2K(b) B cell, providing a novel receptor without additional cell loss. Despite the efficiency of receptor editing in generating nonautoreactive Ag receptors, we show in this study that this process does not inactivate the autoantibody-encoding gene(s) in every autoreactive B cell. In fact, receptor editing can generate allelically and isotypically included B cells that simultaneously express the original autoreactive and a novel nonautoreactive Ag receptors. Such dual Ab-expressing B cells differentiate into transitional and mature B cells retaining the expression of the autoantibody despite the high avidity interaction between the autoantibody and the self-Ag in this system. Moreover, we find that these high avidity autoreactive B cells retain the autoreactive Ag receptor within the cell as a consequence of autoantigen engagement and through a Src family kinase-dependent process. Finally, anti-H-2K(b) IgM autoantibodies are found in the sera of older 3-83Igi mice, indicating that dual Ab-expressing autoreactive B cells are potentially functional and capable of differentiating into IgM autoantibody-secreting plasma cells under certain circumstances. These results demonstrate that autoreactive B cells reacting with ubiquitous membrane bound autoantigens can bypass mechanisms of central tolerance by coexpressing nonautoreactive Abs. These dual Ab-expressing autoreactive B cells conceal their autoantibodies within the cell manifesting a superficially tolerant phenotype that can be partially overcome to secrete IgM autoantibodies.
- Published
- 2005
- Full Text
- View/download PDF
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