4,923 research outputs found
A combined approach for comparative exoproteome analysis of Corynebacterium pseudotuberculosis
Background: Bacterial exported proteins represent key components of the host-pathogen interplay. Hence, we
sought to implement a combined approach for characterizing the entire exoproteome of the pathogenic
bacterium Corynebacterium pseudotuberculosis, the etiological agent of caseous lymphadenitis (CLA) in sheep and
goats.
Results: An optimized protocol of three-phase partitioning (TPP) was used to obtain the C. pseudotuberculosis
exoproteins, and a newly introduced method of data-independent MS acquisition (LC-MSE) was employed for
protein identification and label-free quantification. Additionally, the recently developed tool SurfG+ was used for in
silico prediction of sub-cellular localization of the identified proteins. In total, 93 different extracellular proteins of
C. pseudotuberculosis were identified with high confidence by this strategy; 44 proteins were commonly identified
in two different strains, isolated from distinct hosts, then composing a core C. pseudotuberculosis exoproteome.
Analysis with the SurfG+ tool showed that more than 75% (70/93) of the identified proteins could be predicted as
containing signals for active exportation. Moreover, evidence could be found for probable non-classical export of
most of the remaining proteins.
Conclusions: Comparative analyses of the exoproteomes of two C. pseudotuberculosis strains, in addition to
comparison with other experimentally determined corynebacterial exoproteomes, were helpful to gain novel
insights into the contribution of the exported proteins in the virulence of this bacterium. The results presented
here compose the most comprehensive coverage of the exoproteome of a corynebacterial species so far
Pediatric Pulmonary Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Case Report and Review of the Literature
Non-Hodgkinâs lymphoma (NHL) is a common malignancy of childhood; however, a lung primary presentation is an uncommon finding, as is finding an association with the Epstein-Barr virus (EBV). We report the case of a 23-month-old female who developed EBV-associated diffuse large B-cell lymphoma (DLBCL) that was initially thought to be pneumonia. Extensive tissue necrosis, focal angioinvasion, and angiodestruction were observed. She was refractory to various therapy regimens, subsequently developed DLBCL in the central nervous system, and eventually expired. Although EBV+ DLBCL was initially considered to occur predominantly in elderly patients over 50 years of age, it is now increasingly recognized to occur in younger patients with primarily nodal involvement who have overall better prognoses. To our knowledge, this case is the first reported EBV+ DLBCL occurring in a patient below two years of age with lung involvement as the initial clinical presentation
Gravitational waves: search results, data analysis and parameter estimation
The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity
Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment:interim analysis from a phase II clinical trial
BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV(+) individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patientâs HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patientsâ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-Îł) production were measured in CD4(+) and CD8(+) T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+) T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-Îł expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+) T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016) SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-021-00426-z
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