Nasal immunization with the c-terminal domain of bcla3 induced specific igg production and attenuated disease symptoms in mice infected with clostridioides difficile spores

Clostridioides difficile is a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance an immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets for new therapies. In this context, spore surface proteins of C. difficile, are potential antigens for the development of vaccines targeting C. difficile spores. Here, we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced in Escherichia coli and tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTD was also exposed on the surface of B. subtilis spores, a mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTD induced antibody production in mice and attenuated some C. difficile infection symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization routes need to be optimized, our results suggest BclA3CTD as a potentially effective antigen to develop a new vaccination strategy targeting C. difficile spores

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

Indexación: Web of Science; Scopus; Scielo.Background: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3). Results: As a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents. Conclusions: Our results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0241-

Stability in community-acquired pneumonia: one step forward with markers?

Background: Biological markers as an expression of systemic inflammation have been recognised as useful for evaluating the host response in community-acquired pneumonia (CAP). The objective of this study was to evaluate whether the biological markers procalcitonin (PCT) and C-reactive protein (CRP) might reflect stability after 72 h of treatment and the absence of subsequent severe complications. Methods: A prospective cohort study was performed in 394 hospitalised patients with CAP. Clinical stability was evaluated using modified Halm's criteria: temperature (37.2uC; heart rate (100 beats/min; respiratory rate (24 breaths/min; systolic blood pressure >90 mm Hg; oxygen saturation >90%; or arterial oxygen tension >60 mm Hg. PCT and CRP levels were measured on day 1 and after 72 h. Severe complications were defined as mechanical ventilation, shock and/or intensive care unit (ICU) admission, or death after 72 h of treatment. Results: 220 patients achieved clinical stability at 72 h and had significantly lower levels of CRP (4.2 vs 7 mg/dl) and of PCT (0.33 vs 0.48 ng/ml). Regression logistic analyses were performed to calculate several areas under the ROC curve (AUC) to predict severe complications. The AUC for clinical stability was 0.77, 0.84 when CRP was added (p=0.059) and 0.77 when PCT was added (p=0.45). When clinical stability was achieved within 72 h and marker levels were below the cut-off points (0.25 ng/ml for PCT and 3 mg/dl for CRP), no severe complications occurred. Conclusions: Low levels of CRP and PCT at 72 h in addition to clinical criteria might improve the prediction of absence of severe complications

Analysis of the invasion of water lilies (Eichhornia crassipes (Mart) Solms) in the Cointzio dam, Michoacán, Mexico

Objective: to analyze the growth dynamics of the water lily (Eichhornia crassipes) in the Cointzio dam due to the availability of water. Design/Methodology/Approach: a monthly series of 45 Sentinel 2 and Landsat satellite images was used, with which the percentage of invasion of the water lily in the total area of the reservoir was calculated. The relative coverage of the lily was analyzed looking for growth patterns over time, as well as precipitation data, total reservoir area over time, and water storage data in the 2010-2020 period to broaden the context. Results: Three ascending and two descending patterns of the water lily cover were identified; a 15-month upward growth pattern with slight inland slope changes; decreasing patterns are associated with decreased storage. The largest lily covers were found in critical storage stages during the 2010-2020 period. Study limitations/implications: faced with climate change conditions, the filling pattern of the dam could change, aggravating problems related to water supply. Conclusions: containment/mitigation efforts have a reduced effect because the lily recovers the covered area easily, growing about 400% between October 2017 and June 2018, so it is necessary to implement a containment strategy using the biophysical interactions of the basin in conjunction with social, political, economic and governance interactions.Objective: to analyze the growth dynamics of the water lily (Eichhornia crassipes)in the Cointzio dam due to the water availability.Design/Methodology/Approach: a monthly series of 45 Sentinel 2 and Landsatsatellite images were used, with which the percentage of invasion of the water lilyin the total area of the reservoir was calculated. The relative coverage of the lilywas analyzed looking for growth patterns over time, as well as the precipitationdata, total reservoir area over time, and water storage data for the 2010-2020period to broaden its context.Results: Three ascending and two descending patterns of the water lily coveragewere identified; a 15-month upward growth pattern with slight inland slope changes; decreasing patterns are associated with decreased water storage. Thelargest lily covers were found in critical storage stages during the 2010-2020period.Study limitations/implications: faced with climate change conditions, the fillingpattern of the dam could change, aggravating problems related to the water supply.Conclusions: containment/mitigation efforts have a reduced effect because the lilyeasily recovers the covered area, growing about 400% between October 2017 andJune 2018, therefore it is necessary to implement a containment strategy using thebiophysical interactions of the basin in conjunction with social, political, economicand governance interactions

Nasal immunization with the c-terminal domain of bcla3 induced specific igg production and attenuated disease symptoms in mice infected with clostridioides difficile spores

Indexación: Scopus.Clostridioides difficile is a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance an immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets for new therapies. In this context, spore surface proteins of C. difficile, are potential antigens for the development of vaccines targeting C. difficile spores. Here, we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced in Escherichia coli and tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTD was also exposed on the surface of B. subtilis spores, a mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTD induced antibody production in mice and attenuated some C. difficile infection symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization routes need to be optimized, our results suggest BclA3CTD as a potentially effective antigen to develop a new vaccination strategy targeting C. difficile spores. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/1422-0067/21/18/669

A High Statistics Measurement of the Lambdac+ Lifetime

A high statistics measurement of the Lambdac+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat.) +/- 2.5 (syst.) fs from 8034 +/- 122 Lambdac -> pKpi decays represents a significant improvement over the present world average.Comment: Submitted to Physical Review Letter

Search for CP Violation in the decays D+ -> K_S pi+ and D+ -> K_S K+

A high statistics sample of photo-produced charm from the FOCUS(E831) experiment at Fermilab has been used to search for direct CP violation in the decays D+->K_S pi+ and D+ -> K_S K+. We have measured the following asymmetry parameters relative to D+->K-pi+pi+: A_CP(K_S pi+) = (-1.6 +/- 1.5 +/- 0.9)%, A_CP(K_S K+) = (+6.9 +/- 6.0 +/- 1.5)% and A_CP(K_S K+) = (+7.1 +/- 6.1 +/- 1.2)% relative to D+->K_S pi+. The first errors quoted are statistical and the second are systematic. We also measure the relative branching ratios: \Gamma(D+->\bar{K0}pi+)/\Gamma(D+->K-pi+pi+) = (30.60 +/- 0.46 +/- 0.32)%, \Gamma(D+->\bar{K0}K+)/\Gamma(D+->K-pi+pi+) = (6.04 +/- 0.35 +/- 0.30)% and \Gamma(D+->\bar{K0}K+)/\Gamma(D+->\bar{K0}pi+) = (19.96 +/- 1.19 +/- 0.96)%.Comment: 4 pages, 3 figure

A Measurement of the Ds+ Lifetime

A high statistics measurement of the Ds+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, Ds+ -> phi(1020)pi+ and Ds+ -> \bar{K}*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5 (stat.) +/- 5.1 (syst.) fs using 8961 +/- 105 Ds+ -> phi(1020)pi+ and 4680 +/- 90 Ds+ -> \bar{K}*(892)0K+ decays. This is a significant improvement over the present world average.Comment: 5 pages, 3 figures, 2 tables, submitted to PR