Increased Production of Outer Membrane Vesicles by Salmonella Interferes with Complement-Mediated Innate Immune Attack

Bacterial outer membrane vesicles (OMVs) enriched with bioactive proteins, toxins, and virulence factors play a critical role in host-pathogen and microbial interactions. The two-component system PhoP-PhoQ (PhoPQ) of Salmonella enterica orchestrates the remodeling of outer membrane lipopolysaccharide (LPS) molecules and concomitantly upregulates OMV production. In this study, we document a novel use of nanoparticle tracking analysis to determine bacterial OMV size and number. Among the PhoPQ-activated genes tested,; pagC; expression had the most significant effect on the upregulation of OMV production. We provide the first evidence that PhoPQ-mediated upregulation of OMV production contributes to bacterial survival by interfering with complement activation. OMVs protected bacteria in a dose-dependent manner, and bacteria were highly susceptible to complement-mediated killing in their absence. OMVs from bacteria expressing PagC bound to complement component C3b in a dose-dependent manner and inactivated it by recruiting complement inhibitor Factor H. As we also found that Factor H binds to PagC, we propose that PagC interferes with complement-mediated killing of Salmonella in the following two steps: first by engaging Factor H, and second, through the production of PagC-enriched OMVs that divert and inactivate the complement away from the bacteria. Since PhoPQ activation occurs intracellularly, the resultant increase in PagC expression and OMV production is suggested to contribute to the local and systemic spread of Salmonella released from dying host cells that supports the infection of new cells.; IMPORTANCE; Bacterial outer membrane vesicles (OMVs) mediate critical bacterium-bacterium and host-microbial interactions that influence pathogenesis through multiple mechanisms, including the elicitation of inflammatory responses, delivery of virulence factors, and enhancement of biofilm formation. As such, there is a growing interest in understanding the underlying mechanisms of OMV production. Recent studies have revealed that OMV biogenesis is a finely tuned physiological process that requires structural organization and selective sorting of outer membrane components into the vesicles. In Salmonella, outer membrane remodeling and OMV production are tightly regulated by its PhoPQ system. In this study, we demonstrate that PhoPQ-regulated OMV production plays a significant role in defense against host innate immune attack. PhoPQ-activated PagC expression recruits the complement inhibitor Factor H and degrades the active C3 component of complement. Our results provide valuable insight into the combination of tools and environmental signals that Salmonella employs to evade complement-mediated lysis, thereby suggesting a strong evolutionary adaptation of this facultative intracellular pathogen to protect itself during its extracellular stage in the host

Investigation of slag formed in the submerged arc welding of the minerals Urals

Dilatometric tests and estimation external and internal surfaces of welded crusts obtained in the process of submerged arc welding of mineral raw materials Urals region are performed. Separation and porosity welding crusts, thermal expansion coefficient of slag and weld metal are investigated.Проведены дилатометрические исследования и оценка внешней и внутренней поверхностей шлаковых корок, полученных в процессе сварки под слоем флюса из минерального сырья Уральского региона. Исследованы отделяемость и пористость сварочных корок, коэффициенты теплового расширения шлака и наплавленного металла

Spatial coupling of particle and fluid models for streamers: where nonlocality matters

Particle models for streamer ionization fronts contain correct electron energy distributions, runaway effects and single electron statistics. Conventional fluid models are computationally much more efficient for large particle numbers, but create too low ionization densities in high fields. To combine their respective advantages, we here show how to couple both models in space. We confirm that the discrepancies between particle and fluid fronts arise from the steep electron density gradients in the leading edge of the fronts. We find the optimal position for the interface between models that minimizes computational effort and reproduces the results of a pure particle model.Comment: 4 pages, 5 figure

Evaluation of ENTLN Performance Characteristics Based on the Ground Truth Natural and Rocket-Triggered Lightning Data Acquired in Florida

The performance characteristics of the Earth Networks Total Lightning Network (ENTLN) were evaluated by using as ground truth natural cloud-to-ground (CG) lightning data acquired at the Lightning Observatory in Gainesville (LOG) and rocket-triggered lightning data obtained at Camp Blanding (CB), Florida, in 2014 and 2015. Two ENTLN processors (data processing algorithms) were evaluated. The old processor (P2014) was put into use in June 2014 and the new one (P2015) has been operational since August 2015. Based on the natural-CG-lightning data set (219 flashes containing 608 strokes), the flash detection efficiency (DE), flash classification accuracy (CA), stroke DE, and stroke CA for the new processor were found to be 99%, 97%, 96%, and 91%, respectively, and the corresponding values for the old processor were 99%, 91%, 97%, and 68%. The stroke DE and stroke CA for first strokes are higher than those for subsequent strokes. Based on the rocket-triggered lightning data set (36 CG flashes containing 175 strokes), the flash DE, flash CA, stroke DE, and stroke CA for the new processor were found to be 100%, 97%, 97%, and 86%, respectively, while the corresponding values for the old processor were 100%, 92%, 97%, and 42%. The median values of location error and absolute peak current estimation error were 215 m and 15% for the new processor, and 205 m and 15% for the old processor. For both natural and triggered CG lightning, strokes with higher peak currents were more likely to be both detected and correctly classified by the ENTLN

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

Atmospheric electrification in dusty, reactive gases in the solar system and beyond

Detailed observations of the solar system planets reveal a wide variety of local atmospheric conditions. Astronomical observations have revealed a variety of extrasolar planets none of which resembles any of the solar system planets in full. Instead, the most massive amongst the extrasolar planets, the gas giants, appear very similar to the class of (young) Brown Dwarfs which are amongst the oldest objects in the universe. Despite of this diversity, solar system planets, extrasolar planets and Brown Dwarfs have broadly similar global temperatures between 300K and 2500K. In consequence, clouds of different chemical species form in their atmospheres. While the details of these clouds differ, the fundamental physical processes are the same. Further to this, all these objects were observed to produce radio and X-ray emission. While both kinds of radiation are well studied on Earth and to a lesser extent on the solar system planets, the occurrence of emission that potentially originate from accelerated electrons on Brown Dwarfs, extrasolar planets and protoplanetary disks is not well understood yet. This paper offers an interdisciplinary view on electrification processes and their feedback on their hosting environment in meteorology, volcanology, planetology and research on extrasolar planets and planet formation