Prednisolone Targets Claudins in Mouse Brain Blood Vessels

Endothelial cells in brain capillaries are crucial for the function of the blood–brain barrier (BBB), and members of the tight junction protein family of claudins are regarded to be primarily responsible for barrier properties. Thus, the analysis of bioactive substances that can affect the BBB’s permeability is of great importance and may be useful for the development of new therapeutic strategies for brain pathologies. In our study, we tested the hypothesis that the application of the glucocorticoid prednisolone affects the murine blood–brain barrier in vivo. Isolated brain tissue of control and prednisolone-injected mice was examined by employing immunoblotting and confocal laser scanning immunofluorescence microscopy, and the physiological and behavioral effects were analyzed. The control tissue samples revealed the expression of barrier-forming tight junction proteins claudin-1, -3, and -5 and of the paracellular cation and water-channel-forming protein claudin-2. Prednisolone administration for 7 days at doses of 70 mg/kg caused physiological and behavioral effects and downregulated claudin-1 and -3 and the channel-forming claudin-2 without altering their localization in cerebral blood vessels. Changes in the expression of these claudins might have effects on the ionic and acid–base balance in brain tissue, suggesting the relevance of our findings for therapeutic options in disorders such as cerebral edema and psychiatric failure

Predation on Live and Artificial Insect Prey Shows Different Global Latitudinal Patterns

AimLong-standing theory predicts that the intensity of biotic interactions increases from high to low latitudes. Studies addressing geographic variation in predation on insect prey have often relied on prey models, which lack many characteristics of live prey. Our goals were to explore global latitudinal patterns of predator attack rates on standardised live insect prey and to compare the patterns in predation on live insects with those on plasticine prey models.LocationGlobal forested areas.Time Period2021–2023.Major TaxaArthropods, birds.MethodsWe measured predation rates in 43 forested locations distributed across five continents from 34.1° S to 69.5° N latitude. At each location, we exposed 20 sets of three bait types, one set per tree. Each set included three live fly larvae (maggots), three live fly puparia and three plasticine models of the puparia. We used glue rings to isolate half of the sets from non-flying predators.ResultsArthropod attack rates on plasticine prey decreased linearly from low to high latitudes, whereas attack rates on maggots had a U shaped distribution, with the lowest predation rates at temperate latitudes and the highest rates at tropical and boreal latitudes. This difference emerged from intensive predator attacks on live maggots, but not on plasticine models, in boreal sites. Site-specific attack rates of arthropod predators on live and plasticine prey were not correlated. In contrast, bird attack rates on live maggots and plasticine models were positively correlated, but did not show significant latitudinal changes.Main ConclusionsLatitudinal patterns in predation differ between major groups of predators and between types of prey. Poleward decreases in both arthropod and combined arthropod and bird predation on plasticine models do not mirror patterns of predation on our live prey, the latter likely reflecting real patterns of predation risk better than do patterns of attack on artificial prey

SARS-CoV-2-Induced Pathology—Relevance to COVID-19 Pathophysiology

In spite of intensive studies of different aspects of a new coronavirus infection, many issues still remain unclear. In a screening analysis of histopathology in l200 lethal cases, authors succeeded in performing a wide spectrum of immune histochemical reactions (CD2, CD 3, CD 4, CD 5, CD 7, CD 8, CD14, CD 20, CD 31, CD 34, CD 56, CD 57, CD 68, CD 163, collagen 1,3, spike protein SARS-CoV-2, caspase-3, MLCM; ACE2 receptor, occludin, and claudin-1 and -3) and electron microscopy. The results of the histological and IHC studies of deceased people with varying degrees of severity of coronavirus infection confirmed the ability of these pathogens to cause cytoproliferative changes, primarily in epithelial and endothelial cells. Lesions of various organs are possible, while the reasons for significant differences in organotropy remain unclear. Severe respiratory failure in COVID-19 in humans is associated with a very peculiar viral pneumonia. In the pathogenesis of COVID-19, the most important role is played by lesions of the microcirculatory bed, the genesis of which requires further study, but direct viral damage is most likely. Endothelial damage can be associated with both thrombosis in vessels of various calibers, leading to characteristic complications, and the development of DIC syndrome with maximal kidney damage. Such lesions can be the basis of clinically diagnosed septic shock, while usually there are no morphological data in favor of classical sepsis caused by bacteria or fungi. A massive infiltration of the lung tissue and other organs, mainly by T lymphocytes, including those with suppressor properties, makes it necessary to conduct a differential diagnosis between the morphological manifestation of the protective cellular immune response and direct viral lesions but does not exclude the hypothesis of an immunopathological component of pathogenesis. In many of the deceased, even in the absence of clear clinical symptoms, a variety of extrapulmonary lesions were also detected. The mechanism of their development probably has a complex nature: direct lesions associated with the generalization of viral infection and vascular disorders associated with endothelial damage and having an autoimmune nature. Many aspects of the pathogenesis of coronavirus infection require further comprehensive study

Functional Profiling of In Vitro Reactivated Memory B Cells Following Natural SARS-CoV-2 Infection and Gam-COVID-Vac Vaccination

Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions

Functional Profiling of In Vitro Reactivated Memory B Cells Following Natural SARS-CoV-2 Infection and Gam-COVID-Vac Vaccination

Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions

Predation on Live and Artificial Insect Prey Shows Different Global Latitudinal Patterns

International audienceAim Long‐standing theory predicts that the intensity of biotic interactions increases from high to low latitudes. Studies addressing geographic variation in predation on insect prey have often relied on prey models, which lack many characteristics of live prey. Our goals were to explore global latitudinal patterns of predator attack rates on standardised live insect prey and to compare the patterns in predation on live insects with those on plasticine prey models. Location Global forested areas. Time Period 2021–2023. Major Taxa Arthropods, birds. Methods We measured predation rates in 43 forested locations distributed across five continents from 34.1° S to 69.5° N latitude. At each location, we exposed 20 sets of three bait types, one set per tree. Each set included three live fly larvae (maggots), three live fly puparia and three plasticine models of the puparia. We used glue rings to isolate half of the sets from non‐flying predators. Results Arthropod attack rates on plasticine prey decreased linearly from low to high latitudes, whereas attack rates on maggots had a U shaped distribution, with the lowest predation rates at temperate latitudes and the highest rates at tropical and boreal latitudes. This difference emerged from intensive predator attacks on live maggots, but not on plasticine models, in boreal sites. Site‐specific attack rates of arthropod predators on live and plasticine prey were not correlated. In contrast, bird attack rates on live maggots and plasticine models were positively correlated, but did not show significant latitudinal changes. Main Conclusions Latitudinal patterns in predation differ between major groups of predators and between types of prey. Poleward decreases in both arthropod and combined arthropod and bird predation on plasticine models do not mirror patterns of predation on our live prey, the latter likely reflecting real patterns of predation risk better than do patterns of attack on artificial prey