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Abstract Identifying high-affinity antibodies in human serum is challenging due to extremely low number of circulating B cells specific to the desired antigens. Delays caused by a lack of information on the immunogenic proteins of viral origin hamper the development of therapeutic antibodies. We propose an efficient approach allowing for enrichment of high-affinity antibodies against pathogen proteins with simultaneous epitope mapping, even in the absence of structural information about the pathogenic immunogens. To screen therapeutic antibodies from blood of recovered donors, only pathogen transcriptome is required to design an antigen polypeptide library, representing pathogen proteins, exposed on the bacteriophage surface. We developed a two-dimensional screening approach enriching lentiviral immunoglobulin libraries from the convalescent or vaccinated donors against bacteriophage library expressing the overlapping set of polypeptides covering the spike protein of SARS-CoV-2. This platform is suitable for pathogen-specific immunoglobulin enrichment and allows high-throughput selection of therapeutic human antibodies.

IntroductionMarginal zone and follicular B cells are known to contribute to the development of angiotensin II-induced hypertension in mice, but the effector function(s) mediating this effect (e.g., antigen presentation, antibody secretion and/or cytokine production) are unknown. B cell differentiation into antibody secreting cells (ASCs) requires the transcription factor Blimp-1. Here, we studied mice with a Blimp-1 deficiency in follicular B cells to evaluate whether antibody secretion underlies the pro-hypertensive action of B cells.Methods10- to 14-week-old male follicular B cell Blimp-1 knockout (FoB-Blimp-1-KO) and floxed control mice were subcutaneously infused with angiotensin II (0.7 mg/kg/d) or vehicle (0.1% acetic acid in saline) for 28 days. BP was measured by tail-cuff plethysmography or radiotelemetry. Pulse wave velocity was measured by ultrasound. Aortic collagen was quantified by Masson's trichrome staining. Cell types and serum antibodies were quantified by flow cytometry and a bead-based multiplex assay, respectively.ResultsIn control mice, angiotensin II modestly increased serum IgG3 levels and markedly increased BP, cardiac hypertrophy, aortic stiffening and fibrosis. FoB-Blimp-1-KO mice exhibited impaired IgG1, IgG2a and IgG3 production despite having comparable numbers of B cells and ASCs to control mice. Nevertheless, FoB-Blimp-1-KO mice still developed hypertension, cardiac hypertrophy, aortic stiffening and fibrosis following angiotensin II infusion.ConclusionsInhibition of follicular B cell differentiation into ASCs did not protect against angiotensin II-induced hypertension or vascular compliance. Follicular B cell functions independent of their differentiation into ASCs and ability to produce high-affinity antibodies, or other B cell subtypes, are likely to be involved in angiotensin II-induced hypertension.

Abstract JEM-EUSO is an international program for the development of space-based Ultra-High Energy Cosmic Ray observatories. The program consists of a series of missions which are either under development or in the data analysis phase. All instruments are based on a wide-field-of-view telescope, which operates in the near-UV range, designed to detect the fluorescence light emitted by extensive air showers in the atmosphere. We describe the simulation software ESAF in the framework of the JEM-EUSO program and explain the physical assumptions used. We present here the implementation of the JEM-EUSO, POEMMA, K-EUSO, TUS, Mini-EUSO, EUSO-SPB1 and EUSO-TA configurations in ESAF. For the first time ESAF simulation outputs are compared with experimental data.

Objectives Presentation of teachers' opinions on the perception of time and managing their professional tasks during working time. Material and methods The research was of a diagnostic nature, conducted through usage of a diagnostic survey, particularly the Time Methapor questionnaire by Małgorzata Sobol-Kwapińska. Additionally, the respondents answered questions contained in the inventory of teacher’s tasks, developed by the author. Results The assessment of individual time categories by the majority of respondents is in the upper limit of low results, with the exception of the Fast passing of time scale and the Pleasant time subscale, which obtained an average result. The respondents considered most of the given tasks to be urgent and important (44%), followed by tasks that were not urgent and important (25%), urgent and not important (19%), and not urgent and not important (12%). Conclusions Research has shown that teachers experience time calmly and confidently to a small extent, and derive joy and pleasure from it to an average degree. They have a low sense of efficient and creative use of time. They do not see time as an enemy, so they rarely point to its negative aspects. They have a feeling of time passing quickly. Some results suggest that they may have problems achieving goals, planning and organizing their own time. The distribution of tasks included in the Time Management matrix shows that almost half of them were considered urgent and important. This may be due to the fact that these tasks fall into key areas of their work. The obtained results require further research, which may enrich the area of pedeutology with the issue of time as a category and bring closer various solutions in planning professional work and personal development of teachers.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

Abstract The association between constipation and cardiovascular risk is unclear. This population-level matched cohort study compared the association of constipation with hypertension and incident cardiovascular events in 541,172 hospitalized patients aged ≥ 60 years. For each constipation admission, one exact age-matched non-constipated admission was randomly selected from all hospitalizations within 2 weeks to form the comparison cohort. The association of constipation with hypertension and cardiovascular events (myocardial infarction, angina, stroke and transient ischemic attack) were analysed using a series of binary logistic regressions adjusting for age, sex, cardiovascular risk factors, gastrointestinal disorders and sociological factors. Patients with constipation had a higher multivariate-adjusted risk for hypertension (odds ratio [OR], 1.96; 95% confidence interval [CI] 1.94–1.99; P

This article aims to analyze the role of regional economic integration for the economic development of Latin America, taking as a reference the contributions of Celso Furtado. Based on theoretical and empirical (historical) arguments, it is intended to demonstrate that Celso Furtado ́s regarding the integration of Latin American countries involve a complex adequacy of national, economic and political projects, around a regional project.

Protein signatures of unstable and stable atherosclerosis are defined by quantitative proteomics using a preclinical mouse model of plaque instability/rupture.

Tepa sites have oÁen been the focus of archaeological investigations in the lowland areas of Soviet and post- -Soviet Central Asia. is bias frequently led to paying only a lile aention to the surrounding landscape and its potential for the study of historical selement and land use. Moreover, in these environs archaeologists face particularly unfavourable conditions in the landscape, which has been radically transformed by decades of mechanised agriculture and selement growth. e newly launched project of the Czech-Uzbekistani Archaeological Mission aims to answer the challenges of research in the heavily exploited lowlands of southern Uzbekistan and explore the surroundings, supposedly an economic territory, of Khaytabad Tepa, a walled selement occupied between the Achaemenid period and the Middle Ages. For the investigation of various parts of a culturally and physically diverse landscape (village areas, fields, tepa mounds), a flexible methodology was developed, building on an intensive surface survey as the dominant research component to analyse the Khaytabad Tepa surroundings. Given the initial stage of the research, this report focuses on the background, objectives, and methodology of the project and evaluates the 2021 pilot season. e amount and chronological range of collected material point to the great potential of the adopted approach as well as the research area itself. e identified artefact scaers indicate a substantially more complex selement development than has been acknowledged so far: e collected poery assemblages largely correspond to the occupation timespan of the central walled selement. e widespread distribution of Iron Age and Middle Ages material suggests an extensive exploitation of the area in these particular periods.

Objectives The article aims to moot various problems experienced by adolescents brought up in families and local environment prone to social pathologies. What serves as the grounds for discussion herein is the example of Bytom (a Polish city located in Upper Silesia) which, after 1989, was particularly affected by the transformations connected with the political, social and economic changes following the fall of communism. Material and methods In the course of research, the diagnostic study method was applied together with the following instruments: a questionnaire, document analysis, and observation. The survey was conducted among adolescents over the age of 13 and among their teachers in a selected school located in Bytom Results It was established that both the family and local environment affect the process of social adaptation when it comes to adolescents. The following factors can pose a threat to young people’s development: a low standard of living, bad example set by adults, poverty, unemployment, addictions, loosened family bonds, and peer pressure. Conclusions Growing up in dysfunctional environment may lead to a dearth of interests and life aspirations, limited models of spending leisure time, and a lack of authorities. The youth need support of educational and social welfare institutions.

IntroductionDepletion of mature B cells affords protection against experimental hypertension. However, whether B cell-mediated hypertension is dependent on differentiation into antibody-secreting cells (ASCs) remains unclear. Using the proteasome inhibitor, bortezomib, the present study tested the effect of ASC reduction on angiotensin II-induced hypertension.MethodsMale C57BL6/J mice were infused with angiotensin II (0.7 mg/kg/day; s.c.) for 28 days via osmotic minipump to induce hypertension. Normotensive control mice received saline infusion. Bortezomib (750 μg/kg) or vehicle (0.1% DMSO) was administered (i.v.) 3 days prior to minipump implantation, and twice weekly thereafter. Systolic blood pressure was measured weekly using tail-cuff plethysmography. Spleen and bone marrow B1 (CD19+B220−), B2 (B220+CD19+) and ASCs (CD138hiSca-1+Blimp-1+) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay.ResultsBortezomib treatment reduced splenic ASCs by ∼68% and ∼64% compared to vehicle treatment in normotensive (2.00 ± 0.30 vs. 0.64 ± 0.15 × 105 cells; n = 10–11) and hypertensive mice (0.52 ± 0.11 vs. 0.14 ± 0.02 × 105 cells; n = 9–11), respectively. Bone marrow ASCs were also reduced by bortezomib in both normotensive (4.75 ± 1.53 vs. 1.71 ± 0.41 × 103 cells; n = 9–11) and hypertensive mice (4.12 ± 0.82 vs. 0.89 ± 0.18 × 103 cells; n = 9–11). Consistent with ASC reductions, bortezomib reduced serum IgM and IgG2a in all mice. Despite these reductions in ASCs and antibody levels, bortezomib did not affect angiotensin II-induced hypertension over 28 days (vehicle: 182 ± 4 mmHg vs. bortezomib: 177 ± 7 mmHg; n = 9–11).ConclusionReductions in ASCs and circulating IgG2a and IgM did not ameliorate experimental hypertension, suggesting other immunoglobulin isotypes or B cell effector functions may promote angiotensin II-induced hypertension.

Graphical AbstractCardiac fibrosis developed from fibrotic remodelling due to hypertension leads to heart failure. Immune cells are abundantly accumulated in fibrotic regions, but exact mechanisms how they contributed to cardiac fibrosis are not clear. Here we demonstrated that CD8 T cells are major contributor to cardiac fibrosis in hypertensive hearts. Stressed cardiomyocytes express STING-dependent RAE-1 that activates NKG2D + CD8 T cells to induce apoptosis of stressed cardiomyocytes. Preventing STING signalling in stressed cardiomyocytes attenuates cardiac fibrosis. Pharmacologically inhibiting cardiomyocayte-RAE-1 and CD8+ T cell-NKG2D axis may be a potential therapeutic strategy to prevent cardiac fibrosis in HFpEF patients.

Treatment with radioactive iodine (RAI) in women with differenti ated thyroid cancer is associated with decreased serum concentrations of anti-Mülle rian hormone (AMH); however, other markers have not been investigated. Therefore, t his study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the p articipants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatmen t. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the who le group. When we compared serum levels of AMH in younger vs older women separate ly, we observed a significant reduction of this hormone’s serum level after RAI tr eatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significan tly impacts the functional ovarian reserve in premenopausal women with PTC.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS. [ABSTRACT FROM AUTHOR]

The main aim of the study was to diagnose interpersonal skills of professionally active school counselors. The research was diagnostic and descriptive. Interpersonal Competence Questionnaire (ICQ-R), compiled by Waldemar Klinkosz, Justyna Iskra and Magdalena Dawidowicz, was used to collect the research material. A diagnosis of five dimensions of interpersonal competences of counselors, necessary for effective functioning in interpersonal relations was made. They were: initiating relationships, assertive interactions, self-disclosure, and emotional support. The analysis of research results indicates that the surveyed counselors are people who are able to initiate relationships, meet people and conduct conversations with them. In relations with others, they are focused on providing emotional support and self-disclosure; they are able to express their opinions and positions. They deal well with the problems and conflicts that they have to solve in the educational environment. They can emphasize their position on important matters, and enforce their rights and clearly express expectations. Their interpersonal skills predispose them to perform the tasks of a school counselor.

Dihalni premori (ali apnoične atake, pavze, apneje) zaradi nedonošenosti so ena najpogosteje postavljenih diagnoz v neonatalnih intenzivnih enotah. Dihalni premori so prehodne narave in nastanejo zaradi motnje v prilagoditvi dihalnega centra in dihal na zunajmaternično življenje ter nezrelosti receptorjev, ki zaznavajo delne tlake kisika in ogljikovega dioksida. Pomembno podaljšujejo trajanje hospitalizacije ter imajo lahko škodljive dolgoročne posledice. V preglednem prispevku opredeljujemo dihalne premore zaradi nedonošenosti. Predstavljamo klasifikacijo, epidemiologijo, patofiziološko ozadje in nadzorovanje srčno-dihalnih funkcij nedonošenčkov. Opisujemo, kako postaviti diagnozo dihalnih premorov zaradi nedonošenosti, sekundarne vzroke apneje in diferencialnodiagnostične možnosti ter nekatera stanja, ki so povezana z dihalnimi premori zaradi nedonošenosti. Velik del prispevka je namenjen predstavitvi možnih terapevtskih ukrepov, med njimi tudi takih, ki še niso prodrli v splošno klinično prakso, saj so za potrditev njihove učinkovitosti potrebne nadaljnje raziskave. Sklepni del članka ponuja pregled raziskav, v katerih so proučevali genetsko podlago dihalnih premorov zaradi nedonošenosti in predstavitev njihovih rezultatov.

Two types of magnetite nanoparticles: unmodified (Fe3O4 NPs), and modified with poly(sodium acrylate) (Fe3O4/PSA NPs) were synthesized by the co-precipitation method and characterized using different techniques: X-ray diffraction (XRD), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Brunauer–Emmett–Teller (BET) adsorption, Fourier-transform infrared spectroscopy (FTIR). Additionally, magnetic properties and the effect of pH on the zeta potential were analyzed for both types of nanoparticles. Magnetites were used as adsorbents for seven heavy metal ions (Zn(II), Cu(II), Ni(II), Cd(II), Pb(II), Cr(III), Cr(VI)) within the pH range of 3–7. Research revealed nanometric particle sizes, a specific surface area of 140–145 m2/g, and superparamagnetic properties of both tested materials. Moreover, the presence of PSA functional groups in modified magnetite was confirmed, which lowered the pH of the isoelectric point. Both types of magnetite were effective metal ion adsorbents, with metal cations more effectively removed on Fe3O4/PSA NPs and Cr(VI) anions on Fe3O4 NPs. The adsorption of most of the examined cations (performed at pH = 5) can be well described by the Langmuir isotherm model, whereas the adsorption of Cr(VI) ions on modified magnetite correlated better with the Freundlich model. The Dubinin–Radushkevich model confirmed that chemisorption is the predominant process. The adsorption of all metal ions was well-characterized by the pseudo-second-order kinetic model.

Objectives The main aim of the research was to become acquainted with the conditions of work and the tasks of the school counsellor resulting from the psychological and pedagogical help performed at educational facilities. Material and methods The following two methods were used to obtain the research material: the diagnostic survey and assessment. Results The results of quantitative analyses were classified into the following areas: the conditions of work, the school counsellor’s duties, the forms of pedagogical help in their work with the students, parents and teachers, the factors that influence the school counsellor’s model of work and individual features important in the profession of school counsellor. The mentioned analyses indicate that the contemporary counsellor is mainly a woman (the profession is feminised), with higher education, systematically improving and supplementing their knowledge so as to perform the tasks set by the pedagogical supervision and family, school and local environment. Conclusions Thanks to adequate professional preparation and application of a wide range of forms of help for the students, teacher and parents, the school counsellor constitutes a significant link of psychological and pedagogical help performed at the educational facilities.

Gene-drives use CRISPR-Cas9 to be transmitted in a super-Mendelian fashion. Here the authors develop an allelic-drive for selective inheritance of a desired allele.

Artykuł porusza problem zagrożenia wypaleniem zawodowym w środowisku terapeutów zajęciowych pracujących z osobami z niepełnosprawnością intelektualną. Ważny z punktu widzenia różnych dyscyplin naukowych, między innymi pedagogiki specjalnej, psychologii, medycyny czy profilaktyki społecznej. Opisane w artykule badania przeprowadzono w warsztatach terapii zajęciowej, wykorzystując metodę sondażu diagnostycznego i technikę ankiety. Badania pozwoliły na określenie indywidualnych, środowiskowych i organizacyjnych zagrożeń wypaleniem zawodowym. Wskazały na najczęściej występujące składniki wypalenia zawodowego. Nakreśliły kierunki indywidualnych działań zapobiegających zjawisku wypalenia zawodowego.

Bacterial microcompartments are organelle-like structures composed entirely of proteins. They have evolved to carry out several distinct and specialized metabolic functions in a wide variety of bacteria. Their outer shell is constructed from thousands of tessellating protein subunits, encapsulating enzymes that carry out the internal metabolic reactions. The shell proteins are varied, with single, tandem and permuted versions of the PF00936 protein family domain comprising the primary structural component of their polyhedral architecture, which is reminiscent of a viral capsid. While considerable amounts of structural and biophysical data have been generated in the last 15 years, the existing functionalities of current resources have limited our ability to rapidly understand the functional and structural properties of microcompartments (MCPs) and their diversity. In order to make the remarkable structural features of bacterial microcompartments accessible to a broad community of scientists and non-specialists, we developed MCPdb: The Bacterial Microcompartment Database (https://mcpdb.mbi.ucla.edu/). MCPdb is a comprehensive resource that categorizes and organizes known microcompartment protein structures and their larger assemblies. To emphasize the critical roles symmetric assembly and architecture play in microcompartment function, each structure in the MCPdb is validated and annotated with respect to: (1) its predicted natural assembly state (2) tertiary structure and topology and (3) the metabolic compartment type from which it derives. The current database includes 163 structures and is available to the public with the anticipation that it will serve as a growing resource for scientists interested in understanding protein-based metabolic organelles in bacteria.

Several genes of the eut, pdu, and cob/cbi operons are responsible for the metabolism of ethanolamine (EA) and 1,2-propanediol (PD) and are essential during the pathogenic lifecycles of various enteric pathogens. Studies concerning EA and PD metabolism have primarily focused on bacterial genera from the family Enterobacteriaceae, especially the genus Salmonella. Listeria monocytogenes is a member of the Firmicutes phylum and is the causative agent of the rare but highly fatal foodborne disease listeriosis. The eut, pdu, and cob/cbi operons are organized as a single large locus collectively referred to as the cobalamin-dependent gene cluster (CDGC). The CDGC is well conserved in L. monocytogenes; however, functional characterization of the genes in this cluster and how they may contribute to Listeria virulence and stress tolerance in food production environments is highly limited. Previous work suggests that the degradation pathway of PD is essential for L. monocytogenes establishment in the gastrointestinal tract. In contrast, EA metabolism may be more important during intracellular replication. Other studies indicate that the CDGC is utilized when L. monocytogenes is exposed to food and food production relevant stress conditions. Perhaps most noteworthy, L. monocytogenes exhibits attenuated growth at cold temperatures when a key EA utilization pathway gene was deleted. This review aims to summarize the current knowledge of these pathways in L. monocytogenes and their significance in virulence and stress tolerance, especially considering recent developments.

Interaction between B and CD4 T cells is crucial for their optimal responses in adaptive immunity. Immune responses augmented by their partnership promote chronic inflammation. Here we report that interaction between B and CD4 T cells augments their atherogenicity to promote lipid-induced atherosclerosis. Genetic deletion of the gene encoding immunoglobulin mu (μ) heavy chain (μMT) in ApoE−/− mice resulted in global loss of B cells including those in atherosclerotic plaques, undetectable immunoglobulins and impaired germinal center formation. Despite unaffected numbers in the circulation and peripheral lymph nodes, CD4 T cells were also reduced in spleens as were activated and memory CD4 T cells. In hyperlipidemic μMT−/− ApoE−/− mice, B cell deficiency decreased atherosclerotic lesions, accompanied by absence of immunoglobulins and reduced CD4 T cell accumulation in lesions. Adoptive transfer of B cells deficient in either MHCII or co-stimulatory molecule CD40, molecules required for B and CD4 T cell interaction, into B cell-deficient μMT−/− ApoE−/− mice failed to increase atherosclerosis. In contrast, wildtype B cells transferred into μMT−/− ApoE−/− mice increased atherosclerosis and increased CD4 T cells in lesions including activated and memory CD4 T cells. Transferred B cells also increased their expression of atherogenic cytokines IL-1β, TGF-β, MCP-1, M-CSF, and MIF, with partial restoration of germinal centers and plasma immunoglobulins. Our study demonstrates that interaction between B and CD4 T cells utilizing MHCII and CD40 is essential to augment their function to increase atherosclerosis in hyperlipidemic mice. These findings suggest that targeting B cell and CD4 T cell interaction may be a therapeutic strategy to limit atherosclerosis progression.

The propagation of cosmic rays through the heliosphere has been solved for more than half a century by stochastic methods based on Ito’s lemma. This work presents the estimation of statistical error of solution of Fokker–Planck equation by the 1D backward in time stochastic differential equations method. The error dependence on simulation statistics and energy is presented for different combinations of input parameters. The 1% precision criterion in mean value units of intensity standard deviation is defined as a function of solar wind velocity and diffusion coefficient value.

The breastfeeding of infants by mothers who are infected with SARS-CoV-2 has become a dramatic healthcare problem. The WHO recommends that infected women should not abandon breastfeeding; however, there is still the risk of contact transmission. Convalescent donor milk may provide a defense against the aforementioned issue and can eliminate the consequences of artificial feeding. Therefore, it is vital to characterize the epitope-specific immunological landscape of human milk from women who recovered from COVID-19. We carried out a comprehensive ELISA-based analysis of blood serum and human milk from maternity patients who had recovered from COVID-19 at different trimesters of pregnancy. It was found that patients predominantly contained SARS-CoV-2 N-protein-specific immunoglobulins and had manifested the antibodies for all the antigens tested in a protein-specific and time-dependent manner. Women who recovered from COVID-19 at trimester I–II showed a noticeable decrease in the number of milk samples with sIgA specific to the N-protein, linear NTD, and RBD-SD1 epitopes, and showed an increase in samples with RBD conformation-dependent sIgA. S-antigens were found to solely induce a sIgA1 response, whereas N-protein sIgA1 and sIgA2 subclasses were involved in 100% and 33% of cases. Overall, the antibody immunological landscape of convalescent donor milk suggests that it may be a potential defense agent against COVID-19 for infants, conferring them with a passive immunity.