Modulation of alternative splicing during early infection of human primary B lymphocytes with Epstein-Barr virus (EBV): a novel function for the viral EBNA-LP protein.

Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides-besides transcription-an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP-together with the RBM4 splicing factor-in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.

Epstein-Barr virus inactivates the transcriptome and disrupts the chromatin architecture of its host cell in the first phase of lytic reactivation.

Epstein-Barr virus (EBV), a herpes virus also termed HHV 4 and the first identified human tumor virus, establishes a stable, long-term latent infection in human B cells, its preferred host. Upon induction of EBV's lytic phase, the latently infected cells turn into a virus factory, a process that is governed by EBV. In the lytic, productive phase, all herpes viruses ensure the efficient induction of all lytic viral genes to produce progeny, but certain of these genes also repress the ensuing antiviral responses of the virally infected host cells, regulate their apoptotic death or control the cellular transcriptome. We now find that EBV causes previously unknown massive and global alterations in the chromatin of its host cell upon induction of the viral lytic phase and prior to the onset of viral DNA replication. The viral initiator protein of the lytic cycle, BZLF1, binds to >105 binding sites with different sequence motifs in cellular chromatin in a concentration dependent manner implementing a binary molar switch probably to prevent noise-induced erroneous induction of EBV's lytic phase. Concomitant with DNA binding of BZLF1, silent chromatin opens locally as shown by ATAC-seq experiments, while previously wide-open cellular chromatin becomes inaccessible on a global scale within hours. While viral transcripts increase drastically, the induction of the lytic phase results in a massive reduction of cellular transcripts and a loss of chromatin-chromatin interactions of cellular promoters with their distal regulatory elements as shown in Capture-C experiments. Our data document that EBV's lytic cycle induces discrete early processes that disrupt the architecture of host cellular chromatin and repress the cellular epigenome and transcriptome likely supporting the efficient de novo synthesis of this herpes virus.

Epstein-Barr virus reprograms human B lymphocytes immediately in the prelatent phase of infection.

Epstein-Barr virus (EBV) is a human tumor virus and a model of herpesviral latency. The virus efficiently infects resting human B lymphocytes and induces their continuous proliferation in vitro, which mimics certain aspects of EBV's oncogenic potential in vivo. How lymphoblastoid cell lines (LCLs) evolve from the infected lymphocytes is uncertain. We conducted a systematic time-resolved longitudinal study of cellular functions and transcriptional profiles of newly infected naïve primary B lymphocytes. EBV reprograms the cells comprehensively and globally. Rapid and extensive transcriptional changes occur within 24 h and precede any metabolic and phenotypic changes. Within 72 h, the virus activates the cells, changes their phenotypes with respect to cell size, RNA, and protein content, and induces metabolic pathways to cope with the increased demand for energy, supporting an efficient cell cycle entry on day 3 postinfection. The transcriptional program that EBV initiates consists of 3 waves of clearly discernable clusters of cellular genes that peak on day 2, 3, or 4 and regulate RNA synthesis, metabolic pathways, and cell division, respectively. Upon onset of cell doublings on day 4, the cellular transcriptome appears to be completely reprogrammed to support the proliferating cells, but 3 additional clusters of EBV-regulated genes fine-tune cell signaling, migration, and immune response pathways, eventually. Our study reveals that more than 11,000 genes are regulated upon EBV infection as naïve B cells exit quiescence to enter a germinal center-like differentiation program, which culminates in immortalized, proliferating cells that partially resemble plasmablasts and early plasma cells.

Effectiveness of experimental and commercial pertussis vaccines in the elimination of Bordetella pertussis isolates with different genetic profiles in murine model.

The aim of this study was to compare the elimination of Bordetella pertussis clinical isolates, representing different genotypes in relation to alleles encoding virulence factors (MLST-multi-locus antigen sequence typing), MLVA type (multi-locus variable-number tandem repeat analysis) and PFGE group (pulsed-field gel electrophoresis) from the lungs of naive mice or mice were immunised with the commercial whole-cell pertussis vaccine, the acellular pertussis vaccine and the experimental whole-cell pertussis vaccine. Molecular data indicate that the resurgence of pertussis in populations with high vaccine coverage is associated with genomic adaptation of B. pertussis, to vaccine selection pressure. Pertactin-negative B. pertussis isolates were suspected to contribute to the reduced vaccine effectiveness. It was shown that one of the isolates used is PRN deficient. The mice were intranasally challenged with bacterial suspension containing approximately 5 × 10 7 CFU/ml B. pertussis. The immunogenicity of the tested vaccines against PT (pertussis toxin), PRN (pertactin), FHA (filamentous haemagglutinin) and FIM (fimbriae types 2 and 3) was examined. The commercial whole-cell and acellular pertussis vaccines induced an immunity effective at eliminating the genetically different B. pertussis isolates from the lungs. However, the elimination of the PRN-deficient isolate from the lungs of mice vaccinated with commercial vaccines was delayed as compared to the PRN ( +) isolate, suggesting phenotypic differences with the circulating isolates and vaccine strains. The most effective vaccine was the experimental vaccine with the composition identical to that of the strains used for infection.

An Experiencer, An Animal or An Object? Erection Salience Decreases Men's Perceived Agency.

Three experiments investigated the influence of penile erection on ascriptions of mental capabilities to men. Drawing on sexual objectification literature and the distinction between agency and experience in mind perception, three competing predictions were formulated. The mind redistribution hypothesis assumed that penile erection would lower agency and heighten experience attributions, the animalistic dehumanization hypothesis predicted the decrease in agency, but not experience, and the literal objectification hypothesis implied the simultaneous decrease in both agency and experience. In Experiment 1 (N = 219; 128 females), erection salience lowered agency, but not experience capabilities ascribed to male targets. Experiment 2 (N = 201, 113 females) replicated the negative effect of erection salience on perceived agency (but not experience) and revealed that erection salience lowered intentions to hire a male target. This effect was explained with the loss of perceived agency. Experiment 3 (N = 203, 98 females) verified the causal relationship between penile erection, agency and hiring intentions. Taken together, these results supported the animalistic dehumanization hypothesis.

Is liberal bias universal? An international perspective on social psychologists.

Based on our comparison of political orientation and research interests of social psychologists in capitalist Western countries versus post-Communist Eastern European countries, we suggest that Duarte and colleagues' claim of liberal bias in the field seems American-centric. We propose an alternative account of political biases which focuses on the academic tendency to explain attitudes of lower status groups.

So different yet so alike? Political collective narcissism predicts blatant dehumanization of political outgroups among conservatives and liberals.

Previous research found that political polarization goes hand in hand with being strongly identified with a political ingroup. In this research, we assumed this should be the case only among those who identify with their political ingroup in a narcissistic way (stemming from frustrated needs and predicting outgroup hostility). This hypothesis was tested in one experimental (Study 4, n = 525) and three cross-sectional (Study 1, n = 320; Study 2, n = 316; Study 3, n = 500) studies conducted among American and Polish participants. In all studies, we found a consistent positive link between political narcissism, but not political identification, and the blatant dehumanization of political outgroups. This relationship held over and above metadehumanization, measured in Studies 2 and 3. In Studies 3 and 4, we additionally found that political narcissism may also predict aggressive inclinations towards political outgroups, measured with the voodoo doll task. These findings suggest that differentiation between political narcissism and political identification may help to better understand the psychological underpinnings of political polarization.

A post-Brexit intergroup contact intervention reduces affective polarization between Leavers and Remainers short-term.

With mounting evidence of the harmful societal consequences of affective polarization, it is crucial to find ways of addressing it. Employing a randomized controlled trial, this study tested the effectiveness of an intervention based on theories of intergroup contact and interpersonal communication in reducing affective polarization in the context of Brexit. Participants were 120 UK self-identified Leavers and Remainers. Sixty Leaver-Remainer dyads were randomized to engage in either a facilitated intergroup interaction or a control interaction, which was equivalent in structure and tone but was unrelated to Brexit identities. Different aspects of affective polarization were assessed one month prior, immediately after, and one month after the intervention. Results indicate that the intervention increased warmth toward the outgroup, reduced unfavourable attributions of the sources of outgroup positions, and increased willingness to compromise, but only short-term. There were no statistically significant longer-term effects of the intervention. Evidence of selective attrition further suggests that those with more extreme baseline opinions were more likely to drop out. Our findings highlight the challenges of designing effective interventions that engender enduring attitude change in polarized contexts and of engaging those with extreme political views. This study can provide a useful framework for future research.

Structural damages in adsorbed vaccines affected by freezing.

This study was planned to evaluate structural damages in adsorbed vaccines affected by freezing using scanning electron microscopy and X-ray analysis of the elements. Randomly selected 42 vials of eight different types of WHO pre-qualified adsorbed freeze-sensitive vaccines from 10 manufacturers were included in the study. Vaccines were kept at 5 °C. Selected numbers of vials from each type were then exposed to -25 °C for 24 h periods. All samples were evaluated for their structure using scanning electron microscopy, X-ray analysis of the elements and precipitation time. Scanning electron microscopy of vaccines affected by freezing showed either smooth or rough surfaced conglomerates associated with phosphate content of the precipitate. These vaccines precipitated 2-15 times faster compared to non-frozen samples. Non-frozen samples showed uniform flocculent structure either dense or dispersed. X-ray analysis of precipitates in frozen samples confirmed that the precipitate is mainly aluminium clutters. Scanning electron microscopy confirmed that the lattice structure of bonds between adsorbent and the antigen is broken and aluminium forms conglomerates that grow in size and weight. The precipitation time of vaccines affected by freezing is 4.5 times faster on average compared to non-frozen samples. These facts form the basis of the "shake test".

A vicious circle? Longitudinal relationships between different modes of in-group identity and COVID-19 conspiracy thinking.

Since March 2020, when the World Health Organization declared the spread of COVID-19 a global pandemic, conspiracy theories have continued to rise. This research examines the role of different forms of in-group identity in predicting conspiracy thinking in the context of the coronavirus pandemic. We hypothesized that conspiracy thinking would be predicted positively by national narcissism (i.e., a belief in in-group's greatness which is contingent on its external validation and makes in-group members sensitive to psychological threats) but negatively by secure national identification (i.e., a confidently held ingroup evaluation, which serves as a buffer against psychological threats). In a three-wave longitudinal study conducted on a representative sample of adult Poles (N = 650), conspiracy thinking was positively predicted by national narcissism, but negatively by national identification. Further, we found evidence that conspiracy thinking strengthened national narcissism (but not national identification) over time. Implications for intra- and intergroup processes are discussed.

When the sun goes down: low political knowledge and high national narcissism predict climate change conspiracy beliefs.

The present research empirically examines the links between political knowledge, national narcissism, and climate change conspiracy beliefs. National narcissism (i.e., an unrealistic belief about in-group's greatness which is maladaptive both from the perspective of intra- and inter-group processes) was previously linked to conspiracy beliefs. In this research, we hypothesized that low theoretical political knowledge would boost national narcissism and further lead to adopting climate change conspiracy theories. METHODS: This hypothesis was tested in a two-wave study conducted among Polish participants (N = 558). RESULTS: We found negative effect of political knowledge on climate change conspiracy beliefs. Moreover, national narcissism mediated between theoretical political knowledge and conspiracy beliefs. CONCLUSION: People having low political knowledge are prone to believe in climate change conspiracy theories. Moreover, those less informed about the way political system works in their country are more narcissistically identified with their nation and, thus, deny the climate change.

COVID-19 Vaccines over Three Years after the Outbreak of the COVID-19 Epidemic.

The outbreak of COVID-19 started in December 2019 and spread rapidly all over the world. It became clear that the development of an effective vaccine was the only way to stop the pandemic. It was the first time in the history of infectious diseases that the process of the development of a new vaccine was conducted on such a large scale and accelerated so rapidly. At the end of 2020, the first COVID-19 vaccines were approved for marketing. At the end of March 2023, over three years after the outbreak of the COVID-19 pandemic, 199 vaccines were in pre-clinical development and 183 in clinical development. The candidate vaccines in the clinical phase are based on the following platforms: protein subunit, DNA, RNA, non-replication viral vector, replicating viral vector, inactivated virus, virus-like particles, live attenuated virus, replicating viral vector combined with an antigen-presenting cell, non-replication viral vector combined with an antigen-presenting cell, and bacterial antigen-spore expression vector. Some of the new vaccine platforms have been approved for the first time for human application. This review presents COVID-19 vaccines currently available in the world, procedures for assurance of the quality and safety of the vaccines, the vaccinated population, as well as future perspectives for the new vaccine platforms in drug and therapy development for infectious and non-infectious diseases.

Affective Polarization and Political Belief Systems: The Role of Political Identity and the Content and Structure of Political Beliefs.

We investigate the extent that political identity, political belief content (i.e., attitude stances), and political belief system structure (i.e., relations among attitudes) differences are associated with affective polarization (i.e., viewing ingroup partisans positively and outgroup partisans negatively) in two multinational, cross-sectional studies (Study 1 N = 4,152, Study 2 N = 29,994). First, we found a large, positive association between political identity and group liking-participants liked their ingroup substantially more than their outgroup. Second, political belief system content and structure had opposite associations with group liking: Sharing similar belief system content with an outgroup was associated with more outgroup liking, but similarity with the ingroup was associated with less ingroup liking. The opposite pattern was found for political belief system structure. Thus, affective polarization was greatest when belief system content similarity was low and structure similarity was high.

Anamnestic immunological response profile in laboratory animals after immunization with recombinant hepatitis B vaccines of different generations.

Hepatitis B vaccines containing preS1 and preS2 fragments are assumed to be more immunogenic than those containing SHBs protein alone, which may be of importance for immunization of people with poorly induced or without any immunological response after vaccination. The aim of this study was to evaluate: The following conclusions can be drawn on the basis of obtained results:

Diphtheria-tetanus-pertussis vaccine: past, current & future.

The diphtheria-tetanus-pertussis (DTP) vaccine can prevent diphtheria, tetanus and pertussis. The component antigens of the DTP vaccine had long been monovalent vaccines. The pertussis vaccine was licensed in 1914. The same year, the mixtures of diphtheria toxin and antitoxin were put into use. In 1926, alum-precipitated diphtheria toxoid was registered, and in 1937 adsorbed tetanus toxoid was put on the market. The development of numerous effective DTP vaccines quickly stimulated efforts to combine DTP with other routine vaccines for infants. This overview covers the most important information regarding the invention of DTP vaccines, their modifications and the needs that should be focused on in the future.

Evaluation of precipitation time of the aluminum salts adsorbed potentially frozen vaccines used in the Polish National Immunization Schedule for their pre-qualification before the administration.

Purpose: Vaccines adsorbed on aluminum adjuvants irreversibly lose potency after freezing and their safety is affected. To prevent the administration of such vaccines, the World Health Organization developed the Shake Test designed to determine whether adsorbed vaccines have been frozen or not. However, the Shake Test is difficult and time-consuming when routinely conducted at the place of vaccination. In this study, a modified shake test for prequalification of potentially frozen vaccines was elaborated. Materials and Methods: Vaccines used in the Polish Immunization Schedule were investigated and the analysis includes an assessment of precipitation time and the influence of the container type, amount and type of aluminum compound, and a volume of vaccine dose on the precipitation time. Results: Significant differences between the precipitation time of frozen and non-frozen vaccines routinely used in the Polish Immunization Schedule were observed. The precipitation time of all non-frozen vaccines was above 30 minutes. The longest precipitation time of frozen vaccines was 10 minutes. Conclusion: The finding of the study can be used in practice by the personnel administering vaccines to patients. Step-by-step recommendations for the preparation of the test have been proposed in the article.

Threatened Masculinity: Gender-Related Collective Narcissism Predicts Prejudice Toward Gay and Lesbian People among Heterosexual Men in Poland.

We examined the relationships between different types of in-group positivity and prejudice toward gay and lesbian people among heterosexual men. We assumed that prejudice toward gay and lesbian people among heterosexual men should be predicted by gender-related collective narcissism (i.e., an unrealistic belief about in-group's greatness which is contingent on external validation and extremely sensitive to any signs of threats) and not secure gender in-group identification (i.e., a confidently held in-group evaluation which is independent of the recognition of the group by others and serves as a buffer against threats). Across two studies (final Ns = 212 and 180) we found that gender-related collective narcissism (but not secure gender in-group identification or gender self-esteem) is positively related to prejudice toward gay and lesbian people among heterosexual men. The results of Study 2 demonstrated that this relationship was largely accounted for by the perceived out-group threat.

COVID-19: Why Do People Refuse Vaccination? The Role of Social Identities and Conspiracy Beliefs: Evidence from Nationwide Samples of Polish Adults.

In the present research, we focus on COVID-19 vaccine hesitancy, and empirically examine how different forms of social identity (defensive vs. secure national identity and identification with all humanity) and conspiracy beliefs are associated with COVID-19 vaccine hesitancy. In two cross-sectional nationwide surveys (Study 1, n = 432, and Study 2, n = 807), we found that willingness to vaccinate against COVID-19 was negatively linked to national narcissism, but positively related to a secure national identification, that is, national identification without the narcissistic component. In both studies, we also found that the relationship between narcissistic (vs. secure) national identity and unwillingness to vaccinate against COVID-19 was mediated by COVID-19 vaccine conspiracy beliefs. These effects were present even when we accounted for basic demographics (Studies 1 and 2) and identification with all humanity (Study 2), which had been found to be a significant predictor of health behaviors during COVID-19. In line with previous research, identification with all humanity was positively associated with the willingness to vaccinate against COVID-19. We discuss the implications for understanding the role of the way in which people identify with their national and supranational groups in antiscience attitudes and (mal)adaptive behaviors during COVID-19 pandemic.

From Individual Anxiety to Collective Narcissism? Adult Attachment Styles and Different Types of National Commitment.

National narcissism and national identification, two distinct types of national commitment, differ in terms of their psychological concomitants. Therefore, in the current article, we hypothesized that they would also relate to different adult attachment styles. Namely, we proposed that national narcissism would be positively associated with higher attachment anxiety, while national identification would be associated with lower attachment anxiety and avoidance. These hypotheses were tested in three cross-sectional surveys (Study 1 N = 570; Study 3 N = 558; Study 4 N = 649) and one longitudinal survey (Study 2 N = 808). In all studies, we found a consistent positive relationship between attachment anxiety and national narcissism, and a negative relationship between attachment avoidance and national identification. Finally, we also demonstrated indirect effects of attachment anxiety (via national narcissism) on maladaptive group-related outcomes: conspiracy beliefs, non-normative collective action, and willingness to conspire.

[Number of vaccinations performed and immunological system]. / Liczba wykonanych szczepien a uklad odpornosciowy.

The study did not support the hypothesis of a causal link between vaccinations and chronic diseases and autoimmune diseases. Vaccinations do not weaken the immune system. A man can produce about 10 billion different antibodies. During the lifetime human organism produces from 1 to 100 million different antibodies. Vaccination creates antibodies to about 150 antigens. We describe the capacity of the infant's immune system to respond to vaccines as well as discuss the plausibility of theories that relate vaccines to the development if specific chronic disease.