Shimmering emerging adulthood: in search of the invariant IDEA model for collectivistic countries.

Emerging adulthood is the youth trajectory characterized by self-focus, identity exploration, feeling between adolescence and adulthood, instability, and experimentation. This trajectory was first identified in industrialized individualistic countries with gender equality and technological progress. To measure transition to adulthood, the Inventory of the Dimensions of Emerging Adulthood (IDEA) was created. Although emerging adulthood is considered universal, adaptations of the questionnaire across the 12 countries show different patterns, and its cross-cultural invariance has been underinvestigated. This study tests IDEA in three collectivistic countries - Armenia, China, and Russia. The sample consisted of 868 students (total male - 152, total female - 716) aged 18 to 29 years old. We tested the questionnaire separately in the three countries to check that this model fits, but we failed to prove it. After that we used a factor-analytic approach to find a common version for the three countries. We got a five-factor correlated model in accordance with the theory, but it was reduced from 31 items to 21, and three items moved to other factors. Finally, we provided measurement invariance and reached configural level. To test the narrower facets of factors we used multi-group alignment and found that variances in six parameters differ, mainly in Instability. Despite the difference in the questionnaire items, we proposed a common model for three countries that we called questionnaire IDEA-collectivistic countries (IDEA-CC).

Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Changes in social norms during the early stages of the COVID-19 pandemic across 43 countries.

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat.

Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis.

The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude the human-specific functional interactions of stem cells with their bone marrow microenvironment. Instead, human mesenchymal cells can be exploited for the in vivo engineering of humanized niches, which confer robust engraftment of human healthy and malignant blood samples. However, mesenchymal cells are associated with major reproducibility issues in tissue formation. Here, we report the fast and standardized generation of human mini-bones by a custom-designed human mesenchymal cell line. These resulting humanized ossicles (hOss) consist of fully mature bone and bone marrow structures hosting a human mesenchymal niche with retained stem cell properties. As compared to mouse bones, we demonstrate superior engraftment of human cord blood hematopoietic cells and primary acute myeloid leukemia samples and also validate hOss as a metastatic site for breast cancer cells. We further report the engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically described osteolytic lesions. Collectively, our human mini-bones constitute a powerful preclinical platform to model bone-developing tumors using patient-derived materials.

Cdc42-Borg4-Septin7 axis regulates HSC polarity and function.

Aging of hematopoietic stem cells (HSCs) is caused by the elevated activity of the small RhoGTPase Cdc42 and an apolar distribution of proteins. Mechanisms by which Cdc42 activity controls polarity of HSCs are not known. Binder of RhoGTPases proteins (Borgs) are known effector proteins of Cdc42 that are able to regulate the cytoskeletal Septin network. Here, we show that Cdc42 interacts with Borg4, which in turn interacts with Septin7 to regulate the polar distribution of Cdc42, Borg4, and Septin7 within HSCs. Genetic deletion of either Borg4 or Septin7 results in a reduced frequency of HSCs polar for Cdc42 or Borg4 or Septin7, a reduced engraftment potential and decreased lymphoid-primed multipotent progenitor (LMPP) frequency in the bone marrow. Taken together, our data identify a Cdc42-Borg4-Septin7 axis essential for the maintenance of polarity within HSCs and for HSC function and provide a rationale for further investigating the role of Borgs and Septins in the regulation of compartmentalization within stem cells.

Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells.

During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the nuclear periphery. Beside X chromosome reactivation resulting in a highly penetrant aging-like hematopoietic malignancy, little is known about XCI in aged hematopoietic stem cells (HSCs). Here, we demonstrate that LaminA/C defines a distinct repressive nuclear compartment for XCI in young HSCs, and its reduction in aged HSCs correlates with an impairment in the overall control of XCI. Integrated omics analyses reveal higher variation in gene expression, global hypomethylation, and significantly increased chromatin accessibility on the X chromosome (Chr X) in aged HSCs. In summary, our data support the role of LaminA/C in the establishment of a special repressive compartment for XCI in HSCs, which is impaired upon aging.

Perceptions of the appropriate response to norm violation in 57 societies.

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate.

Does Culture Mediate the Effect of Promotion/Prevention Regulatory Focus on Subjective Well-Being? Evidence from an Armenian Sample.

Background: Many studies have proven that promotion focus corresponds to the logic of individualistic culture, while prevention focus is characteristic of collectivistic culture. Armenia, as a post-Soviet country, has not been included in cross-cultural studies, since it is not viewed as a typically collectivistic or individualistic society. Objective: To investigate how promotion and prevention regulatory foci can predict subjective well-being, as conditioned by individualistic-collectivistic cultural orientations within Armenian society, and to reveal the links between regulatory focus and subjective well-being within Armenian culture, considering the effect of personality-culture fit. Design: We carried out two studies. In Study 1, regression analysis was conducted to reveal how promotion and prevention foci predicted different aspects of subjective well-being. In Study 2, mediation analysis was conducted to reveal how vertical and horizontal collectivism and individualism mediate the linkage between a promotion or prevention focus, and different aspects of subjective well-being. Results: Regression analysis replicated the findings of other studies, showing that promotion focus has a great predictive role in subjective well-being, while prevention focus neither predicts or obviates different aspects of subjective well-being. Mediation analysis indicated that vertical collectivism had a partially mediating effect on the linkage between promotion and cognitive, emotional, and psychological aspects of subjective well-being. Vertical individualism had a mediating effect on the linkage between prevention and social well-being. Conclusion: Vertical collectivism is a consistent pattern in people experiencing subjective well-being when they behave in a promotion-based way in different settings in the Armenian cultural context.

Development of Humanized Ossicles: Bridging the Hematopoietic Gap.

Ectopic 'humanized ossicles' (hOss) are miniaturized, engineered human bone organs in mice displaying a similar structure and function to native mouse bones. However, they are composed of human mesenchymal derived cells forming a humanized bone marrow niche. This in vivo reconstitution of human skeletal and hematopoietic compartments provides an opportunity to investigate the cellular and molecular processes involved in their establishment and functions in a human setting. However, current hOs strategies vary in their engineering methods and their downstream applications, undermining comprehensive exploitation of their potential. This review describes the specificities of the hOs models and highlights their potential and limits. Ultimately, we propose directions for the development of hOss as a technological platform for human hematopoietic studies.

LaminA/C regulates epigenetic and chromatin architecture changes upon aging of hematopoietic stem cells.

BACKGROUND: The decline of hematopoietic stem cell (HSC) function upon aging contributes to aging-associated immune remodeling and leukemia pathogenesis. Aged HSCs show changes to their epigenome, such as alterations in DNA methylation and histone methylation and acetylation landscapes. We previously showed a correlation between high Cdc42 activity in aged HSCs and the loss of intranuclear epigenetic polarity, or epipolarity, as indicated by the specific distribution of H4K16ac. RESULTS: Here, we show that not all histone modifications display a polar localization and that a reduction in H4K16ac amount and loss of epipolarity are specific to aged HSCs. Increasing the levels of H4K16ac is not sufficient to restore polarity in aged HSCs and the restoration of HSC function. The changes in H4K16ac upon aging and rejuvenation of HSCs are correlated with a change in chromosome 11 architecture and alterations in nuclear volume and shape. Surprisingly, by taking advantage of knockout mouse models, we demonstrate that increased Cdc42 activity levels correlate with the repression of the nuclear envelope protein LaminA/C, which controls chromosome 11 distribution, H4K16ac polarity, and nuclear volume and shape in aged HSCs. CONCLUSIONS: Collectively, our data show that chromatin architecture changes in aged stem cells are reversible by decreasing the levels of Cdc42 activity, revealing an unanticipated way to pharmacologically target LaminA/C expression and revert alterations of the epigenetic architecture in aged HSCs.

The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment.

The spindle assembly checkpoint plays a pivotal role in preventing aneuploidy and transformation. Many studies demonstrate impairment of this checkpoint in cancer cells. While leukemia is frequently driven by transformed hematopoietic stem and progenitor cells (HSPCs), the biology of the spindle assembly checkpoint in such primary cells is not very well understood. Here, we reveal that the checkpoint is fully functional in murine progenitor cells and, to a lesser extent, in hematopoietic stem cells. We show that HSPCs arrest at prometaphase and induce p53-dependent apoptosis upon prolonged treatment with anti-mitotic drugs. Moreover, the checkpoint can be chemically and genetically abrogated, leading to premature exit from mitosis, subsequent enforced G1 arrest, and enhanced levels of chromosomal damage. We finally demonstrate that, upon checkpoint abrogation in HSPCs, hematopoiesis is impaired, manifested by loss of differentiation potential and engraftment ability, indicating a critical role of this checkpoint in HSPCs and hematopoiesis.