Brain organoid protocols and limitations.

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends the scope of our understanding of human biology and diseases. Brain organoids especially open an opportunity for human brain research and modeling many human neurological diseases, which have lagged due to the inaccessibility of human brain samples and lack of similarity with other animal models. Brain organoids can be generated through various protocols and mimic whole brain or region-specific. To provide an overview of brain organoid technology, we summarize currently available protocols and list several factors to consider before choosing protocols. We also outline the limitations of current protocols and challenges that need to be solved in future investigation of brain development and pathobiology.

Buprenorphine and methadone differentially alter early brain development in human cortical organoids.

Buprenorphine (BUP) and methadone (MTD) are used for medication-assisted treatment (MAT) in opioid use disorder. Although both medications show improved maternal and neonatal outcomes compared with illicit opioid use during pregnancy, BUP has exhibited more favorable outcomes to newborns than MTD. The underlying cellular and molecular mechanisms for the difference between BUP and MTD are largely unknown. Here, we examined the growth and neuronal activity in human cortical organoids (hCOs) exposed to BUP or MTD. We found that the growth of hCOs was significantly restricted in the MTD-treated but not in the BUP-treated hCOs and BUP attenuated the growth-restriction effect of MTD in hCOs. Furthermore, a κ-receptor agonist restricted while an antagonist alleviated the growth-restriction effect of MTD in hCOs. Since BUP is not only a µ-agonist but a κ-antagonist, the prevention of this growth-restriction by BUP is likely due to its κ-receptor-antagonism. In addition, using multielectrode array (MEA) technique, we discovered that both BUP and MTD inhibited neuronal activity in hCOs but BUP showed suppressive effects only at higher concentrations. Furthermore, κ-receptor antagonist nBNI did not prevent the MTD-induced suppression of neuronal activity in hCOs but the NMDA-antagonism of MTD (that BUP lacks) plays a role in the inhibition of neuronal activity. We conclude that, although both MTD and BUP are µ-opioid agonists, a) the additional κ-receptor antagonism of BUP mitigates the MTD-induced growth restriction during neurodevelopment and b) the lack of NMDA antagonism of BUP (in contrast to MTD) induces much less suppressive effect on neural network communications.

Alzheimer's disease like neuropathology in Down syndrome cortical organoids.

Introduction: Down syndrome (DS) is a genetic disorder with an extra copy of chromosome 21 and DS remains one of the most common causes of intellectual disabilities in humans. All DS patients have Alzheimer's disease (AD)-like neuropathological changes including accumulation of plaques and tangles by their 40s, much earlier than the onset of such neuropathological changes in AD patients. Due to the lack of human samples and appropriate techniques, our understanding of DS neuropathology during brain development or before the clinical onset of the disease remains largely unexplored at the cellular and molecular levels. Methods: We used induced pluripotent stem cell (iPSC) and iPSC-derived 3D cortical organoids to model Alzheimer's disease in Down syndrome and explore the earliest cellular and molecular changes during DS fetal brain development. Results: We report that DS iPSCs have a decreased growth rate than control iPSCs due to a decreased cell proliferation. DS iPSC-derived cortical organoids have a much higher immunoreactivity of amyloid beta (Aß) antibodies and a significantly higher amount of amyloid plaques than control organoids. Although Elisa results did not detect a difference of Aß40 and Aß42 level between the two groups, the ratio of Aß42/Aß40 in the detergent-insoluble fraction of DS organoids was significantly higher than control organoids. Furthermore, an increased Tau phosphorylation (pTau S396) in DS organoids was confirmed by immunostaining and Western blot. Elisa data demonstrated that the ratio of insoluble Tau/total Tau in DS organoids was significantly higher than control organoids. Conclusion: DS iPSC-derived cortical organoids mimic AD-like pathophysiologyical phenotype in vitro, including abnormal Aß and insoluble Tau accumulation. The molecular neuropathologic signature of AD is present in DS much earlier than predicted, even in early fetal brain development, illustrating the notion that brain organoids maybe a good model to study early neurodegenerative conditions.

Informational advantages in social networks: The core-periphery divide in peer performance ratings.

Organizations frequently rely on peer performance ratings to capture employees' unique and difficult to observe contributions at work. Though useful, peers exhibit meaningful variance in the accuracy and informational utility they offer about ratees. In this research, we develop and test theory which suggests that raters' social network positions explains this variance in systematic ways. Drawing from information processing theory, we posit that members who occupy core (peripheral) positions in the network have greater (less) access to firsthand and secondhand performance information about ratees, which is in turn associated with more (less) accurate performance ratings. To overcome difficulties in obtaining a "true" performance score in interdependent field settings, we employ an external criterion comparison method to benchmark our arguments, such that larger validity coefficients between established predictors of performance (i.e., a ratee's general mental ability [GMA] and conscientiousness) and peer performance ratings should reflect more (less) accurate ratings for core (peripheral) members. In Study 1, we use an organization-wide network in a technology startup company to examine the validity coefficient of a ratee's GMA on performance as rated by central versus peripheral members. In Study 2, we attempt to replicate and extend Study 1's conclusions in team networks using ratee conscientiousness as a benchmark indicator. Findings from both studies generally support the hypotheses that core network members provide distinct, and presumably more accurate, peer performance ratings than peripheral network members. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Not even the past: The joint influence of former leader and new leader during leader succession in the midst of organizational change.

Leader succession often occurs during organizational change processes, but the implications of leader succession, in terms of reactions to the change, rarely have been investigated. Employee attitudes and behaviors during organizational change may be influenced jointly by a former leader who recently has transitioned out of the team and the new leader who recently has transitioned into it. We predict an interaction between former and new leaders' transformational leadership on employees' behavioral resistance to and support for change. On the basis of contrast effect theory, a highly transformational former leader constrains the potential effectiveness of the new leader, but a former leader low in transformational leadership enhances this potential effectiveness. We also propose conditional indirect effects transmitted through commitment to the changing organization. Our research was conducted in a large Chinese hospitality organization that was implementing radical organizational change, during which virtually all aspects of processes and products are changed. We collected a 2-wave multisource data from employees who had recently experienced a leader succession and their newly assigned leaders. On the basis of a final sample of 203 employees from 22 teams, we found empirical support for the proposed interaction effects. The conditional indirect effects were also consistent with our expectations, but the effect on behavioral resistance to change was stronger than the effect on behavioral support for change. (PsycINFO Database Record

Achieving more with less: Extra milers' behavioral influences in teams.

Teams are composed of individual members who collectively contribute to team success. As a result, contemporary team research tends to focus on how team overall properties (e.g., the average of team personality and behavior) affect team processes and effectiveness while overlooking the potential unique influences of specific members on team outcomes. Drawing on minority influence theory (Grant & Patil, 2012), we extend previous teams research by demonstrating that an extra miler (i.e., a team member exhibiting the highest frequency of extra-role behaviors in a team) can influence team processes and, ultimately, team effectiveness beyond the influences of all the other members. Specifically, based on a field study, we report that the extra miler's behavioral influences (i.e., helping and voice) on team monitoring and backup processes and team effectiveness are contingent on his or her network position in the team, such that the member tends to have stronger influence on team outcomes when he or she is in a central position. We also find that even a single extra miler in a vital position plays a more important role in driving team processes and outcomes than do all the other members. Therefore, our research offers an important contribution to the team literature by demonstrating the disproportionate influences of specific team members on team overall outcomes.