Transcription factor induction of vascular blood stem cell niches in vivo.

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

Juvenile incarceration in an adult correctional facility as a risk factor for adolescent childrearing?

INTRODUCTION: Recent trends in reproductive rights have contributed to lasting concerns about adolescent childrearing in American society. Beyond being generally unprepared when raising a child, having a child during adolescence is associated with a variety of environmental, social, and psychological consequences for both the parents and the child. It is important to understand the factors contributing to adolescent childrearing. Although research has identified many factors that contribute to adolescent childrearing, a notable gap remains when considering the role of the correctional system and, in particular, the age-specific effects of confining adolescents in adult correctional facilities. METHODS: The current study examined the age-specific effects of time spent in adult correctional facilities from 13 to 34 years of age on childrearing between 14 and 35 years of age using the National Longitudinal Survey of Youth-1997 (NLSY97). The NLSY97 is a nationally representative sample of Males (51%) and Females (49%) born in the United States. Respondents of the NLSY97 were interviewed about life events beginning at age 7 and continued to participate in the study as recently as 2021. RESULTS: The results of the lagged growth curve models suggest that the time spent incarcerated between 13 and 17 years of age heightens the risk of childrearing between 14 and 18 years of age, an effect that is not observed during adulthood. CONCLUSION: Overall, the results suggest that the conditions adolescents are exposed to during incarceration in an adult correctional facility could contribute to a heightened likelihood of adolescent childrearing.

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development.

The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation.

Dorsal/ventral parcellation of the amygdala: relevance to impulsivity and aggression.

Investigations into the specific association of amygdala volume, a critical aspect of the fronto-limbic emotional circuitry, and aggression have produced results broadly consistent with the 'larger is more powerful' doctrine. However, recent reports suggest that the ventral and dorsal aspects of the amygdala play functionally specific roles, respectively, in the activation and control of behavior. Therefore, parceling amygdala volume into dorsal and ventral components might prove productive in testing hypotheses regarding volumetric association to aggression, and impulsivity, a related aspect of self-control. We sought to test this hypothesis in a group of 41 psychiatric patients who received standard magnetic resonance imaging and a psychometric protocol including aggression and impulsivity measures. Whole amygdala volumes were not associated with aggression or impulsivity, but significant correlations were found when dorsal/ventral amygdalae were analyzed separately. Specifically, left and right ventral amygdala volume was positively associated with motor impulsivity, and left dorsal amygdala was negatively associated with aggression. Results are discussed in terms of an activation and control model of brain-behavior relations. Potential relevance to the continuum of amygdala hyper- to hypo-activation and aggression is discussed.

Prefrontal regional correlates of self-control in male psychiatric patients: Impulsivity facets and aggression.

Investigating the organization of trait aggression and impulsivity in the prefrontal cortex (PFC) advances our understanding of the neuropsychobiology of self-control. While the orbital aspect of the PFC (OFC) has received attention, there is reason to believe the lateral aspect is also relevant. In the current study using magnetic resonance imaging, gray matter volumes in lateral PFC (LPFC) were derived in a heterogeneous male psychiatric sample (N=36) in which OFC volumes had previously been reported. In an analysis using self-report measures of trait impulsivity and aggression, the left LPFC accounted for significant variance in attentional aspects of impulsivity (13%) and aggression (10%) but not motor aspects of impulsivity, as hypothesized. The OFC was associated with motor impulsivity (left-20%; right-14%) and was also more robustly associated with aggression (left-36%; right-16%). A social/emotional information processing model was explored, based upon whether the LPFC or the OFC depended upon one another for their association to trait aggression and impulsivity. It was demonstrated that association of the LPFC to both aggression and attentional impulsivity depended upon the OFC, while the converse was not supported. The LPFC appears relevant to the higher-order aspects of a cortical self-control network, and that relevance is dependent upon the robust contribution of the OFC.

The diagnostic utility of the Rarely Missed Index of the Wechsler Memory Scale-Third Edition in detecting response bias in an adult male incarcerated setting.

The purpose of this study was to utilize a known-group research design to evaluate the diagnostic utility of the Rarely Missed Index (RMI) of the Wechsler Memory Scale-Third Edition [Wechsler, D. (1997). Wechsler Adult Intelligence Test-3rd Edition. San Antonio, TX: The Psychological Corporation] in assessing response bias in an adult male incarcerated setting. Archival data from a sample of 60 adult male inmates who presented for neuropsychological testing were reviewed. Evaluees were assigned to one of two groups; probable malingerers (PM; n=30) and a group of valid test responders (n=30) (1999). Using the recommended cut-off score of 136 or less, the sensitivity of the RMI was extremely low at 33%. Its specificity was 83%. The positive predictive power of the RMI with the published base rate of 22.8 was 38%; with a negative predictive power of 81%. The positive predictive power of the RMI with a published base rate of 70.5 was 82%. The negative predictive power using a base rate of 70.5% was 34%. Results of the receiver operating characteristics (ROC) analysis indicated that the RMI score with a cut-off 136 or less performed only slightly better than chance in delineating probable malingerers from valid responders in this setting. Overall, the findings suggest that the RMI may not be a reliable index for detecting response bias in this setting and perhaps in similar settings.