Robust induction of functional astrocytes using NGN2 expression in human pluripotent stem cells.

Emerging evidence of species divergent features of astrocytes coupled with the relative inaccessibility of human brain tissue underscore the utility of human pluripotent stem cell (hPSC) technologies for the generation and study of human astrocytes. However, existing approaches for hPSC-astrocyte generation are typically lengthy or require intermediate purification steps. Here, we establish a rapid and highly scalable method for generating functional human induced astrocytes (hiAs).

Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome.

The intellectual disability (ID) in Down syndrome (DS) is thought to result from a variety of developmental deficits such as alterations in neural progenitor division, neurogenesis, gliogenesis, cortical architecture, and reduced cortical volume. However, the molecular processes underlying these neurodevelopmental changes are still elusive, preventing an understanding of the mechanistic basis of ID in DS. In this study, we used a pair of isogenic (trisomic and euploid) induced pluripotent stem cell (iPSC) lines to generate cortical spheroids (CS) that model the impact of trisomy 21 on brain development.

Neurodevelopment in Down syndrome: Concordance in humans and models.

Great strides have been made over the past 30 years in understanding the neurodevelopmental changes underlying the intellectual disability (ID) in Down syndrome (DS). Detailed studies of human tissue coupled with findings from rodent and induced pluripotent stem cells (iPSCs) model systems have uncovered the changes in neurogenesis, synaptic connectivity, and myelination that drive the anatomical and physiological changes resulting in the disability. However, there remain significant conflicting data between human studies and the models.

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs With Trisomy 21.

The intellectual disability found in people with Down syndrome is associated with numerous changes in early brain development, including the proliferation and differentiation of neural progenitor cells (NPCs) and the formation and maintenance of myelin in the brain. To study how early neural precursors are affected by trisomy 21, we differentiated two isogenic lines of induced pluripotent stem cells derived from people with Down syndrome into brain-like and spinal cord-like NPCs and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.

DNA templates with blocked long 3' end single-stranded overhangs (BL3SSO) promote bona fide Cas9-stimulated homology-directed repair of long transgenes into endogenous gene loci.

Knock-in of large transgenes by Cas9-mediated homology-directed repair (HDR) is an extremely inefficient process. Although the use of single-stranded oligonucleotides (ssODN) as an HDR donor has improved the integration of smaller transgenes, they do not support efficient insertion of large DNA sequences. In an effort to gain insights into the mechanism(s) governing the HDR-mediated integration of larger transgenes and to improve the technology, we conducted knock-in experiments targeting the human EMX1 locus and applied rigorous genomic PCR analyses in the human HEK293 cell line.

Longitudinal neuroanatomical and behavioral analyses show phenotypic drift and variability in the Ts65Dn mouse model of Down syndrome.

Mouse models of Down syndrome (DS) have been invaluable tools for advancing knowledge of the underlying mechanisms of intellectual disability in people with DS. The Ts(17)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with DS, including neuroanatomical changes and impaired learning and memory. In this study, we use rigorous metrics to evaluate multiple cohorts of Ts65Dn ranging from 2014 to the present, including a stock of animals recovered from embryos frozen within ten generations after the colony was first created in 2010.

Spatiotemporal development of spinal neuronal and glial populations in the Ts65Dn mouse model of Down syndrome.

Background: Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS.

Control of helicase loading in the coupled DNA replication and recombination systems of bacteriophage T4.

The Gp59 protein of bacteriophage T4 promotes DNA replication by loading the replicative helicase, Gp41, onto replication forks and recombination intermediates. Gp59 also blocks DNA synthesis by Gp43 polymerase until Gp41 is loaded, ensuring that synthesis is tightly coupled to unwinding. The distinct polymerase blocking and helicase loading activities of Gp59 likely involve different binding interactions with DNA and protein partners.

Predicting psychological symptoms: the role of perceived thought control ability.

The suppression of intrusive thoughts, which have been related significantly to depressive and anxious symptoms (Blumberg, 2000), has become an area of interest for those treating individuals with psychological disorders. The current study sought to extend the findings of Luciano, Algarabel, Tomas, and Martínez (2005), who developed the Thought Control Ability Questionnaire (TCAQ) and found that scores on this measure were predictive of psychopathology. In particular, this study examined the relationship between scores on the TCAQ and the Personality Assessment Inventory.

The relationship between maternal and paternal psychological symptoms and ratings of adolescent functioning.

Families with an adolescent between the ages of 11 and 18 years participated in a study examining the relationship between parental depressive and anxiety symptomatology and parental ratings of adolescents' functioning. This study indicated that mothers, fathers, and adolescents exhibited significant cross-informant correspondence (i.e.

Childhood discipline, perceptions of parents, and current functioning in female college students.

This study examined the relationships among the childhood discipline styles experienced by 116 female college students, their perceptions of their parents, and their current functioning. Results of this study indicated that female college students' report of childhood discipline, their perceptions of their parents, and their outcomes were related uniquely when examining responses for mothers and fathers. Further, regression analyses suggested that negative perceptions of mothers may mediate the relationship between maternal psychologically assaultive discipline and female college students' depression and self-esteem and mediate partially the relationship between maternal psychologically and physically assaultive discipline and female college students' anxiety.

Retrospective reports of college students' childhood problems.

College students and a subsample of their mothers and fathers participated in a study examining their retrospective reports of childhood emotional and behavioral problems experienced by college students. College students and their mothers and fathers exhibited moderate correspondence in their recollection of internalizing and externalizing problems that college students experienced during their childhood. In contrast, college students tended to endorse significantly greater levels of both internalizing and externalizing problems relative to their mothers and fathers.