Anderssonkiilerich0331
Mouse embryonic stem cells (ESCs) have played a crucial role in biomedical research where they can be used to elucidate gene function through the generation of genetically modified mice. A critical requirement for the success of this technology is the ability of ESCs to contribute to viable chimaeras with germ-line transmission of the genetically modified allele. We have identified several ESC clones that cause embryonic death of chimaeras at mid to late gestation stages. These clones had a normal karyotype, were pathogen free and their in vitro differentiation potential was not compromised. Chimaeric embryos developed normally up to E13.5 but showed a significant decrease in embryo survival by E17.5 with frequent haemorrhaging. We investigated the relationship between the ESCs transcriptional and epigenomic state and their ability to contribute to viable chimaeras. RNA sequencing identified four genes (Gtl2, Rian, Mirg and Rtl1as) located in the Dlk1-Dio3 imprinted locus that were expressed at lower levels in the compromised ESC clones and this was confirmed by qRT-PCR. Bisulphite sequencing analysis showed significant hypermethylation at the Dlk1-Dio3 imprinted locus with no consistent differences in methylation patterns at other imprinted loci. Treatment of the compromised ESCs with 5-azacytidine reactivated stable expression of Gtl2 and rescued the lethal phenotype but only gave low level chimaeras.Congenital central hypoventilation syndrome (CCHS) is a rare life-threatening condition affecting the autonomic nervous system that usually presents shortly after birth as hypoventilation or central apnea during sleep. In the majority of cases, heterozygous polyalanine expansion mutations within the third exon of the paired-like homeobox 2B (PHOX2B) gene underlie CCHS. Here, we report the generation of two induced pluripotent stem cell (iPSC) lines from two identical twins with a heterozygous PHOX2B expansion mutation (+5 alanine residues). Both generated lines highly express pluripotency markers, can differentiate into the three germ layers, retain the disease-causing mutation and display normal karyotypes.The genotype of apolipoprotein E (APOE) is closely associated with susceptibility to Alzheimer's disease. Here, we described the generation and characterization of human induced pluripotent stem cells from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female patient with Alzheimer's disease having APOE3/4 genotype. The generated iPSCs expressed pluripotent stem cell markers that were observed using immunocytochemistry. Moreover, they displayed a normal karyotype and had the potential to differentiate spontaneously into three germ layers in vitro. Our model could provide valuable insights into pathological mechanisms, and offer a unique opportunity for developing drugs against specific phenotypes for Alzheimer's disease therapy.
The Fostering Connections to Success and Increasing Adoptions Act of 2008 created the option for U.S. states to extend the foster care age limit up to the 21 st birthday. The law provides foster youth extra protections while they transition to adulthood.
To inform states' efforts to better design and implement extended foster care (EFC), we examine the impact of the policy change on length of EFC stay and factors associated with youth's time in EFC.
We use two samples of foster youth in California that extended the foster care age limit to 21 in 2012 37,827 youths who turned 18 between the years 2008 and 2014 and 711 youths who participated in an interview-based panel study.
Leveraging California's child welfare administrative data and California Youth Transitions to Adulthood Study's (CalYOUTH) survey data, we investigated predictors of months youths remained in EFC with linear regression and Cox proportional hazard regression.
Almost half of youth eligible for EFC remained in care until their 21 st birthday. These cohorts stayed in foster care up to 16 months longer (p < .001) than previous cohorts without an EFC option. Multiple individual factors were associated with youths' length of stay in EFC. However, a youth's county of placement made a greater difference on their time in EFC-up to 16 months (p < .05).
Our findings underscore the importance that placement location has on how long youth remain in EFC, and expands our understanding of how county and state context shape EFC participation.
Our findings underscore the importance that placement location has on how long youth remain in EFC, and expands our understanding of how county and state context shape EFC participation.
Approximately one-third of children in residential care are elementary-school aged. Yet, little is known about the subset of younger children in residential care and the nature of these placements.
This study identified latent classes of younger children in residential care and compared the purposes for placement, treatment processes, and outcomes across classes.
The sample included 216 children (ages 5-10) placed in therapeutic residential care.
A three-step latent class model was used to estimate conditional effects of class membership on impairment at discharge, length of stay, and discharge placement. A content analysis of a randomly selected sample of case records from each class was used to explore placement processes.
There were three classes identified (class 1 child welfare/multi-problem families; class 2 mental-health/angry-oppositional; class 3 strong families/attachment). All classes experienced large improvements in functioning. Children in class 3 were in care longer (CI
1.72, 15.48) and experienced greater reductions in impairment (CI
-11.17, -32.06) than class 2. compound library chemical Classes did not differ in rates of discharge to family-based care, however, more children in classes 1 (20.9%) and 3 (21.6%) discharged to group-based placements than class 2 (11.1%). The content analysis revealed similarities in reasons for placement and treatment processes across classes with some distinctions. Service goals were similar across classes and focused on emotional management, social skills, and developing trust.
The results supported individualized approaches to facilitate discharge to stable, family-based care and reduced risks for re-entry and prolonged out-of-home care for younger children.
The results supported individualized approaches to facilitate discharge to stable, family-based care and reduced risks for re-entry and prolonged out-of-home care for younger children.