The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.
SUMMARY Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are pre-marked by the poised or active enhancer mark H3K4Me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages.
Objective The National Institutes of Health (NIH) spend billions of dollars annually on biomedical research. A crucial, yet currently insufficient step is the translation of scientific evidence-based guidelines and recommendations into constructs and language accessible to every-day patients and community members. By building a community of solution that integrates primary care with public health and community-based organizations, evidence-based medical care can be translated into language and constructs accessible to community members and readily implemented to improve health. Methods Using a community-based participatory research approach, the High Plains Research Network (HPRN) and its Community Advisory Council developed a multi-component process to translate evidence into messages and dissemination methods to improve health in rural Colorado. This process, called Boot Camp Translation has brought together various community members, organizations, and primary care to build a community of solution to address local health problems. Results The HPRN has conducted 4 Boot Camp Translations on topics including colon cancer prevention, asthma diagnosis and management, hypertension treatment and management, and the patient-centered medical home. Each Boot Camp follows a standard agenda that requires flexibility and creativity. Thus far, the HPRN has used Boot Camp Translation to engage over a thousand rural community members and providers. Dissemination of Boot Camp messaging through the community of solution has led to increased colon cancer screening, improved care for asthma, and increased rates of controlled blood pressure. Conclusions Boot Camp translation successfully engages community members in a process to translate evidence-based medical care into locally relevant, culturally appropriate language and constructs. Boot Camp Translation is an appropriate method for engaging community members in patient-centered outcomes research. Boot Camp Translation may be an appropriate first step in building a local or regional community of solution aimed at improving health of the community.
The study of facial growth is explored in many fields of science, including anatomy, genetics, and forensics. In the field of forensics, it acts as a valuable tool for combating child pornography. The present research proposes a new method, based on relative measurements and fixed references of the human face—specifically considering measurements of the diameter of the iris (iris ratio)—for the analysis of facial growth in association with age in children and sub-adults. The experimental sample consisted of digital photographs of 1000 Brazilian subjects, aged between 6 and 22 years, distributed equally by sex and divided into five specific age groups (6, 10, 14, 18, and 22 year olds ± one month). The software package SAFF-2D® (Forensic Facial Analysis System, Brazilian Federal Police, Brazil) was used for positioning 11 landmarks on the images. Ten measurements were calculated and used as fixed references to evaluate the growth of the other measurements for each age group, as well the accumulated growth (6–22 years old). The Intraclass Correlation Coefficient (ICC) was applied for the evaluation of intra-examiner and inter-examiner reliability within a specific set of images. Pearson’s Correlation Coefficient was used to assess the association between each measurement taken and the respective age groups. ANOVA and Post-hoc Tukey tests were used to search for statistical differences between the age groups. The outcomes indicated that facial structures grow with different timing in children and adolescents. Moreover, the growth allometry expressed in this study may be used to understand what structures have more or less proportional variation in function for the age ranges studied. The diameter of the iris was found to be the most stable measurement compared to the others and represented the best cephalometric measurement as a fixed reference for facial growth ratios (or indices). The method described shows promising potential for forensic applications, especially as part of the armamentarium against crimes involving child pornography and child abuse.
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