Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells.

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation

Asphalt Crack Treatment FAQs and Technical Resources

Crack treatment is one of the most used pavement preservation practices and although the technique is simple, there are several nuances that make it more of an art than science. The purpose of this document is to provide: \u2022 An overview of crack treatment, \u2022 Guidance on several FAQs, and \u2022 A high-level summary of several technical resources. Crack sealing is an important preventive treatment in a pavement preservation program to extend a pavement\u2019s serviceable life. Many factors go into determining \u201cif\u201d and \u201chow to\u201d best implement a crack treatment program. The following information is a compilation of synthesizing several technical documents and interviews with some local technical/industry representatives. Although much of this information is research based, some is anecdotal and/or advice from experienced practitioners. The intent is to provide an overview so agencies can draw their own conclusions on how to best implement a crack treatment program

GATA4 Regulates Epithelial Cell Proliferation to Control Intestinal Growth and Development in MiceSummary

Background & Aims: The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown. Methods: By using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E)9.5 and E18.5. Results: We found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2), cyclin-dependent kinase 6 (Cdk6), and frizzled 5 (Fzd5). Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine. Conclusions: Our data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling. Keywords: Transcriptional Regulation, WNT Signaling, Villus Morphogenesi

Hospital Readmissions

ObjectivesTo evaluate readmission rates and associated factors to identify potentially preventable readmissions.BackgroundThe decision to penalize hospitals for readmissions is compelling health care systems to develop processes to minimize readmissions. Research to identify preventable readmissions is critical to achieve these goals.MethodsWe performed a retrospective review of University HealthSystem Consortium database for cancer patients hospitalized from January 2010 to September 2013. Outcome measures were 7-, 14-, and 30-day readmission rates and readmission diagnoses. Hospital and disease characteristics were evaluated to evaluate relationships with readmission.ResultsA total of 2,517,886 patients were hospitalized for cancer treatment. Readmission rates at 7, 14, and 30 days were 2.2%, 3.7%, and 5.6%, respectively. Despite concern that premature hospital discharge may be associated with increased readmissions, a shorter initial length of stay predicted lower readmission rates. Furthermore, high-volume centers and designated cancer centers had higher readmission rates. Evaluating institutional data (N = 2517 patients) demonstrated that factors associated with higher readmission rates include discharge from a medical service, site of malignancy, and emergency primary admission. When examining readmission within 7 days for surgical services, the most common readmission diagnoses were infectious causes (46.3%), nausea/vomiting/dehydration (26.8%), and pain (6.1%).ConclusionsA minority of patients after hospitalization for cancer-related therapy are readmitted with potentially preventable conditions such as nausea, vomiting, dehydration, and pain. However, most factors associated with readmission cannot be modified. In addition, high-volume centers and designated cancer centers have higher readmission rates, which may indicate that readmission rates may not be an appropriate marker for quality improvement