Novel correlative analysis identifies multiple genomic variations impacting ASD with macrocephaly.

Autism spectrum disorders (ASD) display both phenotypic and genetic heterogeneity, impeding the understanding of ASD and development of effective means of diagnosis and potential treatments. Genes affected by genomic variations for ASD converge in dozens of gene ontologies (GOs), but the relationship between the variations at the GO level have not been well elucidated. In the current study, multiple types of genomic variations were mapped to GOs and correlations among GOs were measured in ASD and control samples.

Adipocyte-specific deletion of zinc finger protein 407 results in lipodystrophy and insulin resistance in mice.

PPARγ deficiency in humans and model organisms impairs the transcriptional control of adipogenesis and mature adipocyte function resulting in lipodystrophy and insulin resistance. Zinc finger protein 407 (ZFP407) positively regulates PPARγ target gene expression and insulin-stimulated glucose uptake in cultured adipocytes. The in vivo physiological role of ZFP407 in mature adipocytes, however, remains to be elucidated.

Deletion of the Dishevelled family of genes disrupts anterior-posterior axis specification and selectively prevents mesoderm differentiation.

The Dishevelled proteins transduce both canonical Wnt/β-catenin and non-canonical Wnt/planar cell polarity (PCP) signaling pathways to regulate many key developmental processes during embryogenesis. Here, we disrupt both canonical and non-canonical Wnt pathways by targeting the entire Dishevelled family of genes (Dvl1, Dvl2, and Dvl3) to investigate their functional roles in the early embryo. We identified several defects in anterior-posterior axis specification and mesoderm patterning in Dvl1; Dvl2; Dvl3 embryos.

VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood.

Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells.

Background: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages.

Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema.

Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively.

Factors that influence minority use of high-volume hospitals for colorectal cancer care.

Background: Previous studies suggest that minorities cluster in low-quality hospitals despite living close to better performing hospitals. This may contribute to persistent disparities in cancer outcomes.

Objective: The purpose of this work was to examine how travel distance, insurance status, and neighborhood socioeconomic factors influenced minority underuse of high-volume hospitals for colorectal cancer.

What factors influence minority use of National Cancer Institute-designated cancer centers?

Background: National Cancer Institute (NCI) cancer centers provide high-quality care and are associated with better outcomes. However, racial and ethnic minority populations tend not to use these settings. The current study sought to understand what factors influence minority use of NCI cancer centers.

Do hospitals that serve a high percentage of Medicaid patients perform well on evidence-based guidelines for colon cancer care?

Background: Previous work suggests hospitals serving high percentages of patients with Medicaid are associated with worse colon cancer survival. It is unclear if practice patterns in these settings explain differential outcomes.

Hypothesis: High Medicaid hospitals (HMH) have lower compliance with evidence-based care processes (examining 12 or more lymph nodes (LN) during surgical staging and providing appropriate chemo-therapy).

Adequacy of lymph node examination in colorectal surgery: contribution of the hospital versus the surgeon.

Background: Examination of at least 12 lymph nodes (LNs) in the staging of colon cancer (CC) was recommended by the National Comprehensive Cancer Network in 2000; however, rates of an adequate examination remain low. This study compares the impact of the hospital contextual variance against that of the operating surgeon on delivery of an adequate LN examination.

Study Design: Retrospective analysis of California Cancer Registry data for all CC operations (2001-2006).

Racial and ethnic differences in lymph node examination after colon cancer resection do not completely explain disparities in mortality.

Background: In 1999, a multidisciplinary panel of experts in colorectal cancer reviewed the relevant medical literature and issued a consensus recommendation for a 12-lymph node (LN) minimum examination after resection for colon cancer. Some authors have shown racial/ethnic differences in receipt of this evidence-based care. To date, however, none has investigated the correlation between disparities in LN examination and disparities in outcomes after colon cancer treatment.

Cell-Penetrating Penta-Peptides (CPP5s): Measurement of Cell Entry and Protein-Transduction Activity.

Previously, we developed cell-penetrating penta-peptides (CPP5s). In the present study, VPTLK and KLPVM, two representative CPP5s, were used to characterize the cell-penetration and protein-transduction activities of these small molecules. Various inhibitors of endocytosis and pinocytosis (chlorpromazine, cytochalasin D, Filipin III, amiloride, methyl-β-cyclodextrin, and nocodazole) were tested.