The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells. We show that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling. After isolation, adult Krt1-15-EGFP-positive cells reconstituted all components of the cutaneous epithelium and had a higher proliferative potential than Krt1-15-EGFP-negative cells. Genetic profiling of hair follicle stem cells revealed several known and unknown receptors and signaling pathways important for maintaining the stem cell phenotype. Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair.

Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.

Although the relationship between asthma and exposure to fine particulate matter (PM2.5) has been frequently measured, reported conclusions have not been consistent. As emergency department (ED) visits are an effective way to estimate health outcomes for people with asthma and short-term exposure to PM2.5, this review systematically searched five databases without language or geographical restrictions from inception to January 13, 2015 to study the impact of PM2.5 on asthma ED visits. A random-effects model was used to calculate the pooled risk ratio (RR) and 95% confidence intervals (CI). With respect to short-term effects, asthma ED visits increased at higher PM2.5 concentrations (RR 1.5% per 10 μg/m(3); 95% CI 1.2-1.7%), and children were more susceptible (3.6% per 10 μg/m(3); 95% CI 1.8, 5.3%) than adults (1.7, 95% CI 0.7%, 2.8%) to increased PM2.5; the ED visits increased during the warm season by 3.7% (95% CI 0.5, 6.9%) per 10 μg/m(3) increase in PM2.5, which was higher than the corresponding increase during the cold season (2.6, 95% CI 0.7-4.6%). This demonstrates that ambient PM2.5 has an adverse impact on asthma ED visits after short-term exposure and that children are a high-risk population when PM2.5 concentrations are high, particularly in warm seasons, during which measures should be taken to prevent PM2.5.

Ultra-small gold nanoclusters (Au NCs) are highly promising materials for tumor imaging and therapy because of their low toxicity, intrinsic fluorescence, and the availability of multifunctional groups for covalent linkage of diverse bioactive molecules. Au NCs stabilized by bovine serum albumin (BSA) were prepared via an improved "green" synthetic routine. To ameliorate the selective affinity of Au NCs for high folate receptor (FR) expressing tumors, folic acid (FA) was immobilized on the surface of Au NCs. Subsequently, a near-infrared (NIR) fluorescent dye MPA was conjugated with Au-FA NCs for in vitro and in vivo fluorescence imaging. Similarly, Doxorubicin (DOX), a widely used clinical anticancer drug, was also conjugated to the folate-modified Au NCs to form a prodrug (Au-FA-DOX). Cellular and in vivo acute toxicity studies demonstrated the low toxicity of the Au-FA-MPA to normal cells and tissues. Additionally, in vitro and in vivo study of the dynamic behavior and targeting ability of Au-FA-MPA to different tumors validated the high selective affinity of Au-FA-MPA to FR positive tumors. With regard to the Au-FA-DOX, high anti-tumor activity was displayed by this pro-drug due to the FR mediated uptake. Herein, all of the results supported the potential of using ligand-modified Au NCs for tumor imaging and targeted therapy.

Centromere and kinetochore proteins have a pivotal role in centromere structure, kinetochore formation and sister chromatid separation. However, the molecular architecture and the precise dynamic function of the centromere-kinetochore complex during mitosis remain poorly understood. Here we report the isolation and characterization of human CENP-H. Confocal microscopic analyses of HeLa cells with anti-human CENP-H-specific antibody demonstrated that CENP-H colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. CENP-H was present outside centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. Furthermore, CENP-H was detected at neocentromeres, but not at inactive centromeres in stable dicentric chromosomes. In vitro binding assays of human CENP-H with centromere-kinetochore proteins suggest that the CENP-H binds to itself and MCAK, but not to CENP-A, CENP-B or CENP-C. CENP-H multimers were observed in cells in which both FLAG-tagged CENP-H and hemagglutinin-tagged CENP-H were expressed. These results suggest that CENP-H multimers localize constitutively to the inner kinetochore plate and play an important fundamental role in organization and function of the active human centromere-kinetochore complex.

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