Differences in fine particle chemical composition on clear and cloudy days.

Clouds are prevalent and alter PM2.5 mass and chemical composition. Cloud-affected satellite retrievals are often removed from data products, hindering estimates of tropospheric chemical composition during cloudy times. We examine surface fine particulate matter (PM2.5) chemical constituent concentrations in the Interagency Monitoring of PROtected Visual Environments network during Cloudy and Clear Sky times defined using Moderate Resolution Imaging Spectroradiometer (MODIS) cloud flags from 2010-2014 with a focus on differences in particle hygroscopicity and aerosol liquid water (ALW). Cloudy and Clear Sky periods exhibit significant differences in PM2.5 and chemical composition that vary regionally and seasonally. In the eastern US, relative humidity alone cannot explain differences in ALW, suggesting emissions and in situ chemistry exert determining impacts. An implicit clear sky bias may hinder efforts to quantitatively to understand and improve model representation of aerosol-cloud interactions.

Non-cell autonomous control of apoptosis by ligand-independent Hedgehog signaling in Drosophila.

Hedgehog (Hh) signaling is important for development and homeostasis in vertebrates and invertebrates. Ligand-independent, deregulated Hh signaling caused by loss of negative regulators such as Patched causes excessive cell proliferation, leading to overgrowth in Drosophila and tumors in humans, including basal-cell carcinoma and medulloblastoma. We show that in Drosophila deregulated Hh signaling also promotes cell survival by increasing the resistance to apoptosis. Surprisingly, cells with deregulated Hh activity do not protect themselves from apoptosis; instead, they promote cell survival of neighboring wild-type cells. This non-cell autonomous effect is mediated by Hh-induced Notch signaling, which elevates the protein levels of Drosophila inhibitor of apoptosis protein-1 (Diap-1), conferring resistance to apoptosis. In summary, we demonstrate that deregulated Hh signaling not only promotes proliferation but also cell survival of neighboring cells. This non-cell autonomous control of apoptosis highlights an underappreciated function of deregulated Hh signaling, which may help to generate a supportive micro-environment for tumor development.

The sex determination gene doublesex regulates the A/P organizer to direct sex-specific patterns of growth in the Drosophila genital imaginal disc.

Each Drosophila genital imaginal disc contains primordia for both male and female genitalia and analia. The sexually dimorphic development of this disc is governed by the sex-specific expression of doublesex (dsx). We present data that substantially revises our understanding of how dsx controls growth and differentiation in the genital disc. The classical view of genital disc development is that in each sex, dsx autonomously "represses" the development of the inappropriate genital primordium while allowing the development of the appropriate primordium. Instead, we show that dsx regulates the A/P organizer to control growth of each genital primordium, and then directs each genital primordium to differentiate defined adult structures in both sexes.

Hyperactivation of the folded gastrulation pathway induces specific cell shape changes.

During Drosophila gastrulation, mesodermal precursors are brought into the interior of the embryo by formation of the ventral furrow. The first steps of ventral furrow formation involve a flattening of the apical surface of the presumptive mesodermal cells and a constriction of their apical diameters. In embryos mutant for folded gastrulation (fog), these cell shape changes occur but the timing and synchrony of the constrictions are abnormal. A similar phenotype is seen in a maternal effect mutant, concertina (cta). fog encodes a putative secreted protein whereas cta encodes an (alpha)-subunit of a heterotrimeric G protein. We have proposed that localized expression of the fog signaling protein induces apical constriction by interacting with a receptor whose downstream cellular effects are mediated by the cta G(alpha)protein.

In order to test this model, we have ectopically expressed fog at the blastoderm stage using an inducible promoter. In addition, we have examined the constitutive activation of cta protein by blocking GTP hydrolysis using both in vitro synthesized mutant alleles and cholera toxin treatment. Activation of the fog/cta pathway by any of these procedures results in ectopic cell shape changes in the gastrula. Uniform fog expression rescues the gastrulation defects of fog null embryos but not cta mutant embryos, arguing that cta functions downstream of fog expression. The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviors and invagination. Epistasis experiments indicate that this pathway requires snail but not twist expression.

Human papillomavirus infection in women with multicentric squamous cell neoplasia.

Tissues from 32 women with multicentric squamous cell neoplasia of the anogenital region (72 anatomically distinct lesions at the cervix, vagina, vulva, perineum, or anus) were tested for the presence of human papillomavirus with the polymerase chain reaction or in situ hybridization. All the women had invasive carcinomas or grade 3 intraepithelial neoplasia lesions at a minimum of one site and one or two squamous cell lesions at another site(s). Human papillomavirus was detected in all of the multicentric lesions in 87.5% (28/32) of the women and in at least one lesion in 12.5% (4/32). In the 28 women with detectable human papillomavirus at all sites, 61% (17/28) had the same virus type(s) at all sites (types 6, 16, 6 and 16, 33) and 25% (7/28) had 6 or 16 at one site and both viruses at the other site(s). Four women (15%) had different virus patterns in the separate lesions.

Hormonal control of gene expression: interactions between two trans-acting regulators in Drosophila.

The steroid hormone 20-hydroxyecdysone (20HE) and the Broad-Complex locus (BRC) are involved in regulating developmental changes in gene expression around the time of metamorphosis in Drosophila. We have investigated the regulatory interactions between 20HE, BRC, and a set of genes expressed in the fat body of third-instar Drosophila larvae. RNA levels for two hormone-inducible genes, Larval Serum Protein-2 and P1, accumulate to normal levels in BRC-mutant larvae. In contrast, RNA levels for the P6 gene were affected by mutations at BRC. On the basis of the results of experiments in which hormone concentrations were varied in BRC-mutant or wild-type larvae, we conclude that 20HE can both increase and decrease P6 RNA levels in the absence of BRC product(s). BRC appears to be a trans-acting modulator of the response of P6 to the hormone. We propose that BRC attenuates the repressive effect of the hormone, expanding the range of hormone concentrations that induce the gene, thus allowing P6 RNA to reach high levels during the third larval instar. The results are discussed in relation to other genes that are regulated by the same two trans-acting factors. A model is presented that refines the model of Ashburner et al. (1974, Cold Spring Harbor Symp. Quant. Biol. 38: 655-662) for the hormonal regulation of gene activity.

Evidence of prevalent genital-type human papillomavirus infections in adults and children.

Recombinant proteins encoded by the E2, E7, L1, and L2 open reading frames (ORF) of human papillomavirus (HPV) types 6b, 16, and 18 were used in Western blot assays to detect serum IgG antibodies in women attending a sexually transmitted diseases clinic (n = 92) and in hospitalized children (n = 81). Antibodies to late gene products (L1 or L2 ORF) were more common than antibodies to early gene products (E2 or E7), both in the adults and the children; overall, the antibody prevalences in the children and the sexually active adults were not significantly different. Human sera with high titers of antibodies to the HPV16 E7 recombinant protein immunoprecipitated the genuine HPV16 E7 protein from the cervical carcinoma cell line CaSki. As an independent measure of HPV infection, the polymerase chain reaction was used to detect HPV6b and HPV16 in oral mucosal scrapings from adults (n = 35) and preschool children (n = 21). In adults, HPV6b and HPV16 DNA were detected in 17% and 23% of oral mucosal samples, respectively. In preschool children, HPV6b and HPV16 DNA were found in 24% and 19% of oral samples, respectively.