Culturing Keratinocytes and Fibroblasts in a Three-Dimensional Mesh Results in Epidermal Differentiation and Formation of a Basal Lamina-Anchoring Zone

The purpose of this study was to characterize an in vitro co-culture model in which fibroblasts grown in a three-dimensional nylon mesh were recombined with human keratinocytes. The cultures were kept for 3 and 5 weeks and then processed for electron microscopy. Keratinocytes showed reconstruction of an epidermis consisting of a basal layer with hemidesmosome's, a stratified epithelium with tonofilament's and desmosomes, a granular layer with keratinosomes and keratohyaline granules, and a transitional stratum corneum. Anchoring filaments, lamina densa, anchoring fibrils, bundles of elastin-associated microfibrils (diameters 10 nm) and fine collagen fibrils were formed. Collagen fibrils near the epidermis were much thinner than those in the lower levels.The present study shows that the dermal model containing metabolically active fibroblasts in their natural environment will support epidermal morphogenesis and differentiation including the formation of a basal lamina and anchoring zone

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD

Search for Colour Singlet and Colour Reconnection Effects in Hadronic Z Decays at LEP

A search is performed in symmetric 3-jet hadronic Z decay events for evidence of colour singlet production or colour reconnection effects. Asymmetries in the angular separation of particles are found to be sensitive indicators of such effects. Upper limits on the level of colour singlet production and colour reconnection effects are established for a variety of models

Proton-Antiproton Pair Production in Two-Photon Collisions at LEP

The reaction e^+e^- -> e^+e^- proton antiproton is studied with the L3 detector at LEP. The analysis is based on data collected at e^+e^- center-of-mass energies from 183 GeV to 209 GeV, corresponding to an integrated luminosity of 667 pb^-1. The gamma gamma -> proton antiproton differential cross section is measured in the range of the two-photon center-of-mass energy from 2.1 GeV to 4.5 GeV. The results are compared to the predictions of the three-quark and quark-diquark models

Z Boson Pair-Production at LEP

Events stemming from the pair-production of Z bosons in e^+e^- collisions are studied using 217.4 pb^-1 of data collected with the L3 detector at centre-of-mass energies from 200 GeV up to 209 GeV. The special case of events with b quarks is also investigated. Combining these events with those collected at lower centre-of-mass energies, the Standard Model predictions for the production mechanism are verified. In addition, limits are set on anomalous couplings of neutral gauge bosons and on effects of extra space dimensions

Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA

Deep-inelastic positron-proton interactions at low values of Bjorken-x down to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons are studied with the H1 experiment at HERA. The inclusive cross section for pi^0 mesons produced at small angles with respect to the proton remnant (the forward region) is presented as a function of the transverse momentum and energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x. Measurements are also presented of the transverse energy flow in events containing a forward pi^0 meson. Hadronic final state calculations based on QCD models implementing different parton evolution schemes are confronted with the data.Comment: 27 pages, 8 figures and 3 table

Inclusive D* Production in Two-Photon Collisions at LEP

Inclusive D^{*+-} production in two-photon collisions is studied with the L3 detector at LEP, using 683 pb^{-1} of data collected at centre-of-mass energies from 183 to 208 GeV. Differential cross sections are determined as functions of the transverse momentum and pseudorapidity of the D^{*+-} mesons in the kinematic region 1 GeV < P_T < 12 GeV and |eta| < 1.4. The cross sections sigma(e^+e^- -> e^+e^-D^{*+-}X) in this kinematical region is measured and the sigma(e^+e^- -> e^+e^- cc{bar}X) cross section is derived. The measurements are compared with next-to-leading order perturbative QCD calculations

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4