Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism

Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA

A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e ± p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q 2, and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result

Multi-leptons with High Transverse Momentum at HERA

Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb-1. The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e+p collision data with a scalar sum of the lepton transverse momenta above 100GeV while 1.94 ± 0.17 events are expected. Such events are not observed in e-p collisions for which 1.19 ± 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions. © SISSA 2009

Events with an Isolated Lepton and Missing Transverse Momentum and Measurement of W Production at HERA

A search for events containing an isolated electron or muon and missing transverse momentum produced in e±p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb-1. The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e+p data, at large hadronic transverse momentum PTX \u3c 25GeV, a total of 23 events are observed compared to a prediction of 14.0 ±1.9. The total single W boson production cross section is measured as 1.06 ± 0.16 (stat.) ± 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 ± 0.19 pb

Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA

A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy √s= 318 Gev where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q 2 < 200 GeV 2 in photon virtuality, 0.00035 < xP < 0.09 in proton fractional momentum loss, 0.09 <{pipe}t{pipe}< 0.55 GeV 2 in squared four-momentum transfer at the proton vertex and 0.0018 < β <0.816 in β=x/xP, where x is the Bjorken scaling variable. © 2012 The Author(s)

NRG-ERBB3 signaling drives secretory acinus formation

Acini are essential for the secretory function of multiple exocrine organs. During acini formation, a cluster of epithelial end bud progenitors must undergo secretory program initiation, maturation and cell polarization to form a unit of single layered secretory cells enclosing a central lumen. Yet, how this complex process is regulated remains unknown. Using the developing salivary gland as a model, we reveal the EGF receptor ERBB3 as a master driver of acinus formation. We discovered ERBB3 to be enriched in end buds, and through conditional deletion of epithelial Erbb3, to be essential in multiple steps of secretory cell program initiation, cell maturation, expansion and polarization. Moreover, we demonstrate that addition of a single factor, ERBB3 ligand neuregulin-1, to isolated epithelia ex vivo is sufficient to recapitulate the complex outcomes of in vivo acinus formation in multiple exocrine organs. Finally, we reveal a new ERBB3-mTOR1/2 signaling link that governs the full formation of the secretory acinus

NRG-ERBB3 signaling drives secretory acinus formation

Acini are essential for the secretory function of multiple exocrine organs. During acini formation, a cluster of epithelial end bud progenitors must undergo secretory program initiation, maturation and cell polarization to form a unit of single layered secretory cells enclosing a central lumen. Yet, how this complex process is regulated remains unknown. Using the developing salivary gland as a model, we reveal the EGF receptor ERBB3 as a master driver of acinus formation. We discovered ERBB3 to be enriched in end buds, and through conditional deletion of epithelial Erbb3, to be essential in multiple steps of secretory cell program initiation, cell maturation, expansion and polarization. Moreover, we demonstrate that addition of a single factor, ERBB3 ligand neuregulin-1, to isolated epithelia ex vivo is sufficient to recapitulate the complex outcomes of in vivo acinus formation in multiple exocrine organs. Finally, we reveal a new ERBB3-mTOR1/2 signaling link that governs the full formation of the secretory acinus