Ekspresija nuklearnog antigena stanične proliferacije i proteina retinoblastoma u presađenoj fetalnoj suznoj žlijezdi štakora

A model of ectopic organogenesis of the rat fetal lacrimal gland was developed to study lacrimal gland organogenesis. It was done by its transplantation under the renal capsule. In transplants, expression of the tumor suppressor retinoblastoma gene (Rb) and proliferation cell nuclear antigen (PCNA) was assessed at the protein level. Eyes of 17- and 20-day-old rat fetuses were isolated under a dissecting microscope. Lacrimal glands were found and transplanted under the renal capsule of an adult male. After 14 days, transplants were routinely prepared for immunohistochemistry. DAKO Animal Research kit (Peroxidase) was used for detection of monoclonal mouse anti-PCNA and monoclonal mouse anti-human retinoblastoma gene product. In transplants, teratoma-like structures developed that contained lacrimal gland epithelial cells and ducts as well as epidermis. PCNA signal was detected in the nuclei of excretory duct cells and in epidermal basal layer cells. Some transplant cells were found to have the ability of proliferation preserved even after a 14-day period. PCNA signal was absent in well differentiated epithelial cells of lacrimal gland. Intranuclear Rb protein expression was only detected in several scattered cells, indicating the proliferating compartment to be usually larger than the differentiating one in fetal tissues. Assessment of the PCNA and Rb gene expression could prove important for elucidation of pathologic processes of the lacrimal gland, such as tumors or dry eye syndrome.Razvijen je model ektopične organogeneze fetalne suzne žlijezde štakora za ispitivanje organogeneze suzne žlijezde. To je postignuto presađivanjem suzne žlijezde ispod bubrežne kapsule. U presatcima je procjenjivana ekspresija gena tumorske supresije retinoblastoma (Rb) i jezgrenog antigena proliferirajućih stanica (PCNA) na razini bjelančevina. Oči fetusa štakora starih 17 i 20 dana izolirane su pod disekcijskim mikroskopom. Suzne žlijezde su pronađene i presađene pod bubrežnu kapsulu odraslog mužjaka. Nakon 14 dana su presatci rutinski pripravljeni za imunohistokemijsku analizu. Za otkrivanje monoklonskog mišjeg anti-PCNA i monoklonskog mišjeg anti-humanog proizvoda gena retinoblastoma uporabljen je DAKO Animal Research test (peroksidaza). U presatcima su se razvile teratomu slične strukture koje su sadržavale epitelne stanice suzne žlijezde i kanale, te epidermis. Signal PCNA otkriven je u jezgrama stanica odvodnog kanala, te u stanicama epidermnog bazalnog sloja. Time je pokazano kako su neke stanice presatka zadržale sposobnost proliferacije i nakon 14-dnevnog razdoblja. Signal PCNA bio je odsutan u dobro diferenciranim epitelnim stanicama suzne žlijezde. Unutarstanična ekspresija proteina Rb otkrivena je samo u nekoliko razasutih stanica, što pokazuje da je proliferirajući odjeljak u fetalnim tkivima obično veći od diferencirajućeg odjeljka. Procjena ekspresije PCNA i gena Rb mogla bi biti važna za pojašnjenje patoloških procesa u suznoj žlijezdi, kao što su tumori ili sindrom suhog oka

Integration of CT urography improves diagnostic confidence of 68Ga-PSMA-11 PET/CT in prostate cancer patients

Background: To prove the feasibility of integrating CT urography (CTU) into 68Ga-PSMA-11 PET/CT and to analyze the impact of CTU on assigning focal tracer accumulation in the ureteric space to either ureteric excretion or metastatic disease concerning topographic attribution and diagnostic confidence. Methods: Ten prostate cancer patients who underwent 68Ga-PSMA-11 PET/CT including CTU because of biochemical relapse or known metastatic disease were retrospectively analyzed. CTU consisted of an excretory phase 10 min after injection of 80 mL iodinated contrast material. Ureter opacification at CTU was evaluated using the following score: 0, 0% opacification; 1, < 50%; 2, 50–99%; 3, 100%. Topographic attribution and confidence of topographic attribution of focal tracer accumulation in the ureteric space were separately assessed for 68Ga-PSMA-11 PET/CT without and with CTU. Diagnostic confidence was evaluated using the following score: 0, < 25% confidence; 1, 26–50%; 2, 51–75%; 3, 76–100%. Results: At CTU, mean ureter opacification score was 2.6 ± 0.7. At 68Ga-PSMA-11 PET/CT without CTU, mean confidence of topographic attribution of focal tracer accumulation was 2.5 ± 0.7 in total and 2.6 ± 0.7 for metastatic disease. At 68Ga-PSMA-11 PET/CT with CTU, mean confidence of topographic attribution of focal areas of tracer accumulation was significantly higher with 2.9 ± 0.2 in total and 2.7 ± 0.9 for metastatic disease (p < 0.001). In 4 of 34 findings (12%) attribution to either ureteric excretion or metastatic disease was discrepant between 68Ga-PSMA-11 PET/CT without and with CTU (n.s). Conclusions: Integration of CTU into 68Ga-PSMA-11 PET/CT is feasible and increases diagnostic confidence of assigning focal areas of tracer accumulation in the ureteric space to either metastatic disease or ureteric excretion

Ectodermal Influx and Cell Hypertrophy Provide Early Growth for All Murine Mammary Rudiments, and Are Differentially Regulated among Them by Gli3

Mammary gland development starts in utero with one or several pairs of mammary rudiments (MRs) budding from the surface ectodermal component of the mammalian embryonic skin. Mice develop five pairs, numbered MR1 to MR5 from pectoral to inguinal position. We have previously shown that Gli3Xt-J/Xt-J mutant embryos, which lack the transcription factor Gli3, do not form MR3 and MR5. We show here that two days after the MRs emerge, Gli3Xt-J/Xt-J MR1 is 20% smaller, and Gli3Xt-J/Xt-J MR2 and MR4 are 50% smaller than their wild type (wt) counterparts. Moreover, while wt MRs sink into the underlying dermis, Gli3Xt-J/Xt-J MR4 and MR2 protrude outwardly, to different extents. To understand why each of these five pairs of functionally identical organs has its own, distinct response to the absence of Gli3, we determined which cellular mechanisms regulate growth of the individual MRs, and whether and how Gli3 regulates these mechanisms. We found a 5.5 to 10.7-fold lower cell proliferation rate in wt MRs compared to their adjacent surface ectoderm, indicating that MRs do not emerge or grow via locally enhanced cell proliferation. Cell-tracing experiments showed that surface ectodermal cells are recruited toward the positions where MRs emerge, and contribute to MR growth during at least two days. During the second day of MR development, peripheral cells within the MRs undergo hypertrophy, which also contributes to MR growth. Limited apoptotic cell death counterbalances MR growth. The relative contribution of each of these processes varies among the five MRs. Furthermore, each of these processes is impaired in the absence of Gli3, but to different extents in each MR. This differential involvement of Gli3 explains the variation in phenotype among Gli3Xt-J/Xt-J MRs, and may help to understand the variation in numbers and positions of mammary glands among mammals

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe