Structure-based discovery of a novel small-molecule inhibitor of TEAD palmitoylation with anticancer activity.

The paralogous oncogenic transcriptional coactivators YAP and TAZ are the distal effectors of the Hippo signaling pathway, which plays a critical role in cell proliferation, survival and cell fate specification. They are frequently deregulated in most human cancers, where they contribute to multiple aspects of tumorigenesis including growth, metabolism, metastasis and chemo/immunotherapy resistance. Thus, they provide a critical point for therapeutic intervention.

FEATURES OF INTESTINAL MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: EFFECTS ON MARKERS OF INFLAMMATION AND HEPATIC STEATOSIS.

Objective: The aim: To study the state of the intestinal microbiota (ІМ) in patients with Nonalcoholic fatty liver disease (NAFLD) and to determine changes in its composition at the level of basic phylotypes.

Patients And Methods: Materials and methods: The study included 114 patients with NAFLD with metabolic disorders and 64 patients of control group. Determination of the composition of the ІМ at the level of major phylotypes was performed by identifying total bacterial DNA and DNA of Bacteroidetes, Firmicutes and Actinobacteria by quantitative polymerase chain reaction (PCR) in real time (qRT-PCR) using universal primers for the 16S rRNA gene and taxon-specific primers of production (Thermo Fisher Scientific).

Emerging Mechanisms of Growth and Patterning Regulation by Dachsous and Fat Protocadherins.

Dachsous (Ds) and Fat are evolutionarily conserved cell adhesion molecules that play a critical role in development of multiple organ systems, where they coordinate tissue growth and morphogenesis. Much of our understanding of Ds-Fat signaling pathway comes from studies in , where they initiate a signaling pathway that regulate growth by influencing Hippo signaling and morphogenesis by regulating Planar Cell Polarity (PCP). In this review, we discuss recent advances in our understanding of the mechanisms by which Ds-Fat signaling pathway regulates these critical developmental processes.

Assays Used for Discovering Small Molecule Inhibitors of YAP Activity in Cancers.

YAP/TAZ are transcriptional coactivators that function as the key downstream effectors of Hippo signaling. They are commonly misregulated in most human cancers, which exhibit a higher level of expression and nuclear localization of YAP/TAZ, and display addiction to YAP-dependent transcription. In the nucleus, these coactivators associate with TEA domain transcription factors (TEAD1-4) to regulate the expression of genes that promote cell proliferation and inhibit cell death.

Measurement of the helicity asymmetry for the reaction : The CBELSA/TAPS Collaboration.

A measurement of the double-polarization observable for the reaction is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C H OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons.

Observation of the pη^{'} Cusp in the New Precise Beam Asymmetry Σ Data for γp→pη.

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748  MeV to W=2045  MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447  MeV (W=1896  MeV)].

Three-body nature of N(*) and Δ(*) resonances from sequential decay chains.

The Nπ^{0}π^{0} decays of positive-parity N^{*} and Δ^{*} resonances at about 2 GeV are studied at ELSA by photoproduction of two neutral pions off protons. The data reveal clear evidence for several intermediate resonances: Δ(1232), N(1520)3/2^{-}, and N(1680)5/2^{+}, with spin parities J^{P}=3/2^{+}, 3/2^{-}, and 5/2^{+}. The partial wave analysis (within the Bonn-Gatchina approach) identifies N(1440)1/2^{+} and the N(ππ)_{S wave} (abbreviated as Nσ here) as further isobars and assigns the final states to the formation of nucleon and Δ resonances and to nonresonant contributions.

N(1520) 3/2(-) helicity amplitudes from an energy-independent multipole analysis based on new polarization data on photoproduction of neutral pions.

New data on the polarization observables T, P, and H for the reaction γp→pπ(0) are reported. The results are extracted from azimuthal asymmetries when a transversely polarized butanol target and a linearly polarized photon beam are used. The data were taken at the Bonn electron stretcher accelerator ELSA using the CBELSA/TAPS detector.

First measurement of the helicity asymmetry for γp → pπ0 in the resonance region.

The first measurement of the helicity dependence of the photoproduction cross section of single neutral pions off protons is reported for photon energies from 600 to 2300 MeV, covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, and BnGa partial wave analyses. Strikingly large differences between data and predictions are observed, which are traced to differences in the helicity amplitudes of well-known and established resonances.

Evidence for a parity doublet Delta(1920)P33 and Delta(1940)D33 from gammap-->ppi;{0}eta.

Evidence is reported for the existence of a parity doublet of Delta resonances with total angular momentum J=3/2 from photoproduction of the ppi;{0}eta final state. The two parity partners Delta(1920)P33 and Delta(1940)D33 make significant contributions to the reaction. Cascades of resonances into Delta(1232)eta, N(1535)pi, and Na0(980) are clearly observed.

Modification of the omega-meson lifetime in nuclear matter.

Information on hadron properties in the nuclear medium has been derived from the photoproduction of omega mesons on the nuclei C, Ca, Nb, and Pb using the Crystal Barrel/TAPS detector at the ELSA tagged photon facility in Bonn. The dependence of the omega-meson cross section on the nuclear mass number has been compared with three different types of models: a Glauber analysis, a Boltzmann-Uehling-Uhlenbeck analysis of the Giessen theory group, and a calculation by the Valencia theory group. In all three cases, the inelastic omega width is found to be 130-150 MeV/c(2) at normal nuclear matter density for an average 3-momentum of 1.

Observation of in-medium modifications of the omega meson.

The photoproduction of omega mesons on nuclei has been investigated using the Crystal Barrel/TAPS experiment at the ELSA tagged photon facility in Bonn. The aim is to study possible in-medium modifications of the omega meson via the reaction gamma + A --> omega + X --> pi(0)gamma + X('). Results obtained for Nb are compared to a reference measurement on a LH2 target.

Photoproduction of eta mesons off protons for 0.75 GeV

Total and differential cross sections for the reaction p(gamma,eta)p have been measured for photon energies in the range from 750 MeV to 3 GeV. The low-energy data are dominated by the S11 wave which has two poles in the energy region below 2 GeV. Eleven nucleon resonances are observed in their decay into peta.

Neutral-pion photoproduction off protons in the energy range 0.3 GeV

Single pi(0) photoproduction has been studied with the CB-ELSA experiment at Bonn using tagged photon energies between 0.3 and 3.0 GeV.

[Surgical tactics in spontaneous pneumothorax].

219 cases of nonspecific spontaneous pneumothorax have been analysed. The bullous lung disease was the reason of pneumothorax in 55% of cases. Diagnostic and curative thoracoscopy is an important element of diagnosis.

Some problems of tracheobronchoplasty for lung cancer in a Regional Hospital in Russia.

Tracheobronchoplastic procedures formed part of the operation for lung cancer in 41 patients of a Regional Hospital in Russia over the past 2 and a half years. Twenty-nine patients underwent sleeve lobectomy; in a further 12 patients, right pneumonectomy was combined with resection of other mediastinal structures. In 16 patients, sleeve lobectomy was indicated by the high risk of pneumonectomy.

[The use of a pedicled greater omentum in pneumonectomies for the prevention of bronchial fistulas].

Expanded (13) and combined (9) pneumonectomy with laparotomy and plastics of the bronchial stump with the greater omentum on a vascular pedicle were conducted on 22 patients in the period from 1988 (June) to 1990 (April). The omentum was used for the prevention of bronchial fistulas and correction of defects in the pericardium. Laparotomy and omentopexy did not aggravate the patients' condition essentially and did not affect the terms of treatment.