Gallstone pancreatitis vs alcohol-induced pancreatitis: does aetiology affect the extent of pancreatic necrosis?

This is the final version. Available on open access from Mattioli 1885 via the DOI in this recordBackground and aim: The impact of different aetiologies of acute pancreatitis on the development of pancreatic necrosis (PN) is unclear. This study assessed the extent and progression of pancreatic and peripan-creatic necrosis on the computed tomography (CT) scan of patients with gallstone (GP) and alcohol-induced (AIP) pancreatitis and evaluated their impact on disease severity. Methods: Patients ≥ 18-year-old with GP, AIP and PN on CT ( January 2010 – September 2018), were considered. The radiological extent of PN and clinical outcomes were analysed with a logistic regression model. Results: Eighty-one patients, 59 with GP, 22 with AIP, were included. GP had a larger extent of PN when the body and/or tail of the pancreas were involved (P = 0.009). Gallstone disease (P = 0.028) and higher American Society of Anesthetists scores (P = 0.043) were predictors of necrosis diffuse to different areas of the pancreas. Predictors of single/multiple organ failure were GP (P = 0.040), necrosis > 50% of the pancreas (P = 0.002) with a diffuse pattern (P = 0.004). Conclusions: Patients with GP had a wider extent of necrosis in the pancreatic body and/or tail. The onset of organ failure can be predicted in subjects with GP and larger amount of PN

DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions

ICF, An Immunodeficiency Syndrome: DNA Methyltransferase 3B Involvement, Chromosome Anomalies, and Gene Dysregulation

The immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) is the only disease known to result from a mutated DNA methyltransferase gene, namely, DNMT3B. Characteristic of this recessive disease are decreases in serum immunoglobulins despite the presence of B cells and, in the juxtacentromeric heterochromatin of chromosomes 1 and 16, chromatin decondensation, distinctive rearrangements, and satellite DNA hypomethylation. Although DNMT3B is involved in specific associations with histone deacetylases, HP1, other DNMTs, chromatin remodelling proteins, condensin, and other nuclear proteins, it is probably the partial loss of catalytic activity that is responsible for the disease. In microarray experiments and real-time RT-PCR assays, we observed significant differences in RNA levels from ICF vs. control lymphoblasts for pro- and anti-apoptotic genes (BCL2L10, CASP1, and PTPN13); nitrous oxide, carbon monoxide, NF-κB, and TNFa signalling pathway genes (PRKCH, GUCY1A3, GUCY1B3, MAPK13; HMOX1, and MAP4K4); and transcription control genes (NR2F2 and SMARCA2). This gene dysregulation could contribute to the immunodeficiency and other symptoms of ICF and might result from the limited losses of DNA methylation although ICF-related promoter hypomethylation was not observed for six of the above examined genes. We propose that hypomethylation of satellite 2at1qh and 16qh might provoke this dysregulation gene expression by trans effects from altered sequestration of transcription factors, changes in nuclear architecture, or expression of noncoding RNAs

End-bridging monte carlo simulation of bulk and grafted amorphous polyethylene above and below the glass transition

The very efficient end-bridging Monte Carlo (EBMC) method has been employed in order to simulate an amorphous, polydisperse 80-chain large C156 polyethylene (PE) system in atomistic detail over a wide range of temperatures (from 600 down to 150 K) and determine its glass transition temperature (Tg). Two sets of simulations have been performed: one with a bulk, isotropic sample and the other with a thin film in which all the 80 PE chains were grafted on a hard substrate on one side (corresponding to a high grafting density equal to = 1.75 nm-2) and exposed to vacuum on the other side. In the simulations, a united-atom model was employed for PE ensuring that only the purely amorphous phase of PE was simulated at all temperatures. In all cases, very long simulations were carried out in order to give enough time for the system to relax at all length scales. For all temperatures studied, the longest relaxation time was found to be present by descriptors associated with the system's long-range conformational characteristics. In contrast, more local, internal structural features were always faster in equilibrating. As a result, the time autocorrelation function for the chain end-to-end unit vector, fu(t), was found to drop to zero and then clearly fluctuate around this value only for temperatures higher than about 220 K for both systems. For lower temperatures, fu(t) did not relax completely, even after 2 × 107 CPU seconds. Additional volumetric simulation data demonstrated a sharp change in the density and potential energy of both systems in the neighborhood of the 230 K, which are considered as features of the glass transition for amorphous PE. The Tg value suggested by the present EBMC simulations for amorphous (bulk or grafted) PE is (230 ± 10) K, which is consistent with the value of 237 K measured experimentally by Wunderlich [J. of Chem. Phys. 1962, 37, 1203] and Loufakis and Wunderlich [J. Phys. Chem. 1988, 92, 4205] for PE in the limit of zero crystallinity. Further, the predicted change in the heat capacity at constant pressure at the glass transition is cp = 1.2 × 10-4 kcal g-1 K-1, which is very close to the value of 1.5 × 10-4 kcal g-1 K-1 measured experimentally by Wunderlich [J. of Chem. Phys. 1962, 37, 1203]. Additional results on the temperature dependence of the conformational and structural properties in the two PE systems are also reported and discussed in detail. -------------------------------------------------------------------------------

Nuclear receptor expression in human differentiated thyroid tumors

Background: Nuclear receptors (NRs) play a key role in endocrine signaling and metabolism and are important therapeutic targets in a number of hormone-dependent malignancies. Studies on the role of NRs in thyroid cancer are limited

NiCuMo-SiO2 catalyst for pyrolysis oil upgrading: model acidic treatment study

The main reasons of catalysts deactivation in hydro-processing pyrolysis liquids are by coke deposition, poisoning by bio-oil impurities (S, N, K, Cl, etc.), leaching of catalyst components, structural degradation in the presence of H2O, and sintering. The deactivation of catalysts by the acidity of the pyrolysis liquid is a specific concern, and this deactivation mechanism was studied by treating newly developed NiCuMo-SiO2 catalysts in 1 M acetic acid water solution (pH = 2-3). The activity of the acid-treated catalysts was subsequently investigated in the hydrodeoxygenation of gaseous propionic acid, in a tubular reactor at 225 degrees C with n-hexane and n-octane serving as diluent and internal standard, respectively. The samples treated by acid at different times (15-360 min) were characterized by X-ray diffraction (XRD), high resolution transition electron microscopy (HRTEM), X-ray fluorescence (XRF), CO chemisorption, N-2 physical adsorption, and X-ray photoelectron spectroscopy (XPS). XRF and HRTEM studies together with the residual mass of catalyst pointed out at gradual leaching of catalyst components. Among the catalyst components, dissolution of nickel was the most pronounced, while molybdenum content decreased to a lesser extent. This is due to the formation of more acid stable molybdenum blues. The amount of copper decreased only slightly, due its higher electrochemical potential. Oxidation of metallic species Cu and Ni is shown to obtain Cu2O, NiO and Ni(OH)(2)-like phases. Interestingly, the acidic treatment resulted in increasing active surface of the catalyst, nevertheless, the catalyst activity in propionic acid conversion irreversibly decreased in time by the acetic acid treatment due to loss of the active components (substantially nickel)