Enhanced viscosity reduction in heavy oils by subcritical water

We determine the chemical changes associated with viscosity reduction when heavy oil is cracked in subcritical water. The viscosity reduction has a temperature threshold for onset of 290 °C—this suggests an enhanced acid cracking regime associated with the maximisation of water dissociation at these conditions aided by the already increased solubility. The mean molecular weight is reduced by nearly 50%. Oxygen and sulphur are reduced by about half of this—either by expelled gas effluent (H 2S) or by conversion into mono-aromatic base sulphur-containing structures. The amount of lower branched paraffins is increased.</p

Enhanced viscosity reduction in heavy oils by subcritical water

We determine the chemical changes associated with viscosity reduction when heavy oil is cracked in subcritical water. The viscosity reduction has a temperature threshold for onset of 290 °C—this suggests an enhanced acid cracking regime associated with the maximisation of water dissociation at these conditions aided by the already increased solubility. The mean molecular weight is reduced by nearly 50%. Oxygen and sulphur are reduced by about half of this—either by expelled gas effluent (H 2S) or by conversion into mono-aromatic base sulphur-containing structures. The amount of lower branched paraffins is increased.</p

Body mass index at diagnosis of a childhood brain tumor; a reflection of hypothalamic-pituitary dysfunction or lifestyle?

Purpose: Childhood brain tumor survivors (CBTS) are at risk of becoming overweight, which has been shown to be associated with hypothalamic-pituitary (HP) dysfunction during follow-up. Body mass index (BMI) at diagnosis is related to BMI at follow-up. It is uncertain, however, whether aberrant BMI at brain tumor diagnosis reflects early hypothalamic dysfunction or rather reflects genetic and sociodemographic characteristics. We aimed to examine whether BMI at childhood brain tumor diagnosis is associated with HP dysfunction at diagnosis or its development during follow-up. Methods: The association of BMI at diagnosis of a childhood brain tumor to HP dysfunction at diagnosis or during follow-up was examined in a Dutch cohort of 685 CBTS, excluding children with craniopharyngioma or a pituitary tumor. Individual patient data were retrospectively extracted from patient charts. Results: Of 685 CTBS, 4.7% were underweight, 14.2% were overweight, and 3.8% were obese at diagnosis. Being overweight or obese at diagnosis was not associated with anterior pituitary deficiency or diabetes insipidus at diagnosis or during follow-up. In children with suprasellar tumors, being obese at diagnosis was associated with central precocious puberty. Conclusion: Overweight or obesity at diagnosis of a childhood brain tumor seems not to be associated with pituitary deficiencies. These results suggest that genetics and lifestyle may be more important etiologic factors for higher BMI at diagnosis in these children than hypothalamic dysfunction. To improve the long-term outcome of CBTS with regards to overweight and obesity, more attention should be given to lifestyle already at the time of brain tumor treatment

Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients

Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients. MTG2 - Moleculaire genetica van gastrointestinale tumorenMolecular tumour pathology - and tumour genetic

Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients

BackgroundColibactin, a genotoxin produced by polyketide synthase harboring (pks+) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pks+Escherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas. Previous research showed that a recurrent APC splice variant perfectly fits SBS88.MethodsIn this study, we explore the presence of colibactin-associated signatures and fecal pks in an unexplained polyposis cohort. Somatic targeted Next-Generation Sequencing (NGS) was performed for 379 patients. Additionally, for a subset of 29 patients, metagenomics was performed on feces and mutational signature analyses using Whole-Genome Sequencing (WGS) on Formalin-Fixed Paraffin Embedded (FFPE) colorectal tissue blocks.ResultsNGS showed somatic APC variants fitting SBS88 or ID18 in at least one colorectal adenoma or carcinoma in 29% of patients. Fecal metagenomic analyses revealed enriched presence of pks genes in patients with somatic variants fitting colibactin-associated signatures compared to patients without variants fitting colibactin-associated signatures. Also, mutational signature analyses showed enrichment of SBS88 and ID18 in patients with variants fitting these signatures in NGS compared to patients without.ConclusionsThese findings further support colibactins ability to mutagenize colorectal mucosa and contribute to the development of colorectal adenomas and carcinomas explaining a relevant part of patients with unexplained polyposis.Hereditary cancer genetic

APC mosaicism, not always isolated: two first-degree relatives with apparently distinct APC mosaicism

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Enhanced viscosity reduction in heavy oils by subcritical water

We determine the chemical changes associated with viscosity reduction when heavy oil is cracked in subcritical water. The viscosity reduction has a temperature threshold for onset of 290 °C—this suggests an enhanced acid cracking regime associated with the maximisation of water dissociation at these conditions aided by the already increased solubility. The mean molecular weight is reduced by nearly 50%. Oxygen and sulphur are reduced by about half of this—either by expelled gas effluent (H 2S) or by conversion into mono-aromatic base sulphur-containing structures. The amount of lower branched paraffins is increased

Responsiveness of the individual work performance questionnaire.

Background: Individual work performance is an important outcome measure in studies in the workplace. Nevertheless, its conceptualization and measurement has proven challenging. To overcome limitations of existing scales, the Individual Work Performance Questionnaire (IWPQ) was recently developed. The aim of the current study was to gain insight into the responsiveness of the IWPQ. Methods: Data were used from the Be Active & Relax randomized controlled trial. The aim of the trial was to investigate the effectiveness of an intervention to stimulate physical activity and relaxation of office workers, on need for recovery. Individual work performance was a secondary outcome measure of the trial. In total, 39 hypotheses were formulated concerning correlations between changes on the IWPQ scales and changes on similar constructs (e.g., presenteeism) and distinct constructs (e.g., need for recovery) used in the trial. Results: 260 Participants completed the IWPQ at both baseline and 12 months of follow-up. For the IWPQ scales, 23%, 15%, and 38%, respectively, of the hypotheses could be confirmed. In general, the correlations between change scores were weaker than expected. Nevertheless, at least 85% of the correlations were in the expected direction. Conclusions: Based on results of the current study, no firm conclusions can be drawn about the responsiveness of the IWPQ. Several reasons may account for the weaker than expected correlations. Future research on the IWPQ’s responsiveness should be conducted, preferably in other populations and intervention studies, where greater changes over time can be expected. (aut. ref.

Organization and dynamics of the cortical complexes controlling insulin secretion in beta-cells

Insulin secretion in pancreatic beta-cells is regulated by cortical complexes that are enriched at the sites of adhesion to extracellular matrix facing the vasculature. Many components of these complexes, including bassoon, RIM, ELKS and liprins, are shared with neuronal synapses. Here, we show that insulin secretion sites also contain the non-neuronal proteins LL5 beta (also known as PHLDB2) and KANK1, which, in migrating cells, organize exocytotic machinery in the vicinity of integrin-based adhesions. Depletion of LL5 beta or focal adhesion disassembly triggered by myosin II inhibition perturbed the clustering of secretory complexes and attenuated the first wave of insulin release. Although previous analyses in vitro and in neurons have suggested that secretory machinery might assemble through liquid-liquid phase separation, analysis of endogenously labeled ELKS in pancreatic islets indicated that its dynamics is inconsistent with such a scenario. Instead, fluorescence recovery after photobleaching and single-molecule imaging showed that ELKS turnover is driven by binding and unbinding to low-mobility scaffolds. Both the scaffold movements and ELKS exchangewere stimulated by glucose treatment. Our findings help to explain how integrin-based adhesions control spatial organization of glucose-stimulated insulin release.Nephrolog