708 research outputs found

    Butyrylcholinesterase distribution in the mouse gastrointestinal tract: An immunohistochemical study

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    Butyrylcholinesterase (BChE) is a hydrolytic enzyme that together with acetylcholinesterase (AChE) belongs to the cholinesterase family. Whereas AChE has a well-established role in regulating cholinergic neurotransmission in central and peripheral synapses, the physiological role of BChE remains elusive. In this morphological immunohistochemical and double-label confocal microscopy study we investigated the distribution of BChE in the mouse gastrointestinal tract. BChE-positive cells were detected in the liver (both in hepatocytes and cholangiocytes), in the keratinised layers of the squamous epithelium of the oesophagus and forestomach, in the oxyntic mucosa of the stomach, in the mucus-secreting cells of duodenal Brunner glands and the small and large intestinal mucosa. Interestingly, BChE-positive cells were often detected close to gastrointestinal proliferative niches. In the oxyntic mucosa, the close proximity of ghrelin-producing and BChE-positive parietal cells suggests that BChE may be involved in ghrelin hydrolysation through paracrine action. To our knowledge, this is the first comprehensive morphological study performed to gain insight into the physiological role of BChE in the gastrointestinal tract

    A smartphone-based chemosensor to evaluate antioxidants in agri-food matrices by in situ AuNP formation

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    In recent years, there has been a continuously growing interest in antioxidants by both customers and food industry. The beneficial health effects of antioxidants led to their widespread use in fortified functional foods, as dietary supplements and as preservatives. A variety of analytical methods are available to evaluate the total antioxidant capacity (TAC) of food extracts and beverages. However, most of them are expensive, time-consuming, and require laboratory instrumentation. Therefore, simple, cheap, and fast portable sensors for point-of-need measurement of antioxidants in food samples are needed. Here, we describe a smartphone-based chemosensor for on-site assessment of TAC of aqueous matrices, relying on the antioxidant-induced formation of gold nanoparticles. The reaction takes place in ready-to-use analytical cartridges containing an hydrogel reaction medium preloaded with Au(III) and is monitored by using the smartphone’s CMOS camera. An analytical device including an LED-based lighting system was developed to ensure uniform and reproducible illumination of the analytical cartridge. The chemosensor permitted rapid TAC measurements of aqueous samples, including teas, herbal infusions, beverages, and extra virgin olive oil extracts, providing results that correlated with those of the reference methods for TAC assessment, e.g., oxygen radical absorbance capacity (ORAC)

    A Catastrophe Theory Based Model for Optimal Control of Chemical Reactions by means of Oriented Electric Fields

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    The e ect of oriented external electric  elds (OEEF) on chemical reactivity has been studied theoretically and computationally in the last decades. A central goal in this research area is to predict the orientation and the smallest amplitude electric  eld that renders a barrierles chemical process with the smallest possible strength. Recently, a model to  nd the optimal electric  eld has been proposed and described (J. M. Bo ll et. al., J. Chem. Theory Comput. 18, 935 (2022)). We here proof that this model is based on Catastrophe and Optimum Control Theories. Based on both theories a technical treatment of the model is given and applied to a two-dimensional generic example that provides insight into its nature and capability. Finally, the model is applied to determine the optimal OEEF for the trans-to-cis isomerization of a [3]cumulene derivative

    Compositions of Dust and Sea Salts in the Dome C and Dome Fuji Ice Cores From Last Glacial Maximum to Early Holocene Based on Ice‐Sublimation and Single‐Particle Measurements

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    We analyzed the chemical compositions of dust and sea‐salt particles in the EPICA Dome C (EDC) ice core during 26–7 kyr BP using an ice‐sublimation technique and compared the results with existing data of the Dome Fuji (DF) ice core. Combined with ion concentration data, our data suggested similar sea‐salt fluxes in both cores and significantly lower dust flux in the EDC core. The differences in modal size and aspect ratio of dust particles between the two cores support the dominance of Patagonian source suggested by earlier works. The compositions of calcic dust showed major change at ~17 kyr BP, possibly reflecting a relative increase in dust transported via the upper troposphere. The calcium sulfate fraction was higher in the DF core than in the EDC core after ~17 kyr BP, suggesting that higher Patagonian dust contribution to the DF region. Abundant NaCl particles were found in the DF core in comparison with the EDC core from the LGM to early Holocene, possibly because of the high concentration of terrestrial dust in the DF core that reduced acid availability for sea‐salt modification. During the Holocene, the lower NaCl fraction and Cl−/Na+ ratio in the EDC core suggested that most Cl− was lost to the atmosphere from snow at Dome C, while it was preserved at Dome Fuji as NaCl and solid solution

    Schizophrenia: The new etiological synthesis

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    Schizophrenia has been an evolutionary paradox: it has high heritability, but it is associated with decreased reproductive success. The causal genetic variants underlying schizophrenia are thought to be under weak negative selection. To unravel this paradox, many evolutionary explanations have been suggested for schizophrenia. We critically discuss the constellation of evolutionary hypotheses for schizophrenia, highlighting the lack of empirical support for most existing evolutionary hypotheses—with the exception of the relatively well supported evolutionary mismatch hypothesis. It posits that evolutionarily novel features of contemporary environments, such as chronic stress, low-grade systemic inflammation, and gut dysbiosis, increase susceptibility to schizophrenia. Environmental factors such as microbial infections (e.g., Toxoplasma gondii) can better predict the onset of schizophrenia than polygenic risk scores. However, researchers have not been able to explain why only a small minority of infected people develop schizophrenia. The new etiological synthesis of schizophrenia indicates that an interaction between host genotype, microbe infection, and chronic stress causes schizophrenia, with neuroinflammation and gut dysbiosis mediating this etiological pathway. Instead of just alleviating symptoms with drugs, the parasite x genotype x stress model emphasizes that schizophrenia treatment should focus on detecting and treating possible underlying microbial infection(s), neuroinflammation, gut dysbiosis, and chronic stress.</p

    Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): A study protocol

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    Introduction Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC. Methods and analysis The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) or 68 Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy. Ethics and dissemination The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities. The study is currently open in Italy. Trail registration number NCT03387592; Pre-results. EudraCT-2016-000767-17. Protocol version Clinical Study Protocol Version 1, 7 November 2016

    Soil deformation analysis through fluid-dynamic modelling and DInSAR measurements: a focus on groundwater withdrawal in the Ravenna area (Italy)

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    This study aims at assessing the deformation processes affecting an area NW of the city of Ravenna (northern Italy), caused by groundwater withdrawal activities. In situ data, geologic and structural maps, piezometric measurements, underground water withdrawal volumes, and satellite C-band SAR data were used to jointly exploit two different techniques: 1) fluid-dynamic and geomechanical modelling (by RSE S.p.A), and 2) Differential Synthetic Aperture Radar Interferometry (DInSAR) analysis (by CNR - IREA). The results of the comparative analysis presented in this work brought new evidence about the contribution of groundwater withdrawal to the total subsidence affecting the area during the 2000-2017 time interval. In particular, they show an increase of the subsidence from year 2000 to 2010 and a decrease from year 2010 to 2017. These results are generally in line with groundwater withdrawal data that report a reduction of the extracted water volumes during the considered temporal interval. Meantime, they show a delay effect in the subsidence process, partially recovered during the 2010-2017 thanks to a stabilisation of the extracted groundwater volumes. The presented results shade new light on the groundwater withdrawal contribution to the subsidence of the analysed zone, although further investigations are foreseen to better clarify the ongoing scenario
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