Predisposition to Alcohol Drinking and Alcohol Consumption Alter Expression of Calcitonin Gene-Related Peptide, Neuropeptide Y, and Microglia in Bed Nucleus of Stria Terminalis in a Subnucleus-Specific Manner

Excessive alcohol consumption is often linked to anxiety states and has a major relay center in the anterior part of bed nucleus of stria terminalis (BNST). We analyzed the impact of (i) genetic predisposition to high alcohol preference and consumption, and (ii) alcohol intake on anterior BNST, namely anterolateral (AL), anteromedial (AM), and anteroventral (lateral + medial subdivisions: AVl, AVm) subnuclei. We used two rat lines selectively bred for low- and high-alcohol preference and consumption, named Sardinian alcohol-non preferring (sNP) and -preferring (sP), respectively, the latter showing also inherent anxiety-related behaviors. We analyzed the modulation of calcitonin gene-related peptide (CGRP; exerting anxiogenic effects in BNST), neuropeptide Y (NPY; exerting mainly anxiolytic effects), and microglia activation (neuroinflammation marker, thought to increase anxiety). Calcitonin gene-related peptide-immunofluorescent fibers/terminals did not differ between alcohol-naive sP and sNP rats. Fiber/terminal NPY-immunofluorescent intensity was lower in BNST-AM and BNST-AVm of alcohol-naive sP rats. Activation of microglia (revealed by morphological analysis) was decreased in BNST-AM and increased in BNST-AVm of alcohol-naive sP rats. Prolonged (30 consecutive days), voluntary alcohol intake under the homecage 2-bottle “alcohol vs. water” regimen strongly increased CGRP intensity in BNST of sP rats in a subnucleus-specific manner: in BNST-AL, BNST-AVm, and BNST-AM. CGRP area sum, however, decreased in BNST-AM, without changes in other subnuclei. Alcohol consumption increased NPY expression, in a subnucleus-specific manner, in BNST-AL, BNST-AVl, and BNST-AVm. Alcohol consumption increased many size/shapes parameters in microglial cells, indicative of microglia de-activation. Finally, microglia density was increased in ventral anterior BNST (BNST-AVl, BNST-AVm) by alcohol consumption. In conclusion, genetic predisposition of sP rats to high alcohol intake could be in part mediated by anterior BNST subnuclei showing lower NPY expression and differential microglia activation. Alcohol intake in sP rats produced complex subnucleus-specific changes in BNST, affecting CGRP/NPY expression and microglia and leading to hypothesize that these changes might contribute to the anxiolytic effects of voluntarily consumed alcohol repeatedly observed in sP rats

Study of 124^{124}Sn+136^{136}Xe fusion-evaporation: analysis of a rare-event experiment

7 pages, 4 figuresFusion-evaporation in the $^{124}$Sn+$^{136}$Xe system is studied using a high intensity xenon beam provided by the Ganil accelerator and the LISE3 wien filter for the selection of the products. Due to the mass symmetry of the entrance system, the rejection of the beam by the spectrometer was of the order of $5times10^8$. We have thus performed a detailed statistical analysis to estimate random events and to infer the fusion-evaporation cross sections. No signicant decay events were detected and upper limit cross sections of 172~pb, 87~pb and 235~pb were deduced for the synthesis of $^{257}$Rf, $^{258}$Rf and $^{259}$Rf, respectively

Coordination of Substrate Binding and ATP Hydrolysis in Vps4-Mediated ESCRT-III Disassembly

Vps4 disassembly of ESCRT-III plays an important role in MVB sorting, viral budding, and cytokinesis. An in vitro system was developed to investigate this process. These studies revealed new insights into the mechanisms of Vps4 function

Hepatoselective Nitric Oxide (NO) Donors, V-PYRRO/NO and V-PROLI/NO, in Nonalcoholic Fatty Liver Disease: A Comparison of Antisteatotic Effects with the Biotransformation and Pharmacokinetics

ABSTRACT V-PYRRO/NO [O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate] and V-PROLI/NO (O2-vinyl-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate), two structurally similar diazeniumdiolate derivatives, were designed as liver-selective prodrugs that are metabolized by cytochrome P450 isoenzymes, with subsequent release of nitric oxide (NO). Yet, their efficacy in the treatment of nonalcoholic fatty liver disease (NAFLD) and their comparative pharmacokinetic and metabolic profiles have not been characterized. The aim of the present work was to compare the effects of V-PYRRO/NO and V-PROLI/NO on liver steatosis, glucose tolerance, and liver fatty acid composition in C57BL/6J mice fed a high-fat diet, as well as to comprehensively characterize the ADME (absorption, distribution, metabolism and excretion) profiles of both NO donors. Despite their similar structure, V-PYRRO/NO and V-PROLI/NO showed differences in pharmacological efficacy in the murine model of NAFLD. V-PYRRO/NO, but not V-PROLI/NO, attenuated liver steatosis, improved glucose tolerance, and favorably modified fatty acid composition in the liver. Both compounds were characterized by rapid absorption following i.p. administration, rapid elimination from the body, and incomplete bioavailability. However, V-PYRRO/NO was eliminated mainly by the liver, whereas V-PROLI/NO was excreted mostly in unchanged form by the kidney. V-PYRRO/NO was metabolized by CYP2E1, CYP2C9, CYP1A2, and CYP3A4, whereas V-PROLI/NO was metabolized mainly by CYP1A2. Importantly, V-PYRRO/NO was a better NO releaser in vivo and in the isolated, perfused liver than V-PROLI/NO, an effect compatible with the superior antisteatotic activity of V-PYRRO/NO. In conclusion, V-PYRRO/NO displayed a pronounced antisteatotic effect associated with liver-targeted NO release, whereas V-PROLI/NO showed low effectiveness, was not taken up by the liver, and was eliminated mostly in unchanged form by the kidney

System ekspertowy wspomagający proces przygotowania produkcji jachtów

Expert systems can be defined as computer programs, whose main task is to simulate a human expert, usually in a narrow field of expertise. Possible applications of modern information technology are very extensive, ranging from medicine, geology and technology to applications in the field of economic and financial decision support. The purpose of this paper is to present the practical application of an expert system that supports the process of managing the production of yachts and has a high suitability for use in this application. Using the expert system described in the paper reduces the time during the design and production preparation process.Systemy ekspertowe można określić jako programy komputerowe, których podstawowym zadaniem jest symulowanie działanie człowieka – eksperta, na ogół w wąskiej dziedzinie. Możliwości zastosowań tej nowoczesnej technologii informatycznej są bardzo duże, począwszy od medycyny, przez geologię, technikę aż do zastosowań w dziedzinie wspomagania podejmowania decyzji gospodarczych i finansowych. Celem niniejszego artykułu jest prezentacja praktycznego zastosowania systemu ekspertowego, który wspomaga proces przygotowania produkcji rekreacyjnych jednostek pływających i wykazuje dużą przydatność użytkową z jego stosowania. Korzystanie z opisanego systemu ekspertowego skraca czas w procesach projektowania i przygotowania produkcji jachtów

Forcing of morphological changes of Aspergillus terreus mycelium by the addition of inorganic microparticles

Grzyby nitkowe są producentem wielu cennych substancji. Forma morfologiczna grzybów ma wpływ na jego produktywność. Badania nad sterowanie morfologią grzybów nitkowych mają na celu intensyfikację produkcji ich metabolitów oraz kontrole nad wielkością peletek w hodowlach wgłębnych, Niniejsza praca ma na celu zbadanie wpływu dodatku nieorganicznych mikrocząstek talku (Mg3(OH)2Si4010) oraz tlenku glinu (Al203 na rozmiar peletek Aspergillus terreus ATCC 20542 i biosyntezę lowastatyny.Filamentous fungi produce many valuable substances. A morphological form of fungi has an impact on his productivity. Studies on controlling the fungal morphology are directed towards the intensification of metabolites excretion and control over the size of pellets in submerged cultures. This paper aims at the investigation of influence of talcum (Mg)3(OH)2Si4O)10) and aluminum trioxide (Al203) addition on the size of Aspergillus terreus ATCC 20542 pellets and lovastatin production