299 research outputs found

    AN INVERTIBLE TRANSFORMATION AND SOME OF ITS APPLICATIONS

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    Several applications of an explicitly invertible transformation are reported. This transformation is elementary and therefore all the results obtained via it might be considered trivial; yet the findings highlighted in this paper are generally far from appearing trivial until the way they are obtained is revealed. Various contexts are considered: algebraic and Diophantine equations, nonlinear Sturm–Liouville problems, dynamical systems (with continuous and with discrete time), nonlinear partial differential equations, analytical geometry, functional equations. While this transformation, in one or another context, is certainly known to many, it does not seem to be as universally known as it deserves to be, for instance it is not routinely taught in basic University courses (to the best of our knowledge). The main purpose of this paper is to bring about a change in this respect; but we also hope that some of the findings reported herein — and the multitude of analogous findings easily obtainable via this te..

    Identification of Design Principles for the Preparation of Colloidal Plexcitonic Materials

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    : Colloidal plexcitonic materials (CPMs) are a class of nanosystems where molecular dyes are strongly coupled with colloidal plasmonic nanoparticles, acting as nanocavities that enhance the light field. As a result of this strong coupling, new hybrid states are formed, called plexcitons, belonging to the broader family of polaritons. With respect to other families of polaritonic materials, CPMs are cheap and easy to prepare through wet chemistry methodologies. Still, clear structure-to-properties relationships are not available, and precise rules to drive the materials' design to obtain the desired optical properties are still missing. To fill this gap, in this article, we prepared a dataset with all CPMs reported in the literature, rationalizing their design by focusing on their three main relevant components (the plasmonic nanoparticles, the molecular dyes, and the capping layers) and identifying the most used and efficient combinations. With the help of statistical analysis, we also found valuable correlations between structure, coupling regime, and optical properties. The results of this analysis are expected to be relevant for the rational design of new CPMs with controllable and predictable photophysical properties to be exploited in a vast range of technological fields

    Traditional knowledge on ethno-veterinary and fodder plants in South Angola: an ethnobotanic field survey in Mopane woodlands in Bibala, Namibe province

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    Livestock is a critical resource to improve income and household livelihoods in many rural areas. To date, very few studies have investigated farmers’ local knowledge on plants used in managing animal health and welfare in Angolan Mopane woodland. This is a very dry ecosystem where animal husbandry (mostly cattle and goats breeding) is highly widespread and is often the main form of subsidence, greatly contributing to local communities food security, especially in periods of resources shortage. An ethnobotanical research project was carried out in Bibala (Namibe province – Angola) in 2010 – 2012, in order to collect information on different traditional uses of plants, involving an interviewed sample of 66 informants. Fifty-eight of them (87.9%) listed a total of 39 species used as ethno-veterinary and/or fodder plants. Ten ethno-veterinary species (28 citations) were reported by 20 informants as used to treat diseases commonly affecting animals in the studied area, namely respiratory tract problems (Laphangium luteoalbum, Gyrocarpus americanus, Craibia brevicaudata subsp. baptistarum, Lepisanthes senegalensis, Ptaeroxylon obliquum, Ximenia americana) and skin diseases and wounds (Aloe littoralis, Blepharis sp., Ficus thonningii), or acting as a general tonic (Faidherbia albida). Thirty-four plants (235 citations) were cited by 58 informants as fodder. In this category of use, the most cited species were Terminalia prunioides (30 citations), Faidherbia albida (28 citations) and Spirostachys africana (21 citations). Our study shows that communities living in South Angola Mopane woodlands still retain a valuable traditional knowledge about plants used to maintain animal health and welfare. This body of knowledge and related skills can play a crucial role in the resilience of livestock systems facing present environmental and socioeconomic changes

    DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions

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    Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling

    Catalytic Mechanism of Fungal Lytic Polysaccharide Monooxygenases Investigated by First-Principles Calculations

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    Lytic polysaccharide monooxygenases (LPMOs) are Cu-containing enzymes that facilitate the degradation of recalcitrant polysaccharides by the oxidative cleavage of glycosidic bonds. They are gaining rapidly increasing attention as key players in biomass conversion, especially for the production of second-generation biofuels. Elucidation of the detailed mechanism of the LPMO reaction is a major step toward the assessment and optimization of LPMO efficacy in industrial biotechnology, paving the way to utilization of sustainable fuel sources. Here, we used density functional theory calculations to study the reaction pathways suggested to date, exploiting a very large active-site model for a fungal AA9 LPMO and using a celloheptaose unit as a substrate mimic. We identify a copper oxyl intermediate as being responsible for H-atom abstraction from the substrate, followed by a rapid, water-assisted hydroxyl rebound, leading to substrate hydroxylation

    Thermolubricity of gas monolayers on graphene

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    Nanofriction of Xe, Kr and N2 monolayers deposited on graphene was explored with a quartz crystal microbalance (QCM) at temperatures between 25 and 50 K. Graphene was grown by chemical vapour deposition and transferred to the QCM electrodes with a polymer stamp. Graphene was found to strongly adhere to the gold electrodes at temperatures as low as 5 K and at frequencies up to 5 MHz. At low temperatures, the Xe monolayers are fully pinned to the graphene surface. Above 30 K, the Xe film slides and the depinning onset coverage beyond which the film starts sliding decreases with temperature. Similar measurements repeated on bare gold show an enhanced slippage of the Xe films and a decrease of the depinning temperature below 25 K. Nanofriction measurements of Kr and N2 confirm this scenario. This thermolubric behaviour is explained in terms of a recent theory of the size dependence of static friction between adsorbed islands and crystalline substrates

    Oxidative Modification of Fibrinogen Is Associated With Altered Function and Structure in the Subacute Phase of Myocardial Infarction.

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    Objective— Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post–acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored. Approach and Results— In 39 patients with post–acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma ( P &lt;0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values; P &lt;0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis ( P &lt;0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified. Conclusions— Here, we report for the first time that patients with post–acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture. </jats:sec

    Absence of Adiponutrin (PNPLA3) and Monoacylglycerol Lipase Synergistically Increases Weight Gain and Aggravates Steatohepatitis in Mice

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    Altered lipid metabolic pathways including hydrolysis of triglycerides are key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether adiponutrin (patatin-like phospholipase domain containing protein-3-PNPLA3) and monoacylglycerol lipase (MGL) synergistically contribute to disease progression remains unclear. We generated double knockout (DKO) mice lacking both Mgl and Pnpla3; DKO mice were compared to Mgl-/- after a challenge by high-fat diet (HFD) for 12 weeks to induce steatosis. Serum biochemistry, liver transaminases as well as histology were analyzed. Fatty acid (FA) profiling was assessed in liver and adipose tissue by gas chromatography. Markers of inflammation and lipid metabolism were analyzed. Bone marrow derived macrophages (BMDMs) were isolated and treated with oleic acid. Combined deficiency of Mgl and Pnpla3 resulted in weight gain on a chow diet; when challenged by HFD, DKO mice showed increased hepatic FA synthesis and diminished beta-oxidation compared to Mgl-/-.DKO mice exhibited more pronounced hepatic steatosis with inflammation and recruitment of immune cells to the liver associated with accumulation of saturated FAs. Primary BMDMs isolated from the DKO mice showed increased inflammatory activities, which could be reversed by oleic acid supplementation. Pnpla3 deficiency aggravates the effects of Mgl deletion on steatosis and inflammation in the liver under HFD challenge

    Monoacylglycerol Lipase Inhibition Protects From Liver Injury in Mouse Models of Sclerosing Cholangitis

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    Background and Aims Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2-arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis, a disease so far lacking effective pharmacological therapy. Approach and Results To this aim we analyzed the effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding to induce sclerosing cholangitis in wild-type (WT) and knockout (MGL(-/-)) mice and tested pharmacological inhibition with JZL184 in the multidrug resistance protein 2 knockout (Mdr2(-/-)) mouse model of sclerosing cholangitis. Cholestatic liver injury and fibrosis were assessed by serum biochemistry, liver histology, gene expression, and western blot characterization of BA and FA synthesis/transport. Moreover, intestinal FAs and fecal microbiome were analyzed. Transfection and silencing were performed in Caco2 cells. MGL(-/-) mice were protected from DDC-induced biliary fibrosis and inflammation with reduced serum liver enzymes and increased FA/BA metabolism and beta-oxidation. Notably, pharmacological (JZL184) inhibition of MGL ameliorated cholestatic injury in DDC-fed WT mice and protected Mdr2(-/-) mice from spontaneous liver injury, with improved liver enzymes, inflammation, and biliary fibrosis. In vitro experiments confirmed that silencing of MGL decreases prostaglandin E-2 accumulation in the intestine and up-regulates peroxisome proliferator-activated receptors alpha and gamma activity, thus reducing inflammation. Conclusions Collectively, our study unravels MGL as a metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for sclerosing cholangitis
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