bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of TRPV6 channel activity by cholesterol depletion in Jurkat T cell line
Authors: Kever Lyudmila , Cherezova Alena , Zenin Valery , Negulyaev Yuri , Komissarchik Yan , Semenova Svetlana 
Published: May 2019

AbstractTransient receptor potential vanilloid 6 (TRPV6) channels are key players in calcium metabolism of healthy and cancerous cells. Nevertheless, the mechanisms controlling abundance of these channels in plasma membrane of the cells to regulate Ca2+transport is still poorly understood. In this study, we provide the first evidence that TRPV6 calcium channels and Ca2+influx in Jurkat T cell line are modulated by cholesterol, a main lipid component of the plasma membrane. Using patch‐clamp technique, we found that activity of TRPV6 channels decreased by cholesterol sequestration with methyl‐β‐cyclodextrin (MβCD). Continuous measurement of intracellular Ca2+revealed a reduction of Ca2+influx into Jurkat cells following cholesterol depletion. Immunofluorescence and immunoelectron microscopy analyses of MβCD‐treated cells detected the lower surface expression of the TRPV6 proteins in comparison with control cells. In general, our data showed that cholesterol regulates TRPV6 channel activity and TRPV6‐mediated Ca2+influx in cells, apparently affecting the localization and density of the calcium channels in the plasma membrane of Jurkat T cells.
Metal‐ and Catalyst‐Free Electrochemical Synthesis of Quinazolinones from Alkenes and 2‐Aminobenzamides
Authors: Teng Qing‐Hu , Sun Yu , Yao Yan , Tang Hai‐Tao , Li Jia‐Rong , Pan Ying‐Ming 
Published: May 2019

AbstractA metal‐ and catalyst‐free electrochemical approach to the preparation of quinazolinones with alkenes and 2‐aminobenzamides via selective anodic oxidative difunctionalization/C−C bond cleavage/cyclization/oxidation has been developed. The synthesis process features convenient operation, low cost, and environmental friendliness, which make it a promising method for the preparation of quinazolinone derivatives.
Synthesis and Characterization of Degradation‐Resistant Cu@CuPd Nanowire Catalysts for the Efficient Production of Formate and CO from CO2
Authors: Hou Yuhui , Erni Rolf , Widmer Roland , Rahaman Motiar , Guo Huizhang , Fasel Roman , Moreno‐García Pavel , Zhang Yucheng , Broekmann Peter 
Published: May 2019

AbstractNot only are the product selectivity and the activity of electrocatalysts important aspects for the evaluation of their overall performance, but also their stability and resistance against structural and compositional degradation during the electrocatalytic reaction. Palladium nanoparticles (Pd‐NPs) have already been identified as superior electrocatalysts for the electrochemical conversion of CO2 into formate at extremely low overpotentials and into carbon monoxide (CO) at medium overpotentials. However, these catalysts suffer from fast degradation, owing to irreversible CO poisoning of Pd reaction sites. Herein, we report on nanoparticulate bimetallic Pd45Cu55 catalysts, demonstrating a similar selectivity and activity to the pure Pd‐NPs, but showing additional superior degradation stability and resistance against CO poisoning. Pd45Cu55 catalysts were synthesized by means of a galvanic displacement reaction using copper nanowires (Cu‐NWs) as the starting material (template) for the galvanic displacement reaction, which leaves a surface‐confined alloy film and respective nanoparticles on the Cu‐NW template (denoted as Cu@CuPd‐NWs). A faradaic efficiency (FE) up to FEformate ≈80 % can be achieved at −0.3 V vs. RHE, thus clearly proving that the ‘anomalous’ CO2 reaction mechanism via the CO2 hydrogenation pathway, discussed for pure Pd‐NPs, can also be transferred to Pd‐based bimetallic systems. At medium overpotentials, the product selectivity changes from selective formate to predominant CO formation with a maximum faradaic efficiency of FECO=86 %. Extended CO2 electrolyses demonstrate, for both formate and CO production, superior degradation stability, for example, FECO remains at 85 %±5 % for the duration of 20 h. For the first time, identical location high‐angle annular dark‐field scanning transmission electron microscopy (IL‐HAADF‐STEM) in combination with energy‐dispersive X‐ray spectrometry and identical location scanning electron microscopy (IL‐SEM) were applied to demonstrate the compositional and structural stability of the bimetallic catalyst under CO2 reduction conditions.
Intrinsic Properties of Macroscopically Tuned Gallium Nitride Single‐Crystalline Facets for Electrocatalytic Hydrogen Evolution
Authors: Hu Haixiao , Chang Bin , Sun Xiucai , Huo Qin , Zhang Baoguo , Li Yanlu , Shao Yongliang , Zhang Lei , Wu Yongzhong , Hao Xiaopeng 
Published: May 2019

AbstractThe anisotropy of crystalline materials results in different physical and chemical properties on different facets, which warrants an in‐depth investigation. Macroscopically facet‐tuned, high‐purity gallium nitride (GaN) single crystals were synthesised and machined, and the electrocatalytic hydrogen evolution reaction (HER) was used as the model reaction to show the differences among the facets. DFT calculations revealed that the Ga and N sites of GaN (100) had a considerably smaller ΔGH* value than those of the metal Ga site of GaN (001) or N site of GaN (00−1), thereby indicating that GaN (100) should be more catalytically active for the HER on account of its nonpolar facet. Subsequent experiments testified that the electrocatalytic performance of GaN (100) was considerably more efficient than that of other facets for both acidic and alkaline HERs. Moreover, the GaN crystal with a preferentially (100) active facet had an excellently durable alkaline electrocatalytic HER for more than 10 days. This work provides fundamental insights into the exploration of the intrinsic properties of materials and designing advanced materials for physicochemical applications.
Dissociation of the Signaling Protein K‐Ras4B from Lipid Membranes Induced by a Molecular Tweezer
Authors: Li Lei , Erwin Nelli , Möbitz Simone , Niemeyer Felix , Schrader Thomas , Winter Roland Hermann Alfons 
Published: May 2019

AbstractOncogenic Ras mutations occur in more than 30 % of human cancers. K‐Ras4B is the most frequently mutated isoform of Ras proteins. Development of effective K‐Ras4B inhibitors has been challenging, hence new approaches to inhibit this oncogenic protein are urgently required. The polybasic domain of K‐Ras4B with its stretch of lysine residues is essential for its plasma membrane targeting and localization. Employing CD and fluorescence spectroscopy, confocal fluorescence, and atomic force microscopy we show that the molecular tweezer CLR01 is able to efficiently bind to the lysine stretch in the polybasic domain of K‐Ras4B, resulting in dissociation of the K‐Ras4B protein from the lipid membrane and disintegration of K‐Ras4B nanoclusters in the lipid bilayer. These results suggest that targeting of the polybasic domain of K‐Ras4B by properly designed tweezers might represent an effective strategy for inactivation of K‐Ras4B signaling.
From 3D to 2D: Structural, Spectroscopic and Theoretical Investigations of the Dimensionality Reduction in the [PtAl2]δ− Polyanions of the Isotypic MPtAl2 Series (M=Ca–Ba, Eu)
Authors: Stegemann Frank , Block Theresa , Klenner Steffen , Zhang Yuemei , Fokwa Boniface P. T. , Timmer Alexander , Mönig Harry , Doerenkamp Carsten , Eckert Hellmut , Janka Oliver 
Published: May 2019

AbstractFour new MPtAl2 (M=Ca, Sr, Ba, Eu) compounds, adopting the orthorhombic MgCuAl2‐type structure, have been synthesized from the elements using tantalum ampoules. All compounds are obtained as platelet‐shaped crystallites and exhibit an increasing moisture sensitivity with increasing size of the formal M cation. Structural investigations indicate a pronounced elongation of the crystallographic b‐axis, which results in a significant distortion of the [PtAl2]δ− polyanion. Within the polyanion, layer‐like arrangements can be found with bonding Pt−Al interactions within the slab; the increase of the b‐axis can be attributed to increasing Al−Al distances and therefore decreasing interactions between the slabs, caused by the differently‐sized formal M cations. While the alkaline earth (M=Ca, Sr) representatives exhibit Pauli paramagnetism, BaPtAl2 shows diamagnetic behavior, finally EuPtAl2 is ferromagnetic with TC=54.0(5) K. The effective magnetic moment indicates that the Eu atoms are in a divalent oxidation state, which is confirmed by 151Eu Mössbauer spectroscopic investigations. Measurements below the Curie‐temperature show a full magnetic hyperfine field splitting with Bhf=21.7(1) T. 27Al and 195Pt magic‐angle spinning NMR spectroscopy corroborates the presence of single crystallographic sites for the Pt and Al atoms. The large 27Al nuclear electric quadrupolar coupling constants confirm unusually strong electric field gradients, in agreement with the structural distortions and the respective theoretical calculations. X‐ray photoelectron spectroscopy has been utilized to investigate the charge transfer within the polyanion. The Pt 4f binding energy decreases with decreasing electronegativity / ionization energy of the alkaline earth elements, suggesting an increasing electron density at the Pt atoms. Theoretical investigations underline the platinide character of the investigated compounds by Bader charge calculations. The analysis of the integrated crystal orbital Hamilton population (ICOHP) values, electron localization function (ELF) and isosurface analyses lead to a consistent structural picture, indicating stable layer‐like arrangements of the [PtAl2]δ− polyanion.
Computer‐Assisted Selective Optimization of Side‐Activities—from Cinalukast to a PPARα Modulator
Authors: Pollinger Julius , Schierle Simone , Neumann Sebastian , Ohrndorf Julia , Kaiser Astrid , Merk Daniel 
Published: May 2019

AbstractAutomated computational analogue design and scoring can speed up hit‐to‐lead optimization and appears particularly promising in selective optimization of side‐activities (SOSA) where possible analogue diversity is confined. Probing this concept, we employed the cysteinyl leukotriene receptor 1 (CysLT1R) antagonist cinalukast as lead for which we discovered peroxisome proliferator‐activated receptor α (PPARα) modulatory activity. We automatically generated a virtual library of close analogues and classified these roughly 8000 compounds for PPARα agonism and CysLT1R antagonism using automated affinity scoring and machine learning. A computationally preferred analogue for SOSA was synthesized, and in vitro characterization indeed revealed a marked activity shift toward enhanced PPARα activation and diminished CysLT1R antagonism. Thereby, this prospective application study highlights the potential of automating SOSA.
Analysis, Simulation, and Optimization of Stochastic Vesicle Dynamics in Synaptic Transmission
Authors: Zhang Calvin , Peskin Charles S. 
Published: May 2019

AbstractSynaptic transmission is the mechanism of information transfer from one neuron to another (or from a neuron to a muscle or to an endocrine cell). An important step in this physiological process is the stochastic release of neurotransmitter from vesicles that fuse with the presynaptic membrane and spill their contents into the synaptic cleft. We are concerned here with the formulation, analysis, and simulation of a mathematical model that describes the stochastic docking, undocking, and release of synaptic vesicles and their effect on synaptic signal transmission. The focus of this paper is on the parameterp0, the probability of release for each docked vesicle when an action potential arrives. We study the influence of this parameter on the statistics of the release process and on the theoretical capability of the model synapse in reconstructing various desired outputs based on the timing and amount of neurotransmitter release. This theoretical capability is assessed by formulating and solving an optimal filtering problem. Methods for parameter identification are proposed and applied to simulated data. © 2019 Wiley Periodicals, Inc.
Synthesis of Oxazolidinones by using Carbon Dioxide as a C1 Building Block and an Aluminium‐Based Catalyst
Authors: Sengoden Mani , North Michael , Whitwood Adrian C. 
Published: May 2019

AbstractOxazolidinone synthesis through the coupling of carbon dioxide and aziridines was catalysed by an aluminium(salphen) complex at 50–100 °C and 1–10 bar pressure under solvent‐free conditions. The process was applicable to a variety of substituted aziridines, giving products with high regioselectivity. It involved the use of a sustainable and reusable aluminium‐based catalyst, used carbon dioxide as a C1 source and provided access to pharmaceutically important oxazolidinones as illustrated by a total synthesis of toloxatone. This protocol was scalable, and the catalyst could be recovered and reused. A catalytic cycle was proposed based on stereochemical, kinetic and Hammett studies.
Folic acid functionalized nanoparticles as pharmaceutical carriers in drug delivery systems
Authors: Narmani Asghar , Rezvani Melina , Farhood Bagher , Darkhor Parvaneh , Mohammadnejad Javad , Amini Bahram , Refahi Soheila , Abdi Goushbolagh Nouraddin 
Published: May 2019

AbstractConventional chemotherapeutic approaches in cancer therapy such as surgery, chemotherapy, and radiotherapy have several disadvantages due to their nontargeted distributions in the whole body. On the other hand, nanoparticles (NPs) based therapies are remarkably progressing to solve several limitations of conventional drug delivery systems (DDSs) including nonspecific biodistribution and targeting, poor water solubility, weak bioavailability and biodegradability, low pharmacokinetic properties, and so forth. The enhanced permeability and retention effect escape from P‐glycoprotein trap in cancer cells as a passive targeting mechanism, and active targeting strategies are also other most important advantages of NPs in cancer diagnosis and therapy. Folic acid (FA) is one of the biologic molecules which has been targeted overexpressed‐folic acid receptor (FR) on the surface of cancer cells. Therefore, conjugation of FA to NPs most easily enhances the FR‐mediated targeting delivery of therapeutic agents. Here, the recent works in FA which have been decorated NPs‐based DDSs are discussed and cancer therapy potency of these NPs in clinical trials are presented.
Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary
Authors: Kiss Zoltán , Rokszin György , Abonyi‐Tóth Zsolt , Jermendy György , Kempler Péter , Barkai László , Wittmann István 
Published: May 2019

AbstractBACKGROUNDThere are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40).METHODSWe identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all‐cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period.RESULTSThe risks of all‐cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95‐2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71‐1.13; P = 0.36) and stroke (1.06, 0.87‐1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15‐1.59; P = .0003), dialysis (2.20, 1.76‐2.75; P < .0001), hypoglycemia (7.70, 6.45‐9.18; P < .0001), and ketoacidosis (22.12, 19.60‐25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes.CONCLUSIONSA comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.
A heterochronic shift in skeletal development in the barn owl (Tyto furcata): A description of the ocular skeleton and tubular eye shape formation
Authors: Franz‐Odendaal Tamara A. , Krings Markus 
Published: May 2019

AbstractBackgroundThe eyes of some birds of prey (Strigiformes and some eagles) are tubular in shape, which contrasts strongly with those in others, which are more globose (e.g., Galliformes) or flat (most diurnal birds). Regardless, all birds have an ocular skeleton composed of a ring of ossicles (annulus ossicularis sclerae) and a cartilage cup within the sclera.ResultsWe show that the tubular eye of the barn owl, Tyto furcata, grows substantially in length to achieve its long axial length several weeks after hatching, well after the period when the visual input adjusts the optical system and when the scleral ossicles mineralize. This is in contrast to the chicken. The conjunctival papillae are morphologically different in each species, however, they are present for about 3 days in both birds before they degenerate.ConclusionsOur data shows a heterochronic shift in the timing of scleral cartilage development and ossicle mineralization (but not induction) to later in development compared to in the chicken. These shifts likely relate to the altricial vs precocial nature of these birds and suggests that the scleral ossicles are likely functionally important bones for vision in owls and possibly other altricial species.
Study of the effect of culture mediums on the amino acid metabolites for Corynebacterium glutamicum using high‐speed micellar electrokinetic chromatography
Authors: Wang Wei , Bai Ruiguang , Zhang Huimin , Cai Xiaoyu 
Published: May 2019

AbstractCorynebacterium glutamicum (C. glutamicum) is a well‐known workhorse for the industrial production of amino acids. Different carbon, nitrogen, and sulfur source may force the bacterium to produce specific metabolites. In this work, a method of high‐speed MEKC with LIF detection was developed to rapidly analyze the amino acid metabolites released by C. glutamicum, which is fed with different culture mediums. Corynebacterium glutamicum was cultured in microbial fuel cells to monitor its metabolism process and collect its metabolites. In the CE system, a microliter‐scale sample reservoir was designed and applied to perform tiny volume sample injection. With the assistance of microwave, the derivatization time for amino acids with FITC was greatly shortened to 6 min. Under the optimized condition, the eight candidate amino acids of metabolites could be rapidly separated within 2 min. The whole analysis process for real samples, from sampling to determination, could be shortened to less than 10 min. The results showed that C. glutamicum could produce additional l‐lysine and l‐valine as the metabolites when fed with glucose and l‐methionine, respectively. The method proved that culture mediums used to feed C. glutamicum had great effect on the bacterium's metabolites.
Chiral separation of cathinone derivatives using β‐cyclodextrin‐assisted capillary electrophoresis–Comparison of four different β‐cyclodextrin derivatives used as chiral selectors
Authors: Hägele Johannes S. , Hubner Eva‐Maria , Schmid Martin G. 
Published: May 2019

AbstractIn the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness‐changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different β‐cyclodextrin derivatives. As chiral selectors, native β‐cyclodextrin as well as three of its derivatives namely acetyl‐β‐cyclodextrin, 2‐hydroxypropyl‐β‐cyclodextrin, and carboxymethyl‐β‐cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of β‐cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra‐ and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.
Small‐molecule‐mediated chemical knock‐down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure
Authors: Adams Volker , Bowen T. Scott , Werner Sarah , Barthel Peggy , Amberger Christina , Konzer Anne , Graumann Johannes , Sehr Peter , Lewis Joe , Provaznik Jan , Benes Vladimir , Büttner Petra , Gasch Alexander , Mangner Norman , Witt Christian C. , Labeit Dittmar , Linke Axel , Labeit Siegfried 
Published: May 2019

AbstractBackgroundChronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small‐molecule inhibitor of MuRF1 in treating CHF‐induced diaphragm myopathy and loss of contractile function.MethodsMyocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham‐operated animals (sham) served as controls. One week post‐left anterior descending coronary artery ligation animals were randomized into two groups—one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946—a recently described MuRF1‐interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed.ResultsChronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P < 0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and up‐regulation of the MuRF1 and MuRF2 was attenuated after infarct.ConclusionsOur murine CHF model presented with diaphragm fibre atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Compound ID#704946 rescued from this partially, possibly by targeting MuRF1/MuRF2. However, at this stage of our study, we refrain to claim specific mechanism(s) and targets of compound ID#704946, because the nature of changes after 12 weeks of feeding is likely to be complex and is not necessarily caused by direct mechanistic effects.