bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients
Authors: Kagaya Hideaki , Niioka Takenori , Saito Mitsuru , Inoue Takamitsu , Numakura Kazuyuki , Yamamoto Ryohei , Akamine Yumiko , Habuchi Tomonori , Satoh Shigeru , Miura Masatomo
Published: March 2018

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation. Significant correlations between the AUC/D of tacrolimus and everolimus were found for patients with the CYP3A5*1 allele or CYP3A5*3/*3 at both one month and one year. At both stages, the determination coefficients were higher and the slopes of regression equations were larger for patients with CYP3A5*3/*3 compared to the CYP3A5*1 allele. A good correlation between single doses of tacrolimus and everolimus was found for CYP3A5*3/*3 patients at 1 year after transplantation (r = 0.794, p < 0.001). The variability of the AUC0–24/D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC0–12/D of everolimus. Clinicians may be able to comprehensively carry out the dose adjustments of tacrolimus and everolimus based on relationship with AUCs of both drugs in each CYP3A5 genotype.
Bias-Exchange Metadynamics Simulation of Membrane Permeation of 20 Amino Acids
Authors: Cao Zanxia , Bian Yunqiang , Hu Guodong , Zhao Liling , Kong Zhenzhen , Yang Yuedong , Wang Jihua , Zhou Yaoqi
Published: March 2018

Thermodynamics of the permeation of amino acids from water to lipid bilayers is an important first step for understanding the mechanism of cell-permeating peptides and the thermodynamics of membrane protein structure and stability. In this work, we employed bias-exchange metadynamics simulations to simulate the membrane permeation of all 20 amino acids from water to the center of a dipalmitoylphosphatidylcholine (DPPC) membrane (consists of 256 lipids) by using both directional and torsion angles for conformational sampling. The overall accuracy for the free energy profiles obtained is supported by significant correlation coefficients (correlation coefficient at 0.5–0.6) between our results and previous experimental or computational studies. The free energy profiles indicated that (1) polar amino acids have larger free energy barriers than nonpolar amino acids; (2) negatively charged amino acids are the most difficult to enter into the membrane; and (3) conformational transitions for many amino acids during membrane crossing is the key for reduced free energy barriers. These results represent the first set of simulated free energy profiles of membrane crossing for all 20 amino acids.
Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement
Authors: Lescoat Alain , Ballerie Alice , Augagneur Yu , Morzadec Claudie , Vernhet Laurent , Fardel Olivier , Jégo Patrick , Jouneau Stéphane , Lecureur Valérie
Published: March 2018

Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.
An Anion Conductance, the Essential Component of the Hydroxyl-Radical-Induced Ion Current in Plant Roots
Authors: Pottosin Igor , Zepeda-Jazo Isaac , Bose Jayakumar , Shabala Sergey
Published: March 2018

Oxidative stress signaling is essential for plant adaptation to hostile environments. Previous studies revealed the essentiality of hydroxyl radicals (HO•)-induced activation of massive K+ efflux and a smaller Ca2+ influx as an important component of plant adaptation to a broad range of abiotic stresses. Such activation would modify membrane potential making it more negative. Contrary to these expectations, here, we provide experimental evidence that HO• induces a strong depolarization, from −130 to −70 mV, which could only be explained by a substantial HO•-induced efflux of intracellular anions. Application of Gd3+ and NPPB, non-specific blockers of cation and anion conductance, respectively, reduced HO•-induced ion fluxes instantaneously, implying a direct block of the dual conductance. The selectivity of an early instantaneous HO•-induced whole cell current fluctuated from more anionic to more cationic and vice versa, developing a higher cation selectivity at later times. The parallel electroneutral efflux of K+ and anions should underlie a substantial leak of the cellular electrolyte, which may affect the cell’s turgor and metabolic status. The physiological implications of these findings are discussed in the context of cell fate determination, and ROS and cytosolic K+ signaling.
Individual versus Combinatorial Effects of Silicon, Phosphate, and Iron Deficiency on the Growth of Lowland and Upland Rice Varieties
Authors: Chaiwong Nanthana , Prom-u-thai Chanakan , Bouain Nadia , Lacombe Benoit , Rouached Hatem
Published: March 2018

Mineral nutrient homeostasis is essential for plant growth and development. Recent research has demonstrated that the occurrence of interactions among the mechanisms regulating the homeostasis of different nutrients in plants is a general rule rather than an exception. Therefore, it is important to understand how plants regulate the homeostasis of these elements and how multiple mineral nutrient signals are wired to influence plant growth. Silicon (Si) is not directly involved in plant metabolism but it is an essential element for a high and sustainable production of crops, especially rice, because of its high content in the total shoot dry weight. Although some mechanisms underlying the role of Si in plants responses to both abiotic and biotic stresses have been proposed, the involvement of Si in regulating plant growth in conditions where the availability of essential macro- and micronutrients changes remains poorly investigated. In this study, the existence of an interaction between Si, phosphate (Pi), and iron (Fe) availability was examined in lowland (Suphanburi 1, SPR1) and upland (Kum Hom Chiang Mai University, KH CMU) rice varieties. The effect of Si and/or Fe deficiency on plant growth, Pi accumulation, Pi transporter expression (OsPHO1;2), and Pi root-to-shoot translocation in these two rice varieties grown under individual or combinatorial nutrient stress conditions were determined. The phenotypic, physiological, and molecular data of this study revealed an interesting tripartite Pi-Fe-Si homeostasis interaction that influences plant growth in contrasting manners in the two rice varieties. These results not only reveal the involvement of Si in modulating rice growth through an interaction with essential micro- and macronutrients, but, more importantly, they opens new research avenues to uncover the molecular basis of Pi-Fe-Si signaling crosstalk in plants.
Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection
Authors: Panou Margarita-Maria , Prescott Emma , Hurdiss Daniel , Swinscoe Gemma , Hollinshead Michael , Caller Laura , Morgan Ethan , Carlisle Louisa , Müller Marietta , Antoni Michelle , Kealy David , Ranson Neil , Crump Colin , Macdonald Andrew
Published: March 2018

BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.
Alternative Respiratory Pathway Component Genes (AOX and ND) in Rice and Barley and Their Response to Stress
Authors: Wanniarachchi Vajira , Dametto Lettee , Sweetman Crystal , Shavrukov Yuri , Day David , Jenkins Colin , Soole Kathleen
Published: March 2018

Plants have a non-energy conserving bypass of the classical mitochondrial cytochrome c pathway, known as the alternative respiratory pathway (AP). This involves type II NAD(P)H dehydrogenases (NDs) on both sides of the mitochondrial inner membrane, ubiquinone, and the alternative oxidase (AOX). The AP components have been widely characterised from Arabidopsis, but little is known for monocot species. We have identified all the genes encoding components of the AP in rice and barley and found the key genes which respond to oxidative stress conditions. In both species, AOX is encoded by four genes; in rice OsAOX1a, 1c, 1d and 1e representing four clades, and in barley, HvAOX1a, 1c, 1d1 and 1d2, but no 1e. All three subfamilies of plant ND genes, NDA, NDB and NDC are present in both rice and barley, but there are fewer NDB genes compared to Arabidopsis. Cyanide treatment of both species, along with salt treatment of rice and drought treatment of barley led to enhanced expression of various AP components; there was a high level of co-expression of AOX1a and AOX1d, along with NDB3 during the stress treatments, reminiscent of the co-expression that has been well characterised in Arabidopsis for AtAOX1a and AtNDB2.
Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations
Authors: Mei Longcan , Zhou Yanping , Zhu Lizhe , Liu Changlin , Wu Zhuo , Wang Fangkui , Hao Gefei , Yu Di , Yuan Hong , Cui Yanfang
Published: March 2018

A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis.
The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum
Authors: Szymanska Kamila , Makowska Krystyna , Gonkowski Slawomir
Published: March 2018

Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT—used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms.
Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters
Authors: Ilgü Hüseyin , Jeckelmann Jean-Marc , Colas Claire , Ucurum Zöhre , Schlessinger Avner , Fotiadis Dimitrios
Published: March 2018

The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.
p53 as a Dichotomous Regulator of Liver Disease: The Dose Makes the Medicine
Authors: Krstic Jelena , Galhuber Markus , Schulz Tim J. , Schupp Michael , Prokesch Andreas
Published: March 2018

Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues. The transcription factor p53 is well established as a tumor suppressor and has recently been described as a central metabolic player both in physiological and pathological settings. Given that liver is a dynamic tissue with direct exposition to ingested nutrients, hepatic p53, by integrating cellular stress response, metabolism and cell cycle regulation, has emerged as an important regulator of liver homeostasis and dysfunction. The underlying evidence is reviewed herein, with a focus on clinical data and animal studies that highlight a direct influence of p53 activity on different stages of liver diseases. Based on current literature showing that activation of p53 signaling can either attenuate or fuel liver disease, we herein discuss the hypothesis that, while hyper-activation or loss of function can cause disease, moderate induction of hepatic p53 within physiological margins could be beneficial in the prevention and treatment of liver pathologies. Hence, stimuli that lead to a moderate and temporary p53 activation could present new therapeutic approaches through several entry points in the cascade from hepatic steatosis to HCC.
A Smart Sensor Data Transmission Technique for Logistics and Intelligent Transportation Systems
Authors: Sun Kyunghee , Ryoo Intae
Published: March 2018

When it comes to Internet of Things systems that include both a logistics system and an intelligent transportation system, a smart sensor is one of the key elements to collect useful information whenever and wherever necessary. This study proposes the Smart Sensor Node Group Management Medium Access Control Scheme designed to group smart sensor devices and collect data from them efficiently. The proposed scheme performs grouping of portable sensor devices connected to a system depending on the distance from the sink node and transmits data by setting different buffer thresholds to each group. This method reduces energy consumption of sensor devices located near the sink node and enhances the IoT system’s general energy efficiency. When a sensor device is moved and, thus, becomes unable to transmit data, it is allocated to a new group so that it can continue transmitting data to the sink node.
Osteoclast Formation within a Human Co-Culture System on Bone Material as an In Vitro Model for Bone Remodeling Processes
Authors: Schmid Franziska , Kleinhans Claudia , Schmid Freia , Kluger Petra
Published: March 2018

Bone remodeling can be mimicked in vitro by co-culture models. Based on bone cells, such co-cultures help to study synergistic morphological changes and the impact of materials and applied substances. Hence, we examined the formation of osteoclasts on bovine bone materials to prove the bone resorption functionality of the osteoclasts in three different co-culture set-ups using human monocytes (hMCs) and (I) human mesenchymal stem cells (hMSCs), (II) osteogenic differentiated hMSCs (hOBs), and (III) hOBs in addition of soluble monocyte-colony stimulating factor (M-CSF) and cytokine receptor activator of NFκB ligand (RANKL). We detected osteoclast-specific actin morphology, as well as the expression of cathepsin K and CD51/61 in single cells in set-up II and in numerous cells in set-up III. Resorption pits on bone material as characteristic proof of functional osteoclasts were not found in set-up I and II, but we detected such resorption pits in set–up III. We conclude in co-culture models without M-CSF and RANKL that monocytes can differentiate into osteoclasts that show the characteristic actin structures and protein expression. However, to receive functional bone resorbing osteoclasts in vitro, the addition of M-CSF and RANKL is needed. Moreover, we suggest the use of bone or bone-like materials for future studies evaluating osteoclastogenesis.
Post-War Land Cover Changes and Fragmentation in Halgurd Sakran National Park (HSNP), Kurdistan Region of Iraq
Authors: Hamad Rahel , Kolo Kamal , Balzter Heiko
Published: March 2018

Context: The fundamental driving force of land use and land cover (LULC) change is related to spatial and temporal processes caused by human activities such as agricultural expansion and demographic change. Landscape metrics were used to analyze post-war changes in a rural mountain landscape, the protected area of Halgurd-Sakran National Park (HSNP) in north-east Iraq. Therefore, the present work attempts to identify the temporal trends of the most fragmented land cover types between two parts of the national park. Objectives: The objectives of this study are to compare two land cover classification algorithms, maximum likelihood classification (MLC) and random forest (RF) in the upper and lower parts of HSCZ, and to examine whether landscape configuration in the park has changed over time by comparing the fragmentation, connectivity and diversity of LULC classes. Methods: Two Landsat images were used to analyze LULC fragmentation and loss of habitat connectivity (before and after the Fall of Baghdad in 2003). Seven landscape pattern metrics, percentage of land (PLAND), number of patch (NP), largest patch index (LPI), mean patch size (MPS), euclidian nearest neighborhood distance (ENN_AM), interspersion and juxtaposition (IJI) and cohesion at class level were selected to assess landscape composition and configuration. Results: A significant change in LULC classes was noticed in the lower part of the park, especially for pasture, cultivated and forest-lands. The fragmentation trends and their changes were observed in both parts of the park, however, more were observed in the lower part. The inherent causes of these changes are the socio-economic factors created by the 1991–2003 UN post-war economic sanctions. The changes increased during sanctions and decreased afterwards. The fall of Baghdad in 2003, followed by rapid economic boom, marked the greatest cause in land use change, especially in changes-susceptible cultivated areas. Conclusions: Shrinkage of forest patches in the lower part of the park increases the distance between them, which contributes to a decline in biological diversity from decreasing habitat area. Lastly, the results confirm the applicability of the combined method of remote sensing and landscape metrics.
On Recursive Modification in Child L1 French
Authors: Roberge Yves , Pérez-Leroux Ana Teresa , Frolova Anna
Published: March 2018

This paper investigates nominal recursive modification (RM) in the L1 acquisition of French. Although recursion is considered the fundamental property of human languages, recursive self-embedding is found to be difficult for children in a variety of languages and constructions. Despite these challenges, the acquisition of RM proves to be resilient; acquirable even under severely degraded input conditions. From a minimalist perspective on the operations of narrow syntax, recursive embedding is essentially the application of a sequence of Merge operations (Chomsky 1995; Trotzke and Zwart 2014); therefore, given the universality of Merge, we do not expect to find cross-linguistic differences in how difficult recursion is. But if the challenging nature of recursion stems from factors which might differ from language to language, we expect different outcomes cross-linguistically. We compare new data from French to existing English data (Pérez-Leroux et al. 2012) in order to examine to what extent language-specific properties of RM structures determine the acquisition path. While children’s production differs significantly from their adult’s counterparts, we find no differences between French-speaking and English-speaking children. Our findings suggest that the challenging nature of recursion does not stem from the grammar itself and that what shapes the acquisition path is the interaction between universal properties of language and considerations not specific to language, namely computational efficiency.
Machining of Fibre Reinforced Plastic Composite Materials
Authors: Caggiano Alessandra
Published: March 2018

Fibre reinforced plastic composite materials are difficult to machine because of the anisotropy and inhomogeneity characterizing their microstructure and the abrasiveness of their reinforcement components. During machining, very rapid cutting tool wear development is experienced, and surface integrity damage is often produced in the machined parts. An accurate selection of the proper tool and machining conditions is therefore required, taking into account that the phenomena responsible for material removal in cutting of fibre reinforced plastic composite materials are fundamentally different from those of conventional metals and their alloys. To date, composite materials are increasingly used in several manufacturing sectors, such as the aerospace and automotive industry, and several research efforts have been spent to improve their machining processes. In the present review, the key issues that are concerning the machining of fibre reinforced plastic composite materials are discussed with reference to the main recent research works in the field, while considering both conventional and unconventional machining processes and reporting the more recent research achievements. For the different machining processes, the main results characterizing the recent research works and the trends for process developments are presented.
Electronic, Optical, and Lattice Dynamical Properties of Tetracalcium Trialuminate (Ca4Al6O13)
Authors: Mei Huayue , Zhong Yuhan , Wang Peida , Jia Zhenyuan , Li Chunmei , Cheng Nanpu
Published: March 2018

The electronic, optical, and lattice dynamical properties of tetracalcium trialuminate (Ca4Al6O13) with a special sodalite cage structure were calculated based on the density functional theory. Theoretical results show that Ca4Al6O13 is ductile and weakly anisotropic. The calculated Young’s modulus and Poisson ratio are 34.18 GPa and 0.32, respectively. Ca4Al6O13 is an indirect-gap semiconductor with a band gap of 5.41 eV. The top of the valence band derives from O 2p states, and the bottom of conduction band consists of Ca 3d states. Transitions from O 2p, 2s states to empty Ca 4s, 3d and Al 3s, 3p states constitute the major peaks of the imaginary part of the dielectric function. Ca4Al6O13 is a good UV absorber for photoelectric devices due to the high absorption coefficient and low reflectivity. The lattice vibration analysis reveals that O atoms contribute to the high-frequency portions of the phonon spectra, while Ca and Al atoms make important contributions to the middle- and low-frequency portions. At the center of the first Brillouin zone, lattice vibrations include the Raman active modes (E, A1), infrared active mode (T2), and silentmodes (T1, A2). Typical atomic displacement patterns were also investigated to understand the vibration modes more intuitively.
The Preparation of TiO2 Film by the Sol-Gel Method and Evaluation of Its Self-Cleaning Property
Authors: Liang Yu , Sun Sijia , Deng Tongrong , Ding Hao , Chen Wanting , Chen Ying
Published: March 2018

TiO2 sol was produced by the sol-gel method through the hydrolysis and the aging of tetrabutyl titanate and the TiO2 film was obtained by dipping and uniform lifting of the acid-treated and ultrasound-treated clean glass slides into the TiO2 sol followed by aging, drying, and calcination. The effect of the hydrolysis control agents to the formed sol was researched and the crystalline state, the morphology, and the photocatalytic properties of the products after calcination were characterized. The structural morphology, the contact angles before and after illumination, and the self-cleaning properties of the TiO2 film were characterized as well. The results showed that by using acetylacetone as the hydrolysis control agent, the formed TiO2 sol had relatively high stability. The product after the calcination of the TiO2 sol was of single anatase type with crystalline size of 18–20 nm and it could degrade nearly 100% of methylene blue after 90 min illumination. The formed TiO2 film is compact, continuous, smooth, and had the properties of super-hydrophilicity (after 30 min illumination due to its contact angle decreasing from 21° to nearly 0°) and anti-fogging capability, which indicated its excellent self-cleaning property.
The Effect of Poly (Glycerol Sebacate) Incorporation within Hybrid Chitin–Lignin Sol–Gel Nanofibrous Scaffolds
Authors: Abdullah Turdimuhammad , Gzara Lassaad , Simonetti Giovanna , Alshahrie Ahmed , Salah Numan , Morganti Pierfrancesco , Chianese Angelo , Fallahi Afsoon , Tamayol Ali , Bencherif Sidi , Memic Adnan
Published: March 2018

Chitin and lignin primarily accumulate as bio-waste resulting from byproducts of crustacean crusts and plant biomass. Recently, their use has been proposed for diverse and unique bioengineering applications, amongst others. However, their weak mechanical properties need to be improved in order to facilitate their industrial utilization. In this paper, we fabricated hybrid fibers composed of a chitin–lignin (CL)-based sol–gel mixture and elastomeric poly (glycerol sebacate) (PGS) using a standard electrospinning approach. Obtained results showed that PGS could be coherently blended with the sol–gel mixture to form a nanofibrous scaffold exhibiting remarkable mechanical performance and improved antibacterial and antifungal activity. The developed hybrid fibers showed promising potential in advanced biomedical applications such as wound care products. Ultimately, recycling these sustainable biopolymers and other bio-wastes alike could propel a “greener” economy.
Numerical Solution for Fuzzy Enzyme Kinetic Equations by the Runge–Kutta Method
Authors: Barazandeh Yousef , Ghazanfari Bahman
Published: March 2018

One of the most important biochemical reactions is catalyzed by enzymes. A numerical method to solve nonlinear equations of enzyme kinetics, known as the Michaelis and Menten equations, together with fuzzy initial values is introduced. The numerical method is based on the fourth order Runge–Kutta method, which is generalized for a fuzzy system of differential equations. The convergence and stability of the method are also presented. The capability of the method in fuzzy enzyme kinetics is demonstrated by some numerical examples.
Phocoenamicins B and C, New Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp.
Authors: Pérez-Bonilla Mercedes , Oves-Costales Daniel , De la Cruz Mercedes , Kokkini Maria , Martín Jesús , Vicente Francisca , Genilloud Olga , Reyes Fernando
Published: March 2018

Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, displayed activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds 1 and 2 belonging to the spirotetronate class of polyketides. Their structures were determined using a combination of HRMS, 1D and 2D NMR experiments and comparison with the spectra reported for phocoenamicin. Antibacterial activity tests of the pure compounds against these pathogens revealed minimal inhibitory concentration (MIC) values ranging from 4 to 64 µg/mL for MRSA, and 16 to 32 µg/mL for M. tuberculosis H37Ra, with no significant activity found against M. bovis and vancomycin-resistant Enterococcus faecium (VRE) at concentrations below 128 µg/mL, and weak activity detected against Bacillus subtilis grown on agar plates.
GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization
Authors: Scandolera Amandine , Hubert Jane , Humeau Anne , Lambert Carole , De Bizemont Audrey , Winkel Chris , Kaouas Abdelmajid , Renault Jean-Hugues , Nuzillard Jean-Marc , Reynaud Romain
Published: March 2018

The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.
GC-MS-Based Endometabolome Analysis Differentiates Prostate Cancer from Normal Prostate Cells
Authors: Lima Ana , Araújo Ana , Pinto Joana , Jerónimo Carmen , Henrique Rui , Bastos Maria , Carvalho Márcia , Guedes de Pinho Paula
Published: March 2018

Prostate cancer (PCa) is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA) has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography–mass spectrometry (GC-MS) based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR) expression, DU145 and PC3 (which lack AR expression), and one normal prostate cell line (PNT2). Regarding the metastatic potential, PC3 is from an adenocarcinoma grade IV with high metastatic potential, DU145 has a moderate metastatic potential, and LNCaP has a low metastatic potential. Using multivariate analysis, alterations in levels of several intracellular metabolites were detected, disclosing the capability of the endometabolome to discriminate all PCa cell lines from the normal prostate cell line. Discriminant metabolites included amino acids, fatty acids, steroids, and sugars. Six stood out for the separation of all the studied PCa cell lines from the normal prostate cell line: ethanolamine, lactic acid, β-Alanine, L-valine, L-leucine, and L-tyrosine.
Modeling and Analysis of an Opto-Fluidic Sensor for Lab-on-a-Chip Applications
Authors: Muniswamy Venkatesha , Bangalore Muniraju Chaya , Kumar Pattnaik Prasant , Krishnaswamy Narayan
Published: March 2018

In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of microparticles in the microfluidic channel for lab-on-a-chip (LOC) sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of microparticles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1 Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI) integrated optical waveguide at an infrared wavelength of 1550 nm for single mode sensing operation is presented. The optical loss is found to be 5.7 × 10−4 dB/cm with an effective index of 2.3. The model presented in this work can be effectively used to detect the nature of microparticles and continuous monitoring of pathological parameters for sensing applications.
Novel Semisynthetic Derivatives of Bile Acids as Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibitors
Authors: Salomatina Oksana , Popadyuk Irina , Zakharenko Alexandra , Zakharova Olga , Fadeev Dmitriy , Komarova Nina , Reynisson Jóhannes , Arabshahi H. , Chand Raina , Volcho Konstantin , Salakhutdinov Nariman , Lavrik Olga
Published: March 2018

An Important task in the treatment of oncological and neurodegenerative diseases is the search for new inhibitors of DNA repair system enzymes. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the DNA repair system enzymes involved in the removal of DNA damages caused by topoisomerase I inhibitors. Thus, reducing the activity of Tdp1 can increase the effectiveness of currently used anticancer drugs. We describe here a new class of semisynthetic small molecule Tdp1 inhibitors based on the bile acid scaffold that were originally identified by virtual screening. The influence of functional groups of bile acids (hydroxy and acetoxy groups in the steroid framework and amide fragment in the side chain) on inhibitory activity was investigated. In vitro studies demonstrate the ability of the semisynthetic derivatives to effectively inhibit Tdp1 with IC50 up to 0.29 µM. Furthermore, an excellent fit is realized for the ligands when docked into the active site of the Tdp1 enzyme.
Erratum: Antonsen, S.; et al. Synthesis of Racemic β-Chamigrene, a Spiro[5.5]undecane Sequiterpene. Molecules 2014, 19, 20664–20670
Authors:   Molecules Editorial Office
Published: March 2018

The Molecules Editorial Office wishes to make the following erratum to this paper [1].[...]
Supramolecular Control over the Interparticle Distance in Gold Nanoparticle Arrays by Cyclodextrin Polyrotaxanes
Authors: Paulo Coelho Joao , Osío Barcina José , Junquera Elena , Aicart Emilio , Tardajos Gloria , Gómez-Graña Sergio , Cruz-Gil Pablo , Salgado Cástor , Díaz-Núñez Pablo , Peña-Rodríguez Ovidio , Guerrero-Martínez Andrés
Published: March 2018

Amphiphilic nonionic ligands, synthesized with a fixed hydrophobic moiety formed by a thiolated alkyl chain and an aromatic ring, and with a hydrophilic tail composed of a variable number of oxyethylene units, were used to functionalize spherical gold nanoparticles (AuNPs) in water. Steady-state and time-resolved fluorescence measurements of the AuNPs in the presence of α-cyclodextrin (α-CD) revealed the formation of supramolecular complexes between the ligand and macrocycle at the surface of the nanocrystals. The addition of α-CD induced the formation of inclusion complexes with a high apparent binding constant that decreased with the increasing oxyethylene chain length. The formation of polyrotaxanes at the surface of AuNPs, in which many α-CDs are trapped as hosts on the long and linear ligands, was demonstrated by the formation of large and homogeneous arrays of self-assembled AuNPs with hexagonal close packing, where the interparticle distance increased with the length of the oxyethylene chain. The estimated number of α-CDs per polyrotaxane suggests a high rigidization of the ligand upon complexation, allowing for nearly perfect control of the interparticle distance in the arrays. This degree of supramolecular control was extended to arrays formed by AuNPs stabilized with polyethylene glycol and even to binary arrays. Electromagnetic simulations showed that the enhancement and distribution of the electric field can be finely controlled in these plasmonic arrays.
Cyclodextrin-Based Magnetic Nanoparticles for Cancer Therapy
Authors: Mrówczyński Radosław , Jędrzak Artur , Szutkowski Kosma , Grześkowiak Bartosz , Coy Emerson , Markiewicz Roksana , Jesionowski Teofil , Jurga Stefan
Published: March 2018

Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-β-cyclodextrin (SH-βCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine.
Synthesis of Gold Nanoparticles Using Leaf Extract of Ziziphus zizyphus and their Antimicrobial Activity
Authors: Aljabali Alaa , Akkam Yazan , Al Zoubi Mazhar , Al-Batayneh Khalid , Al-Trad Bahaa , Abo Alrob Osama , Alkilany Alaaldin , Benamara Mourad , Evans David
Published: March 2018

(1) Background: There is a growing need for the development of new methods for the synthesis of nanoparticles. The interest in such particles has raised concerns about the environmental safety of their production methods; (2) Objectives: The current methods of nanoparticle production are often expensive and employ chemicals that are potentially harmful to the environment, which calls for the development of “greener” protocols. Herein we describe the synthesis of gold nanoparticles (AuNPs) using plant extracts, which offers an alternative, efficient, inexpensive, and environmentally friendly method to produce well-defined geometries of nanoparticles; (3) Methods: The phytochemicals present in the aqueous leaf extract acted as an effective reducing agent. The generated AuNPs were characterized by Transmission electron microscopy (TEM), Scanning electron microscope (SEM), and Atomic Force microscopy (AFM), X-ray diffraction (XRD), UV-visible spectroscopy, energy dispersive X-ray (EDX), and thermogravimetric analyses (TGA); (4) Results and Conclusions: The prepared nanoparticles were found to be biocompatible and exhibited no antimicrobial or antifungal effect, deeming the particles safe for various applications in nanomedicine. TGA analysis revealed that biomolecules, which were present in the plant extract, capped the nanoparticles and acted as stabilizing agents.
Association between Sarcopenia and Metabolic Syndrome in Middle-Aged and Older Non-Obese Adults: A Systematic Review and Meta-Analysis
Authors: Zhang Huaqi , Lin Song , Gao Tianlin , Zhong Feng , Cai Jing , Sun Yongye , Ma Aiguo
Published: March 2018

The associations between sarcopenia and metabolic syndrome (MetS) in non-obese middle-aged and older adults remain controversial. Thus, this meta-analysis aimed to evaluate the overall prevalence of MetS and the correlations between sarcopenia and MetS in middle-aged and older non-obese adults. We performed a systematic searched strategy using PUBMED, EMBASE and Web of Science databases for relevant observational studies investigating sarcopenia and MetS up to 11 May 2017. The polled prevalence of MetS and odds ratios with 95% confidence intervals (CI), as well as subgroup analyses were calculated using a random effects model. Twelve articles with a total of 35,581 participants were included. The overall prevalence of MetS was 36.45% (95% CI, 28.28–45.48%) in middle-aged and older non-obese adults with sarcopenia. Our analysis demonstrated a positive association between sarcopenia and MetS (OR = 2.01, 95% CI, 1.63–2.47). The subgroup analysis showed that both larger cohort size and the use of dual-energy X-ray absorptiometry to measure body composition can enhance the relationship. Our study revealed that a higher proportion of MetS in middle-aged and older non-obese people with sarcopenia. Moreover, sarcopenia was positively associated with MetS in this population. Further large-scale prospective cohort studies are needed to investigate the causality between sarcopenia and MetS.
Vitamin D, Hypercalciuria and Kidney Stones
Authors: Letavernier Emmanuel , Daudon Michel
Published: March 2018

The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements.