bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis‐inducing agents enhance TRAIL‐induced apoptosis through upregulation of death receptor 5
Authors: Lee Young‐Sun , Lee Dae‐Hee , Jeong So Yeon , Park Seong Hye , Oh Sang Cheul , Park Yong Seok , Yu Jian , Choudry Haroon A , Bartlett David L , Lee Yong J 
Published: August 2018

AbstractFerroptosis is considered genetically and biochemically distinct from other forms of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death. When human colon cancer HCT116, CX‐1, and LS174T cells were treated with ferroptotic agents such as sorafenib (SRF), erastin, and artesunate, data from immunoblot assay showed that ferroptotic agents induced endoplasmic reticulum (ER) stress and the ER stress response‐mediated expression of death receptor 5 (DR5), but not death receptor 4. An increase in the level of DR5, which is activated by binding to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and initiates apoptosis, was probably responsible for synergistic apoptosis when cells were treated with ferroptotic agent in combination with TRAIL. This collateral effect was suppressed in C/EBP (CCAAT‐enhancer‐binding protein)‐homologous protein (CHOP)‐deficient mouse embryonic fibroblasts or DR5 knockdown HCT116 cells, but not in p53‐deficient HCT116 cells. The results from in vitro studies suggest the involvement of the p53‐independent CHOP/DR5 axis in the synergistic apoptosis during the combinatorial treatment of ferroptotic agent and TRAIL. The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor‐bearing mice.
Dynamic perspectives into the mechanisms of mutation‐induced p53‐DNA binding loss and inactivation using active perturbation theory: Structural and molecular insights toward the design of potent reactivators in cancer therapy
Authors: Olotu Fisayo. A. , Soliman Mahmoud E. S. 
Published: August 2018

AbstractThe DNA‐binding ability of p53 represents the crux of its tumor suppressive activities, which involves transcriptional activation of target genes responsible for apoptosis and cell‐cycle arrest. Mutational occurrences within or in close proximity to the DNA‐binding surface of p53 have accounted for the loss of direct DNA‐binding ability and inactivation implicated in many cases of cancer. Moreover, the design of therapeutic compounds that can restore DNA‐binding ability in p53 mutants has been identified as a way forward in curtailing their oncogenic activities. However, there is still the need for more insights into evaluate the perturbations that occur at the DNA‐binding interface of mp53 relative to DNA‐binding loss, inactivation, and design of potent reactivators, hence the purpose of this study. Therefore, we evaluated p53‐structural (R175H) and contact (R273C) mutational effects using tunnel perturbation analysis and other computational tools. We identified significant perturbations in the active tunnels of p53, which resulted in altered geometry and loss, unlike in the wild‐type p53. This corroborated with structural, DNA‐binding, and interaction network analysis, which showed that loss of flexibility, repulsion of DNA‐interactive residues, and instability occurred at the binding interface of both mutants. Also, these mutations altered bonding interactions and network topology at the DNA‐binding interface, resulting in the reduction of p53‐DNA binding proximity and affinity. Therefore, these findings would aid the structure‐based design of novel chemical entities capable of restoring p53‐DNA binding and activation.
Osteocyte‐intrinsic mTORC1 signaling restrains trabecular bone accrual in mice
Authors: Liu Qingbai , Liu Cunchang , Yang Yanjun , Yang Huilin , Chen Jianquan 
Published: August 2018

AbstractMechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling plays important physiological roles in bone homeostasis by regulating multiple steps of osteoblast differentiation as well as its activity. However, its potential role in osteocytes has not been explored. In this study, we deleted Raptor, a specific and essential component of mTORC1, in osteocytes using Dmp1‐Cre. Deletion of Raptor in osteocytes did not affect bone development and growth, but caused compartment‐specific effects on bone mass. Osteocyte‐specific deletion of Raptor had no obvious effect on cortical bone compartments, but led to increased trabecular bone mass. Mechanistically, Raptor deletion resulted in decreased bone resorption without altering bone formation activity. Thus, our study revealed an unexpected role of osteocyte‐intrinsic mTORC1 signaling in limiting trabecular bone mass, suggesting that osteocyte‐specific inhibition of mTORC1 may be used as a novel approach to treatment of osteoporosis.
Effect of the autism‐associated lncRNA Shank2‐AS on architecture and growth of neurons
Authors: Luo Ting , Liu Ping , Wang Xiao‐Yan , Li Le‐Zhi , Zhao Li‐Ping , Huang Jin , Li Ya‐Min , Ou Jin‐Lan , Peng Xiao‐Qing 
Published: August 2018

AbstractThe pathogenic mechanism of autism is complex, and current research has shown that long noncoding RNAs (lncRNAs) may play important roles in this process. The antisense lncRNA of SH3 and multiple ankyrin repeat domains 2 (Shank2‐AS) is upregulated in patients with autism spectrum disorder (ASD), whereas the expression of its sense strand gene Shank2 is downregulated. In neuronal cells, Shank2‐AS and Shank2 can form a double‐stranded RNA and inhibit Shank2 expression. Overexpression of Shank2‐AS decreases neurite numbers and lengths, thereby inhibiting the proliferation of neuronal cells and promoting their apoptosis. Overexpression of Shank2 inhibits the abovementioned effects of Shank2‐AS, and transfection of a vector containing the 10th intron of Shank2 (Shank2‐AS is reverse‐transcribed from this region) also blocks the function of Shank2‐AS. Shank2 small interfering RNA plays a role similar to Shank2‐AS. Therefore, Shank2‐AS is abnormally expressed in patients with ASD and may affect the structure and growth of neurons by regulating Shank2 expression, thereby facilitating the development of ASD.
High expression of miR‐510 was associated with CGG expansion located at upstream of FMR1 into full mutation
Authors: Fazeli Zahra , Ghaderian Sayyed Mohammad Hossein , Najmabadi Hossein , Omrani Mir Davood 
Published: August 2018

AbstractMicroRNAs (miRNAs) have been found to play an important role in the regulation of gene expression in eukaryotic organisms at the posttranscriptional level. More than half of miRNA genes have been recognized to be located in different fragile sites. Among them, miR‐510 was located on chromosome X in the 27.3Xq region, flanking to a fragile X site. The CGG expansion and its methylation at the promoter of FMR1 located in this fragile site were associated with clinical symptoms of fragile X syndrome (FXS). The aim of the current study was to investigate whether the miR‐510 expression was correlated with the CGG expansion of FMR1 in female carriers of full mutation. For this purpose, mesenchymal stem cells were isolated from peripheral blood of FMR1 full mutation female carriers. After differentiation of these cells into neuronal cells, the expression of miR‐510 was analyzed by quantitative polymerase chain reaction. Furthermore, the target genes of miR‐510 in the nervous system were also predicted by in silico method. The obtained results indicated that the CGG expansion of FMR1 was associated with the enhanced expression of miR‐510. Furthermore, the bioinformatics analysis suggested that VHL and PPP2R5E genes could be considered as the most important target genes of miR‐510 in the nervous system. This study showed that miR‐510 and its target genes, specifically VHL and PPP2R5E, may represent the new targets for future therapy options of FXS.
Dynamics of steroid‐induced oocyte maturation in three amphibian species: Mathematical modeling and simulation
Authors: Manzano Carolina , Benzal Maria Graciela , Zelarayán Liliana Isabel 
Published: August 2018

AbstractOocyte maturation in vertebrates involves morphological, biochemical, and functional changes through which meiosis, previously arrested in Profase I, is resumed. Within these changes, germinal vesicle breakdown (GVBD) constitutes morphological evidence of the resumption of the cellular cycle. Sex steroids (progestins and androgens) play a key role in oocyte maturation and are considered inducers of this process. The aims of this study were to analyze the effect of sex steroids on the oocyte maturation of amphibians and to model and simulate the dynamics of this process through the experimental data obtained. The oocytes of sexually mature females of Scinax fuscovarius, Pleurodema borellii, and Physalaemus biligonigerus were treated with different concentrations (0.001–1 µM) of sex steroids progesterone (P
4) and testosterone (T) for 24 hr. Dose– and time–response curves were performed with the results achieved. Sex steroids induced oocyte maturation in a dose‐dependent manner in all three species. The dose at which the highest maturation percentage was found was 1 μM. No significant differences were observed between GVBD percentages of P
4 and T. However, time–response curves show that oocytes responded earlier and achieved higher GVBD percentages when treated with P
4. Gompertz mathematical model was proposed in this study to simulate GVBD dynamics. This model properly fits the corresponding experimental data and allows the analysis of the behavior of oocyte maturation in amphibians and the quantification of parameters with biological meaning that are indicative of sex steroids efficiency in this process.
Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis
Authors: Noureddini Mahdi , Mobasseri Narges , Karimian Mohammad , Behjati Mohaddeseh , Nikzad Hossein 
Published: August 2018

AbstractBackgroundThe Arg399Gln polymorphism in the X‐ray repair cross‐complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1‐Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta‐analysis and an in silico analysis.MethodsIn a case–control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1‐Arg399Gln genotyping was performed using the polymerase chain reaction‐restriction fragment length polymorphism method. In the meta‐analysis, 14 eligible studies were included to which our case–control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein.ResultsOur case–control study revealed a significant association between the XRCC1‐Arg399Gln polymorphism and PCa risk. The data from overall meta‐analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein.ConclusionsBased on these results, the XRCC1‐Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.
A simple gradient equilibrium method for better separation in countercurrent chromatography
Authors: Quan Kai‐Jun , Xi Xing‐jun , Huang Xin‐Yi , Duan Wen‐Da , Pei Dong , Di Duo‐Long 
Published: August 2018

AbstractThe stationary phase retention is one of the most important parameters in countercurrent chromatography. In this work, a simple gradient equilibrium method was developed to further improve the stationary phase retention based on the optimized condition in the traditional equilibrium model. Meanwhile, this novel gradient equilibrium method was used to separate three flavone model compounds and compared with the conventional isocratic equilibrium method to evaluate the separation efficiency. The results show that better resolution or shorter separation time could be achieved with gradient equilibrium compared to isocratic equilibrium. So this novel equilibrium method has enormous potential for obtaining a better separation or saving the separating time in the preparative separation of target compounds.
Profiling of headspace volatiles from Escherichia coli cultures using silicone‐based sorptive media and thermal desorption GC–MS
Authors: Devaraj Harish , Pook Chris , Swift Simon , Aw Kean C. , McDaid Andrew J. 
Published: August 2018

AbstractHeadspace sorptive extraction technique using silicone based sorptive media coated stir bars is used for the first time here to extract, identify, and quantify heavy volatile organic compounds present in Escherichia coli culture headspace. Detection of infection presence is largely accomplished in laboratories through physical sampling and subsequent growth of cultures for biochemical testing. The use of volatile biomarkers released from pathogens as indicators for pathogenic presence can vastly reduce the time needed whilst improving the success rates for infection detection. To validate this, by using a contactless headspace sorptive extraction technique, the volatile compounds released from E. coli, grown in vitro, have been extracted and identified. Two different sorptive media for extracting these headspace volatiles were compared in this study and the identified volatiles were quantified. The large phase volume and wider retention of this sorptive technique compared to traditional sampling approach enabled preconcentration and collection of wider range of volatiles towards developing an extensive database of such heavy volatiles associated with E. coli. This supplements the existing data of potential bacterial markers and use of internal standards in these tests allows semi‐quantitative estimation of these compounds towards the development and optimization of novel pathogen sensing devices.
Selective separation and purification of β‐estradiol from marine sediment using an optimized core–shell molecularly imprinted polymer
Authors: He Xiuping , Lian Ziru , Wang Jiangtao 
Published: August 2018

AbstractThe core–shell molecularly imprinted polymers were optimized to provide reliable connections that allow molecularly imprinted polymers to be fixed on SiO2 surface for the efficient separation and purification of β‐estradiol from marine sediment for the first time. To achieve the goal, different preparation methods were used and finally the polymer using 3‐methacryloxypropyltrimethoxysilane as coupling agent exhibited the best result, which further confirmed that 3‐methacryloxypropyltrimethoxysilane played an indispensable role on improving the inter‐particle connections. An offline molecularly imprinted solid‐phase extraction with high‐performance liquid chromatography method was successfully applied to the isolation and enrichment of β‐estradiol from marine sediment samples with high adsorption capacity, excellent clean‐up efficiency, and great enrichment effect as well as high recovery (>90%) and accuracy (RSD < 8.5%, n = 3). It proved the successful grafting of molecularly imprinted polymers on SiO2 surface and the applicability of the offline molecularly imprinted solid‐phase extraction method in the selective extraction and enrichment of β‐estradiol from marine sediment.
Composite Biomaterials as Long‐Lasting Scaffolds for 3D Bioprinting of Highly Aligned Muscle Tissue
Authors: García‐Lizarribar Andrea , Fernández‐Garibay Xiomara , Velasco‐Mallorquí Ferran , Castaño Albert G. , Samitier Josep , Ramon‐Azcon Javier 
Published: August 2018

AbstractNew biocompatible materials have enabled the direct 3D printing of complex functional living tissues, such as skeletal and cardiac muscle. Gelatinmethacryloyl (GelMA) is a photopolymerizable hydrogel composed of natural gelatin functionalized with methacrylic anhydride. However, it is difficult to obtain a single hydrogel that meets all the desirable properties for tissue engineering. In particular, GelMA hydrogels lack versatility in their mechanical properties and lasting 3D structures. In this work, a library of composite biomaterials to obtain versatile, lasting, and mechanically tunable scaffolds are presented. Two polysaccharides, alginate and carboxymethyl cellulose chemically functionalized with methacrylic anhydride, and a synthetic material, such as poly(ethylene glycol) diacrylate are combined with GelMA to obtain photopolymerizable hydrogel blends. Physical properties of the obtained composite hydrogels are screened and optimized for the growth and development of skeletal muscle fibers from C2C12 murine cells, and compared with pristine GelMA. All these composites show high resistance to degradation maintaining the 3D structure with high fidelity over several weeks. Altogether, in this study a library of biocompatible novel and totally versatile composite biomaterials are developed and characterized, with tunable mechanical properties that give structure and support myotube formation and alignment.
Branched Poly(ethylene imine)s as Anti‐algal and Anti‐cyanobacterial Agents with Selective Flocculation Behavior to Cyanobacteria over Algae
Authors: Mikula Premysl , Mlnarikova Marie , Takahashi Haruko , Babica Pavel , Kuroda Kenichi , Blaha Ludek , Sovadinova Iva 
Published: August 2018

AbstractPoly(ethylene imine)s (PEIs) have been widely studied for biomedical applications, including antimicrobial agents against potential human pathogens. The interactions of branched PEIs (B‐PEIs) with environmentally relevant microorganisms whose uncontrolled growth in natural or engineered environments causes health, economic, and technical issues in many sectors of water management are studied. B‐PEIs are shown to be potent antimicrobials effective in controlling the growth of environmentally relevant algae and cyanobacteria with dual‐functionality and selectivity. Not only did they effectively inhibit growth of both algae and cyanobacteria, mostly without causing cell death (static activity), but they also selectively flocculated cyanobacteria over algae. Thus, unmodified B‐PEIs provide a cost‐effective and chemically facile framework for the further development of effective and selective antimicrobial agents useful for control of growth and separation of algae and cyanobacteria in natural or engineered environments.
Molar Mass Analysis of Hydrophobically Modified Hyaluronic Acid by SEC‐MALLS: Facing the Challenges of Amphiphilic Biomacromolecules
Authors: Botha Carlo , Kuntz Jean‐François , Moire Claudine , Farcet Céline , Pfukwa Helen , Pasch Harald 
Published: August 2018

AbstractA size exclusion chromatography–multiangle laser light scattering (SEC‐MALLS) method is developed for determining the molar masses of amphiphilic hyaluronan (HA), consisting of a hydrophilic polymer backbone modified to varying extents with hydrophobic, polymerizable acrylate groups. The polymers are prepared via the base‐catalyzed esterification of HA with acrylic anhydride. Various parameters are investigated including mobile phase composition, temperature, pH, salt type, and concentration in order to find the most suitable conditions for completely dissolving the modified polymers irrespective of the degree of substitution (DS), and for suppressing secondary polymer interactions. The hydrolytic and the thermal stability of the different materials at various experimental conditions are also extensively investigated. HAs with DS varying from 0 to 3.4 are subsequently analyzed at the optimized experimental conditions for the mobile phase being DMSO/H2O 60/40(v/v) with 0.05 M LiBr and an operating temperature of 40 °C. The refractive index increments (dn/dc) of the HAs are determined and the results show a dependence of dn/dc on DS.
Rigid–Flexible Coupling Polymer Electrolytes toward High‐Energy Lithium Batteries
Authors: Zhou Qian , Zhang Jianjun , Cui Guanglei 
Published: August 2018

AbstractPolymer electrolytes have aroused wide interest in lithium batteries, but their comprehensive performances (including ionic conductivity, electrochemical window, and mechanical strength) need to be enhanced for high‐energy lithium batteries. A rigid–flexible coupling strategy is proposed to enhance the comprehensive performances of polymer electrolytes. To date, “rigid–flexible coupling” has been widely applied in gel and solid polymer electrolytes. For many kinds of polymer electrolytes, their ionic conductivity, electrochemical window, interfacial stability, and mechanical properties are significantly improved by “rigid–flexible coupling,” breaking their inherent application barriers in high‐energy lithium battery. Herein, recent key progress in rigid–flexible coupling polymer electrolytes is reviewed in terms of their design concepts, chemical‐physical properties, electrochemical performances, and battery properties. This overview also conducts a perspective for rigid–flexible coupling polymer electrolytes. It is hoped that fresh and established researchers can obtain a clear perspective of “rigid–flexible coupling” and this mini review can also throw light on the exploration of high‐energy polymer lithium batteries.
Dietary Galacto‐Oligosaccharides and Resistant Starch Protect Against Altered CB1 and 5‐HT1A and 2A Receptor Densities in Rat Brain: Implications for Preventing Cognitive and Appetite Dysfunction During a High‐Fat Diet
Authors: Yu Yinghua , Patch Craig , Weston‐Green Katrina , Zhou Yuan , Zheng Kuiyang , Huang Xu‐Feng 
Published: August 2018

ScopeA high‐fat, but low‐fiber, diet is associated with obesity and cognitive dysfunction, while dietary fiber supplementation can improve cognition.Methods and resultsThis study examines whether dietary fibers, galacto‐oligosaccharides (GOS) and resistant starch (RS), could prevent high‐fat (HF)‐diet‐induced alterations in neurotransmitter receptor densities in brain regions associated with cognition and appetite. Rats are fed a HF diet, HF diet with GOS, HF diet with RS, or a low‐fat (LF, control) diet for 4 weeks. Cannabinoid CB1 (CB1R) and 5HT1A (5HT1AR) and 5‐HT2A (5HT2AR) receptor binding densities are examined. In the hippocampus and hypothalamus, a HF diet significantly increases CB1R binding, while HF + GOS and HF + RS diets prevented this increase. HF diet also increases hippocampal and hypothalamic 5‐HT1AR binding, while HF + GOS and HF + RS prevented the alterations. Increased 5‐HT2A binding is prevented by HF + GOS and HF + RS in the medial mammillary nucleus.ConclusionsThese results demonstrate that increased CB1R, 5‐HT1AR and 5‐HT2AR induced by a HF diet can be prevented by GOS and RS supplementation in brain regions involved in cognition and appetite. Therefore, increased fiber intake may have beneficial effects on improving learning and memory, as well as reducing excessive appetite, during the chronic consumption of a HF (standard Western) diet.
A hybrid parallel algorithm for large sparse linear systems
Authors: Rao S. Chandra Sekhara , Kamra Rabia 
Published: August 2018

SummaryLarge sparse linear systems arise in many areas of scientific computing, and the solution of these systems is the most time‐consuming part in many large‐scale problems. We present a hybrid parallel algorithm, named incomplete WZ parallel solver (IWZPS), for the solution of large sparse nonsingular diagonally dominant linear systems on distributed memory architectures. The method is a combination of both direct and iterative techniques. We compare the present hybrid parallel sparse algorithm IWZPS with the direct and iterative sparse solvers, namely, MUMPS and ILUPACK, respectively. In addition, we compare it with a hybrid parallel solver, DDPS.