bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve growth factor prevents arsenic‐induced toxicity in PC12 cells through the AKT/GSK‐3β/NFAT pathway
Authors: Tan Zhen , Kang Ting , Zhang Xiuli , Tong Yingying , Chen Siyu 
Published: September 2018

AbstractThe potential risk of arsenic‐related neurodegeneration has been a growing concern. Arsenic exposure has been reported to disrupt neurite growth and neuron body integrity in vitro; however, its underlying mechanism remains unclear. Previously, we showed that arsenic sulfide (AS) exerted cytotoxicity in gastric and colon cancer cells through regulating nuclear factor of the activated T cells (NFAT) pathway. The NFAT pathway regulates axon path finding and neural development. Using neural crest cell line PC12 cells as a model, here we show that AS caused mitochondrial membrane potential collapse, reactive oxygen species production, and cytochrome c release, leading to mitochondria‐mediated apoptosis via the AKT/GSK‐3β/NFAT pathway. Increased glycogen synthase kinase‐3 beta (GSK‐3β) activation leads to the inactivation of NFAT and its antiapoptotic effects. Through inhibiting GSK‐3β activity, both nerve growth factor (NGF) and Tideglusib, a GSK‐3β inhibitor partially rescued the PC12 cells from the AS‐induced cytotoxicity and restored the expression of NFATc3. In addition, overexpression of NFATc3 stimulated neurite outgrowth and potentiated the effect of NGF on promoting the neurite outgrowth. Collectively, our results show that NFATc3 serves as the downstream target of NGF and plays a key role in preventing AS‐induced neurotoxicity through regulating the AKT/GSK‐3β/NFAT pathway in PC12 cells.
Recovery from hypoxia‐induced internalization of cardiac Na+/H+ exchanger 1 requires an adequate intracellular store of antioxidants
Authors: Şimşek Gül , Vaughan‐Jones Richard D. , Swietach Pawel , Kandilci H. Burak 
Published: September 2018

AbstractThe heart is highly active metabolically but relatively underperfused and, therefore, vulnerable to ischemia. In addition to acidosis, a key component of ischemia is hypoxia that can modulate gene expression and protein function as part of an adaptive or even maladaptive response. Here, using cardiac‐derived HL‐1 cells, we investigate the effect of various hypoxic stimuli on the expression and activity of Na+/H
+ exchanger 1 (NHE1), a principal regulator of intracellular pH. Acute (10 min) anoxia produced a reversible decrease in the sarcolemmal NHE1 activity attributable to NHE1 internalization. Treatment with either 1% O
2 or dimethyloxaloylglycine (DMOG; 1 mM) for 48‐hr stabilized hypoxia‐inducible factor 1 and reduced the sarcolemmal NHE1 activity by internalization, but without a change in total NHE1 immunoreactivity or message levels of the coding gene (
SLC9A1) determined in whole‐cell lysates. Unlike the effect of DMOG, which was rapidly reversed on washout, reoxygenation after a prolonged period of hypoxia did not reverse the effects on NHE1, unless media were also supplemented with a membrane‐permeant derivative of glutathione (GSH). Without a prior hypoxic episode, GSH supplementation had no effect on the NHE1 activity. Thus, posthypoxic NHE1 reinsertion can only take place if cells have a sufficient reservoir of a reducing agent. We propose that oxidative stress under prolonged hypoxia depletes intracellular GSH to an extent that curtails NHE1 reinsertion once the hypoxic stimulus is withdrawn. This effect may be cardioprotective, as rapid postischaemic restoration of the NHE1 activity is known to trigger reperfusion injury by producing an intracellular Na
+‐overload, which is proarrhythmogenic.
Long noncoding RNA H19 participates in metformin‐mediated inhibition of gastric cancer cell invasion
Authors: Li Peiwen , Tong Linhao , Song Yongxi , Sun Jingxu , Shi Jinxin , Wu Zhonghua , Diao Yao , Li Yaming , Wang Zhenning 
Published: September 2018

AbstractRecent research suggests that the first‐line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit‐8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked‐down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked‐down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.
Heme oxygenase‐1 reduces the sensitivity to imatinib through nonselective activation of histone deacetylases in chronic myeloid leukemia
Authors: Wei Danna , Lu Tingting , Ma Dan , YU Kunlin , Li Xinyao , Chen Bingqing , Xiong Ji , Zhang Tianzhuo , Wang Jishi 
Published: September 2018

AbstractResistance towards imatinib (IM) remains troublesome in treating many chronic myeloid leukemia (CML) patients. Heme oxygenase‐1 (HO‐1) is a key enzyme of antioxidative metabolism in association with cell resistance to apoptosis. Our previous studies have shown that overexpression of HO‐1 resulted in resistance development to IM in CML cells, while the mechanism remains unclear. In the current study, the IM‐resistant CML cells K562R indicated upregulation of some of the histone deacetylases (HDACs) compared with K562 cells. Therefore, we herein postulated HO‐1 was associated with HDACs. Silencing HO‐1 expression in K562R cells inhibited the expression of some HDACs, and the sensitivity to IM was increased. K562 cells transfected with HO‐1 resisted IM and underwent obvious some HDACs. These findings related to the inhibitory effects of high HO‐1 expression on the reactive oxygen species (ROS) signaling pathway that negatively regulated HDACs. Increased expression of HO‐1 activated HDACs by inhibiting ROS production. In summary, HO‐1, which is involved in the development of drug resistance in CML cells by regulating the expression of HDACs, is probably a novel target for improving CML therapy.
Mll‐COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts
Authors: Rojas Adriana , Sepulveda Hugo , Henriquez Berta , Aguilar Rodrigo , Opazo Tatiana , Nardocci Gino , Bustos Fernando , Lian Jane B. , Stein Janet L. , Stein Gary S. , van Zundert Brigitte , van Wijnen Andre J. , Allende Miguel L. , Montecino Martin 
Published: September 2018

AbstractExpression of Runx2/p57 is a hallmark of the osteoblast‐lineage identity. Although several regulators that control the expression of Runx2/p57 during osteoblast‐lineage commitment have been identified, the epigenetic mechanisms that sustain this expression in differentiated osteoblasts remain to be completely determined. Here, we assess epigenetic mechanisms associated with Runx2/p57 gene transcription in differentiating MC3T3 mouse osteoblasts. Our results show that an enrichment of activating histone marks at the Runx2/p57 P1 promoter is accompanied by the simultaneous interaction of Wdr5 and Utx proteins, both are components of COMPASS complexes. Knockdown of Wdr5 and Utx expression confirms the activating role of both proteins at the Runx2‐P1 promoter. Other chromatin modifiers that were previously described to regulate Runx2/p57 transcription in mesenchymal precursor cells (Ezh2, Prmt5, and Jarid1b proteins) were not found to contribute to Runx2/p57 transcription in full‐committed osteoblasts. We also determined the presence of additional components of COMPASS complexes at the Runx2/p57 promoter, evidencing that the Mll2/COMPASS‐ and Mll3/COMPASS‐like complexes bind to the P1 promoter in osteoblastic cells expressing Runx2/p57 to modulate the H3K4me1 to H3K4me3 transition.
Efficient processing of bioglycerol to a novel biobased polyunsaturated monomer
Authors: Gómez Claudia L , Echeverri David A , Inciarte Helen C , Rios Luis A 
Published: September 2018

AbstractBACKGROUNDCommercial synthesis of polyunsaturated monomers, like polyester resins, involves an energy‐demanding esterification process, which is usually carried out at 150–220 °C and long reaction times (>12 h). In addition, most of these monomers come from petrochemical sources and, therefore, are not renewable. In this research, a new polyunsaturated monomer was synthesized using crude glycerol from biodiesel production (bioglycerol), through an alternative and efficient process.RESULTSBioglycerol was transformed to a polyunsaturated resin through maleinization and methacrylation reactions, under mild conditions (<100 °C and 2 h). The effects of temperature and molar ratio of reactants on these reactions were evaluated through a factorial design. The so‐obtained monomer was highly functionalized (5.05 double bonds per molecule) and negligible acid value (<2 mg KOH g−1). To assess its reactivity, the monomer was copolymerized with methyl methacrylate (MMA), affording a rigid material with excellent mechanical properties. In general, the properties were better than those obtained for commercial unsaturated polyester thermosets (flexural modulus, 3783.4 MPa; flexural strength, 161.5 MPa; surface hardness, 76 (Shore D) and Tg, 100.9 °C). This new monomer could also be suitable for the production of other polymers such as alkyd resins.CONCLUSIONA new route to polyunsaturated monomers was developed from bioglycerol at relatively low temperatures, without solvents and with minimum intermediate purification stages. The monomer was suitable for reacting with MMA, affording a material with mechanical properties resembling those of a commercial unsaturated polyester thermoset. © 2018 Society of Chemical Industry
Potential of sugar beet vinasse as a feedstock for biocatalyst production within an integrated biorefinery context
Authors: Suhaili Nurashikin , Cárdenas‐Fernández Max , Ward John M , Lye Gary J 
Published: September 2018

AbstractBACKGROUNDThis work explores the feasibility of vinasse as an inexpensive feedstock for industrial biocatalyst production within the context of an integrated sugar beet biorefinery. As an exemplar, production of CV2025 ω‐Transaminase (ω‐TAm) in Escherichia coli BL21 was studied.RESULTSCharacterisation of vinasse showed that it comprised mainly of glycerol along with several reducing sugars, sugar alcohols, acetate, polyphenols and protein. Preliminary results showed E. coli BL21 cell growth and CV2025 ω‐TAm production were feasible in cultures using 17% to 25% (v/v) vinasse with higher concentrations demonstrating inhibitory effects. The d‐galactose present in vinasse facilitated auto‐induction of the pQR801 plasmid enabling CV2025 ω‐TAm expression without addition of expensive Isopropyl‐β‐d‐thiogalactopyranoside (IPTG). Assessment of different vinasse pre‐processing options confirmed simple dilution of the vinasse was sufficient to reduce the concentration of polyphenols to below inhibitory levels. Optimisation experiments, carried out using a controlled, 24‐well microbioreactor platform, showed supplementation of diluted vinasse medium with 10 g L−1 yeast extract enabled enhancements of 2.8, 2.5, 5.4 and 3‐fold in specific growth rate, maximum biomass concentration, CV2025 ω‐TAm volumetric and specific activity, respectively. Investigation into the metabolic preferences of E. coli BL21 when grown in vinasse showed a preference for D‐mannitol utilisation before simultaneous metabolism of glycerol, d‐xylitol, d‐dulcitol and acetate. Scale‐up of optimised conditions for batch CV2025 ω‐TAm production to a 7.5 L stirred tank reactor (STR) was demonstrated based on matched volumetric mass transfer coefficient (kLa). The results showed good comparability with respect to cell growth, substrate consumption and CV2025 ω‐TAm production representing over a 700‐fold volumetric scale translation. Further enhancements in CV2025 ω‐TAm production were possible in the STR when operated at higher kLa values.CONCLUSIONThis work describes the promising application of vinasse for production of microbial enzymes and insights into carbon source utilisation in complex feedstocks. Exploitation of vinasse as a fermentation feedstock could be further extended to other processes involving different microorganisms and target enzymes. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Dynamic Linkage Between Economic Growth and Human Development: Time Series Evidence from Nigeria
Authors: Chikalipah Sydney , Okafor Godwin 
Published: September 2018

AbstractA consensus among academics and policymakers holds that investing in human development not only improves lives, but also by itself promotes stellar economic growth. We investigate these claims by estimating the two‐way causality between economic growth and human development in Nigeria over the period from 1961 to 2015. By employing three statistical frameworks (Gregory–Hansen Cointegration, Stock–Watson Dynamic Ordinary Least Square and Vector Error Correction Model), our estimates suggest the following. First, economic growth and human development share a long run relationship, that is, they are cointegrated. Second, despite the two variables sharing a long run relationship, only economic growth can exercise a positive effect on human development, and no evidence of reverse causality was observable. Far importantly, we prescribe a policy recommendations from these findings. © 2018 John Wiley & Sons, Ltd.
Exploration and validation of diphosphate‐based Plasmodium LytB inhibitors using computational approaches
Authors: Bhuyan Rajabrata , Seal Alpana 
Published: September 2018

AbstractLytB or IspH is an indispensable enzyme and a suitable drug target of Plasmodium falciparum that participate in isoprenoid biosynthesis of nonmevalonate pathway (MEP). Recently, we have investigated the structural dynamics of Plasmodium LytB and proposed some novel diphosphate‐based inhibitors using molecular modeling and docking studies. Here, we have tried to characterize those previously screened molecules by quantitative structure activity relationships and pharmacophore‐based analyses, as well as validated the dynamics of their interactions with LytB protein. Five total compounds having PubChem CID 516, 125696, 165275, 448012, and 9921431 were predicted with significant inhibitory activity by quantitative structure activity relationships and pharmacophore models. Again, the molecular dynamics simulation results showed that these five compounds are able to form stable complexes with the receptor through many direct and water mediated interactions. The binding free energies calculated by Poisson‐Boltzmann surface area method resulted within the range between −99.77 and − 43.74 kcal/mol, which favoured their profound inhibitory affinity. Residues of LytB like His41, His74, Ser222, Ser223, and Asn224 in LytB were the main protagonists in contributing the majority of interaction energies to the ligands. Finally, the ADMET, toxicity, and drug‐likeness scores also affirm these compounds to be considered for further development of new antimalarial inhibitor in the future.
Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients
Authors: Sasaki Reina , Meyer Keith , Moriyama Mitsuhiko , Kato Naoya , Yokosuka Osamu , Ray Ratna B. , Aurora Rajeev , Ray Ranjit , Kanda Tatsuo 
Published: September 2018

AbstractAltered immune parameters associated with hepatitis C virus (HCV) genotype 1b infection and their correlation with virus eradication in direct‐acting antivirals (DAA)‐treated patients were examined. Thirty‐one HCV‐infected patients were treated with DAAs for 12 weeks. Pre‐DAA‐treatment and post‐DAA‐treatment sera were analyzed for cytokines/chemokines using MILLIPLEX MAP. Serum complement level and antibody neutralization activity were measured separately. Sera from 11 spontaneously cleared HCV subjects were included for comparison. Rapid virological responders (RVR) or end‐of‐treatment responders (EOTR) were defined as patients with HCV RNA negative at week 4 or positive at week 4 and negative at week 12, respectively. HCV RNA eradication and a decrease in liver fibrosis‐related cytokines after treatment were observed when compared with pretreatment sera from RVR and EOTR. In pretreatment sera, interferons and T‐helper 1 or 2 cell‐associated cytokines/chemokines were significantly higher among RVR as compared with EOTR. Furthermore, serum complement and virus neutralizing antibody levels were higher in pretreatment RVR sera. Eradication of HCV RNA by DAA decreased liver fibrosis‐related cytokines. Pretreatment sera from RVR displayed an enhanced cytokine/chemokine, complement and virus neutralizing antibody response as compared with EOTR sera. Our results suggested that enhanced host immune status may play an additive role on HCV RNA clearance by DAA.
Priorities for science to overcome hurdles thwarting the full promise of the ‘digital agriculture’ revolution
Authors: Shepherd Mark , Turner James A , Small Bruce , Wheeler David 
Published: September 2018

AbstractThe world needs to produce more food, more sustainably, on a planet with scarce resources and under changing climate. The advancement of technologies, computing power and analytics offers the possibility that ‘digitalisation of agriculture’ can provide new solutions to these complex challenges. The role of science is to evidence and support the design and use of digital technologies to realise these beneficial outcomes and avoid unintended consequences. This requires consideration of data governance design to enable the benefits of digital agriculture to be shared equitably and how digital agriculture could change agricultural business models; that is, farm structures, the value chain and stakeholder roles, networks and power relations, and governance. We argue that this requires transdisciplinary research (at pace), including explicit consideration of the aforementioned socio‐ethical issues, data governance and business models, alongside addressing technical issues, as we now have to simultaneously deal with multiple interacting outcomes in complex technical, social, economic and governance systems. The exciting prospect is that digitalisation of science can enable this new, and more effective, way of working. The question then becomes: how can we effectively accelerate this shift to a new way of working in agricultural science? As well as identifying key research areas, we suggest organisational changes will be required: new research business models, agile project management; new skills and capabilities; and collaborations with new partners to develop ‘technology ecosystems’. © 2018 The Authors. © 2018 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Decoupling the academic book
Authors: Hill Steven A. 
Published: September 2018

Key points

Technological and policy developments are changing the context for long‐form scholarly writing.
In the face of a changing context, the structures supporting the publication of academic books have been stable.
There may be potential benefits in separating the functions of the journal in a decoupled model.
Separating functions could also be applied to long‐form scholarly works, with potential benefits that are worth exploring.
Examining the Influence of Organophosphorus Flame Retardants on the Thermal Behavior of Aromatic Polybenzoxazines
Authors: Taylor Martin , Cavalli Gabriel , Hamerton Ian 
Published: September 2018

Abstract2,2‐bis(3,4‐Dihydro‐3‐phenyl‐2H‐1,3‐benzoxazine)propane (BA‐a) is blended with three commercial organophosphorus compounds, bis(4‐ hydroxyphenyl)phenylphosphine oxide (BHPPO), diphenyl phosphorami‐date (DPPA), and 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO), at different loadings (1–10 wt%). Incorporation of all dopants results in a reduction in the initiation temperature for the curing mechanism (by some 30–60 K), but only the DOPO truly moves the curing into a lower temperature regime by decreasing the end temperature by 25 K (DPPA lowered this by 5 K). DPPA and DOPO are also shown to have a significant effect on the enthalpy of polymerization each decreasing the value by 50 J g−1. Differential scanning calorimetry rescan indicates all three additives have a positive impact on the glass transition temperature of poly(BA‐a) with increases of 9 K (BHPPO) and 14 K (DPPA, DOPO). Thermogravimetric analysis indicates that all additives have little effect on the magnitude of char formed (BHPPO and DPPA both increased the char yield by 3%, whereas DOPO reduces the nal char yield by 3%). However, importantly, the mechanism of thermal degradation for poly(BA‐a) differs for all three additives and is shown to change with increasing concentra‐ tion. DOPO has the greatest effect on promoting the formation of char at elevated temperatures.
Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations
Authors: Pchelina Sofya , Baydakova Galina , Nikolaev Mikhael , Senkevich Konstantin , Emelyanov Anton , Kopytova Alena , Miliukhina Irina , Yakimovskii Andrey , Timofeeva Alla , Berkovich Olga , Fedotova Ekatrina , Illarioshkin Sergey , Zakharova Ekaterina 
Published: September 2018

ABSTRACTIntroduction: Glucocerebrosidase 1 mutations, the most common genetic contributor to Parkinson's disease (PD), have been associated with decreased glucocerebrosidase enzymatic activity in PD patients with glucocerebrosidase 1 mutations (glucocerebrosidase 1–PD). However, it is unknown whether this decrease in enzymatic activity leads to lysosphingolipid accumulations.Methods: The levels of hexosylsphingosines, globotriaosylsphingosine, sphingomyelin, and sphingomyelin‐509 were measured in dried blood spots from glucocerebrosidase 1–PD patients (n = 23), sporadic PD patients (n = 105), Gaucher disease patients (n = 32), and controls (n = 88) by liquid chromatography‐tandem mass spectrometry.Results: Glucocerebrosidase 1–PD patients had increased hexosylsphingosine levels when compared with sporadic PD patients (P < .001) and controls (P < .0001). Hexosylsphingosine levels were increased in glucocerebrosidase 1 mutation carriers of glucocerebrosidase 1 (L444P; N370S; n = 11, P = .001) and glucocerebrosidase 1 polymorphic variants (E326K, T369M) associated with PD (n = 12, P = .04) when compared with controls.Conclusions: Lysosphingolipid accumulations in PD patients who bear glucocerebrosidase 1 mutations suggest that substrate reduction therapy might be viewed as a possible strategy for glucocerebrosidase 1–PD treatment. © 2018 International Parkinson and Movement Disorder Society