bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the Substrate Selectivity of the Hypoxia‐Inducible Factor Prolyl Hydroxylase 2 Catalytic Domain
Authors: Abboud Martine I. , Chowdhury Rasheduzzaman , Leung Ivanhoe K. H. , Lippl Kerstin , Loenarz Christoph , Claridge Timothy D. W. , Schofield Christopher J. 
Published: August 2018

AbstractIn animals, the response to chronic hypoxia is mediated by upregulation of the α,β‐heterodimeric hypoxia‐inducible factors (HIFs). Levels of HIFα isoforms, but not HIFβ, are regulated by their post‐translational modification as catalysed by prolyl hydroxylase domain enzymes (PHDs). Different roles for the human HIF‐1/2α isoforms and their two oxygen‐dependent degradation domains (ODDs) are proposed. We report kinetic and NMR analyses of the ODD selectivity of the catalytic domain of wild‐type PHD2 (which is conserved in nearly all animals) and clinically observed variants. Studies using Ala scanning and “hybrid” ODD peptides imply that the relatively rigid conformation of the (hydroxylated) proline plays an important role in ODD binding. They also reveal differential roles in binding for the residues on the N‐ and C‐terminal sides of the substrate proline. The overall results indicate how the PHDs achieve selectivity for HIFα ODDs and might be of use in identifying substrate‐selective PHD inhibitors.
Safety and feasibility of balloon aortic valvuloplasty in non‐TAVI centers: The “BAV for life” experience
Authors: Attisano Tiziana , Silverio Angelo , Stabile Eugenio , Briguori Carlo , Tuccillo Bernardino , Scotto Di Uccio Fortunato , Di Lorenzo Emilio , Tesorio Tullio , Giordano Arturo , Calabrò Paolo , Cappelli Bigazzi Maurizio , Golino Paolo , Scherillo Marino , Vigorito Francesco , Quaranta Gaetano , Esposito Giovanni , Mauro Ciro , Musumeci Giuseppe , Tarantini Giuseppe , Galasso Gennaro ,   on behalf of BAV for Life Investigators
Published: August 2018

AbstractObjectivesTo evaluate the safety and the feasibility of balloon aortic valvuloplasty (BAV) procedure made by trained operators in centers not performing transcatheter aortic valve implantation (TAVI).BackgroundBAV is a valuable therapeutic tool for patients with symptomatic severe aortic valve stenosis (AS) at prohibitive risk for TAVI or surgery.MethodsConsecutive high‐risk AS patients underwent BAV in five non‐TAVI centers, where BAV operators had completed a 6‐month training period in high‐volume TAVI centers (Group A). All clinical, echocardiographic, and procedural data were prospectively collected and compared with data of patients treated in TAVI center (Group B).ResultsBetween June 2016 and June 2017, 55 patients (83.9 ± 7.0 years) were enrolled: 25 in Group A and 30 in Group B. After BAV, a substantial reduction of the peak‐to‐peak aortic valve gradient was obtained in both groups (−35.3 ± 15.2 vs −28.8 ± 13.9 mmHg, P =0.25). No major bleeding or vascular complications occurred. In‐hospital death was observed in three patients of Group A and two patients of Group B (P =0.493). The mean follow‐up time was 303 ± 188 days; no patients were lost. The 1‐year survival free from overall death (Group A 75.8% vs Group B 68.8%; P =0.682) and heart failure rehospitalization (Group A 73.0% vs Group B 66.8%; P =0.687) was similar in the two groups. At multivariable analysis, low left ventricular (LV) ejection fraction (HR: 0.943; P = 0.011) and cardiogenic shock (HR: 5.128; P = 0.002) at admission were independent predictors of mortality.ConclusionsBAV is a safe and effective procedure that can be performed by trained operators in centers not performing TAVI.
Electropolymerization of Dithieno[3,2‐b:2′,3′‐d]arsole
Authors: Imoto Hiroaki , Yamazawa Chieko , Hayashi Shotaro , Aono Masami , Naka Kensuke 
Published: August 2018

AbstractDithieno[3, 2‐b:2′,3′‐d]arsole is a molecule with a high oxidation potential (>1.2 V vs. Ag/AgCl) whose polymerization has not been achieved in common organic electrolytic solutions. Herein, we report the electropolymerization of dithieno[3, 2‐b:2′,3′‐d]arsole, which was performed in a dichloromethane solution using the trifluoroborate diethyl ether complex (BF3−OEt2) as an electrolyte. Under these conditions, the oxidation potential of dithieno[3, 2‐b:2′,3′‐d]arsole decreased to 0.5 V. The potential‐sweep electropolymerization of this molecule afforded an insoluble polymerized film on indium tin oxide or Pt working electrodes. The polymer film was subjected to X‐ray photoelectron spectroscopy analysis and the corresponding spectra revealed the presence of H, C, S, and As, which are the constituent elements of the monomer. Moreover, the polymer resulted to be a low band gap material according to the low energy band observed in its absorption spectra.
Parotid gland chondroma masquerading as pleomorphic adenoma in fine needle aspiration cytology: A diagnostic challenge
Authors: Chatterjee Debajyoti , Bhagat Ranjeev , Bansal Vinisha , Punia Rajpal Singh , Gupta Nitin 
Published: August 2018

AbstractChondroid neoplasm of parotid gland is extremely rare. Only a few cases of extraskeletal chondroma and one case of chondrosarcoma of parotid gland have been reported in the literature. The cytological features of parotid gland chondroma are not well documented. A 61‐year female patient presented with a slow growing left preauricular mass for past 6 years. Computer tomography scan showed a well circumscribed mass in the superficial lobe of left parotid gland. Fine needle aspiration cytology (FNAC) showed uniform chondrocytes embedded in a chondroid matrix, and was diagnosed as pleomorphic adenoma. Histological examination of the excised specimen showed a benign cartilaginous tumor, consistent with chondroma. There was no epithelial or myoepithelial component on extensive search. Chondroma is an extremely rare tumor of parotid gland and can be misdiagnosed as pleomorphic adenoma on cytology examination. However, absence of epithelial and myoepithelial component can give a clue toward a pure chondroid neoplasm. This report highlights the diagnostic features of chondroma of parotid gland and its diagnostic pitfalls in FNAC.
Injection system for fast capillary electrophoresis based on pressure regulation with flow restrictors
Authors: Furter Jasmine S. , Hauser Peter C. 
Published: August 2018

AbstractA fast automated system for rapid electrophoretic separations in short conventional capillaries employing contactless conductivity detection is presented. The instrument is based on pneumatic pressurization and does not require a conventional pump. The required pressures and flow rates for the different steps of the injection and flushing processes are produced with the help of two flow restrictors. The device is implemented on a microfluidic breadboard with dimensions of ca. 13 × 20 cm and employs miniature valves. Nine inorganic cations, namely NH4+, K+, Na+, Ca2+, Mg2+, Mn2+, Sr2+, Li+, and Ba2+, could be separated in a capillary of 10 μm inner diameter and 6 cm effective length within 25 s. Following a reduction of the effective length to 4 cm, still five inorganic cations could be separated in a time span of 12 s. The repeatability of peak areas was better than 3.1 % and limits of detection between 3.5 and 5.5 μM were achieved.
Assessing the performance of commercial farms in England and Wales: Lessons for supporting the sustainable intensification of agriculture
Authors: Firbank Les G. , Elliott John , Field Rob H. , Lynch John Michael , Peach Will J. , Ramsden Stephen , Turner Carla 
Published: August 2018

AbstractUnderstanding the trade‐offs between yield, ecosystem services, and other societal benefits is a fundamental prerequisite for the sustainable intensification of agriculture. Here, we develop and test an holistic approach to assessing farm performance across production, social, financial, and environmental dimensions. A longlist of potential indicators was reduced to a smaller subset of Headline Indicators, covering financial performance, levels of food production (standardized in terms of energy content), social characteristics of the farmer (including age, level of education, and degree of business cooperation), hours worked on the farm and provision of public access, and environmental quality (including impacts on climate regulation and water quality). A new index for biodiversity was created and validated, based on land use and management. Data were collected from 59 English and Welsh farms, using a questionnaire structured to be similar to the UK Farm Business Survey. Data were analyzed per farm and per unit area. The main overall variation in Headline Indicators was due to positive relationships between production, profitability and predicted levels of nitrate and GHG emissions, while social variables and biodiversity were generally unrelated to production. Cereal production was associated with relatively low levels of GHG emissions per unit of food production. There were strong differences in indicator profiles between farm types. Such metrics have value in helping understand how best to drive sustainable intensification, especially as it should involve reducing the pollution footprint of food production.
Directional coupling of oligodendrocyte connexin‐47 and astrocyte connexin‐43 gap junctions
Authors: Fasciani Ilaria , Pluta Paula , González‐Nieto Daniel , Martínez‐Montero Paloma , Molano Jesús , Paíno Carlos L. , Millet Oscar , Barrio Luis C. 
Published: August 2018

AbstractIntercellular communication via gap junction channels between oligodendrocytes and between astrocytes as well as between these cell types is essential to maintain the integrity of myelin in the central nervous system. Oligodendrocyte gap junction connexin‐47 (Cx47) is a key element in this crosstalk and indeed, mutations in human Cx47 cause severe myelin disorders. However, the permeation properties of channels of Cx47 alone and in heterotypic combination with astrocyte Cx43 remain unclear. We show here that Cx47 contains three extra residues at 5′ amino‐terminus that play a critical role in the channel pore structure and account for relative low ionic conductivity, cationic permselectivity and voltage‐gating properties of oligodendrocyte‐oligodendrocyte Cx47 channels. Regarding oligodendrocyte‐astrocyte coupling, heterotypic channels formed by Cx47 with Cx43 exhibit ionic and chemical rectification, which creates a directional diffusion barrier for the movement of ions and larger negatively charged molecules from cells expressing Cx47 to those with Cx43. The restrictive permeability of Cx47 channels and the diffusion barrier of Cx47‐Cx43 channels was abolished by a mutation associated with leukodystrophy, the Cx47P90S, suggesting a novel pathogenic mechanism underlying myelin disorders that involves alterations in the panglial permeation.
SOX17 transcription factor negatively regulates oligodendrocyte precursor cell differentiation
Authors: Fauveau Melissa , Wilmet Baptiste , Deboux Cyrille , Benardais Karelle , Bachelin Corinne , Temporão Ana C. , Kerninon Christophe , Nait Oumesmar Brahim 
Published: August 2018

AbstractOligodendrocyte development is a critical process timely and spatially regulated to ensure proper myelination of the central nervous system. HMG‐box transcription factors are key regulators of oligodendrocyte lineage progression. Among these factors, Sox17 was previously identified as a positive regulator of oligodendrocyte development. However, the role of Sox17 in oligodendroglial cell lineage progression and differentiation is still poorly understood. To define the functional role of Sox17, we generated new transgenic mouse models with inducible overexpression of Sox17, specifically in oligodendroglial cells. Here, we report that gain of Sox17 function has no effect on oligodendrocyte progenitor cells (OPCs) specification. During early postnatal development, Sox17 overexpression increases the pool of OPCs at the expense of differentiated oligodendrocytes. However, the oligodendroglial cell population, OPC proliferation and apoptosis remained unchanged in Sox17 transgenic mice. RNA sequencing, quantitative RT‐PCR and immunohistochemical analysis showed that Sox17 represses the expression of the major myelin genes, resulting in a severe CNS hypomyelination. Overall, our data highlight an unexpected role for Sox17 as a negative regulator of OPC differentiation and myelination, suggesting stage specific functions for this factor during oligodendroglial cell lineage progression.
Renewed interest for low‐dose radiation therapy in follicular lymphomas: From biology to clinical applications
Authors: Ciammella Patrizia , Luminari Stefano , Arcaini Luca , Filippi Andrea Riccardo 
Published: August 2018

AbstractFollicular lymphoma (FL) is the most common subtype of indolent non‐Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a “watchful waiting” approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40 Gy were considered appropriate in first line curative treatment for localized disease (stages I‐II), but several publications investigating low‐dose radiotherapy (LDRT) of 4Gy (2 × 2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.
HIV/AIDS and economic growth: Evidence from West Africa
Authors: Dauda Rasaki Stephen 
Published: August 2018

SummaryHuman immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the leading causes of morbidity and mortality in West Africa. Prevalence among the most productive age group in West and Central Africa stood at 1.5%, 3.4.0%, 2.5%, and 2.1% in 1990, 2000, 2010, and 2015 respectively. This study examined the effect of HIV/AIDS on economic growth in West Africa with focus on 11 countries. The augmented Solow model, rooted in the neoclassical growth theory, was used, which was operationalized using dynamic panel data modeling approach. Incidence, prevalence, number of people living with HIV/AIDS (PLWHA), and AIDS‐related deaths were used to measure HIV/AIDS. Estimations using system GMM returned statistically significant results while those of first difference and difference GMM were not. From the outcome of system GMM analysis, a percentage increase in incidence, prevalence, PLWHA, and AIDS deaths correspondingly reduced growth significantly through their effects on life expectancy by 0.15%, 0.02%, 0.004%, and 0.03%. Acquired immune deficiency syndrome deaths and PLWHA lowered economic growth through enrolment but not significantly. The import of the findings is that HIV/AIDS threatens growth through life expectancy in West Africa. Therefore, its spread in the subregion should be effectively contained while proper treatment should be provided for all infected persons.
A totally recombinant fibrin matrix for mesenchymal stem cell culture and delivery
Authors: Wang Ou , Ismail Ayman , Fabian Frank Marco , Lin Haishuang , Li Qiang , Elowsky Christian , Carlson Mark A. , Burgess Wilson , Velander William H. , Kidambi Srivatsan , Lei Yuguo 
Published: August 2018

AbstractMesenchymal stem cells (MSCs) have been widely studied for tissue engineering and treating diseases in laboratories, clinical trials, and clinics. Fibrin matrices are often used to culture MSCs or increase the retention of MSCs at the injection site. However, fibrins made with the human plasma derived fibrinogen have high cost and risk of human pathogen transmission. In this article, we studied if fibrin matrices made with recombinant human fibrinogen, recombinant human thrombin, and recombinant human factor XIII could be used to culture and deliver MSCs. We systematically investigated the relationships between the fibrin matrix formulation, its nanostructure, and the behaviors of the cells in the matrix including the cell morphology, viability, and growth. We found that the fibrinogen concentration significantly affected the matrix structure and cell behaviors. We then used an optimized fibrin matrix to deliver human MSCs into mice subcutaneously. We found that the matrix could significantly enhance the retention of MSCs at the injection site. To our best knowledge, this is the first study on using fibrin matrices made with entirely recombinant proteins for culturing and delivering MSCs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3135–3142, 2018.
Retracted: Upregulated microRNA‐485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF‐β‐MAPK signaling pathway by inhibiting RhoA expression
Authors: Tian Yu , Han Yu‐Xiang , Guo Hui‐Fang , Jin Hong‐Tao , Sun Chao , Qi Xuan , Ma Li‐Yan , Bo Shi‐Wei 
Published: August 2018

AbstractLupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end‐stage renal disease. This study aims to determine whether microRNA‐485 (miR‐485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF‐β‐MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA‐
RhoA. The target gene of miR‐485 was confirmed by dual‐luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR‐485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL‐6), transforming growth factor‐β1 (TGF‐β1), and p38 mitogen‐activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR‐485 were recorded. The overexpression of miR‐485 or siRNA‐
RhoA or the combination of miR‐485 and siRNA‐
RhoA was demonstrated to lead to a reduction of levels of RhoA, IL‐6, TGF‐β, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR‐485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA‐mediated TGF‐β‐MAPK signaling pathway in LN mice.
Retracted: Downregulation of long noncoding RNA Sox2ot protects PC‐12 cells from hydrogen peroxide–induced injury in spinal cord injury via regulating the miR‐211‐myeloid cell leukemia‐1 isoform2 axis
Authors: Yin Dong , Zheng Xiaoqing , Zhuang Jianxiong , Wang Liangze , Liu Bin , Chang Yunbing 
Published: August 2018

AbstractThis study aimed to investigate the effects and possible mechanisms of long noncoding RNA (lncRNA) Sox2 overlapping transcript (Sox2ot) on hydrogen peroxide (H2O2)‐induced injury in pheochromocytoma (PC‐12) cells. PC‐12 cells were treated with H2O2 to cell injury. The cells were transfected with short‐hairpin RNA directed against Sox2ot (sh‐Sox2ot), small interfering RNA directed against myeloid cell leukemia‐1 (MCL‐1) isoform2 (si‐MCL‐1), a miR‐211 mimic, a miR‐211 inhibitor, and their negative controls. Under different transfected treatments, cell viability, migration, invasion, and apoptosis as well as the expressions of apoptosis‐ and autophagy‐related proteins were investigated. Besides, the regulatory relationships between Sox2ot and miR‐211, miR‐211 and MCL‐1, as well as between MCL‐1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Suppression of Sox2ot inhibited H2O2‐induced PC‐12 cell injury by increasing cell viability, migration, invasion, and decreasing apoptosis and autophagy. Moreover, suppression of Sox2ot increased miR‐211 expression and alleviated H2O2‐induced injury in PC‐12 cells possibly via upregulation of miR‐211. Furthermore, MCL‐1 isoform2 was identified as a direct target of miR‐211 and could be negatively regulated by miR‐211. Suppression of miR‐211 aggravated H2O2‐induced cell injury by regulation of MCL‐1 isoform2. Besides, inhibition of miR‐211 suppressed the activation of the Akt/mTOR/p70S6K signaling pathway in H2O2‐treated PC‐12 cells, which was reversed after knockdown of MCL‐1 isoform2 at the same time. Our findings indicate that downregulation of Sox2ot may protect PC‐12 cells from H2O2‐induced injury in SCI via targeting the miR‐211/MCL‐1 isoform2 axis. MCL‐1 isoform2 may further regulate the activation of the Akt/mTOR/p70S6K pathway to mediate H2O2‐induced injury. The Sox2ot‐miR‐211‐MCL‐1 isoform2 axis may be a promising therapeutic strategy for SCI.
Inhibition of cyclin‐dependent kinase 7 suppresses human hepatocellular carcinoma by inducing apoptosis
Authors: Zhong Liqiang , Yang Sihao , Jia Yuming , Lei Kaijian 
Published: August 2018

AbstractIncreasing evidence has shown that THZ1, a covalent cyclin‐dependent kinase 7 (CDK7) inhibitor, exhibits therapeutic effects in various tumors. However, the possible effect of THZ1 on hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the roles of THZ1 in HCC cells and in subcutaneous HCC model and illustrate the molecular mechanisms. The phosphorylation levels of Ser2, Ser5, and Ser7 within RNA polymerase II (RNAPII) C‐terminal domain (CTD) and the expression levels of Ki67, Mcl‐1, survivin, XIAP, and p53 in HCC cells under different conditions were examined by Western blot analysis. Cell growth and apoptosis were assessed via 3‐(4,5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Tumor volume was assessed in HCC mice with THZ1 or vehicle treatment and immunohistochemical (IHC) analysis was conducted on excised tumors. THZ1 significantly inhibited the phosphorylation of Ser2, Ser5, and Ser7 within RNAPII‐CTD in the dose‐dependent and irreversible manner. MTT assay and flow cytometry analysis showed that THZ1 inhibited HCC cell proliferation and induced apoptosis, respectively. Western blot analysis indicated THZ1 significantly upregulated p53 expression and downregulated the expressions of Mcl‐1, survivin, XIAP, and Ki67. THZ1 suppressed tumor growth in Hep3B xenografted mice in a time‐dependent manner. IHC analysis indicated that tumors in THZ1 group had less Ki67+ cells and more cleaved caspase‐3+ cells than those in vehicle group. THZ1 exhibited anti‐HCC effects through irreversibly inhibiting CDK7 activity, decreasing RNAPII‐CTD phosphorylation, inducing p53 expression and inhibiting antiapoptotic gene expressions, which subsequently induced apoptosis and inhibited proliferation of HCC cells.