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  • Elsevier  (1,461,879)
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  • 1
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    Elsevier
    Publication Date: 2018-02-05
    Description: Publication date: 15 May 2018 Source: NeuroImage, Volume 172 Author(s): Soroosh Afyouni, Thomas E. Nichols Estimates of functional connectivity using resting state functional Magnetic Resonance Imaging (rs-fMRI) are acutely sensitive to artifacts and large scale nuisance variation. As a result much effort is dedicated to preprocessing rs-fMRI data and using diagnostic measures to identify bad scans. One such diagnostic measure is DVARS, the spatial root mean square of the data after temporal differencing. A limitation of DVARS however is the lack of concrete interpretation of the absolute values of DVARS, and finding a threshold to distinguish bad scans from good. In this work we describe a sum of squares decomposition of the entire 4D dataset that shows DVARS to be just one of three sources of variation we refer to as D -var (closely linked to DVARS), S -var and E -var. D -var and S -var partition the sum of squares at adjacent time points, while E -var accounts for edge effects; each can be used to make spatial and temporal summary diagnostic measures. Extending the partitioning to global (and non-global) signal leads to a rs-fMRI DSE table, which decomposes the total and global variability into fast ( D -var), slow ( S -var) and edge ( E -var) components. We find expected values for each component under nominal models, showing how D -var (and thus DVARS) scales with overall variability and is diminished by temporal autocorrelation. Finally we propose a null sampling distribution for DVARS-squared and robust methods to estimate this null model, allowing computation of DVARS p-values. We propose that these diagnostic time series, images, p-values and DSE table will provide a succinct summary of the quality of a rs-fMRI dataset that will support comparisons of datasets over preprocessing steps and between subjects.
    Print ISSN: 1053-8119
    Electronic ISSN: 1095-9572
    Topics: Medicine , Psychology
    Published by Elsevier
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  • 2
    Publication Date: 2018-02-05
    Description: Publication date: Available online 3 February 2018 Source: Trends in Cell Biology Author(s): Carlotta Giorgi, Alberto Danese, Sonia Missiroli, Simone Patergnani, Paolo Pinton Calcium (Ca 2+ ) is considered one of the most-important biological cations, because it is implicated in cell physiopathology and cell fate through a finely tuned signaling system. In support of this notion, Ca 2+ is the primary driver of cell proliferation and cell growth; however, it is also intimately linked to cell death. Functional abnormalities or mutations in proteins that mediate Ca 2+ homeostasis usually lead to a plethora of diseases and pathogenic states, including cancer, heart failure, diabetes, and neurodegenerative disease. In this review, we examine recent discoveries in the highly localized nature of Ca 2+ -dependent signal transduction and its roles in cell fate, inflammasome activation, and synaptic transmission.
    Print ISSN: 0962-8924
    Electronic ISSN: 1879-3088
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2018-02-21
    Description: Publication date: Available online 19 February 2018 Source: Seminars in Cell & Developmental Biology Author(s): Solana Alculumbre, Salvatore Raieli, Caroline Hoffmann, Rabie Chelbi, François-Xavier Danlos, Vassili Soumelis Plasmacytoid pre-dendritic cells (pDC) are a specialized DC population with a great potential to produce large amounts of type I interferon (IFN). pDC are involved in the initiation of antiviral immune responses through their interaction with innate and adaptive immune cell populations. In a context-dependent manner, pDC activation can induce their differentiation into mature DC able to induce both T cell activation or tolerance. In this review, we described pDC functions during immune responses and their implication in the clearance or pathogenicity of human diseases during infection, autoimmunity, allergy and cancer. We discuss recent advances in the field of pDC biology and their implication for future studies.
    Print ISSN: 1084-9521
    Electronic ISSN: 1096-3634
    Topics: Biology , Medicine
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  • 4
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    Elsevier
    Publication Date: 2018-02-21
    Description: Publication date: Available online 19 February 2018 Source: Trends in Microbiology Author(s): Ludmila Chistoserdova, Marina G. Kalyuzhnaya Methylotrophy is a field of study dealing with microorganisms capable of utilization of compounds devoid of carbon–carbon bonds (C1 compounds). In this review, we highlight several emerging trends in methylotrophy. First, we discuss the significance of the recent discovery of lanthanide-dependent alcohol dehydrogenases for understanding both the occurrence and the distribution of methylotrophy functions among bacteria, and then we discuss the newly appreciated role of lanthanides in biology. Next, we describe the detection of other methylotrophy pathways across novel bacterial taxa and insights into the evolution of methylotrophy. Further, data are presented on the occurrence and activity of aerobic methylotrophs in hypoxic and anoxic environments, questioning the prior assumptions on niche separation of aerobic and anaerobic methylotrophy. The concept of communal function in aerobic methane oxidation is also briefly discussed. Finally, we review recent research in engineering methylotrophs for biotechnological applications as well as recent progress in engineering synthetic methylotrophy.
    Print ISSN: 0966-842X
    Electronic ISSN: 1878-4380
    Topics: Biology
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  • 5
    Publication Date: 2018-02-21
    Description: Publication date: Available online 20 February 2018 Source: Trends in Endocrinology & Metabolism Author(s): Robert P. Fisher Dependence on glycolysis under aerobic conditions, a frequent metabolic derangement in cancer cells, suggests a therapeutic opportunity. Now, through chemical genetics, CDK8, a kinase associated with the Mediator transcriptional coactivator complex, has emerged as an upstream inducer of glycolysis and a possible target for anticancer drug discovery.
    Print ISSN: 1043-2760
    Electronic ISSN: 1879-3061
    Topics: Medicine
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  • 6
    Publication Date: 2018-02-21
    Description: Publication date: May 2018 Source: Virology, Volume 518 Author(s): Chunhua Wang, Shuaifeng Zhou, Wanhua Xue, Liang Shen, Wei Huang, Yi Zhang, Xuguang Li, Junzhi Wang, Hong Zhang, Xuejun Ma The management of hand-foot-and-mouth disease(HFMD) epidemic is difficult due to the frequent emergence of non-EV71 and non-CVA16 enteroviruses and some cases testing negative for HFMD-associated causative agents. To clarify the virus spectrum of mild and severe HFMD, a comprehensive virome analysis of 238 samples was performed using next-generation sequencing (NGS). The data revealed total thirteen mammalian- and plant- virus families and diverse viral populations including enteroviruses, common respiratory viruses, diarrhea-related viruses, plant viruses and anelloviruses. A total of 18 viruses from 7 virus families were identified in severe cases, versus 37 viruses from 12 virus families in mild cases. Moreover, complicated mixed-infections of enteroviruses with common respiratory viruses were mainly found in severe cases( P  = 0.013), while diarrhea-related viruses were mainly found in mild cases( P  〈 0.001). This study provides the preliminary understanding of viromes both in mild and severe cases, which may benefit the detection of etiologic agents and prevention of HFMD.
    Print ISSN: 0042-6822
    Electronic ISSN: 1096-0341
    Topics: Medicine
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  • 7
    Publication Date: 2018-02-21
    Description: Publication date: Available online 20 February 2018 Source: Trends in Neurosciences Author(s): David Weinshenker It has been known for decades that degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs in both Alzheimer’s disease (AD) and Parkinson’s disease (PD), but it was given scant attention. It is now recognized that hyperphosphorylated tau in the LC is the first detectable AD-like neuropathology in the human brain, α-synuclein inclusions in the LC represent an early step in PD, and experimental LC lesions exacerbate neuropathology and cognitive/behavioral deficits in animal models. The purpose of this review is to consider the causes and consequences of LC pathology, dysfunction, and degeneration, as well as their implications for early detection and treatment.
    Print ISSN: 0166-2236
    Electronic ISSN: 1878-108X
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2018-02-22
    Description: Publication date: 1 March 2018 Source: Analytical Biochemistry, Volume 544 Author(s): Franziska Pögel neé Steinicke, Imke Oltmann-Norden, Hermann Wätzig Surface Plasmon Resonance Biosensors (SPR) are one of the most powerful tools to characterize protein binding, e.g. for drug discovery, like target identification, ligand fishing, assay development, lead selection and manufacturing quality control. However, there is increasing concern about its reproducibility in the light of the reproducibility crisis. Therefore an appropriate analytical instrument qualification (AIQ) is required for quality assurance of SPR instruments. AIQ is a prerequisite for analytical method validation and it is consisting of four parts, Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ). PQ regularly executed is supposed to continuously control the performance of the instrument under actual running conditions. In this work a performance qualification method was developed for the SPR instrument Biacore X100. This method is suitable for the routinely control of the instrument performance for antibody-antigen binding measurements. Control charts were designed to get a clearly representable and easy implementable tool to check the critical parameters. These control charts and a straightforward protocol now allow the design and application of an individual performance qualification procedure that can be used in the laboratory routine. They serve as reference for individual standard operation procedures (SOPs).
    Print ISSN: 0003-2697
    Electronic ISSN: 1096-0309
    Topics: Biology , Chemistry and Pharmacology
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  • 9
    Publication Date: 2018-02-22
    Description: Publication date: 1 March 2018 Source: Analytical Biochemistry, Volume 544 Author(s): Laura Trapiella-Alfonso, Sylvain Broussy, Wang-Qing Liu, Michel Vidal, Edouard Lecarpentier, Vassilis Tsatsaris, Nathalie Gagey-Eilstein Angiogenesis and its involved proteins, particularly Vascular Endothelial Growth Factor family (VEGFs) and VEGF receptors (VEGFRs), have been considered as a target of therapeutic interest for numerous inflammatory and vascular diseases. Acting on this biological process through interaction with VEGFs or VEGFRs has received considerable attention. Indeed, VEGFs and VEGFRs are currently targeted by drugs such as monoclonal antibodies. The feasibility of a therapeutic strategy based on blocking the VEGF/VEGFR interaction by using ligands “other-than-biologics” is also explored. To help to the discovery of new molecules, screening assays have been developed, particularly to evaluate the VEGFA/VEGFR1 interaction. Despite the therapeutic importance of VEGFB and PlGF (Placental Growth Factor), no assays have been developed to evaluate molecules against their interactions with VEGFR1. Here, we present new versatile colorimetric immunoassays to screen and evaluate the specific interaction of discovered molecules with different growth factors (VEGFA, VEGFB, PlGF) and receptors (VEGFR1, VEGFR2). These tests, based on competitive immunoassay format, will provide essential information on specificity and selectivity of molecules for their targets and will help to work on the pharmaco-modulation of molecules for targeting one specific interaction.
    Print ISSN: 0003-2697
    Electronic ISSN: 1096-0309
    Topics: Biology , Chemistry and Pharmacology
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  • 10
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Jasmine Tay, Lin Foo, Giulia Masini, Phillip R. Bennett, Carmel M. Mceniery, Ian B. Wilkinson, Christoph C. Lees Background and Objectives Pre-eclampsia (PE) and fetal growth restriction (FGR) are considered to be placentally-mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset PE considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in PE and FGR. Study Design We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 ‘PE only’, 16 ‘FGR only’, 15 ‘PE and FGR’) and compared these with 107 healthy person observations. Cardiac output (CO) was the primary outcome measure, and was assessed using an inert gas rebreathing method (Innocor®), from which peripheral vascular resistance was derived (PVR); arterial function was assessed by Vicorder ®, a cuff-based oscillometric device. Cardiovascular parameters were normalised for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range 24-40 weeks. Results Compared with healthy control pregnancies, women with PE had higher CO Z scores (1.87 ± 1.35; p=0.0001) and lower PVR Z scores (-0.76± 0.89; p=0.025); those with FGR had higher PVR Z scores (0.57± 1.18; p=0.04) and those with both PE and FGR had lower CO Z scores (-0.80 ± 1.3; p= 0.007) and higher PVR Z scores (2.16 ± 1.96; p=0.0001). These changes were not related to gestational age of onset. All those affected by PE and/or FGR had abnormally raised augmentation index (AIx) and pulse wave velocity (PWV). Furthermore, in PE, low CO was associated with low birthweight and high CO with high birthweight. (r=0.42, p=0.03). Conclusions PE is associated with high CO, but if PE presents with FGR, the opposite is true; both conditions are, nevertheless, defined by hypertension. FGR without PE is associated with high PVR. Though 'early' and 'late' gestation PE are considered to be different diseases, we show that the haemodynamic characteristics of PE were unrelated to gestation age at onset, but strongly associated with the presence or absence of FGR. FGR more commonly co-exists with PE at early gestation, thus explaining the conflicting results of previous studies. Furthermore, anti-hypertensive agents act by reducing CO or PVR and are administered without reference to cardiovascular function in PE. The underlying pathology (PE, FGR, PE and FGR) defines cardiovascular phenotype, providing a rational basis for choice of therapy where high or low CO or PVR are the predominant features.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 11
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Biochemical Pharmacology Author(s): Jun Gu, Yu-qi Fan, Hui-li Zhang, Jian-an Pan, Jian-ying Yu, Jun-feng Zhang, Chang-qian Wang The clinical use of doxorubicin (DOX) is limited by cardiotoxicity, involving the dysregulation of autophagy and apoptosis in the myocardium, which were partly reversed by resveratrol (RSV) supplement. However, a definitive mechanisms accounting for DOX’s cardiotoxicity and the protective role of RSV remain poorly defined. The aim of the present study was to clarify the specific role of E2F transcription factor 1(E2F1) in regulating autophagy and apoptosis in DOX-induced cardiotoxicity as well as the protective effects of RSV. Autophagy and apoptosis were successfully induced by the serum deprivation strategy in H9c2 cardiomyocytes. DOX inhibited autophagy through activating E2F1/mammalian target of rapamycin complex 1 (mTORC1) pathway and further induced apoptosis by activating E2F1/AMP-activated protein kinase α2 (AMPKα2) pathway in starved H9C2 cells. And RSV supplement showed increased autophagy and decreased apoptosis, accompanied with inhibitory effect on E2F1/mTORC1 as well as E2F1/AMPKα2 pathway. Moreover, the favorable effect of RSV on autophagy and apoptosis was dependent on E2F1. The same result was observed in the mouse model of DOX-induced cardiotoxicity in both non-myocardial ischemia and myocardial ischemia condition. Injection with DOX and RSV in combination, resulted in a reduced apoptotic ratio and activated autophagy process compared with the DOX treatment alone. In conclusions, RSV, which has been suggested to attenuate DOX-induced cytotoxicity, significantly blocks induction of E2F1/mTORC1 and E2F1/AMPKα2 pathway by DOX, leading to acceleratory autophagy and inhibitory apoptosis. And E2F1 plays a key role for the protective effect of RSV. Graphical abstract
    Print ISSN: 0006-2952
    Electronic ISSN: 1873-2968
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 12
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Author(s): Jung-Chun Lin Alternative splicing has been widely demonstrated to function as pivotal regulation in specifying cellular fates and biological functions. The relative expression or cellular localization of a splicing factor constitutes an important mechanism in spatiotemporal programming of cell- and stage-specific splicing profiles. In this study, results of deep RNA-sequencing (RNA-Seq) analyses first revealed the reprogrammed splicing profile and reduced expression of serine/arginine-rich splicing factor protein kinase 1 (SRPK1) throughout the development of brown adipose tissue (BAT). A gradual increase in the exon 10-skipped SRPK1 transcript, a potential target of a nonsense-mediated decay (NMD) mechanism, was noted during brown adipogenesis. Elevated RBM4a constituted the regulatory mechanism that led to skipping of SRPK1 exon 10. Moreover, brown adipogenesis-induced upregulation of microRNA (mi R )-485 interfered with SRPK1 expression by targeting its 3′-untranslated region (UTR). Depletion of endogenous SRPK1 enhanced the development of C3H10T1/2 cells toward brown adipocytes. Taking our results together, multiple post-transcriptional regulations reduced SRPK1 expression, which subsequently affected brown adipogenesis.
    Print ISSN: 1388-1981
    Electronic ISSN: 1879-2618
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
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  • 13
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Biochemical and Biophysical Research Communications Author(s): Jiabi Zhang, Juan Shan, Xuelu Chen, Shengfu Li, Dan Long, Youping Li A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4 + CD25 − T cells were purified, stimulated with anti-CD3/CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol. Initially, we determined that Interleukin (IL)-17 expression by celastrol-treated Th17 was significantly decreased compared with untreated cells; however, the frequency of Foxp3+ cells was increased in celastrol-treated cells. We verified that celastrol inhibited phospho-STAT3 expression in cultured Th17 cells and up-regulated phospho-STAT5 expression in iTreg cells. Furthermore, T cells treated with celastrol were more likely to participate in FAO metabolism instead of glycolysis. Celastrol suppressed the expression of glucose transporter, Glut1, and the rate-limiting enzyme, HK2, in addition to mTOR, HIF-1α, c-Myc and Akt expression in Th17 cells. Conversely, celastrol promoted FAO of lipids by up-regulating CPT1A and AMPKα expression in iTreg cells. Our results suggest that celastrol suppresses Th17 cell induction, while promoting the generation of iTreg cells. We found that celastrol inhibits glycolysis in Th17 cells and promotes FAO by iTreg cells, suggesting that celastrol could mediate the metabolism of Th17 and iTreg cells.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
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  • 14
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Author(s): Lisa Rein-Fischboeck, Elisabeth M. Haberl, Rebekka Pohl, Verena Schmid, Susanne Feder, Sabrina Krautbauer, Gerhard Liebisch, Christa Buechler Adipose tissue dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis (NASH). The adapter protein alpha-syntrophin (SNTA) is expressed in adipocytes. Knock-down of SNTA increases preadipocyte proliferation and formation of small lipid droplets, which are both characteristics of healthy adipose tissue. To elucidate a potential protective role of SNTA in NASH, SNTA null mice were fed a methionine-choline-deficient (MCD) diet or an atherogenic diet which are widely used as preclinical NASH models. MCD diet mediated loss of fat mass was largely improved in SNTA−/− mice compared to the respective wild type animals. Hepatic lipids were mostly unchanged while the oxidative stress marker malondialdehyde was only induced in the wild type mice. The expression of inflammatory markers and macrophage immigration into the liver were reduced in SNTA−/− animals. This protective function of SNTA loss was absent in atherogenic diet induced NASH. Here, hepatic expression of inflammatory and fibrotic genes was similar in both genotypes though mutant mice gain less body fat during feeding. Hepatic cholesterol and ceramide were strongly induced in both strains upon feeding the atherogenic diet, while hepatic sphingomyelin, phosphatidylserine and phosphatidylethanolamine levels were suppressed. SNTA deficient mice are protected from fat loss and NASH in the experimental MCD model. NASH induced by an atherogenic diet is not influenced by loss of SNTA. The present study suggests the use of different experimental NASH models to study the pathophysiological role of proteins like SNTA in NASH.
    Print ISSN: 1388-1981
    Electronic ISSN: 1879-2618
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
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  • 15
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Author(s): Ying-Chen Lin, Koichi Kobayashi, Hajime Wada, Yuki Nakamura Phosphatidylglycerol (PG) is an indispensable lipid class in photosynthetic activity. However, the importance of PG biosynthesis in non-photosynthetic organs remains elusive. We previously identified phosphatidylglycerophosphate phosphatase 1 (PGPP1), which catalyzes the last step of PG biosynthesis in Arabidopsis thaliana . In the present report, we noted considerably shorter roots of the pgpp1 - 1 mutant compared to the wild type. We observed defective order of columella cells in the root apices, which was complemented by introducing the wild-type PGPP1 gene. Although PGPP1 is chloroplast-localized in leaf mesophyll cells, we observed mitochondrial localization of PGPP1 in root cells, suggesting possible dual targeting of PGPP1. Moreover, we identified previously uncharacterized 2 protein tyrosine phosphatase-like proteins as functional PGPPs. These proteins, designated PTPMT1 and PTPMT2, complemented growth and lipid phenotypes of Δ gep4 , a Saccharomyces cerevisiae mutant of PGPP. The ptpmt1 - 1 ptpmt2 - 1 exhibited no visible phenotype; however, the pgpp1 - 1 ptpmt1 - 1 ptpmt2 - 1 significantly enhanced the root phenotype of pgpp1 - 1 without further affecting the photosynthesis, suggesting that these newly found PGPPs are involved in the root phenotype. Radiolabeling experiment of mutant roots showed that decreased PG biosynthesis is associated with the mutation of PGPP1 . These results suggest that PG biosynthesis is required for the root growth.
    Print ISSN: 1388-1981
    Electronic ISSN: 1879-2618
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
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  • 16
    Publication Date: 2018-02-22
    Description: Publication date: Available online 20 February 2018 Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Wan Wang, Dan Wang, Chuiyu Kong, Shuangyue Li, Liping Xie, Zhe Lin, Yuan Zheng, Jianli Zhou, Yi Han, Yong Ji Protein S-nitrosylation plays an important role in the progression of cardiovascular diseases. eNOS can be S-nitrosylated in endothelial cells, and this modification reversibly attenuates enzyme activity. Under physiological conditions, eNOS directly interacts with β-catenin. However, whether and how eNOS S-nitrosylation regulates the β-catenin signal pathway and participates in endothelial dysfunction remains unknown. Here, we show that OxLDL induces the S-nitrosylation of eNOS, which enhances the interaction between eNOS and β-catenin, transcriptional activity of β-catenin, cell migration and adhesion molecule expression in endothelial cells. In addition, these effects are partially abolished after eNOS is mutated at Cys94 and Cys99, but not Cys441, in endothelial cells. Furthermore, OxLDL increases iNOS expression. The specific iNOS inhibitor 1400 W decreases eNOS S-nitrosylation and the association of eNOS and β-catenin, thereby blocking the β-catenin signal pathway to alleviate OxLDL-induced endothelial dysfunction. Taken together, OxLDL induces eNOS S-nitrosylation at Cys94 and Cys99 via an iNOS-dependent manner, which may increase β-catenin activation and trigger endothelial injury. This study describes a novel mechanism of endothelial dysfunction.
    Print ISSN: 0925-4439
    Electronic ISSN: 1879-260X
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
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  • 17
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Biomaterials, Volume 162 Author(s): Huan Liu, Xue Qu, Eunkyoung Kim, Miao Lei, Kai Dai, Xiaoli Tan, Miao Xu, Jinyang Li, Yangping Liu, Xiaowen Shi, Peng Li, Gregory F. Payne, Changsheng Liu Open wounds and burns are prone to infection and there remains considerable interest in developing safe and effective mechanisms to confer antimicrobial activities to wound dressings. We report a biomimetic wound dressing for the in situ and sustained generation of reactive oxygen species (ROS). Specifically, we fabricate a catechol-modified chitosan film that mimics features of the melanin capsule generated during an insect immune response to infection. We use an electrochemical reverse engineering approach to demonstrate that this catechol-chitosan film possesses redox-activities and can be repeatedly oxidized and reduced. In vitro tests demonstrate that this film catalyzes the transfer of electrons from physiological reductant ascorbate to O 2 for sustained ROS generation, and confers ascorbate-dependent antimicrobial activities. In vivo antimicrobial experiment with a rat subcutaneous model indicates the catechol-chitosan film at reduced state inhibits the bacterial growth and alleviates the infection of the incisions. Open wound healing tests with a mouse model indicate that the catechol-chitosan film suppresses the bacterial population at the wound site, induces less inflammation and promotes wound healing. We envision this biomimetic approach for the sustained, localized and in situ generation of ROS could provide new opportunities for wound management by protecting against pathogen infection and potentially even enlisting ROS-mediated wound healing mechanisms. Graphical abstract
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 18
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Biomaterials, Volume 162 Author(s): Benjamin A. Juliar, Mark T. Keating, Yen P. Kong, Elliot L. Botvinick, Andrew J. Putnam Matrix stiffness is a well-established instructive cue in two-dimensional cell cultures. Its roles in morphogenesis in 3-dimensional (3D) cultures, and the converse effects of cells on the mechanics of their surrounding microenvironment, have been more elusive given the absence of suitable methods to quantify stiffness on a length-scale relevant for individual cell-extracellular matrix (ECM) interactions. In this study, we applied traditional bulk rheology and laser tweezers-based active microrheology to probe mechanics across length scales during the complex multicellular process of capillary morphogenesis in 3D, and further characterized the relative contributions of neovessels and supportive stromal cells to dynamic changes in stiffness over time. Our data show local ECM stiffness was highly heterogeneous around sprouting capillaries, and the variation progressively increased with time. Both endothelial cells and stromal support cells progressively stiffened the ECM, with the changes in bulk properties dominated by the latter. Interestingly, regions with high micro-stiffness did not necessarily correlate with remodeled regions of high ECM density as shown by confocal reflectance microscopy. Collectively, these findings, especially the large spatiotemporal variations in local stiffness around cells during morphogenesis in soft 3D fibrin gels, underscore that characterizing ECM mechanics across length scales. provides an opportunity to attain a deeper mechanobiological understanding of the microenvironment's roles in cell fate and tissue patterning.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 19
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Biomaterials, Volume 162 Author(s): Jinfeng Liu, Yihan Chen, Guohua Wang, Qing Lv, Yali Yang, Jing Wang, Pingyu Zhang, Jie Liu, Yu Xie, Li Zhang, Mingxing Xie Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NB CD3 ) or isotype antibody (NB con ) were prepared and characterized. There was significant adhesion of NB CD3 to T lymphocytes compared with NB con in vitro . The signal intensity of the adherent NB CD3 was significantly higher than that of the NB con in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NB CD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NB CD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 20
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Biomaterials, Volume 162 Author(s): Gyeonghui Yu, Heesun Jung, Yoon Young Kang, Hyejung Mok To determine whether exosomes are efficient carriers for immune stimulating molecules into lymph nodes, comparative studies of exosomes (EXOs) derived from different origins (cells and serums) in terms of physicochemical properties and delivery efficiency were performed. Serum-derived EXOs were of a preferable size and generated higher yields than RAW264.7 cell-derived exosomes (RAW-EXO). In particular, fetal bovine serum-derived exosomes (bo-EXO), with a size below 50 nm, were delivered not only to surface zones (subcapsular sinus (SCS) macrophage zone) but also to inner paracortex zones (T cell zone) of lymph nodes, which allowed an efficient delivery of immune stimulating molecules to antigen presenting cells and T cells. The encapsulation of immune stimulating biomolecules (monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG ODN)) within EXOs greatly increased intracellular delivery to macrophages via phagocytic pathways, which induced higher TNF-α and IL-6 secretion than free MPLA and free CpG ODN. MPLA-incorporated exosomes activated and differentiated T cells after subcutaneous injection, which elevated cytokine IFN-γ and TNF-α induction for CD3 + T cells. Taken together, bo-EXOs might serve as efficient carrier systems of immune stimulators to lymph nodes for desired immune responses.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 21
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Biomaterials, Volume 162 Author(s): Manping Lin, Shilong Mao, Jinfeng Wang, Juan Xing, Yuanliang Wang, Kaiyong Cai, Yanfeng Luo The transmission of cell traction force (CTF) to underlying biomaterials is essential for adhered cells to measure and respond to their mechanical microenvironment. Given that the protein layer adsorbed on materials lies between the cells and materials, we hypothesize that the interfacial strength of protein-material interfaces (i.e., the adsorption force of proteins, F ad ) should have an important role in regulating the transmission of CTF. To test this hypothesis, rat mesenchymal stem cells (rMSCs) were cultured on poly(dimethyl siloxane) (PDMS) substrates with different F ad of fibronectin (FN), and the transmission of CTF was observed by immunofluorescence staining of FN and deformation of PDMS. As revealed, FN on substrates with low F ad is more liable to be desorbed by CTF, which prevents the transmission of CTF to substrates. In contrast, high F ad facilitates the transmission of CTF from rMSCs to the FN layer and PDMS substrates so that rMSCs can perceive the mechanical properties of substrates. We further demonstrated that the divergent transmission of CTF on low and high F ad substrates regulates the lineage specifications of rMSCs. Our study confirms the important role of F ad in CTF transmission and provides a new perspective to gain insights into cell-material interactions and cell fates, which may help to guide the design of better biomaterials. Graphical abstract
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 22
    Publication Date: 2018-02-06
    Description: Publication date: Available online 3 February 2018 Source: Global Ecology and Conservation Author(s): Emmanuel Ngulube Chidumayo Charcoal production in Sub-Saharan Africa is often perceived to have serious ecological and environmental effects even although it does not necessarily result in forest conversion to other land uses. Forest recovery through natural or assisted regeneration is particularly appealing for managing tropical dry forests following degradation by charcoal production because of the coppicing ability of the majority of tree species. However, the impacts of crop cultivation and tree enrichment planting on the regeneration of indigenous trees following charcoal production have rarely been investigated. The present study was conducted on adjacent cultivated and control subplots for over 20 years after charcoal production at a site in central Zambia, southern Africa, to assess the effects of short term crop cultivation, tree enrichment planting and tree shading on Piliostigma thonningii , a potential agroforestry species in sub-Saharan Africa. Seedling emergence, sapling survival and annual tree growth were monitored from 2000 to 2017 and aboveground wood biomass estimated using an allometric equation developed from trees cut at the site and the surrounding area. Seedling emergence from untreated seeds occurred over a 6-year period and tree shading significantly reduced seedling germination and survival. Saplings grew very slowly and none transitioned into a tree after 12 years of observations. Although crop cultivation had no significant effect on the population dynamics of P . thonningii , it reduced tree growth rates, biomass production and peak biomass accumulation. Peak aboveground wood biomass on post-cultivation blocks of 13.7 t ha −1 represented only 61% of the 22.5 t ha −1 on control blocks. Some of the major challenges in cultivating P . thonningii as an agroforestry species are seed dormancy and slow sapling growth and these need to be resolved if the species is to be widely cultivated.
    Print ISSN: 2351-9894
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering
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  • 23
    Publication Date: 2018-02-06
    Description: Publication date: Available online 4 February 2018 Source: Gynecologic Oncology Author(s): Kathleen N. Moore, Mansoor Raza Mirza, Ursula A. Matulonis Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through “trapping” the PARP enzyme on damaged DNA. Phase I and III studies have demonstrated activity and benefit of niraparib in both BRCA mutated ( BRCA m) and BRCA wild-type ( BRCA wt) cancers. Phase I testing of niraparib established the maximally tolerated dose of 300 mg by mouth (PO) daily, and the phase 3 ENGOT-OV16/NOVA study demonstrated the benefit of niraparib maintenance therapy compared to placebo after completion of and response to platinum-based chemotherapy in both BRCA m and BRCA wt ovarian cancer patient populations. Toxicities seen with niraparib include hematologic, gastrointestinal, fatigue, and cardiovascular. Hematologic toxicities include thrombocytopenia, anemia, neutropenia and leukopenia; upfront dose modification to 200 mg niraparib for patients with baseline weight of ≤77 kg and/or baseline platelets of ≤150,000 K/uL should be considered to avoid significant hematologic toxicity, especially thrombocytopenia, based on recent analyses of the ENGOT-OV16/NOVA study. Cardiovascular toxicities include hypertension, tachycardia, as well as palpitations, and patients should be monitored for hypertension. PARP inhibitors have been associated with low risks of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and the overall risk of AML and MDS is 0.9% of all patients treated with niraparib. Niraparib testing is ongoing in newly diagnosed ovarian cancer patients as maintenance therapy following completion of platinum-based chemotherapy, in BRCA wt cancers as treatment, as well as in combinations with other biologic drugs such as immunotherapy and anti-angiogenic agents.
    Print ISSN: 0090-8258
    Electronic ISSN: 1095-6859
    Topics: Medicine
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  • 24
    Publication Date: 2018-02-22
    Description: Publication date: 1 May 2018 Source: Cancer Letters, Volume 421 Author(s): Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial–mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation. Knockdown of ADAM9 inhibited the IL-6-induced EMT. Additionally, ADAM9 expression was positively correlated with IL-6 and Snail expression in human HCC specimens. Taken together, our results showed that ADAM9 is an important mediator of IL-6-induced HCC cell migration and invasion, and may provide a novel therapeutic target for HCC management.
    Print ISSN: 0304-3835
    Topics: Medicine
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  • 25
    Publication Date: 2018-02-22
    Description: Publication date: February 2018 Source: Current Opinion in Cell Biology, Volume 50 Author(s): Francisco J Calero-Cuenca, Cátia S Janota, Edgar R Gomes The position of the nucleus within cells is a key event during cell migration. The movement and positioning of the nucleus strongly impacts cell migration. Notably, the last two years largely contributed to emphasise the dynamicity of the nucleus–cytoskeleton interactions that occur during cell migration. Nuclei are under continuous tension from opposing intracellular forces and its tether to the cytoskeleton can be regulated at different levels. Interestingly, it was showed how nuclear positioning is highly related to cell function. In most migrating cells, including cancer cells, the nucleus can be the rate limiting step of cell migration and is placed away from the leading edge. By contrast, leukocytes position their nucleus close to the lamellipodia at the leading edge, and the nucleus contributes to drilling through the endothelium. Differences in cell migration in 2D versus 3D environments are also evident. The mechanisms and forces at play during nuclear positioning and translocation are clearly affected by the nature of the substrate. As such nuclear positioning during cell migration can vary between cell types and environments. In this review we aim to give an overview of the latest discoveries in the field revealing how nuclear positioning is tightly regulated, not only by intrinsic nuclear properties, such as deformability, nuclear envelope content or nucleus–cytoskeleton connectivity, but also by the microenvironment.
    Print ISSN: 0955-0674
    Electronic ISSN: 1879-0410
    Topics: Biology , Medicine
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  • 26
    Publication Date: 2018-02-22
    Description: Publication date: Available online 20 February 2018 Source: Current Opinion in Immunology Author(s): Gwendalyn J .Randolph
    Print ISSN: 0952-7915
    Electronic ISSN: 1879-0372
    Topics: Biology , Medicine
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  • 27
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Valérie Cornuault, Sara Pose, J. Paul Knox The data included in this article are related to the research article entitled “Disentangling pectic homogalacturonan and rhamnogalacturonan-I polysaccharides: evidence for sub-populations in fruit parenchyma systems” (Cornuault et al., 2018) [1]. Cell wall properties are an important contributor to fruit texture. These datasets compile textural and immunochemical analysis of polysaccharides of four economically important fruit crops: tomato, strawberry, aubergine and apple with contrasting textures and related taxonomical origins. Cell wall components and their extractability were assessed using characterized monoclonal antibodies. In addition, textural data obtained for the four parenchyma systems show variations in the mechanical properties. The two datasets are a basis to relate cell wall composition and organization to the mechanical properties of the fruit parenchyma tissues.
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    Topics: Biology
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  • 28
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Pankaj Kumar Singh, Sayak Ganguli, Amita Pal Blackgram ( Vigna mungo ) is one of primary legumes cultivated throughout India, Cv.T9 being one of its common high yielding cultivar. This article reports RNA sequencing data and a pipeline for prediction of novel long non-coding RNAs from the sequenced data. The raw data generated during sequencing are available at Sequence Read Archive (SRA) of NCBI with accession number- SRX1558530
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  • 29
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Jeeranan Manokawinchoke, Praphawi Nattasit, Tanutchaporn Thongngam, Prasit Pavasant, Kevin A. Tompkins, Hiroshi Egusa, Thanaphum Osathanon Indirect immobilized ligand has been shown as an effective technique to activate Notch signalling in vitro. The data presented in this article are related to the published article entitled “Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells” (Manokawinchoke et al. 2017) [1]. This data article describes gene expression in indirect immobilized Jagged1 treated human dental pulp cells (hDPs) using high throughput RNA sequencing technique. These data are valuable to analyze the regulation of Notch signalling in hDPs for understanding its molecular mechanism(s). Raw RNA sequencing data were deposited in the NCBI Sequence Read Archive ( SRP100068 ) and NCBI Gene Expression Omnibus ( GSE94989 ).
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  • 30
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Rinat Sultanov, Olga Lebedeva, Georgij Arapidi, Maria Lagarkova, Sergei Kiselev The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1] . iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e.g., plasmids, Sendai virus, synthetic mRNAs and recombinant proteins). To evaluate the contribution of the reprogramming process isogenic system should be utilized (Shutova et al., 2016) [2] . Isogenic iPSC lines, obtained in different ways can serve the ideal system to investigate DNA methylation changes. The data presented in this article report methylation profiles for iPSC lines derived from fibroblasts of a healthy donor and PARK8-associated Parkinson's disease patient via integrating (lentiviral transfection) and non-integrating (Sendai virus infection) reprogramming using an Illumina 450K Methylation BeadChip platform. The data on DNA methylation of neurons differentiated from iPSC lines are also provided here.
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  • 31
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Samer Kahwaji, Mary Anne White The data presented in this article include the molar masses, melting temperatures, latent heats of fusion and temperature-dependent heat capacities of fifteen fatty acid phase change materials (PCMs). The data are used in conjunction with the thermodynamic models discussed in Kahwaji and White (2018) [1] to develop a computational tool that calculates the eutectic compositions and thermal properties of eutectic mixtures of PCMs. The computational tool is part of this article and consists of a Microsoft Excel® file available in Mendeley Data repository [2] . A description of the computational tool along with the properties of nearly 100 binary mixtures of fatty acid PCMs calculated using this tool are also included in the present article. The Excel® file is designed such that it can be easily modified or expanded by users to calculate the properties of eutectic mixtures of other classes of PCMs.
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  • 32
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Yutong Wu, Meiqi Gao, Song Li, Yuping Ren, Gaowu Qin A seamless Cu nanowire array grown on Cu wire is prepared by combining thermal oxidation method and electrochemical reduction. The data set described in this paper includes the structure of the Cu nanowires electrode, electrocatalytic active surface area, linear sweep voltammetry and amperometry measurement for nitrate sensing. The electrochemical data show that Cu nanowire arrays exhibited a linear response to nitrate ions over a concentration range from 50 μM to 600 μM ( R 2 = 0.9974) with a sensitivity of 0.357 μA μM −1 cm − 1 and detection limit of 12.2 μM at a signal-to-noise ratio of 3, respectively.
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  • 33
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Cheng-Hui Zeng, Hao-Ran Li, Zi-Qi Liu, Fei Chen, Shengliang Zhong In this data article, we present the structural and PARD data of the Ln-MOFs. Detailed structure, luminescence and sensing properties were discussed in our previous study (Zeng et al., in press) [1] The data includes the SBU structure patterns of these Ln-MOFs, thermostability of Ln-MOFs in water and also detailed structure information listed in Tables 1–8 .
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  • 34
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Elena Golikova, Olga Kniazeva, Sergei Korsun Glaciers in the fjords of Svalbard have been receding over last decades. Tempelfjorden, a typical glaciated fjord in West Spitsbergen (78°24′06″ N, 17°02′30″ E), has been sampled in summer 1995 and 2001–2007 for modern benthic foraminifera. We have normalized the abundances and unified the taxonomy of all these published and unpublished data sets and then compiled the record of foraminiferal assemblages changing over years into a comprehensive database. The record includes data on living and dead abundances of benthic foraminiferal species in the surface sediments (0–2 cm) and downcore abundances of living foraminifera (only for 2004). This database portrays benthic foraminifera, this key group of microfossils, in a gradually changing Arctic environment.
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  • 35
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Qiansuo Wang, Yougui Song This article presents clay minerals and major elements data of Miocene red clay from Zhuanglang core (ZL) from the eastern Longzhong Basin, China. The dataset including the contents of main clay minerals such as smectite, kaolinite, illite and chlorite and other important clay minerals parameters as illite crystallinity, Illite 5 Å/10 Å, kaolinite/(illite +chlorite) ratio and major elements and its ratio as SiO 2 , Al 2 O 3 , MgO, Na 2 O, K 2 O, K 2 O/Al 2 O 3 and SiO 2 /Al 2 O 3 in the Mid-Miocene climatic optimum (MMCO). The X-ray diffraction (XRD) and X-ray Fluorescence (XRF) experiments were made at the State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, Chinese Academy of Sciences. The data provide the evidence for understanding the MMCO and its driving factors.
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  • 36
    Publication Date: 2018-02-22
    Description: Publication date: April 2018 Source: Data in Brief, Volume 17 Author(s): Theophilus Aanuoluwa Adagunodo, Sebastian Lüning, Adekunle Michael Adeleke, Julius Oluwasegun Omidiora, Ahzegbobor Philips Aizebeokhai, Kehinde David Oyeyemi, Olaide Sakiru Hammed This article evaluates the occurrence of 0 ≤ M ≤ 8 earthquake data sets for the period of 50 years (that is, January 1, 1966 to December 31, 2015) in African and Western Asia region. It is bounded by latitude 40° S to 40° N and longitude 30° W to 60° E with the focal depth of 0–700 km. Seventy seven thousand, six hundred and ninety-six data points were presented for the analysis. The data used were extracted from earthquake catalog of Advanced National Seismic system via http://quake.geo.berkeley.edu/cnss/ , an official website of the Northern California Earthquake Data Centre, USA. Each datum comprised the earthquake occurrence date, time of the earthquake occurrence, epicenter’s coordinates, focal depth and magnitude. The Gutenberg-Richter’s relationship being the longest observed empirical relationship in seismology, analysis of variance and time series were used to analyze the seismicity of the study area. Annual distributions of earthquake occurrence based on magnitude variations with the limit 0 ≤ M ≤ 8 were presented. The two constants a and b in the Gutenberg-Richter’s equation, magnitude of completeness (MC) adjusted R-Square and F -value for the period of 1966–1975, 1976–1985, 1986–1995, 1996–2005, 2006–2015, and the entire period of investigation ranging from 1966 to 2015 were determined so as to investigate the variations of these parameters on earthquake occurrence over time. The histograms of earthquake occurrence against magnitude of earthquakes for the selected years (1966–1975, 1976–1985, 1986–1995, 1996–2005, 2006–2015, and 1966–2015), and the decadal frequency distributions of earthquake occurrence were also plotted. The focal depth occurrence for each magnitude bins (0–0.9, 1–1.9, 2–2.9, 3–3.9, 4–4.9, 5–5.9, 6–6.9, 7–7.9, 8–8.9) were grouped into shallow, intermediate, and deep depths ranging from 0 to 70, 71 to 300, and 301 to 700 km as being used in seismology. The neural network analysis was also applied to the magnitude of the earthquake. The network uses a time series magnitude data as input with the output being the magnitude of the following day. If the nature of the earthquakes time series is stochastic, modeling and prediction is possible. The earthquake data sets presented in this article can further be adopted in the study of seismicity pattern, b -value using series of models, earthquake prediction and variations of earthquake parameters on African and/or Arabian plates. When this approach is integrated with other technique(s), it can provide insights to stability of African lithospehric plates especially the coastal region of Africa.
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  • 37
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: DNA Repair Author(s): Timsi Rao, Simonne Longerich, Weixing Zhao, Hideki Aihara, Patrick Sung, Yong Xiong Fanconi-associated nuclease 1 (FAN1) removes interstrand DNA crosslinks (ICLs) through its DNA flap endonuclease and exonuclease activities. Crystal structures of human and bacterial FAN1 bound to a DNA flap have been solved. The Pseudomonas aeruginosa bacterial FAN1 and human FAN1 (hFAN1) missing a flexible loop are monomeric, while intact hFAN1 is homo-dimeric in structure. Importantly, the monomeric and dimeric forms of FAN1 exhibit very different DNA binding modes. Here, we interrogate the functional differences between monomeric and dimeric forms of FAN1 and provide an explanation for the discrepancy in oligomeric state between the two hFAN1 structures. Specifically, we show that the flexible loop in question is needed for hFAN1 dimerization. While monomeric and dimeric bacterial or human FAN1 proteins cleave a short 5′ flap strand with similar efficiency, optimal cleavage of a long 5′ flap strand is contingent upon protein dimerization. Our study therefore furnishes biochemical evidence for a role of hFAN1 homodimerization in biological processes that involve 5′ DNA Flap cleavage.
    Print ISSN: 1568-7864
    Electronic ISSN: 1568-7856
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  • 38
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Experimental and Molecular Pathology Author(s): Lan Liu, Zhaoting Yang, Weidong Ni, Yanhua Xuan Background A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker. Methods ADAMTS-6 expression was detected by immunohistochemistry (IHC) in 171 paraffin-embedded ESCC specimens; relationships with patients' clinicopathological features and Twist-1 expression were analyzed by the Pearson Chi-square method, respectively. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan–Meier method and compared using the long-rank test. Results ADAMTS-6 was expressed mainly in the cytoplasm and nucleus; the expression was significantly higher in tumor tissues. Increased expression of ADAMTS-6 correlated with clinical stage ( P  = 0.009), pT stage ( P  = 0.042), lymph node metastasis ( P  = 0.014) and recurrence ( P  = 0.033). There were no significant correlations between ADAMTS-6 expression and other clinicopathological parameters including age, sex, tumor size, distant metastasis, differentiation, …chemotherapy, radiotherapy, CD68 expression and epithelial mesenchymal transition (EMT) status. Kaplan–Meier survival curves revealed that upregulated expression of ADAMTS-6 indicated short OS ( P  = 0.001) and DFS ( P  = 0.002). Multivariate analysis confirmed that high ADAMTS-6 expression was an independent factor for ESCC prognosis. ADAMTS-6 expression was significantly correlated with Twist-1 expression in ESCC cancer cells ( P  = 0.007) and stromal cells ( P  〈 0.001). Patients with ESCC revealing expression of both ADAMTS-6 and Twist-1 exhibited significantly reduced OS and DFS rates than other patients. Conclusions High ADAMTS-6 expression is a useful marker of poor prognosis in patients with ESCC.
    Print ISSN: 0014-4800
    Electronic ISSN: 1096-0945
    Topics: Medicine
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  • 39
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Global Ecology and Conservation Author(s): Jennifer Rebecca Kelly Research has given the illegal trade of feline derivatives in Mexico as well as Central and South America little attention. The purpose of this article is to: 1) Begin a dialogue among human dimensions of wildlife scholars about the economic and cultural values of feline derivatives throughout Mexico, Central and South America; 2) Present the range of economic values that emerged in my interview and participant observation data from Costa Rica; 3) Offer an explanation of how sociological concepts influence the buying and selling of dead jaguars ( Panthera onca ), pumas ( Puma concolor ), and ocelots ( Leopardus pardalis ) in Costa Rica. The principal results are: 1) The sociological concepts of social status and masculine identity interlace with and motivate the illegal trade; 2) The value of feline parts in Costa Rica ranges from $25 to $5000; 3) This value differs by culture and geographic residency of the seller (urban versus rural) and diverged from values discovered in other countries; 4) The men who adorn their homes with illegal trophies are not necessarily the poachers. The value of jaguar skin has been recorded for as little as $100 in a 1983 study conducted in Belize and for as high as $600 in a study done in Venezuela in approximately 2011. Because of cultural differences, Cabécar sell a feline skin for as little as $25 and up to $400 if it includes teeth and nails, but Ticos, who are non-indigenous Costa Ricans, sell the skins from $500-$5000. Non-indigenous, wealthy urban men indicate prestige by the display of feline parts. My findings align with existing research that jaguar skins are sold to people in larger cities and that adornment of feline derivatives is a masculine tradition that can be linked with Amerindian cultures and ancient times. Historically jaguars have been associated with elitist symbolism and evidence in this study suggests this continues in today's culture as a sign of social status. Results suggest that money alone does not drive illegal hunting. The contribution of this study urges researchers to: 1) develop a typology which includes the characteristics of not only the poachers, but also the buyers of illegal wildlife parts; 2) evaluate concepts of culture, geographic residency, masculine identity, and social status in the illegal trade of feline derivatives in Mexico, Central, and South America.
    Print ISSN: 2351-9894
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering
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  • 40
    Publication Date: 2018-02-07
    Description: Publication date: 28 April 2018 Source: Cancer Letters, Volume 420 Author(s): Shuangbing Xu, Yan Li, Yanwei Lu, Jing Huang, Jinghua Ren, Sheng Zhang, Zhongyuan Yin, Kai Huang, Gang Wu, Kunyu Yang Phosphoinositide 3-kinase (PI3K) activity is aberrantly activated in nasopharyngeal carcinoma. However, the underlying mechanisms remain unclear. Here, we found that Leucine zipper tumor suppressor 2 (LZTS2) was downregulated and predicted poor prognosis in nasopharyngeal carcinoma patients. Furthermore, we identified the PI3K subunit p85 as a novel LZTS2-interacting protein using an unbiased proteomics approach. Moreover, we demonstrated that LZTS2 competes with p110 for p85 binding and inhibits activation of the PI3K/AKT signaling pathway. Functionally, we showed that LZTS2 suppresses tumorigenesis and radioresistance in nasopharyngeal carcinoma in a p85-dependent manner. Taken together, our results not only provide understanding of the molecular mechanisms by which PI3K/AKT signaling is activated but also suggest that targeting the LZTS2/PI3K/AKT signaling axis is a promising therapeutic strategy for radiosensitization of nasopharyngeal carcinoma.
    Print ISSN: 0304-3835
    Topics: Medicine
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  • 41
    Publication Date: 2018-02-22
    Description: Publication date: 7 May 2018 Source: Journal of Theoretical Biology, Volume 444 Author(s): Guirong Liu, Zhimei Liu, Zhen Jin We establish an SIS-UAU model to present the dynamics of epidemic and information spreading in overlay networks. The overlay network is represented by two layers: one where the dynamics of the epidemic evolves and another where the information spreads. We theoretically derive the explicit formulas for the basic reproduction number of awareness R 0 a by analyzing the self-consistent equation and the basic reproduction number of disease R 0 d by using the next generation matrix. The formula of R 0 d shows that the effect of awareness can reduce the basic reproduction number of disease. In particular, when awareness does not affect epidemic spreading, R 0 d is shown to match the existing theoretical results. Furthermore, we demonstrate that the disease-free equilibrium is globally asymptotically stable if R 0 d 〈 1 ; and the endemic equilibrium is globally asymptotically stable if R 0 d > 1 . Finally, numerical simulations show that information plays a vital role in preventing and controlling disease and effectively reduces the final disease scale.
    Print ISSN: 0022-5193
    Electronic ISSN: 1095-8541
    Topics: Biology
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  • 42
    Publication Date: 2018-02-22
    Description: Publication date: 7 May 2018 Source: Journal of Theoretical Biology, Volume 444 Author(s): Corey Melnick, Massoud Kaviany The transient response potential cation channel TRPV1 responds to high temperature, but many of the mechanisms driving its thermal actuation remain unclear. Its recently resolved structure has enabled a number of molecular dynamics (MD) studies focused on illuminating these mechanisms. We add to these efforts by performing the first all-atom MD simulations of its most recently resolved structure at different temperatures. While the complete, thermally induced transition of TRPV1 from its closed to open configuration remains elusive, our analysis of the hydrogen bonding networks, thermodynamics, hydration, and principal components of motion provide a wealth of information on the mechanisms which initiate or influence the thermal opening in TRPV1. In particular, we (i) support the previously proposed mechanism driving thermal actuation in the extracellular pore of TRPV1, (ii) present new hypotheses regarding the thermal actuation in the C-terminal and adjacent linker domains, and (iii) support and build upon the existing hypothesis regarding the role of the vanilloid binding pocket and lipids embedded therein.
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  • 43
    Publication Date: 2018-02-22
    Description: Publication date: 7 May 2018 Source: Journal of Theoretical Biology, Volume 444 Author(s): Tuomas Nurmi, Kalle Parvinen, Vesa Selonen We propose a novel mathematical model for a metapopulation in which dispersal occurs on two levels: juvenile dispersal from the natal site is mandatory but it may take place either locally within the natal patch or globally between patches. Within each patch, individuals live in sites. Each site can be inhabited by at most one individual at a time and it may be of high or low quality. A disperser immigrates into a high-quality site whenever it obtains one, but it immigrates into a low-quality site only with a certain probability that depends on the time within the dispersal season. The vector of these low-quality-site-acceptance probabilities is the site-selection strategy of an individual. We derive a proxy for the invasion fitness in this model and study the joint evolution of long-distance-dispersal propensity and site-selection strategy. We focus on the way different ecological changes affect the evolutionary dynamics and study the interplay between global patch-to-patch dispersal and local site-selection. We show that ecological changes affect site-selection mainly via the severeness of competition for sites, which often leads to effects that may appear counterintuitive. Moreover, the metapopulation structure may result in extremely complex site-selection strategies and even in evolutionary cycles. The propensity for long-distance dispersal is mainly determined by the metapopulation-level ecological factors. It is, however, also strongly affected by the winter-survival of the site-holders within patches, which results in surprising non-monotonous effects in the evolution of site-selection due to interplay with long-distance dispersal. Altogether, our results give new additional support to the recent general conclusion that evolution of site-selection is often dominated by the indirect factors that take place via density-dependence, which means that evolutionary responses can rarely be predicted by intuition.
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  • 44
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: Experimental Cell Research Author(s): Julia I. Heger, Karolin Froehlich, Jana Pastuschek, Astrid Schmidt, Christin Baer, Ralf Mrowka, Claudia Backsch, Ekkehard Schleußner, Udo R. Markert, André Schmidt Background The use of fetal bovine serum (FBS) as growth supplement for human cell and tissue culture is widely spread in basic research as well as in clinical approaches, although several limitations must be considered, such as unstable composition and availability, biosafety and ethical aspects. Regarding interspecies differences, xenogeneic growth factors may evoke incompatibilities and non-desired interactions with human cells resulting in imprecise outcome of human-relevant data. Methods In this study the functionality of human serum (HS) has been investigated in comparison to FBS by assessing proliferation, migration and invasion of the human cervical cancer cell lines SiHa and HeLa. The effects of both sera on spheroid formation were analyzed microscopically. Results Both, FBS and HS, stimulate cell proliferation and migration similarly, whereas HS significantly enhanced cell invasion. The spheroid formation assay revealed remarkable differences between both sera, especially for SiHa cells. While in FBS supplemented medium cells only formed loose aggregates, HS induced regularly shaped spheroids under all tested conditions. Conclusion We were able to demonstrate that HS and FBS differently influence behavior of cells in culture which may have an impact on experimental results, especially in 3D cultures.
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  • 45
    Publication Date: 2018-02-22
    Description: Publication date: June 2018 Source: Magnetic Resonance Imaging, Volume 49 Author(s): Riccardo Lattanzi, Bei Zhang, Florian Knoll, Jakob Assländer, Martijn A. Cloos Purpose Magnetic Resonance Fingerprinting reconstructions can become computationally intractable with multiple transmit channels, if the B 1 + phases are included in the dictionary. We describe a general method that allows to omit the transmit phases. We show that this enables straightforward implementation of dictionary compression to further reduce the problem dimensionality. Methods We merged the raw data of each RF source into a single k -space dataset, extracted the transceiver phases from the corresponding reconstructed images and used them to unwind the phase in each time frame. All phase-unwound time frames were combined in a single set before performing SVD-based compression. We conducted synthetic, phantom and in-vivo experiments to demonstrate the feasibility of SVD-based compression in the case of two-channel transmission. Results Unwinding the phases before SVD-based compression yielded artifact-free parameter maps. For fully sampled acquisitions, parameters were accurate with as few as 6 compressed time frames. SVD-based compression performed well in-vivo with highly under-sampled acquisitions using 16 compressed time frames, which reduced reconstruction time from 750 to 25 min. Conclusion Our method reduces the dimensions of the dictionary atoms and enables to implement any fingerprint compression strategy in the case of multiple transmit channels.
    Print ISSN: 0730-725X
    Electronic ISSN: 1873-5894
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  • 46
    Publication Date: 2018-02-22
    Description: Publication date: June 2018 Source: Magnetic Resonance Imaging, Volume 49 Author(s): Faisal Khosa, Rachel E. Clough, Xiaoen Wang, Ananth J. Madhuranthakam, Robert L. Greenman Hemorrhage and lipid deposits contribute to instability in atherosclerotic plaques. Unstable carotid artery plaques can lead to cerebral ischemic events. While MRI studies have shown the ability to identify plaque components, the identification of hemorrhage and lipids has proven to be problematic. The purpose of this study was to quantitatively evaluate the potential of the MRI fat/water separation method known as iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL) to complement and improve existing methods for the identification of hemorrhage and lipids in carotid artery plaques. Fifteen asymptomatic subjects with 50–79% stenosis of at least one carotid artery were enrolled. Hemorrhage and lipid components within carotid plaques were identified using previously published criteria based on the multiple contrast-weighted (MCW) method (3D Time-of-Flight (3D-TOF), T1-Weighted (T1W) and T2-Weighted (T2W)). The hemorrhage:muscle, lipid:muscle and intra-plaque lipid:hemorrhage signal intensity ratios (SIR) and contrast to noise ratios (CNR) were measured on MCW and compared to IDEAL black-blood images. No differences were found between any of the MCW methods for any of the SIRs measured. The IDEAL Fat images had higher lipid:muscle and lipid/hemorrhage SIRs (p 〈 0.001) compared to IDEAL Water and all MCW image sequence types. The mean values of IDEAL Fat hemorrhage:muscle SIR and CNR were nearly unity (1.1 ± 0.6) and nearly zero (0.1 ± 1.1), respectively. The IDEAL Water imaging was not significantly different than any of the MCW methods for any of the SIRs or for the hemorrhage:muscle CNR of 3D-TOF, while its CNRs were significantly higher than IDEAL Fat lipid:muscle (p 〈 0.05) and lipid:hemorrhage (p 〈 0.001) and all MCW methods (p 〈 0.001). The addition of IDEAL Water and Fat imaging to the MCW method shows potential to improve the identification of hemorrhage and lipid structures in carotid artery plaques.
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  • 47
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Methods Author(s): Lisa A. Della Ripa, Zoe A. Petros, Alexander G. Cioffi, Dennis W. Piehl, Joseph M. Courtney, Martin D. Burke, Chad M. Rienstra Cholesterol (Chol) is vital for cell function as it is essential to a myriad of biochemical and biophysical processes. The atomistic details of Chol’s interactions with phospholipids and proteins is therefore of fundamental interest, and NMR offers unique opportunities to interrogate these properties at high resolution. Towards this end, here we describe approaches for examining the structure and dynamics of Chol in lipid bilayers using high levels of 13 C enrichment in combination with magic-angle spinning (MAS) methods. We quantify the incorporation levels and demonstrate high sensitivity and resolution in 2D 13 C- 13 C and 1 H- 13 C spectra, enabling de novo assignments and site-resolved order parameter measurements obtained in a fraction of the time required for experiments with natural abundance sterols. We envision many potential future applications of these methods to study sterol interactions with drugs, lipids and proteins.
    Print ISSN: 1046-2023
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  • 48
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Annette Fox, Kanta Subbarao, Patrick Reading In this issue of Immunity , Goodwin et al. (2018) offer hope for an RSV vaccine for young infants by demonstrating that RSV infection in very young infants induces neutralizing antibodies that are close to the germline and have unusual epitope specificity. Teaser In this issue of Immunity , Goodwin et al. (2018) offer hope for an RSV vaccine for young infants by demonstrating that RSV infection in very young infants induces neutralizing antibodies that are close to the germline and have unusual epitope specificity.
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  • 49
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Ashleigh S. Boyd, Neil P. Rodrigues Immune surveillance is an established regulatory mechanism that spares tissues from malignant transformation. Agudo et al. (2018) find that the chief cell type to generate tissues in the body—somatic stem cells—is subject to immune surveillance only during proliferation. Teaser Immune surveillance is an established regulatory mechanism that spares tissues from malignant transformation. Agudo et al. (2018) find that the chief cell type to generate tissues in the body—somatic stem cells—is subject to immune surveillance only during proliferation.
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  • 50
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Jasmine Li, Stephen J. Turner Understanding how cell fate decisions are made during cellular differentiation and the mechanisms that drive them is a holy grail of cell biology. In this issue of Immunity , Hu et al. (2018) and Johnson et al. (2018) demonstrate that key transcriptional regulators and global changes in nuclear architecture underlie differentiation decisions during T cell development. Teaser Understanding how cell fate decisions are made during cellular differentiation and the mechanisms that drive them is a holy grail of cell biology. In this issue of Immunity , Hu et al. (2018) and Johnson et al. (2018) demonstrate that key transcriptional regulators and global changes in nuclear architecture underlie differentiation decisions during T cell development.
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  • 51
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Audrey Baeyens, Susan R. Schwab In many contexts, innate lymphoid cells (ILCs) are primarily tissue resident. By contrast, in a recent issue of Science , Huang et al. (2018) show that inflammatory type 2 ILCs migrate from the intestine to the lungs and that this movement is guided by sphingosine-1-phosphate receptors. Teaser In many contexts, innate lymphoid cells (ILCs) are primarily tissue resident. By contrast, in a recent issue of Science , Huang et al. (2018) show that inflammatory type 2 ILCs migrate from the intestines to the lungs and that this movement is guided by sphingosine-1-phosphate receptors.
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  • 52
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Nàdia Villacampa, Michael T. Heneka In this issue of Immunity , Mrdjen et al. (2018) use high-dimensional single-cell proteomics and high parametric mass cytometry to provide insight into the long-lasting issue of how to identify and characterize both resident and recruited leukocyte populations in healthy, aged, and diseased CNS. Teaser In this issue of Immunity , Mrdjen et al. (2018) use high-dimensional single-cell proteomics and high parametric mass cytometry to provide insight into the long-lasting issue of how to identify and characterize both resident and recruited leukocyte populations in healthy, aged, and diseased CNS.
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  • 53
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Matthew D. Lewis, Jean Langhorne In malaria, the immune responses leading to protective immunity versus immunopathology are unclear. Mamedov et al. (2018) identify a subset of clonally expanded γδ T cells in late-stage infection that produce M-CSF and may interact with myeloid cells to control recrudescent infection. Teaser In malaria, the immune responses leading to protective immunity versus immunopathology are unclear. Mamedov et al. (2018) identify a subset of clonally expanded γδ T cells in late-stage infection that produce M-CSF and may interact with myeloid cells to control recrudescent infection.
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  • 54
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: 20 February 2018 Source: Immunity, Volume 48, Issue 2 Author(s): Mary F. Fontana, Marion Pepper Activated B cells mature in germinal centers (GCs), but GC initiation during infection is poorly understood. Gaya et al. (2018) show that NKT cells, activated by CD169 + macrophages, produce an early wave of interleukin-4 (IL-4) that promotes GC formation during viral infection. Teaser Activated B cells mature in germinal centers (GCs), but GC initiation during infection is poorly understood. Gaya et al. (2018) show that NKT cells, activated by CD169 + macrophages, produce an early wave of interleukin-4 (IL-4) that promotes GC formation during viral infection.
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  • 55
    Publication Date: 2018-02-23
    Description: Publication date: 16 January 2018 Source: Immunity, Volume 48, Issue 1 Author(s): Zsolt Czimmerer, Bence Daniel, Attila Horvath, Dominik Rückerl, Gergely Nagy, Mate Kiss, Matthew Peloquin, Marietta M. Budai, Ixchelt Cuaranta-Monroy, Zoltan Simandi, Laszlo Steiner, Bela Nagy, Szilard Poliska, Csaba Banko, Zsolt Bacso, Ira G. Schulman, Sascha Sauer, Jean-Francois Deleuze, Judith E. Allen, Szilvia Benko, Laszlo Nagy The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-κB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1β production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli. Graphical abstract Teaser The molecular bases of repressive transcriptional mechanisms contributing to macrophage polarization are not well understood. Czimmerer et al. show that in alternatively polarized macrophages, IL-4-activated STAT6 represses a large set of enhancers modulating the transcriptional program. STAT6-repressed enhancers are characterized by reduced chromatin accessibility, eRNA expression, LDTF, and p300 binding. IL-4-STAT6-mediated repression limits the inflammatory responsiveness including inflammasome activation, IL-1β production, and pyroptosis. Thus, the IL4-STAT6 pathway establishes an epigenomic signature to selectively repress the macrophage inflammation program.
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  • 56
    Publication Date: 2018-02-23
    Description: Publication date: 16 January 2018 Source: Immunity, Volume 48, Issue 1 Author(s): Fei Zhao, Christine Xiao, Kathy S. Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W. Locasale, Brent A. Hanks Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO) while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti-melanoma immunity, enhanced the activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression in a transgenic melanoma model. This work implicates a role for tumor-mediated metabolic reprogramming of local DCs in immune evasion and immunotherapy resistance. Graphical abstract Teaser Previous studies suggest that DC tolerization plays a role in tumor-mediated immune evasion. The mechanism by which cancers promote this process remains poorly understood. Zhao et al. demonstrate that melanomas generate a site of immune privilege by driving DC fatty acid oxidation via a Wnt5a-β-catenin-PPAR-γ signaling pathway that culminates in the induction of IDO enzyme activity. Inhibiting this pathway reverses DC tolerization and enhances anti-PD-1 antibody efficacy in a transgenic model of melanoma.
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  • 57
    Publication Date: 2018-02-23
    Description: Publication date: 16 January 2018 Source: Immunity, Volume 48, Issue 1 Author(s): Kevin R. McCarthy, Akiko Watanabe, Masayuki Kuraoka, Khoi T. Do, Charles E. McGee, Gregory D. Sempowski, Thomas B. Kepler, Aaron G. Schmidt, Garnett Kelsoe, Stephen C. Harrison Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs) from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are uncommon. We analyzed Bmem compartments in three unrelated, adult donors and found frequent cross-group BCRs, both HA-head directed and non-head directed. Members of a clonal lineage from one donor had a BCR structure similar to that of a previously described Ab, encoded by different gene segments. Comparison showed that both Abs contacted the HA receptor-binding site through long heavy-chain third complementarity determining regions. Affinities of the clonal-lineage BCRs for historical influenza-virus HAs from both group 1 and group 2 viruses suggested that serial responses to seasonal influenza exposures had elicited the lineage and driven affinity maturation. We propose that appropriate immunization regimens might elicit a comparably broad response. Graphical abstract Teaser Hemagglutinins (HAs) from the two influenza A subtype groups have similar structures, but cross-reacting serum antibodies are rare. McCarthy et al. nonetheless found, in three donors, abundant cross-group B cell receptors (BCRs), many with epitopes on the HA head. Members of one clonal lineage had a BCR structure similar to that of a previously described, genetically unrelated antibody. Serial responses to seasonal influenza appear to have elicited the lineage and driven affinity maturation. Appropriate immunization regimens might elicit comparable responses.
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  • 58
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: The International Journal of Biochemistry & Cell Biology Author(s): Qingling Yuan, Yang Liu, Yuxia Fan, Zheng Liu, Xiaoming Wang, Meng Jia, Zushi Geng, Jing Zhang, Xiubo Lu Background Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Besides, increasing evidence has demonstrated that long non-coding RNA (lncRNA) HOTTIP played a crucial role in cancer pathogenesis. MiR-637-mediated Akt1 was involved in cell growth, invasion and migration in various malignancies. This study was aimed to investigate the potential biological effect and regulatory mechanism of HOTTIP on cell proliferation, invasion and migration in PTC. Methods Expression of HOTTIP, miR-637 and Akt1 were determined by quantitative RT-PCR (qRT-PCR) and western blotting in PTC tissues, normal tissues, PTC cells (TPC-1 and HTH83) or non-tumor thyroid cells (Nthy-ori 3-1). Cell proliferation, invasion and migration following HOTTIP knockdown were investigated in PTC cells. The target of HOTTIP was validated by RNA immunoprecipitation (RIP) and pull-down assay. Moreover, a xenograft model was performed. Results HOTTIP was upregulated in human PTC tissues and PTC cell lines. In addition, HOTTIP knockdown inhibited the proliferation, invasion and migration in vitro together with in vivo tumorigenesis of PTC cells. Additionally, HOTTIP knockdown downregulated Akt1 expression and suppressed cell proliferation, invasion and migration in PTC cells by regulating miR-637. In contrast, miR-637 inhibitor reversed above-mentioned tendencies caused by HOTTIP knockdown. Conclusion HOTTIP is a potential oncogene in PTC and may serve as a therapeutic target for malignancies.
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    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 59
    Publication Date: 2018-02-23
    Description: Publication date: 16 January 2018 Source: Immunity, Volume 48, Issue 1 Author(s): Johanna Emgård, Hana Kammoun, Bethania García-Cassani, Julie Chesné, Sara M. Parigi, Jean-Marie Jacob, Hung-Wei Cheng, Elza Evren, Srustidhar Das, Paulo Czarnewski, Natalie Sleiers, Felipe Melo-Gonzalez, Egle Kvedaraite, Mattias Svensson, Elke Scandella, Matthew R. Hepworth, Samuel Huber, Burkhard Ludewig, Lucie Peduto, Eduardo J. Villablanca, Henrique Veiga-Fernandes, João P. Pereira, Richard A. Flavell, Tim Willinger Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Graphical abstract Teaser ILC3s maintain healthy organ function in the intestine, but how ILC3s directly detect environmental cues is poorly understood. Emgård et al. find that GPR183 and oxysterols control the localization and LTi function of ILC3s and thereby promote the formation of colonic lymphoid tissues in the steady state and inflammation.
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  • 60
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Computer Methods and Programs in Biomedicine, Volume 157 Author(s): Chih Yuan Wu, Usman Iqbal, Yu-Chuan (Jack) Li
    Print ISSN: 0169-2607
    Electronic ISSN: 1872-7565
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  • 61
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: The International Journal of Biochemistry & Cell Biology Author(s): Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis. The coagulants, thrombin and factor Xa (FXa) evoke fibrogenic effects via cleavage of the N-terminus of protease-activated receptors (PARs). Whilst the formation and activity of plasmin, the principle plasminergic mediator is suppressed in the airspaces of patients with IPF, localized increases are likely to occur in the lung interstitium. Plasmin-evoked proteolytic activation of factor XII (FXII), matrix metalloproteases (MMPs) and latent, matrix-bound growth factors such as epidermal growth factor (EGF) indirectly implicate plasmin in pulmonary fibrosis. Another plasminergic protease, urokinase plasminogen activator (uPA) is associated with regions of fibrosis in the remodelled lung of IPF patients and elicits fibrogenic activity via binding its receptor (uPAR). Plasminogen activator inhibitor-1 (PAI-1) formed in the injured alveolar epithelium also contributes to pulmonary fibrosis in a manner that involves vitronectin binding. This review describes the mechanisms by which components of the two systems primarily involved in fibrin homeostasis contribute to interstitial fibrosis, with a particular focus on IPF. Selectively targeting the receptor-mediated mechanisms of coagulant and plasminergic proteases may limit pulmonary fibrosis, without the bleeding complications associated with conventional anti-coagulant and thrombolytic therapies. Graphical abstract
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  • 62
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: The International Journal of Biochemistry & Cell Biology Author(s): Chao Zhong, Zhenhuang Chen, Xiaocui Luo, Cuicui Wang, Hui Jiang, Jianzhong Shao, Minxin Guan, Liquan Huang, Xiao Huang, Jinfu Wang
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  • 63
    Publication Date: 2018-02-23
    Description: Publication date: 15 March 2018 Source: International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 4 Author(s): Brian Marples, Scott M. Welford
    Print ISSN: 0360-3016
    Electronic ISSN: 1879-355X
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  • 64
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Computer Methods and Programs in Biomedicine, Volume 157 Author(s): Gi Jung Hyun, Jin Wan Park, Jin Hee Kim, Kyoung Joon Min, Young Sik Lee, Sun Mi Kim, Doug Hyun Han Background and objective Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder hypothesized to involve impaired visuospatial working memory (VSWM). However, there are few studies utilizing neuropsychological tests to measure VSWM in ADHD adolescents. The Rey–Osterrieth complex figure test (ROCF) is commonly used as a neuropsychological test to assess visuospatial working memory for individuals with ADHD. We assessed working memory using the ROCF test on a digital Galaxy tablet with the technically new Gaussian filter method. Methods Thirty adolescents with ADHD and 30 healthy control adolescents were recruited for participation in the current study. All adolescents were assessed with K-WISC-IV, Children's depression inventory, and the Korean ADHD rating scale. All adolescents were asked to copy the ROCF from paper onto a Galaxy tablet screen using a wireless pen. Results There was a significant difference in representative value of the deviation of the original images from template images ( R -value) in copy and delayed recall between ADHD adolescents and healthy adolescents. There was no significant difference in R -value of immediate recall between ADHD adolescents and healthy adolescents. In all adolescents (ADHD and healthy) and ADHD adolescents, the R -value of copy was negatively correlated with visuospatial index and working memory index, and the R -value of delayed recall was negatively correlated with WMI. The R -value of copy and delayed recall was positively correlated with K-ARS in all adolescents and ADHD adolescents. Conclusions ADHD adolescents showed differences in the R -values of copy and delayed recall in the digital ROCF version compared to healthy adolescents. The digital ROCF assessment tool can represent different patterns of visuospatial working memory abilities in ADHD adolescents compared to healthy adolescents.
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    Electronic ISSN: 1872-7565
    Topics: Biology , Medicine
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  • 65
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Computer Methods and Programs in Biomedicine, Volume 157 Author(s): Tao Wan, Xiaoqing Shang, Weilin Yang, Jianhui Chen, Deyu Li, Zengchang Qin Background and Objective Coronary artery segmentation is a fundamental step for a computer-aided diagnosis system to be developed to assist cardiothoracic radiologists in detecting coronary artery diseases. Manual delineation of the vasculature becomes tedious or even impossible with a large number of images acquired in the daily life clinic. A new computerized image-based segmentation method is presented for automatically extracting coronary arteries from angiography images. Methods A combination of a multiscale-based adaptive Hessian-based enhancement method and a statistical region merging technique provides a simple and effective way to improve the complex vessel structures as well as thin vessel delineation which often missed by other segmentation methods. The methodology was validated on 100 patients who underwent diagnostic coronary angiography. The segmentation performance was assessed via both qualitative and quantitative evaluations. Results Quantitative evaluation shows that our method is able to identify coronary artery trees with an accuracy of 93% and outperforms other segmentation methods in terms of two widely used segmentation metrics of mean absolute difference and dice similarity coefficient. Conclusions The comparison to the manual segmentations from three human observers suggests that the presented automated segmentation method is potential to be used in an image-based computerized analysis system for early detection of coronary artery disease.
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    Topics: Biology , Medicine
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  • 66
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Computer Methods and Programs in Biomedicine, Volume 157 Author(s): Chun-Ta Li, Dong-Her Shih, Chun-Cheng Wang Background and Objective:  With the rapid development of wireless communication technologies and the growing prevalence of smart devices, telecare medical information system (TMIS) allows patients to receive medical treatments from the doctors via Internet technology without visiting hospitals in person. By adopting mobile device, cloud-assisted platform and wireless body area network, the patients can collect their physiological conditions and upload them to medical cloud via their mobile devices, enabling caregivers or doctors to provide patients with appropriate treatments at anytime and anywhere. In order to protect the medical privacy of the patient and guarantee reliability of the system, before accessing the TMIS, all system participants must be authenticated. Methods:  Mohit et al. recently suggested a lightweight authentication protocol for cloud-based health care system. They claimed their protocol ensures resilience of all well-known security attacks and has several important features such as mutual authentication and patient anonymity. In this paper, we demonstrate that Mohit et al.’s authentication protocol has various security flaws and we further introduce an enhanced version of their protocol for cloud-assisted TMIS, which can ensure patient anonymity and patient unlinkability and prevent the security threats of report revelation and report forgery attacks. Results:  The security analysis proves that our enhanced protocol is secure against various known attacks as well as found in Mohit et al.’s protocol. Compared with existing related protocols, our enhanced protocol keeps the merits of all desirable security requirements and also maintains the efficiency in terms of computation costs for cloud-assisted TMIS. Conclusions:  We propose a more secure mutual authentication and privacy preservation protocol for cloud-assisted TMIS, which fixes the mentioned security weaknesses found in Mohit et al.’s protocol. According to our analysis, our authentication protocol satisfies most functionality features for privacy preservation and effectively cope with cloud-assisted TMIS with better efficiency.
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  • 67
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Computer Methods and Programs in Biomedicine, Volume 157 Author(s): Shoko Miyauchi, Ken’ichi Morooka, Tokuo Tsuji, Yasushi Miyagi, Takaichi Fukuda, Ryo Kurazume Background and Objective This paper proposes a new method for mapping surface models of human organs onto target surfaces with the same genus as the organs. Methods In the proposed method, called modified Self-organizing Deformable Model (mSDM), the mapping problem is formulated as the minimization of an objective function which is defined as the weighted linear combination of four energy functions: model fitness, foldover-free, landmark mapping accuracy, and geometrical feature preservation. Further, we extend mSDM to speed up its processes, and call it Fast mSDM. Results From the mapping results of various organ models with different number of holes, it is observed that Fast mSDM can map the organ models onto their target surfaces efficiently and stably without foldovers while preserving geometrical features. Conclusions Fast mSDM can map the organ model onto the target surface efficiently and stably, and is applicable to medical applications including Statistical Shape Model. Graphical abstract
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  • 68
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: Journal of Magnetic Resonance Author(s): Mathias Sawall, Erik von Harbou, Annekathrin Moog, Richard Behrens, Henning Schröder, Joël Simoneau, Ellen Steimers, Klaus Neymeyr Spectral data preprocessing is an integral and sometimes inevitable part of chemometric analyses. For Nuclear Magnetic Resonance (NMR) spectra a possible first preprocessing step is a phase correction which is applied to the Fourier transformed free induction decay (FID) signal. This preprocessing step can be followed by a separate baseline correction step. Especially if series of high-resolution spectra are considered, then automated and computationally fast preprocessing routines are desirable. A new method is suggested that applies the phase and the baseline corrections simultaneously in an automated form without manual input, which distinguishes this work from other approaches. The underlying multi-objective optimization or Pareto optimization provides improved results compared to consecutively applied correction steps. The optimization process uses an objective function which applies strong penalty constraints and weaker regularization conditions. The new method includes an approach for the detection of zero baseline regions. The baseline correction uses a modified Whittaker smoother. The functionality of the new method is demonstrated for experimental NMR spectra. The results are verified against gravimetric data. The method is compared to alternative preprocessing tools. Additionally, the simultaneous correction method is compared to a consecutive application of the two correction steps. Graphical abstract
    Print ISSN: 1090-7807
    Electronic ISSN: 1096-0856
    Topics: Medicine , Physics
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  • 69
    Publication Date: 2018-02-22
    Description: Publication date: Available online 20 February 2018 Source: Trends in Biotechnology Author(s): Aleksandr Ovsianikov, Ali Khademhosseini, Vladimir Mironov Tissue engineering (TE) is a highly interdisciplinary research field driven by the goal to restore, replace, or regenerate defective tissues. Throughout more than two decades of intense research, different technological approaches, which can be principally categorized into scaffold-based and scaffold-free strategies, have been developed. In this opinion article, we discuss the emergence of a third strategy in TE. This synergetic strategy integrates the advantages of both of these traditional approaches, while being clearly distinct from them. Its characteristic attributes, numerous practical benefits, and recent literature reports supporting our opinion, are discussed in detail.
    Print ISSN: 0167-7799
    Electronic ISSN: 1879-3096
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
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  • 70
    Publication Date: 2018-02-22
    Description: Publication date: Available online 21 February 2018 Source: Trends in Endocrinology & Metabolism Author(s): Allison W. Xu Bile acids facilitate dietary fat absorption upon release into the small intestine after a meal. A recent study by Liu and colleagues identifies a gut–brain axis wherein bile acids signal an energy-replete state to hypothalamic AgRP neurons via activation of neuronal FGF receptors, which orchestrate whole-body glucose metabolism.
    Print ISSN: 1043-2760
    Electronic ISSN: 1879-3061
    Topics: Medicine
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  • 71
    facet.materialart.
    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Magnetic Resonance Imaging, Volume 47
    Print ISSN: 0730-725X
    Electronic ISSN: 1873-5894
    Topics: Medicine
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  • 72
    Publication Date: 2018-02-23
    Description: Publication date: Available online 22 February 2018 Source: Lung Cancer Author(s): Noriaki Sakakura, Tetsuya Mizuno, Hiroaki Kuroda, Takaaki Arimura, Yasushi Yatabe, Kenichi Yoshimura, Yukinori Sakao Objectives The eighth tumor-node-metastasis (TNM) classification system for lung cancer has been used since January 2017 and must be applied to an individual institution’s database. Methods We analyzed pathological stage data of 2756 patients who underwent resection of non–small-cell lung cancer, particularly in terms of the degree of visceral pleural invasion and involved neighboring structures. Results Few patients had stage IIA disease (103, 4%); stratification between stages IB and IIA was insufficient ( p  = 0.129). When T2a tumors were divided into PL1 and PL2 subgroups based on the degree of pleural invasion, there was a significant prognostic difference between the subgroups ( p 〈  0.001). By incorporating T2a tumors with PL2 (T2a-PL2) into the T2b category, modified stages IB, IIA (234, 8%), and IIB were well stratified (IB vs. IIA, p 〈  0.001; IIA vs. IIB, p  = 0.011). Focusing on T3 tumors with PL3 (T3-PL3) invading neighboring structures, multivariate analysis for surveying pT3N0-2M0 tumors revealed that completeness of resection ( p  = 0.002), implementation of any postoperative therapies ( p  = 0.003), and subcategorization of whether only the pleura was infiltrated or other deeper structures were also invaded ( p  = 0.024) were significant and crucial predictors. N2 disease showed worse outcome than N0-1 diseases, with marginal difference ( p  = 0.054). Conclusion T2a-PL2 tumors could be categorized into a worse prognostic T2b category. For T3-PL3 tumors involving resectable neighboring organs, subcategorization of whether there is only pleura infiltration (T3a) or other deeper structure invasion (T3b) could be a practical consideration.
    Print ISSN: 0169-5002
    Electronic ISSN: 1872-8332
    Topics: Medicine
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  • 73
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: The American Journal of Pathology Author(s): Martin S. Taylor, Raghu R. Chivukula, Laura C. Myers, William R. Jeck, Avinash Waghray, Purushothama R. Tata, Martin K. Selig, Walter J. O’Donnell, Carol F. Farver, B. Taylor Thompson, Jayaraj Rajagopal, Richard L. Kradin Improved tools have led to a burgeoning understanding of lung regeneration in mice, but it is not yet known how these insights may be relevant to acute lung injury in humans. We report in detail two cases of fulminant idiopathic acute lung injury requiring extracorporeal membrane oxygenation in previously healthy young adults with acute respiratory distress syndrome, one of whom required lung transplantation. Biopsies showed diffuse alveolar injury with a striking paucity of alveolar epithelial regeneration, rare hyaline membranes, and diffuse contiguous airspace lining by macrophages. This novel constellation was termed “diffuse alveolar injury with delayed epithelization”. Additionally, mirroring data from murine models of lung injury/regeneration, peribronchiolar basaloid pods (previously described as “squamous metaplasia”) and ciliated bronchiolarization were identified in these patients and in 39% of 57 historical cases with diffuse alveolar damage. These findings demonstrate a common and clinically relevant human disease correlate for murine models of severe acute lung injury. Evidence suggests that peribronchiolar basaloid pods and bronchiolarization are related spatially and temporally and likely represent overlapping sequential stages of the response to severe distal airway injury.
    Print ISSN: 0002-9440
    Electronic ISSN: 1525-2191
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  • 74
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    Elsevier
    Publication Date: 2018-02-23
    Description: Publication date: April 2018 Source: Protein Expression and Purification, Volume 144
    Print ISSN: 1046-5928
    Electronic ISSN: 1096-0279
    Topics: Biology , Medicine
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  • 75
    Publication Date: 2018-02-23
    Description: Publication date: Available online 21 February 2018 Source: Radiotherapy and Oncology Author(s): Adam Michał Czerwiński, Barbara Więckowska Background and purpose External beam radiotherapy (EBRT) is one of three key treatment modalities of cancer patients. Its utilisation and outcomes depend on a plethora of variables, one of which is the distance a patient must travel to undergo the treatment. The relation between distance and utilisation is clearly visible in Poland. At the same time no strategic investment plan is observed. This work proposes a method of resolving these two issues. Materials and methods We propose a mixed-integer linear programming model that aims to optimise the distribution of linear accelerators among selected locations in such a way that a patient’s journey to the nearest EBRT is as short as possible. The optimisation is done with observance of international guidelines concerning EBRT capacity. With the use of proposed theoretical framework, we develop a national, strategic plan for linear accelerator investments. Results According to model assumptions decentralisation of EBRT, together with new equipment purchases, is required to ensure optimal access to EBRT. Conclusions The results were incorporated into Healthcare Needs Maps for Poland. The plan based on the results of this study, implemented by 2025, should deal with the most pressing concerns of Polish EBRT.
    Print ISSN: 0167-8140
    Electronic ISSN: 1879-0887
    Topics: Medicine
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  • 76
    Publication Date: 2018-02-24
    Description: Publication date: Available online 22 February 2018 Source: The American Journal of Human Genetics Author(s): Saud H. AlDubayan, Marios Giannakis, Nathanael D. Moore, G. Celine Han, Brendan Reardon, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Reiko Nishihara, Zhirong Qian, Li Liu, Matthew B. Yurgelun, Sapna Syngal, Levi A. Garraway, Shuji Ogino, Charles S. Fuchs, Eliezer M. Van Allen Colorectal cancer (CRC) heritability has been estimated to be around 30%. However, mutations in the known CRC-susceptibility genes explain CRC risk in fewer than 10% of affected individuals. Germline mutations in DNA-repair genes (DRGs) have recently been reported in CRC, but their contribution to CRC risk is largely unknown. We evaluated the gene-level germline mutation enrichment of 40 DRGs in 680 unselected CRC individuals and 27,728 ancestry-matched cancer-free adults. Significant findings were then examined in independent cohorts of 1,661 unselected CRC individuals and 1,456 individuals with early-onset CRC. Of the 680 individuals in the discovery set, 31 (4.56%) individuals harbored germline pathogenic mutations in known CRC-susceptibility genes, and another 33 (4.85%) individuals had DRG mutations that have not been previously associated with CRC risk. Germline pathogenic mutations in ATM and PALB2 were enriched in both the discovery (OR = 2.81 and p = 0.035 for ATM and OR = 4.91 and p = 0.024 for PALB2 ) and validation (OR = 2.97 and adjusted p = 0.0013 for ATM and OR = 3.42 and adjusted p = 0.034 for PALB2 ) sets. Biallelic loss of ATM was evident in all individuals with matched tumor profiling. CRC individuals also had higher rates of actionable mutations in the HR pathway, which can substantially increase the risk of developing cancers other than CRC. Our analysis provides evidence for ATM and PALB2 as CRC-risk genes, underscoring the importance of the homologous recombination pathway in CRC. In addition, we identified frequent complete homologous recombination deficiency in CRC tumors, representing a unique opportunity to explore targeted therapeutic interventions such as poly-ADP ribose polymerase inhibitor (PARPi).
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    Electronic ISSN: 1537-6605
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  • 77
    Publication Date: 2018-02-24
    Description: Publication date: 15 April 2018 Source: Analytical Biochemistry, Volume 547 Author(s): Preety, Nidhi Chauhan, Swati Sharma, Vinita Hooda Copper oxide nanoparticles (nano CuO) provide Cu 2+ ions which can be easily harnessed for protein determination as an alternative to the use of copper sulfate (CuSO 4 ). In the present work, nano CuO of size 〈25 nm were substituted for CuSO 4 in two of the well-known protein assays viz. Lowry method and bicinchoninic acid (BCA) method. Use of nano CuO in the Lowry's assay had no effect on the assay time (30 min) but significantly lowered the limit of detection (LOD) from 0.01 to 0.001 μg/ml, while the BCA method when performed using nano CuO resulted in notable reduction of not only the assay time from 30 to 20 min but also the LOD from 0.1 to 0.001 μg/ml. Nano CuO based protein determination in the human serum and urd bean seeds extract produced reliable, reproducible and consistent results. Nano CuO also alleviated the inhibition of both the methods by common interfering substances such as ammonium sulfate, glucose, EDTA, SDS, Triton X-100, dithiothreitol and 2-mercaptoethanol. Hence, successful modification and improvement of Lowry and BCA methods by substitution of CuSO 4 with nano CuO for protein determination has been demonstrated.
    Print ISSN: 0003-2697
    Electronic ISSN: 1096-0309
    Topics: Biology , Chemistry and Pharmacology
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  • 78
    Publication Date: 2018-02-24
    Description: Publication date: 15 April 2018 Source: Analytical Biochemistry, Volume 547 Author(s): Akihiro Tomura, Kazuo Umemura We demonstrated the attachment of different kinds of dyes, Uranine, Rhodamime 800 (R800), and Indocyanine green (ICG), to single-walled carbon nanotubes pre-wrapped with single-stranded DNAs (ssDNA-SWCNTs). A new but simple method was employed, in which a dye solution was added to ssDNA-SWCNTs that had been prepared beforehand in the conventional way. Resulting conjugates of dyes, DNA, and SWCNTs were precisely evaluated by ultraviolet to near-infrared fluorescence/absorbance spectrometry and atomic force microscopy. In particular, simultaneous measurements of fluorescence and absorbance spectroscopy enabled us to find differences in the behaviors of the dyes on SWCNT surfaces. As a result, the fluorescence/absorbance spectra of dyes showed significant changes upon adsorption on SWCNTs. The fluorescence/absorbance peaks of Uranine, R800, and ICG were quenched by 41.3/2.8%, 72.3/48.9%, and 88.3/45.0%, respectively, in the presence of 11.5 μg/mL SWCNTs. We concluded firstly that by pre-wrapping SWCNTs with ssDNA, stable hybrids with these components were obtained even if the dyes used were relatively hydrophobic and secondly that Uranine retained light absorption on the surface of SWCNT while R800 and ICG did not.
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    Topics: Biology , Chemistry and Pharmacology
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  • 79
    Publication Date: 2018-02-24
    Description: Publication date: Available online 23 February 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Inmaculada Moreno, Ettore Cicinelli, Iolanda Garcia-Grau, Marta Gonzalez, Davide Bau, Felipe Vilella, Dominique DE. Ziegler, Leonardo Resta, Diana Valbuena, Carlos Simon Background Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae , Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma . Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to one week. Objective We sought to develop a molecular diagnostic tool for chronic endometritis based on Real-Time-PCR (RT-PCR) equivalent to using the three classical methods together, overcoming the bias of using any of them alone. Study design Endometrial samples from patients assessed for chronic endometritis (n=113) using at least one or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by RT-PCR for the presence of nine chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus , Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus . The sensitivity and specificity of the molecular analysis versus the classical diagnostic techniques were compared in the 65 patients assessed by all three-recognised classical methods. Results The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or non-cultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological+hysteroscopical diagnosis revealing a 58.64% of non-concordant results. Only 13 out of 65 patients (20%) had consistent histology+hysterocopy+microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of non-culturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing (NGS). In the endometrial samples with concordant histology+hysteroscopy+microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, 0% false positive and 25% false negative rates. Conclusion The molecular microbiology method describe herein is a fast, and inexpensive diagnostic tool that allows for the identification of culturable and non-culturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all three classical diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of suffering from this ghost endometrial pathology.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 80
    Publication Date: 2018-02-24
    Description: Publication date: 15 April 2018 Source: Analytical Biochemistry, Volume 547 Author(s): Ya Han, Yaning Gao, Tian He, Daidong Wang, Ning Guo, Xiaotian Zhang, Shizhong Chen, Hong Wang Following the FDA approval of three monoclonal antibodies of PD-1/PD-L1, this pathway has become a promising target for cancer treatment. Currently small-molecule inhibitors have not been extensively investigated, and appropriate screening methods for such inhibitors are urgently required. In this study, surface plasmon resonance (SPR) technology was used to evaluate the affinity and competitive inhibition of nine caffeoylquinic acid compounds (CQAs) against PD-1/PD-L1. As a result, four small molecules including 1-CQA, 3-CQA, 4-CQA and 5-CQA were determined as PD-1/PD-L1 inhibitors. This study provided an efficient method for screening small-molecule inhibitors targeting PD-1/PD-L1 pathway.
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    Electronic ISSN: 1096-0309
    Topics: Biology ,