The Krebs Cycle Enzyme Isocitrate Dehydrogenase 3A Couples Mitochondrial Metabolism to Synaptic Transmission

Publication date: 26 December 2017
Source:Cell Reports, Volume 21, Issue 13
Author(s): Berrak Ugur, Huan Bao, Michal Stawarski, Lita R. Duraine, Zhongyuan Zuo, Yong Qi Lin, G. Gregory Neely, Gregory T. Macleod, Edwin R. Chapman, Hugo J. Bellen
Neurotransmission is a tightly regulated Ca²⁺-dependent process. Upon Ca²⁺ influx, Synaptotagmin1 (Syt1) promotes fusion of synaptic vesicles (SVs) with the plasma membrane. This requires regulation at multiple levels, but the role of metabolites in SV release is unclear. Here, we uncover a role for isocitrate dehydrogenase 3a (idh3a), a Krebs cycle enzyme, in neurotransmission. Loss of idh3a leads to a reduction of the metabolite, alpha-ketoglutarate (αKG), causing defects in synaptic transmission similar to the loss of syt1. Supplementing idh3a flies with αKG suppresses these defects through an ATP or neurotransmitter-independent mechanism. Indeed, αKG, but not glutamate, enhances Syt1-dependent fusion in a reconstitution assay. αKG promotes interaction between the C2-domains of Syt1 and phospholipids. The data reveal conserved metabolic regulation of synaptic transmission via αKG. Our studies provide a synaptic role for αKG, a metabolite that has been proposed as a treatment for aging and neurodegenerative disorders.

Graphical abstract

Teaser

Ugur et al. find that loss of the mitochondrial enzyme IDH3A leads to a reduction in alpha-ketoglutarate (αKG) and impairs synaptic transmission through an ATP-independent pathway. idh3a mutants phenocopy loss of the Ca²⁺ sensor syt1 at neuromuscular junctions, and αKG promotes membrane fusion by enhancing Syt1-lipid interaction in vitro.


http://ift.tt/2E26vvg

Compartment diversity in innate immune reprogramming

Publication date: Available online 27 December 2017
Source:Microbes and Infection
Author(s): Orhan Rasid, Jean-Marc Cavaillon
Pathogens or endogenous molecules can reprogram innate immunity. This process can take the form of priming or tolerance depending on the activating signal, and favors enhanced resistance of infection and other insults, by modulating inflammation. Similarly to their organ-specific properties, reprogramming of macrophages and NK cells, is also compartmentalized.



http://ift.tt/2pH38aj

Alternative Strategies for Vaccination to Brucellosis

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): David W. Pascual, Xinghong Yang, Hongbin Wang, Zakia Goodwin, Carol Hoffman, Beata Clapp
Brucellosis remains burdensome for livestock and humans worldwide. Better vaccines for protection are needed to reduce disease incidence. Immunity to brucellosis and barriers to protection are discussed. The benefits and limitations of conventional and experimental brucellosis vaccines are outlined, and novel vaccination strategies needed to ultimately protect against brucellosis are introduced.



http://ift.tt/2E278VY

Cellular interactions of covR/S mutant group A Streptococci

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Emma L. Langshaw, Manisha Pandey, Michael F. Good
Group A Streptococci (GAS) are responsible for a wide array of non-invasive and invasive diseases and varying immune sequelae with high rates of mortality and morbidity. GAS strains with a mutation in their covR/S regulatory system are hypervirulent with an increased capacity for causing invasive disease. CovR/S mutants augment their virulence through the up-regulation of important virulence factors and target host immune surveillance primarily by inhibiting neutrophils. An in-depth understanding of the immunopathogenesis of covR/S mutants will facilitate the development of vaccine strategies and design. Ultimately, by targeting separate virulence mechanisms, multi-component vaccines may provide improved protective efficacy against hypervirulent GAS infections.



http://ift.tt/2pH3UDX

Exploiting the apicoplast: apicoplast-targeting drugs and malaria vaccine development

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Leanne M. Low, Danielle I. Stanisic, Michael F. Good
The apicoplast, a relic plastid found in most Apicomplexan parasites, is a notable drug target. Certain antibiotics elicit a delayed death phenotype by targeting this organelle. Here, we review apicoplast targeting drugs and their targets, particularly those that cause delayed death, and highlight its potential uses in malaria vaccine development.



http://ift.tt/2pEozbQ

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Brian M.O. Ogendi, Rakesh K. Bakshi, Kanupriya Gupta, Richa Kapil, LaDraka T. Brown, Stephen J. Jordan, Steffanie Sabbaj, Christen G. Press, Jeannette Y. Lee, William M. Geisler
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38⁺HLA-DR⁺), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3⁺CCR5⁺ and CCR4⁺, respectively), and T cell homing marker (CCR7) for both CD4⁺ and CD8⁺ T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4⁺ and CD8⁺ T cells expressing these markers. These finding suggest a dynamic interplay of CD4⁺ and CD8⁺ T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection a significantly higher proportion of CD8⁺ T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections.



http://ift.tt/2DYLlyp

Rickettsial genomics and the paradigm of genome reduction associated with increased virulence

Publication date: Available online 27 December 2017
Source:Microbes and Infection
Author(s): Awa Diop, Didier Raoult, Pierre-Edouard Fournier
Rickettsia species are arthropod endosymbiotic α-proteobacteria that can infect mammalian hosts during their obligate intracellular lifecycle, and cause a range of mild to severe diseases in humans. Paradoxically, during their adaptation to a bottleneck lifestyle, rickettsial genomes have undergone an evolution marked by a progressive chromosomic and plasmidic degradation resulting in a genome reduction from 1.5 to 1.1 Mb, with a coding capacity of 69 to 84%. A striking finding of rickettsial genomics has been that the most virulent species had genomes that were drastically reduced and degraded when compared to closely related less virulent or non pathogenic species. This paradoxical evolution, which is not unique to members of the genus Rickettsia but has been identified as a convergent evolution of several major human pathogenic bacteria, parallels a selected loss of genes associated with transcriptional regulators, but with a high preservation of toxin-antitoxin (TA) modules and recombination and DNA repair proteins. In addition, these bacteria have undergone a proliferation of genetic elements, notably short palindromic elements, whose role remains unknown. Recent proteomic and transcriptomics analyses have revealed a differential level or degradation of gene expression that may, at least partially, explain differences in virulence among Rickettsia species. However, future investigations are mandatory to provide novel insights into the mechanisms by which genomic reductive evolution contributes to an emergence of pathogenesis.



http://ift.tt/2E3us5x

Observations on bradyzoite biology

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Vincent Tu, Rama Yakubu, Louis M. Weiss
Tachyzoites of the Apicomplexan Toxoplasma gondii cause acute infection, disseminate widely in their host, and eventually differentiates into a latent encysted form called bradyzoites that are found within tissue cysts. During latent infection, whenever transformation to tachyzoites occurs, any tachyzoites that develop are removed by the immune system. In contrast, cysts containing bradyzoites are sequestered from the immune system. In the absence of an effective immune response released organisms that differentiate into tachyzoites cause acute infection. Tissue cysts, therefore, serve as a reservoir for the reactivation of toxoplasmosis when the host becomes immunocompromised by conditions such as HIV infection, organ transplantation, or due to the impaired immune response that occurs when pathogens are acquired in utero. While tachyzoites and bradyzoites are well defined morphologically, there is no clear consensus on how interconversion occurs or what exact signal(s) mediate this transformation. Advances in research methods have facilitated studies on T. gondii bradyzoites providing important new insights into the biology of latent infection.



http://ift.tt/2pGuopq

Inducible nitric oxide synthase in innate immune cells is important for restricting cyst formation of Toxoplasma gondii in the brain but not required for the protective immune process to remove the cysts

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Qila Sa, Ashish Tiwari, Eri Ochiai, Jeremi Mullins, Yasuhiro Suzuki
Significantly larger numbers of Toxoplasma gondii cysts were detected in the brains of RAG1^-/-NOS2^-/- than RAG1^-/- mice following infection. In contrast, the cyst numbers markedly decreased in a same manner in both strains of mice after receiving CD8⁺ immune T cells. Thus, NOS2-mediated innate immunity is important for inhibiting formation of cysts in the brain but not required for the T cell-initiated cyst removal, which is associated with phagocyte accumulation. Treatment with chloroquine, an inhibitor of endolysosomal acidification, partially but significantly inhibited the T cell-mediated cyst removal, suggesting that phagosome-lysomose fusion could be involved in the T. gondii cyst elimination.



http://ift.tt/2E2aQP4

Airway microbial metagenomics

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Katarzyna Pienkowska, Lutz Wiehlmann, Burkhard Tümmler
High-throughput untargeted metagenome sequencing provides information about the composition of the microbial communities of viruses, bacteria, archaea and unicellular eukaryotes in the habitat of interest. This review outlines the sampling, processing, sequencing and bioinformatic analysis of secretions of the respiratory tract and summarizes our current knowledge of the upper and lower human airways metagenome in health and disease.



http://ift.tt/2pIxEjT

Are miRNAs critical determinants in Herpes Simplex Virus pathogenesis?

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Siddheshvar Bhela, Barry T. Rouse
miRNAs are small noncoding RNA that play a crucial role in gene regulation by inhibiting translation or promoting mRNA degradation. Viruses themselves express miRNAs that can target either the host or viral mRNA transcriptome. Moreover, viral infection of cells causes a drastic change in host miRNAs. This complex interaction between the host and viruses often favors the virus to evade immune elimination and favors the establishment and maintenance of latency. In this review we discuss the function of both host and viral miRNAs in regulating herpes simplex virus pathogenesis and also discuss the prospect of using miRNAs as biomarkers and therapeutic tools.



http://ift.tt/2DZrfUu

Immune responses to congenital cytomegalovirus infection

Publication date: Available online 26 December 2017
Source:Microbes and Infection
Author(s): Ilija Brizić, Lea Hiršl, William J. Britt, Astrid Krmpotić, Stipan Jonjić
Human cytomegalovirus (HCMV) is the most common cause of viral infection acquired in utero. Even though the infection has been studied for several decades, immune determinants important for virus control and mechanisms of long-term sequelae caused by infection are still insufficiently characterized. Animal models of congenital HCMV infection provide unique opportunity to study various aspects of human disease. In this review, we summarize current knowledge on the role of immune system in congenital CMV infection, with emphasis on lessons learned from mouse model of congenital CMV infection.



http://ift.tt/2pEorZU

Redox Clocks: Time to Rethink Redox Interventions

Publication date: Available online 26 December 2017
Source:Free Radical Biology and Medicine
Author(s): Andras D. Nagy, Akhilesh B. Reddy
Redox interventions have been controversial in the management of chronic disease. The key reason is believed to be a lack of clarity in our understanding of how endogenous dynamics unfold in biochemical redox mechanisms in live cells. Time-resolved, quantitative research strategies combined with high throughput analysis tools may result in realistic characterisation of related in vivo processes. Here we review new evidence about redox dynamics in live cells. We discuss a potential of this line of research to establish new and affordable ways of redox interventions which may efficiently decrease mortality related to largely preventable chronic diseases.

Graphical abstract

http://ift.tt/2Cg1KAg

Redox-responsive polymeric micelles formed by conjugating gambogic acid with bioreducible poly(amido amine)s for the co-delivery of docetaxel and MMP-9 shRNA

Publication date: Available online 26 December 2017
Source:Acta Biomaterialia
Author(s): Yanan Kang, Lu Lu, Jinshuai Lan, Yue Ding, Jing Yang, Yong Zhang, Yuan Zhao, Tong Zhang, Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers, which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy, flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere^® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer.Statement of SignificanceThe PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere^® , indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin, methotrexate and other drugs with carboxy groups in their structure.

Graphical abstract

http://ift.tt/2CcOlXq

Comparison of In-Vivo and Ex-Vivo Viscoelastic Behavior of the Spinal Cord

Publication date: Available online 26 December 2017
Source:Acta Biomaterialia
Author(s): Nicole L. Ramo, Snehal S. Shetye, Femke Streijger, Jae H.T. Lee, Kevin L. Troyer, Brian K. Kwon, Peter Cripton, Christian M. Puttlitz
Despite efforts to simulate the in-vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex-vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex-vivo, the viscoelastic behavior of in-vivo and ex-vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex-vivo and in-vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex-vivo samples experienced a higher stress and greater relaxation than in-vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1 to 1 second). The results of this study underscore the necessity of utilizing material models developed from in-vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in-vivo model in future high-resolution finite element modeling efforts.Statement of SignificanceNeural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex-vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in-vivo response). Therefore, this study directly compared the mechanical response of ex-vivo and in-vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex-vivo data (which are easier to obtain) and emphasizes the importance of future in-vivo experimental animal work.

Graphical abstract

http://ift.tt/2Cbzlcd

Scholar : Autophagy, Volume 13, Issue 11, 2017 is now available online on Taylor & Francis Online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content Autophagy, Volume 13, Issue 11, 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Editorials BRD4 is a newly characterized transcriptional regulator that represses autophagy and lysosomal function Xin Wen & Daniel J. Klionsky Pages: 1801-1803 | DOI: 10.1080/15548627.2017.1364334 Brief Reports Stress-response transcription factors Msn2 and Msn4 couple TORC2-Ypk1 signaling and mitochondrial respiration to ATG8 gene expression and autophagy | Ariadne Vlahakis, Nerea Lopez Muniozguren & Ted Powers Pages: 1804-1812 | DOI: 10.1080/15548627.2017.1356949 Original Articles Lipopolysaccharide mediates hepatic stellate cell activation by regulating autophagy and retinoic acid signaling Ming Chen, Jiaxing Liu, Wenqi Yang & Wenhua Ling Pages: 1813-1827 | DOI: 10.1080/15548627.2017.1356550 Research Paper Regulation of autophagy, mitochondrial dynamics, and cellular bioenergetics by 4-hydroxynonenal in primary neurons Matthew Dodson, Willayat Y. Wani, Matthew Redmann, Gloria A. Benavides, Michelle S. Johnson, Xiaosen Ouyang, Stacey S. Cofield, Kasturi Mitra, Victor Darley-Usmar & Jianhua Zhang Pages: 1828-1840 | DOI: 10.1080/15548627.2017.1356948 Basic Research Paper The intracellular microbial sensor NLRP4 directs Rho-actin signaling to facilitate Group A Streptococcus-containing autophagosome-like vacuole formation Takashi Nozawa, Chihiro Aikawa, Atsuko Minowa-Nozawa & Ichiro Nakagawa Pages: 1841-1854 | DOI: 10.1080/15548627.2017.1358343 Restoring diabetes-induced autophagic flux arrest in ischemic/reperfused heart by ADIPOR (adiponectin receptor) activation involves both AMPK-dependent and AMPK-independent signaling Yajing Wang, Bin Liang, Wayne Bond Lau, Yunhui Du, Rui Guo, Zheyi Yan, Lu Gan, Wenjun Yan, Jianli Zhao, Erhe Gao, Walter Koch & Xin-Liang Ma Pages: 1855-1869 | DOI: 10.1080/15548627.2017.1358848 Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF motif crucial for complex formation Jing-Xiang Zheng, Yan Li, Yue-He Ding, Jun-Jie Liu, Mei-Jun Zhang, Meng-Qiu Dong, Hong-Wei Wang & Li Yu Pages: 1870-1883 | DOI: 10.1080/15548627.2017.1359381 Autophagy protects auditory hair cells against neomycin-induced damage | Zuhong He, Lingna Guo, Yilai Shu, Qiaojun Fang, Han Zhou, Yongze Liu, Dingding Liu, Ling Lu, Xiaoli Zhang, Xiaoqiong Ding, Dong Liu, Mingliang Tang, Weijia Kong, Suhua Sha, Huawei Li, Xia Gao & Renjie Chai Pages: 1884-1904 | DOI: 10.1080/15548627.2017.1359449 Research Paper Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy Natalya Kaverina, Anton V. Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R. Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs & Ilya V. Ulasov Pages: 1905-1923 | DOI: 10.1080/15548627.2017.1360466 Basic Research Paper Mask mitigates MAPT- and FUS-induced degeneration by enhancing autophagy through lysosomal acidification | Mingwei Zhu, Sheng Zhang, Xiaolin Tian & Chunlai Wu Pages: 1924-1938 | DOI: 10.1080/15548627.2017.1362524 Autophagy is required for gamete differentiation in the moss Physcomitrella patens | Victoria Sanchez-Vera, Chandra Shekar Kenchappa, Katarina Landberg, Simon Bressendorff, Stefan Schwarzbach, Tom Martin, John Mundy, Morten Petersen, Mattias Thelander & Eva Sundberg Pages: 1939-1951 | DOI: 10.1080/15548627.2017.1366406 Research Paper - Basic Science Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway Haiyan Liu, Ali Javaheri, Rebecca J. Godar, John Murphy, Xiucui Ma, Nidhi Rohatgi, Jana Mahadevan, Krzysztof Hyrc, Paul Saftig, Connie Marshall, Michael L. McDaniel, Maria S. Remedi, Babak Razani, Fumihiko Urano & Abhinav Diwan Pages: 1952-1968 | DOI: 10.1080/15548627.2017.1368596 Research Paper-Basic Science Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2K2 and PLK1 in neuronal autophagy Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li & Yu Xue Pages: 1969-1980 | DOI: 10.1080/15548627.2017.1371393 Basic Research Paper Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis | Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Feng, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S. Ostrom, Yanyun Zhang, Xiangjun Chen & Congfeng Xu Pages: 1981-1994 | DOI: 10.1080/15548627.2017.1375633 Views and Commentaries Recycling the danger via lipid droplet biogenesis after autophagy Yuan Li, Wei-Xing Zong & Wen-Xing Ding Pages: 1995-1997 | DOI: 10.1080/15548627.2017.1371394 Destructive cellular paths underlying familial and sporadic Parkinson disease converge on mitophagy | Xinnan Wang Pages: 1998-1999 | DOI: 10.1080/15548627.2017.1327511 Autophagic Punctum NBR1-mediated antiviral xenophagy in plant immunity Anders Hafrén & Daniel Hofius Pages: 2000-2001 | DOI: 10.1080/15548627.2017.1339005 Lipid droplets and lipotoxicity during autophagy | Truc B. Nguyen & James A. Olzmann Pages: 2002-2003 | DOI: 10.1080/15548627.2017.1359451 Presenilins at the crossroad of a functional interplay between PARK2/PARKIN and PINK1 to control mitophagy: Implication for neurodegenerative diseases Frédéric Checler, Thomas Goiran & Cristine Alves da Costa Pages: 2004-2005 | DOI: 10.1080/15548627.2017.1363950 Transcriptional regulation of autophagy and lysosomal function by bromodomain protein BRD4 | Jun-Ichi Sakamaki & Kevin M. Ryan Pages: 2006-2007 | DOI: 10.1080/15548627.2017.1364822 Legionella blocks autophagy by cleaving STX17 (syntaxin 17) | Kohei Arasaki & Mitsuo Tagaya Pages: 2008-2009 | DOI: 10.1080/15548627.2017.1371395 LC3s hire membrane breakers to attack viral shelters | Scott B. Biering, Jayoung Choi, Hailey M. Brown & Seungmin Hwang Pages: 2010-2012 | DOI: 10.1080/15548627.2017.1371396 Autophagy enables retromer-dependent plasma membrane translocation of SLC2A1/GLUT1 to enhance glucose uptake Srirupa Roy & Jayanta Debnath Pages: 2013-2014 | DOI: 10.1080/15548627.2017.1371397 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Electric Power Components and Systems, Volume 45, Issue 14, August 27, 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Electric Power Components and Systems, Volume 45, Issue 14, August 27, 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles Real-Time Differential Pricing Scheme for Active Consumers with Electric Vehicles Kumarsinh Jhala, Balasubramaniam Natarajan, Anil Pahwa & Larry Erickson Pages: 1487-1497 | DOI: 10.1080/15325008.2017.1362074 Time-Series Modeling of Aggregated Electric Vehicle Charging Station Load Henry M. Louie Pages: 1498-1511 | DOI: 10.1080/15325008.2017.1336583 Active Power Control of Grid-connected Permanent Magnet Synchronous Generator-based Wind Turbines in the Presence of Voltage Sags Devbratta Thakur & Jin Jiang Pages: 1512-1524 | DOI: 10.1080/15325008.2017.1347214 Multi-objective Economic Dispatch Considering Wind Power Penetration Using Stochastic Weight Trade-off Chaotic NSPSO Anongpun Man-Im, Weerakorn Ongsakul, Jai Govind Singh & Chanwit Boonchuay Pages: 1525-1542 | DOI: 10.1080/15325008.2017.1362067 Optimal Placement of Intermittent Renewable Energy Resources and Energy Storage System in Smart Power Distribution Networks Eric Galvan, Paras Mandal, Ashraf Ul Haque & Tzu-Liang (Bill) Tseng Pages: 1543-1553 | DOI: 10.1080/15325008.2017.1362605 Harmonics-Based Enhanced Passive Islanding Method for Grid-Connected System Rahul Somalwar, Sumant G. Kadwane & Dusmanta Kumar Mohanta Pages: 1554-1563 | DOI: 10.1080/15325008.2017.1361485 A Random Forest Classifier-based Digital Protection Scheme for Busbar Nidhi Narayan & Bhavesh R. Bhalja Pages: 1564-1572 | DOI: 10.1080/15325008.2017.1346003 Ant Colony Optimized Fuzzy Control Solution for Frequency Oscillation Suppression Yogesh Krishan Bhateshvar, Hitesh Datt Mathur, Houria Siguerdidjane & Ramesh C. Bansal Pages: 1573-1584 | DOI: 10.1080/15325008.2017.1362073 Modeling and Full Decoupling Control of a Grid-Connected Five-Level Diode-Clamped Converter Francisco Umbría, Francisco Gordillo & Francisco Salas Pages: 1585-1598 | DOI: 10.1080/15325008.2017.1334161 Coupled-Inductor-Based High-Step-Down-Ratio Converter with Output Current Ripple Reduction Kuo-Ing Hwu & Wen-Zhuang Jiang Pages: 1599-1606 | DOI: 10.1080/15325008.2017.1362069 A Novel Power Flow Algorithm for Hybrid AC/DC Power Grids Xinyi Zhang, Xueshan Han, Ming Yang, Donglei Sun, Yumin Zhang & Wuyang Gai Pages: 1607-1616 | DOI: 10.1080/15325008.2017.1362075 Browse articles in this special issue on: 'Advancements in Civil and Structural Engineering' To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Human–Computer Interaction, Volume 33, Issue 2, 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Human–Computer Interaction, Volume 33, Issue 2, 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles The Usability Construct: A Dead End? Noam Tractinsky Pages: 131-177 | DOI: 10.1080/07370024.2017.1298038 Commentaries Commentary: Usability—A Sensitizing Concept Morten Hertzum Pages: 178-181 | DOI: 10.1080/07370024.2017.1302800 Commentary: Usability and the Primacy of Practice Olav W. Bertelsen Pages: 182-185 | DOI: 10.1080/07370024.2017.1321991 Commentary: Usability and Theory Building Kasper Hornbæk Pages: 186-189 | DOI: 10.1080/07370024.2017.1321992 Commentary: Usability in Vivo Stuart Reeves Pages: 190-194 | DOI: 10.1080/07370024.2017.1324306 Commentary: Usability in Theory and Practice Jan Stage Pages: 195-197 | DOI: 10.1080/07370024.2017.1333908 Commentary: Actionable Constructs for Practitioners Virpi Roto Pages: 198-200 | DOI: 10.1080/07370024.2017.1325326 Commentary: Appreciative Disagreements Jeffrey Bardzell Pages: 201-204 | DOI: 10.1080/07370024.2017.1326826 Errata Erratum Pages: 205-205 | DOI: 10.1080/07370024.2017.1391519 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Change and continuity in the long-distance exchange networks between western/central Anatolia, northern Levant and northern Mesopotamia, c.3200–1600 BCE

Publication date: March 2018
Source:Journal of Anthropological Archaeology, Volume 49
Author(s): Michele Massa, Alessio Palmisano
This paper investigates and offers explanations for the distribution of specific products (ivory and lapis lazuli artefacts, "Syrian" bottles) and technologies (metrology) that have often been invoked as tracers of long-distance trade contacts and/or political units in Anatolia, northern Levant and northern Mesopotamia during the Early and Middle Bronze Ages. Unlike former studies investigating third and second millennia exchange networks as separate entities, we examine comparatively and systematically a large corpus of published archaeological data by adopting a quantitative and spatial approach. Through this analysis, we propose that a significant degree of similarity in the shape, infrastructure and motivations behind the development and maintenance of these long-distance exchanges existed between the third and early second millennia BC.



http://ift.tt/2l5A7QB

Scholar : These new articles for Asian Security are available online

The online platform for Taylor & Francis Online content New for Asian Security and online now on Taylor & Francis Online: Original Articles Be Careful What You Wish For: Security Challenges Facing the Korean Peninsula During a Potential Unification Process Mason Richey, Ohn Daewon, Jangho Kim & Jaejeok Park Pages: 1-19 | DOI: 10.1080/14799855.2017.1414043 Privateering in Cyberspace: Should Patriotic Hacking Be Promoted as National Policy? Forrest B. Hare Pages: 1-10 | DOI: 10.1080/14799855.2017.1414803 Interested in the political-economic topics surrounding China? You wouldn't want to miss this exclusive collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Signatures of protein expression revealed by secretome analyses of cancer associated fibroblasts and melanoma cell lines

Publication date: 1 March 2018
Source:Journal of Proteomics, Volume 174
Author(s): Tarcísio Liberato, Dayelle S. Pessotti, Isabella Fukushima, Eduardo S. Kitano, Solange M.T. Serrano, André Zelanis
The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: a paired set of fibroblasts - Hs 895. T, a cell line obtained from a lung node metastatic site from a patient who had melanoma and Hs 895.Sk, a skin fibroblast cell line (derived from the same patient); two malignant metastatic melanoma cell lines - A375, a malignant melanoma cell line from primary source and SH-4, a cell line derived from pleural effusion of a patient with metastatic melanoma. Clustering of expression profiles together with functional enrichment analysis resulted in patterns that mirrored each cell type. In addition, these patterns might be the result of cell-specific protein expression programs and reveal the emergence of trends in the co-expression of functionally related proteins in cellular melanoma models.SignificanceMelanoma is an aggressive skin cancer and a lethal melanocytic neoplasm with increasing annual number of cases, faster than any other solid tumor. In this context, the imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Therefore, the identification of protein expression patterns in malignant cells together with functional enrichment analysis provide insights into cell-specific protein expression programs and may reveal the emergence of trends in the co-expression of functionally related proteins regardless of cell type. Moreover, the identification of networks of protein interactions together with their expression profiles can be used for the targeted analysis of co-expressed proteins, allowing the identification of regulatory motifs in melanoma protein-protein interaction networks.

Graphical abstract

http://ift.tt/2Dk1Bc8

An evaluation of the biocompatibility and osseointegration of novel glass fiber reinforced composite implants: In vitro and in vivo studies

Publication date: Available online 26 December 2017
Source:Dental Materials
Author(s): Ya-Hui Chan, Wei-Zhen Lew, Emily Lu, Thomas Loretz, Luke Lu, Che-Tong Lin, Sheng-Wei Feng
ObjectivesThe aim of this study was to evaluate the in vitro biocompatibility and in vivo osseointegration of three novel bioactive glass fiber reinforced composite (GFRC) implants and to compare these with metal (Ti6Al4V) implants.MethodsThe surfaces of these experimental substrates were characterized by scanning electron microscopy (SEM), a 2D profilometer and by contact angle measurement. In vitro biological performance was assessed using MG-63 human osteoblast-like cell morphology, cell proliferation assays and the alkaline phosphatase (ALP) activity testing. Furthermore, in vivo osseointegration performance was examined by installing samples into rabbit femurs and evaluated the results using micro-CT, histology and histomorphometrical analysis; these assessments were carried out after 1, 2, 4 and 8 weeks of healing.ResultsThe results showed that moderate surface roughness, moderate hydrophilic exposure and moderate homogenous exposure of bioactive glass fibers were present for all of the GFRC substrates. Furthermore, MG-63 cells, when cultured on all of the GFRC substrates, grew well and exhibited a more differentiated phenotype than cells grown on titanium alloy (Ti6Al4V) substrate. Histological evaluation revealed more newly-formed bone regeneration within the thread of the GFRC implants during the initial healing period. In addition, the novel GFRC implants with a bioactive Bio-fiber structure and glass particles within the epoxy resin matrix showed better bone volume/tissue volume (BV/TV) values at 4 weeks and this was accompanied by bone-implant contact (BIC) values at 8 weeks comparable to the Ti6Al4V group.SignificanceThese findings demonstrated that novel GFRC implants seem to show improved osteogenesis and osseointegration functionality and have potential as a substitute for Ti6Al4V, or other metal-based materials, when used for clinically dental and orthopedic applications.

Graphical abstract

http://ift.tt/2Dkb2YR

Development of radiopaque, biocompatible, antimicrobial, micro-particle fillers for micro-CT imaging of simulated periodontal pockets

Publication date: Available online 26 December 2017
Source:Dental Materials
Author(s): M. Elashiry, M.M. Meghil, S. Kalathingal, A. Buchanan, M. Rajendran, R. Elrefai, M. Ochieng, A. Elawady, R.M. Arce, K.H. Sandhage, C.W. Cutler
ObjectivesApproximately 10⁹ bacteria can be harbored within periodontal pockets (PP) along with inflammatory byproducts implicated in the pathophysiology of systemic diseases linked to periodontitis (PD). Calculation of this inflammatory burden has involved estimation of total pocket surface area using analog data from conventional periodontal probing which is unable to determine the three-dimensional (3-D) nature of PP. The goals of this study are to determine the radiopacity, biocompatibility, and antimicrobial activity of transient micro-particle fillers in vitro and demonstrate their capability for 3-D imaging of artificial PP (U.S. Patent publication number: 9814791 B2).MethodsRelative radiopacity values of various metal oxide fillers were obtained from conventional radiography and micro-computed tomography (μCT) using in vitro models. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to measure the biocompatibility of calcium tungstate (CaWO4) particles by determination of viable keratinocytes percentage (%) after exposure. After introducing an antibacterial compound (K21) to the radiopaque agent, antimicrobial tests were conducted using Porphyromonas gingivalis (P. gingivalis) and Streptococcus gordonii (S. gordonii) strains and blood agar plates.ResultsCaWO4 micro-particle-bearing fillers exhibited an X-ray radiopacity distinct from tooth structures that enabled 3-D visualization of an artificial periodontal pocket created around a human tooth. MTT assays indicated that CaWO4 micro-particles are highly biocompatible (increasing the viability of exposed keratinocytes). Radiopaque micro-particle fillers combined with K21 showed significant antimicrobial activity for P. gingivalis and S. gordonii.SignificanceThe plausibility of visualizing PP with 3-D radiographic imaging using new radiopaque, biocompatible, transient fillers was demonstrated in vitro. Antibacterial (or other) agents added to this formula could provide beneficial therapeutic features along with the diagnostic utility.



http://ift.tt/2Dkb42V

Exercise as a Countermeasure to Declining Central Nervous System Function in Multiple Sclerosis

Publication date: Available online 26 December 2017
Source:Clinical Therapeutics
Author(s): Robert W. Motl, Brian M. Sandroff
PurposeThe decline of central nervous system (CNS) function is a hallmark characteristic of multiple sclerosis (MS) that can manifest as cognitive impairment. We believe that exercise represents a potential behavioral approach for counteracting the declines in CNS structure and associated function among persons with MS (ie, exercise as a countermeasure of CNS decline). This theory is important because disease-modifying drugs represent a first-line approach for modifying the immune system and its effects on the CNS, but these drugs do not generally demonstrate robust improvements in cognitive performance.MethodsTo the best of our knowledge, this article presents the first argument positioning exercise as a countermeasure for CNS decline in MS.FindingThe reviewed research indicates a proliferating body of evidence describing physical fitness, physical activity, and exercise effects on cognitive performance and neuroimaging outcomes (ie, CNS functioning) in MS, with the consistent and strong association between cognitive performance and neuroimaging outcomes in this population as a backdrop.ImplicationsWe further present a framework and future research directions for better positioning exercise as a possible neuroprotective behavior against declining CNS function in MS.



http://ift.tt/2pGYLMg

Phase 1b Study of the Safety, Pharmacokinetics, and Disease-Related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis

Publication date: Available online 26 December 2017
Source:Clinical Therapeutics
Author(s): David L. Gossage, Blanka Cieslarová, Sophe Ap, Hao Zheng, Yan Xin, Preeti Lal, Guang Chen, Victoria Smith, John S. Sundy
PurposeAndecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers.MethodsIn this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics.FindingsA total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t1/2 was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab.ImplicationsAndecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.



http://ift.tt/2DXoDql

Biological and pharmaceutical activities of mushroom β-Glucan discussed as a potential functional food ingredient

Publication date: Available online 27 December 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Asma Ashraf Khan, Adil Gani, Firdous A. Khanday, F.A. Masoodi
Mushroom species have been recognized as medicinal plant due to presence of various bioactive compounds. The well known bioactive compound for biological and pharmaceutical activities present in mushroom species is β-glucan. The β-glucan from other sources like yeasts and cereals is well summarized in the literature, but mushroom β-glucan is not well documented. Mushroom β-glucans provide a unique opportunity for the discovery of novel therapeutic agents and have attracted a great deal of attention due to many health benefits such as immunomodulatory, anticancerous, cardioprotective, hepatoprotective, antioxidative and antimicrobial activities. Mushroom β-glucans have the potential to enhance innate and cell mediated immune response. They exhibit varying degree of antitumor activities in humans due to the difference in their structure, water solubility, size and molecular mass; these differences in turn contribute to their medicinal properties. This review summarizes the literature on the structure-function relationship and nutraceutical potential of β-glucan obtained from various mushroom species.



http://ift.tt/2l5MUTa

The effect of premedication with peppermint oil capsules (Colpermin) prior to colonoscopy: A double blind randomized placebo-controlled trial

Publication date: Available online 19 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Hassan Al Moussawi, Mariam Al Khatib, Malak El Ahmar, Houssam Al Masri, Ali Leddy, Tamer Akel, Ali Khalil
Background and study aimsColonoscopy is the cornerstone of diagnosing colonic diseases. Investigators have evaluated the effectiveness of antispasmodic agents in colonoscopy with conflicting evidence. The aim of this study is to determine the efficacy of enteric coated peppermint oil capsules (Colpermin®), an antispasmodic agent, on outcomes during colonoscopy.Patients and methodsA total of 80 patients undergoing elective colonoscopy were recruited and randomized in a double blinded fashion to receive either placebo or peppermint oil capsules administered 4 h prior to the procedure.ResultsPeppermint oil capsules did not affect caecal intubation time when compared with placebo. Patients' tolerance, endoscopist's satisfaction and demand on sedation were also not affected.ConclusionThis randomized controlled trial does not support the routine use of peppermint oil capsules prior to colonoscopy as a tool for procedure optimization, and patients' and endoscopist's satisfaction.



http://ift.tt/2Dl9luv

Systematic gastric biopsy in iron deficiency anaemia

Publication date: Available online 19 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Hela Elloumi, Meriam Sabbah, Achraf Debbiche, Asma Ouakaa, Norsaf Bibani, Dorra Trad, Dalila Gargouri, Jamel Kharrat
Background and study aimsGastric biopsies are recommended in patients with iron deficiency anaemia to identify atrophic gastritis. However, in practice, only duodenal biopsies are routinely performed. The aim of our study was to determine the value of gastric biopsies in iron deficiency anaemia.Patients and methodsA prospective study including all patients referred for gastrointestinal endoscopy for iron deficiency anaemia from May 2008 to September 2014 was performed. All patients having endoscopic lesions which may explain occult bleeding were excluded, as well as patients using non-steroidal anti-inflammatory drugs or anticoagulation treatment. Two fundic biopsies, two antral biopsies, and one biopsy from the lesser curve were taken in all patients. Following entities were particularly looked for: chronic gastritis, Helicobacter pylori infection, intestinal metaplasia, endocrine hyperplasia and villous atrophy. In cases where intestinal metaplasia was present in the fundus and associated with endocrine hyperplasia and glandular atrophy, immunohistochemical study was performed to confirm autoimmune gastritis.ResultsOne hundred seventy-seven patients (mean age 50 years, range: 15–90) were included. Chronic gastritis was found in 149 cases (84%). Infection by Helicobacter pylori was found in 107 cases (60%). Fundic intestinal metaplasia was observed in 25 patients (14%) and was associated with Helicobacter pylori infection in 52% of cases. Atrophic gastritis was observed in 14 cases (8%) and autoimmune gastritis was confirmed in 5 cases by immunohistochemical study. One patient had on gastric biopsy a carcinoma with signet ring cells.ConclusionIntestinal metaplasia was frequently observed and was mostly related to Helicobacter pylori infection. These patients require monitoring, especially if they are young because it represents a pre neoplastic condition. However, in our study autoimmune gastritis often described in the literature in case of iron deficiency anaemia was rarely seen raising the question of relative cost-efficiency of fundic biopsies during iron deficiency anaemia.



http://ift.tt/2CdtK5m

Association between antioxidants and mild acute pancreatitis

Publication date: Available online 21 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Tevfik Solakoglu, Huseyin Koseoglu, Semra Isikoglu, Ozcan Erel, Osman Ersoy
Background and study aimsThe mechanisms underlying acute pancreatitis have not been well elucidated. Over the last 20 years, there has been increasing awareness regarding the role played by oxidative stress in acute pancreatitis, but it is less well defined in human clinical trials. The aim of this study was to identify the relationship between antioxidants and acute pancreatitis.Patients and methodsWe performed a cross-sectional trial on patients with mild acute pancreatitis. The study population consisted of 53 patients with mild acute pancreatitis and 55 healthy controls. Serum paraoxonase, arylesterase activity, total antioxidant status, total oxidant status and thiol levels were measured, and oxidative stress index was calculated.ResultsParaoxonase, arylesterase activity, thiol and total antioxidant status levels were significantly lower in the acute pancreatitis group than in the control group (p = .024, p < .001, p < .001, p = .010, respectively). Oxidative stress index and total oxidant status levels were higher in the acute pancreatitis group than in the control group, but the difference was not statistically significant (p = .135, p = .253, respectively).ConclusionsThis study demonstrates that decreased antioxidant levels are associated with mild acute pancreatitis. No association was observed between mild acute pancreatitis and total oxidant status.



http://ift.tt/2Dl9spA

Study of the relationship between cVEMP and ABR 500 Hz

Publication date: Available online 19 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Amani Mohamed El-Gharib, Trandil Hassan Elmahallawy
ObjectiveTo evaluate the possible contribution of the saccular projections in generation ABR 500 Hz at high intensity by investigating the relationship between cVEMP and ABR 500 Hz in normal subjects and those with unilateral saccular dysfunction.SubjectsTwenty dizzy adults with unilateral affected cVEMP compared to twenty healthy subjects.MethodsAll subjects were subjected to basic audiological evaluation (pure tone audiometry, speech audiometry and immittancemetry), cVEMP and ABR using 500 Hz tone burst at 90 dB nHL. The dizzy patients within the study group were subjected to VNG to exclude another vestibular affection.The resultsWe found that patient's abnormal cVEMPs response mostly had prolonged ABR 500 Hz wave V latency, whereas unaffected ears presented with normal findings.ConclusionUsing ABR 500 Hz in the battery approach tests of vestibular assessment can produce valuable data for judgment on the site of a lesion.



http://ift.tt/2C9ZTdN

Conserved FcγR- glycan discriminates between fucosylated and afucosylated IgG in humans and mice

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Gillian Dekkers, Arthur E.H. Bentlage, Rosina Plomp, Remco Visser, Carolien A.M. Koeleman, Anna Beentjes, Juk Yee Mok, Wim J.E. van Esch, Manfred Wuhrer, Theo Rispens, Gestur Vidarsson
The binding strength between IgG and FcγR is influenced by the composition of the N-linked glycan at position N297 in the Fc-domain of IgG. Particularly, afucosylation increases the binding affinity of human IgG1 to human FcγRIIIa up to ∼20 fold, and additional galactosylation of the afucosylated IgG increases the affinity up to ∼40 fold. The increase in affinity for afucosylated IgG has previously been shown to depend on direct carbohydrate-carbohydrate interactions between the IgG-Fc glycan with an N-linked glycan at position 162 unique to hFcγRIIIa and hFcγRIIIb. Here we report that the N162 glycosylation site is also found in the orthologous mouse FcγR, mFcγRIV. The N162-glycan in mFcγRIV was also responsible for enhancing the binding to mouse IgG with reduced fucose similar to hFcγRIIIa. However, unlike hFcγRIIIa, mFcγRIV did not bind more avidly to IgG with increased galactose and reduced fucose. Overall, these results suggest the N162-glycan in the human FcγRIII family and its orthologous mouse FcγRIV to be functionally conserved.

Graphical abstract

http://ift.tt/2DjRXGx

VP2 (PTA motif) encoding DNA vaccine confers protection against lethal challenge with infectious pancreatic necrosis virus (IPNV) in trout

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Sohrab Ahmadivand, Mehdi Soltani, Mahdi Behdani, Øystein Evensen, Ehsan Alirahimi, Elahe Soltani, Reza Hassanzadeh, Javad Ashrafi-Helan
IPNV in Atlantic salmon is represented by various strains with different virulence and immunogenicity linked to various motifs of the VP2 capsid. IPNV variant with P217, T221, A247 (PTA) motif is found to be avirulent in Atlantic salmon, but virulent in rainbow trout, and other salmonid species. This study describes a DNA vaccine delivered intramuscularly encoding the VP2 protein of infectious pancreatic necrosis virus (IPNV) with PTA motif that confers high protection in rainbow trout (Oncorhynchus mykiss). Intramuscular injection of 2, 5 and 10 μg of DNA (pcDNA3.1-VP2) in rainbow trout fry (4–5 g), confers relative protection of 75–83% in the different vaccine groups at 30 days post vaccination (450° days). The VP2 gene is expressed in spleen, kidney, muscle and liver at day 30 post-vaccination (RT-PCR), and IFN-1 and Mx-1 mRNA are upregulated at early time post vaccination, and so also for IgM, IgT, CD4 and CD8 in the head kidney of vaccinated fish compared to controls, 15 and 30 days post vaccination. Significant increase of serum anti-IPNV antibodies was found 30–90 days post-vaccination that was correlated with protection levels. Mortality corresponded with viral VP4 gene expression were significantly decreased in vaccinated and challenged fish. This shows for the first time that a VP2-encoding DNA vaccine delivered intramuscularly elicits a high level of protection alongside with high levels of circulating antibodies in rainbow trout and a lowered viral replication.



http://ift.tt/2DlzJ7r

Role of complement anaphylatoxin receptors in a mouse model of acute burn-induced pain

Publication date: February 2018
Source:Molecular Immunology, Volume 94
Author(s): Michael Morgan, Jennifer R. Deuis, Trent M. Woodruff, Richard J. Lewis, Irina Vetter
The complement system is an essential component of the innate immune response. The anaphylatoxins C3a and C5a are key drivers of the complement system, acting through the receptors C3aR, C5aR1 and C5aR2 to regulate inflammation. While a role for C5a activation of C5aR1 in inflammatory and neuropathic pain has been established, the role of the complement system in burn-induced pain has not been investigated. To address this gap, we assessed the role of complement receptors C3aR, C5aR1 and C5aR2 in a mouse model of acute burn-induced pain. Superficial burn injury was induced in C57BL/6 mice by firm application of left hind paw plantar surface to a hot plate set at 52.5 °C for 25 s. Development of burn-induced mechanical allodynia, thermal allodynia, weight bearing changes and edema was assessed in C3aR^−/−, C5aR1^−/− and C5aR2^−/− mice and compared to their wild type controls over three days. Burn-induced mechanical allodynia, thermal allodynia and weight bearing changes developed normally C3aR^−/−, C5aR1^−/− and C5aR2^−/− mice. However, burn-induced edema was significantly reduced in C5aR2^−/− male mice, but not C5aR2^−/− female mice. These results suggest that the complement system has a limited role in the development of acute burn-induced pain.



http://ift.tt/2CdaqF2

Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance

Publication date: Available online 19 December 2017
Source:Molecular Immunology
Author(s): Kristen B. Long, Arthur I. Collier, Gregory L. Beatty
Macrophages have emerged as promising therapeutic targets in cancer. Within tumor tissue, macrophages foster tumor development, invasion, and metastasis. As the phenotype of macrophages is inherently pliable and dependent on cues received from the surrounding microenvironment, macrophages co-evolve with malignant and other non-malignant cells during cancer progression. In doing so, they establish a microenvironment that is therapeutically resistant and thwarts the productivity of T cell immunosuveillance. Strategies designed to deplete, inhibit, or redirect macrophages with anti-tumor activity are being explored to reverse the pro-tumor properties of macrophages that are commonly observed in cancer. In this review, we discuss our current understanding of the mechanisms that regulate macrophage recruitment to tumors, their impact on the tumor microenvironment, and their promise as therapeutic targets for improving the efficacy of cytotoxic- and immune-based therapies.



http://ift.tt/2DjWmJl

STING, DCs and the link between innate and adaptive tumor immunity

Publication date: Available online 20 December 2017
Source:Molecular Immunology
Author(s): Ralph E. Vatner, Edith M. Janssen
Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process.



http://ift.tt/2DlzBEZ

Neutrophils: Homing in on the myeloid mechanisms of metastasis

Publication date: Available online 18 December 2017
Source:Molecular Immunology
Author(s): Joshua Leach, Jennifer P. Morton, Owen J. Sansom
The metastasis cascade is complex and comprises several stages including local invasion into surrounding tissue, intravasation and survival of tumour cells in the circulation, and extravasation and colonisation of a distant site. It is increasingly clear that these processes are driven not only by signals within the tumour cells, but are also profoundly influenced by stromal cells and signals in the tumour microenvironment. Amongst the many cell types within the tumour microenvironment, immune cells such as lymphocytes, macrophages and neutrophils play a prominent role in tumour development and progression. Neutrophils, however, have only recently emerged as important players, particularly in metastasis. Here we review the current evidence suggesting a multi-faceted role for neutrophils in the metastatic cascade.



http://ift.tt/2CbaPrW

Familial esophageal squamous cell carcinoma with damaging rare/germline mutations in KCNJ12/KCNJ18 and GPRIN2 genes

Publication date: Available online 23 December 2017
Source:Cancer Genetics
Author(s): Narjes Khalilipour, Ancha Baranova, Amir Jebelli, Alireza Heravi-Moussavi, Sergey Bruskin, Mohammad Reza Abbaszadegan
In Iran, esophageal cancer is the fourth common cancers in women and sixth common cancers in men. Here we evaluated the importance of familial risk factors and the role of genetic predisposition in esophagheal squamouse cell Carcinoma (ESCC) using Whole-Exome Sequencing (WES). Germline damaging mutations were identified in WES data from 9 probands of 9 unrelated ESCC pedigrees. Mutations were confirmed with Sanger sequencing and evaluated amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) in 50 non-related ethnically matched samples and in complete genomics database. Sixteen candidate variants were detected in ESCC 9 probands. Four of these 16 variants were rare damaging mutations including novel mutations in KCNJ12/KCNJ18, and GPRIN2 genes. This WES study in Iranian patients with ESCC, provides insight into the identification of novel germline mutations in familial ESCC. Our data suggest an association between specific mutations and increased risk of ESCC



http://ift.tt/2Dkjw2v

Molecular approaches identify a cryptic MECOM rearrangement in a child with a rapidly progressive myeloid neoplasm

Publication date: Available online 19 December 2017
Source:Cancer Genetics
Author(s): Roberto R. Capela de Matos, Moneeb A.K. Othman, Gerson M. Ferreira, Elaine S. Costa, Joana. B. Melo, Isabel. M. Carreira, Mariana T. de Souza, Bruno A. Lopes, Mariana Emerenciano, Marcelo G.P. Land, Thomas Liehr, Raul C. Ribeiro, Maria Luiza M. Silva
Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities. MECOM encodes a transcription factor that plays an essential role in cell proliferation and maintenance and also in epigenetic regulation.Aberrant expression of this gene is associated with reduced survival. Hence, its detailed characterization provides biological and clinical information relevant to the management of pediatric myeloid neoplasms. In this work, we describe a rare karyotype harboring three copies of MECOM with overexpression of the gene in a child with a very aggressive myeloid neoplasm.Cytogenetic studies defined the karyotype as 46,XX,der(7)t(3;7)(q26.2;q21.2). Array comparative genomic hybridization (aCGH) revealed a gain of 26.04 Mb in the 3q26.2–3qter region and a loss of 66.6 Mb in the 7q21.2–7qter region. RT-qPCR analysis detected elevated expression of the MECOM and CDK6 genes (458.5-fold and 35.2-fold, respectively). Overall, we show the importance of performing detailed molecular cytogenetic analysis of MECOM to enable appropriate management of high-risk pediatric myeloid neoplasms.



http://ift.tt/2CbaPIh

Drinking water pollution with respective of fluoride in the semi-arid region of Basara, Nirmal district, Telangana State, India

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Adimalla Narsimha, Venkatayogi Sudarshan
Fluoride is an essential microelement for human health. Statistically, smaller quantities (<1.0mg/L) in drinking water are usually considered to have a beneficial effect on the rate of occurrence of dental caries, particularly among children, but excessive continuous exposure (>1.5mg/L) to fluoride can give rise to a number of adverse effects, including dental fluorosis, skeletal fluorosis, increased rate of bone fractures, decreased birth rates, increased rate of urolithiasis (kidney stones), impaired thyroid function, and impaired development of intelligence in children [1–5]. The data suggested that the north-eastern part of the Basara region having high fluoride concentration, which is unsuitable for drinking purposes. Hence, this unsuitable drinking water cause fluorosis in this Basara and surrounding villages, and especially based on the findings suggests, where the fluoride levels are in below maximum permissible limits that water ingests to the people to avoid further fluorosis.



http://ift.tt/2CaCaue

Dataset on information strategies for energy conservation: A field experiment in India

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Victor L. Chen, Magali A. Delmas, Stephen L. Locke, Amarjeet Singh
The data presented in this article are related to the research article entitled: "Information strategies for energy conservation: a field experiment in India" (Chen et al., 2017) [1]. The availability of high-resolution electricity data offers benefits to both utilities and consumers to understand the dynamics of energy consumption for example, between billing periods or times of peak demand. However, few public datasets with high-temporal resolution have been available to researchers on electricity use, especially at the appliance-level. This article describes data collected in a residential field experiment for 19 apartments at an Indian faculty housing complex during the period from August 1, 2013 to May 12, 2014. The dataset includes detailed information about electricity consumption. It also includes information on apartment characteristics and hourly weather variation to enable further studies of energy performance. These data can be used by researchers as training datasets to evaluate electricity usage consumption.



http://ift.tt/2DhWVTS

Data on empirically estimated corporate survival rate in Russia

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Evgeny A. Kuzmin
The article presents data on the corporate survival rate in Russia in 1991–2014. The empirical survey was based on a random sample with the average number of non-repeated observations (number of companies) for the survey each year equal to 75,958 (24,236 minimum and 126,953 maximum). The actual limiting mean error ∆p was 2.24% with 99% integrity. The survey methodology was based on a cross joining of various formal periods in the corporate life cycles (legal and business), which makes it possible to talk about a conventionally active time life of companies' existence with a number of assumptions. The empirical survey values were grouped by Russian regions and industries according to the classifier and consolidated into a single database for analysing the corporate life cycle and their survival rate and searching for deviation dependencies in calculated parameters. Preliminary and incomplete figures were available in the paper entitled "Survival Rate and Lifecycle in Terms of Uncertainty: Review of Companies from Russia and Eastern Europe" (Kuzmin and Guseva, 2016) [3]. The further survey led to filtered processed data with clerical errors excluded. These particular values are available in the article. The survey intended to fill a fact-based gap in various fundamental surveys that involved matters of the corporate life cycle in Russia within the insufficient statistical framework. The data are of interest for an analysis of Russian entrepreneurship, assessment of the market development and incorporation risks in the current business environment. A further heuristic potential is achievable through an ability of forecasted changes in business demography and model building based on the representative data set.



http://ift.tt/2Catwf8

Heavy metals analysis and quality assessment in drinking water – Khorramabad city, Iran

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Mansour Ghaderpoori, Bahram kamarehie, Ali Jafari, Afshin Ghaderpoury, Mohammadamin Karami
Continuous monitoring of drinking water quality is essential in terms of heavy metals and toxic substances. The general objective of this study were to determine the concentration of heavy metals in drinking water of Khorramabad city and to determine the water quality indices (The heavy metal pollution index and heavy metal evaluation index). According to the city map, 45 points were selected for drinking water sampling through the city distribution system. The results of this study showed that the average concentration of heavy metals such as Zn, Pb, Cd, Cr, and Cu were 47.01μg/l, 3.2μg/l, 0.42μg/l, 5.08μg/l, and 6.79μg/l, respectively. The HPI and HEI (water quality indices) for Zn, Pb, Cd, Cr, and Cu were 46.58, 46.58, respectively. According to the indices, the city drinking water quality is good in terms of heavy metals.



http://ift.tt/2DkQLCE

Data on fluoride concentration levels in semi-arid region of Medak, Telangana, South India

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Adimalla Narsimha, Venkatayogi Sudarshan
According to the World Health Organization recommendation, the optimal fluoride concentration levels in drinking water have to be in the range of 0.5 and 1.5mg/L since this permissible range is essential for normal mineralization of bones and teeth as well as for dental enamel formation in human's body Bell and budwig, 1970;Adimalla and Venkatayogi, 2017;Narsimha and Sudarshan, 2013,2016;2017[1,2,4,5,6]. If continues intake of high fluoride (>1.5) water can severely cause dental and skeletal fluorosis. The investigated area people majorly depend on groundwater for drinking purposes and fluoride concentration ranged from 0.2 to 7.4mg/L with mean concentration of 2.7mg/L and data was compared with WHO guidelines for drinking purposes. Overall, data reveals that the 57% of groundwater samples data was not safe for drinking purposes. Therefore, distribution of fluoride in the groundwater of Medak region in Telangana was suggested to intake drinking water, which are below level of fluoride concentration in the groundwater and take care about health implications.



http://ift.tt/2DiT0X0

Data-independent proteome profile of Mycoplasma gallisepticum under normal conditions and heat stress

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Ivan Butenko, Olga Pobeguts, Daria Matyushkina, Sergey Kovalchuk, Nickolay Anikanov, Gleb Fisunov, Vadim Govorun
The data reported is a large-scale untargeted proteome profile for Mycoplasma gallisepticum – a model organism for studying both regulation in genome-reduced bacteria and intracellular infection (Mazin et al., 2014) [1,2]. While seminal whole-proteome studies were performed on Mycoplasma genitalium [3] and a few proteome datasets are available for Mycoplasma pneumoniae, no data-independent (DIA) proteome profiling has been published for bacteria of Mycoplasma genus. Since DIA-based proteome profiling allows to extract evidence on presence and quantity of any protein of interest in a post-acquisition manner and the data presented is describing a model which is suitable to study both proteome regulation in general and details of mycoplasma infection process [4], the proteome profiling data presented here is of value for deep annotation. The data was deposited to the PRIDE repository (PXD008198).



http://ift.tt/2Ccrv2e

Smart campus: Data on energy consumption in an ICT-driven university

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Segun I. Popoola, Aderemi A. Atayero, Theresa T. Okanlawon, Benson I. Omopariola, Olusegun A. Takpor
In this data article, we present a comprehensive dataset on electrical energy consumption in a university that is practically driven by Information and Communication Technologies (ICTs). The total amount of electricity consumed at Covenant University, Ota, Nigeria was measured, monitored, and recorded on daily basis for a period of 12 consecutive months (January–December, 2016). Energy readings were observed from the digital energy meter (EDMI Mk10E) located at the distribution substation that supplies electricity to the university community. The complete energy data are clearly presented in tables and graphs for relevant utility and potential reuse. Also, descriptive first-order statistical analyses of the energy data are provided in this data article. For each month, the histogram distribution and time series plot of the monthly energy consumption data are analyzed to show insightful trends of energy consumption in the university. Furthermore, data on the significant differences in the means of daily energy consumption are made available as obtained from one-way Analysis of Variance (ANOVA) and multiple comparison post-hoc tests. The information provided in this data article will foster research development in the areas of energy efficiency, planning, policy formulation, and management towards the realization of smart campuses.



http://ift.tt/2DlyR2F