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https://www.readbyqxmd.com/read/28088065/methionine-enkephalin-menk-mounts-antitumor-effect-via-regulating-dendritic-cells-dcs
#1
Yiming Meng, Xinghua Gao, Wenna Chen, Nicolas P Plotnikoff, Noreen Griffin, Guirong Zhang, Fengping Shan
MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity...
January 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088038/evidence-of-functional-duplicity-of-nestin-expression-in-the-adult-mouse-midbrain
#2
Parisa Farzanehfar, Shi Sheng Lu, Anupa Dey, Dharshani Musiienko, Hamzah Baagil, Malcolm K Horne, Tim D Aumann
Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28087693/de-novo-genome-and-transcriptome-assembly-of-the-canadian-beaver-castor-canadensis
#3
Si Lok, Tara A Paton, Zhuozhi Wang, Gaganjot Kaur, Susan Walker, Ryan K C Yuen, Wilson W L Sung, Joseph Whitney, Janet A Buchanan, Brett Trost, Naina Singh, Beverly Apresto, Nan Chen, Matthew Coole, Travis J Dawson, Karen Y Ho, Zhizhou Hu, Sanjeev Pullenayegum, Kozue Samler, Arum Shipstone, Fiona Tsoi, Ting Wang, Sergio L Pereira, Pirooz Rostami, Carol Ann Ryan, Amy Hin Yan Tong, Karen Ng, Yogi Sundaravadanam, Jared T Simpson, Burton K Lim, Mark D Engstrom, Christopher J Dutton, Kevin C R Kerr, Maria Franke, William Rapley, Richard F Wintle, Stephen W Scherer
The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 ×) long-reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by shortreads (80 ×) and checked for accuracy by congruency against an independent short-read assembly...
January 13, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#4
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087594/a-human-proteome-array-approach-to-identifying-key-host-proteins-targeted-by-toxoplasma-kinase-rop18
#5
Zhaoshou Yang, Yongheng Hou, Taofang Hao, Hee-Sool Rho, Jun Wan, Yizhao Luan, Xin Gao, Jianping Yao, Aihua Pan, Zhi Xie, Jiang Qian, Wanqin Liao, Heng Zhu, Xingwang Zhou
Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty-eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087360/the-synthetic-peptide-pnpp-19-induces-peripheral-antinociception-via-activation-of-no-cgmp-katp-pathway-role-of-enos-and-nnos
#6
A C N Freitas, G Silva, D F Pacheco, V Lemos, I D G Duarte, M E de Lima
BACKGROUND AND PURPOSE: The peptide PnPP-19, derived from the spider toxin PnTx2-6, potentiates erectile function by activating the nitrergic system. Since NO has been studied as an antinociceptive molecule and PnPP-19 is known to induce peripheral antinociception, we intended to evaluate whether PnPP-19 could induce peripheral antinociception through activation of this pathway. EXPERIMENTAL APPROACH: Nociceptive thresholds were measured by paw pressure test. PGE2 (2 μg/paw) was administered intraplantarly together with PnPP-19 and inhibitors/blockers of NOS, guanylyl cyclase and KATP channels...
January 10, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28086931/the-release-and-trans-synaptic-transmission-of-tau-via-exosomes
#7
Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow, Eva-Maria Mandelkow
BACKGROUND: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood...
January 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28086874/new-developments-in-anti-malarial-target-candidate-and-product-profiles
#8
REVIEW
Jeremy N Burrows, Stephan Duparc, Winston E Gutteridge, Rob Hooft van Huijsduijnen, Wiweka Kaszubska, Fiona Macintyre, Sébastien Mazzuri, Jörg J Möhrle, Timothy N C Wells
A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28081368/smart-metal-organic-framework-coatings-triggered-anti-biofilm-compound-release
#9
Birgit Claes, Tom Boudewijns, Laurens Muchez, Geert Hooyberghs, Erik V Van der Eycken, Jozef Vanderleyden, Hans P Steenackers, Dirk E De Vos
Metal-organic frameworks (MOFs) have a large potential for delivery of active molecules. Here, a MOF coating is investigated as a smart host matrix for triggered release of anti-biofilm compounds. Besides a coating consisting of the regular Fe-terephthalate MIL-88B(Fe), a new hydrophobic MIL-88B(Fe) coating is synthesized in hydrothermal conditions using palmitic acid as a lattice terminating group. These porous materials are used as a host matrix for the anti-biofilm compound 5-(4-chlorophenyl)-N-(2-isobutyl)-2-aminoimidazole, which has a specific biofilm inhibiting effect at concentrations at which no activity against planktonic cells is detected...
January 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28081210/mutations-in-hyal2-encoding-hyaluronidase-2-cause-a-syndrome-of-orofacial-clefting-and-cor-triatriatum-sinister-in-humans-and-mice
#10
Martina M A Muggenthaler, Biswajit Chowdhury, S Naimul Hasan, Harold E Cross, Brian Mark, Gaurav V Harlalka, Michael A Patton, Miho Ishida, Elijah R Behr, Sanjay Sharma, Kenneth Zahka, Eissa Faqeih, Brian Blakley, Mike Jackson, Melissa Lees, Vernon Dolinsky, Leroy Cross, Philip Stanier, Claire Salter, Emma L Baple, Fowzan S Alkuraya, Andrew H Crosby, Barbara Triggs-Raine, Barry A Chioza
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28080986/clinical-implications-of-globally-emerging-azole-resistance-in-aspergillus-fumigatus
#11
REVIEW
Jacques F Meis, Anuradha Chowdhary, Johanna L Rhodes, Matthew C Fisher, Paul E Verweij
Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28080202/chemical-probes-targeting-epigenetic-proteins-applications-beyond-oncology
#12
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors and antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about four thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro...
January 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28080054/bond-dissociation-energies-for-diatomic-molecules-containing-3d-transition-metals-benchmark-scalar-relativistic-coupled-cluster-calculations-for-twenty-molecules
#13
Lan Cheng, Jürgen Gauss, Branko Ruscic, Peter B Armentrout, John F Stanton
Benchmark scalar-relativistic coupled-cluster calculations for dissociation energies of the twenty diatomic molecules containing 3d transition metals in the 3dMLBE20 database (Xu et al., J. Chem. Theory Comput. 2015, 11, 2036) ) are reported. Electron correlation and basis set effects are systematically studied. The agreement between theory and experiment is in general satisfactory. For a subset of sixteen molecules, the standard deviation between computational and experimental values is 9 kJ/mol with the maximum deviation being 15 kJ/mol...
January 12, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28080023/microbial-nanoscopy-breakthroughs-challenges-and-opportunities
#14
Yves F Dufrêne
Studying the structure, properties, and interactions of microbial cells is key to understanding the functions of the microbiome. Recent advances in nanotechnology have offered new tools to probe microbes at the single-molecule and single-cell levels. In this issue of ACS Nano, Kumar et al. present an atomic force microscopy method that is capable of imaging the nanoscale organization of bacterial proteins in native, curved membranes. This study represents an important step forward in the development of nanoscopy techniques for analyzing biological systems with large curvature and vertical dimensions, such as membrane vesicles and bacterial cells...
January 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#15
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079891/crb3-regulates-contact-inhibition-by-activating-the-hippo-pathway-in-mammary-epithelial-cells
#16
Xiaona Mao, Pingping Li, Yaochun Wang, Zheyong Liang, Jie Liu, Juan Li, Yina Jiang, Gang Bao, Lei Li, Bofeng Zhu, Yu Ren, Xinhan Zhao, Jianmin Zhang, Yu Liu, Jin Yang, Peijun Liu
The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079382/single-molecule-transport-at-a-rectifying-gaas-contact
#17
Andrea Vezzoli, Richard James Brooke, Nicolo Ferri, Simon J Higgins, Walther Schwarzacher, Richard J Nichols
In most single- or few-molecule devices, the contact electrodes are simple ohmic resistors. Here we describe a new type of single-molecule device in which metal and semiconductor contact electrodes impart a function, namely current rectification, which is then modified by a molecule bridging the gap. We study junctions with the structure Au STM tip/X/n-GaAs substrate, where 'X' is either a simple alkanedithiol or a conjugated unit bearing thiol/methylthiol contacts, and we detect current jumps corresponding to the attachment and detachment of single molecules...
January 12, 2017: Nano Letters
https://www.readbyqxmd.com/read/28079365/twist-and-shout-single-molecule-mechanochemistry
#18
Hongbin Li, Gilbert C Walker
Chemical reactions can be accelerated by various means, including applied mechanical forces. If the direction of the force does not project well onto the desired reaction coordinate, then only poor acceleration is achieved. Recent developments in single polymer mechanics illustrate how to overcome this limitation, in a simple cis-trans isomerization reaction. Generalizing the approach, synthetic chemistry can be used to attach tethers to different parts of reacting molecular fragments to direct the force usefully...
January 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/28079286/design-synthesis-biological-evaluation-and-3d-qsar-analysis-of-podophyllotoxin-dioxazole-combination-as-tubulin-targeting-anticancer-agents
#19
Zi-Zhen Wang, Wen-Xue Sun, Xue Wang, Ya-Han Zhang, Han-Yue Qiu, Jin-Liang Qi, Yan-Jun Pang, Gui-Hua Lu, Xiao-Ming Wang, Fu-Gen Yu, Yong-Hua Yang
The advancement of cancer fighting drugs has never been a simple linear process. Those drugs design professionals begin to find inspiration from the nature after failing to find the ideal products by creative drugs design and high-throughput screening. To obtain new molecules for inhibiting tubulin, podophyllotoxin was adopted as the leading compound and 1,3,4-oxadiazole was brought in to the C-4 site of podophyllotoxin in this research. A series of seventeen podophyllotoxin derived esters have been achieved and then evaluated their antitumor activities against four different cancer cell lines: A549, MCF-7, HepG2 and HeLa...
January 12, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#20
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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