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https://www.readbyqxmd.com/read/29223138/plant-expressed-fc-fusion-protein-tetravalent-dengue-vaccine-with-inherent-adjuvant-properties
#1
Mi Young Kim, Alastair Copland, Kaustuv Nayak, Anmol Chandele, Muhammad Shamsher Ahmed, Qibo Zhang, Gil Reynolds Diogo, Matthew John Paul, Sven Hofmann, Moon-Sik Yang, Yong-Suk Jang, Julian K-C Ma, Rajko Reljic
Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi-Pasteur Denvaxia vaccine does not protect children under the age of nine and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant-expression to produce a humanised and highly immunogenic Poly-Immunoglobulin G Scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralising antibodies and evidence of cell-mediated immunity...
December 9, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29223097/recent-advances-in-microtubule-stabilizing-agents
#2
REVIEW
Ya-Nan Cao, Ling-Li Zheng, Dan Wang, Xiao-Xia Liang, Feng Gao, Xian-Li Zhou
Highly dynamic mitotic spindle microtubules are superb therapeutic targets for a group of chemically diverse and clinically successful anticancer drugs. Microtubule-targeted drugs disrupt microtubule dynamics in distinct ways, and they are primarily classified into two groups: microtubule destabilizing agents (MDAs), such as vinblastine, colchicine, and combretastatin-A4, and microtubule stabilizing agents (MSAs), such as paclitaxel and epothilones. Systematic discovery and development of new MSAs have been aided by extensive research on paclitaxel, yielding a large number of promising anticancer compounds...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29223096/discovery-of-aliphatic-chain-hydroxamates-containing-indole-derivatives-with-potent-class-i-histone-deacetylase-inhibitory-activities
#3
Shi-Wei Chao, Liang-Chieh Chen, Chia-Chun Yu, Chang-Yi Liu, Tony Eight Lin, Jih-Hwa Guh, Chen-Yu Wang, Chun-Yung Chen, Kai-Cheng Hsu, Wei-Jan Huang
Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC50 values of 3.9 and 4.5 nM for HDAC1, respectively...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29223083/activity-toxicity-molecular-docking-and-environmental-effects-of-three-imidazolinone-herbicides-enantiomers
#4
Jingqian Xie, Lu Zhao, Kai Liu, Fangjie Guo, Lidi Gao, Weiping Liu
All imidazolinone (IMI) herbicides are chiral consisting of two enantiomers; however, studies on the enantioselectivities of their interactions are limited. This study is a systematic assessment of the enantiomers and racemates of IMI herbicides, including semi-preparation and determination of absolute configurations, stereoselective bioactivity toward target organisms (Echinochloa crus-galli and Microcystis aeruginosa), and toxicity toward Michigan Cancer Foundation-7 (MCF-7) cells. R-imidazolinones were found to be more active than S-IMIs in the inhibition of target organisms, and neither enantiomer had estrogenic activity...
December 6, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29222951/neuronal-pas-domain-protein-4-npas4-controls-neuronal-homeostasis-in-pentylenetetrazole-induced-epilepsy-through-the-induction-of-homer1a
#5
Wei Shan, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Masahiro Sokabe, Kiyofumi Yamada
Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyper-excitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222932/a-fibers-mediate-cold-hyperalgesia-in-patients-with-oxaliplatin-induced-neuropathy
#6
Julia Forstenpointner, Violetta C Oberlojer, Dennis Naleschinski, Johanna Höper, Stephanie M Helfert, Andreas Binder, Janne Gierthmühlen, Ralf Baron
Cold hyperalgesia is a common side effect of oxaliplatin treatment; still the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin-induced acute neuropathy with (n=6) and without (n=7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A-fiber afferents in combination with quantitative sensory testing. Additionally, an interview-based questionnaire assessed the severity of symptoms and the impact on daily activities...
December 9, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29222786/nerve-growth-factor-induced-angiogenesis-1-endothelial-cell-tube-formation-assay
#7
Philip Lazarovici, Adi Lahiani, Galit Gincberg, Dikla Haham, Arnon Fluksman, Ofra Benny, Cezary Marcinkiewicz, Peter I Lelkes
Nerve growth factor (NGF) is a neurotrophin promoting survival, proliferation, differentiation, and neuroprotection in the embryonal and adult nervous system. NGF also induces angiogenic effects in the cardiovascular system, which may be beneficial in engineering new blood vessels and for developing novel anti-angiogenesis therapies for cancer. Angiogenesis is a cellular process characterized by a number of events, including endothelial cell migration, invasion, and assembly into capillaries. In vitro endothelial tube formation assays are performed using primary human umbilical vein endothelial cells, human aortic endothelial cells, and other human or rodent primary endothelial cells isolated from the vasculature of both tumors and normal tissues...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222774/preparation-of-adult-rat-sensory-neuron-cultures-and-their-application-to-growth-cone-turning-assays
#8
Christine A Webber, Douglas W Zochodne
The directional trajectory of growing peripheral nerve axons in the adult impacts their successful regeneration to denervated target tissues. Misdirected axons in neuromas, injured nerve trunks, or nerves with attempted repair diminish the success of regeneration. The behavior of adult rodent peripheral sensory neurons in vitro, in turn, is helpful in predicting axonal behavior in vivo. Here, we describe the adaptation of embryonic neuron growth cone turning assays, an important technique in developmental neurobiology, to adult rat sensory neurons...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222745/mir-26a-functions-as-a-tumor-suppressor-in-ambient-particulate-matter-bound-metal-triggered-lung-cancer-cell-metastasis-by-targeting-lin28b-il6-stat3-axis
#9
Yan-Yang Lu, Yi Lin, Dong-Xiao Ding, Shu Su, Qiao-Qiao Chi, You-Chi Zhang, Jian Sun, Xu Zhang, Hui-Min Zhu, Qian-Sheng Huang, Yu-Lang Chi, Guo-Zhu Ye, Shu Tao, Si-Jun Dong
Exposure to ambient particulate matter (PM) has been linked to the increasing incidence and mortality of lung cancer, but the principal toxic components and molecular mechanism remain to be further elucidated. In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 μg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion...
December 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29222693/neuroblastoma-pathogenesis-deregulation-of-embryonic-neural-crest-development
#10
REVIEW
Julie A Tomolonis, Saurabh Agarwal, Jason M Shohet
Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development...
December 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29222622/toll-like-receptor-4-knockdown-attenuates-brain-damage-and-neuroinflammation-after-traumatic-brain-injury-via-inhibiting-neuronal-autophagy-and-astrocyte-activation
#11
Hongsheng Jiang, Yanzhou Wang, Xin Liang, Xiaofeng Xing, Xiuzhen Xu, Caifeng Zhou
Toll-like receptor 4 (TLR4) has been linked to various pathophysiological conditions, such as traumatic brain injury (TBI). It is reported that posttraumatic neuroinflammation is an essential event in the progression of brain injury after TBI. Recent evidences indicate that TLR4 mediates glial phagocytic activity and inflammatory cytokines production. Thus, TLR4 may be an important therapeutic target for neuroinflammatory injury post-TBI. This study was designed to explore potential effects and underlying mechanisms of TLR4 in rats suffered from TBI...
December 8, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29222611/kiwifruit-svp2-controls-developmental-and-drought-stress-pathways
#12
Rongmei Wu, Tianchi Wang, Ben A W Warren, Susan J Thomson, Andrew C Allan, Richard C Macknight, Erika Varkonyi-Gasic
Genome-wide targets of Actinidia chinensis SVP2 confirm roles in ABA- and dehydration-mediated growth repression and reveal a conservation in mechanism of action between SVP genes of taxonomically distant Arabidopsis and a woody perennial kiwifruit. The molecular mechanisms underlying growth and dormancy in woody perennials are largely unknown. In Arabidopsis, the MADS-box transcription factor SHORT VEGETATIVE PHASE (SVP) plays a key role in the progression from vegetative to floral development, and in woody perennials SVP-like genes are also proposed to be involved in controlling dormancy...
December 8, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/29222528/structure-and-dynamics-of-cas9-hnh-domain-catalytic-state
#13
Zhicheng Zuo, Jin Liu
The bacterial CRISPR-Cas9 immune system has been harnessed as a powerful and versatile genome-editing tool and holds immense promise for future therapeutic applications. Despite recent advances in understanding Cas9 structures and its functional mechanism, little is known about the catalytic state of the Cas9 HNH nuclease domain, and identifying how the divalent metal ions affect the HNH domain conformational transition remains elusive. A deeper understanding of Cas9 activation and its cleavage mechanism can enable further optimization of Cas9-based genome-editing specificity and efficiency...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222508/crispr-cpf1-mediates-efficient-homology-directed-repair-and-temperature-controlled-genome-editing
#14
Miguel A Moreno-Mateos, Juan P Fernandez, Romain Rouet, Charles E Vejnar, Maura A Lane, Emily Mis, Mustafa K Khokha, Jennifer A Doudna, Antonio J Giraldez
Cpf1 is a novel class of CRISPR-Cas DNA endonucleases, with a wide range of activity across different eukaryotic systems. Yet, the underlying determinants of this variability are poorly understood. Here, we demonstrate that LbCpf1, but not AsCpf1, ribonucleoprotein complexes allow efficient mutagenesis in zebrafish and Xenopus. We show that temperature modulates Cpf1 activity by controlling its ability to access genomic DNA. This effect is stronger on AsCpf1, explaining its lower efficiency in ectothermic organisms...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222463/the-genome-sequence-of-bipolaris-cookei-reveals-mechanisms-of-pathogenesis-underlying-target-leaf-spot-of-sorghum
#15
Alex Z Zaccaron, Burton H Bluhm
Bipolaris cookei (=Bipolaris sorghicola) causes target leaf spot, one of the most prevalent foliar diseases of sorghum. Little is known about the molecular basis of pathogenesis in B. cookei, in large part due to a paucity of resources for molecular genetics, such as a reference genome. Here, a draft genome sequence of B. cookei was obtained and analyzed. A hybrid assembly strategy utilizing Illumina and Pacific Biosciences sequencing technologies produced a draft nuclear genome of 36.1 Mb, organized into 321 scaffolds with L50 of 31 and N50 of 378 kb, from which 11,189 genes were predicted...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222455/binding-modes-of-teixobactin-to-lipid-ii-molecular-dynamics-study
#16
Yang Liu, Yaxin Liu, Mary B Chan-Park, Yuguang Mu
Teixobactin (TXB) is a newly discovered antibiotic targeting the bacterial cell wall precursor Lipid II (LII). In the present work, four binding modes of TXB on LII were identified by a contact-map based clustering method. The highly flexible binary complex ensemble was generated by parallel tempering metadynamics simulation in a well-tempered ensemble (PTMetaD-WTE). In agreement with experimental findings, the pyrophosphate group and the attached first sugar subunit of LII are found to be the minimal motif for stable TXB binding...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222437/digital-pcr-for-gene-expression-impact-from-inherent-tissue-rna-degradation
#17
Melanie J Millier, Lisa K Stamp, Paul A Hessian
Subtle molecular differences indicate the heterogeneity present in a number of disease settings. Digital-PCR (dPCR) platforms achieve the necessary levels of sensitivity and accuracy over standard quantitative RT-PCR (qPCR) that promote their use for such situations, detecting low abundance transcript and subtle changes from gene expression. An underlying requisite is good quality RNA, principally dictated by appropriate tissue handling and RNA extraction. Here we consider the application of dPCR to measures of gene expression in pathological tissues with inherent necrosis, focusing on rheumatoid subcutaneous nodules...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222335/single-cell-transcriptome-sequencing-reveals-that-cell-division-cycle-5-like-protein-is-essential-for-porcine-oocyte-maturation
#18
Xiao-Man Liu, Yan-Kui Wang, Yun-Hua Liu, Xiao-Xia Yu, Pei-Chao Wang, Xuan Li, Zhi-Qiang Du, Cai-Xia Yang
The brilliant cresyl blue (BCB) test is used in both basic biological research and assisted reproduction to identify oocytes likely to be developmentally competent. However, the underlying molecular mechanism targeted by the BCB test is still unclear. To explore this question, we first confirmed that BCB-positive porcine oocytes had higher rates of meiotic maturation, better rates of cleavage and development into blastocysts, and lower death rates. Subsequent single-cell transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes identified 155 genes that were significantly differentially expressed between BCB-negative and BCB-positive oocytes...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222306/therapy-of-primary-cns-lymphoma-role-of-intensity-radiation-and-novel-agents
#19
REVIEW
Andrés José María Ferreri
Primary central nervous system (CNS) lymphomas represent a subgroup of malignancies with specific characteristics, an aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumor burden and histological type. Despite the high sensitivity to conventional chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment efficacy is limited by several factors, including the biology and microenvironment of this malignancy and the "protective" effect of the blood-brain barrier, which limits the access of most drugs to the CNS...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#20
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
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