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https://www.readbyqxmd.com/read/27935841/the-cytoplasmic-tail-domain-of-epstein-barr-virus-gh-regulates-membrane-fusion-activity-through-altering-gh-binding-to-gp42-and-epithelial-cell-attachment
#1
Jia Chen, Theodore S Jardetzky, Richard Longnecker
: Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD)...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27934879/xp11-2-translocation-renal-cell-carcinoma-with-nono-tfe3-gene-fusion-morphology-prognosis-and-potential-pitfall-in-detecting-tfe3-gene-rearrangement
#2
Qiu-Yuan Xia, Zhe Wang, Ni Chen, Hua-Lei Gan, Xiao-Dong Teng, Shan-Shan Shi, Xuan Wang, Xue Wei, Sheng-Bing Ye, Rui Li, Heng-Hui Ma, Zhen-Feng Lu, Xiao-Jun Zhou, Qiu Rao
Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3 have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years...
December 9, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27933304/preclinical-validation-lv-il-12-transduction-of-patient-leukemia-cells-for-immunotherapy-of-aml
#3
Ju Huang, Yuanfeng Liu, Bryan C Au, Dwayne L Barber, Andrea Arruda, Axel Schambach, Michael Rothe, Mark D Minden, Christopher J Paige, Jeffrey A Medin
Interleukin-12 (IL-12) is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27932952/evaluating-tools-for-live-imaging-of-structural-plasticity-at-the-axon-initial-segment
#4
Adna S Dumitrescu, Mark D Evans, Matthew S Grubb
The axon initial segment (AIS) is a specialized neuronal compartment involved in the maintenance of axo-dendritic polarity and in the generation of action potentials. It is also a site of significant structural plasticity-manipulations of neuronal activity in vitro and in vivo can produce changes in AIS position and/or size that are associated with alterations in intrinsic excitability. However, to date all activity-dependent AIS changes have been observed in experiments carried out on fixed samples, offering only a snapshot, population-wide view of this form of plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932492/novel-regulatory-roles-of-mff-and-drp1-in-e3-ubiquitin-ligase-march5-dependent-degradation-of-mid49-and-mcl1-and-control-of-mitochondrial-dynamics
#5
Edward Cherok, Shan Xu, Sunan Li, Shweta Das, W Alex Meltzer, Michal Zalzman, Chunxin Wang, Mariusz Karbowski
MARCH5, an OMM-associated E3 ubiquitin ligase, controls mitochondrial function. Despite its importance, the mechanism and factors controlling MARCH5 activity are largely unknown. Here we report that the MARCH5 C-terminal domain plays a critical role in degradation of MARCH5 substrates, likely by facilitating release of ubiquitinated proteins from the OMM. We also found that the mitochondrial fission proteins Drp1 and Mff negatively regulate MARCH5's activity toward MiD49 and Mcl1. Knockouts of either Drp1 or Mff led to reduced expression, shorter half-lives, and increased ubiquitination of MiD49 and Mcl1...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27930669/development-of-rna-fish-assay-for-detection-of-oncogenic-fgfr3-tacc3-fusion-genes-in-ffpe-samples
#6
Masahiro Kurobe, Takahiro Kojima, Kouichi Nishimura, Shuya Kandori, Takashi Kawahara, Takayuki Yoshino, Satoshi Ueno, Yuichi Iizumi, Koji Mitsuzuka, Yoichi Arai, Hiroshi Tsuruta, Tomonori Habuchi, Takashi Kobayashi, Yoshiyuki Matsui, Osamu Ogawa, Mikio Sugimoto, Yoshiyuki Kakehi, Yoshiyuki Nagumo, Masakazu Tsutsumi, Takehiro Oikawa, Koji Kikuchi, Hiroyuki Nishiyama
INTRODUCTION AND OBJECTIVES: Oncogenic FGFR3-TACC3 fusions and FGFR3 mutations are target candidates for small molecule inhibitors in bladder cancer (BC). Because FGFR3 and TACC3 genes are located very closely on chromosome 4p16.3, detection of the fusion by DNA-FISH (fluorescent in situ hybridization) is not a feasible option. In this study, we developed a novel RNA-FISH assay using branched DNA probe to detect FGFR3-TACC3 fusions in formaldehyde-fixed paraffin-embedded (FFPE) human BC samples...
2016: PloS One
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#7
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27929754/hpv-16-e5-oncoprotein-is-expressed-in-early-stage-carcinogenesis-and-can-be-a-target-of-immunotherapy
#8
Paolini Francesca, Curzio Gianfranca, Marcelo Nazario Cordeiro, Silvia Massa, Luciano Mariani, Fulvia Pimpinelli, Antonio Carlos de Freitas, Rosella Franconi, Aldo Venuti
HPV16 persistent infection is a well-known condition that precedes human cancer development. High risk HPV E5 proteins cooperate with E6/E7 oncogenes to promote hyper-proliferation of infected cells leading to possible cancer progression. Thus, presence of E5 viral transcripts could be a key marker of active infection and, in turn, a target of immunotherapy. Purpose of the study is to detect E5 transcripts in clinical samples and to explore the activity of novel anti-HPV16 E5 DNA vaccines. HPV transcripts were detected by PCR with specific primers encompassing the splice-donor sites of E5 transcript...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929705/snapin-is-critical-for-lysosomal-acidification-and-autophagosome-maturation-in-macrophages
#9
Bo Shi, Qi-Quan Huang, Robert Birkett, Renee Doyle, Andrea Dorfleutner, Christian Stehlik, Congcong He, Richard M Pope
We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929061/structural-basis-for-epstein-barr-virus-host-cell-tropism-mediated-by-gp42-and-ghgl-entry-glycoproteins
#10
Karthik Sathiyamoorthy, Yao Xiong Hu, Britta S Möhl, Jia Chen, Richard Longnecker, Theodore S Jardetzky
Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. For Epstein-Barr virus (EBV), gHgL/gp42 complexes bind HLA class II to activate membrane fusion with B cells, but gp42 inhibits fusion and entry into epithelial cells. To clarify the mechanism by which gp42 controls the cell specificity of EBV infection, here we determined the structure of gHgL/gp42 complex bound to an anti-gHgL antibody (E1D1)...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27928633/rna-processing-body-p-body-dynamics-in-mesophyll-protoplasts-re-initiating-cell-division
#11
Dilbag S Bhullar, Michael B Sheahan, Ray J Rose
The ability of plants to regenerate lies in the capacity of differentiated cells to reprogram and re-enter the cell cycle. Reprogramming of cells requires changes in chromatin organisation and gene expression. However, there has been less focus on changes at the post transcription level. We have investigated P-bodies, sites of post transcriptional gene regulation, in plant cell reprogramming in cultured mesophyll protoplasts; by using a YFP-VARICOSE (YFP-VCSc) translational fusion. We showed an early increase in P-body number and volume, followed by a decline, then a subsequent continued increase in P-body number and volume as cell division was initiated and cell proliferation continued...
December 7, 2016: Protoplasma
https://www.readbyqxmd.com/read/27928549/switching-the-rate-and-pattern-of-cell-division-for-neural-tube-closure
#12
Yosuke Ogura, Yasunori Sasakura
The morphogenetic movement associated with neural tube closure (NTC) requires both positive and negative regulations of cell proliferation. The dual requirement of cell division control during NTC underscores the importance of the developmental control of cell division. In the chordate ascidian, midline fusions of the neural ectoderm and surface ectoderm (SE) proceed in the posterior-to-anterior direction, followed by a single wave of asynchronous and patterned cell division in SE. Before NTC, SE exhibits synchronous mitoses; disruption of the synchrony causes a failure of NTC...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27928159/effect-of-trem-1-blockade-and-single-nucleotide-variants-in-experimental-renal-injury-and-kidney-transplantation
#13
A Tammaro, J Kers, D Emal, I Stroo, G J D Teske, L M Butter, N Claessen, J Damman, M Derive, G Navis, S Florquin, J C Leemans, M C Dessing
Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development of delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition receptor expressed on a variety of innate immune cells. TREM-1 expression increases following acute and chronic renal injury. However, the function of TREM-1 in renal IR is still unclear. Here, we investigated expression and function of TREM-1 in a murine model of renal IR using different TREM-1 inhibitors: LP17, LR12 and TREM-1 fusion protein...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928014/histidine-375-modulates-cd4-binding-in-hiv-1-crf01_ae-envelope-glycoproteins
#14
Daria Zoubchenok, Maxime Veillette, Jérémie Prévost, Eric Sanders-Buell, Kshitij Wagh, Bette Korber, Agnès L Chenine, Andrés Finzi
: The envelope glycoproteins (Env) from human immunodeficiency virus type 1 (HIV-1) mediate viral entry. The binding of the HIV-1 gp120 glycoprotein to CD4 triggers conformational changes in gp120 that allow high-affinity binding to its coreceptors. Contrary to all other Envs from the same phylogenetic group M, which possess a serine (S) at position 375, those from CRF01_AE strains possess a histidine (H) at this location. This residue is part of the Phe43 cavity where residue 43 of CD4 (a phenylalanine) engages with the gp120...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27927993/suppression-of-extracellular-invertase-inhibitor-gene-expression-improves-seed-weight-in-soybean-glycine-max
#15
Xiaofei Tang, Tao Su, Mei Han, Lai Wei, Weiwei Wang, Zhiyuan Yu, Yongguo Xue, Hongbin Wei, Yejie Du, Steffen Greiner, Thomas Rausch, Lijun Liu
Cell wall invertase (CWI) and vacuolar invertase (VI) play multiple functions in plant growth. As well as depending on transcriptional and post-transcriptional regulation, there is growing evidence that CWI and VI are also subject to post-translational control by small inhibitory proteins. Despite the significance of this, genes encoding inhibitors, their molecular and biochemical properties, and their potential roles in regulating seed production have not been well documented in soybean (Glycine max). In this study, two invertase inhibitor isoforms, GmCIF1 and GmC/VIF2, were characterized to possess inhibitory activities in vitro via heterologous expression...
December 7, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27927751/rab2a-and-rab27a-cooperatively-regulate-transition-from-granule-maturation-to-exocytosis-through-the-dual-effector-noc2
#16
Kohichi Matsunaga, Masato Taoka, Toshiaki Isobe, Tetsuro Izumi
Exocytosis of secretory granules entails budding from the trans-Golgi network, sorting and maturation of cargo proteins, and trafficking and fusion to the plasma membrane. Rab27a regulates the late steps in this process, such as granule recruitment to the fusion site, whereas Rab2a functions in the early steps, such as granule biogenesis and maturation. Here, we demonstrate that these two small GTPases simultaneously bind to Noc2 in GTP-dependent manners, although Rab2a binds only after Rab27a has bound. In pancreatic beta cells, the ternary Rab2a-Noc2-Rab27a complex specifically localizes on perinuclear immature granules, whereas the binary Noc2-Rab27a complex localizes on peripheral mature granules...
December 7, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27927611/prenatal-myonuclei-play-a-crucial-role-for-skeletal-muscle-hypertrophy-in-rodents
#17
Fuminori Kawano, Yusuke Ono, Ryo Fujita, Atsuya Watanabe, Ryo Masuzawa, Kazuhiro Shibata, Shunsuke Hasegawa, Ken Nakata, Naoya Nakai
Multi-nucleated muscle fibers are formed by the fusion of myogenic progenitor cells during embryonic and fetal myogenesis. However, the role of prenatally incorporated myonuclei in the skeletal muscle fibers of adult animals is poorly understood. We demonstrated, using the muscle-specific reporter mice, that the prenatal myonuclei remained in the adult soleus muscle, although cardiotoxin injection caused the loss of prenatal myonuclei. Overloading by the tendon transection of synergists failed to induce compensatory hypertrophy in regenerated soleus muscle fibers of adult rats, whereas unloading by tail suspension normally induced the fiber atrophy...
December 7, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27926786/nut-midline-carcinoma-of-the-larynx-an-international-series-and-review-of-the-literature
#18
Henrik Hellquist, Christopher A French, Justin A Bishop, Andrés Coca-Pelaz, Evan J Propst, António Paiva Correia, Bo-Yee Ngan, Ronald Grant, Nicole A Cipriani, David Vokes, Rui Henrique, Fernando Pardal, Jose Ramon Vizcaino, Alessandra Rinaldo, Alfio Ferlito
AIMS: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that characteristically locates to the midline of the head and neck, and mediastinum. NMC is characterised by chromosomal rearrangements of the gene encoding nuclear protein in testis, NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare and we report a case series of seven cases...
December 7, 2016: Histopathology
https://www.readbyqxmd.com/read/27926526/use-of-capture-based-next-generation-sequencing-to-detect-alk-fusion-in-plasma-cell-free-dna-of-patients-with-non-small-cell-lung-cancer
#19
Shaohua Cui, Wei Zhang, Liwen Xiong, Feng Pan, Yanjie Niu, Tianqing Chu, Huimin Wang, Yizhuo Zhao, Liyan Jiang
Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK-positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK-positive samples were identified by capture-based NGS among the 24 samples with tissue ALK-positivity...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926512/depression-of-oncogenecity-by-dephosphorylating-and-degrading-bcr-abl
#20
Miao Gao, Zheng-Lan Huang, Kun Tao, Qing Xiao, Xin Wang, Wei-Xi Cao, Min Xu, Jing Hu, Wen-Li Feng
Aberrant phosphorylation and overexpression of BCR-ABL fusion protein are responsible for the main pathogenesis in chronic myeloid leukemia (CML). Phosphorylated BCR-ABL Y177 recruits GRB2 adaptor and triggers leukemic RAS-MAPK and PI3K-AKT signals. In this study, we engineered a SPOA system to dephosphorylate and degrade BCR-ABL by targeting BCR-ABL Y177. We tested its effect on BCR-ABL phosphorylation and expression, as well as cell proliferation and apoptosis in CML cells. We found that SPOA remarkably dephosphorylated BCR-ABL Y177, prevented GRB2 recruitment, and uncoupled RAS-MAPK and PI3K-AKT signals...
December 1, 2016: Oncotarget
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