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https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#1
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906130/braf-activates-pax3-to-control-muscle-precursor-cell-migration-during-forelimb-muscle-development
#2
Jaeyoung Shin, Shuichi Watanabe, Soraya Hoelper, Marcus Krüger, Sawa Kostin, Jochen Pöling, Thomas Kubin, Thomas Braun
Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27903989/repression-of-yap-by-nctd-disrupts-nsclc-progression
#3
Jiwei Guo, Yan Wu, Lijuan Yang, Jing Du, Kaikai Gong, Weiwei Chen, Juanjuan Dai, XueLin Li, Sichuan Xi
The efficacy of available lung cancer therapeutic interference is significantly limited by various resistance mechanisms to those drugs. Activation of the oncogene YAP underlying the initiation, progression, and metastasis of lung cancer associates with poor prognosis and confers drug resistance against targeted therapy. In this study, we evaluated the specificity of norcantharidin (NCTD) in repressing YAP to inhibit non-small cell lung carcinoma (NSCLC) progression. Our study revealed that YAP signal pathways were aberrantly activated in lung cancer tissues and cells which rendered more proliferative and invasive phenotypes to human lung cancer cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903745/inhibiting-microglia-expansion-prevents-diet-induced-hypothalamic-and-peripheral-inflammation
#4
Caroline André, Omar Guzman-Quevedo, Charlotte Rey, Julie Rémus-Borel, Samantha Clark, Ashley Castellanos-Jankiewicz, Elodie Ladeveze, Thierry Leste-Lasserre, Agnes Nadjar, Djoher Nora Abrous, Sophie Laye, Daniela Cota
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fat mass, and specifically showed increased microglia number in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet, since feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#5
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27903703/retinal-and-non-retinal-contributions-to-extraclassical-surround-suppression-in-the-lateral-geniculate-nucleus
#6
Tucker G Fisher, Henry J Alitto, W Martin Usrey
: Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain control, and temporal features of visual responses. Despite evidence for the involvement of both retinal and non-retinal circuits in the generation of extraclassical suppression, we lack an understanding of the relative roles played by these pathways and how they interact during visual stimulation...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903492/angiotensinogen-import-in-isolated-proximal-tubules-evidence-for-mitochondrial-trafficking-and-uptake
#7
Bryan A Wilson, Nildris Cruz-Diaz, Yixin Su, James C Rose, TanYa M Gwathmey, Mark C Chappell
The renal proximal tubules are a key functional component of the kidney and express the angiotensin precursor angiotensinogen; however, it is unclear the extent that tubular angiotensinogen reflects local synthesis or internalization. Therefore, the current study established the extent that angiotensinogen is internalized by proximal tubules and the intracellular distribution. Proximal tubules were isolated from the kidney cortex of male sheep by enzymatic digestion and a discontinuous Percoll gradient. Tubules were incubated with radiolabeled 125I-angiotensinogen for 2 hrs at 37°C in serum/phenol-free DMEM/F12 media...
November 30, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27903131/hypoxic-expansion-of-human-mesenchymal-stem-cells-enhances-3d-maturation-of-tissue-engineered-intervertebral-discs
#8
Katherine Deline Hudson, Lawrence J Bonassar
Culture of three dimensional (3D) constructs in hypoxic conditions (1-5% O2) has been shown to increase production of extracellular matrix (ECM) components in primary intervertebral disc (IVD) cells, and drive chondrogenesis of human mesenchymal stem cells (MSCs). Growing evidence that suggests that two dimensional (2D) expansion under hypoxic conditions may have an even greater influence on chondrogenesis in MSCs. This study aims to determine the effects of hypoxia during 2D expansion and subsequent 3D culture on the in vitro maturation of tissue engineering IVDs (TE-IVDs) made with human MSCs, using a previously developed TE-IVD system...
November 30, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27902702/selective-inhibitor-of-nuclear-export-sine-compounds-alter-new-world-alphavirus-capsid-localization-and-reduce-viral-replication-in-mammalian-cells
#9
Lindsay Lundberg, Chelsea Pinkham, Cynthia de la Fuente, Ashwini Brahms, Nazly Shafagati, Kylie M Wagstaff, David A Jans, Sharon Tamir, Kylene Kehn-Hall
The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27902468/synthesis-of-a-cell-penetrating-peptide-modified-superparamagnetic-iron-oxide-and-mri-detection-of-bladder-cancer
#10
Chen Ding, Kaijie Wu, Weiyi Wang, Zhenfeng Guan, Lei Wang, Xinyang Wang, Rong Wang, Li Liu, Jinhai Fan
Bladder cancer is the most common malignancy of the urinary tract for which the accurate measurement of minimal residual disease is critical to treatment and determining prognosis. Although cystoscope examination and voided urine cytology remain the current standard of care for detecting residual disease, these approaches are limited by mechanical trauma and lack sensitivity. To develop a new accurate noninvasive method, we developed a novel contrast agent where the surface of superparamagnetic iron oxide (SPIO) nanoparticles is functionalized with a bladder cancer-specific fluorescein isothiocyanate (FITC) labeled cell penetrating peptide (CPP)-polyarginine peptides (R11) for active targeting and imaging...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902378/neuronal-retrograde-transport-of-borna-disease-virus-occurs-in-signaling-endosomes
#11
Caroline M Charlier, Solène Debaisieux, Charlotte Foret, Anne Thouard, Giampetro Schiavo, Daniel Gonzalez-Dunia, Cécile Evelyne Malnou
Long-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuro-invasive viruses, such as Borna Disease Virus (BDV), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. Although BDV is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. In this work, we combined different methodological approaches, such as confocal microscopy and biochemical purification of endosomes, to study BDV retrograde transport...
November 8, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902361/qualitative-proteomic-analysis-of-tipula-oleracea-nudivirus-tonv-occlusion-bodies
#12
Anne Bézier, Grégoire Harichaux, Karine Musset, Valérie Labas, Elisabeth A Herniou
Nudiviruses are arthropod-specific large double-stranded circular DNA viruses, related to baculoviruses, which replicate in the nucleus of the cells they infect. Up to date six fully sequenced nudiviral genomes are available in databases and protein profile from nudivirus particles were mainly characterized by polyacrylamide gel electrophoresis. However, only few direct matches were completed between genomic and proteomic data to the exception of the major occlusion body protein from Penaeus monodon nudivirus (PmNV) and four nucleocapsid proteins from Helicoverpa zea nudivirus 2 (HzNV-2)...
November 16, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901466/differentiation-alters-stem-cell-nuclear-architecture-mechanics-and-mechano-sensitivity
#13
Su-Jin Heo, Tristan P Driscoll, Stephen D Thorpe, Nandan L Nerurkar, Brendon M Baker, Michael T Yang, Christopher S Chen, David A Lee, Robert L Mauck
Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical loading induced calcium signaling and differentiated marker expression...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27901130/huwe1-plays-important-role-in-mouse-preimplantation-embryo-development-and-the-dysregulation-is-associated-with-poor-embryo-development-in-humans
#14
L J Chen, W M Xu, M Yang, K Wang, Y Chen, X J Huang, Q H Ma
HUWE1 is a HECT domain containing ubiquitin ligase implicated in neurogenesis, spermatogenesis and cancer development. The purpose of the current study is to investigate the role of HUWE1 in early embryo development. Here we demonstrate that Huwe1 is expressed in both nucleus and cytoplasm of preimplantation mouse embryos as well as gametes. Hypoxia (5% O2) treatment could significantly increase Huwe1 expression during mouse embryo development process. HUWE1 knockdown inhibited normal embryonic development and reduced blastocyst formation, and increased apoptotic cell numbers were observed in the embryos of HUWE1 knockdown group...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900558/the-role-of-viral-protein-ac34-in-nuclear-relocation-of-subunits-of-the-actin-related-protein-2-3-complex
#15
Jingfang Mu, Yongli Zhang, Yangyang Hu, Xue Hu, Yuan Zhou, Xinwen Chen, Yun Wang
The actin nucleator actin-related protein complex (Arp2/3) is composed of seven subunits: Arp2, Arp3, p40/ARPC1 (P40), p34/ARPC2 (P34), p21/ARPC3 (P21), p20/ARPC4 (P20), and p16/ARPC5 (P16). Arp2/3 plays crucial roles in a variety of cellular activities through regulation of actin polymerization. Autographa californica multiple nucleopolyhedrovirus (AcMNPV), one of the best-studied alphabaculoviruses, induces Arp2/3 nuclear relocation and mediates nuclear actin polymerization to assist in virus replication...
December 5, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27900041/immunohistochemical-expression-and-serum-level-of-survivin-protein-in-colorectal-cancer-patients
#16
Katarzyna Jakubowska, Anna Pryczynicz, Violetta Dymicka-Piekarska, Waldemar Famulski, Katarzyna Guzińska-Ustymowicz
Survivin is one of the apoptosis-related inhibitors that is associated with a more aggressive behavior and a poor prognosis in numerous types of malignancies, including colorectal cancer (CRC). The objective of the present study was to perform immunohistochemical tissue analysis of survivin expression and serum analysis of survivin levels in CRC patients. The study group consisted of 55 CRC patients. Survivin expression was assessed by immunohistochemistry in 38 patients using monoclonal antibodies. Color reactions were observed in the nucleus and cytoplasm of the cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899926/bioinformatic-analyses-of-subgroup-a-members-of-the-wheat-bzip-transcription-factor-family-and-functional-identification-of-tabzip174-involved-in-drought-stress-response
#17
Xueyin Li, Biane Feng, Fengjie Zhang, Yimiao Tang, Liping Zhang, Lingjian Ma, Changping Zhao, Shiqing Gao
Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum) is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis, and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27899890/causal-role-of-thalamic-interneurons-in-brain-state-transitions-a-study-using-a-neural-mass-model-implementing-synaptic-kinetics
#18
Basabdatta Sen Bhattacharya, Thomas P Bond, Louise O'Hare, Daniel Turner, Simon J Durrant
Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons, and constitute around 20-25% of the LGN cell population. However, there is a definite gap in knowledge about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay (TCR), thalamic reticular nucleus (TRN), to study the causality of IN on LGN oscillations and state-transitions...
2016: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/27899605/poly-a-specific-ribonuclease-regulates-the-processing-of-small-subunit-rrnas-in-human-cells
#19
Hideaki Ishikawa, Harunori Yoshikawa, Keiichi Izumikawa, Yutaka Miura, Masato Taoka, Yuko Nobe, Yoshio Yamauchi, Hiroshi Nakayama, Richard J Simpson, Toshiaki Isobe
Ribosome biogenesis occurs successively in the nucleolus, nucleoplasm, and cytoplasm. Maturation of the ribosomal small subunit is completed in the cytoplasm by incorporation of a particular class of ribosomal proteins and final cleavage of 18S-E pre-rRNA (18S-E). Here, we show that poly(A)-specific ribonuclease (PARN) participates in steps leading to 18S-E maturation in human cells. We found PARN as a novel component of the pre-40S particle pulled down with the pre-ribosome factor LTV1 or Bystin. Reverse pull-down analysis revealed that PARN is a constitutive component of the Bystin-associated pre-40S particle...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899576/the-nuclear-and-organellar-trna-derived-rna-fragment-population-in-arabidopsis-thaliana-is-highly-dynamic
#20
Valérie Cognat, Geoffrey Morelle, Cyrille Megel, Stéphanie Lalande, Jean Molinier, Timothée Vincent, Ian Small, Anne-Marie Duchêne, Laurence Maréchal-Drouard
In the expanding repertoire of small noncoding RNAs (ncRNAs), tRNA-derived RNA fragments (tRFs) have been identified in all domains of life. Their existence in plants has been already proven but no detailed analysis has been performed. Here, short tRFs of 19-26 nucleotides were retrieved from Arabidopsis thaliana small RNA libraries obtained from various tissues, plants submitted to abiotic stress or fractions immunoprecipitated with ARGONAUTE 1 (AGO1). Large differences in the tRF populations of each extract were observed...
November 28, 2016: Nucleic Acids Research
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