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https://www.readbyqxmd.com/read/28819303/automated-segmentation-of-light-sheet-fluorescent-imaging-to-characterize-experimental-doxorubicin-induced-cardiac-injury-and-repair
#1
René R Sevag Packard, Kyung In Baek, Tyler Beebe, Nelson Jen, Yichen Ding, Feng Shi, Peng Fei, Bong Jin Kang, Po-Heng Chen, Jonathan Gau, Michael Chen, Jonathan Y Tang, Yu-Huan Shih, Yonghe Ding, Debiao Li, Xiaolei Xu, Tzung K Hsiai
This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819009/the-aaa-atpase-p97-a-cellular-multitool
#2
REVIEW
Lasse Stach, Paul S Freemont
The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes...
August 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28818608/potential-resistance-mechanisms-revealed-by-targeted-sequencing-from-lung-adenocarcinoma-patients-with-primary-resistance-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-tkis
#3
Jia Zhong, Lei Li, Zhijie Wang, Hua Bai, Gai Fei, Jian Chunduan, Jun Zhao, Minglei Zhuo, Yuyang Wang, Shuhang Wang, Wanchun Zang, Meina Wu, Tongtong An, Guanhua Rao, Jie Wang
BACKGROUND: EGFR-TKIs have greatly improved the prognosis of lung adenocarcinoma. However, approximately 5%-10% lung adenocarcinoma patients with EGFR sensitive mutations have primary resistance to EGFR-TKIs treatment. The underlying mechanism is unknown. METHODS: This study used next-generation sequencing (NGS) to explore the mechanisms of primary resistance by analyzing 11 patients with primary resistance and 11 patients sensitive to EGFR-TKIs. NGS targeted sequencing was performed on the Illumina X platform for 483 cancer-related genes...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28818570/prevalence-and-risk-factors-of-deep-vein-thrombosis-in-patients-undergoing-lumbar-spine-surgery
#4
Koji Yamasaki, Masahiro Hoshino, Keita Omori, Hidetoshi Igarashi, Takashi Tsuruta, Hiroyuki Miyakata, Yasuhiro Nemoto, Hiromi Matsuzaki, Takanori Iriuchishima
BACKGROUND: Spinal surgery is classified as a moderate risk for DVT. The occurrence of DVT after various spinal surgical procedures was reviewed retrospectively, and the perioperative risk factors in the high-risk group were identified. In addition, the administration of the factor Xa inhibitor to DVT subjects with unstable thrombosis was evaluated to reveal its effectiveness in the prevention of PTE and postoperative complications. METHODS: This study included 588 subjects who underwent lumbar spine surgery...
August 14, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28816267/-nuclear-export-signal-of-androgen-receptor-regulated-of-androgen-receptor-stability-in-prostate-cancer
#5
Y Q Gong, C J Zhang, S M He, X S Li, L Q Zhou, Y L Guo
OBJECTIVE: To investigate the mechanisms of nuclear export signal of androgen receptor (NES(AR)) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer. METHODS: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NES(AR) (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NES(AR), and lysine mutants of NES(AR) pEGFP-NES(AR) K776R, pEGFP-NES(AR) K807R and pEGFP-NES(AR) K776R/K807R, were transiently transfected into prostate cancer cell line PC3...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28815880/immunogenicity-efficacy-and-safety-of-nuwiq-%C3%A2-human-cl-rhfviii-in-previously-untreated-patients-with-severe-haemophilia-a-interim-results-from-the-nuprotect-study
#6
R J Liesner, M Abashidze, O Aleinikova, C Altisent, M J Belletrutti, A Borel-Derlon, M Carcao, H Chambost, A K C Chan, L Dubey, J Ducore, N A Fouzia, M Gattens, Y Gruel, B Guillet, N Kavardakova, M El Khorassani, A Klukowska, T Lambert, S Lohade, M Sigaud, V Turea, J K M Wu, V Vdovin, A Pavlova, M Jansen, L Belyanskaya, O Walter, S Knaub, E J Neufeld
INTRODUCTION: Nuwiq(®) (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq(®) in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq(®) in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. METHODS: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum...
August 16, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28814521/hiv-fusion-in-dendritic-cells-mainly-occurs-at-the-surface-and-is-limited-by-low-cd4-levels
#7
Lise Chauveau, Daniel Aaron Donahue, Blandine Monel, Francoise Porrot, Timothée Bruel, Lea Richard, Nicoletta Casartelli, Olivier Schwartz
HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in a large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with VSV-G strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or contrarily, in an endocytic compartment. Here, we examined the pathways of HIV-1 entry in MDDCs...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28808421/crosstalk-between-mitochondrial-fission-and-oxidative-stress-in-paraquat-induced-apoptosis-in-mouse-alveolar-type-ii-cells
#8
Guangju Zhao, Kaiqiang Cao, Changqin Xu, Aifang Sun, Wang Lu, Yi Zheng, Haixiao Li, Guangliang Hong, Bing Wu, Qiaomeng Qiu, Zhongqiu Lu
Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c)...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808086/a-pharmacological-study-of-arabidopsis-cell-fusion-between-the-persistent-synergid-and-endosperm
#9
Kazuki Motomura, Tomokazu Kawashima, Frédéric Berger, Tetsu Kinoshita, Tetsuya Higashiyama, Daisuke Maruyama
Cell fusion is a pivotal process in fertilization and multinucleate cell formation. A plant cell is ubiquitously surrounded by hard cell wall, and very few cell fusions have been observed except for gamete fusions. We recently reported that the fertilized central cell (the endosperm) absorbs the persistent synergid, a highly differentiated cell necessary for pollen tube attraction. The synergid-endosperm fusion (SE fusion) appears to eliminate the persistent synergid from fertilized ovule in Arabidopsis thaliana Here, we analyzed the effects of various inhibitors on SE fusion by an in vitro-culture system...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28806414/alpha-tocopherol-attenuates-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-npm-alk
#10
Yuki Uchihara, Fumihito Ueda, Kenji Tago, Yosuke Nakazawa, Tomoyuki Ohe, Tadahiko Mashino, Shigenobu Yokota, Tadashi Kasahara, Hiroomi Tamura, Megumi Funakoshi-Tago
Anaplastic large cell lymphomas (ALCL) are mainly characterized by harboring the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The ALK inhibitor, crizotinib specifically induced apoptosis in Ba/F3 cells expressing NPM-ALK by inhibiting the activation of NPM-ALK and its downstream molecule, signal transducer and activator of transcription factor 3 (STAT3). We found that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties...
2017: PloS One
https://www.readbyqxmd.com/read/28806393/craf-gene-fusions-in-pediatric-low-grade-gliomas-define-a-distinct-drug-response-based-on-dimerization-profiles
#11
P Jain, T M Fierst, H J Han, T E Smith, A Vakil, P J Storm, A C Resnick, A J Waanders
Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28802831/validation-of-a-targeted-rna-sequencing-assay-for-kinase-fusion-detection-in-solid-tumors
#12
Julie W Reeser, Dorrelyn Martin, Jharna Miya, Esko A Kautto, Ezra Lyon, Eliot Zhu, Michele R Wing, Amy Smith, Matthew Reeder, Eric Samorodnitsky, Hannah Parks, Karan R Naik, Joseph Gozgit, Nicholas Nowacki, Kurtis D Davies, Marileila Varella-Garcia, Lianbo Yu, Aharon G Freud, Joshua Coleman, Dara L Aisner, Sameek Roychowdhury
Kinase gene fusions are important drivers of oncogenic transformation and can be inhibited with targeted therapies. Clinical grade diagnostics using RNA sequencing to detect gene rearrangements in solid tumors are limited, and the few that are available require prior knowledge of fusion break points. To address this, we have analytically validated a targeted RNA sequencing assay (OSU-SpARKFuse) for fusion detection that interrogates complete transcripts from 93 kinase and transcription factor genes. From a total of 74 positive and 36 negative control samples, OSU-SpARKFuse had 93...
August 8, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28802000/pmepa1-induced-by-rankl-p38-mapk-pathway-has-a-novel-role-in-osteoclastogenesis
#13
Noboru Funakubo, Xianghe Xu, Toshio Kukita, Seiji Nakamura, Hiroshi Miyamoto, Akiko Kukita
Osteoclasts are multinucleated cells formed by fusion of preosteoclasts (POCs) derived from cells of the monocyte/macrophage lineage. We have reported a culture system that supports the formation of POCs from stroma-depleted rat bone marrow cells. Global gene expression analysis of this culture system identified genes highly expressed in POCs. Here, we have analyzed the expression and function of one of these highly expressed genes, prostate transmembrane protein androgen induced 1 (Pmepa1), a target of TGF-β and binds Nedd4 ubiquitin ligase, which plays a role in intracellular trafficking...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28798402/nutlin-3-enhances-the-bortezomib-sensitivity-of-p53-defective-cancer-cells-by-inducing-paraptosis
#14
Dong Min Lee, In Young Kim, Min Ji Seo, Mi Ri Kwon, Kyeong Sook Choi
The proteasome inhibitor, bortezomib, is ineffective against many solid tumors. Nutlin-3 is a potent antagonist of human homolog of murine double minute 2/p53 interaction exhibiting promising therapeutic anti-cancer activity. In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib alone did not markedly alter cellular morphology, and nutlin-3 alone induced only a transient mitochondrial dilation...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28798075/cytokines-of-the-il-1-family-recognized-targets-in-chronic-inflammation-underrated-in-organ-transplantations
#15
REVIEW
Ilja Striz
Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28797659/a-preliminary-evaluation-study-of-new-generation-multiplex-str-kits-comprising-of-the-codis-core-loci-and-the-european-standard-set-loci
#16
Jolena Ying Ying Tan, Yuen Peng Tan, Shilen Ng, Annabel Suan Tay, Yong Han Phua, Wei Jie Tan, Terenze Yao Rui Ong, Li Min Chua, Christopher Kiu Choong Syn
The GlobalFiler™ (Life Technologies), Investigator(®) 24plex QS (Qiagen), and PowerPlex(®) Fusion 6C (Promega) kits are the latest generation 6-dye fluorescent chemistry STR-PCR amplification kits. These kits allow for the simultaneous amplification of the CODIS core loci and the European Standard Set loci, as well as a few Y-STR loci in addition to the standard sex-determining marker Amelogenin. The present study was designed to be a preliminary evaluation of the three STR-PCR kits in terms of sensitivity, profile recovery from degraded DNA samples, tolerance to PCR inhibitors, and detection of minor components in DNA mixtures...
July 25, 2017: Journal of Forensic and Legal Medicine
https://www.readbyqxmd.com/read/28795691/evaluation-of-in-vitro-and-in-vivo-activity-of-a-multityrosine-kinase-inhibitor-al3810-against-human-thyroid-cancer
#17
Qin Xie, Hui Chen, Jing Ai, Ying-Lei Gao, Mei-Yu Geng, Jian Ding, Yi Chen
Thyroid cancer is the most common type of endocrine neoplasia. Despite recent breakthroughs in treatment of the disease, the treatment of advanced, progressive thyroid cancers remains challenging with limited therapeutic options available. In this study, we evaluated a novel and orally bioavailable small-molecule multiple tyrosine kinases inhibitor, AL3810, in preclinical models of thyroid cancer in vitro and in vivo. AL3810 (2-5 μmol/L) dose-dependently inhibited the proliferation of human thyroid cancer cell lines TT, SW579 and TPC-1 in vitro with IC50 values ranging from 0...
August 10, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28794284/genomic-profiling-of-er-breast-cancers-after-short-term-estrogen-suppression-reveals-alterations-associated-with-endocrine-resistance
#18
Jennifer M Giltnane, Katherine E Hutchinson, Thomas P Stricker, Luigi Formisano, Christian D Young, Monica V Estrada, Mellissa J Nixon, Liping Du, Violeta Sanchez, Paula Gonzalez Ericsson, Maria G Kuba, Melinda E Sanders, Xinmeng J Mu, Eliezer M Van Allen, Nikhil Wagle, Ingrid A Mayer, Vandana Abramson, Henry Gόmez, Monica Rizzo, Weiyi Toy, Sarat Chandarlapaty, Erica L Mayer, Jason Christiansen, Danielle Murphy, Kerry Fitzgerald, Kai Wang, Jeffrey S Ross, Vincent A Miller, Phillip J Stephens, Roman Yelensky, Levi Garraway, Yu Shyr, Ingrid Meszoely, Justin M Balko, Carlos L Arteaga
Inhibition of proliferation in estrogen receptor-positive (ER(+)) breast cancers after short-term antiestrogen therapy correlates with long-term patient outcome. We profiled 155 ER(+)/human epidermal growth factor receptor 2-negative (HER2(-)) early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 10 to 21 days before surgery. Twenty-one percent of tumors remained highly proliferative, suggesting that these tumors harbor alterations associated with intrinsic endocrine therapy resistance...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28794268/force-induced-transcellular-tunnel-formation-in-endothelial-cells
#19
Win Pin Ng, Kevin D Webster, Caroline Stefani, Eva M Schmid, Emmanuel Lemichez, Patricia Bassereau, Daniel A Fletcher
The endothelium serves as a protective semipermeable barrier in blood vessels and lymphatic vessels. Leukocytes and pathogens can pass directly through the endothelium by opening holes in endothelial cells, known as transcellular tunnels, which are formed by contact and self-fusion of the apical and basal plasma membranes. Here we test the hypothesis that the actin cytoskeleton is the primary barrier to transcellular tunnel formation using a combination of atomic force microscopy and fluorescence microscopy of live cells...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28792845/discovery-of-pan-autophagy-inhibitors-through-a-high-throughput-screen-highlights-macroautophagy-as-an-evolutionarily-conserved-process-across-3-eukaryotic-kingdoms
#20
Piyush Mishra, Adrian N Dauphinee, Carl Ward, Sovan Sarkar, Arunika H L A N Gunawardena, Ravi Manjithaya
Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate autophagic degradation of peroxisomes in the budding yeast Saccharomyces cerevisiae. Being a pathway-specific rather than a target-driven assay, we identified small molecule modulators that acted at key steps of autophagic flux...
August 9, 2017: Autophagy
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