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Maria Askmyr, Sofia von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos
Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML...
2017: PloS One
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
Yu Xiong, Manon Mouginot, Loic Reppel, Chongsheng Qian, Jean-Francois Stoltz, Danièle Bensoussan, Véronique Decot
The ability of natural killer (NK) cells to kill tumor cells without antigen recognition makes them appealing as an adoptive immunotherapy. However, NK cells are not routinely used in the context of leukemic relapse after hematopoietic stem cell transplantation. Patients who experience relapse can be treated with donor lymphocyte infusions (DLI) based on small-cell fractions frozen at the time of transplantation. Since peripheral blood stem cells (PBSCs) are increasingly used as a stem cell source and as a source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype, subset repartition, and functionality...
October 10, 2017: Immunologic Research
Claus Wasternack, Miroslav Strnad
Jasmonates (JAs) are signals in plant stress responses and development. One of the first observed and prominent responses to JAs is the induction of biosynthesis of different groups of secondary compounds. Among them are nicotine, isoquinolines, glucosinolates, anthocyanins, benzophenanthridine alkaloids, artemisinin, and terpenoid indole alkaloids (TIAs), such as vinblastine. This brief review describes modes of action of JAs in the biosynthesis of anthocyanins, nicotine, TIAs, glucosinolates and artemisinin...
October 7, 2017: New Biotechnology
Ying Wang, Yanli Xia, Dong Kuang, Yaqi Duan, Guoping Wang
AIMS: Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. MAIN METHODS: CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot...
October 3, 2017: Life Sciences
Haiou Li, Ruifeng Yao, Sui Ma, Shuai Hu, Suhua Li, Yupei Wang, Chun Yan, Daoxin Xie, Jianbin Yan
Ubiquitin-mediated protein degradation plays an essential role in plant growth and development as well as responses to environmental and endogenous signals. F-box protein is one of the key components of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which recruit specific substrate proteins for subsequent ubiquitination and 26S proteasome-mediated degradation to regulate developmental processes and signaling networks. However, it is not easy to obtain purified F-box proteins with high activity due to their unstable protein structures...
September 5, 2017: Plant Journal: for Cell and Molecular Biology
A M Masudul Azad Chowdhury, Hiroki Katoh, Atsushi Hatanaka, Hiroko Iwanari, Nanami Nakamura, Takao Hamakubo, Tohru Natsume, Tsuyoshi Waku, Akira Kobayashi
Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation...
October 2, 2017: Scientific Reports
Rudresh Hiremath, Jebin Ibrahim, Krishna Prasanthi, Harish T Reddy, Rushit Sandeep Shah, Ch Haritha
INTRODUCTION: Metabolic syndrome is complex disorder unifying dyslipidemia, insulin resistance and hyper insulinemia. Rising global epidemic of obesity has tremendous impact on metabolic syndrome. Ultrasound is becoming widely utilized modality for measuring the visceral adiposity. AIM: To determine the usefulness of ultrasonographic measurements in the estimation of regional adiposity and to compare them with anthropometric measurements and to correlate ultrasonographic measurements of regional adiposity and metabolic syndrome...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
Qiangzhou Rong, Yi Zhou, Xunli Yin, Zhihua Shao, Xueguang Qiao
Optical manipulation using optical micro- and nano-fibers has shown potential for controlling bacterial activities such as E. coli trapping, propelling, and binding. Most of these manipulations have been performed using the propagation of the fundamental mode through the fiber. However, along the maximum mode-intensity axis, the higher-order modes have longer evanescent field extensions and larger field amplitudes at the fiber waist than the fundamental mode, opening up new possibilities for manipulating E...
September 1, 2017: Biomedical Optics Express
Alex Albaugh, Teresa Head-Gordon
With polarization becoming an increasingly common feature in classical molecular simulation, it is important to develop methods that can efficiently and accurately evaluate the many-body polarization solution. In this work we expand the theoretical framework of our inertial extended Langrangian, self-consistent field iteration-free method (iEL/0-SCF), introduced for point induced dipoles, to the polarization model of a Drude oscillator. When applied to the polarizable simple point charge model (PSPC) for water, our iEL/0-SCF method for Drude polarization is as stable as a well-converged SCF solution and more stable than traditional extended Lagrangian (EL) approaches or EL formulations based on two temperature ensembles where Drude particles are kept "colder" than the real degrees of freedom...
October 2, 2017: Journal of Chemical Theory and Computation
Rajarshi Choudhury, Thomas Bonacci, Xianxi Wang, Andrew Truong, Anthony Arceci, Yanqiong Zhang, Christine A Mills, Jennifer L Kernan, Pengda Liu, Michael J Emanuele
The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation...
September 26, 2017: Cell Reports
Satoshi Fujii, Shuntaro Tsubaki, Naomi Inazu, Eiichi Suzuki, Yuji Wada
Scandium is being explored as an alloying element for aluminum alloys, which are gaining importance as high-performance lightweight structural alloys in the transportation industry. A few years ago, Sc was also found to be suitable for use in electrical devices. High-Sc-content ScAlN thin films have attracted significant attention because of their strong piezoelectricity. The piezoelectric response of ScAlN suggests that ScAlN thin films formed on a hard substrate would be suitable surface acoustic wave wideband filters for next-generation wireless communication systems...
September 27, 2017: Materials
Koichiro Saka, Chen-Yi Lai, Masanori Nojima, Masahiro Kawahara, Makoto Otsu, Hiromitsu Nakauchi, Teruyuki Nagamune
Hematopoietic stem cells (HSCs) are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability. Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network. Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events. We here tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity...
September 25, 2017: Stem Cell Reviews
Jia Yu Wang, Guang Zhi Liu, James S Wilmott, Ting La, Yu Chen Feng, Hamed Yari, Xu Guang Yan, Rick F Thorne, Richard A Scolyer, Xu Dong Zhang, Lei Jin
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA, however, there is little understanding of how MTH1 itself is regulated. Here we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. While Skp2 along with other components of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex were physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression...
September 25, 2017: Cancer Research
Zeliha Esin Celik, Mehmet Kaynar, Pinar Karabagli, Nursadan Gergerlioglu, Serdar Goktas
BACKGROUND: Ring Box Protein-1 (RBX-1), a component of SCF E3 ubiquitin ligases, has a crucial role in bladder urothelial cell carcinoma (UCC) carcinogenesis and progression. OBJECTIVES: In the present study, it is aimed to determine the expression of RBX-1 protein in bladder UCC and the association between tumor grade, stage and RBX-1 expression. METHODS: Ninety UCC samples and 20 samples containing foci of normal bladder urothelium were recruited and analyzed immunohistochemically in terms of RBX-1 expression...
September 15, 2017: Cancer Biomarkers: Section A of Disease Markers
Fanfan Zhang, Ding Tang, Yi Shen, Zhihui Xue, Wenqing Shi, Lijun Ren, Guijie Du, Yafei Li, Zhukuan Cheng
Telomere bouquet formation, a highly conserved meiotic event, plays an important role in homologous pairing and therefore progression of meiosis; however, the underlying molecular mechanism remains largely unknown. Here, we identified ZYGOTENE 1 (ZYGO1), a novel F-box protein in rice (Oryza sativa), and verified its essential role in bouquet formation during early meiosis. In zygo1 mutants, zygotene chromosome aggregation and telomere clustering failed to occur. The suppressed telomere clustering in homologous pairing aberration in rice meiosis 1 (pair1) zygo1 and rice completion of meiotic recombination (Oscom1) zygo1 double mutants, together with the altered localization of OsSAD1 (a SUN protein associated with the nuclear envelope) in zygo1 showed that ZYGO1 has a significant function in bouquet formation...
September 22, 2017: Plant Cell
William Grey, Adam Ivey, Thomas A Milne, Torsten Haferlach, David Grimwade, Frank Uhlmann, Edwige Voisset, Veronica Yu
The Cdc28 protein kinase subunits, Cks1 and Cks2, play dual roles in Cdk-substrate specificity and Cdk-independent protein degradation, in concert with the E3 ubiquitin ligase complexes SCF(Skp2) and APC(Cdc20). Notable targets controlled by Cks include p27 and Cyclin A. Here, we demonstrate that Cks1 and Cks2 proteins interact with both the Mll(N) and Mll(C) subunits of Mll1 (Mixed-lineage leukemia 1), and together, the Cks proteins define Mll1 levels throughout the cell cycle. Overexpression of CKS1B and CKS2 is observed in multiple human cancers, including various MLL-rearranged (MLLr) AML subtypes...
September 19, 2017: Biochimica et Biophysica Acta
Wei Hu, Lin Lin, Chao Yang
The commutator direct inversion of the iterative subspace (commutator DIIS or C-DIIS) method developed by Pulay is an efficient and the most widely used scheme in quantum chemistry to accelerate the convergence of self-consistent field (SCF) iterations in Hartree-Fock theory and Kohn-Sham density functional theory. The C-DIIS method requires the explicit storage of the density matrix, the Fock matrix, and the commutator matrix. Hence, the method can only be used for systems with a relatively small basis set, such as the Gaussian basis set...
October 4, 2017: Journal of Chemical Theory and Computation
Shu Yang, Bo Wu, Haimei Sun, Tingyi Sun, Kai Han, Dandan Li, Fengqing Ji, Guoquan Zhang, Deshan Zhou
Diabetic gastroparesis is a common complication of diabetes mellitus (DM) that is characterized by decreased serum insulin and insulin-like growth factor-1 (IGF-1). Despite the fact that insulin treatment but not glycemic control potently accelerated gastric emptying in type 1 DM patients, the role of insulin/InsR and IGF-1/IGF-1R signaling in diabetic gastroparesis remains incompletely elucidated. In this study, type 1 DM mice were established and treated with insulin or Voglibose for 8 weeks. The gastric emptying was delayed from DM week 4 when the gastric InsR and IGF-1R were declined...
September 20, 2017: Bioscience Reports
Daniel Elieh Ali Komi, Korneel Grauwet
Mast cells secrete a wide spectrum of stored or newly synthesized pro-inflammatory, anti-inflammatory, and/or immunosuppressive mediators and express several costimulatory and inhibitory surface molecules. Mast cells finely tune activities of T cells, B cells, and regulatory cells and effectively contribute to the development of different T cell-associated responses by influencing their recruitment, activation, proliferation, and differentiation. The interaction between mast cells and T cells, with regard to cellular functionality and immune responses, can be assessed in both activating and inhibitory regulations...
September 19, 2017: Clinical Reviews in Allergy & Immunology
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