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https://www.readbyqxmd.com/read/28108746/myeloid-derived-suppressor-cells-can-be-efficiently-generated-from-human-hematopoietic-progenitors-and-peripheral-blood-monocytes
#1
Sílvia Casacuberta-Serra, Marta Parés, Arantxa Golbano, Elisabet Coves, Carmen Espejo, Jordi Barquinero
Myeloid-derived suppressor cells (MDSCs) play an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex-vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34(+) hematopoietic progenitors from apheresis products and CD14(+) cells isolated from buffy coats were cultured in the presence of different combinations of cytokines...
January 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28101194/inhibition-of-nedd8-and-fat10-ligase-activities-through-the-degrading-enzyme-nedd8-ultimate-buster-1-a-potential-anticancer-approach
#2
Ka-Liong Tan, Francesco Pezzella
The capabilities of tumour cells to survive through deregulated cell cycles and evade apoptosis are hallmarks of cancer. The ubiquitin-like proteins (UBL) proteasome system is important in regulating cell cycles via signaling proteins. Deregulation of the proteasomal system can lead to uncontrolled cell proliferation. The Skp, Cullin, F-box containing complex (SCF complex) is the predominant E3 ubiquitin ligase, and has diverse substrates. The ubiquitin ligase activity of the SCF complexes requires the conjugation of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to cullin proteins...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100228/association-of-stem-cell-factor-gene-expression-with-severity-and-atopic-state-in-patients-with-bronchial-asthma
#3
Safaa I Tayel, Sally M El-Hefnway, Eman M Abd El Gayed, Gehan A Abdelaal
BACKGROUND: Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients. METHODS: This study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons...
January 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28097090/a-comparative-study-of-the-degradation-of-yeast-cyclins-cln1-and-cln2
#4
Inma Quilis, J Carlos Igual
The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1 and Cln2 in order to further investigate the possible differences between them. Both cyclins show the same half-life but, while Cln2 degradation depends on ubiquitin ligases SCF(G)(rr1) and SCF(C)(dc4), Cln1 is affected only by SCF(G)(rr1)...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28094984/a-generalized-grid-based-fast-multipole-method-for-integrating-helmholtz-kernels
#5
Pauli Parkkinen, Sergio A Losilla, Eelis Solala, Elias A Toivanen, Wen-Hua Xu, Dage Sundholm
A grid-based fast multipole method (GB-FMM) for optimizing three-dimensional (3D) numerical molecular orbitals in the dual bubbles and cube basis has been developed and implemented. The present GB-FMM method is a generalization of our recently published GB-FMM approach for numerically calculating electrostatic potentials and two-electron interaction energies. The orbital optimization is performed by integrating the Helmholtz kernel in the dual basis. The steep part of the functions in the vicinity of the nuclei is represented by one-center bubbles functions, whereas the remaining cube part is expanded on an equidistant 3D grid...
January 17, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28094936/computation-of-the-isotropic-hyperfine-coupling-constant-efficiency-and-insights-from-a-new-approach-based-on-wave-function-theory
#6
Emmanuel Giner, Lorenzo Tenti, Celestino Angeli, Nicolas Ferré
The present paper reports an original computational strategy for the computation of the isotropic hyperfine coupling constants (hcc). The algorithm proposed here is based on an approach recently introduced by some of the authors, namely the first order breathing orbital self consistent field (FOBO-SCF). The approach is an almost parameter-free wave function method capable to accurately treat the spin delocalization together with the spin polarization effects while staying in a restricted formalism and avoiding spin contamination...
January 17, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#7
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28078840/mast-cell-and-cancer-with-special-emphasis-on-il-37-an-anti-inflammatory-and-inhibitor-of-innate-immunity-new-frontiers
#8
F Carinci, G Lessiani, E Spinas, S K Kritas, G Ronconi, Al Caraffa, P Conti
Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic protein-1 (MCP-1), RANTES and stem cell factor (SCF) to selectively secrete inflammatory molecules including chemical mediators and cytokines (TNF, IL-6 and IL-1). However, MC differentiation pathways and heterogeneity in cancer are still poorly understood...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28069738/fbxl5-inactivation-in-mouse-brain-induces-aberrant-proliferation-of-neural-stem-progenitor-cells
#9
Takayoshi Yamauchi, Masaaki Nishiyama, Toshiro Moroishi, Atsuki Kawamura, Keiichi I Nakayama
FBXL5 is the substrate recognition subunit of an SCF-type ubiquitin ligase that serves as a master regulator of iron metabolism in mammalian cells. We previously showed that mice with systemic deficiency of FBXL5 fail to sense intracellular iron levels and die in utero at embryonic day (E) 8.5 as a result of iron overload and subsequent oxidative stress. This early embryonic mortality has thus impeded study of the role of FBXL5 in brain development. We have now generated mice lacking FBXL5 specifically in Nestin-expressing neural stem-progenitor cells (NSPCs) in the brain...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28068319/fbxo32-suppresses-breast-cancer-tumorigenesis-through-targeting-klf4-to-proteasomal-degradation
#10
H Zhou, Y Liu, R Zhu, F Ding, Y Wan, Y Li, Z Liu
Krüppel-like factor 4 (KLF4, GKLF) is a zinc-finger transcription factor involved in a large variety of cellular processes, including apoptosis, cell cycle progression, as well as stem cell renewal. KLF4 is critical for cell fate decision and has an ambivalent role in tumorigenesis. Emerging data keep reminding us that KLF4 dysregulation either facilitates or impedes tumor progression, making it important to clarify the regulating network of KLF4. Like most transcription factors, KLF4 has a rather short half-life within the cell and its turnover must be carefully orchestrated by ubiquitination and ubiquitin-proteasome system...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28051267/reduced-expression-of-scf-in-serum-and-follicle-from-patients-with-polycystic-ovary-syndrome
#11
J Tan, X-Y Wen, Q Su, Z-H Huang, J-X He, C-L Xin, Q-F Wu, Y Zou
OBJECTIVE: In humans, stem cell factor (SCF), produced by cumulus granulosa cells during the follicular phase, plays a crucial role in follicular development. Remarkably, polycystic ovary syndrome (PCOS), one of the main reasons affecting women fertility, is accompanied by some abnormal follicles. Is there a relationship between SCF and PCOS? This study aimed to compare the expression of SCF in follicle and serum from patients with and without PCOS undergoing in vitro fertilization (IVF) treatment and to investigate the potential relationship between aberrant SCF expression and PCOS...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28051179/the-hypoparathyroidism-associated-mutation-in-drosophila-gcm-compromises-protein-stability-and-glial-cell-formation
#12
Xiao Xi, Lu Lu, Chun-Chun Zhuge, Xuebing Chen, Yuanfen Zhai, Jingjing Cheng, Haian Mao, Chang-Ching Yang, Bertrand Chin-Ming Tan, Yi-Nan Lee, Cheng-Ting Chien, Margaret S Ho
Differentiated neurons and glia are acquired from immature precursors via transcriptional controls exerted by factors such as proteins in the family of Glial Cells Missing (Gcm). Mammalian Gcm proteins mediate neural stem cell induction, placenta and parathyroid development, whereas Drosophila Gcm proteins act as a key switch to determine neuronal and glial cell fates and regulate hemocyte development. The present study reports a hypoparathyroidism-associated mutation R59L that alters Drosophila Gcm (Gcm) protein stability, rendering it unstable, and hyperubiquitinated via the ubiquitin-proteasome system (UPS)...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#13
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28045993/change-in-the-interstitial-cells-of-cajal-and-nnos-positive-neuronal-cells-with-aging-in-the-stomach-of-f344-rats
#14
Yong Hwan Kwon, Nayoung Kim, Ryoung Hee Nam, Ji Hyun Park, Sun Min Lee, Sung Kook Kim, Hye Seung Lee, Yong Sung Kim, Dong Ho Lee
The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28045046/an-allosteric-conduit-facilitates-dynamic-multisite-substrate-recognition-by-the-scf-cdc4-ubiquitin-ligase
#15
Veronika Csizmok, Stephen Orlicky, Jing Cheng, Jianhui Song, Alaji Bah, Neda Delgoshaie, Hong Lin, Tanja Mittag, Frank Sicheri, Hue Sun Chan, Mike Tyers, Julie D Forman-Kay
The ubiquitin ligase SCF(Cdc4) mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4(WD40) binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket...
January 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28033308/effects-of-polysaccharide-of-gastrodia-elata-blume-and-electro-acupuncture-on-expressions-of-brain-derived-neurotrophic-factor-and-stem-cell-factor-protein-in-caudate-putamen-of-focal-cerebral-ischemia-rats
#16
Huai-Bin Li, Feng Wu, Hua-Chun Miao, Ke-Ren Xiong
BACKGROUND The aim of this study was to explore the neural protective effect of polysaccharide of Gastrodia elata Blume (PGB) and electro-acupuncture (EA) on focal cerebral ischemia rats. MATERIAL AND METHODS A total of 40 Sprague-Dawley rats were randomly divided into 5 groups (normal group, model group, PGB group, EA group and PGB+EA group). The model was prepared by middle cerebral artery occlusion (MCAO). Two week after modeling, rats were given PGB, EA, or a combination of the 2 in continuous treatment for 2 successive weeks...
December 23, 2016: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/28009085/protein-tyrosine-phosphatase-prl2-mediates-notch-and-kit-signals-in-early-t-cell-progenitors
#17
Michihiro Kobayashi, Sarah Nabinger, Yunpeng Bai, Momoko Yoshimoto, Rui Gao, Sisi Chen, Chonghua Yao, Yuanshu Dong, Lujuan Zhang, Sonia Rodriguez, Yumi Yashiro-Ohtani, Warren S Pear, Nadia Carlesso, Mervin C Yoder, Reuben Kapur, Mark H Kaplan, H Daniel Lacorazza, Zhong-Yin Zhang, Yan Liu
The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors...
December 23, 2016: Stem Cells
https://www.readbyqxmd.com/read/28007894/the-pseudophosphatase-styx-targets-the-f-box-of-fbxw7-and-inhibits-scffbxw7-function
#18
Veronika Reiterer, Cristina Figueras-Puig, Francois Le Guerroue, Stefano Confalonieri, Manuela Vecchi, Dasaradha Jalapothu, Sandip M Kanse, Raymond J Deshaies, Pier Paolo Di Fiore, Christian Behrends, Hesso Farhan
The F-box protein FBXW7 is the substrate-recruiting subunit of an SCF ubiquitin ligase and a major tumor-suppressor protein that is altered in several human malignancies. Loss of function of FBXW7 results in the stabilization of numerous proteins that orchestrate cell proliferation and survival. Little is known about proteins that directly regulate the function of this protein. In the current work, we have mapped the interactome of the enigmatic pseudophosphatase STYX We reasoned that a catalytically inactive phosphatase might have adopted novel mechanisms of action...
December 22, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28004932/efficient-implementation-of-energy-decomposition-analysis-for-second-order-m%C3%A3-ller-plesset-perturbation-theory-and-application-to-anion-%C3%AF-interactions
#19
Jonathan Thirman, Martin Head-Gordon
Energy decomposition analysis (EDA) is a widely used tool for extracting physical and chemical insights from electronic structure calculations of intermolecular interactions, as well as for the development of advanced force fields for describing those interactions. Recently, the absolutely localized molecular orbital (ALMO) EDA has been extended from the self-consistent field level to the second-order Møller-Plesset (MP2) theory level. This paper reports an efficient implementation of the MP2 ALMO-EDA that scales optimally, employs the resolution of the identity (RI) approximation for post-SCF matrix elements, and is shared-memory parallel...
January 17, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28004388/lcn2-overexpression-in-bone-enhances-the-hematopoietic-compartment-via-modulation-of-the-bone-marrow-microenvironment
#20
Delfina Costa, Elisa Principi, Edoardo Lazzarini, Fiorella Descalzi, Ranieri Cancedda, Patrizio Castagnola, Sara Tavella
Lipocalin-2 (LCN2) is a member of the lipocalin family whose expression is modulated in several conditions, including cell differentiation, innate immunity, stress and cancer. Although it is known that it is expressed in bone, its function in this tissue remains poorly studied. To this end, we took advantage of transgenic mice lines that expressed LCN2 driven by a bone specific type I collagen (LCN2-Tg). In the bone marrow (BM) of LCN2-Tg mice we observed an increased number of phenotypically long-term hematopoietic stem cells (LT-HSC) that also displayed a higher proliferation rate compared to wild type controls (Wt)...
December 22, 2016: Journal of Cellular Physiology
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