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https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#1
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#2
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28296942/co-ingestion-of-carbohydrate-and-whey-protein-increases-fasted-rates-of-muscle-protein-synthesis-immediately-after-resistance-exercise-in-rats
#3
Wanyi Wang, Zhenping Ding, Geoffrey J Solares, Soon-Mi Choi, Bo Wang, Aram Yoon, Roger P Farrar, John L Ivy
The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise...
2017: PloS One
https://www.readbyqxmd.com/read/28292892/noncanonical-role-of-arabidopsis-cop1-spa-complex-in-repressing-bin2-mediated-pif3-phosphorylation-and-degradation-in-darkness
#4
Jun-Jie Ling, Jian Li, Danmeng Zhu, Xing Wang Deng
The E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) has been known to mediate key signaling factors for degradation via the ubiquitin/26S proteasome pathway in both plants and animals. Here, we report a noncanonical function of Arabidopsis COP1, the central repressor of photomorphogenesis, in the form of a COP1/ SUPPRESSOR of phyA-105 (SPA) complex. We show that the COP1/SPA complex associates with and stabilizes PHYTOCHROME INTERACTING FACTOR 3 (PIF3) to repress photomorphogenesis in the dark. We identify the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) as a kinase of PIF3, which induces PIF3 degradation via 26S proteasome during skotomorphogenesis...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288968/depletion-of-tcf3-and-lef1-maintains-mouse-embryonic-stem-cell-self-renewal
#5
Shoudong Ye, Tao Zhang, Chang Tong, Xingliang Zhou, Kan He, Qian Ban, Dahai Liu, Qi-Long Ying
Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs...
March 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28283665/il-18-dependent-nkg2d-ligand-upregulation-on-accessory-cells-is-mediated-by-the-pi3k-gsk-3-pathway
#6
Joshua D Brandstadter, Huiyao Chen, Songfu Jiang, Xiaopei Huang, Yiping Yang
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway...
March 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28281664/genetic-interactions-and-functional-analyses-of-the-fission-yeast-gsk3-and-amk2-single-and-double-mutants-defective-in-torc1-dependent-processes
#7
Charalampos Rallis, StJohn Townsend, Jürg Bähler
The Target of Rapamycin (TOR) signalling network plays important roles in aging and disease. The AMP-activated protein kinase (AMPK) and the Gsk3 kinase inhibit TOR during stress. We performed genetic interaction screens using synthetic genetic arrays (SGA) with gsk3 and amk2 as query mutants, the latter encoding the regulatory subunit of AMPK. We identified 69 negative and 82 positive common genetic interactors, with functions related to cellular growth and stress. The 120 gsk3-specific negative interactors included genes functioning in translation and ribosomes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279122/biochemical-changes-induced-by-grapeseed-extract-and-low-level-laser-therapy-administration-during-intraoral-wound-healing-in-rat-liver-an-experimental-and-in-silico-study
#8
Mehmet Erman Erdemli, Ramin Ekhteiari Salmas, Serdar Durdagi, Hasan Akgul, Mehmet Demirkol, Zeynep Aksungur, Zeliha Selamoglu
In the present study, the changes that occur in rat liver tissue as a result of the use of grapeseed extract (GSE) and low level laser therapy (LLLT) in intraoral wound healing are analyzed using biochemical parameters. Diode laser application groups received 8 J/cm(2) dose LLLT once a day for 4 days (810 nm wavelength, continuous mode, 0.25 W, 9 sec.). As a result of the biological parameter analysis, it was determined that the oxidative damage caused by the intraoral wounds and recovery period on 7(th) and 14(th) days could be substantially removed with GSE applications that have antioxidant capacity especially in rat liver tissue...
March 9, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28276699/p120-catenin-in-canonical-wnt-signaling
#9
Mireia Duñach, Beatriz Del Valle-Pérez, Antonio García de Herreros
Canonical Wnt signaling controls β-catenin protein stabilization, its translocation to the nucleus and the activation of β-catenin/Tcf-4-dependent transcription. In this review, we revise and discuss the recent results describing actions of p120-catenin in different phases of this pathway. More specifically, we comment its involvement in four different steps: (i) the very early activation of CK1ɛ, essential for Dvl-2 binding to the Wnt receptor complex; (ii) the internalization of GSK3 and Axin into multivesicular bodies, necessary for a complete stabilization of β-catenin; (iii) the activation of Rac1 small GTPase, required for β-catenin translocation to the nucleus; and (iv) the release of the inhibitory action caused by Kaiso transcriptional repressor...
March 3, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28275367/ppar-%C3%AE-agonists-as-antineoplastic-agents-in-cancers-with-dysregulated-igf-axis
#10
REVIEW
Veronica Vella, Maria Luisa Nicolosi, Stefania Giuliano, Maria Bellomo, Antonino Belfiore, Roberta Malaguarnera
It is now widely accepted that insulin resistance and compensatory hyperinsulinemia are associated to increased cancer incidence and mortality. Moreover, cancer development and progression as well as cancer resistance to traditional anticancer therapies are often linked to a deregulation/overactivation of the insulin-like growth factor (IGF) axis, which involves the autocrine/paracrine production of IGFs (IGF-I and IGF-II) and overexpression of their cognate receptors [IGF-I receptor, IGF-insulin receptor (IR), and IR]...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28265857/differences-in-5-ht2a-and-mglu2-receptor-expression-levels-and-repressive-epigenetic-modifications-at-the-5-ht2a-promoter-region-in-the-roman-low-rla-i-and-high-rha-i-avoidance-rat-strains
#11
Luna Fomsgaard, Jose L Moreno, Mario de la Fuente Revenga, Tomasz Brudek, Dea Adamsen, Cristobal Rio-Alamos, Justin Saunders, Anders Bue Klein, Ignasi Oliveras, Toni Cañete, Gloria Blazquez, Adolf Tobeña, Albert Fernandez-Teruel, Javier Gonzalez-Maeso, Susana Aznar
The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT2A and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors...
March 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28256546/promoting-in-vivo-remyelination-with-small-molecules-a-neuroreparative-pharmacological-treatment-for-multiple-sclerosis
#12
Eva María Medina-Rodríguez, Ana Bribián, Amanda Boyd, Valle Palomo, Jesús Pastor, Alfonso Lagares, Carmen Gil, Ana Martínez, Anna Williams, Fernando de Castro
Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255027/akt-activation-mediates-acquired-resistance-to-fibroblast-growth-factor-receptor-inhibitor-bgj398
#13
Jharna Datta, Senthilkumar Damodaran, Hannah Parks, Cristina Ocrainiciuc, Jharna Miya, Lianbo Yu, Elijah P Gardner, Eric Samorodnitsky, Michele R Wing, Darshna Bhatt, John Hays, Julie W Reeser, Sameek Roychowdhury
Activation of FGFR signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, or 4 is seen in multiple tumors, including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid tumors. As we move forward with FGFR inhibitors clinically, we anticipate the emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated cancer cell lines...
March 2, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28244152/glycogen-synthase-kinase-3-regulates-photic-signaling-in-the-suprachiasmatic-nucleus
#14
Jodi R Paul, Alex S McKeown, Jennifer A Davis, Stacie K Totsch, Eric M Mintz, Timothy W Kraft, Rita M Cowell, Karen L Gamble
Glycogen synthase kinase 3 (GSK3) is a serine-threonine kinase that regulates mammalian circadian rhythms at the behavioral, molecular and neurophysiological levels. In the central circadian pacemaker, the suprachiasmatic nucleus (SCN), inhibitory phosphorylation of GSK3 exhibits a rhythm across the 24h day. We have recently shown that GSK3 is capable of influencing both the molecular clock and SCN neuronal activity rhythms. However, it is not known whether GSK3 regulates the response to environmental cues such as light...
February 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28238722/hormetic-modulation-of-hepatic-insulin-sensitivity-by-advanced-glycation-end-products
#15
Nelly T Fabre, Karina Thieme, Karolline S Silva, Sérgio Catanozi, Ana Mercedes Cavaleiro, Danilo A C Pinto, Maristela M Okamoto, Mychel Raony P T Morais, Bárbara Falquetto, Telma M Zorn, Ubiratan F Machado, Marisa Passarelli, Maria Lúcia Correa-Giannella
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes...
February 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28228270/torc1-inhibits-gsk3-mediated-elo2-phosphorylation-to-regulate-very-long-chain-fatty-acid-synthesis-and-autophagy
#16
Christine Zimmermann, Aline Santos, Kenneth Gable, Sharon Epstein, Charulatha Gururaj, Pierre Chymkowitch, Dennis Pultz, Steven V Rødkær, Lorena Clay, Magnar Bjørås, Yves Barral, Amy Chang, Nils J Færgeman, Teresa M Dunn, Howard Riezman, Jorrit M Enserink
No abstract text is available yet for this article.
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28191677/uvb-represses-melanocyte-cell-migration-and-acts-through-%C3%AE-catenin
#17
Juliette U Bertrand, Valérie Petit, Elke Hacker, Irina Berlin, Nicholas K Hayward, Marie Pouteaux, Evelyne Sage, David C Whiteman, Lionel Larue
The exposure of skin to ultraviolet (UV) radiation can have both beneficial and deleterious effects: it can lead, for instance, to increased pigmentation and vitamin D synthesis but also to inflammation and skin cancer. UVB may induce genetic and epigenetic alterations, and have reversible effects associated with post-translational and gene regulation modifications. β-catenin is a main driver in melanocyte development; although infrequently mutated in melanoma, its cellular localization and activity is frequently altered...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28148649/c3g-shows-regulated-nucleo-cytoplasmic-exchange-and-represses-histone-modifications-associated-with-euchromatin
#18
Dhruv Kumar Shakyawar, Kunal Dayma, Anesh Ramadhas, Chavvakula Varalakshmi, Vegesna Radha
C3G (RapGEF1) is a ubiquitously expressed guanine nucleotide exchange factor that functions in signaling pathways regulating cell proliferation, apoptosis, and actin reorganization. It is essential for differentiation, and early embryonic development in mice. Over-expressed C3G shows predominant cytoplasmic localization, but endogenous C3G is a component of nuclear fractions in a variety of cell types. Co-expression of Importin-α and inhibition of nuclear export by Leptomycin B resulted in predominant nuclear localization of C3G...
February 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#19
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28146408/the-antimalarial-effect-of-curcumin-is-mediated-by-the-inhibition-of-glycogen-synthase-kinase-3%C3%AE
#20
Amatul Hamizah Ali, Suhaini Sudi, Rusliza Basir, Noor Embi, Hasidah Mohd Sidek
Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development...
February 2017: Journal of Medicinal Food
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