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FEBS Open Bio

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https://www.readbyqxmd.com/read/28396843/clostridioides-difficile-630%C3%AE-erm-in-silico-and-in-vivo-quantitative-growth-and-extensive-polysaccharide-secretion
#1
Henning Dannheim, Sabine E Will, Dietmar Schomburg, Meina Neumann-Schaal
Antibiotic-associated infections with Clostridioides difficile are a severe and often lethal risk for hospitalized patients, and can also affect populations without these classical risk factors. For a rational design of therapeutical concepts, a better knowledge of the metabolism of the pathogen is crucial. Metabolic modeling can provide a simulation of quantitative growth and usage of metabolic pathways, leading to a deeper understanding of the organism. Here, we present an elaborate genome-scale metabolic model of C...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396842/uptake-of-3-iodothyronamine-hormone-analogs-inhibits-the-growth-and-viability-of-cancer-cells
#2
Michael Rogowski, Lauren Gollahon, Grazia Chellini, Fariba M Assadi-Porter
3-Iodothyronamine (T1AM) is a structural analog of thyroid hormone that has been demonstrated to have potent affects on numerous physiological systems. Most studies on T1AM have explored its effects in healthy functional systems; while its potential therapeutic uses and safety, and efficacy in pathological conditions are largely unknown. We sought to evaluate the effects of T1AM and its structural analog SG-2 on cancer cell growth and viability. We analyzed the cytotoxicity of these analogs on MCF7 breast cancer cells, HepG2 hepatocellular cancer cells as well as normal control cells using primary human foreskin fibroblasts and mouse preadipocytes control cells...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396841/ubiquitin-ligase-smurf1-functions-as-a-prognostic-marker-and-promotes-growth-and-metastasis-of-clear-cell-renal-cell-carcinoma
#3
Mang Ke, Licai Mo, Weilin Li, Xianjun Zhang, Feiping Li, Hongyuan Yu
Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor-adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor-adjacent specimens...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396840/suppression-of-a-single-pair-of-mushroom-body-output-neurons-in-drosophila-triggers-aversive-associations
#4
Yutaro Ueoka, Makoto Hiroi, Takashi Abe, Tetsuya Tabata
Memory includes the processes of acquisition, consolidation and retrieval. In the study of aversive olfactory memory in Drosophila melanogaster, flies are first exposed to an odor (conditioned stimulus, CS+) that is associated with an electric shock (unconditioned stimulus, US), then to another odor (CS-) without the US, before allowing the flies to choose to avoid one of the two odors. The center for memory formation is the mushroom body which consists of Kenyon cells (KCs), dopaminergic neurons (DANs) and mushroom body output neurons (MBONs)...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396839/inhibition-of-the-tgf%C3%AE-signalling-pathway-by-cgmp-and-cgmp-dependent-kinase-i-in-renal-fibrosis
#5
Elisabeth Schinner, Veronika Wetzl, Andrea Schramm, Frieder Kees, Peter Sandner, Johannes-Peter Stasch, Franz Hofmann, Jens Schlossmann
Agents that enhance production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) ameliorate the progression of renal fibrosis. However, the molecular mechanism of this process is not fully understood. We hypothesize that the antifibrotic effects of cGMP and cGMP-dependent kinase I (cGKI) are mediated via regulation of the TGFβ signalling pathway, both via ERK and the Smad-dependent route. Kidney fibrosis was induced by unilateral ureter obstruction (UUO) in wild-type and cGKI-deficient (cGKI-KO) mice...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396838/thermo-kinetic-analysis-space-expansion-for-cyclophilin-ligand-interactions-identification-of-a-new-nonpeptide-inhibitor-using-biacore%C3%A2-t200
#6
Martin A Wear, Matthew W Nowicki, Elizabeth A Blackburn, Iain W McNae, Malcolm D Walkinshaw
We have established a refined methodology for generating surface plasmon resonance sensor surfaces of recombinant his-tagged human cyclophilin-A. Our orientation-specific stabilisation approach captures his-tagged protein under 'physiological conditions' (150 mm NaCl, pH 7.5) and covalently stabilises it on Ni(2+)-nitrilotriacetic acid surfaces, very briefly activated for primary amine-coupling reactions, producing very stable and active surfaces (≥ 95% specific activity) of cyclophilin-A. Variation in protein concentration with the same contact time allows straightforward generation of variable density surfaces, with essentially no loss of activity, making the protocol easily adaptable for studying numerous interactions; from very small fragments, ~ 100 Da, to large protein ligands...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396837/myostatin-promotes-tenogenic-differentiation-of-c2c12-myoblast-cells-through-smad3
#7
Kazutaka Uemura, Masanori Hayashi, Toshiro Itsubo, Ayumu Oishi, Hiroko Iwakawa, Masatoshi Komatsu, Shigeharu Uchiyama, Hiroyuki Kato
Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in developing and adult skeletal muscle and negatively regulates skeletal muscle growth. Recently, myostatin has been found to be expressed in tendons and increases tendon fibroblast proliferation and the expression of tenocyte markers. C2C12 is a mouse myoblast cell line, which has the ability to transdifferentiate into osteoblast and adipocyte lineages. We hypothesized that myostatin is capable of inducing tenogenic differentiation of C2C12 cells...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396836/down-regulation-of-mir-146a-5p-and-its-potential-targets-in-hepatocellular-carcinoma-validated-by-a-tcga-and-geo-based-study
#8
Xin Zhang, Zhi-Hua Ye, Hai-Wei Liang, Fang-Hui Ren, Ping Li, Yi-Wu Dang, Gang Chen
Our previous research has demonstrated that miR-146a-5p is down-regulated in hepatocellular carcinoma (HCC) and might play a tumor-suppressive role. In this study, we sought to validate the decreased expression with a larger cohort and to explore potential molecular mechanisms. GEO and TCGA databases were used to gather miR-146a-5p expression data in HCC, which included 762 HCC and 454 noncancerous liver tissues. A meta-analysis of the GEO-based microarrays, TCGA-based RNA-seq data, and additional qRT-PCR data validated the down-regulation of miR-146a-5p in HCC and no publication bias was observed...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396835/using-a-biologically-annotated-library-to-analyze-the-anticancer-mechanism-of-serine-palmitoyl-transferase-spt-inhibitors
#9
Osamu Sano, Ken-Ichi Kazetani, Ryutaro Adachi, Osamu Kurasawa, Tomohiro Kawamoto, Hidehisa Iwata
Mechanistic understanding is crucial to anticancer drug discovery. Here, we reveal that inhibition of serine palmitoyl transferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, induced death in a lung cancer cell line via a necrosis-dependent pathway. To elucidate the mechanism of cell death induced by SPT inhibition, a biologically annotated library of diverse compounds was screened with an SPT inhibitor. This analysis identified suppressors of SPT inhibitor-mediated cell death. Further analysis using hit compounds from this screening revealed that SPT inhibitors induce COX-2 expression, leading to necrosis-dependent cell death...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396834/toxic-effects-of-dimethyl-sulfoxide-on-red-blood-cells-platelets-and-vascular-endothelial-cells-in-vitro
#10
Xiaoyang Yi, Minxia Liu, Qun Luo, Hailong Zhuo, Hui Cao, Jiexi Wang, Ying Han
Dimethyl sulfoxide (DMSO) is widely used in biological studies as a cryoprotective agent for cells and tissues, and also for cryopreserved platelets (PLTs). However, few data on the toxic effects of DMSO following intravenous infusion of cryopreserved PLTs are available. The aim of this study was to explore dose-related effects of DMSO on red blood cells (RBCs), PLTs and vascular endothelial cells in vitro. The results showed that DMSO treatments had significant effects on RBCs, affecting osmotic fragility and increasing hemolysis...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396833/activation-of-ppar%C3%AE-by-baicalin-attenuates-pulmonary-hypertension-in-an-infant-rat-model-by-suppressing-hmgb1-rage-signaling
#11
Zhenjie Chen, Qiuxia Wang
Pulmonary hypertension (PH) is a vascular disease, and proinflammatory factors are strongly implicated in its pathogenesis, causing right ventricular (RV) hypertrophy and heart failure. Baicalin exhibits potent anti-inflammation activity. This study aimed to investigate the curative effects of baicalin in an infant rodent model of PH and to further explore the underlying mechanisms. A PH model in infant rats was induced by hypoxia and the resulting rats were administered baicalin in incremental dosages. Invasive hemodynamic methods were used to measure mean pulmonary arterial pressure (mPAP) and RV end-diastolic pressure (RVEDP)...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396832/azd0530-sensitizes-drug-resistant-alk-positive-lung-cancer-cells-by-inhibiting-src-signaling
#12
Yi Zhao, Yi Yang, Yunhua Xu, Shun Lu, Hong Jian
Most tumors develop resistance to targeted cancer drugs, even though these drugs have produced substantial clinical responses. Here we established anaplastic lymphoma kinase (ALK)-positive drug-resistant lung cancer cell lines, which are resistant to ceritinib (LDK378). We found that ceritinib treatment resulted in robust upregulation of SRC activity, as measured by the phosphorylation of the SRC substrate paxillin. Knockdown of SRC alone with siRNA effectively sensitized ceritinib resistance in ALK-positive cells...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396831/cryptochrome-2-extensively-regulates-transcription-of-the-chloroplast-genome-in-tomato
#13
Paolo Facella, Fabrizio Carbone, Antonio Placido, Gaetano Perrotta
Light plays a key role in the regulation of many physiological processes required for plant and chloroplast development. Plant cryptochromes (crys) play an important role in monitoring, capturing, and transmitting the light stimuli. In this study, we analyzed the effects of CRY2 overexpression on transcription of tomato chloroplast genome by a tiling array, containing about 90 000 overlapping probes (5-nucleotide resolution). We profiled transcription in leaves of wild-type and CRY2-overexpressing plants grown in a diurnal cycle, to generate a comprehensive map of chloroplast transcription and to monitor potential specific modulations of the chloroplast transcriptome induced by the overexpression of CRY2...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396830/the-g2-checkpoint-a-node-based-molecular-switch
#14
Mark C de Gooijer, Arnout van den Top, Irena Bockaj, Jos H Beijnen, Thomas Würdinger, Olaf van Tellingen
Tight regulation of the eukaryotic cell cycle is paramount to ensure genomic integrity throughout life. Cell cycle checkpoints are present in each phase of the cell cycle and prevent cell cycle progression when genomic integrity is compromised. The G2 checkpoint is an intricate signaling network that regulates the progression of G2 to mitosis (M). We propose here a node-based model of G2 checkpoint regulation, in which the action of the central CDK1-cyclin B1 node is determined by the concerted but opposing activities of the Wee1 and cell division control protein 25C (CDC25C) nodes...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396829/a-new-education-section%C3%A2-for-febs-open-bio
#15
EDITORIAL
Angel Herráez, Luciane V Mello
No abstract text is available yet for this article.
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286738/tsc2-rheb-signaling-mediates-erk-dependent-regulation-of-mtorc1-activity-in-c2c12-myoblasts
#16
Mitsunori Miyazaki, Tohru Takemasa
The enhanced rate of protein synthesis in skeletal muscle cells results in a net increase in total protein content that leads to skeletal muscle growth/hypertrophy. The mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent regulation of the activity of mechanistic target of rapamycin (mTOR) and subsequent protein synthesis has been suggested as a regulatory mechanism; however, the exact molecular processes underlying such a regulation are poorly defined. The purpose of this study was to investigate regulatory mechanisms involved in the MEK/ERK-dependent pathway leading to mTORC1 activation in skeletal muscle cells...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286737/pdgf-induced-fibroblast-growth-requires-monounsaturated-fatty-acid-production-by-stearoyl-coa-desaturase
#17
Alexandra Coomans de Brachène, Nicolas Dif, Audrey de Rocca Serra, Chloé Bonnineau, Amélie I Velghe, Yvan Larondelle, Donatienne Tyteca, Jean-Baptiste Demoulin
Stearoyl-coenzyme A desaturase (SCD) catalyzes the Δ9-cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up-regulated by platelet-derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286736/overexpression-of-heparanase-attenuated-tgf-%C3%AE-stimulated-signaling-in-tumor-cells
#18
Tahira Batool, Jianping Fang, Uri Barash, Aristidis Moustakas, Israel Vlodavsky, Jin-Ping Li
Heparan sulfate (HS) mediates the activity of various growth factors including TGF-β. Heparanase is an endo-glucuronidase that specifically cleaves and modifies HS structure. In this study, we examined the effect of heparanase expression on TGF-β1-dependent signaling activities. We found that overexpression of heparanase in human tumor cells (i.e., Fadu pharyngeal carcinoma, MCF7 breast carcinoma) attenuated TGF-β1-stimulated Smad phosphorylation and led to a slower cell proliferation. TGF-β1-stimulated Akt and Erk phosphorylation was also affected in the heparanase overexpression cells...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286735/mitotic-phosphorylation-of-ccctc-binding-factor-ctcf-reduces-its-dna-binding-activity
#19
Takeshi Sekiya, Kensaku Murano, Kohsuke Kato, Atsushi Kawaguchi, Kyosuke Nagata
During mitosis, higher order chromatin structures are disrupted and chromosomes are condensed to achieve accurate chromosome segregation. CCCTC-binding factor (CTCF) is a highly conserved and ubiquitously expressed C2H2-type zinc finger protein which is considered to be involved in epigenetic memory through regulation of higher order chromatin architecture. However, the regulatory mechanism of CTCF in mitosis is still unclear. Here we found that the DNA-binding activity of CTCF is regulated in a phosphorylation-dependent manner during mitosis...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286734/identifying-the-receptor-subtype-selectivity-of-retinoid-x-and-retinoic-acid-receptors-via-quantum-mechanics
#20
Motonori Tsuji, Koichi Shudo, Hiroyuki Kagechika
Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands...
March 2017: FEBS Open Bio
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