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https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#1
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431088/stationary-phase-genes-upregulated-by-polyamines-are-responsible-for-the-formation-of-escherichia-coli-persister-cells-tolerant-to-netilmicin
#2
Alexander G Tkachenko, Natalya M Kashevarova, Elena A Tyuleneva, Mikhail S Shumkov
Persisters are rare phenotypic variants of regular bacterial cells that survive lethal antibiotics or stresses owing to slowing down of their metabolism. Recently, we have shown that polyamine putrescine can upregulate persister cell formation in Escherichia coli via the stimulation of rpoS expression, encoding a master regulator of general stress response. We hypothesized that rmf and yqjD, the stationary-phase genes responsible for ribosome inactivation, might be good candidates for the similar role owing to their involvement in translational arrest and the ability to be affected by polyamines...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#3
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430915/genetic-knockout-and-rescue-studies-in-mice-unravel-abnormal-phosphorus-threshold-in-hypophosphatemic-rickets
#4
Cheryl P Sanchez, Subburaman Mohan
No abstract text is available yet for this article.
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430907/food-intake-affects-sperm-egg-fusion-through-the-gip-psg17-axis-in-mice
#5
Tatsunori Shimizu, Takehiro Sato, Katsushi Tsukiyama, Hiroki Fujita, Shunsuke Kato, Manabu Hoizumi, Hiromitsu Shirasawa, Takuma Narita, Yukihiro Terada, Yutaka Seino, Yuichiro Yamada
In addition to overeating, starvation also reduces fecundity in mammals. However, little is known about the molecular mechanisms linking food intake to fertility, especially in males. Gastric inhibitory polypeptide (GIP), which is released from intestinal K-cells after meal ingestion, stimulates insulin secretion from pancreatic β-cells through the action of incretin and has several extra-pancreatic effects. Here, we identified GIP receptor (Gipr) expression in mouse spermatids. Microarray analysis revealed that pregnancy-specific glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly decreased in GIP receptor-knockout (Gipr-/-) testes...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430876/ift25-an-intraflagellar-transporter-protein-dispensable-for-ciliogenesis-in-somatic-cells-is-essential-for-sperm-flagella-formation
#6
Hong Liu, Wei Li, Yong Zhang, Zhengang Zhang, Xuejun Shang, Ling Zhang, Shiyang Zhang, Yanwei Li, Andres V Somoza, Brandon Delpi, George L Gerton, James A Foster, Rex A Hess, Gregory J Pazour, Zhibing Zhang
Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, IFT25, a component of the IFT complex is not required for the formation of cilia in somatic tissues. In mice, the gene is highly expressed in the testis, and its expression is up-regulated during the final phase when sperm flagella are formed. To investigate the role of IFT25 in sperm flagella formation, the gene was specifically disrupted in male germ cells. All homozygous knockout mice survived to adulthood and did not show any gross abnormalities...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430577/synthetic-lethal-interaction-between-the-tumour-suppressor-stag2-and-its-paralog-stag1
#7
Lorena Benedetti, Matteo Cereda, LeeAnn Monteverde, Nikita Desai, Francesca D Ciccarelli
Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430356/crispr-cas9-an-rna-guided-highly-precise-synthetic-tool-for-plant-genome-editing
#8
REVIEW
Yeliz Demirci, Baohong Zhang, Turgay Unver
CRISPR/Cas 9 is a newly developed and naturally occurred genome editing tool, which is originally used by bacteria for immune defence. In the past years, it has been quickly employed and modified to precisely edit genome sequences in both plants and animals. Compared with the well-developed zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR/Cas 9 has lots of advantages, including easier to design and implement, higher targeting efficiency, and less expensive. Thus, it is becoming one of the most powerful tools for knockout of an individual gene as well as insertion of one gene and/or control of gene transcription...
April 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28429777/interleukin-6-increases-the-expression-and-activity-of-insulin-degrading-enzyme
#9
Mirian A Kurauti, José M Costa-Júnior, Sandra M Ferreira, Gustavo J Santos, Carlos H G Sponton, Everardo M Carneiro, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Luiz F Rezende, Antonio C Boschero
Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429746/the-small-g-protein-arf6-expressed-in-keratinocytes-by-hgf-stimulation-is-a-regulator-for-skin-wound-healing
#10
Yuki Miura, Van Ngo Thai Bich, Momoko Furuya, Hiroshi Hasegawa, Satoru Takahashi, Naohiro Katagiri, Tsunaki Hongu, Yuji Funakoshi, Norihiko Ohbayashi, Yasunori Kanaho
The earlier step of cutaneous wound healing process, re-epithelialization of the wounded skin, is triggered by a variety of growth factors. However, molecular mechanisms through which growth factors trigger skin wound healing are less understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is essential for the skin wound healing. Arf6 mRNA expression was dramatically induced in keratinocytes at the wounded skin, which was specifically suppressed by the c-Met inhibitor...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429080/effect-of-gpr84-deletion-on-obesity-and-diabetes-development-in-mice-fed-long-chain-or-medium-chain-fatty-acid-rich-diets
#11
Eugene Du Toit, Liam Browne, Helen Irving-Rodgers, Helen M Massa, Nicolette Fozzard, Michael P Jennings, Ian R Peak
PURPOSE: Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice...
April 20, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28428709/disruption-of-the-tweak-fn14-pathway-prevents-5-fluorouracil-induced-diarrhea-in-mice
#12
Takuhito Sezaki, Yuki Hirata, Teruki Hagiwara, Yuki I Kawamura, Tadashi Okamura, Rieko Takanashi, Kenta Nakano, Miwa Tamura-Nakano, Linda C Burkly, Taeko Dohi
AIM: To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil (5-FU)-induced diarrhea. METHODS: Diarrhea was induced in wild-type (WT), Fn14 knockout (KO), and IL-13 receptor (IL-13R)α1 KO BALB/c mice using a single injection of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was performed on ileal tissues and cells. Murine colon carcinoma-bearing mice were co-treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to cytokines was also analyzed...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428639/obestatin-stimulates-glucose-induced-insulin-secretion-through-ghrelin-receptor-ghs-r
#13
Geetali Pradhan, Chia-Shan Wu, Jong Han Lee, Preeti Kanikarla, Shaodong Guo, Vijay K Yechoor, Susan L Samson, Yuxiang Sun
Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin's effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428632/cyclophosphamide-induced-hcn1-channel-upregulation-in-interstitial-cajal-like-cells-leads-to-bladder-hyperactivity-in-mice
#14
Qian Liu, Zhou Long, Xingyou Dong, Teng Zhang, Jiang Zhao, Bishao Sun, Jingzhen Zhu, Jia Li, Qingqing Wang, Zhenxing Yang, Xiaoyan Hu, Longkun Li
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428628/inflammatory-and-neuropathic-nociception-is-preserved-in-gpr55-knockout-mice
#15
Lawrence M Carey, Tannia Gutierrez, Liting Deng, Wan-Hung Lee, Ken Mackie, Andrea G Hohmann
The G-protein coupled receptor GPR55 has been postulated to serve as a novel cannabinoid receptor. A previous report indicated that GPR55 knockout mice fail to develop mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55 in the control of nociceptive responding. However, GPR55 knockout mice remain incompletely characterized in models of pathological pain. Here we provide a comprehensive assessment of responses of GPR55 knockout and wild-type mice to mechanical and thermal (heat, cold) stimulation in multiple, mechanistically distinct models of inflammatory and neuropathic pain...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428612/granzyme-k-deficient-mice-show-no-evidence-of-impaired-anti-viral-immunity
#16
Lars T Joeckel, Cody C Allison, Mark Pellegrini, Catherina H Bird, Phillip Ian Bird
The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease we have deleted the granzyme K gene in mice (mutant allele: Gzmk(tm1.1Pib); MGI:5636646). Gzmk(-/-) mice are healthy, anatomically normal, fecund, and show normal hematopoietic development. Gzmk(-/-) mice readily recover from Lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection...
April 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28428264/cb1-cannabinoid-receptor-drives-oocyte-maturation-and-embryo-development-via-pi3k-akt-and-mapk-pathways
#17
Angela Patricia López-Cardona, Serafín Pérez-Cerezales, Raúl Fernández-González, Ricardo Laguna-Barraza, Eva Pericuesta, Naiara Agirregoitia, Alfonso Gutiérrez-Adán, Ekaitz Agirregoitia
Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation. In a mouse model, we observed that activation of the cannabinoid receptor (CB)1 during in vitro oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of the CB1 receptor, in vivo oocyte maturation was impaired and embryo development delayed. The CB2 receptor was unable to rescue these effects...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28428263/different-requirements-of-functional-telomeres-in-neural-stem-cells-and-terminally-differentiated-neurons
#18
Anastasia Lobanova, Robert She, Simon Pieraut, Charlie Clapp, Anton Maximov, Eros Lazzerini Denchi
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#19
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#20
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mattew, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jun Song, Rose Ackermann, Yui Koike, Anna Schwendeman, Liangxue Lai, Subramaniam Pennathur, Minerva Garcia-Barrio, Jianglin Fan, Y Eugene Chen
OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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