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FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology

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https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#1
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27920150/heterotrimeric-kinesin-2-together-with-kinesin-1-steers-vesicular-acetylcholinesterase-movements-toward-the-synapse
#2
Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27903619/interleukin-10-mediated-regenerative-postnatal-tissue-repair-is-dependent-on-regulation-of-hyaluronan-metabolism-via-fibroblast-specific-stat3-signaling
#3
Swathi Balaji, Xinyi Wang, Alice King, Louis D Le, Sukanta S Bhattacharya, Chad M Moles, Manish J Butte, Vinicio A de Jesus Perez, Kenneth W Liechty, Thomas N Wight, Timothy M Crombleholme, Paul L Bollyky, Sundeep G Keswani
The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)-dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox-mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3 knockdown postnatal mice-plus syngeneic fibroblast cell-transplant models-we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27903618/hypolipidemic-effect-of-oleanolic-acid-is-mediated-by-the-mir-98-5p-pgc-1%C3%AE-axis-in-high-fat-diet-induced-hyperlipidemic-mice
#4
Siyu Chen, Xiaoan Wen, Wenxiang Zhang, Chen Wang, Jun Liu, Chang Liu
Oleanolic acid (OA) is an active component of the traditional Chinese herb olea europaea l. and has been found to exhibit a significant lipid-lowering effect; however, its direct molecular target is still unknown, which limits its clinical application and the possible structure modification to improve its beneficial functions. In this regard, we carried out the present study to identify potential hepatic targets of OA to mediate its lipid-lowering effect. We found that both acute and chronic OA treatments reduced serum levels of triglycerides, total cholesterol, and LDL cholesterol, and decreased hepatic expression levels of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), which is an important regulator in maintaining hepatic lipid homeostasis, and its downstream target genes...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895108/the-effect-of-dietary-fish-oil-on-weight-gain-and-insulin-sensitivity-is-dependent-on-apoe-genotype-in-humanized-targeted-replacement-mice
#5
Kenna E Slim, David Vauzour, Noemi Tejera, Peter J Voshol, Aedin Cassidy, Anne Marie Minihane
We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895107/long-noncoding-rna-h19-accelerates-tenogenic-differentiation-and-promotes-tendon-healing-through-targeting-mir-29b-3p-and-activating-tgf-%C3%AE-1-signaling
#6
Ying-Fei Lu, Yang Liu, Wei-Ming Fu, Jia Xu, Bin Wang, Yu-Xin Sun, Tian-Yi Wu, Liang-Liang Xu, Kai-Ming Chan, Jin-Fang Zhang, Gang Li
Tendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895106/saliva-exosomes-from-pancreatic-tumor-bearing-mice-modulate-nk-cell-phenotype-and-antitumor-cytotoxicity
#7
Stergios Katsiougiannis, David Chia, Yong Kim, Ram P Singh, David T W Wong
Tumor exosomes are emerging as antitumor immunity regulators; however, their effects on secondary exosome secretion by distal organs have not been explored. We have previously demonstrated that suppression of exosomes at the distal tumor site of pancreatic ductal adenocarcinoma (PDAC) ablated the development of salivary biomarker profile. Here, we explore the function of salivary exosomes from tumor-bearing mice in immune surveillance. We provide evidence that salivary exosomes from mice with PDAC exhibit a suppressive effect that results in reduced tumor-killing capacity by NK cells...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895105/robot-assisted-mechanical-therapy-attenuates-stroke-induced-limb-skeletal-muscle-injury
#8
Chandan K Sen, Savita Khanna, Hallie Harris, Richard Stewart, Maria Balch, Mallory Heigel, Seth Teplitsky, Surya Gnyawali, Cameron Rink
The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT(-)) or RAMT(+) groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27881487/osteogenesis-requires-fak-dependent-collagen-synthesis-by-fibroblasts-and-osteoblasts
#9
Dhaarmini Rajshankar, Yongqiang Wang, Christopher A McCulloch
Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6 kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked, shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced bone volume (4-fold in tails; P < 0...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27881485/visualization-of-ligand-induced-gi-protein-activation-in-chemotaxing-cells
#10
Kazuyuki Masuda, Jun-Ichi Kitakami, Tohru Kozasa, Tatsuhiko Kodama, Sigeo Ihara, Takao Hamakubo
Cell migration to chemoattractants is critically important in both normal physiology and the pathogenesis of many diseases. In GPCR-mediated chemotaxis, GPCRs transduce the gradient of an extracellular chemotactic ligand into intracellular responses via the activation of heterotrimeric G proteins. However, ligand-induced G protein activation has not been directly imaged as yet in mammalian chemotaxing cells. We developed a Förster resonance energy transfer (FRET) probe (R10-Gi) by linking the Gi protein α subunit to the regulator of G protein signaling domain...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27881484/cell-penetrating-peptides-recruit-type-a-scavenger-receptors-to-the-plasma-membrane-for-cellular-delivery-of-nucleic-acids
#11
Carmen Juks, Annely Lorents, Piret Arukuusk, Ülo Langel, Margus Pooga
Scavenger receptors (SRs) are a large family of multifunctional receptors that are involved in a range of physiologic and pathologic processes. The ability of class A scavenger receptors (SRs)-As to bind anionic ligands facilitates the internalization of negatively charged cell-penetrating peptide (CPP)-nucleic acid nanocomplexes and thus makes them attractive targets for delivery of various nucleic acids. Recently, we demonstrated that SR-A3 and SR-A5 are recruited from intracellular membranes to the plasma membrane after incubation with PepFect 14-splice-switching oligonucleotide complexes...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27871067/the-lncrna-snhg5-mir-32-axis-regulates-gastric-cancer-cell-proliferation-and-migration-by-targeting-klf4
#12
Lianmei Zhao, Taotao Han, Yanshuang Li, Jiazeng Sun, Shang Zhang, Yanxin Liu, Baoen Shan, Dexian Zheng, Juan Shi
Long noncoding RNAs (lncRNAs) are emerging as important regulators in cellular processes, including the development, proliferation, and migration of cancer cells. We have demonstrated in a prior study that small nucleolar RNA host gene 5 (SNHG5) is dysregulated in gastric cancer (GC). To further explore the underlying mechanisms of SNGH5 function in the development of GC, in this study, we screened the microRNAs interacting with SNHG5 and elucidated their roles in GC. We showed that SNHG5 contains a putative miR-32-binding site and that deletion of this site abolishes the responsiveness to miR-32...
November 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27864378/loss-of-scleraxis-in-mice-leads-to-geometric-and-structural-changes-in-cortical-bone-as-well-as-asymmetry-in-fracture-healing
#13
Jennifer A McKenzie, Evan Buettmann, Adam C Abraham, Michael J Gardner, Matthew J Silva, Megan L Killian
Scleraxis (Scx) is a known regulator of tendon development, and recent work has identified the role of Scx in bone modeling. However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx (ScxGFP) reporter and Scx knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, as well as callus healing response. Botulinum toxin (BTX) was used to investigate muscle unloading effects on callus shape...
November 18, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27864377/mitochondrial-and-redox-abnormalities-in-autism-lymphoblastoid-cells-a-sibling-control-study
#14
Shannon Rose, Sirish C Bennuri, Rebecca Wynne, Stepan Melnyk, S Jill James, Richard E Frye
Autism spectrum disorder (ASD) is associated with physiological abnormalities including abnormal redox and mitochondrial metabolism. Lymphoblastoid cell lines (LCLs) from some children with ASD exhibit increased oxidative stress, decreased glutathione redox capacity, and highly active mitochondria with increased vulnerability to reactive oxygen species (ROS). Because unaffected siblings (Sibs) of individuals with ASD share some redox abnormalities, we sought to determine whether LCLs from Sibs share ASD-associated mitochondrial abnormalities...
November 18, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27864376/probing-function-and-structure-of-trehalose-6-phosphate-phosphatases-from-pathogenic-organisms-suggests-distinct-molecular-groupings
#15
Megan Cross, Romain Lepage, Siji Rajan, Sonja Biberacher, Neil D Young, Bo-Na Kim, Mark J Coster, Robin B Gasser, Jeong-Sun Kim, Andreas Hofmann
The trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccharide in many pathogens but is neither required nor synthesized in mammalian hosts. As such, trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis, is likely an attractive target for novel chemotherapeutics. Based on a survey of genomes from a panel of parasitic nematodes and bacterial organisms and by way of a structure-based amino acid sequence alignment, we derive the topological structure of monoenzyme TPPs and classify them into 3 groups...
November 18, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27856558/human-polymorphisms-in-nicotinic-receptors-a-functional-analysis-in-ips-derived-dopaminergic-neurons
#16
Cristina Deflorio, Stéphane Blanchard, Maria Carla Carisì, Delphine Bohl, Uwe Maskos
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic strategies are currently available for nicotine addiction, and it is therefore crucial to understand the etiological and pathophysiological factors contributing to this addiction. The neuronal α5 nicotinic acetylcholine receptor (nAChR) subunit is critically involved in nicotine dependence. In particular, the human polymorphism α5D398N corresponds to the strongest correlation with nicotine dependence risk found to date in occidental populations, according to meta-analysis of genome-wide association studies...
November 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27856557/activating-transcription-factor-3-attenuates-chemokine-and-cytokine-expression-in-mouse-skeletal-muscle-after-exercise-and-facilitates-molecular-adaptation-to-endurance-training
#17
Rodrigo Fernández-Verdejo, Aline M Vanwynsberghe, Ahmed Essaghir, Jean-Baptiste Demoulin, Tsonwin Hai, Louise Deldicque, Marc Francaux
Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type...
November 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27849555/role-of-post-transcriptional-regulation-of-mrna-stability-in-renal-pathophysiology-focus-on-chronic-kidney-disease
#18
REVIEW
Eva Feigerlová, Shyue-Fang Battaglia-Hsu
Chronic kidney disease (CKD) represents an important public health problem. Its progression to end-stage renal disease is associated with increased morbidity and mortality. The determinants of renal function decline are not fully understood. Recent progress in the understanding of post-transcriptional regulation of mRNA stability has helped the identification of both the trans- and cis-acting elements of mRNA as potential markers and therapeutic targets for difficult-to-diagnose and -treat diseases, including CKDs such as diabetic nephropathy...
November 14, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27836988/sphingomyelinase-like-phosphodiesterase-3b-mediates-radiation-induced-damage-of-renal-podocytes
#19
Anis Ahmad, Alla Mitrofanova, Jacek Bielawski, Yidong Yang, Brian Marples, Alessia Fornoni, Youssef H Zeidan
The molecular mechanisms responsible for the development of proteinuria and glomerulosclerosis in radiation nephropathy remain largely unknown. Podocytes are increasingly recognized as key players in the pathogenesis of proteinuria in primary and secondary glomerular disorders. The lipid-modulating enzyme sphingomyelin phosphodiesterase acid-like 3B (SMPDL3b) is a key determinant of podocyte injury and a known off target of the anti-CD20 antibody rituximab (RTX). The current study investigates the role of sphingolipids in radiation-induced podocytopathy...
November 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27836987/rankl-induces-bach1-nuclear-import-and-attenuates-nrf2-mediated-antioxidant-enzymes-thereby-augmenting-intracellular-reactive-oxygen-species-signaling-and-osteoclastogenesis-in-mice
#20
Hiroyuki Kanzaki, Fumiaki Shinohara, Kanako Itohiya, Yuuki Yamaguchi, Yuta Katsumata, Masazumi Matsuzawa, Sari Fukaya, Yutaka Miyamoto, Satoshi Wada, Yoshiki Nakamura
Reactive oxygen species (ROS) play a role in intracellular signaling during osteoclastogenesis. We previously reported that transcriptional factor nuclear factor E2-related factor 2 (Nrf2) was exported from the nucleus to the cytoplasm by receptor activator of nuclear factor-κB ligand (RANKL), and that Nrf2 negatively regulated osteoclastogenesis via antioxidant enzyme up-regulation. Knockout mice of BTB and CNC homology 1 (Bach1)-the competitor for Nrf2 in transcriptional regulation-was known to attenuate RANKL-mediated osteoclastogenesis, although the mechanism remains unclear...
November 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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