11,714 results match your criteria FASEB journal : official publication of the Federation of American Societies for Experimental Biology[Journal]


Pressure-induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling.

FASEB J 2018 Dec 14:fj201801474RR. Epub 2018 Dec 14.

Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Macroscale loading of bone generates a complex local mechanical microenvironment that drives osteogenesis and bone mechanoadaptation. One such mechanical stimulus generated is hydrostatic pressure (HP); however, the effect of HP on mesenchymal stem cells (MSCs) and the mechanotransduction mechanisms utilized by these cells to sense this stimulus are yet to be fully elucidated. In this study, we demonstrate that cyclic HP is a potent mediator of cytoskeletal reorganization and increases in osteogenic responses in MSCs. Read More

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December 2018

Nanoparticle-mediated lysosomal reacidification restores mitochondrial turnover and function in β cells under lipotoxicity.

FASEB J 2018 Dec 14:fj201801292R. Epub 2018 Dec 14.

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.

Chronic exposure of pancreatic β cells to high concentrations of free fatty acids leads to lipotoxicity (LT)-mediated suppression of glucose-stimulated insulin secretion. This effect is in part caused by a decline in mitochondrial function as well as by a reduction in lysosomal acidification. Because both mitochondria and lysosomes can alter one another's function, it remains unclear which initiating dysfunction sets off the detrimental cascade of LT, ultimately leading to β-cell failure. Read More

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December 2018

Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality.

FASEB J 2018 Dec 14:fj201801670R. Epub 2018 Dec 14.

Centre for Molecular and Translational Oncology (COMT), University of Parma, Parma, Italy.

The chondroitin sulfate proteoglycan 4 ( CSPG4) gene encodes a transmembrane proteoglycan (PG) constituting the largest and most structurally complex macromolecule of the human surfaceome. Its transcript shows an extensive evolutionary conservation and, due to the elaborated intracellular processing of the translated protein, it generates an array of glycoforms with the potential to exert variant-specific functions. CSPG4-mediated molecular events are articulated through the interaction with more than 40 putative ligands and the concurrent involvement of the ectodomain and cytoplasmic tail. Read More

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December 2018

Distinction of sporadic and familial forms of ALS based on mitochondrial characteristics.

FASEB J 2018 Dec 14:fj201801843R. Epub 2018 Dec 14.

Laboratory of Bioenergetics and Biomembranes, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.

Bioenergetic failure, oxidative stress, and changes in mitochondrial morphology are common pathologic hallmarks of amyotrophic lateral sclerosis (ALS) in several cellular and animal models. Disturbed mitochondrial physiology has serious consequences for proper functioning of the cell, leading to the chronic mitochondrial stress. Mitochondria, being in the center of cellular metabolism, play a pivotal role in adaptation to stress conditions. Read More

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December 2018

Nonthermal atmospheric plasma enhances myoblast differentiation by eliciting STAT3 phosphorylation.

FASEB J 2018 Dec 14:fj201800695RR. Epub 2018 Dec 14.

Department of Otolaryngology, School of Medicine, Ajou University, Suwon, South Korea.

The use of nonthermal atmospheric plasma (NTP) in the biomedical field has recently expanded into cell death induction in cancer, infection prevention, inflammation treatment, and wound-healing enhancement. NTP has been demonstrated to enhance skin and muscle regeneration, but its effects on tissue regeneration, following deep tissue or muscle damage, remains underinvestigated. In this study, we determined the effects of NTP on muscle differentiation and the mechanisms of NTP's contribution to differentiation and regeneration. Read More

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December 2018

Conformational stability and dynamics of the cancer-associated isoform Δ133p53β are modulated by p53 peptides and p53-specific DNA.

FASEB J 2018 Dec 12:fj201801973R. Epub 2018 Dec 12.

Basic Science Program, Leidos Biomedical Research, Inc., Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland, USA; and.

p53 is a tumor suppressor protein that maintains genome stability, but its Δ133p53β and Δ160p53β isoforms promote breast cancer cell invasion. The sequence truncations in the p53 core domain raise key questions related to their physicochemical properties, including structural stabilities, interaction mechanisms, and DNA-binding abilities. Herein, we investigated the conformational dynamics of Δ133p53β and Δ160p53β with and without binding to p53-specific DNA by using molecular dynamics simulations. Read More

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December 2018

Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA-540 expression.

FASEB J 2018 Dec 12:fj201802015R. Epub 2018 Dec 12.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Levels of augmenter of liver regeneration (ALR), a multifunctional protein, are reduced in steatohepatitis. ALR depletion from ALR /Alb-Cre [ALR-L-knockout (KO)] mouse causes robust steatosis and apoptosis of hepatocytes, and pericellular fibrosis between 1 and 2 wk postbirth. Steatosis regresses by 4 wk upon reappearance of ALR-expressing hepatocytes. Read More

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December 2018

Amelioration of amyloid β-FcγRIIb neurotoxicity and tau pathologies by targeting LYN.

FASEB J 2018 Dec 12:fj201800926R. Epub 2018 Dec 12.

School of Biological Sciences, Seoul National University, Seoul, South Korea; and.

SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ). Read More

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December 2018
2 Reads

Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4.

FASEB J 2018 Dec 12:fj201801498R. Epub 2018 Dec 12.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Peroxisomes are essential organelles for the specialized oxidation of a wide variety of fatty acids, but they are also able to degrade fatty acids that are typically handled by mitochondria. Using a combination of pharmacological inhibition and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 genome editing technology to simultaneously manipulate peroxisomal and mitochondrial fatty acid β-oxidation (FAO) in HEK-293 cells, we identified essential players in the metabolic crosstalk between these organelles. Depletion of carnitine palmitoyltransferase (CPT)2 activity through pharmacological inhibition or knockout (KO) uncovered a significant residual peroxisomal oxidation of lauric and palmitic acid, leading to the production of peroxisomal acylcarnitine intermediates. Read More

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December 2018

P300/CBP-associated factor regulates transcription and function of isocitrate dehydrogenase 2 during muscle differentiation.

FASEB J 2018 Dec 10:fj201800788R. Epub 2018 Dec 10.

Laboratorio di Epigenetica, Istituti Clinici Scientifici Maugeri, Pavia, Italy.

The epigenetic enzyme p300/CBP-associated factor (PCAF) belongs to the GCN5-related N-acetyltransferase (GNAT) family together with GCN5. Although its transcriptional and post-translational function is well characterized, little is known about its properties as regulator of cell metabolism. Here, we report the mitochondrial localization of PCAF conferred by an 85 aa mitochondrial targeting sequence (MTS) at the N terminus region of the protein. Read More

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December 2018

Cystathionine γ-lyase deficiency aggravates obesity-related insulin resistance via FoxO1-dependent hepatic gluconeogenesis.

FASEB J 2018 Dec 10:fj201801894R. Epub 2018 Dec 10.

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.

Hepatic gluconeogenesis makes a significant contribution to the pathogenesis of obesity and its related insulin resistance. Cystathionine γ-lyase (CSE; also cystathionase), a principal hydrogen sulfide (HS)-synthesizing enzyme in the liver, is involved in glucose and lipid metabolism disorders. However, the roles and precise mechanisms of CSE/HS in obesity and its related insulin resistance remain obscure. Read More

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December 2018
1 Read

Collagen biomaterial stimulates the production of extracellular vesicles containing microRNA-21 and enhances the proangiogenic function of CD34 cells.

FASEB J 2018 Dec 7:fj201801332R. Epub 2018 Dec 7.

Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

CD34 cells are promising for revascularization therapy, but their clinical use is limited by low cell counts, poor engraftment, and reduced function after transplantation. In this study, a collagen type I biomaterial was used to expand and enhance the function of human peripheral blood CD34 cells, and potential underlying mechanisms were examined. Compared to the fibronectin control substrate, biomaterial-cultured CD34 cells from healthy donors had enhanced proliferation, migration toward VEGF, angiogenic potential, and increased secretion of CD63CD81 extracellular vesicles (EVs). Read More

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December 2018
5.043 Impact Factor

NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.

FASEB J 2018 Dec 7:fj201801638R. Epub 2018 Dec 7.

Institute of Biochemistry, Member of the German Center for Lung Research, Justus-Liebig-University, Giessen, Germany.

Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA-binding capacity. The NF-κB p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA-binding and dimerization in p65-deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA-binding (p65 E/I) or dimerization (p65 FL/DD). Read More

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December 2018
1 Read

Activating β-catenin/Pax6 axis negatively regulates osteoclastogenesis by selectively inhibiting phosphorylation of p38/MAPK.

FASEB J 2018 Dec 7:fj201801977R. Epub 2018 Dec 7.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Balance of osteoclast formation is regulated by the receptor activator of NF-κB ligand and extracellular negative regulators such as IFN-γ and IFN-β. However, very little is known about the intrinsic negative regulatory factors of osteoclast differentiation. Recently, the paired-box homeodomain transcription factor Pax6 was shown to negatively regulate receptor activator of NF-κB ligand-mediated osteoclast differentiation. Read More

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December 2018

Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth.

FASEB J 2018 Dec 6:fj201801463R. Epub 2018 Dec 6.

Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC) Unité Mixte de Recherche (UMR) 7178, Université de Strasbourg, Strasbourg, France.

Bone loss and immune dysregulation are among the main adverse outcomes of spaceflight challenging astronaut's health and safety. However, consequences on B-cell development and responses are still under-investigated. To fill this gap, we used advanced proteomics analysis of femur bone and marrow to compare mice flown for 1 mo on board the BION-M1 biosatellite, followed or not by 1 wk of recovery on Earth, to control mice kept on Earth. Read More

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December 2018
2 Reads

Microgravity-induced hepatogenic differentiation of rBMSCs on board the SJ-10 satellite.

FASEB J 2018 Dec 6:fj201802075R. Epub 2018 Dec 6.

Key Laboratory of Microgravity, Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.

Bone marrow-derived mesenchymal stem cells (BMSCs) are able to differentiate into functional hepatocytelike cells, which are expected to serve as a potential cell source in regenerative medicine, tissue engineering, and clinical treatment of liver injury. Little is known about whether and how space microgravity is able to direct the hepatogenic differentiation of BMSCs in the actual space microenvironment. In this study, we examined the effects of space microgravity on BMSC hepatogenic differentiation on board the SJ-10 Recoverable Scientific Satellite. Read More

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December 2018
4 Reads
5.043 Impact Factor

Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.

FASEB J 2018 Dec 6:fj201801845R. Epub 2018 Dec 6.

Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA; and.

Mesenchymal stem cell (MSC)-mediated immunomodulation affects both innate and adaptive immune systems. These responses to environmental cues, such as pathogen-associated molecular patterns, damage-associated molecular patterns, or proinflammatory cytokines, are crucial for resolution of inflammation, as well as successful tissue healing and regeneration. We observed that intermittent, repeated exposure of MSCs to LPS induced stronger NF-κB activation than singular stimulation. Read More

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December 2018
1 Read

Roles of CD133 in microvesicle formation and oncoprotein trafficking in colon cancer.

FASEB J 2018 Dec 6:fj201802018R. Epub 2018 Dec 6.

Division of Life Sciences, Korea University, Seoul, South Korea.

Extracellular vesicles contain various cellular components that are involved in tumor growth, metastasis, and immune escape. Extracellular vesicles are classified into 2 groups, namely, exosomes and microvesicles (MV). Although the formation and roles of exosomes have been studied, the exact functions of MVs and mechanisms underlying MV release are not fully understood. Read More

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December 2018
3 Reads

MMP14 empowers tumor-initiating breast cancer cells under hypoxic nutrient-depleted conditions.

FASEB J 2018 Dec 6:fj201801127R. Epub 2018 Dec 6.

Institute of Molecular Medicine and Cell Research, Medical Faculty, University of Freiburg, Freiburg, Germany.

Tumor-initiating cells (TICs) existing in breast cancer are thought to be involved in initiation, progression, and relapse of tumors. In these processes, the epithelial-to-mesenchymal transition (EMT) and proteases are crucial factors that also dependent on the tumor milieu, including hypoxic nutrient-deprived, as well as normoxic nutrient-rich, environments. Therefore, we investigated EMT and proteases in TICs and their response to different environments by means of a newly generated immortalized TIC (iTIC) line. Read More

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December 2018
2 Reads

Evidence for functional interactions between the placenta and brain in pregnant mice.

FASEB J 2018 Dec 6:fj201802037R. Epub 2018 Dec 6.

Division of Animal Sciences, University of Missouri, Columbia, Missouri, USA.

The placenta plays a pivotal role in the development of the fetal brain and also influences maternal brain function, but our understanding of communication between the placenta and brain remains limited. Using a gene expression and network analysis approach, we provide evidence that the placenta transcriptome is tightly interconnected with the maternal brain and fetal brain in d 15 pregnant C57BL/6J mice. Activation of serotonergic synapse signaling and inhibition of neurotrophin signaling were identified as potential mediators of crosstalk between the placenta and maternal brain and fetal brain, respectively. Read More

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December 2018
3 Reads
5.043 Impact Factor

Development of a host-microbiome model of the small intestine.

FASEB J 2018 Dec 6:fj201801414R. Epub 2018 Dec 6.

Center for Microbial Ecology and Technology (CMET), Ghent University, Ghent, Belgium.

The intestinal epithelium plays an essential role in the balance between tolerant and protective immune responses to infectious agents. In vitro models do not typically consider the innate immune response and gut microbiome in detail, so these models do not fully mimic the physiologic aspects of the small intestine. We developed and characterized a long-term in vitro model containing enterocyte, goblet, and immune-like cells exposed to a synthetic microbial community representative of commensal inhabitants of the small intestine. Read More

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December 2018
2 Reads

Blocking Tyr265 nitration of protein phosphatase 2A attenuates nitrosative stress-induced endothelial dysfunction in renal microvessels.

FASEB J 2018 Dec 6:fj201800885RR. Epub 2018 Dec 6.

Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Protein tyrosine (Tyr) nitration, the covalent addition of a nitro group (NO) to Tyr residues, is emerging as a candidate mechanism of endothelial dysfunction. Previous studies have shown that Tyr nitration is primarily induced by nitrosative stress, a process characterized by the production of reactive nitrogen species, especially peroxynitrite anion (ONOO), which is considered a secondary product of NO in the presence of superoxide radicals (O). However, the impact of nitrosative stress-induced Tyr nitration on endothelial dysfunction has not been thoroughly elucidated to date. Read More

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December 2018
1 Read

Global Tudor-SN transgenic mice are protected from obesity-induced hepatic steatosis and insulin resistance.

FASEB J 2018 Dec 6:fj201801253RR. Epub 2018 Dec 6.

Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Tianjin Medical University, Tianjin, China.

In the current study, we explored the impact of Tudor-staphylococcal nuclease (SN) on obesity induced by a high-fat diet (HFD) in mice, because the functional involvement of Tudor-SN in lipid metabolism in vivo is unknown. HFD-transgenic (Tg) mice exhibited reductions in hepatic steatosis and systemic insulin resistance. There was no difference in hepatic lipid accumulation between chow-fed wild-type (WT) and chow-fed Tg mice; consistently, no difference in activation of the lipogenic pathway was detected. Read More

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December 2018
2 Reads
5.043 Impact Factor

Oligomerization of equilibrative nucleoside transporters: a novel regulatory and functional mechanism involving PKC and PP1.

FASEB J 2018 Dec 6:fj201800440RR. Epub 2018 Dec 6.

Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada.

Equilibrative nucleoside transporters (ENTs) translocate nucleosides and nucleobases across plasma membranes, as well as a variety of anti-cancer, -viral, and -parasite nucleoside analogs. They are also key members of the purinome complex and regulate the protective and anti-inflammatory effects of adenosine. Despite their important role, little is known about the mechanisms involved in their regulation. Read More

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December 2018
3 Reads

Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs.

FASEB J 2018 Dec 6:fj201800981R. Epub 2018 Dec 6.

Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

As mechanisms controlling redox homeostasis become impaired with aging, exaggerated oxidant stress may cause disproportional oxidation of cell membranes and circulating phospholipids (PLs), leading to the formation of truncated oxidized PL products (Tr-OxPLs), which exhibit deleterious effects. This study investigated the role of elevated Tr-OxPLs as a factor exacerbating inflammation and lung barrier dysfunction in an animal model of aging. Mass spectrometry analysis of Tr-OxPL species in young (2-4 mo) and aging (18-24 mo) mice revealed elevated basal levels of several products [1-palmitoyl-2-(5-oxovaleroyl)- sn-glycero-phosphocholine (POVPC), 1-palmitoyl-2-glutaroyl- sn-glycero-phosphocholine, lysophosphocholine, 1-palmitoyl-2-(9-oxo-nonanoyl)- sn-glycero-3-phosphocholine, 1-palmitoyl-2-azelaoyl- sn-glycero-3-phosphocholine, O-1-O-palmitoyl-2-O-(5,8-dioxo-8-hydroxy-6-octenoyl)-l-glycero-3-phosphocholine, and others] in the aged lungs. Read More

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December 2018
6 Reads

microRNA-129-5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex.

FASEB J 2018 Dec 6:fj201801094RR. Epub 2018 Dec 6.

Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA.

Choline availability modulates neurogenesis and cerebral cortex development through the regulation of neural progenitor cell (NPC) proliferative and differentiation capacity. In this study, we demonstrated that cortical NPC self-renewal is controlled by choline via the expression of a microRNA (miR-129-5p), whose role in the developing brain has not been examined, and which, in turn, inhibits synthesis of the epidermal growth factor receptor (EGFR) protein. Specifically, we found that low choline (LC) availability led to the upregulation of miR-129-5p expression in cortical NPCs in vitro and in vivo, causing the downregulation of EGFR and thereby disrupting NPC self-renewal and cortical neurogenesis. Read More

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December 2018
1 Read

Recommended housing densities for research mice: filling the gap in data-driven alternatives.

FASEB J 2018 Dec 6:fj201801972R. Epub 2018 Dec 6.

The Jackson Laboratory, Bar Harbor, Maine, USA.

Space recommendations for mice made in the Guide for Care and Use of Laboratory Animals have not changed since 1972, despite important improvements in husbandry and caging practices. The 1996 version of the Guide put forth a challenge to investigators to produce new data evaluating the effects of space allocation on the well-being of mice. In this review, we summarize many studies published in response to this challenge. Read More

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December 2018

Cell surface CD63 increased by up-regulated polylactosamine modification sensitizes human melanoma cells to the BRAF inhibitor PLX4032.

FASEB J 2018 Dec 3:fj201800664RR. Epub 2018 Dec 3.

Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; and.

The BRAF inhibitor PLX4032 is effective in treating BRAF-mutated melanoma; however, because drug resistance develops in most cases, it is critical to develop a new strategy for inhibiting drug-resistant melanoma growth. The melanoma-associated membrane glycoprotein CD63 is involved in cell proliferation and metastasis. Here, we found that cell surface CD63 suppresses the proliferation of human melanoma cells and PLX4032-resistant cells. Read More

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December 2018
1 Read

Preassociation between the 5-HT serotonin receptor and G protein G: molecular determinants and association with low potency activation of adenylyl cyclase.

FASEB J 2018 Dec 3:fj201800805RR. Epub 2018 Dec 3.

Department of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.

According to early models of GPCR signaling, G proteins only interact with activated receptors. However, some GPCRs were shown to assemble with G proteins before receptor activation, in accordance with more recent models. Previously, we found that the 5-HT receptor, as opposed to the 5-HT receptor, was preassociated with G, but the molecular determinants for this interaction are still elusive. Read More

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December 2018
1 Read

Data driven mathematical modelling reveals the dynamic mechanism of MSC-induced neovascularization.

FASEB J 2018 Dec 5:fj201801652R. Epub 2018 Dec 5.

MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China.

Coculture of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) in vitro leads to the formation of a capillary-like reticular structure by ECs, which has great potential as a better substitute for artificial blood vessels in terms of stability and functionality. To investigate the mechanisms of the early neovascularization induced by MSCs, we analyzed the kinematic features of the motion of ECs and concluded that the dynamic interaction between cells and the extracellular matrix would reveal the capillary-like structure formation. Based on this hypothesis, we proposed a mathematical model to simulate the vascular-like migration pattern of ECs in silico, which was confirmed by in vitro studies. Read More

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December 2018

Therapeutic expression of human clotting factors IX and X following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.

FASEB J 2018 Dec 5:fj201801391R. Epub 2018 Dec 5.

Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Adeno-associated viral vectors (AAVs) achieve stable therapeutic expression without long-term toxicity in adults with hemophilia. To avert irreversible complications in congenital disorders producing early pathogenesis, safety and efficacy of AAV-intrauterine gene transfer (IUGT) requires assessment. We therefore performed IUGT of AAV5 or -8 with liver-specific promoter-1 encoding either human coagulation factors IX (hFIX) or X (hFX) into Macaca fascicularis fetuses at ∼0. Read More

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December 2018
2 Reads

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition.

FASEB J 2018 Dec 4:fj201801695R. Epub 2018 Dec 4.

Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; and.

Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN-induced villus atrophy is accompanied by elevated expression of CUGBP, Elav-like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). Read More

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December 2018
1 Read

SIRT6 deacetylase activity regulates NAMPT activity and NAD(P)(H) pools in cancer cells.

FASEB J 2018 Dec 4:fj201800321R. Epub 2018 Dec 4.

Section of Biochemistry, Department of Experimental Medicine, Center for Excellence in Biomedical Research (CEBR), University of Genoa, Genoa, Italy.

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway from nicotinamide. By controlling the biosynthesis of NAD, NAMPT regulates the activity of NAD-converting enzymes, such as CD38, poly-ADP-ribose polymerases, and sirtuins (SIRTs). SIRT6 is involved in the regulation of a wide number of metabolic processes. Read More

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December 2018

Autophagy is required for the directed motility of keratinocytes driven by electric fields.

FASEB J 2018 Dec 3:fj201801294R. Epub 2018 Dec 3.

Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF-biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Read More

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December 2018
1 Read

HOXC6 promotes cervical cancer progression via regulation of Bcl-2.

FASEB J 2018 Dec 3:fj201801099RR. Epub 2018 Dec 3.

Department of Obstetrics and Gynecology, People's Hospital of Linyi City, Linyi City, China; and.

Homeobox C6 ( HOXC6) is a transcription factor that plays an important role in the development of several cancers. However, it is unknown whether HOXC6 regulates cervical cancer progression. In this study, we used quantitative PCR and Western blots to demonstrate that HOXC6 overexpression is associated with cervical cancer progression. Read More

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December 2018
2 Reads

Where cone snails and spiders meet: design of small cyclic sodium-channel inhibitors.

FASEB J 2018 Dec 3:fj201801909R. Epub 2018 Dec 3.

Toxicology and Pharmacology, Katholieke Universiteit (KU) Leuven, Campus Gasthuisberg, Leuven, Belgium.

A 13 aa residue voltage-gated sodium channel (Na) inhibitor peptide, Pn, containing 2 disulfide bridges was designed by using a chimeric approach. This approach was based on a common pharmacophore deduced from sequence and secondary structural homology of 2 Na inhibitors: Conus kinoshitai toxin IIIA, a 14 residue cone snail peptide with 3 disulfide bonds, and Phoneutria nigriventer toxin 1, a 78 residue spider toxin with 7 disulfide bonds. As with the parent peptides, this novel Na channel inhibitor was active on Na1. Read More

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December 2018
3 Reads

Substrates of P4-ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine).

FASEB J 2018 Dec 3:fj201801873R. Epub 2018 Dec 3.

Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

P4-ATPases, a subfamily of P-type ATPases, were initially identified as aminophospholipid translocases in eukaryotic membranes. These proteins generate and maintain membrane lipid asymmetry by translocating aminophospholipids (phosphatidylserine and phosphatidylethanolamine) from the exoplasmic/lumenal leaflet to the cytoplasmic leaflet. The human genome encodes 14 P4-ATPases, and the cellular localizations, substrate specificities, and cellular roles of these proteins were recently revealed. Read More

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December 2018
3 Reads

The role of raptor in the mechanical load-induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy.

FASEB J 2018 Dec 3:fj201801653RR. Epub 2018 Dec 3.

Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.

It is well known that an increase in mechanical loading can induce skeletal muscle hypertrophy, and a long standing model in the field indicates that mechanical loads induce hypertrophy via a mechanism that requires signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Specifically, it has been widely proposed that mechanical loads activate signaling through mTORC1 and that this, in turn, promotes an increase in the rate of protein synthesis and the subsequent hypertrophic response. However, this model is based on a number of important assumptions that have not been rigorously tested. Read More

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December 2018

APOE genotype affects metabolic and Alzheimer-related outcomes induced by Western diet in female EFAD mice.

FASEB J 2018 Dec 3:fj201801756R. Epub 2018 Dec 3.

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.

Development of Alzheimer's disease (AD) is regulated by interactive effects of genetic and environmental risk factors. The most significant genetic risk factor for AD is the ε4 allele of apolipoprotein E ( APOE4), which has been shown to exert greater AD risk in women. An important modifiable AD risk factor is obesity and its associated metabolic dysfunctions. Read More

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December 2018
2 Reads

Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.

FASEB J 2018 Dec 3:fj201801910R. Epub 2018 Dec 3.

Department of Physics, Biological Physical Sciences Institute, University of York, York, United Kingdom.

Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor "recycling" that allows multiple toxin pores to be formed close together. Read More

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December 2018

SND1 acts upstream of SLUG to regulate the epithelial-mesenchymal transition (EMT) in SKOV3 cells.

FASEB J 2018 Dec 3:fj201801728R. Epub 2018 Dec 3.

Key Laboratory of Immune Microenvironment and Disease, School of Basic Medical Sciences, Tianjin Medical University, Ministry of Education, Tianjin, China.

Staphylococcal nuclease domain-containing protein 1 (SND1) has been reported as an oncoprotein in a variety of cancers involving multiple processes, including proliferation, angiogenesis, and metastasis. However, the mechanisms underlying metastasis remain largely unknown. Herein, by using the ovarian cancer cell line SKOV3, which has high metastasis ability, we showed that loss-of-function of SND1 dramatically suppressed the invasion and migration of SKOV3 cells. Read More

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December 2018

GABA promotes β-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity.

FASEB J 2018 Dec 3:fj201801397R. Epub 2018 Dec 3.

Department of Physiology, University of Toronto, Toronto, Ontario, Canada.

γ-Aminobutyric acid (GABA) administration has been shown to increase β-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum) to mice indeed increased pancreatic β-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. Read More

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December 2018

Stress hormone signaling through β-adrenergic receptors regulates macrophage mechanotype and function.

FASEB J 2018 Dec 3:fj201801429RR. Epub 2018 Dec 3.

Department of Integrative Biology and Physiology, University of California, Los Angeles, California, USA.

Critical functions of immune cells require them to rapidly change their shape and generate forces in response to cues from their surrounding environment. However, little is known about how soluble factors that may be present in the microenvironment modulate key aspects of cellular mechanobiology-such as immune cell deformability and force generation-to impact functions such as phagocytosis and migration. Here we show that signaling by soluble stress hormones through β-adrenoceptors (β-AR) reduces the deformability of macrophages; this is dependent on changes in the organization of the actin cytoskeleton and is associated with functional changes in phagocytosis and migration. Read More

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December 2018
1 Read

Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM-1.

FASEB J 2018 Nov 29:fj201801231RR. Epub 2018 Nov 29.

Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain.

Atherosclerosis is a chronic disease characterized by vascular lipid retention and inflammation, and pattern recognition receptors (PRRs) are important contributors in early stages of the disease. Given the implication of the intracellular PRR nucleotide-binding oligomerization domain 1 (NOD1) in cardiovascular diseases, we investigated its contribution to early atherosclerosis. We evidenced NOD1 induction in atherosclerotic human and mouse tissues, predominantly in vascular endothelial cells. Read More

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November 2018
4 Reads

Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney.

FASEB J 2018 Nov 29:fj201802054R. Epub 2018 Nov 29.

Department of Applied Physics, Science for Life Laboratory, Kungliga Tekniska Högskolan (KTH) Royal Institute of Technology, Solna, Sweden.

The central role of calcium signaling during development of early vertebrates is well documented, but little is known about its role in mammalian embryogenesis. We have used immunofluorescence and time-lapse calcium imaging of cultured explanted embryonic rat kidneys to study the role of calcium signaling for branching morphogenesis. In mesenchymal cells, we recorded spontaneous calcium activity that was characterized by irregular calcium transients. Read More

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November 2018
1 Read

Heat shock-induced mitotic arrest requires heat shock protein 105 for the activation of spindle assembly checkpoint.

FASEB J 2018 Nov 29:fj201801369R. Epub 2018 Nov 29.

Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.

Heat shock causes proteotoxic stress that induces various cellular responses, including delayed mitotic progression and the generation of an aberrant number of chromosomes. In this study, heat shock delayed the onset of anaphase by increasing the number of misoriented cells, accompanied by the kinetochore localization of budding uninhibited by benzimidazole-related (BubR)1 in a monopolar spindle (Mps)1-dependent manner. The mitotic delay was canceled by knockdown of mitotic arrest defect (Mad)2. Read More

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November 2018

Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

FASEB J 2018 Nov 29:fj201801489R. Epub 2018 Nov 29.

Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Dendritic cells (DCs) have crucial roles in immune-related diseases. However, it is difficult to explore DCs because of their rareness and heterogeneity. Although previous studies had been performed to detect the phenotypic characteristics of DC populations, the functional diversity has been ignored. Read More

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November 2018

Microglial distribution, branching, and clearance activity in aged rat hippocampus are affected by astrocyte meshwork integrity: evidence of a novel cell-cell interglial interaction.

FASEB J 2018 Nov 29:fj201801539R. Epub 2018 Nov 29.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Aging and neurodegenerative diseases share a condition of neuroinflammation entailing the production of endogenous cell debris in the CNS that must be removed by microglia ( i.e., resident macrophages), to restore tissue homeostasis. Read More

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November 2018

A role for bone marrow-derived cells in diabetic nephropathy.

FASEB J 2018 Nov 29:fj201801825R. Epub 2018 Nov 29.

Department of Future Basic Medicine, Nara Medical University, Nara, Japan.

Diabetes mellitus causes systemic disorders. We previously demonstrated that diabetic condition forced bone marrow-derived cells (BMDCs) to express TNF-α, leading to the development of diabetic neuropathy in mice. Here, we hypothesized that these abnormal BMDCs are also involved in diabetic nephropathy. Read More

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November 2018
3 Reads

The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries.

FASEB J 2018 Nov 29:fj201801680R. Epub 2018 Nov 29.

Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic.

Histone deacetylase 6 (HDAC6) is a multidomain cytosolic hydrolase acting mostly on nonhistone protein substrates. Investigations of the substrate specificity of HDAC6 are confounded by the presence of 2 catalytically active deacetylase domains (DD1 and DD2). In this study, acetylome peptide microarrays and peptide libraries were used to map the substrate specificity of DD1 and DD2 of human HDAC6. Read More

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November 2018