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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/28330853/noncoding-mirnas-bridge-virus-infection-and-host-autophagy-in-shrimp-in-vivo
#1
Yaodong He, Yuechao Sun, Xiaobo Zhang
Autophagy is known to be involved in viral infection. However, the relationship between autophagy and viral infection has not been characterized. MicroRNAs (miRNAs), important regulators of gene transcription, play central roles in many biologic processes, including autophagy and viral infection. It was therefore of interest to investigate the miRNAs regulating viral infection and host autophagy. In this study the viral infection (white spot syndrome virus, WSSV) correlated positively with the host autophagy in shrimp...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#2
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28325757/loss-of-cd73-prevents-accumulation-of-alternatively-activated-macrophages-and-the-formation-of-prefibrotic-macrophage-clusters-in-irradiated-lungs
#3
Simone de Leve, Florian Wirsdörfer, Federica Cappuccini, Alexandra Schütze, Alina V Meyer, Katharina Röck, Linda F Thompson, Jens W Fischer, Martin Stuschke, Verena Jendrossek
While radiotherapy is a mainstay for cancer therapy, pneumonitis and fibrosis constitute dose-limiting side effects of thorax and whole body irradiation. So far, the contribution of immune cells to disease progression is largely unknown. Here we studied the role of ecto-5'-nucelotidase (CD73)/adenosine-induced changes in the myeloid compartment in radiation-induced lung fibrosis. C57BL/6 wild-type or CD73(-/-) mice received a single dose of whole thorax irradiation (WTI, 15 Gy). Myeloid cells were characterized in flow cytometric, histologic, and immunohistochemical analyses as well as RNA analyses...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28325756/a-novel-role-for-myeloid-cell-specific-neuropilin-1-in-mitigating-sepsis
#4
Xiaoyan Dai, Imoh Okon, Zhaoyu Liu, Yue Wu, Huaiping Zhu, Ping Song, Ming-Hui Zou
Sepsis-typically caused by an uncontrolled and amplified host systemic inflammatory response to microbial infection-is a life-threatening complex clinical disorder and remains a major cause of infection-related deaths in the intensive care unit. Emerging evidence suggests that neuropilin 1 (Nrp1), an originally defined coreceptor for class 3 semaphorins and VEGF, plays important roles in the immune system; however, the function and regulation of macrophage Nrp1 in host immune defense against bacterial infection remain unknown...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28325755/loss-of-pink1-leads-to-metabolic-deficits-in-adult-neural-stem-cells-and-impedes-differentiation-of-newborn-neurons-in-the-mouse-hippocampus
#5
Sandeep Kumar Agnihotri, Ruifang Shen, Jihong Li, Xu Gao, Hansruedi Büeler
Emerging evidence suggests that mitochondrial dynamics regulates adult hippocampal neurogenesis (AHN). Although abnormal AHN has been linked to depression, anxiety, and cognitive dysfunction, which are features of neurodegenerative conditions, including Parkinson's disease (PD), the impact of mitochondrial deficits on AHN have not been explored previously in a model of neurodegeneration. Here, we used PTEN-induced kinase 1-deficient (PINK1(-/-) ) mice that lacked a mitochondrial kinase mutated in recessive familial PD...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28314769/infrared-spectroscopic-characterization-of-monocytic-microvesicles-microparticles-released-upon-lipopolysaccharide-stimulation
#6
Joonsup Lee, Beryl Wen, Elizabeth A Carter, Valery Combes, Georges E R Grau, Peter A Lay
Microvesicles (MVs) are involved in cell-cell interactions, including disease pathogenesis. Nondestructive Fourier-transform infrared (FTIR) spectra from MVs were assessed as a technique to provide new biochemical insights into a LPS-induced monocyte model of septic shock. FTIR spectroscopy provided a quick method to investigate relative differences in biomolecular content of different MV populations that was complementary to traditional semiquantitative omics approaches, with which it is difficult to provide information on relative changes between classes (proteins, lipids, nucleic acids, carbohydrates) or protein conformations...
March 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28314768/pseudomonas-aeruginosa-infection-liberates-transmissible-cytotoxic-prion-amyloids
#7
Ron Balczon, K Adam Morrow, Chun Zhou, Bradley Edmonds, Mikhail Alexeyev, Jean-Francois Pittet, Brant M Wagener, Stephen A Moser, Silas Leavesley, Xiangming Zha, Dara W Frank, Troy Stevens
Patients who recover from pneumonia subsequently have elevated rates of death after hospital discharge as a result of secondary organ damage, the causes of which are unknown. We used the bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, as a model for investigating this phenomenon. We show that infection of pulmonary endothelial cells by P. aeruginosa induces production and release of a cytotoxic amyloid molecule with prion characteristics, including resistance to various nucleases and proteases...
March 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28302652/the-entpd1-promoter-polymorphism-860-a-g-rs3814159-is-associated-with-increased-gene-transcription-protein-expression-cd39-ntpdase1-enzymatic-activity-and-thromboembolism-risk
#8
James P Maloney, Brian R Branchford, Gary L Brodsky, Maxwell S Cosmic, David W Calabrese, Christina L Aquilante, Kelly W Maloney, Joseph R Gonzalez, Weiming Zhang, Kerrie L Moreau, Kerri L Wiggins, Nicholas L Smith, Ulrich Broeckel, Jorge Di Paola
Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1) degrades the purines ATP and ADP that are key regulators of inflammation and clotting. We hypothesized that NTPDase1 polymorphisms exist and that they regulate this pathway. We sequenced the ENTPD1 gene (encoding NTPDase1) in 216 subjects then assessed genotypes in 2 cohorts comprising 2213 humans to identify ENTPD1 polymorphisms associated with venous thromboembolism (VTE). The G allele of the intron 1 polymorphism rs3176891 was more common in VTE vs...
March 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28298336/moonlighting-glycolytic-protein-glyceraldehyde-3-phosphate-dehydrogenase-gapdh-an-evolutionarily-conserved-plasminogen-receptor-on-mammalian-cells
#9
Anoop Singh Chauhan, Manoj Kumar, Surbhi Chaudhary, Anil Patidar, Asmita Dhiman, Navdeep Sheokand, Himanshu Malhotra, Chaaya Iyengar Raje, Manoj Raje
Prokaryotic pathogens establish infection in mammals by capturing the proteolytic enzyme plasminogen (Plg) onto their surface to digest host extracellular matrix (ECM). One of the bacterial surface Plg receptors is the multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In a defensive response, the host mounts an inflammatory response, which involves infiltration of leukocytes to sites of inflammation. This requires macrophage exit from the blood and migration across basement membranes, a phenomenon dependent on proteolytic remodeling of the ECM utilizing Plg...
March 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28298335/hyperglycemia-and-hyperinsulinemia-induced-insulin-resistance-causes-alterations-in-cellular-bioenergetics-and-activation-of-inflammatory-signaling-in-lymphatic-muscle
#10
Yang Lee, James D Fluckey, Sanjukta Chakraborty, Mariappan Muthuchamy
Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance...
March 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28292961/modeling-month-season-of-birth-as-a-risk-factor-in-mouse-models-of-chronic-disease-from-multiple-sclerosis-to-autoimmune-encephalomyelitis
#11
Jacob D Reynolds, Laure K Case, Dimitry N Krementsov, Abbas Raza, Rose Bartiss, Cory Teuscher
Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate...
March 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28289056/expression-and-trafficking-of-placental-micrornas-at-the-feto-maternal-interface
#12
Guojing Chang, Jean-François Mouillet, Takuya Mishima, Tianjiao Chu, Elena Sadovsky, Carolyn B Coyne, W Tony Parks, Urvashi Surti, Yoel Sadovsky
During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively in the placenta. Trafficking of these miRNAs among the maternal, placental, and fetal compartments is unknown. To determine miRNA expression and trafficking patterns during pregnancy, we sequenced miRNAs in triads of human placenta and of maternal and fetal blood and found large subject-to-subject variability, with C19MC exhibiting compartment-specific expression...
March 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28283543/kcnq-smit-complex-formation-facilitates-ion-channel-solute-transporter-cross-talk
#13
Daniel L Neverisky, Geoffrey W Abbott
Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmented in vivo by phosphatidylinositol 4,5-bisphosphate (PIP2), which is generated from myo-inositol, an osmolyte transported into cells by sodium-dependent myo-inositol transporters (SMITs). Here, we discovered that KCNQ2/3 channels isoform-specifically colocalize with SMIT1 and SMIT2 at sciatic nerve nodes of Ranvier and in axon initial segments, and form channel-transporter complexes in vitro and in vivo KCNQ2/3 coexpression protected SMIT1 activity from the otherwise inhibitory effects of cellular depolarization imposed by elevating extracellular [K(+)], and KCNQ2 was required for potentiation of SMIT activity by myo-inositol preincubation...
March 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28283542/sex-difference-in-mouse-metabolic-response-to-erythropoietin
#14
Yuanyuan Zhang, Heather M Rogers, Xiaojie Zhang, Constance Tom Noguchi
Erythropoietin (EPO) is the cytokine that regulates red blood cell production. Less understood is the nonerythroid action of EPO, including metabolic regulation of fat accumulation and glucose homeostasis. Although EPO treatment increased hematocrit and improved glucose tolerance in male and female mice, we observed a gender difference in EPO effects in weight control. EPO treatment reduced diet-induced weight gain from 9.6 ± 1.5 g to 4.2 ± 1.4 g in male mice (P < 0.001), while the weight gain in female mice were similar (4...
March 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28280005/kcne2-deletion-impairs-insulin-secretion-and-causes-type-2-diabetes-mellitus
#15
Soo Min Lee, Jasmine Baik, Dara Nguyen, Victoria Nguyen, Shiwei Liu, Zhaoyang Hu, Geoffrey W Abbott
Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28280004/connexin-purinergic-signaling-in-enteric-glia-mediates-the-prolonged-effect-of-morphine-on-constipation
#16
Sukhada Bhave, Aravind Gade, Minho Kang, Kurt F Hauser, William L Dewey, Hamid I Akbarali
Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro)...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28280003/epigenetic-memory-in-response-to-environmental-stressors
#17
Paolo Vineis, Aristotelis Chatziioannou, Vincent T Cunliffe, James M Flanagan, Mark Hanson, Micheline Kirsch-Volders, Soterios Kyrtopoulos
Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28280002/n-acetylcysteine-accelerates-amputation-stump-healing-in-the-setting-of-diabetes
#18
Mohamed A Zayed, Xiachao Wei, Kyoung-Mi Park, Larisa Belaygorod, Uzma Naim, Joseph Harvey, Li Yin, Kendall Blumer, Clay F Semenkovich
Over 60% of lower extremity amputations are performed in patients with diabetes and peripheral arterial disease, and at least 25% require subsequent reamputation due to poor surgical site healing. The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood. N-acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes. We tested the hypothesis that NAC alters the vascular milieu to improve healing of amputation stumps in diabetes using a novel in vivo murine hindlimb ischemia-amputation model...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28274989/nadph-oxidase-nox2-mediates-tlr2-6-dependent-release-of-gm-csf-from-endothelial-cells
#19
Jutta Schuett, Harald Schuett, Raghav Oberoi, Ann-Kathrin Koch, Silke Pretzer, Maren Luchtefeld, Bernhard Schieffer, Karsten Grote
NADPH oxidase-generated reactive oxygen species (ROS) from immune cells are well known to be important for pathogen killing in response to TLR ligands. Here, we investigated a new aspect of NADPH oxidase in the TLR2/6-induced release of the immunologically relevant GM-CSF by endothelial cells. Stimulation of human endothelial cells with TLR2/6 agonist, MALP-2 (macrophage-activating lipopeptide of 2 kDa), induced NADPH oxidase activation and ROS formation. Inhibition by ROS scavengers and NADPH oxidase inhibitors blocked MALP-2-induced GM-CSF release...
March 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28270519/plasminogen-activator-inhibitor-1-regulates-macrophage-dependent-postoperative-adhesion-by-enhancing-egf-her1-signaling-in-mice
#20
Kumpei Honjo, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Hiroshi Shimazu, Salita Eiamboonsert, Douaa Dhahri, Atsuhiko Ichimura, Takashi Dan, Toshio Miyata, Kazuyoshi Takeda, Kazuhiro Sakamoto, Koichi Hattori, Beate Heissig
Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat(-/-) and Serpine1(-/-) In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275...
March 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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