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https://www.readbyqxmd.com/read/29458059/modest-enhancement-of-sensory-axon-regeneration-in-the-sciatic-nerve-with-conditional-co-deletion-of-pten-and-socs3-in-the-dorsal-root-ganglia-of-adult-mice
#1
Zachary R Gallaher, Oswald Steward
Axons within the peripheral nervous system are capable of regeneration, but full functional recovery is rare. Recent work has shown that conditional deletion of two key signaling inhibitors of the PI3K and Jak/Stat pathways-phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3), respectively-promotes regeneration of normally non-regenerative central nervous system axons. Moreover, in studies of optic nerve regeneration, co-deletion of both PTEN and SOCS3 has an even greater effect...
February 16, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29458024/spinal-cord-specific-deletion-of-the-glutamate-transporter-glt1-causes-motor-neuron-death-in-mice
#2
Kaori Sugiyama, Kohichi Tanaka
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder characterized by the selective loss of motor neurons. The precise mechanisms that cause the selective death of motor neurons remain unclear, but a growing body of evidence suggests that glutamate-mediated excitotoxicity has been considered to play an important role in the mechanisms of motor neuron degeneration in ALS. Reductions in glutamate transporter GLT1 have been reported in animal models of ALS and the motor cortex and spinal cord of ALS patients...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29454793/p300-acetyltransferase-mediates-stiffness-induced-activation-of-hepatic-stellate-cells-into-tumor-promoting-myofibroblasts
#3
Changwei Dou, Zhikui Liu, Kangsheng Tu, Hongbin Zhang, Chen Chen, Usman Yaqoob, Yuanguo Wang, Jialing Wen, Jan van Deursen, Delphine Sicard, Daniel Tschumperlin, Hongzhi Zou, Wei-Chien Huang, Raul Urrutia, Vijay H Shah, Ningling Kang
BACKGROUND & AIMS: Hepatic stellate cells (HSCs) contribute to desmoplasia and stiffness of liver metastases by differentiating into matrix-producing myofibroblasts. We investigated whether stiffness due to the presence of tumors increases activation of HSCs into myofibroblasts and their tumor-promoting effects, as well as the role of E1A binding protein p300 (EP300 or p300), a histone acetyltransferase that regulates transcription, in these processes. METHODS: HSCs were isolated from liver tissues of patients, mice in which the p300 gene was flanked by 2 loxP sites (p300F/F mice), and p300+/+ mice (controls)...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29453401/endothelial-smoothened-dependent-hedgehog-signaling-is-not-required-for-sonic-hedgehog-induced-angiogenesis-or-ischemic-tissue-repair
#4
Rajesh Gupta, Alexander R Mackie, Sol Misener, Lijun Liu, Douglas W Losordo, Raj Kishore
Sonic Hedgehog (Shh) signaling induces neovascularization and angiogenesis. It is not known whether the hedgehog signaling pathway in endothelial cells is essential to angiogenesis. Smoothened (Smo) transduces hedgehog signaling across the cell membrane. This study assessed whether endothelial Smoothened-dependent Shh signaling is required for Shh-mediated angiogenesis and ischemic tissue repair. Endothelial-specific smoothened knockout mice, eSmo Null were created using Cre-lox recombination system. eSmo Null mice had no observable phenotype at baseline and showed normal cardiac function...
February 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29452569/up-regulation-of-sftpb-expression-and-attenuation-of-acute-lung-injury-by-pulmonary-epithelial-cell-specific-nampt-knockdown
#5
Guangliang Bi, Lei Wu, Peixin Huang, Shamima Islam, Daniel P Heruth, Li Qin Zhang, Ding-You Li, Venkatesh Sampath, Weimin Huang, Brett A Simon, Ronald Blaine Easley, Shui Qing Ye
Although a deficiency of surfactant protein B (SFTPB) has been associated with lung injury, SFTPB expression has not yet been linked with nicotinamide phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB expression and lung inflammation were investigated in a LPS-induced ALI mouse model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression, achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing epithelial-specific transgene Cre or by the use of epithelial-specific expression of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29452147/combination-of-kras-activation-and-pten-deletion-contributes-to-murine-hepatopancreatic-ductal-malignancy
#6
Yun-Kai Lin, Zheng Fang, Tian-Yi Jiang, Zheng-Hua Wan, Yu-Fei Pan, Yun-Han Ma, Yuan-Yuan Shi, Ye-Xiong Tan, Li-Wei Dong, Yong-Jie Zhang, Hong-Yang Wang
Kras mutations are among the most common genetic abnormalities in human neoplasms, including cholangiocarcinomas, pancreatic cancer and colon cancer. PTEN has previously been associated with cholangiocarcinoma development in murine models. Here, we have established novel mouse models of neoplasms by liver-specific and biliary-pancreatic Kras activation and PTEN deletion. By liver-specific disruption of PTEN and activation of Kras in mice caused rapid development of intrahepatic biliary epithelial proliferative lesions (Intrahepatic cholangiocarcinoma, ICC), which progress through dysplasia to invasive carcinoma...
February 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29452101/socs3-deficiency-in-myeloid-cells-promotes-retinal-degeneration-and-angiogenesis-through-arginase-1-up-regulation-in-experimental-autoimmune-uveoretinitis
#7
Mei Chen, Jiawu Zhao, Imran Ha Ali, Stephen Marry, Josy Augustine, Mohajeet Bhuckory, Aisling Lynch, Adrien Kissenpfennig, Heping Xu
The suppressor of cytokine signalling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysM Cre/+ SOCS3 fl/fl ). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysM Cre/+ SOCS3 fl/fl mice compared to that in WT mice...
February 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29450388/rare-case-of-ocular-tuberculosis-in-a-diabetic-patient-diagnostic-and-therapeutic-dilemmas
#8
Anca Pantalon, Emanuela Găman, Iustina-Silvia Crețu-Silivestru, Ciprian Danielescu
We present the case of a patient who was diagnosed by chance with macular hypopyon during a conventional interdisciplinary examination. The clinical context and the association of a systemic disease, such as uncontrolled type 1 diabetes, rendered further investigations in this patient. Due to his immunocompromised status, etiology such as ocular fungi, lymphomas, tuberculosis was taken into account. Thorough complex investigations oriented the diagnosis towards ocular tuberculosis involvement.
April 2017: Romanian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29449332/inhibition-of-endothelial-notch1-signaling-attenuates-inflammation-by-reducing-cytokine-mediated-histone-acetylation-at-inflammatory-enhancers
#9
Lars la Cour Poulsen, Reidunn Jetne Edelmann, Stig Krüger, Rodrigo Diéguez-Hurtado, Akshay Shah, Tor Espen Stav-Noraas, Anastasia Renzi, Monika Szymanska, Junbai Wang, Manuel Ehling, Rui Benedito, Monika Kasprzycka, Espen Bækkevold, Olav Sundnes, Kim S Midwood, Helge Scott, Philippe Collas, Christian W Siebel, Ralf H Adams, Guttorm Haraldsen, Eirik Sundlisæter, Johanna Hol
OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA to genomic sites occupied by NOTCH1-RBPJ and that NOTCH1 knockdown reduced H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29447913/microbiological-surveillance-of-plasmid-mediated-colistin-resistance-in-human-enterobacteriaceae-isolates-in-romagna-northern-italy-august-2016-july-2017
#10
F Del Bianco, M Morotti, M F Pedna, P Farabegoli, V Sambri
OBJECTIVES: To start a surveillance program to investigate the possible diffusion of mobilized colistin resistance genes in Enterobacteriaceae strains isolated in the Unit of Microbiology of the Great Romagna Hub Laboratory. METHODS: All the colistin resistant Enterobacteriaceae, isolated from August 1st 2016 to July 31st 2017, were prospectively evaluated for mcr-1 a mcr-2. Backdated survey of mcr-3, mcr-4 and mcr-5 was performed on the same group of isolates. Species identification was achieved by Vitek MS and the antibiotic susceptibility testing was performed both with Vitek-2 and Sensititre systems...
February 12, 2018: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29446202/conditional-deletion-of-cadherin-13-perturbs-golgi-cells-and-disrupts-social-and-cognitive-behaviors
#11
Martesa Tantra, Lanboling Guo, Jinsook Kim, Norliyana Zainolabidin, George J Augustine, Volker Eulenburg, Albert I Chen
Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebelluar cortex...
February 15, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29445199/lack-of-t-bet-reduces-monocytic-interleukin-12-formation-and-accelerates-thrombus-resolution-in-deep-vein-thrombosis
#12
Tanja Schönfelder, Moritz Brandt, Sabine Kossmann, Tanja Knopp, Thomas Münzel, Ulrich Walter, Susanne H Karbach, Philip Wenzel
The role of leukocytes in deep vein thrombosis (DVT) resolution is incompletely understood. We determined how depletion of lysozyme positive (LysM + ) cells and a switched-off type 1 immune response influences thrombus resolution. DVT was induced in 12-week-old male mice by inferior vena cava (IVC) stenosis. Toxin mediated depletion of myeloid cells improved thrombus resolution in mice with Cre-inducible expression of the diphtheria toxin receptor in LysM + cells. This correlated with decreased CD45 + cells, a population shift of Gr-1 + to Gr-1 - CD11b + myelomonocytic cells (flow cytometry) and an increase in CC-chemokine ligand 2, interleukin-4 and interleukin-10 mRNA expressions...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445082/pyruvate-kinase-m2-regulates-photoreceptor-structure-function-and-viability
#13
Ammaji Rajala, Yuhong Wang, Richard S Brush, Kristine Tsantilas, Connor S R Jankowski, Ken J Lindsay, Jonathan D Linton, James B Hurley, Robert E Anderson, Raju V S Rajala
Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that is expressed in cancer cells. Its role in tumor metabolism is not definitively established, but investigators have suggested that regulation of PKM2 activity can cause accumulation of glycolytic intermediates and increase flux through the pentose phosphate pathway. Recent evidence suggests that PKM2 also may have non-metabolic functions, including as a transcriptional co-activator in gene regulation. We reported previously that PKM2 is abundant in photoreceptor cells in mouse retinas...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444829/multiplex-immunochromatographic-detection-of-oxa-48-kpc-and-ndm-carbapenemases-impact-of-the-inoculum-antibiotics-and-agar
#14
Ahmad Saleh, Stephan Göttig, Axel Hamprecht
SYNOPSIS For rapid detection of carbapenemase-producing Enterobacteriaceae (CPE), immunochromatographic lateral flow tests (ICT) have recently been developed. The aim of this study was to assess the new multiplex ICT RESIST-3 O.K.N®. and to investigate if it can be performed directly from susceptibility testing plates. Additionally the impact of the inoculum and carbapenem disks on sensitivity and specificity was evaluated. The new ICT was challenged using 63 CRE isolates, including 51 carbapenemase producers...
February 14, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29444819/bace1-deletion-in-the-adult-mouse-reverses-preformed-amyloid-deposition-and-improves-cognitive-functions
#15
Xiangyou Hu, Brati Das, Hailong Hou, Wanxia He, Riqiang Yan
BACE1 initiates the generation of the β-amyloid peptide, which likely causes Alzheimer's disease (AD) when accumulated abnormally. BACE1 inhibitory drugs are currently being developed to treat AD patients. To mimic BACE1 inhibition in adults, we generated BACE1 conditional knockout (BACE1 fl/fl ) mice and bred BACE1 fl/fl mice with ubiquitin-Cre ER mice to induce deletion of BACE1 after passing early developmental stages. Strikingly, sequential and increased deletion of BACE1 in an adult AD mouse model (5xFAD) was capable of completely reversing amyloid deposition...
February 14, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29444710/a-novel-in-vitro-model-for-the-assessment-of-postnatal-myonuclear-accretion
#16
Anita Kneppers, Lex Verdijk, Chiel de Theije, Mark Corten, Ellis Gielen, Luc van Loon, Annemie Schols, Ramon Langen
BACKGROUND: Due to the post-mitotic nature of myonuclei, postnatal myogenesis is essential for skeletal muscle growth, repair, and regeneration. This process is facilitated by satellite cells through proliferation, differentiation, and subsequent fusion with a pre-existing muscle fiber (i.e., myonuclear accretion). Current knowledge of myogenesis is primarily based on the in vitro formation of syncytia from myoblasts, which represents aspects of developmental myogenesis, but may incompletely portray postnatal myogenesis...
February 14, 2018: Skeletal Muscle
https://www.readbyqxmd.com/read/29444209/geranylgeranyl-pyrophosphate-synthase-facilitates-the-organization-of-cardiomyocytes-during-mid-gestation-through-modulating-protein-geranylgeranylation-in-mouse-heart
#17
Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, Chaojun Li
Aims: With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodeling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results: Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function...
February 12, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29443066/constitutive-and-inducible-systems-for-genetic-in-vivo-modification-of-mouse-hepatocytes-using-hydrodynamic-tail-vein-injection
#18
Eric K Hubner, Christian Lechler, Thomas N Rösner, Birgit Kohnke-Ertel, Roland M Schmid, Ursula Ehmer
In research models of liver cancer, regeneration, inflammation, and fibrosis, flexible systems for in vivo gene expression and silencing are highly useful. Hydrodynamic tail vein injection of transposon-based constructs is an efficient method for genetic manipulation of hepatocytes in adult mice. In addition to constitutive transgene expression, this system can be used for more advanced applications, such as shRNA-mediated gene knock-down, implication of the CRISPR/Cas9 system to induce gene mutations, or inducible systems...
February 2, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29438803/sleep-state-dependence-of-optogenetically-evoked-responses-in-neuronal-nitric-oxide-synthase-positive-cells-of-the-cerebral-cortex
#19
Dmitry Gerashchenko, Michelle A Schmidt, Mark R Zielinski, Michele E Moore, Jonathan P Wisor
Slow-wave activity (SWA) in the electroencephalogram during slow-wave sleep (SWS) varies as a function of sleep-wake history. A putative sleep-active population of neuronal nitric oxide synthase (nNOS)-containing interneurons in the cerebral cortex, defined as such by the expression of Fos in animals euthanized after protracted deep sleep, may be a local regulator of SWA. We investigated whether electrophysiological responses to activation of these cells are consistent with their role of a local regulator of SWA...
February 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29438518/obesity-and-high-fat-diet-induce-distinct-changes-in-placental-gene-expression-and-pregnancy-outcome
#20
Erica B Mahany, Xingfa Han, Beatriz C Borges, Sanseray da Silveira Cruz-Machado, Susan J Allen, David Garcia-Galiano, Mark J Hoenerhoff, Nicole H Bellefontaine, Carol F Elias
Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth and neonatal death. In the present study, we aimed to determine the effects of obesity on pregnancy outcome and placental gene expression in preclinical mouse models of genetic and nutritional obesity. The leptin receptor null reactivatable (LepRloxTB), the LepR deficient (Leprdb/+) and high fat diet (HFD) fed mice were assessed for fertility, pregnancy outcome, placental morphology and placental transcriptome using standard qPCR and qPCR arrays...
February 9, 2018: Endocrinology
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