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https://www.readbyqxmd.com/read/28644127/mpi-depletion-enhances-o-glcnacylation-of-p53-and-suppresses-the-warburg-effect
#1
Charles DeRossi, Nataly Shtraizent, Shikha Nayar, Ravi Sachidanandam, Liora S Katz, Adam Prince, Anna P Koh, Adam Vincek, Yoav Hadas, Yujin Hoshida, Donald K Scott, Efrat Eliyahu, Hudson H Freeze, Kirsten C Sadler, Jaime Chu
Rapid cellular proliferation in early development and cancer depends on glucose metabolism to fuel macromolecule biosynthesis. Metabolic enzymes are presumed regulators of this glycolysis-driven metabolic program, known as the Warburg effect, however few have been identified. We uncover a previously unappreciated role for Mannose phosphate isomerase (MPI) as a metabolic enzyme required to maintain Warburg metabolism in zebrafish embryos and in both primary and malignant mammalian cells. The functional consequences of MPI loss are striking: glycolysis is blocked and cells die...
June 23, 2017: ELife
https://www.readbyqxmd.com/read/28642656/local-periarticular-analgesia-in-total-knee-arthroplasty
#2
David Sadigursky, Daniel Pereira Simões, Raphael Araújo de Albuquerque, Monize Zórnio Silva, Rogério Jamil Carneiro Fernandes, Paulo Oliveira Colavolpe
OBJECTIVE: To evaluate the use of infiltration of periarticular analgesic agents intraoperatively in total knee arthroplasty (TKA), with regard to benefits, reduction of pain, opioid consumption, improvement of range of motion and early ambulation. METHODS: To analyze the benefits of periarticular drug infiltration, the patients submitted to TKA were evaluated, being separated into two groups. One group received the local periarticular infiltration protocol containing 0...
March 2017: Acta Ortopedica Brasileira
https://www.readbyqxmd.com/read/28641602/milk-replacers-supplemented-with-either-l-arginine-or-l-carnitine-potentially-improve-muscle-maturation-of-early-reared-low-birth-weight-piglets-from-hyperprolific-sows
#3
J G Madsen, S Mueller, M Kreuzer, M B Bigler, P Silacci, G Bee
As a result of the selection for genotypes with greater sow prolificacy, litter size increased and, concomitantly, average litter birth weight and early postnatal survival rates of low birth weight (L-BtW) offspring decreased. This study compared the impact of l-carnitine (CAR) and l-arginine (ARG) supplemented with a milk replacer and fed to L-BtW piglets born from large litters from days 7 to 28 of age on growth performance, carcass composition, organ and Semitendinosus muscle (STM) development. A total of 30 female and castrated Swiss Large White piglets weaned at 7 days of age were assigned to three milk replacer diets containing either no supplement (CON), CAR (0...
June 23, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28637474/arsenic-trioxide-inhibits-ebv-reactivation-and-promotes-cell-death-in-ebv-positive-lymphoma-cells
#4
Qinyan Yin, Mark Sides, Christopher H Parsons, Erik K Flemington, Joseph A Lasky
BACKGROUND: Epstein-Barr Virus (EBV) is associated with hematopoietic malignancies, such as Burkitt's lymphoma, post-transplantation lymphoproliferative disorder, and diffuse large B-cell lymphoma. The current approach for EBV-associated lymphoma involves chemotherapy to eradicate cancer cells, however, normal cells may be injured and organ dysfunction may occur with currently employed regimens. This research is focused on employing arsenic trioxide (ATO) as EBV-specific cancer therapy takes advantage of the fact the EBV resides within the malignant cells...
June 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28632502/targeting-activated-protein-c-to-treat-hemophilia
#5
Stéphanie G I Polderdijk, Trevor P Baglin, James A Huntington
PURPOSE OF REVIEW: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia...
June 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28631381/tec-controls-pluripotency-and-early-cell-fate-decisions-of-human-pluripotent-stem-cells-via-regulation-of-fgf2-secretion
#6
Tereza Vanova, Zaneta Konecna, Zuzana Zbonakova, Giuseppe La Venuta, Karolina Zoufalova, Sarka Jelinkova, Miroslav Varecha, Vladimir Rotrekl, Pavel Krejci, Walter Nickel, Petr Dvorak, Michaela Kunova Bosakova
Human pluripotent stem cells (hPSC) require signaling provided by fibroblast growth factor (FGF) receptors. This can be initiated by the recombinant FGF2 ligand supplied exogenously, but hPSC further support their niche by secretion of endogenous FGF2. In this study, we describe a role of TEC kinase (tyrosine kinase expressed in hepatocellular carcinoma) in this process. We show that TEC-mediated FGF2 secretion is essential for hPSC self-renewal, and its lack mediates specific differentiation. Following both shRNA- and siRNA-mediated TEC knock-down, hPSC secrete less FGF2...
June 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28630288/intact-pirna-pathway-prevents-l1-mobilization-in-male-meiosis
#7
Simon J Newkirk, Suman Lee, Fiorella C Grandi, Valeriya Gaysinskaya, James M Rosser, Nicole Vanden Berg, Cathryn A Hogarth, Maria C N Marchetto, Alysson R Muotri, Michael D Griswold, Ping Ye, Alex Bortvin, Fred H Gage, Jef D Boeke, Wenfeng An
The PIWI-interacting RNA (piRNA) pathway is essential for retrotransposon silencing. In piRNA-deficient mice, L1-overexpressing male germ cells exhibit excessive DNA damage and meiotic defects. It remains unknown whether L1 expression simply highlights piRNA deficiency or actually drives the germ-cell demise. Specifically, the sheer abundance of genomic L1 copies prevents reliable quantification of new insertions. Here, we developed a codon-optimized L1 transgene that is controlled by an endogenous mouse L1 promoter...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630251/valnoctamide-inhibits-cytomegalovirus-infection-in-developing-brain-and-attenuates-neurobehavioral-dysfunctions-and-brain-abnormalities
#8
Sara Ornaghi, Lawrence S Hsieh, Angélique Bordey, Patrizia Vergani, Michael J Paidas, Anthony N van den Pol
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28628628/transcriptional-mechanisms-associated-with-seed-dormancy-and-dormancy-loss-in-the-gibberellin-insensitive-sly1-2-mutant-of-arabidopsis-thaliana
#9
Sven K Nelson, Camille M Steber
While widespread transcriptome changes were previously observed with seed dormancy loss, this study specifically characterized transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive sleepy1-2 (sly1-2) mutant. The SLY1 gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. DELLA overaccumulation in sly1-2 seeds leads to increased dormancy that can be rescued without DELLA protein destruction either by overexpression of the GA receptor, GA-INSENSITIVE DWARF1b (GID1b-OE) (74% germination) or by extended dry after-ripening (11 months, 51% germination)...
2017: PloS One
https://www.readbyqxmd.com/read/28627422/down-regulation-of-kv4-channel-in-drosophila-mushroom-body-neurons-contributes-to-a%C3%AE-42-induced-courtship-memory-deficits
#10
Ge Feng, Jie Pang, Xin Yi, Qian Song, Jiaxing Zhang, Can Li, Guang He, Yong Ping
Accumulation of amyloid-β (Aβ) is widely believed to be an early event in the pathogenesis of Alzheimer's disease (AD). Kv4 is an A-type K(+) channel, and our previous report shows the degradation of Kv4, induced by the Aβ42 accumulation, may be a critical contributor to the hyperexcitability of neurons in a Drosophila AD model. Here, we used well-established courtship memory assay to investigate the contribution of the Kv4 channel to short-term memory (STM) deficits in the Aβ42-expressing AD model. We found that Aβ42 over-expression in Drosophila leads to age-dependent courtship STM loss, which can be also induced by driving acute Aβ42 expression post-developmentally...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28626871/a-successful-living-donor-liver-re-transplantation-for-graft-failure-within-seven-days-due-to-acute-de-novo-donor-specific-anti-hla-antibody-mediated-rejection
#11
Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Kiyotomo Abe, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Hiroshi Yagi, Naoki Shimojima, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Yasushi Fuchimoto, Kaori Kameyama, Yuko Kitagawa, Tatsuo Kuroda
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28626056/early-reperfusion-after-brain-ischemia-has-beneficial-effects-beyond-rescuing-neurons
#12
Masaki Tachibana, Tetsuro Ago, Yoshinobu Wakisaka, Junya Kuroda, Masahiro Shijo, Yoji Yoshikawa, Motohiro Komori, Ataru Nishimura, Noriko Makihara, Kuniyuki Nakamura, Takanari Kitazono
BACKGROUND AND PURPOSE: Recent studies show that successful endovascular thrombectomy 6 to 12 hours after stroke onset enhances functional outcomes 3 months later. In this study, we investigated the effects of reperfusion after ischemia on repair processes in the ischemic areas, as well as on functional recovery, using mouse stroke models. METHODS: We examined time-dependent histological changes and functional recovery after transient middle cerebral artery occlusion of different durations, including permanent middle cerebral artery occlusion, using the CB-17 (CB-17/lcr-+/+Jcl) mouse strain, which has poor pial collateral blood flow...
June 16, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28625537/the-developmental-stage-of-adult-human-stem-cell-derived-retinal-pigment-epithelium-cells-influences-transplant-efficacy-for-vision-rescue
#13
Richard J Davis, Nazia M Alam, Cuiping Zhao, Claudia Müller, Janmeet S Saini, Timothy A Blenkinsop, Francesca Mazzoni, Melissa Campbell, Susan M Borden, Carol J Charniga, Patty L Lederman, Vanessa Aguilar, Michael Naimark, Michael Fiske, Nathan Boles, Sally Temple, Silvia C Finnemann, Glen T Prusky, Jeffrey H Stern
Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue...
June 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28621427/adhfe1-a-novel-enzyme-involved-in-retinoic-acid-dependent-hox-activation
#14
Yehuda Shabtai, Natalie Shukrun, Abraham Fainsod
Retinoic acid (RA) signaling is a central pathway regulating anterior-posterior patterning of the embryo through its targets, the Hox genes. RA is produced by two sequential oxidations from vitamin A (retinol) and this biosynthesis has to be regulated temporally, spatially and quantitatively. Mining Xenopus embryonic expression databases identified a novel component of the RA metabolic network, ADHFe1. Using Xenopus laevis embryos as our experimental system we determined the temporal and spatial pattern of AdhFe1 expression...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619826/a-toolkit-for-gfp-mediated-tissue-specific-protein-degradation-in-c-elegans
#15
Shaohe Wang, Ngang Heok Tang, Pablo Lara-Gonzalez, Zhiling Zhao, Dhanya K Cheerambathur, Bram Prevo, Andrew D Chisholm, Arshad Desai, Karen Oegema
Proteins essential for embryo production, cell division, and early embryonic events are frequently re-utilized later in embryogenesis, during organismal development, or in the adult. Examining protein function across these different biological contexts requires tissue-specific perturbation. Here, we describe a method that utilizes expression of a fusion between a GFP-targeting nanobody and a SOCS-box containing ubiquitin ligase adaptor to target GFP tagged proteins for degradation. When combined with endogenous locus GFP tagging by CRISPR-Cas9 or rescue of a null mutant with a GFP fusion, this approach enables routine and efficient tissue-specific protein ablation...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28619712/targeting-acetylcholine-receptor-m3-prevents-the-progression-of-airway-hyperreactivity-in-a-mouse-model-of-childhood-asthma
#16
Kruti R Patel, Yan Bai, Kenneth G Trieu, Juliana Barrios, Xingbin Ai
Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation...
June 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28617030/a-real-life-study-of-helicobacter-pylori-eradication-with-bismuth-quadruple-therapy-in-na%C3%A3-ve-and-previously-treated-patients
#17
Blas José Gómez Rodríguez, Luisa Castro Laria, Federico Argüelles Arias, Cristina Castro Márquez, Ángel Caunedo Álvarez, Manuel Romero Gómez
OBJECTIVE: To evaluate the efficacy and safety of a quadruple regimen (BMTO) of the "3-in-1 capsule" (containing bismuth subcitrate potassium, metronidazole and tetracycline) plus omeprazole in naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection in the clinical setting in Seville (Spain). METHODS: This is a prospective study carried out on consecutive patients with a confirmed H. pylori infection and upper gastrointestinal symptoms...
June 15, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28617029/medium-to-long-term-efficacy-and-safety-of-oral-tacrolimus-in-moderate-to-severe-steroid-refractory-ulcerative-colitis
#18
Raúl Vicente Olmedo Martín, Víctor Amo Trillo, Rocío González Grande, Miguel Jiménez Pérez
BACKGROUND: Oral tacrolimus is an effective drug that induces clinical remission in patients with moderate to severe ulcerative colitis refractory to steroids. However, there is little data with regard to its medium to long-term efficacy and safety. The aim of this study was to assess the medium to long-term efficacy and safety of oral tacrolimus in this challenging clinical situation. METHODS: This was a retrospective observational review of the clinical charts of 34 patients with moderate to severe ulcerative colitis refractory to steroids treated with oral tacrolimus at our hospital (July 2001-July 2016)...
June 15, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28610891/n-butyldeoxynojirimycin-delays-motor-deficits-cerebellar-microgliosis-and-purkinje-cell-loss-in-a-mouse-model-of-mucolipidosis-type-iv
#19
Lauren C Boudewyn, Jakub Sikora, Ladislav Kuchar, Jana Ledvinova, Yulia Grishchuk, Shirley L Wang, Kostantin Dobrenis, Steven U Walkley
Mucolipidosis type IV (MLIV) is a lysosomal storage disease exhibiting progressive intellectual disability, motor impairment, and premature death. There is currently no cure or corrective treatment. The disease results from mutations in the gene encoding mucolipin-1, a transient receptor potential channel believed to play a key role in lysosomal calcium egress. Loss of mucolipin-1 and subsequent defects lead to a host of cellular aberrations, including accumulation of glycosphingolipids (GSLs) in neurons and other cell types, microgliosis and, as reported here, cerebellar Purkinje cell loss...
June 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28608540/sevoflurane-vs-propofol-in-post-operative-catheter-related-bladder-discomfort-a-prospective-randomized-study
#20
H-C Kim, H-P Park, J Lee, M-H Jeong, K-H Lee
BACKGROUND: Post-operative catheter-related bladder discomfort (CRBD) causes increased emergence agitation. Muscarinic receptor activation is a major mechanism in CRBD development. Experimental studies showed that sevoflurane has anti-muscarinic effects whereas propofol does not. Our hypothesis was that sevoflurane anaesthesia would reduce the incidence of CRBD following bladder surgery. METHODS: In total, 82 patients undergoing transurethral bladder tumour excision (TURBT) were assigned randomly to two groups according to the maintenance anaesthetic agent received: sevoflurane (n = 41) or propofol (n = 41)...
June 13, 2017: Acta Anaesthesiologica Scandinavica
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