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https://www.readbyqxmd.com/read/29240788/enhanced-heart-failure-mortality-and-renin-activation-in-female-mice-with-experimental-dilated-cardiomyopathy
#1
Ranjana Tripathi, Ryan Sullivan, Tai-Hwang M Fan, Dong Wang, Yao Sun, Guy L Reed, Inna P Gladysheva
Dilated cardiomyopathy (DCM) is the major cause of heart failure affecting both women and men. Limited clinical studies show conflicting data in sex-related differences in the progression of dilated cardiomyopathy and heart failure (HF) outcomes. We examined the comparative sex-related progression of cardiomyopathy and the development of HF (at 4, 7, 13 weeks of age) in a well-established, transgenic mouse model of DCM that recapitulates the progressive stages of human HF. By 13 weeks of age, female mice with DCM had more severe left ventricular systolic dysfunction, left ventricular dilation and wall thinning (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/29234155/analysis-of-neuronal-phosphoproteome-reveals-pink1-regulation-of-bad-function-and-cell-death
#2
Huida Wan, Bin Tang, Xun Liao, Qiufang Zeng, Zhuohua Zhang, Lujian Liao
PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress...
December 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29233822/hematopoietic-stem-cell-gene-therapy-for-ifn%C3%AE-r1-deficiency-protects-mice-from-mycobacterial-infections
#3
Miriam Hetzel, Adele Mucci, Patrick Blank, Ariane Hai Ha Nguyen, Jan Schiller, Olga Halle, Mark-Philipp Kühnel, Sandra Billig, Robert Meineke, Daniel Brand, Vanessa Herder, Wolfgang Baumgärtner, Franz-Christoph Bange, Ralph Goethe, Danny Jonigk, Reinhold Förster, Bernhard Gentner, Jean-Laurent Casanova, Jacinta Bustamante, Axel Schambach, Ulrich Kalinke, Nico Lachmann
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare primary immunodeficiency, characterized by severe infections caused by weakly virulent mycobacteria. Bi-allelic null mutations in genes encoding interferon gamma (IFNγ) receptor 1 or -2 (IFNGR1, IFNGR2) result in a life-threatening disease phenotype in early childhood. Recombinant IFNγ therapy is inefficient and hematopoietic stem cell transplantation (HSCT) has a poor prognosis. Thus, we developed a HSC gene therapy approach using lentiviral vectors expressing Ifnγr1 either constitutively or myeloid-specifically...
December 12, 2017: Blood
https://www.readbyqxmd.com/read/29229770/rb1-promotes-t-cell-maturation-from-premature-apoptosis-by-inhibiting-e2f1
#4
Zili Zhang, Wei Liu, Lingfeng Zhao, Zhibin Huang, Xiaohui Chen, Ning Ma, Jin Xu, Wenqing Zhang, Yiyue Zhang
T lymphocytes are key cellular components of acquired immune system and play essential roles in cell-mediated immunity. T cell development occurs in the thymus where 95% of immature thymocytes are eliminated via apoptosis. It is known that mutation of Zeb1, one of RB1 target genes, resulted in immature T cell decrease in mice. E2F1, an RB1 interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulate thymocyte development in vivo is still need to be further investigated...
December 11, 2017: Development
https://www.readbyqxmd.com/read/29228252/retinal-reflectivity-measurement-for-cone-impairment-estimation-and-visual-assessment-after-diabetic-macular-edema-resolution-recover-dme
#5
Benjamin Guyon, Emeric Elphege, Mathieu Flores, Anne-Sophie Gauthier, Bernard Delbosc, Maher Saleh
Purpose: Photoreceptor loss has been suspected of being involved in incomplete visual recovery after diabetic macular edema (DME) resolution. Recent studies have shown that cone density in the perifoveal area could be estimated by in vivo measurements of the outer retinal reflectivity on optical coherence tomography (OCT). The main objective of this study was to assess the photoreceptor layer reflectivity after DME resolution and to determine its relationship with final visual acuity (VA)...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29227201/early-rescue-from-acute-severe-clostridium-difficile-a-novel-treatment-strategy
#6
Biniam Kidane, Kalvin Lung, Greig McCreery, Chadia El-Khatib, Michael C Ott, Roberto Hernandez-Alejandro, Chris Vinden, Daryl Gray, Neil G Parry, Kenneth A Leslie, Tina S Mele
BACKGROUND: Severe Clostridium difficile infections (CDI) can lead to significant impediments to effective treatment. We developed a novel treatment protocol utilizing bedside gastrointestinal lavage (GIL) for the management of patients with severe, complicated CDI. We describe the development and early outcomes of non-operative bedside GIL in hospitalized patients with severe, complicated CDI following the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework at the Idea stage...
December 11, 2017: Surgical Infections
https://www.readbyqxmd.com/read/29222967/stimulation-of-the-endogenous-incretin-glucose-dependent-insulinotropic-peptide-by-enteral-dextrose-improves-glucose-homeostasis-and-inflammation-in-murine-endotoxemia
#7
Faraaz Ali Shah, Srikanth Singamsetty, Lanping Guo, Byron W Chuan, Sherie McDonald, Bryce A Cooper, Brett J O'Donnell, Darko Stefanovski, Burton Wice, Yingze Zhang, Christopher P O'Donnell, Bryan J McVerry
Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis...
November 21, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29218323/sap97-binding-partner-cript-promotes-dendrite-growth-in-vitro-and-in-vivo
#8
Lei Zhang, Angela Marie Jablonski, Jelena Mojsilovic-Petrovic, Hua Ding, Steven Seeholzer, Ian Paterson Newton, Inke Nathke, Rachael Neve, JinBin Zhai, Yuan Shang, Mingjie Zhang, Robert Gordon Kalb
The dendritic tree is a key determinant of neuronal information processing. In the motor system, the dendritic tree of spinal cord neurons undergoes dramatic remodeling in an activity-dependent manner during early postnatal life. This leads to the proper segmental spinal cord connectivity that subserves normal locomotor behavior. One molecular system driving the establishment of dendrite architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs) assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)-independent manner...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29215954/evolution-of-various-components-of-pain-after-laparoscopic-cholecystectomy-importance-of-its-prognostication-for-effective-pain-control-using-a-local-anesthetic-and-for-making-a-valid-practical-discharge-criteria-model-predicting-early-discharge-of-patients
#9
Singh Mathuria Kaushal-Deep, Mehershree Lodhi, Afzal Anees, Shehtaj Khan, Mohammad Amanullah Khan
OBJECTIVES: Pain continues to be the most important limiting factor affecting the early discharge of patients after laparoscopic cholecystectomy (LC). Our aim was to conduct a randomized case controlled study to predict the evolution of various components of postoperative pain by using ropivacaine 0.2% at intraperitoneal and intraincisional locations; and to further use this information to make a model predicting early discharge of patients. METHODS: Two hundred forty-four patients underwent elective four-port LC...
December 7, 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/29212949/early-pridopidine-treatment-improves-behavioral-and-transcriptional-deficits-in-yac128-huntington-disease-mice
#10
Marta Garcia-Miralles, Michal Geva, Jing Ying Tan, Nur Amirah Binte Mohammad Yusof, Yoonjeong Cha, Rebecca Kusko, Liang Juin Tan, Xiaohong Xu, Iris Grossman, Aric Orbach, Michael R Hayden, Mahmoud A Pouladi
Pridopidine is currently under clinical development for Huntington disease (HD), with on-going studies to better characterize its therapeutic benefit and mode of action. Pridopidine was administered either prior to the appearance of disease phenotypes or in advanced stages of disease in the YAC128 mouse model of HD. In the early treatment cohort, animals received 0, 10, or 30 mg/kg pridopidine for a period of 10.5 months. In the late treatment cohort, animals were treated for 8 weeks with 0 mg/kg or an escalating dose of pridopidine (10 to 30 mg/kg over 3 weeks)...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212017/control-of-huntington-s-disease-associated-phenotypes-by-the-striatum-enriched-transcription-factor-foxp2
#11
Lea J Hachigian, Vitor Carmona, Robert J Fenster, Ruth Kulicke, Adrian Heilbut, Annie Sittler, Luís Pereira de Almeida, Jill P Mesirov, Fan Gao, Eric D Kolaczyk, Myriam Heiman
Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington's disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29210651/mir-25-mediates-retinal-degeneration-via-inhibiting-itgav-and-pedf-in-rat
#12
J Zhang, J Wang, L Zheng, M Wang, Y Lu, Z Li, C Lian, S Mao, X Hou, S Li, J Xu, H Tian, C Jin, F Gao, J Zhang, F Wang, W Li, L Lu, G-T Xu
Age-related macular degeneration (AMD) is the main cause of irreversible blindness in the elderly. Oxidative stress in retinal pigment epithelium (RPE) is deemed to play a pivotal role in the pathogenesis of AMD. miR-25 functions as an essential modulator in response to oxidative-stress in several cell types, but its function in RPE cells is poorly understood. Here, we reported that, in a rat model of retinal degeneration induced by sodium iodate (SI), oxidative stress up-regulated miR-25 in RPE cells in very early stage, accompanied by decreased phagocytosis and reduced growth factor secretion in those cells...
December 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29210524/tsc1-enables-plastid-development-under-dark-conditions-contributing-to-rice-adaptation-to-transplantation-shock
#13
Xiaoliang Shi, Sunlu Chen, Yu Peng, Yufeng Wang, Jiugeng Chen, Zhanghua Hu, Baohe Wang, Aihong Li, Daiyin Chao, Yuhong Li, Sheng Teng
Since its domestication from wild rice thousands of years ago, rice has been cultivated largely through transplantation. During transplantation from the nursery to the paddy field, rice seedlings experience transplantation shock which affects their physiology and production. However, the mechanisms underlying transplantation shock and rice adaptation to this shock are largely unknown. Here, we isolated a transplant-sensitive chloroplast-deficient (tsc1) rice mutant that produces albino leaves after transplantation...
December 6, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/29209926/a-randomized-trial-of-phenylephrine-infusion-versus-bolus-dosing-for-nausea-and-vomiting-during-cesarean-delivery-in-obese-women
#14
Ronald B George, Dolores M McKeen, Jennifer E Dominguez, Terrence K Allen, Patricia A Doyle, Ashraf S Habib
PURPOSE: Hypotension is common after spinal anesthesia for Cesarean delivery. It is associated with nausea, vomiting, and fetal acidosis. Previous research on phenylephrine excluded obese subjects. We compared the incidence of intraoperative nausea and vomiting (IONV) in obese patients who received a prophylactic phenylephrine infusion vs those who received bolus dosing for the treatment of spinal-induced hypotension. METHODS: In this multicentre, double-blinded randomized controlled trial, 160 obese women undergoing elective Cesarean delivery under spinal anesthesia were randomized to receive a prophylactic phenylephrine infusion initiated at 50 μg·min-1 (and titrated according to a predefined algorithm) or 100 μg phenylephrine boluses to treat hypotension...
December 5, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/29208952/major-depletion-of-sox2-stem-cells-in-the-adult-pituitary-is-not-restored-which-does-not-affect-hormonal-cell-homeostasis-and-remodelling
#15
Heleen Roose, Benoit Cox, Matteo Boretto, Conny Gysemans, Annelies Vennekens, Hugo Vankelecom
The pituitary gland contains SOX2-expressing stem cells. However, their functional significance remains largely unmapped. We investigated their importance by depleting SOX2+ cells through diphtheria toxin (DT)-mediated ablation. DT treatment of adult Sox2CreERT2/+;R26iDTR/+ mice (after tamoxifen-induced expression of DT receptor in SOX2+ cells) resulted in 80% obliteration of SOX2+ cells in the endocrine pituitary, coinciding with reduced pituisphere-forming activity. Counterintuitively for a stem cell population, the SOX2+ cell compartment did not repopulate...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29205793/duodenal-graft-complications-requiring-duodenectomy-after-pancreas-and-pancreas-kidney-transplantation
#16
Erica Pieroni, Niccolò Napoli, Carlo Lombardo, Piero Marchetti, Margherita Occhipinti, Carla Cappelli, Davide Caramella, Giovanni Consani, Gabriella Amorese, Maurizio De Maria, Fabio Vistoli, Ugo Boggi
Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow-up period of 126 months (range 23-198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin-independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n=10, 71.5%) and refractory duodenal graft bleeding (n=4, 28.5%). In patients with duodenal graft bleeding, a total duodenectomy was performed...
December 4, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29204778/conversion-of-laparoscopic-adjustable-gastric-banding-to-gastric-bypass-a-comparison-to-primary-gastric-bypass
#17
Abbas Al-Kurd, Ronit Grinbaum, Ala'a Abubeih, Baha Siam, Muhammad Ghanem, Haggi Mazeh, Ido Mizrahi, Nahum Beglaibter
INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) has a considerable failure rate. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the rescue options. This study aims to compare the complication rates and outcomes between LAGB converted to LRYGB and primary LRYGB. MATERIALS AND METHODS: A retrospective analysis was performed in all patients converted from LAGB to LRYGB between January 2007 and March 2017. This group was compared to a matched cohort of primary LRYGB patients operated during the same period...
December 4, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29204649/aav2-mediated-transduction-of-the-mouse-retina-after-optic-nerve-injury
#18
Robert W Nickells, Heather M Schmitt, Margaret E Maes, Cassandra L Schlamp
Purpose: Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. Methods: Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29202463/patients-and-animal-models-of-cng%C3%AE-1-deficient-retinitis-pigmentosa-support-gene-augmentation-approach
#19
Simon M Petersen-Jones, Laurence M Occelli, Paige A Winkler, Winston Lee, Janet R Sparrow, Mai Tsukikawa, Sanford L Boye, Vince Chiodo, Jenina E Capasso, Elvir Becirovic, Christian Schön, Mathias W Seeliger, Alex V Levin, Stylianos Michalakis, William W Hauswirth, Stephen H Tsang
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease...
November 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29198828/altered-differentiation-potential-of-gaucher-s-disease-ipsc-neuronal-progenitors-due-to-wnt-%C3%AE-catenin-downregulation
#20
Ola Awad, Leelamma M Panicker, Rania M Deranieh, Manasa P Srikanth, Robert A Brown, Antanina Voit, Tejasvi Peesay, Tea Soon Park, Elias T Zambidis, Ricardo A Feldman
Gaucher's disease (GD) is an autosomal recessive disorder caused by mutations in the GBA1 gene, which encodes acid β-glucocerebrosidase (GCase). Severe GBA1 mutations cause neuropathology that manifests soon after birth, suggesting that GCase deficiency interferes with neuronal development. We found that neuronopathic GD induced pluripotent stem cell (iPSC)-derived neuronal progenitor cells (NPCs) exhibit developmental defects due to downregulation of canonical Wnt/β-catenin signaling and that GD iPSCs' ability to differentiate to dopaminergic (DA) neurons was strikingly reduced due to early loss of DA progenitors...
November 27, 2017: Stem Cell Reports
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