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https://www.readbyqxmd.com/read/29166608/s-nitrosylation-of-pink1-attenuates-pink1-parkin-dependent-mitophagy-in-hipsc-based-parkinson-s-disease-models
#1
Chang-Ki Oh, Abdullah Sultan, Joseph Platzer, Nima Dolatabadi, Frank Soldner, Daniel B McClatchy, Jolene K Diedrich, John R Yates, Rajesh Ambasudhan, Tomohiro Nakamura, Rudolf Jaenisch, Stuart A Lipton
Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166596/the-gcn2-atf4-signaling-pathway-induces-4e-bp-to-bias-translation-and-boost-antimicrobial-peptide-synthesis-in-response-to-bacterial-infection
#2
Deepika Vasudevan, Nicholas K Clark, Jessica Sam, Victoria C Cotham, Beatrix Ueberheide, Michael T Marr, Hyung Don Ryoo
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29165614/long-term-health-in-recipients-of-transplanted-in-vitro-propagated-spermatogonial-stem-cells
#3
Callista L Mulder, Lisa A E Catsburg, Yi Zheng, Cindy M de Winter-Korver, Saskia K M van Daalen, Madelon van Wely, Steven Pals, Sjoerd Repping, Ans M M van Pelt
STUDY QUESTION: Is testicular transplantation of in vitro propagated spermatogonial stem cells associated with increased cancer incidence and decreased survival rates in recipient mice? SUMMARY ANSWER: Cancer incidence was not increased and long-term survival rate was not altered after transplantation of in vitro propagated murine spermatogonial stem cells (SSCs) in busulfan-treated recipients as compared to non-transplanted busulfan-treated controls. WHAT IS KNOWN ALREADY: Spermatogonial stem cell autotransplantation (SSCT) is a promising experimental reproductive technique currently under development to restore fertility in male childhood cancer survivors...
November 18, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29164613/calmodulin-like-skin-protein-protects-against-spatial-learning-impairment-in-a-mouse-model-of-alzheimer-disease
#4
Shinya Kusakari, Mikiro Nawa, Katsuko Sudo, Masaaki Matsuoka
Humanin and calmodulin-like skin protein (CLSP) inhibits Alzheimer disease (AD)-related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP-1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP overexpression on the pathological phenotype of the AD mouse model...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29163805/thymine-dna-glycosylase-tdg-is-involved-in-the-pathogenesis-of-intestinal-tumors-with-reduced-apc-expression
#5
Jinfei Xu, Salvatore Cortellino, Rossella Tricarico, Wen-Chi Chang, Gabrielle Scher, Karthik Devarajan, Michael Slifker, Robert Moore, Maria Rosaria Bassi, Elena Caretti, Margie Clapper, Harry Cooper, Alfonso Bellacosa
Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163595/alfalfa-root-growth-rate-correlates-with-progression-of-microtubules-during-mitosis-and-cytokinesis-as-revealed-by-environmental-light-sheet-microscopy
#6
Petra Vyplelová, Miroslav Ovečka, Jozef Šamaj
Cell division and expansion are two fundamental biological processes supporting indeterminate root growth and development of plants. Quantitative evaluations of cell divisions related to root growth analyses have been performed in several model crop and non-crop plant species, but not in important legume plant Medicago sativa. Light-sheet fluorescence microscopy (LSFM) is an advanced imaging technique widely used in animal developmental biology, providing efficient fast optical sectioning under physiological conditions with considerably reduced phototoxicity and photobleaching...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29163533/chronic-nkg2d-engagement-in-vivo-differentially-impacts-nk-cell-responsiveness-by-activating-nk-receptors
#7
Christine Koch, Younghoon Kim, Tobias Zöller, Christina Born, Alexander Steinle
Immunosuppression is a typical hallmark of cancer and frequently includes perturbations of the NKG2D tumor recognition system as well as impaired signaling by other activating NK cell receptors. Several in vitro studies suggested that sustained engagement of the NKG2D receptor, as it is occurring in the tumor microenvironment, not only impairs expression and function of NKG2D but also impacts signaling by other activating NK receptors. Here, we made use of a transgenic mouse model of ubiquitous NKG2D ligand expression (H2-K(b)-MICA mice) to investigate consequences of chronic NKG2D engagement in vivo for functional responsiveness by other activating NK receptors such as NKp46 and Ly49D...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163527/engineered-tolerance-tailoring-development-function-and-antigen-specificity-of-regulatory-t-cells
#8
REVIEW
Nicholas A J Dawson, Jens Vent-Schmidt, Megan K Levings
Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation, and solid organ transplantation. Current clinical approaches aim to boost Tregs in vivo either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized, and targeted Treg product...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163471/innate-b-1-b-cells-are-not-enriched-in-red-blood-cell-autoimmune-mice-importance-of-b-cell-receptor-transgenic-selection
#9
Amanda L Richards, Heather L Howie, Linda M Kapp, Jeanne E Hendrickson, James C Zimring, Krystalyn E Hudson
Autoimmune hemolytic anemia (AIHA) results from breakdown of humoral tolerance to RBC antigens. Past analyses of B-cell receptor transgenic (BCR-Tg) mice that recognize RBC autoantigens led to a paradigm in which autoreactive conventional B-2 B cells are deleted whereas extramedullary B-1 B cells escape deletion due to lack of exposure to RBCs. However, BCR-Tg mice utilized to shape the current paradigm were unable to undergo receptor editing or class-switching. Given the importance of receptor editing as mechanism to tolerize autoreactive B cells during central tolerance, we hypothesized that expansion of autoreactive B-1 B cells is a consequence of the inability of the autoreactive BCR to receptor edit...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163135/neuroprotective-effect-of-ligustilide-through-induction-of-%C3%AE-secretase-processing-of-both-app-and-klotho-in-a-mouse-model-of-alzheimer-s-disease
#10
Xi Kuang, Hong-Jing Zhou, Amy H Thorne, Xi-Nan Chen, Lin-Jiao Li, Jun-Rong Du
Emerging evidence suggests that alpha-processing single transmembrane proteins, amyloid precursor protein (APP) and anti-aging protein Klotho, are likely to be involved in the progression of Alzheimer's disease (AD). The natural phthalide Ligustilide (LIG) has been demonstrated to protect against aging- and amyloid-β (Aβ)-induced brain dysfunction in animal models. The present study is to investigate the effects of LIG on cognitive deficits and metabolism of both APP and Klotho and its underlying mechanism in AD double-transgenic (APP/PS1) mice and cultured human cells...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29163089/the-bachd-rat-model-of-huntington-disease-shows-specific-deficits-in-a-test-battery-of-motor-function
#11
Giuseppe Manfré, Erik K H Clemensson, Elisavet I Kyriakou, Laura E Clemensson, Johanneke E van der Harst, Judith R Homberg, Huu Phuc Nguyen
Rationale: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype. Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29163055/study-of-sex-differences-in-duloxetine-efficacy-for-depression-in-transgenic-mouse-models
#12
Yong Xu, Lei Ma, Wei Jiang, Yuhong Li, Gang Wang, Rena Li
Clinical evidences show sex differences in risk of developing depressive disorders as well as effect of antidepressants in depression treatment. However, whether such a sex-dependent risk of depression and efficacy of antidepressants is dependent on endogenous estrogen level remain elusive. The aim of this study is to explore the molecular mechanisms of sex differences in antidepressant duloxetine. In the present study, we used genetic knockout or overexpression estrogen-synthesizing enzyme aromatase (Ar) gene as models for endogenous estrogen deficiency and elevation endogenous estrogen, respectively, to examine the anti-depressive efficacy of duloxetine in males and females by force swimming test (FST)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162812/role-of-epithelial-to-mesenchymal-transition-associated-genes-in-mammary-gland-regeneration-and-breast-tumorigenesis
#13
Shaheen S Sikandar, Angera H Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W Hsieh, Neethan A Lobo, Ferenc A Scheeren, Sopheak Sim, Dalong Qian, Frederick M Dirbas, George Somlo, Stephen R Quake, Michael F Clarke
Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162497/expression-signatures-of-early-stage-and-advanced-medaka-melanomas
#14
Barbara Klotz, Susanne Kneitz, Martina Regensburger, Lena Hahn, Michael Dannemann, Janet Kelso, Birgit Nickel, Yuan Lu, William Boswell, John Postlethwait, Wesley Warren, Manfred Kunz, Ronald B Walter, Manfred Schartl
Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown...
November 18, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29162059/suppression-of-microrna159-impacts-multiple-agronomic-traits-in-rice-oryza-sativa-l
#15
Yafan Zhao, Huili Wen, Sachin Teotia, Yanxiu Du, Jing Zhang, Junzhou Li, Hongzheng Sun, Guiliang Tang, Ting Peng, Quanzhi Zhao
BACKGROUND: microRNAs (miRNAs) are important regulators in plant growth and development. miR159 is a conserved miRNA among different plant species and has various functions in plants. Studies on miR159 are mostly done on model plant, Arabidopsis thaliana. In rice, studies on miR159 were either based upon genome-wide expression analyses focused upon responses to different nitrogen forms and abiotic stress or upon phenotypic studies of transgenic plants overexpressing its precursor. STTM (Short Tandem Target Mimic) is an effective tool to block the activity of endogenous mature miRNA activity in plant...
November 21, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29160102/improving-the-infection-of-bone-marrow-derived-cells-with-an-integrase-defective-lentiviral-vector
#16
S Louise Pay, Xiaoping Qi, Jeffrey F Willard, Juliana Godoy, Kavya Sankhavaram, Ranier Horton, Sayak K Mitter, Judith Quigley, Chang Lung-Ji, Maria B Grant, Michael E Boulton
In lentiviral vector (LV) applications where transient transgene expression is sufficient, integrase-defective lentiviral vectors (IDLVs) are beneficial for reducing the potential for off-target effects associated with insertional mutagenesis. We previously demonstrated that human RPE65 mRNA expression from an integrating lentiviral vector (ILV) induces endogenous Rpe65 and Cralbp mRNA expression in murine bone marrow-derived cells (BMDCs), initiating programming of the cells to retinal pigment epithelium (RPE)-like cells...
November 21, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29159596/human-monoclonal-antibodies-as-candidate-therapeutics-against-emerging-viruses
#17
REVIEW
Yujia Jin, Cheng Lei, Dan Hu, Dimiter S Dimitrov, Tianlei Ying
The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation...
November 20, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/29158846/subcellular-localization-of-survivin-determines-its-function-in-cardiomyocytes
#18
Tien-Jui Tsang, Ying-Chang Hsueh, Erika I Wei, David J Lundy, Bill Cheng, You-Tzung Chen, Shoei-Shen Wang, Patrick C H Hsieh
Rationale: Reducing cardiomyocyte death and enhancing their proliferation after myocardial infarction is perhaps the single largest challenge for cardiac tissue regeneration. Survivin (SVV) is the smallest member of the inhibitor of apoptosis (IAP) family but plays two important roles; inhibiting caspase-9 activation in the intrinsic apoptosis pathway, and regulating microtubule dynamics and chromosome segregation during cell division. Genetic depletion of cardiac SVV leads to incomplete cardiomyocyte division and abnormal heart development...
2017: Theranostics
https://www.readbyqxmd.com/read/29158503/kr%C3%A3-pple-like-factor-4-attenuates-lung-fibrosis-via-inhibiting-epithelial-mesenchymal-transition
#19
Lianjun Lin, Qian Han, Yan Xiong, Ting Li, Zhonghui Liu, Huiying Xu, Yanping Wu, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158353/blood-pressure-control-by-a-secreted-fgfbp1-fibroblast-growth-factor-binding-protein
#20
Elena Tassi, En Yin Lai, Lingli Li, Glenn Solis, Yifan Chen, William E Kietzman, Patricio E Ray, Anna T Riegel, William J Welch, Christopher S Wilcox, Anton Wellstein
Fibroblast growth factors (FGFs) participate in organ development and tissue maintenance, as well as the control of vascular function. The paracrine-acting FGFs are stored in the extracellular matrix, and their release is controlled by a secreted FGF-binding protein (FGF-BP, FGFBP1, and BP1) that modulates FGF receptor signaling. A genetic polymorphism in the human FGFBP1 gene was associated with higher gene expression and an increased risk of familial hypertension. Here, we report on the effects of inducible BP1 expression in a transgenic mouse model...
November 20, 2017: Hypertension
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