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https://www.readbyqxmd.com/read/28102850/japanese-encephalitis-virus-induces-human-neural-stem-progenitor-cell-death-by-elevating-grp78-phb-and-hnrnpc-through-er-stress
#1
Sriparna Mukherjee, Noopur Singh, Nabonita Sengupta, Mahar Fatima, Pankaj Seth, Anita Mahadevan, Susarla Krishna Shankar, Arindam Bhattacharyya, Anirban Basu
Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102196/whole-brain-3d-mapping-of-human-neural-transplant-innervation
#2
Jonas Doerr, Martin Karl Schwarz, Dirk Wiedermann, Anke Leinhaas, Alina Jakobs, Florian Schloen, Inna Schwarz, Michael Diedenhofen, Nils Christian Braun, Philipp Koch, Daniel A Peterson, Ulrich Kubitscheck, Mathias Hoehn, Oliver Brüstle
While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101371/a-novel-plp1-mutation-f240l-identified-in-a-patient-with-connatal-type-pelizaeus-merzbacher-disease
#3
Yongping Lu, Keiko Shimojima, Tomoko Sakuma, Sachiko Nakaoka, Toshiyuki Yamamoto
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive hypomyelination disorder caused by mutations in the proteolipid protein 1 gene (PLP1) located on chromosome Xq22. A male patient showed severe developmental delay, pendular nystagmus and laryngeal wheezing. The auditory brain stem response showed only the first wave and brain magnetic resonance imaging showed white matter hypomyelination, suggesting typical PMD. A novel PLP1 mutation, F240L, which was inherited from his mother, was identified.
2017: Human Genome Variation
https://www.readbyqxmd.com/read/28100038/trim8-regulates-stemness-in-glioblastoma-through-pias3-stat3
#4
Changming Zhang, Subhas Mukherjee, Carol Tucker-Burden, James L Ross, Monica J Chau, Jun Kong, Daniel J Brat
Glioblastoma (GBM) is the most malignant form of primary brain tumor and GBM stem-like cells (GSCs) contribute to the rapid growth, therapeutic resistance and clinical recurrence of these fatal tumors. STAT3 signaling supports the maintenance and proliferation of GSCs, yet regulatory mechanisms are not completely understood. Here we report that tri-partite motif containing protein 8 (TRIM8) activates STAT3 signaling to maintain stemness and self-renewing capabilities of GSCs. TRIM8 (also known as "glioblastoma expressed ring finger protein") is expressed equally in GBM and normal brain tissues, despite its hemizygous deletion in the large majority of GBMs, and its expression is highly correlated with stem cell markers...
January 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28099854/single-cell-transcriptomic-analysis-defines-heterogeneity-and-transcriptional-dynamics-in-the-adult-neural-stem-cell-lineage
#5
Ben W Dulken, Dena S Leeman, Stéphane C Boutet, Katja Hebestreit, Anne Brunet
Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here, we use single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#6
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#7
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098158/pericytes-from-mesenchymal-stem-cells-as-a-model-for-the-blood-brain-barrier
#8
Xiaohe Tian, Oliver Brookes, Giuseppe Battaglia
Blood brain-barrier (BBB) in vitro models have been widely reported in studies of the BBB phenotype. However, established co-culture systems involve brain endothelial cells, astrocytes, neurons and pericytes, and therefore are often consuming and technically challenging. Here we use mesenchymal system cells (MSC) as a potential substitute for pericytes in a BBB model. Both MSC and pericyte markers in 2D culture environment were evaluated on different extracellular matrix compositions. Further experiments indicated that MSC contributed in a similar manner to pericytes in a co-cultured 3D model on increasing trans-endothelial electric resistance (TEER) and decreasing permeability against macromolecules...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097475/svct2-is-expressed-by-cerebellar-precursor-cells-which-differentiate-into-neurons-in-response-to-ascorbic-acid
#9
Karina Oyarce, Carmen Silva-Alvarez, Luciano Ferrada, Fernando Martínez, Katterine Salazar, Francisco Nualart
Ascorbic acid (AA) is a known antioxidant that participates in a wide range of processes, including stem cell differentiation. It enters the cell through the sodium-ascorbate co-transporter SVCT2, which is mainly expressed by neurons in the adult brain. Here, we have characterized SVCT2 expression in the postnatal cerebellum in situ, a model used for studying neurogenesis, and have identified its expression in granular precursor cells and mature neurons. We have also detected SVCT2 expression in the cerebellar cell line C17...
January 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28097180/the-role-of-nurses-in-coping-process-of-family-caregivers-of-vegetative-patients-a-qualitative-study
#10
Zahra Imanigoghary, Hamid Peyrovi, Esmat Nouhi, Majid Kazemi
BACKGROUND: Vegetative state (VS) occurs through return of the brain stem after coma state. After hospital discharge, responsibility of caring for VS patients is transferred to their families, which causes a high burden on them. Nurses have an important role in helping the family caregivers to meet their needs and cope with difficulties. To explore the role of nurses during coping process of family caregivers of VS patients. METHODS: This study is a part of a larger qualitative study which was performed in Kerman province, Iran during 2014- 2015...
January 2017: International Journal of Community Based Nursing and Midwifery
https://www.readbyqxmd.com/read/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#11
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28095779/poly-adp-ribose-polymerase-inhibitors-activate-the-p53-signaling-pathway-in-neural-stem-progenitor-cells
#12
Akiko Okuda, Suguru Kurokawa, Masanori Takehashi, Aika Maeda, Katsuya Fukuda, Yukari Kubo, Hyuma Nogusa, Tomoka Takatani-Nakase, Shujiro Okuda, Kunihiro Ueda, Seigo Tanaka
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP-1), which catalyzes poly(ADP-ribosyl)ation of proteins by using NAD(+) as a substrate, plays a key role in several nuclear events, including DNA repair, replication, and transcription. Recently, PARP-1 was reported to participate in the somatic cell reprogramming process. Previously, we revealed a role for PARP-1 in the induction of neural apoptosis in a cellular model of cerebral ischemia and suggested the possible use of PARP inhibitors as a new therapeutic intervention...
January 17, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#13
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#14
Nigel Kee, Nikolaos Volakakis, Agnete Kirkeby, Lina Dahl, Helena Storvall, Sara Nolbrant, Laura Lahti, Åsa K Björklund, Linda Gillberg, Eliza Joodmardi, Rickard Sandberg, Malin Parmar, Thomas Perlmann
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28094016/a-single-cell-roadmap-of-lineage-bifurcation-in-human-esc-models-of-embryonic-brain-development
#15
Zizhen Yao, John K Mich, Sherman Ku, Vilas Menon, Anne-Rachel Krostag, Refugio A Martinez, Leon Furchtgott, Heather Mulholland, Susan Bort, Margaret A Fuqua, Ben W Gregor, Rebecca D Hodge, Anu Jayabalu, Ryan C May, Samuel Melton, Angelique M Nelson, N Kiet Ngo, Nadiya V Shapovalova, Soraya I Shehata, Michael W Smith, Leah J Tait, Carol L Thompson, Elliot R Thomsen, Chaoyang Ye, Ian A Glass, Ajamete Kaykas, Shuyuan Yao, John W Phillips, Joshua S Grimley, Boaz P Levi, Yanling Wang, Sharad Ramanathan
During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28093317/stem-cell-therapies-in-preclinical-models-of-stroke-is-the-aged-brain-microenvironment-refractory-to-cell-therapy
#16
Raluca Elena Sandu, Adrian Balseanu, Catalin Bogdan, Mark Slevin, Eugen Petcu, Aurel Popa-Wagner
: Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizingimpediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains...
January 13, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#17
Sune Munthe, Bo Halle, Henning B Boldt, Helle Christiansen, Steffen Schmidt, Vivek Kaimal, Jessica Xu, Sonya Zabludoff, Jan Mollenhauer, Frantz R Poulsen, Bjarne W Kristensen
Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions...
January 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28091591/intraarterial-route-increases-the-risk-of-cerebral-lesions-after-mesenchymal-cell-administration-in-animal-model-of-ischemia
#18
Bárbara Argibay, Jesse Trekker, Uwe Himmelreich, Andrés Beiras, Antonio Topete, Pablo Taboada, María Pérez-Mato, Alba Vieites-Prado, Ramón Iglesias-Rey, José Rivas, Anna M Planas, Tomás Sobrino, José Castillo, Francisco Campos
Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089821/the-role-of-stat3-in-glioblastoma-progression-through-dual-influences-on-tumor-cells-and-the-immune-microenvironment
#19
Nakho Chang, Sun Hee Ahn, Doo-Sik Kong, Hye Won Lee, Do-Hyun Nam
Glioblastoma multiforme (GBM) is the most aggressive form of cancer that begins within the brain; generally, the patient has a dismal prognosis and limited therapeutic options. Signal transducer and activator of transcription 3 (STAT3) is a critical mediator of tumorigenesis, tumor progression, and suppression of anti-tumor immunity in GBM. In a high percentage of GBM cells and tumor microenvironments, persistent activation of STAT3 induces cell proliferation, anti-apoptosis, glioma stem cell maintenance, tumor invasion, angiogenesis, and immune evasion...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28089250/pathology-of-behavior-in-pd-what-is-known-and-what-is-not
#20
REVIEW
Kaylena A Ehgoetz Martens, Simon J G Lewis
Abnormal behavior in Parkinson's disease (PD) stems from a complex orchestration of impaired neural networks that result from PD-related neurodegeneration across multiple levels. Typically, cellular and tissue abnormalities generate neurochemical changes and disrupt specific regions of the brain, in turn creating impaired neural circuits and dysfunctional global networks. The objective of this chapter is to provide an overview of the array of pathological changes that have been linked to different behavioral symptoms of PD such as depression, anxiety, apathy, fatigue, impulse control disorders, psychosis, sleep disorders and dementia...
December 29, 2016: Journal of the Neurological Sciences
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