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https://www.readbyqxmd.com/read/28922152/brain-biomarkers-in-familial-alzheimer-s-disease-mouse-models
#1
Yafit Kuttner-Hirshler, Palamadai N Venkatasubramanian, Joan Apolinario, Jacqueline Bonds, Alice M Wyrwicz, Orly Lazarov
Alzheimer's disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer's disease (FAD)...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28918504/autism-spectrum-disorders-and-disease-modeling-using-stem-cells
#2
REVIEW
Anita Brito, Fabiele Baldino Russo, Alysson Renato Muotri, Patricia Cristina Baleeiro Beltrão-Braga
Autism spectrum disorders (ASD) represent a variety of disorders characterized as complex lifelong neurodevelopment disabilities, which may affect the ability of communication and socialization, including typical comportments like repetitive and stereotyped behavior. Other comorbidities are usually present, such as echolalia, hypotonia, intellectual disability and difficulties in processing figured speech. Furthermore, some ASD individuals may present certain abilities, such as eidetic memory, outstanding musical or painting talents and special mathematical skills, among others...
September 16, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#3
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28913662/effects-of-short-term-exposure-to-sevoflurane-on-the-survival-proliferation-apoptosis-and-differentiation-of-neural-precursor-cells-derived-from-human-embryonic-stem-cells
#4
Jin-Woo Park, Mi-Sun Lim, So Yeon Ji, Myung Soo Cho, Seong-Joo Park, Sung-Hee Han, Jin-Hee Kim
PURPOSE: Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Considering short operating times and the popularity of sevoflurane in pediatric anesthesia, it is important to verify the effects of short-period exposure to sevoflurane on the developing brain. METHODS: We measured the effects of short-term exposure (2 h) to 3%, 6%, or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32...
September 14, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28911165/cellular-retinoic-acid-binding-protein-1-modulates-stem-cell-proliferation-to-affect-learning-and-memory-in-male-mice
#5
Yu-Lung Lin, Shawna D Persaud, Jennifer Nhieu, Li-Na Wei
Retinoic acid (RA) is the active ingredient of vitamin A. It exerts its canonical activity by binding to nuclear RA receptors (RARs) to regulate gene expression. Increasingly, RA is also known to elicit nongenomic RAR-independent activities, most widely detected in activating extracellular regulated kinase (ERK)1/2. This study validated the functional role of cellular retinoic acid-binding protein 1 (Crabp1) in mediating nongenomic activity in RA, specifically activating ERK1/2 to rapidly augment the cell cycle by expanding the growth 1 phase and slowing down embryonic stem cell and neural stem cell (NSC) proliferation...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#6
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28904110/the-chromatin-accessibility-signature-of-human-immune-aging-stems-from-cd8-t-cells
#7
Duygu Ucar, Eladio J Márquez, Cheng-Han Chung, Radu Marches, Robert J Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L Stitzel, A Karolina Palucka, George A Kuchel, Jacques Banchereau
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites...
September 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28861081/14%C3%A2-years-after-discovery-clinical-follow-up-on-15-patients-with-inducible-co-stimulator-deficiency
#8
Johanna Schepp, Janet Chou, Andrea Skrabl-Baumgartner, Peter D Arkwright, Karin R Engelhardt, Sophie Hambleton, Tomohiro Morio, Ekkehard Röther, Klaus Warnatz, Raif Geha, Bodo Grimbacher
BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855626/dual-roles-of-a%C3%AE-in-proliferative-processes-in-an-amyloidogenic-model-of-alzheimer-s-disease
#9
David Baglietto-Vargas, Elisabeth Sánchez-Mejias, Victoria Navarro, Sebastián Jimenez, Laura Trujillo-Estrada, Angela Gómez-Arboledas, Maria Sánchez-Mico, Raquel Sánchez-Varo, Marisa Vizuete, José Carlos Dávila, José Manuel García-Verdugo, Javier Vitorica, Antonia Gutierrez
Alzheimer's disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer's patients. In this regard, new evidence linking Alzheimer's disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of Aβ pathology on neurogenesis/gliogenesis remains unclear...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855514/hit-and-run-programming-of-therapeutic-cytoreagents-using-mrna-nanocarriers
#10
H F Moffett, M E Coon, S Radtke, S B Stephan, L McKnight, A Lambert, B L Stoddard, H P Kiem, M T Stephan
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28851693/the-antitumor-effects-of-vaccine-activated-cd8-t-cells-associate-with-weak-tcr-signaling-and-induction-of-stem-like-memory-t-cells
#11
Sha Wu, Wei Zhu, Yibing Peng, Lan Wang, Yuang Hong, Lei Huang, Dayong Dong, Junping Xie, Todd Merchen, Edward Kruse, Zong Sheng Guo, David Bartlett, Ning Fu, Yukai He
To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we studied two alpha-fetoprotein-specific CD8+ T cells (Tet499 and Tet212) that had different antitumor effects. We found that Tet499 required high antigen doses for re-activation, but could survive persistent antigen stimulation and maintain their effector functions. In contrast, Tet212 had a low threshold of re-activation, but underwent exhaustion and apoptosis in the presence of persistent antigen. In vivo, Tet499 cells expanded more than Tet212 upon re-encountering antigen and generated stronger antitumor effects...
August 29, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28837861/klotho-regulates-postnatal-neurogenesis-and-protects-against-age-related-spatial-memory-loss
#12
Ann M Laszczyk, Stephanie Fox-Quick, Hai T Vo, Dailey Nettles, Phyllis C Pugh, Linda Overstreet-Wadiche, Gwendalyn D King
Although the absence of the age-regulating klotho protein causes klotho-deficient mice to rapidly develop cognitive impairment and increasing klotho enhances hippocampal-dependent memory, the cellular effects of klotho that mediate hippocampal-dependent memory function are unknown. Here, we show premature aging of the klotho-deficient hippocampal neurogenic niche as evidenced by reduced numbers of neural stem cells, decreased proliferation, and impaired maturation of immature neurons. Klotho-deficient neurospheres show reduced proliferation and size that is rescued by supplementation with shed klotho protein...
July 29, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28833933/nscs-promote-hippocampal-neurogenesis-metabolic-changes-and-synaptogenesis-in-app-ps1-transgenic-mice
#13
Wei Zhang, Guo-Jun Gu, Qi Zhang, Jian-Hui Liu, Bo Zhang, Yi Guo, Mei-Yun Wang, Qi-Yong Gong, Xu Jian-Rong
Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice...
August 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28827761/copy-number-elevation-of-22q11-2-genes-arrests-the-developmental-maturation-of-working-memory-capacity-and-adult-hippocampal-neurogenesis
#14
S Boku, T Izumi, S Abe, T Takahashi, A Nishi, H Nomaru, Y Naka, G Kang, M Nagashima, A Hishimoto, S Enomoto, G Duran-Torres, K Tanigaki, J Zhang, K Ye, S Kato, P T Männistö, K Kobayashi, N Hiroi
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11...
August 22, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28826528/chemokine-driven-cd4-t-cell-homing-new-concepts-and-recent-advances
#15
Carly E Gregor, Jade Foeng, Iain Comerford, Shaun R McColl
CD4(+) T cells are critical regulators of the adaptive immune system and have diverse roles in regulating responses to the broad array of microbes encountered. Appropriate execution of their effector function requires precise and coordinated migration of these cells to specific lymphoid niches and peripheral sites. This migration is largely controlled by dynamic expression of chemokine receptors and the discrete functions of distinct subsets of CD4(+) T cells can often be determined from their expression of specific chemokine receptors...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28826476/eyeless-uncouples-mushroom-body-neuroblast-proliferation-from-dietary-amino-acids-in-drosophila
#16
Conor W Sipe, Sarah E Siegrist
Cell proliferation is coupled with nutrient availability. If nutrients become limited, proliferation ceases, because growth factor and/or PI3-kinase activity levels become attenuated. Here, we report an exception to this generality within a subpopulation of Drosophila neural stem cells (neuroblasts). We find that most neuroblasts enter and exit cell cycle in a nutrient-dependent manner that is reversible and regulated by PI3-kinase. However, a small subset, the mushroom body neuroblasts, which generate neurons important for memory and learning, divide independent of dietary nutrient conditions and PI3-kinase activity...
August 9, 2017: ELife
https://www.readbyqxmd.com/read/28826352/pcl-pdms-pcl-copolymer-based-microspheres-mediate-cardiovascular-differentiation-from-embryonic-stem-cells
#17
Liqing Song, Mohammad Faisal Ahmed, Yan Li, Julie Bejoy, Changchun Zeng, Yan Li
Poly-ϵ-caprolactone (PCL) based microspheres have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. In addition, PCL and polydimethylsiloxane (PDMS) can be fabricated into thermo-responsive shape memory polymers for various biomedical applications (e.g., smart sutures and vascular stents). However, the influence of biophysical properties of PCL-PDMS based microspheres on stem cell lineage commitment has not been well understood...
August 21, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28822836/fty720-fingolimod-an-oral-s1pr-modulator-mitigates-radiation-induced-cognitive-deficits
#18
Alexander M Stessin, Matei A Banu, Mariano Guardia Clausi, Nicholas Berry, John A Boockvar, Samuel Ryu
PURPOSE: This study evaluates FTY720/Fingolimod, modulator of sphingosine-1-phosphate (S1P) receptor, as a potential mitigator of radiation-induced neurocognitive dysfunction. METHODS AND MATERIALS: To study radiation-induced neurocognitive deficits, 6 week-old C57/Bl/6J mice received 0 or 7Gy cranial irradiation and were treated with FTY720 or vehicle for seven weeks. Fear conditioning and Morris water maze were then employed to test learning and memory. Immunohistochemical staining for neural progenitor cells (NPCs) and mature neurons was used to assess changes in hippocampal neurogenesis...
August 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28822221/brain-plasticity-cognitive-functions-and-neural-stem-cells-a-pivotal-role-for-the-brain-specific-neural-master-gene-srgap2-fam72
#19
Nguyen Thi Thanh Ho, Arne Kutzner, Klaus Heese
Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating protein 2 - family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28818684/t-cell-mediated-rejection-of-human-cd34-cells-is-prevented-by-costimulatory-blockade-in-a-xenograft-model
#20
Annie L Oh, Dolores Mahmud, Benedetta Nicolini, Nadim Mahmud, Vitalyi Senyuk, Pritesh R Patel, Elisa Bonetti, Mario Arpinati, James L M Ferrara, Damiano Rondelli
A xenograft model of stem cell rejection was developed by co-transplantating human CD34(+) and allogeneic CD3(+) T cells into NOD-scid ɣ-chain(null) mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Kinetics experiments showed that 2 weeks after transplantation CD34(+) cells engrafted the marrow and T cells expanded in the spleen. Then, at 4 weeks only memory T cells populated both sites and rejected CD34(+) cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day -1 to +27 (group A), from day -1 to +13 (group B), or from day +14 to +28 (group C)...
August 14, 2017: Biology of Blood and Marrow Transplantation
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