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Granul cell precursors

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https://www.readbyqxmd.com/read/28424053/stress-induced-nuclear-granules-form-in-response-to-accumulation-of-misfolded-proteins-in-caenorhabditis-elegans
#1
Katherine M Sampuda, Mason Riley, Lynn Boyd
BACKGROUND: Environmental stress can affect the viability or fecundity of an organism. Environmental stressors may affect the genome or the proteome and can cause cellular distress by contributing to protein damage or misfolding. This study examines the cellular response to environmental stress in the germline of the nematode, C. elegans. RESULTS: Salt stress, oxidative stress, and starvation, but not heat shock, induce the relocalization of ubiquitin, proteasome, and the TIAR-2 protein into distinct subnuclear regions referred to as stress induced nuclear granules (SINGs)...
April 19, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28379564/shortened-primary-cilium-length-and-dysregulated-sonic-hedgehog-signaling-in-niemann-pick-c1-disease
#2
Sonia Canterini, Jessica Dragotto, Andrea Dardis, Stefania Zampieri, Maria Egle De Stefano, Franco Mangia, Robert P Erickson, Maria Teresa Fiorenza
The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder due to mutations in the NPC1 gene, encoding a transmembrane protein related to the Sonic hedgehog receptor, Patched, and involved in intracellular trafficking of cholesterol. We have recently found that the proliferation of cerebellar granule neuron precursors is significantly reduced in Npc1-/- mice due to the downregulation of Shh expression. This finding prompted us to analyze the formation of the primary cilium, a non-motile organelle that is specialized for Shh signal transduction and responsible, when defective, for several human genetic disorders...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28371026/interaction-and-developmental-activation-of-two-neuroendocrine-systems-that-regulate-light-mediated-skin-pigmentation
#3
Gabriel E Bertolesi, Yi Nong Song, Karen Atkinson-Leadbeater, Jung-Lynn Jonathan Yang, Sarah McFarlane
Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha melanocyte stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion...
March 30, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28359846/long-term-effect-of-neonatal-inhibition-of-app-gamma-secretase-on-hippocampal-development-in-the-ts65dn-mouse-model-of-down-syndrome
#4
Fiorenza Stagni, Alessandra Raspanti, Andrea Giacomini, Sandra Guidi, Marco Emili, Elisabetta Ciani, Alessandro Giuliani, Andrea Bighinati, Laura Calzà, Jacopo Magistretti, Renata Bartesaghi
Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed...
March 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#5
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28296382/human-%C3%AE-defensin-6-a-small-peptide-that-self-assembles-and-protects-the-host-by-entangling-microbes
#6
Phoom Chairatana, Elizabeth M Nolan
Human α-defensin 6 (HD6) is a 32-residue cysteine-rich peptide that contributes to innate immunity by protecting the host at mucosal sites. This peptide is produced in small intestinal Paneth cells, stored as an 81-residue precursor peptide named proHD6 in granules, and released into the lumen. One unusual feature of HD6 is that it lacks the broad-spectrum antimicrobial activity observed for other human α-defensins, including the Paneth cell peptide human α-defensin 5 (HD5). HD6 exhibits unprecedented self-assembly properties, which confer an unusual host-defense function...
March 15, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28230278/deletion-of-psychiatric-risk-gene-cacna1c-impairs-hippocampal-neurogenesis-in-cell-autonomous-fashion
#7
Bianca Völkening, Kai Schönig, Golo Kronenberg, Dusan Bartsch, Tillmann Weber
Ca(2+) is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created Tg(GLAST-CreERT2) /Cacna1c(fl/fl) /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c...
February 23, 2017: Glia
https://www.readbyqxmd.com/read/28188823/hepatic-stellate-cell-interferes-with-nk-cell-regulation-of-fibrogenesis-via-curcumin-induced-senescence-of-hepatic-stellate-cell
#8
Huanhuan Jin, Yan Jia, Zhen Yao, Jingjing Huang, Meng Hao, Shunyu Yao, Naqi Lian, Feng Zhang, Chenxi Zhang, Xingran Chen, Mianli Bian, Jiangjuan Shao, Li Wu, Anping Chen, Shizhong Zheng
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis...
February 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28174113/involvement-of-glun2b-subunit-containing-n-methyl-d-aspartate-nmda-receptors-in-mediating-the-acute-and-chronic-synaptotoxic-effects-of-oligomeric-amyloid-beta-a%C3%AE-in-murine-models-of-alzheimer-s-disease-ad
#9
Gerhard Rammes, Corinna Mattusch, Matthias Wulff, Franziska Seeser, Matthias Kreuzer, Kaichuan Zhu, Jan M Deussing, Jochen Herms, Chris G Parsons
To elucidate whether a permanent reduction of the GluN2B subunit affects the pathology of Alzheimer's disease (AD), we cross-bred mice heterozygous for GluN2B receptors in the forebrain (hetGluN2B) with a mouse model for AD carrying a mutated amyloid precursor protein with the Swedish and Arctic mutation (mAPP) resulting in a hetGluN2B/mAPP transgenic. By means of voltage-sensitive dye imaging (VSDI) in the di-synaptic hippocampal pathway and the recording of field excitatory postsynaptic potentials (fEPSPs), hippocampal slices of all genotypes (WT, hetGluN2B, mAPP and hetGluN2B/mAPP, age 9-18 months) were tested for spatiotemporal activity propagation and LTP induction...
February 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28152379/selective-transduction-of-astrocytic-and-neuronal-cns-subpopulations-by-lentiviral-vectors-pseudotyped-with-chikungunya-virus-envelope
#10
Ioanna Eleftheriadou, Michael Dieringer, Xuan Ying Poh, Julia Sanchez-Garrido, Yunan Gao, Argyro Sgourou, Laura E Simmons, Nicholas D Mazarakis
Lentiviral vectors are gene delivery vehicles that integrate into the host genome of dividing and non-dividing mammalian cells facilitating long-term transgene expression. Lentiviral vector versatility is greatly increased by incorporating heterologous viral envelope proteins onto the vector particles instead of the native envelope, conferring on these pseudotyped vectors a modified tropism and host range specificity. We investigated the pseudotyping efficiency of HIV-1 based lentiviral vectors with alphaviral envelope proteins from the Chikungunya Virus (CHIKV-G) and Sindbis Virus (SINV-G)...
January 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28122547/amyloid-like-aggregation-of-provasopressin-in-diabetes-insipidus-and-secretory-granule-sorting
#11
Nicole Beuret, Franziska Hasler, Cristina Prescianotto-Baschong, Julia Birk, Jonas Rutishauser, Martin Spiess
BACKGROUND: Aggregation of peptide hormone precursors in the trans-Golgi network is an essential process in the biogenesis of secretory granules in endocrine cells. It has recently been proposed that this aggregation corresponds to the formation of functional amyloids. Our previous finding that dominant mutations in provasopressin, which cause cell degeneration and diabetes insipidus, prevent native folding and produce fibrillar aggregates in the endoplasmic reticulum (ER) might thus reflect mislocalized amyloid formation by sequences that evolved to mediate granule sorting...
January 26, 2017: BMC Biology
https://www.readbyqxmd.com/read/28108848/glucagon-like-peptide-1-is-co-localized-with-neurotensin-in-the-chicken-ileum
#12
Kei Nishimura, Kohzy Hiramatsu, Takafumi Watanabe, Kazumi Kita
Glucagon-like peptide (GLP)-1 and neurotensin (NT) are distributed throughout the chicken ileum. Here, we attempt to determine if GLP-1 and NT co-localize in the chicken ileum by using immunofluorescence, immunocytochemistry and in situ hybridization techniques. Three types of enteroendocrine cells, GLP-1(+)/NT(+), GLP-1(+)/NT(-) and GLP-1(-)/NT(+) cells, were detected in the mucosal epithelium by the double immunofluorescence method. The ratio of GLP-1(+)/NT(+) cells at the crypts in the distal ileum was significantly higher than that in the proximal ileum...
January 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28045461/antidepressant-responsiveness-in-adulthood-is-permanently-impaired-after-neonatal-destruction-of-the-neurogenic-pool
#13
S Yu, I Zutshi, R Stoffel, J Zhang, A P Ventura-Silva, N Sousa, P S Costa, F Holsboer, A Patchev, O F X Almeida
The dynamic turnover of hippocampal neurons is implicated in the regulation of cognitive and affective behavior. Extending our previous demonstration that administration of dexamethasone (ND) to neonatal rats depletes the resident population of neural precursor cells (NPC) and restrains the size of the neurogenic regions, we now show that the adverse effects of ND persist into adulthood. Specifically, ND impairs repletion of the neurogenic pool and neurogenesis; ND also compromises cognitive performance, the ability to actively adapt to an acute stressor and, the efficacy of glucocorticoid (GC) negative feedback...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28018222/suppression-of-medulloblastoma-lesions-by-forced-migration-of-preneoplastic-precursor-cells-with-intracerebellar-administration-of-the-chemokine-cxcl3
#14
Manuela Ceccarelli, Laura Micheli, Felice Tirone
Medulloblastoma (MB), tumor of the cerebellum, remains a leading cause of cancer-related mortality in childhood. We previously showed, in a mouse model of spontaneous MB (Ptch1(+/-)/Tis21(-/-)), that a defect of the migration of cerebellar granule neuron precursor cells (GCPs) correlates with an increased frequency of MB. This occurs because GCPs, rather than migrating internally and differentiating, remain longer in the proliferative area at the cerebellar surface, becoming targets of transforming insults...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27966978/quantitative-global-proteomics-of-yeast-pbp1-deletion-mutants-and-their-stress-responses-identifies-glucose-metabolism-mitochondrial-and-stress-granule-changes
#15
Gunnar Seidel, David Meierhofer, Nesli-Ece Şen, Anika Guenther, Sylvia Krobitsch, Georg Auburger
The yeast protein PBP1 is implicated in very diverse pathways. Intriguingly, its deletion mitigates the toxicity of human neurodegeneration factors. Here, we performed label-free quantitative global proteomics to identify crucial downstream factors, either without stress or under cell stress conditions (heat and NaN3). Compared to the wildtype BY4741 strain, PBP1 deletion always triggered downregulation of the key bioenergetics enzyme KGD2 and the prion protein RNQ1 as well as upregulation of the leucine biosynthesis enzyme LEU1...
December 22, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27965576/functional-genomics-identifies-tis21-dependent-mechanisms-and-putative-cancer-drug-targets-underlying-medulloblastoma-shh-type-development
#16
Giulia Gentile, Manuela Ceccarelli, Laura Micheli, Felice Tirone, Sebastiano Cavallaro
We have recently generated a novel medulloblastoma (MB) mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1(+/-)/Tis21(KO) ). Its main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs). By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27965537/region-specific-differences-in-amyloid-precursor-protein-expression-in-the-mouse-hippocampus
#17
Domenico Del Turco, Mandy H Paul, Jessica Schlaudraff, Meike Hick, Kristina Endres, Ulrike C Müller, Thomas Deller
The physiological role of amyloid precursor protein (APP) has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and-at the behavioral level-hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus (DG) and area CA1 of the mouse hippocampus...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27932459/the-basophil-specific-protease-mmcp-8-provokes-an-inflammatory-response-in-the-skin-with-microvascular-hyperpermeability-and-leukocyte-infiltration
#18
Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
Basophils have often been erroneously considered to be minor relatives or blood-circulating precursors of tissue-resident mast cells because of some phenotypic similarity between them, including basophilic secretory granules in the cytoplasm. However, recent studies revealed that the repertoire of serine proteases stored in secretory granules is distinct in them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells despite its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker, but its functional property remains uncertain...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27914933/differential-synthesis-and-release-of-il-18-and-il-18-binding-protein-from-human-platelets-and-their-implications-for-hiv-infection
#19
Ossama Allam, Suzanne Samarani, Mohammad-Ali Jenabian, Jean-Pierre Routy, Cecile Tremblay, Devendra Amre, Ali Ahmad
IL-18 is a pro-inflammatory cytokine belonging to the IL-1 family and is produced in the body from macrophages, epithelial and dendritic cells, keratinocytes, adrenal cortex etc. The cytokine is produced as an inactive precursor that is cleaved inside cells into its mature form by activated caspase 1, which exists as an inactive precursor in human cells and requires assembly of an inflammasomes for its activation. We show here for the first time that human platelets contain transcripts for the IL-18 gene. They synthesize the cytokine de novo, process and release it upon activation...
December 1, 2016: Cytokine
https://www.readbyqxmd.com/read/27879339/mct8-deficiency-in-purkinje-cells-disrupts-embryonic-chicken-cerebellar-development
#20
Joke Delbaere, Pieter Vancamp, Stijn L J Van Herck, Nele M A Bourgeois, Mary J Green, Richard J T Wingate, Veerle M Darras
Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in the Allan-Herndon-Dudley syndrome accompanied by severe locomotor deficits. The underlying mechanisms of the associated cerebellar maldevelopment were studied using the chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar anlage of a 3-day-old embryo allowed knockdown of MCT8 in Purkinje cell precursors. This resulted in the downregulation of the thyroid hormone-responsive gene RORα and the Purkinje cell-specific differentiation marker LHX1/5 at day 6...
February 2017: Journal of Endocrinology
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