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https://www.readbyqxmd.com/read/28624432/zinc-transporter-3-znt3-and-vesicular-zinc-in-central-nervous-system-function
#1
REVIEW
Brendan B McAllister, Richard H Dyck
Zinc transporter 3 (ZnT3) is the sole mechanism responsible for concentrating zinc ions within synaptic vesicles in a subset of the brain's glutamatergic neurons. This vesicular zinc can then be released into the synaptic cleft in an activity-dependent fashion, where it can exert many signaling functions. This review provides a comprehensive discussion of the localization and function of ZnT3 and vesicular zinc in the central nervous system. We begin by reviewing the fundamentals of zinc homeostasis and transport, and the discovery of ZnT3...
June 14, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28612134/ketamine-induced-behavioural-and-brain-oxidative-changes-in-mice-an-assessment-of-possible-beneficial-effects-of-zinc-as-mono-or-adjunct-therapy
#2
Olakunle James Onaolapo, Olayemi Quyyom Ademakinwa, Temitayo Opeyemi Olalekan, Adejoke Yetunde Onaolapo
RATIONALE: We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. OBJECTIVES: Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively...
June 14, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28598208/characterization-and-spatiotemporal-expression-of-klf4-in-large-yellow-croaker-larimichthys-crocea
#3
Yonghua Jiang, Kunhuang Han, Mingyi Cai, Yilei Wang, Ziping Zhang
As one of transcription factors and pluripotency factors, Klf4 plays a crucial role in regulation of cellular processes. In this article, we characterized Klf4 of large yellow croaker (Lc-Klf4), which encodes a 452-amino acid protein (Lc-Klf4) with three highly conserved C2H2 zinc fingers. Lc-Klf4 shares high conservative functions in teleosts with the closest relationship with Stegastes partitus. The spatiotemporal expression showed that Lc-Klf4 was expressed widely in adult tissues with gender difference as follows: brain>gill>eye>heart in female; heart>testis>gill>brain in male; male>female in heart, gill, and testis; and female>male in eye...
June 9, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28596487/znf131-suppresses-centrosome-fragmentation-in-glioblastoma-stem-like-cells-through-regulation-of-haus5
#4
Yu Ding, Jacob A Herman, Chad M Toledo, Jackie M Lang, Philip Corrin, Emily J Girard, Ryan Basom, Jeffrey J Delrow, James M Olson, Patrick J Paddison
Zinc finger domain genes comprise ~3% of the human genome, yet many of their functions remain unknown. Here we investigated roles for the vertebrate-specific BTB domain zinc finger gene ZNF131 in the context of human brain tumors. We report that ZNF131 is broadly required for Glioblastoma stem-like cell (GSC) viability, but dispensable for neural progenitor cell (NPC) viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596078/identification-of-an-oxytocinase-vasopressinase-like-leucyl-cystinyl-aminopeptidase-lnpep-in-teleost-fish-and-evidence-for-hypothalamic-mrna-expression-linked-to-behavioral-social-status
#5
Emma A Elkins, Kayla A Walti, Kathryn E Newberry, Sean C Lema
The vasotocin/vasopressin and isotocin/mesotocin/oxytocin family of nonapeptides regulate social behaviors and physiological functions associated with reproductive physiology and osmotic balance. While experimental and correlative studies provide evidence for these nonapeptides as modulators of behavior across all classes of vertebrates, mechanisms for nonapeptide inactivation in regulating these functions have been largely overlooked. Leucyl-cystinyl aminopeptidase (LNPEP) - also known as vasopressinase, oxytocinase, placental leucine aminopeptidase (P-LAP), and insulin-regulated aminopeptidase (IRAP) - is a membrane-bound zinc-dependent metalloexopeptidase enzyme that inactivates vasopressin, oxytocin, and select other cyclic polypeptides...
June 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28595912/the-effect-of-manganese-exposure-in-atp13a2-deficient-mice
#6
Sheila M Fleming, Nicholas A Santiago, Elizabeth J Mullin, Shanta Pamphile, Swagata Karkare, Andrew Lemkuhl, Osunde R Ekhator, Stephen C Linn, John G Holden, Diana S Aga, Jerome A Roth, Benjamin Liou, Ying Sun, Gary E Shull, Patrick J Schultheis
Loss of function mutations in the P5-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice...
June 6, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28589569/identification-of-novel-bcl11a-variants-in-patients-with-epileptic-encephalopathy-expanding-the-phenotypic-spectrum
#7
Michiko Yoshida, Mitsuko Nakashima, Tohru Okanishi, Sotaro Kanai, Ayataka Fujimoto, Kazuya Itomi, Masafumi Morimoto, Hirotomo Saitsu, Mitsuhiro Kato, Naomichi Matsumoto, Tomohiro Chiyonobu
BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified two novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p...
June 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28588449/long-term-assessment-of-aav-mediated-zinc-finger-nuclease-expression-in-the-mouse-brain
#8
Muzna Zahur, Johan Tolö, Mathias Bähr, Sebastian Kügler
Gene editing tools like TALENs, ZFNs and Crispr/Cas now offer unprecedented opportunities for targeted genetic manipulations in virtually all species. Most of the recent research in this area has concentrated on manipulation of the genome in isolated cells, which then give rise to transgenic animals or modified stem cell lines. Much less is known about applicability of genetic scissors in terminally differentiated, non-dividing cells like neurons of the adult brain. We addressed this question by expression of a pair of ZFNs targeting the murine cathepsin D gene in CNS neurons by means of an optimized AAV viral vector...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28588179/childhood-wilson-disease-bangladesh-perspective
#9
M Rukunuzzaman, A B Karim, M Nurullah, F Sultana, M W Mazumder, M A Rahman, S B Billah, F Begum, M Oliullah
Wilson's disease (WD) is an autosomal recessive disorder affecting copper metabolism causing copper induced damage to various organs. In children liver is commonly involved. Central nervous system, eyes, RBC, kidneys, brain and bones may also be affected. Aim of the study is to evaluate clinical & laboratory profile of Wilson's disease in children. This cross sectional descriptive study was conducted at the department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2011 to December, 2013...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28587098/function-of-metallothionein-3-in-neuronal-cells-do-metal-ions-alter-expression-levels-of-mt3
#10
Jamie Bousleiman, Alexa Pinsky, Sohee Ki, Angela Su, Irina Morozova, Sergey Kalachikov, Amen Wiqas, Rae Silver, Mary Sever, Rachel Narehood Austin
A study of factors proposed to affect metallothionein-3 (MT3) function was carried out to elucidate the opaque role MT3 plays in human metalloneurochemistry. Gene expression of Mt2 and Mt3 was examined in tissues extracted from the dentate gyrus of mouse brains and in human neuronal cell cultures. The whole-genome gene expression analysis identified significant variations in the mRNA levels of genes associated with zinc homeostasis, including Mt2 and Mt3. Mt3 was found to be the most differentially expressed gene in the identified groups, pointing to the existence of a factor, not yet identified, that differentially controls Mt3 expression...
May 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28579120/vitamin-d-and-the-brain-genomic-and-non-genomic-actions
#11
REVIEW
Xiaoying Cui, Helen Gooch, Alice Petty, John J McGrath, Darryl Eyles
1,25(OH)2D3 (vitamin D) is well-recognized as a neurosteroid that modulates multiple brain functions. A growing body of evidence indicates that vitamin D plays a pivotal role in brain development, neurotransmission, neuroprotection and immunomodulation. However, the precise molecular mechanisms by which vitamin D exerts these functions in the brain is still unclear. Vitamin D signalling occurs via the vitamin D receptor (VDR), a zinc-finger protein in the nuclear receptor superfamily. Like other nuclear steroids, vitamin D has both genomic and non-genomic actions...
June 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28577822/genome-wide-association-study-of-language-performance-in-alzheimer-s-disease
#12
Kacie D Deters, Kwangsik Nho, Shannon L Risacher, Sungeun Kim, Vijay K Ramanan, Paul K Crane, Liana G Apostolova, Andrew J Saykin
Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas...
May 31, 2017: Brain and Language
https://www.readbyqxmd.com/read/28576733/neuronal-zinc-%C3%AE-2-glycoprotein-is-decreased-in-temporal-lobe-epilepsy-in-patients-and-rats
#13
Ying Liu, Teng Wang, Xi Liu, Xin Wei, Tao Xu, Maojia Yin, Xueying Ding, Lijuan Mo, Lifen Chen
Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used...
May 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28576725/imaging-of-glial-cell-morphology-sod1-distribution-and-elemental-composition-in-the-brainstem-and-hippocampus-of-the-als-hsod1-g93a-rat
#14
Stefan Stamenković, Tanja Dučić, Vera Stamenković, Alexander Kranz, Pavle R Andjus
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1(G93A) transgenic rat model of ALS...
May 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28573481/copper-pyrithione-a-booster-biocide-induces-abnormal-muscle-and-notochord-architecture-in-zebrafish-embryogenesis
#15
Kelly M Almond, Louis D Trombetta
The metal pyrithiones, principally zinc (ZnPT) and copper (CuPT), are replacing tributyltin (TBT) as antifouling agents. Zebrafish embryos were exposed within the first hour after fertilization to 12 and 64 µg/L of CuPT for 24 h. Morphological abnormalities in notochord and muscle architecture were observed at 96 h post fertilization (hpf). TEM revealed abnormal electron dense deposits in the notochord sheath and muscle fiber degeneration in animals treated with 12 µg/L of CuPT. Embryos that were exposed to 64 µg/L of CuPT displayed severe muscle fiber degeneration including abnormal A and I band patterning and altered z disk arrangement...
June 1, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#16
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 1, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28569061/structure-based-design-of-scaffolds-targeting-pde10a-by-inpharma-nmr
#17
Luca Codutti, Manuela Grimaldi, Teresa Carlomagno
Phosphodiesterases (PDE) hydrolyze both cyclic AMP and GMP (cAMP/cGMP) and are responsible for the regulation of their levels in a multitude of cellular functions. PDE10A is expressed in the brain and is a validated target for both schizophrenia and Huntington disease. Here, we address the identification of novel chemical scaffolds that may bind PDE10A via structure-based drug design. For this task, we use INPHARMA, an NMR-based method that measures protein-mediated interligand NOEs between pairs of weakly, competitively binding ligands...
May 31, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28557351/the-highly-pleiotropic-gene-slc39a8-as-an-opportunity-to-gain-insight-into-the-molecular-pathogenesis-of-schizophrenia
#18
REVIEW
Javier Costas
There is a long way from the initial discovery of a genome-wide significant signal to mechanistic understanding of the association. Identification of the gene and causal polymorphism usually requires an extensive additional effort. The schizophrenia genome-wide significant locus at 4q24 may be a rare exception to this pattern. As discussed in this review, the association at this locus is most probably driven by a functional missense variant at the metal cations transporter SLC39A8. The variant, rs13107325, is almost exclusive of European populations and is one of the most pleiotropic variants of the genome, being associated at genome-wide significant level with several additional traits, such as body mass index, Crohn's disease, blood pressure related-traits, and serum levels of manganese, N-terminal pro-B-type natriuretic peptide and HDL-cholesterol...
May 30, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28554310/ion-channel-and-neurotransmitter-modulators-as-electroceutical-approaches-to-the-control-of-cancer
#19
Jack Tuszynski, Tatiana M Tilli, Michael Levin
The activities of individual cells must be tightly coordinated in order to build and maintain complex 3-dimensional body structures during embryogenesis and regeneration. Thus, one way to view cancer is within systems biology as a network disorder affecting the ability of cells to properly interact with a morphodynamic field of instructive signals that keeps proliferation and migration orchestrated toward the anatomical needs of the host organism. One layer of this set of instructive microenvironmental cues is bioelectrical...
May 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28539940/horizontal-and-vertical-distribution-of-heavy-metals-in-farm-produce-and-livestock-around-lead-contaminated-goldmine-in-dareta-and-abare-zamfara-state-northern-nigeria
#20
O E Orisakwe, O O Oladipo, G C Ajaezi, N A Udowelle
Background. Hitherto studies in response to the June 2010 lead poisoning, Zamfara State, Nigeria, have focused on clinical interventions without information on livestock and other metals. Objective. This study has investigated the distribution of heavy metals in farm produce and livestock around lead-contaminated goldmine in Dareta and Abare, Zamfara State, Nigeria. Methods. Vegetables, soil, water, blood, and different meat samples were harvested from goat, sheep, cattle, and chicken from Dareta, Abare, and Gusau communities...
2017: Journal of Environmental and Public Health
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