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https://www.readbyqxmd.com/read/29449720/biallelic-inactivating-variants-in-the-gtpbp2-gene-cause-a-neurodevelopmental-disorder-with-severe-intellectual-disability
#1
Aida M Bertoli-Avella, Jose M Garcia-Aznar, Oliver Brandau, Fahad Al-Hakami, Zafer Yüksel, Anett Marais, Nana-Maria Grüning, Lia Abbasi Moheb, Omid Paknia, Nahla Alshaikh, Seham Alameer, Makia J Marafi, Fahd Al-Mulla, Nouriya Al-Sannaa, Arndt Rolfs, Peter Bauer
Congenital neurological disorders are genetically highly heterogeneous. Rare forms of hereditary neurological disorders are still difficult to be adequately diagnosed. Pertinent studies, especially when reporting only single families, need independent confirmation. We present three unrelated families in which whole-exome sequencing identified the homozygous non-sense variants c.430[C>T];[C>T] p.(Arg144*), c.1219[C>T];[C>T] p.(Gln407*) and c.1408[C>T];[C>T] p.(Arg470*) in GTPBP2. Their clinical presentations include early onset and apparently non-progressive motor and cognitive impairment, and thereby overlap with findings in a recently described family harbouring a homozygous GTPBP2 splice site variant...
February 15, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29446158/a-neuroscience-perspective-of-the-gut-theory-of-parkinson-s-disease
#2
Lisa M Smith, Louise C Parr-Brownlie
Parkinson's disease is caused by complex interactions between environmental factors and a genetic predisposition. Environmental factors include exposure to pesticides and toxins, heavy metals and accumulation of iron and/or manganese in the brain. However, accumulating evidence indicates that gut-brain health and function is impaired in Parkinson's disease, often a decade before motor symptoms are diagnosed. We present the gut-brain theory of Parkinson's disease and summarise the peripheral and central nervous system pathology, gastrointestinal symptoms experienced by many Parkinson's patients, the route by which gut-brain dysfunction may occur, and changes in gut microbiota that are associated with disease expression...
February 15, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29438105/magnetic-resonance-and-photoacoustic-imaging-of-brain-tumor-mediated-by-mesenchymal-stem-cell-labeled-with-multifunctional-nanoparticle-introduced-via-carotid-artery-injection
#3
Yang Qiao, Joy Gumin, Christopher MacLellan, Feng Gao, Richard Bouchard, Frederick Lang, R Jason Stafford, Marites P Melancon
To evaluate the feasibility of visualizing bone marrow-derived human mesenchymal stem cells (MSCs) labeled with a gold-coated magnetic resonance (MR)-active multifunctional nanoparticle (SPIO@Au) for assessing the extent of MSC homing in glioma- bearing mice following carotid artery MSC injection. MATERIALS AND METHODS: Nanoparticle containing superparamagnetic iron oxide coated with gold (SPIO@Au) having a diameter of ~82 nm and maximum absorbance in the near infrared (NIR) region was synthesized...
February 13, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29432893/improvement-of-cognitive-functions-in-response-to-a-regular-nordic-walking-training-in-elderly-women-a-change-dependent-on-the-training-experience
#4
A Gmiąt, J Jaworska, K Micielska, J Kortas, K Prusik, K Prusik, M Lipowski, A Radulska, N Szupryczyńska, J Antosiewicz, E Ziemann
Although regular physical activity is known to benefit health of aging populations, there are still many factors, which regulate exercise-induced adaptive changes. Among many vitamin D and myokines are under consideration. We, therefore, evaluated the influence of a single session of and regular Nordic Walking (NW) training combined with vitamin D supplementation on cognitive functions and muscle strength and some elements of the amino-acid profile. Thirty-five healthy elderly women (68 ± 5 years old) from health promotion programmes took part in the study...
February 9, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29425576/evidence-based-and-consensus-clinical-practice-guidelines-for-the-iron-treatment-of-restless-legs-syndrome-willis-ekbom-disease-in-adults-and-children-an-irlssg-task-force-report
#5
Richard P Allen, Daniel L Picchietti, Michael Auerbach, Yong Won Cho, James R Connor, Christopher J Earley, Diego Garcia-Borreguero, Suresh Kotagal, Mauro Manconi, William Ondo, Jan Ulfberg, John W Winkelman
BACKGROUND: Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children...
January 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29424844/dietary-lipophilic-iron-alters-amyloidogenesis-and-microglial-morphology-in-alzheimer-s-disease-knock-in-app-mice
#6
Douglas G Peters, Alexis N Pollack, Keith C Cheng, Dongxiao Sun, Takaomi Saido, Michael P Haaf, Qing X Yang, James R Connor, Mark D Meadowcroft
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized pathologically by amyloid beta (Aβ) deposition, microgliosis, and iron dyshomeostasis. Increased labile iron due to homeostatic dysregulation is believed to facilitate amyloidogenesis. Free iron is incorporated into aggregating amyloid peptides during Aβ plaque formation and increases potential for oxidative stress surrounding plaques. The goal of this work was to observe how brain iron levels temporally influence Aβ plaque formation, plaque iron concentration, and microgliosis...
February 9, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29424324/nano-medicine-as-a-newly-emerging-approach-to-combat-human-immunodeficiency-virus-hiv
#7
Muthupandian Saravanan, Tsehaye Asmalash, Atsebaha Gebrekidan, Dawit Gebreegziabiher, Tadele Araya, Haftamu Hilekiros, Hamed Barabadi, Kumaresan Ramanathan
BACKGROUND: Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers...
February 8, 2018: Pharmaceutical Nanotechnology
https://www.readbyqxmd.com/read/29423566/clinical-and-neuroimaging-features-of-autosomal-recessive-spastic-paraplegia-35-spg35-case-reports-new-mutations-and-brief-literature-review
#8
Francesco Mari, Beatrice Berti, Alessandro Romano, Jacopo Baldacci, Riccardo Rizzi, M Grazia Alessandrì, Alessandra Tessa, Elena Procopio, Anna Rubegni, Charles Marques Lourenḉo, Alessandro Simonati, Renzo Guerrini, Filippo Maria Santorelli
Spastic paraplegia 35 (SPG35) is a recessive condition characterized by childhood onset, progressive course, complicated by dystonia, dysarthria, cognitive impairment, and epilepsy. Mutations in the FA2H gene have been described in several families, leading to the proposal of a single entity, named fatty acid hydrolase-associated neurodegeneration (FAHN). Several reports have described a polymorphic radiological picture with white matter lesions of various degrees and a distinct form of neurodegeneration with brain iron accumulation...
February 8, 2018: Neurogenetics
https://www.readbyqxmd.com/read/29415739/hepcidin-an-emerging-and-important-player-in-brain-iron-homeostasis
#9
REVIEW
Driton Vela
Hepcidin is emerging as a new important factor in brain iron homeostasis. Studies suggest that there are two sources of hepcidin in the brain; one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain. The most important source of hepcidin in the brain are glial cells. Role of hepcidin in brain functions has been observed during neuronal iron-load and brain hemorrhage, where secretion of abundant hepcidin is related with the severity of brain damage...
February 7, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29411538/spion-mediated-mir-141-promotes-the-differentiation-of-huaescs-into-dopaminergic-neuron-like-cells-via-suppressing-lncrna-hotair
#10
Te Liu, Hu Zhang, Jiajia Zheng, Jiajia Lin, Yongyi Huang, Jiulin Chen, Zhihua Yu, Lihe Guo, Weidong Pan, Ying Xiong, Chuan Chen
In this study, a bioinformatics analysis and luciferase reporter assay revealed that microRNA-141 could silence the expression of lncRNA-HOTAIR by binding to specific sites on lncRNA-HOTAIR. We used superparamagnetic iron oxide nanoparticles (SPIONs) to mediate the high expression of microRNA-141 (SPIONs@miR-141) in human amniotic epithelial stem cells (HuAESCs), which was followed by the induction of the differentiation of HuAESCs into dopaminergic neuron-like cells (iDNLCs). qPCR, western blot, immunofluorescence staining and HPLC all suggested that SPION-mediated overexpression of miR-141 could promote an increased expression of brain-derived neurotrophic factor (BDNF), DAT and 5-TH in HuAESC-derived iDNLCs...
February 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29409688/classification-and-molecular-pathogenesis-of-nbia-syndromes
#11
REVIEW
Ivano Di Meo, Valeria Tiranti
Brain iron accumulation is the hallmark of a group of seriously invalidating and progressive rare diseases collectively denominated Neurodegeneration with Brain Iron Accumulation (NBIA), characterized by movement disorder, painful dystonia, parkinsonism, mental disability and early death. Currently there is no established therapy available to slow down or reverse the progression of these conditions. Several genes have been identified as responsible for NBIA but only two encode for proteins playing a direct role in iron metabolism...
January 17, 2018: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29409005/environmental-and-dietary-exposure-to-copper-and-its-cellular-mechanisms-linking-to-alzheimer-disease
#12
Heng-Wei Hsu, Stephen C Bondy, Masashi Kitazawa
Metals are commonly found in the environment, household, and workplaces in various forms, and a significant segment of the population is routinely exposed to the trace amount of metals from variety of sources. Exposure to metals, such as aluminum, lead, iron, and copper, from environment has long been debated as a potential environmental risk factor for Alzheimer's disease (AD) for decades, yet results from in vitro, in vivo, and human population remain controversial. In the case of copper, the neurotoxic mechanism of action was classically viewed as its strong affinity to amyloid-beta (Aβ) to help its aggregation and increase oxidative stress via Fenton reaction...
February 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29407213/iron-released-from-reactive-microglia-by-noggin-improves-myelin-repair-in-the-ischemic-brain
#13
Jin A Shin, Yul A Kim, Hye Won Kim, Hee-Sun Kim, Kyung-Eun Lee, Jihee Lee Kang, Eun-Mi Park
We previously reported that the bone morphogenetic protein (BMP) antagonist, noggin, improved the repair process with an increase in the reactive microglia/macrophage population in the ischemic brain. Since BMP plays a role in intracellular iron homeostasis via the hepcidin/ferroportin axis, and iron is required for myelination, this study was aimed to determine whether noggin affected iron status and remyelination in the brain following ischemic stroke. We further examined the effect of blocking the BMP/hepcidin pathway on reactive microglia (BV2) and myelination of oligodendroglial cells (MO3...
January 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29406966/quantifying-iron-deposition-within-the-substantia-nigra-of-parkinson-s-disease-by-quantitative-susceptibility-mapping
#14
Hedi An, Xiaoyan Zeng, Tengfei Niu, Gaiying Li, Jie Yang, Lanlan Zheng, Wei Zhou, Hong Liu, Miaomiao Zhang, Dongya Huang, Jianqi Li
BACKGROUND: Iron deposition within the substantia nigra (SN) has been postulated to play a vital role in Parkinson's disease (PD). The aim of this study was to explore the inherent link of PD patients between their substantia nigra iron accumulation and clinical status using quantitative susceptibility mapping (QSM) which is now considered to be the only quantitative imaging technique of brain iron deposition. METHODS: 44 PD patients and 31 age- and gender-matched healthy controls underwent quantitative susceptibility mapping (QSM) were recruited in this study...
March 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29405739/is-vegetarianism-healthy-for-children
#15
Nathan Cofnas
According to the Academy of Nutrition and Dietetics' influential position statement on vegetarianism, meat and seafood can be replaced with milk, soy/legumes, and eggs without any negative effects in children. The United States Department of Agriculture endorses a similar view. The present paper argues that the Academy of Nutrition and Dietetics ignores or gives short shrift to direct and indirect evidence that vegetarianism may be associated with serious risks for brain and body development in fetuses and children...
February 6, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29404423/host-virus-protein-interaction-network-reveals-the-involvement-of-multiple-host-processes-in-the-life-cycle-of-hepatitis-e-virus
#16
Chandru Subramani, Vidya P Nair, Saumya Anang, Sukhen Das Mandal, Madhu Pareek, Nidhi Kaushik, Akriti Srivastava, Sudipto Saha, Shalimar, Baibaswata Nayak, C T Ranjith-Kumar, Milan Surjit
Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network...
January 2018: MSystems
https://www.readbyqxmd.com/read/29402144/mitochondrial-ferritin-is-a-hif1%C3%AE-inducible-gene-that-protects-from-hypoxia-induced-cell-death-in-brain
#17
Qiong Wu, Wen-Shuang Wu, Lin Su, Xin Zheng, Wenyue Wu, Paolo Santambrogio, Yujing Gou, Qian Hao, Peina Wang, Yaru Li, Bao-Lu Zhao, Guangjun Nie, Sonia Levi, Yan-Zhong Chang
Mitochondrial Ferritin (FtMt) is preferentially expressed in cell types of high metabolic activity and oxygen consumption, which is consistent with its role of sequestering iron and preventing oxygen-derived redox damage. As of yet, the mechanisms of FtMt regulation and the protection FtMt affords remain largely unknown. Here, we report that hypoxia-inducible-factor 1α (HIF-1α) can upregulate FtMt expression. We verify one functional hypoxia response element (HRE) in the positive regulatory region and two HREs possessing HIF-1α binding activity in the minimal promoter region of the human FTMT gene...
February 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29402131/neurotoxicity-linked-to-dysfunctional-metal-ion-homeostasis-and-xenobiotic-metal-exposure-redox-signaling-and-oxidative-stress
#18
Carla Garza-Lombo, Yanahi Posadas, Liliana Quintanar, Maria E Gonsebatt, Rodrigo Franco
SIGNIFICANCE: Essential metals such as copper, iron, manganese and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our lifespan, humans are also exposed to xenobiotic metals from natural and anthropogenic sources including aluminum, arsenic, cadmium, lead and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals is linked to several neurological disorders including neurodegeneration and neurodevelopmental alterations...
February 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29396176/the-relevance-of-gene-panels-in-movement-disorders-diagnosis-a-lab-perspective
#19
REVIEW
Chiara Reale, Celeste Panteghini, Miryam Carecchio, Barbara Garavaglia
Next-Generation Sequencing (NGS) is a group of new methods that allow sequencing a variable number of known genes (targeted resequencing) or even the whole human genome (whole genome sequencing-WGS) and have contributed to an exponential genetic knowledge growth, especially in rare diseases, in the past few years. Since 2015, in the Molecular Neurogenetics Unit of Neurological Institute "Carlo Besta", some gene panels have become available to screen all the known genes associated with Movement Disorders (MD) in children and adults as a diagnostic package...
January 29, 2018: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29395073/impaired-transferrin-receptor-palmitoylation-and-recycling-in-neurodegeneration-with-brain-iron-accumulation
#20
Anthony Drecourt, Joël Babdor, Michael Dussiot, Floriane Petit, Nicolas Goudin, Meriem Garfa-Traoré, Florence Habarou, Christine Bole-Feysot, Patrick Nitschké, Chris Ottolenghi, Metodi D Metodiev, Valérie Serre, Isabelle Desguerre, Nathalie Boddaert, Olivier Hermine, Arnold Munnich, Agnès Rötig
Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous condition characterized by progressive dystonia with iron accumulation in the basal ganglia. How NBIA-associated mutations trigger iron overload remains poorly understood. After studying fibroblast cell lines from subjects carrying both known and unreported biallelic mutations in CRAT and REPS1, we ascribe iron overload to the abnormal recycling of transferrin receptor (TfR1) and the reduction of TfR1 palmitoylation in NBIA...
February 1, 2018: American Journal of Human Genetics
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