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https://www.readbyqxmd.com/read/27913155/early-molecular-stratification-of-high-risk-primary-biliary-cholangitis
#1
Claire Hardie, Kile Green, Laura Jopson, Ben Millar, Barbara Innes, Sarah Pagan, Dina Tiniakos, Jessica Dyson, Muzlifah Haniffa, Venetia Bigley, David E Jones, John Brain, Lucy J Walker
High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27912044/mutations-in-prosc-disrupt-cellular-pyridoxal-phosphate-homeostasis-and-cause-vitamin-b6-dependent-epilepsy
#2
Niklas Darin, Emma Reid, Laurence Prunetti, Lena Samuelsson, Ralf A Husain, Matthew Wilson, Basma El Yacoubi, Emma Footitt, W K Chong, Louise C Wilson, Helen Prunty, Simon Pope, Simon Heales, Karine Lascelles, Mike Champion, Evangeline Wassmer, Pierangelo Veggiotti, Valérie de Crécy-Lagard, Philippa B Mills, Peter T Clayton
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms that are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain can be caused by inborn errors affecting B6 vitamer metabolism or by inactivation of PLP, which can occur when compounds accumulate as a result of inborn errors of other pathways or when small molecules are ingested...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27906505/what-do-we-learn-about-development-from-baby-robots
#3
Pierre-Yves Oudeyer
Understanding infant development is one of the great scientific challenges of contemporary science. In addressing this challenge, robots have proven useful as they allow experimenters to model the developing brain and body and understand the processes by which new patterns emerge in sensorimotor, cognitive, and social domains. Robotics also complements traditional experimental methods in psychology and neuroscience, where only a few variables can be studied at the same time. Moreover, work with robots has enabled researchers to systematically explore the role of the body in shaping the development of skill...
December 1, 2016: Wiley Interdisciplinary Reviews. Cognitive Science
https://www.readbyqxmd.com/read/27903814/blink-associated-contralateral-eccentric-saccades-as-a-rare-sign-of-unilateral-brain-injury
#4
Ilaria Zivi, Eugenio Bertelli, Giacinta Bilotti, Ignazio Alessandro Clemente, Leopold Saltuari, Giuseppe Frazzitta
OBJECTIVE: To describe a rare sign of unilateral brain injury as a form of unwanted blink-associated contralateral eccentric saccades. METHODS: A 62-year-old patient who underwent an ischemic stroke affecting the entire right middle cerebral artery territory came to our attention 1 year after stroke, manifesting with transient contralateral conjugate gaze deviations associated with spontaneous blinking. We complemented the regular neurologic evaluation with brain MRI, study of evoked potentials, electroneurography of the facial nerve, and infrared video-oculoscopy...
November 30, 2016: Neurology
https://www.readbyqxmd.com/read/27890797/3-bromopyruvate-treatment-induces-alterations-of-metabolic-and-stress-related-pathways-in-glioblastoma-cells
#5
Davide Chiasserini, Magdalena Davidescu, Pier Luigi Orvietani, Federica Susta, Lara Macchioni, Maya Petricciuolo, Emilia Castigli, Rita Roberti, Luciano Binaglia, Lanfranco Corazzi
: Glioblastoma (GBM) is the most common and aggressive brain tumours of adults. The metabolic phenotype of GBM cells is highly dependent on glycolysis; therefore, therapeutic strategies aimed at interfering with glycolytic pathways are under consideration. 3-Bromopyruvate (3BP) is a potent antiglycolytic agent, with a variety of targets and possible effects on global cell metabolism. Here we analyzed the changes in protein expression on a GBM cell line (GL15 cells) caused by 3BP treatment using a global proteomic approach...
November 23, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27887593/expression-of-barhl2-and-its-relationship-with-pax6-expression-in-the-forebrain-of-the-mouse-embryo
#6
Elisa V Parish, John O Mason, David J Price
BACKGROUND: The transcription factor Barhl2 is an antiproneural transcription factor with roles in neuronal differentiation. The functions of its homologue in Drosophila development are better understood than its functions in mammalian brain development. Existing evidence suggests that its expression in the embryonic forebrain of the mouse is regional and may complement that of another transcription factor that is important for forebrain development, Pax6. The aim of this study is to provide a more detailed description of the Barhl2 expression pattern in the embryonic forebrain than is currently available, to relate its expression domains to those of Pax6 and to examine the effects of Pax6 loss on Barhl2 expression...
November 25, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27878366/widespread-tau-seeding-activity-at-early-braak-stages
#7
Jennifer L Furman, Jaime Vaquer-Alicea, Charles L White, Nigel J Cairns, Peter T Nelson, Marc I Diamond
Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins...
November 22, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27862612/the-role-of-the-pallidothalamic-fibre-tracts-in-deep-brain-stimulation-for-dystonia-a-diffusion-mri-tractography-study
#8
Verena Eveline Rozanski, Nadia Moreira da Silva, Seyed-Ahmad Ahmadi, Jan Mehrkens, Joao da Silva Cunha, Jean-Christophe Houde, Christian Vollmar, Kai Bötzel, Maxime Descoteaux
BACKGROUND: Deep Brain Stimulation (DBS) of the Globus pallidus internus (GPi) is gold standard treatment in medically refractory dystonia. Recent evidence indicates that stimulation effects are also due to axonal modulation and affection of a fibre network. For the GPi, the pallidothalamic tracts are known to be the major motor efferent pathways. The aim of this study is to explore the anatomic vicinity of these tracts and DBS electrodes in dystonia applying diffusion tractography. METHODS: Diffusion MRI was acquired in ten patients presenting for DBS for dystonia...
November 16, 2016: Human Brain Mapping
https://www.readbyqxmd.com/read/27856824/all-trans-retinoic-acid-augments-the-histopathological-outcome-of-neuroinflammation-and-neurodegeneration-in-lupus-prone-mrl-lpr-mice
#9
Michelle H Theus, Joshua B Sparks, Xiaofeng Liao, Jingjing Ren, Xin M Luo
Recently, we demonstrated that treatment with all-trans-retinoic acid (tRA) induced a paradoxical effect on immune activation during the development of autoimmune lupus. Here, we further describe its negative effects on mediating neuroinflammation and neurodegeneration. Female MRL/lpr mice were orally administered tRA or VARA (retinol mixed with 10% tRA) from 6 to 14 weeks of age. Both treatments had a significant effect on brain weight, which correlated with histopathological evidence of focal astrogliosis, meningitis, and ventriculitis...
November 16, 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27845031/the-temporal-dynamics-underlying-the-comprehension-of-scientific-metaphors-and-poetic-metaphors
#10
Xuemei Tang, Senqing Qi, Botao Wang, Xiaojuan Jia, Wei Ren
The neural mechanisms underlying the processing of novel metaphors created from poetic contexts have been investigated in previous experiments. Considering the different attributes of metaphors, the current study compared the temporal dynamics for processing two kinds of novel metaphors with event-related potentials (ERPs): scientific metaphors and poetic metaphors. Amplitudes of the N400 (350-450 ms) were similar for scientific metaphors and poetic metaphors. Within the LPC window (550-850 ms), ERPs associated with these two kinds of novel metaphors were observed every 100 ms in three successive subwindows...
November 11, 2016: Brain Research
https://www.readbyqxmd.com/read/27844029/dose-dependent-inhibition-of-demyelination-and-microglia-activation-by-ivig
#11
Meike Winter, Christine Baksmeier, Julia Steckel, Sumanta Barman, Manish Malviya, Melanie Harrer-Kuster, Hans-Peter Hartung, Norbert Goebels
OBJECTIVE: Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Clinical trials of IVIG for multiple sclerosis, using diverse dose regimens, yielded controversial results. The aim of this study is to dissect IVIG effector mechanisms on demyelination in an ex vivo model of the central nervous system (CNS)-immune interface. METHODS: Using organotypic cerebellar slice cultures (OSC) from transgenic mice expressing green fluorescent protein (GFP) in oligodendrocytes/myelin, we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement...
November 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27825984/phosphoinositide-3-kinase-%C3%AE-ties-chemoattractant-and-adrenergic-control-of-microglial-motility
#12
Nadine Schneble, Caroline Schmidt, Reinhard Bauer, Jörg P Müller, Shamci Monajembashi, Reinhard Wetzker
Microglial motility is tightly controlled by multitude of agonistic and antagonistic factors. Chemoattractants, released after infection or damage of the brain, provoke directed migration of microglia to the pathogenic incident. In contrast, noradrenaline and other stress hormones have been shown to suppress microglial movement. Here we asked for the signaling reactions involved in the positive and negative control of microglial motility. Using pharmacological and genetic approaches we identified the lipid kinase activity of phosphoinositide 3-kinase species γ (PI3Kγ) as an essential mediator of microglial migration provoked by the complement component C5a and other chemoattractants...
November 5, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27819330/stathmin-like-4-is-critical-for-the-maintenance-of-neural-progenitor-cells-in-dorsal-midbrain-of-zebrafish-larvae
#13
Meng-Ju Lin, Shyh-Jye Lee
A delicate balance between proliferating and differentiating signals is necessary to ensure proper growth and neuronal specification. By studying the developing zebrafish brain, we observed a specific and dynamic expression of a microtubule destabilizer gene, stathmin-like 4 (stmn4), in the dorsal midbrain region. The expression of stmn4 was mutually exclusive to a pan-neuronal marker, elavl3 that indicates its role in regulating neurogenesis. We showed the knockdown or overexpression of stmn4 resulted in premature neuronal differentiation in dorsal midbrain...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27814594/cardiac-allograft-vasculopathy-microvascular-arteriolar-capillaries-capioles-and-survival
#14
Carlos A Labarrere, Beate R Jaeger, Ghassan S Kassab
Cardiac allograft vasculopathy (CAV) is a serious complication of heart transplantation in adults and children. Risk factors include human leukocyte antigen mismatches, number and duration of rejection episodes, type of immunosuppression, antibody-mediated rejection, hypertension, hyperlipidemia, obesity, smoking, diabetes, cytomegalovirus infection, mode of donor brain death, donor age and ischemia/reperfusion injury. Endothelial injury and dysfunction in CAV are characterized by changes in adhesion molecules and up-regulation of major histocompatibility class II antigens followed by endothelial activation of complement C4d...
January 1, 2017: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/27811336/lectin-complement-pathway-and-its-bloody-interactions-in-brain-ischemia
#15
Stefano Fumagalli, Maria-Grazia De Simoni
No abstract text is available yet for this article.
November 3, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27808010/role-of-neuroinflammation-and-latent-transcription-factors-in-pathogenesis-of-parkinson-s-disease
#16
Rishi Pal, Prafulla Chandra Tiwari, Rajendra Nath, Kamlesh Kumar Pant
Parkinson's disease (PD) the second most common age-associated progressive neurodegenerative disorder is characterized by loss of dopaminergic neurons, cytoplasmic inclusions of aggregated proteins (Lewy bodies), and neuroinflammation. The inflammation of neurons causes release of various inflammatory mediators (IFNs, EGF, IL5, IL6, HGF, LIF and BMP2). The hallmarks of neuroinflammation are the presence of activated microglia and reactive astrocytes in the parenchyma of the CNS and increased production of cytokines, chemokines, prostaglandins, complement cascade proteins, and reactive oxygen and nitrogen species (ROS/RNS) which in some cases can result in disruption of the blood brain barrier and direct participation of the adaptive immune system...
November 3, 2016: Neurological Research
https://www.readbyqxmd.com/read/27807543/anticerebral-ischemia-reperfusion-injury-activity-of-synthesized-puerarin-derivatives
#17
Yubin Ji, Pei Jiang, Xinjia Yan
When cerebral ischemia-reperfusion injury happened in patients, multiple pathological processes occur, such as leukocyte infiltration, platelet, and complement activation, which would result in cognitive dysfunction and inflammation. Puerarin has shown protective effect on injury of neural cell. In order to enhance this protective effect of puerarin, puerarin derivatives with different log⁡P values were designed and synthesized. The original phenolic hydroxyl in the puerarin molecules was substituted in order to change the blood-brain barrier permeability and thus enhance the efficacy for preventing cerebral ischemia/reperfusion injury...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27806664/complement-c5a-is-present-in-csf-of-human-newborns-and-is-elevated-in-association-with-preterm-birth
#18
Rozalia Pataky, A Forbes Howie, Guillermina Girardi, James P Boardman
Neuroinflammation contributes to developmental brain injury associated with preterm birth, but the mediators that drive it are incompletely understood. Previous studies have shown that complement C5a is present and injurious in the brains of fetal mice exposed to preterm labour. Here, we demonstrate that C5a is present in the cerebrospinal fluid of newborn human infants, and that levels are elevated in those born preterm. The difference is not explained by systemic infection. The role of complement activation in the neonatal brain and its role as a potential therapeutic target for preterm brain injury warrants further study...
November 2, 2016: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/27805971/recent-advances-in-cerebrospinal-fluid-biomarkers-for-the-detection-of-preclinical-alzheimer-s-disease
#19
Luka Kulic, Paul G Unschuld
PURPOSE OF REVIEW: The concept of preclinical Alzheimer's disease has emerged to describe the long 'silent' phase of the disease when significant pathophysiological changes occur in the brain but clinical symptoms are not yet manifest. In this review, a summary of the recent advances in cerebrospinal fluid (CSF) biomarker-based diagnostics of preclinical Alzheimer's disease will be presented. RECENT FINDINGS: The association between core CSF biomarkers of Alzheimer's disease and between CSF and neuroimaging markers has been a major focus of various recently published studies in cognitively healthy individuals...
December 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27799275/influences-of-brain-size-sex-and-sex-chromosome-complement-on-the-architecture-of-human-cortical-folding
#20
Ari M Fish, Arnaud Cachia, Clara Fischer, Catherine Mankiw, P K Reardon, Liv S Clasen, Jonathan D Blumenthal, Deanna Greenstein, Jay N Giedd, Jean-François Mangin, Armin Raznahan
Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth...
October 31, 2016: Cerebral Cortex
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