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https://www.readbyqxmd.com/read/28098832/therapeutic-potential-of-targeting-the-th17-treg-axis-in-autoimmune-disorders
#1
REVIEW
Patrizia Fasching, Martin Stradner, Winfried Graninger, Christian Dejaco, Johannes Fessler
A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the  pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098153/mecp2-regulates-cortical-plasticity-underlying-a-learned-behaviour-in-adult-female-mice
#2
Keerthi Krishnan, Billy Y B Lau, Gabrielle Ewall, Z Josh Huang, Stephen D Shea
Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2(het) mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2(het) females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097511/brain-calcification-and-movement-disorders
#3
REVIEW
Vladimir S Kostić, Igor N Petrović
Brain calcifications may be an incidental finding on neuroimaging in normal, particularly older individuals, but can also indicate numerous hereditary and nonhereditary syndromes, and metabolic, environmental, infectious, autoimmune, mitochondrial, traumatic, or toxic disorders. Bilateral calcifications most commonly affecting the basal ganglia may often be found in idiopathic cases, and a new term, primary familial brain calcification (PFBC), has been proposed that recognizes the genetic causes of the disorder and that calcifications occurred well beyond the basal ganglia...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28097321/diagnostic-yield-and-novel-candidate-genes-by-exome-sequencing-in-152-consanguineous-families-with-neurodevelopmental-disorders
#4
Miriam S Reuter, Hasan Tawamie, Rebecca Buchert, Ola Hosny Gebril, Tawfiq Froukh, Christian Thiel, Steffen Uebe, Arif B Ekici, Mandy Krumbiegel, Christiane Zweier, Juliane Hoyer, Karolin Eberlein, Judith Bauer, Ute Scheller, Tim M Strom, Sabine Hoffjan, Ehab R Abdelraouf, Nagwa A Meguid, Ahmad Abboud, Mohammed Ayman Al Khateeb, Mahmoud Fakher, Saber Hamdan, Amina Ismael, Safia Muhammad, Ebtessam Abdallah, Heinrich Sticht, Dagmar Wieczorek, André Reis, Rami Abou Jamra
Importance: Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. Objectives: To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. Design, Setting, and Participants: Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID)...
January 11, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#5
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28095295/hematopoietic-stem-cell-transplantation-corrects-osteopetrosis-in-a-child-carrying-a-novel-homozygous-mutation-in-the-fermt3-gene
#6
Eleonora Palagano, Mary A Slatter, Paolo Uva, Ciro Menale, Anna Villa, Mario Abinun, Cristina Sobacchi
Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments...
January 14, 2017: Bone
https://www.readbyqxmd.com/read/28094463/network-over-connectivity-differentiates-autism-spectrum-disorder-from-other-developmental-disorders-in-toddlers-a-diffusion-mri-study
#7
E Conti, J Mitra, S Calderoni, K Pannek, K K Shen, A Pagnozzi, S Rose, S Mazzotti, D Scelfo, M Tosetti, F Muratori, G Cioni, A Guzzetta
Advanced connectivity studies in toddlers with Autism Spectrum Disorder (ASD) are increasing and consistently reporting a disruption of brain connectivity. However, most of these studies compare ASD and typically developing subjects, thus providing little information on the specificity of the abnormalities detected in comparison with other developmental disorders (other-DD). We recruited subjects aged below 36 months who received a clinical diagnosis of Neurodevelopmental Disorder (32 ASD and 16 other-DD including intellectual disability and language disorder) according to DSM-IV TR...
January 17, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28094313/comparison-of-symptoms-healthcare-utilization-and-treatment-in-diagnosed-and-undiagnosed-individuals-with-diarrhea-predominant-irritable-bowel-syndrome
#8
Gregory S Sayuk, Ray Wolf, Lin Chang
OBJECTIVES: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by symptoms including abdominal pain and altered bowel function. Up to 75% of individuals with IBS may be undiagnosed. The aim of this study was to characterize symptoms, healthcare utilization, and treatments in populations with both diagnosed and undiagnosed IBS. METHODS: An online survey was conducted to compare gastrointestinal (GI) symptoms, healthcare visits, well-being, symptom management, and treatment satisfaction in individuals with and without medically diagnosed IBS (Rome III criteria)...
January 17, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28093554/tumour-necrosis-factor-mediated-homeostatic-synaptic-plasticity-in-behavioural-models-testing-a-role-in-maternal-immune-activation
#9
Sarah C Konefal, David Stellwagen
The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093358/mapping-the-functional-connectome-traits-of-levels-of-consciousness
#10
Enrico Amico, Daniele Marinazzo, Carol Di Perri, Lizette Heine, Jitka Annen, Charlotte Martial, Mario Dzemidzic, Murielle Kirsch, Vincent Bonhomme, Steven Laureys, Joaquín Goñi
Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups...
January 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28093220/increased-oxytocin-levels-among-abstinent-heroin-addicts-association-with-aggressiveness-psychiatric-symptoms-and-perceived-childhood-neglect
#11
Lidia M Gerra, Gilberto Gerra, Laura Mercolini, Matteo Manfredini, Lorenzo Somaini, Chiara M Pieri, Maina Antonioni, Michele Protti, Paolo Ossola, Carlo Marchesi
A disruption of the oxytocin system seems to affect a variety of brain functions including emotions, mood and social behavior possibly underlying severe social deficits and susceptibility for substance use and mental health disorders. Early life adversity, such as insecure attachment in childhood, has been suggested to influence oxytocin tone contributing to a condition of neurobiological vulnerability. Aim of the present study was to investigate oxytocin serum levels in abstinent heroin addicted patients, in comparison with healthy controls, and the possible correlation with co-occurring psychiatric symptoms, aggressiveness and perception of parental neglect...
January 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28090585/circadian-forced-desynchrony-of-the-master-clock-leads-to-phenotypic-manifestation-of-depression-in-rats
#12
Miriam Ben-Hamo, Tracy A Larson, Leanne S Duge, Carl Sikkema, Charles W Wilkinson, Horacio O de la Iglesia, Mónica M C González
In mammals, a master circadian clock within the suprachiasmatic nucleus (SCN) of the hypothalamus maintains the phase coherence among a wide array of behavioral and physiological circadian rhythms. Affective disorders are typically associated with disruption of this fine-tuned "internal synchronization," but whether this internal misalignment is part of the physiopathology of mood disorders is not clear. To date, depressive-like behavior in animal models has been induced by methods that fail to specifically target the SCN regulation of internal synchronization as the mode to generate depression...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28090568/pathophysiology-of-intestinal-na-h-exchange
#13
Michael A Gurney, Daniel Laubitz, Fayez K Ghishan, Pawel R Kiela
Several members of the SLC9A family of Na(+)/H(+) exchangers are expressed in the gut, with varying expression patterns and cellular localization. Not only do they participate in the regulation of basic epithelial cell functions, including control of transepithelial Na(+) absorption, intracellular pH (pH i ), cell volume, and nutrient absorption, but also in cellular proliferation, migration, and apoptosis. Additionally, they modulate the extracellular milieu in order to facilitate other nutrient absorption and to regulate the intestinal microbial microenvironment...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28090484/mesenchymal-stromal-cells-in-myeloid-malignancies
#14
REVIEW
Thomas Schroeder, Stefanie Geyh, Ulrich Germing, Rainer Haas
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28089250/pathology-of-behavior-in-pd-what-is-known-and-what-is-not
#15
REVIEW
Kaylena A Ehgoetz Martens, Simon J G Lewis
Abnormal behavior in Parkinson's disease (PD) stems from a complex orchestration of impaired neural networks that result from PD-related neurodegeneration across multiple levels. Typically, cellular and tissue abnormalities generate neurochemical changes and disrupt specific regions of the brain, in turn creating impaired neural circuits and dysfunctional global networks. The objective of this chapter is to provide an overview of the array of pathological changes that have been linked to different behavioral symptoms of PD such as depression, anxiety, apathy, fatigue, impulse control disorders, psychosis, sleep disorders and dementia...
December 29, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#16
Pietro Giusti, Stephen D Skaper, Laura Facci, Morena Zusso
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28088890/nanoparticles-as-a-carrier-system-for-drug-delivery-across-blood-brain-barrier
#17
Alika Sarkar, Ismat Fatima, Qazi Mohammad Sajid Jamal, Usman Sayeed, M Kalim A Khan, Salman Akhtar, Mohammad Amjad Kamal, Alvina Farooqui, Mohammad Haris Siddiqui
Brain, the center of the nervous system and an integral part the body, is protected by two anatomical and biochemical dynamic barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a highly complex multi-cellular organized structure that protects the brain from harmful substances and invading organisms from the bloodstream and thus protecting it from diseases and injuries. However, it also significantly precludes the delivery of drug to the brain, thus, preventing treatment of a number of neurological disorders...
January 13, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28088747/decreased-s100b-serum-levels-after-treatment-in-bipolar-patients-in-a-manic-phase
#18
Meng-Chang Tsai, Tiao-Lai Huang
BACKGROUND: Previous studies have suggested that patients with bipolar disorder might have brain damage. The aim of this study was to investigate the serum levels of brain injury biomarkers and S100A10 in bipolar patients in a manic phase, and evaluate the changes in S100B, neuron specific enolase (NSE), heat shock protein 70 (HSP70) and S100A10 after treatment. METHOD: We consecutively enrolled 17 bipolar inpatients in a manic phase and 30 healthy subjects. Serum brain injury biomarkers and S100A10 were measured with assay kits...
January 3, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28088728/the-association-between-insomnia-related-sleep-disruptions-and-cognitive-dysfunction-during-the-inter-episode-phase-of-bipolar-disorder
#19
Jennifer C Kanady, Adriane M Soehner, Alexandra B Klein, Allison G Harvey
Sleep disturbance and cognitive dysfunction are two domains of impairment during inter-episode bipolar disorder. Despite evidence demonstrating the importance of sleep for cognition in healthy and sleep-disordered samples, this link has been minimally examined in bipolar disorder. The present study tested the association between insomnia-related sleep disruptions and cognitive dysfunction during inter-episode bipolar disorder. Forty-seven participants with bipolar disorder and a comorbid insomnia diagnosis (BD-Insomnia) and 19 participants with bipolar disorder without sleep disturbance in the last six months (BD-Control) participated in the study...
January 5, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28087833/dysregulation-of-map-kinase-signaling-pathways-including-p38mapk-sapk-jnk-and-erk1-2-in-cultured-rat-cerebellar-astrocytes-exposed-to-diphenylarsinic-acid
#20
Takayuki Negishi, Mami Matsumoto, Yayoi Kobayashi, Mikiya Kojima, Fumika Sakaguchi, Kazuaki Takahata, Tomoko Kanehira, Rina Arakaki, Yohei Aoyama, Hikari Yoshida, Rena Yamada, Nobutaka Sumiyoshi, Tomoko Tashiro, Seishiro Hirano, Kenji Yoshida, Kazunori Yukawa
Diphenylarsinic acid (DPAA) was a major compound found in the arsenic poisoning incident that occurred in Kamisu, Ibaraki, Japan in 2003. People exposed to DPAA via contaminated well water suffered from several neurological disorders, including cerebellar symptoms. We previously reported that DPAA induces cellular activation in cultured rat cerebellar astrocytes, dose-dependent promotion of cell growth (low DPAA), cell death (high DPAA), and increased phosphorylation of mitogen-activated protein (MAP) kinases (p38MAPK, SAPK/JNK, and ERK1/2)...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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