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https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#1
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334989/impaired-fetal-muscle-development-and-jak-stat-activation-mark-disease-onset-and-progression-in-a-mouse-model-for-merosin-deficient-congenital-muscular-dystrophy
#2
Andreia M Nunes, Ryan D Wuebbles, Apurva Sarathy, Tatiana M Fontelonga, Marianne Deries, Dean J Burkin, Sólveig Thorsteinsdóttir
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/-embryos. Fetal dyW-/-muscles display the same number of myofibers as wildtype muscles, but by E18.5 dyW-/-muscles are significantly smaller and muscle size is not recovered post-natally...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334633/now-or-not-now-the-influence-of-alexithymia-on-intertemporal-decision-making
#3
Cristina Scarpazza, Manuela Sellitto, Giuseppe di Pellegrino
Optimal intertemporal decisions arise from the balance between an emotional-visceral component, signaling the need for immediate gratification, and a rational, long-term oriented component. Alexithymia, a personality construct characterized by amplified sensitivity to internal bodily signals of arousal, may result in enhanced activation of the emotional-visceral component over the cognitive-rational one. To test this hypothesis, participants with high- and low-alexithymia level were compared at an intertemporal decision-making task, and their choice behavior correlated with their interoceptive sensitivity...
March 20, 2017: Brain and Cognition
https://www.readbyqxmd.com/read/28334068/the-dyslexia-susceptibility-protein-kiaa0319-inhibits-axon-growth-through-smad2-signaling
#4
Filipa Franquinho, Joana Nogueira-Rodrigues, Joana M Duarte, Sofia S Esteves, Christin Carter-Su, Anthony P Monaco, Zoltán Molnár, Antonio Velayos-Baeza, Pedro Brites, Mónica M Sousa
KIAA0319 is a transmembrane protein associated with dyslexia with a presumed role in neuronal migration. Here we show that KIAA0319 expression is not restricted to the brain but also occurs in sensory and spinal cord neurons, increasing from early postnatal stages to adulthood and being downregulated by injury. This suggested that KIAA0319 participates in functions unrelated to neuronal migration. Supporting this hypothesis, overexpression of KIAA0319 repressed axon growth in hippocampal and dorsal root ganglia neurons; the intracellular domain of KIAA0319 was sufficient to elicit this effect...
February 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#5
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
February 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28332351/metabolism-centric-overview-of-the-pathogenesis-of-alzheimer-s-disease
#6
REVIEW
Somang Kang, Yong Ho Lee, Jong Eun Lee
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28330789/schiff-bases-of-putrescine-with-methylglyoxal-protect-from-cellular-damage-caused-by-accumulation-of-methylglyoxal-and-reactive-oxygen-species-in-dictyostelium-discoideum
#7
Seong-Jun Park, Min-Kyu Kwak, Sa-Ouk Kang
Polyamines protect protein glycation in cells against the advanced glycation end product precursor methylglyoxal, which is inevitably produced during glycolysis, and the enzymes that detoxify this α-ketoaldehyde have been widely studied. Nonetheless, nonenzymatic methylglyoxal-scavenging molecules have not been sufficiently studied either in vitro or in vivo. Here, we hypothesized reciprocal regulation between polyamines and methylglyoxal modeled in Dictyostelium grown in a high-glucose medium. We based our hypothesis on the reaction between putrescine and methylglyoxal in putrescine-deficient (odc(-)) or putrescine-overexpressing (odc(oe)) cells...
March 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28330496/calcium-dysregulation-functional-calpainopathy-and-endoplasmic-reticulum-stress-in-sporadic-inclusion-body-myositis
#8
David R Amici, Iago Pinal-Fernandez, Davi A G Mázala, Thomas E Lloyd, Andrea M Corse, Lisa Christopher-Stine, Andrew L Mammen, Eva R Chin
Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca(2+)) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca(2+) dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca(2+) regulation in IBM patients...
March 22, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28329001/experimental-demonstration-of-the-possible-role-of-acanthamoeba-polyphaga-in-the-infection-and-disease-progression-in-buruli-ulcer-bu-using-icr-mice
#9
Bright K Azumah, Phyllis G Addo, Alfred Dodoo, Gordon Awandare, Lydia Mosi, Daniel A Boakye, Michael D Wilson
The transmission of Buruli ulcer (BU), caused by Mycobacterium ulcerans (MU), remains puzzling although a number of hypothesis including through bites of infected aquatic insects have been proposed. We report the results of experiments using ICR mice that give credence to our hypothesis that Acanthamoeba species may play a role in BU transmission. We cocultured MU N2 and MU 1615 which expresses red fluorescent protein (RFP) and Acanthamoeba polyphaga (AP), and confirmed infected AP by Ziehl-Neelsen (ZN) staining...
2017: PloS One
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#10
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28326066/beneficial-microorganisms-for-corals-bmc-proposed-mechanisms-for-coral-health-and-resilience
#11
REVIEW
Raquel S Peixoto, Phillipe M Rosado, Deborah Catharine de Assis Leite, Alexandre S Rosado, David G Bourne
The symbiotic association between the coral animal and its endosymbiotic dinoflagellate partner Symbiodinium is central to the success of corals. However, an array of other microorganisms associated with coral (i.e., Bacteria, Archaea, Fungi, and viruses) have a complex and intricate role in maintaining homeostasis between corals and Symbiodinium. Corals are sensitive to shifts in the surrounding environmental conditions. One of the most widely reported responses of coral to stressful environmental conditions is bleaching...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28326059/unilateral-cochlear-implantation-reduces-tinnitus-loudness-in-bimodal-hearing-a-prospective-study
#12
Jérôme J Servais, Karl Hörmann, Elisabeth Wallhäusser-Franke
Perceptive and receptive aspects of subjective tinnitus like loudness and tinnitus-related distress are partly independent. The high percentage of hearing loss in individuals with tinnitus suggests causality of hearing impairment particularly for the tinnitus percept, leading to the hypothesis that restoration of auditory input has a larger effect on tinnitus loudness than on tinnitus-related distress. Furthermore, it is assumed that high levels of depression or anxiety prevent reductions of tinnitus loudness and distress following restoration of activity in the cochlea...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28326014/the-gabaergic-hypothesis-for-cognitive-disabilities-in-down-syndrome
#13
REVIEW
Andrea Contestabile, Salvatore Magara, Laura Cancedda
Down syndrome (DS) is a genetic disorder caused by the presence of a third copy of chromosome 21. DS affects multiple organs, but it invariably results in altered brain development and diverse degrees of intellectual disability. A large body of evidence has shown that synaptic deficits and memory impairment are largely determined by altered GABAergic signaling in trisomic mouse models of DS. These alterations arise during brain development while extending into adulthood, and include genesis of GABAergic neurons, variation of the inhibitory drive and modifications in the control of neural-network excitability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28325822/structural-basis-for-chemokine-recognition-by-a-g-protein-coupled-receptor-and-implications-for-receptor-activation
#14
Joshua J Ziarek, Andrew B Kleist, Nir London, Barak Raveh, Nicolas Montpas, Julien Bonneterre, Geneviève St-Onge, Crystal J DiCosmo-Ponticello, Chad A Koplinski, Ishan Roy, Bryan Stephens, Sylvia Thelen, Christopher T Veldkamp, Frederick D Coffman, Marion C Cohen, Michael B Dwinell, Marcus Thelen, Francis C Peterson, Nikolaus Heveker, Brian F Volkman
Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to cell surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines and their 20 GPCR targets generates an extensive signaling network to which promiscuity and biased agonism add further complexity. The receptor CXCR4 recognizes both monomeric and dimeric forms of the chemokine CXCL12, which is a distinct example of ligand bias in the chemokine family...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28324998/prediction-of-the-outcome-in-cardiac-arrest-patients-undergoing-hypothermia-using-eeg-wavelet-entropy
#15
Hana Moshirvaziri, Nima Ramezan-Arab, Shadnaz Asgari
Cardiac arrest (CA) is the leading cause of death in the United States. Induction of hypothermia has been found to improve the functional recovery of CA patients after resuscitation. However, there is no clear guideline for the clinicians yet to determine the prognosis of the CA when patients are treated with hypothermia. The present work aimed at the development of a prognostic marker for the CA patients undergoing hypothermia. A quantitative measure of the complexity of Electroencephalogram (EEG) signals, called wavelet sub-band entropy, was employed to predict the patients' outcomes...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28324169/roles-of-centromedian-parafascicular-nuclei-of-thalamus-and-cholinergic-interneurons-in-the-dorsal-striatum-in-associative-learning-of-environmental-events
#16
REVIEW
Ko Yamanaka, Yukiko Hori, Takafumi Minamimoto, Hiroshi Yamada, Naoyuki Matsumoto, Kazuki Enomoto, Toshihiko Aosaki, Ann M Graybiel, Minoru Kimura
The thalamus provides a massive input to the striatum, but despite accumulating evidence, the functions of this system remain unclear. It is known, however, that the centromedian (CM) and parafascicular (Pf) nuclei of the thalamus can strongly influence particular striatal neuron subtypes, notably including the cholinergic interneurons of the striatum (CINs), key regulators of striatal function. Here, we highlight the thalamostriatal system through the CM-Pf to striatal CINs. We consider how, by virtue of the direct synaptic connections of the CM and PF, their neural activity contributes to the activity of CINs and striatal projection neurons (SPNs)...
March 21, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28323589/preventing-high-altitude-cerebral-edema-in-rats-with-repurposed-anti-angiogenesis-pharmacotherapy
#17
Samantha Tarshis, Joanne Maltzahn, Zoe Loomis, David C Irwin
BACKGROUND: High altitude cerebral edema (HACE) is a fulminant, deadly, and yet still unpredictable brain disease. A new prophylactic treatment for HACE and its predecessor, acute mountain sickness (AMS), needs to be developed without the contraindications or adverse effect profiles of acetazolamide and dexamethasone. Since neovascularization signals are likely key contributors to HACE/AMS, our approach was to examine already existing anti-angiogenic drugs to inhibit potential initiating HACE pathway(s)...
December 1, 2016: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28323207/l-type-calcium-channel-clarifying-the-oxygen-sensing-hypothesis
#18
Henrietta Cserne Szappanos, Helena Viola, Livia C Hool
The heart is able to respond acutely to changes in oxygen tension. Since ion channels can respond rapidly to stimuli, the "ion channel oxygen sensing hypothesis" has been proposed to explain acute adaptation of cells to changes in oxygen demand. However the exact mechanism for oxygen sensing continues to be debated. Mitochondria consume the lion's share of oxygen in the heart, fuelling the production of ATP that drives excitation and contraction. Mitochondria also produce reactive oxygen species that are capable of altering the redox state of proteins...
March 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28323164/mapping-the-pharmacological-modulation-of-brain-oxygen-metabolism-the-effects-of-caffeine-on-absolute-cmro2-measured-using-dual-calibrated-fmri
#19
Alberto Merola, Michael A Germuska, Esther Ah Warnert, Lewys Richmond, Daniel Helme, Sharmila Khot, Kevin Murphy, Peter J Rogers, Judith E Hall, Richard G Wise
This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age = 24.7±5.1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule. Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation...
March 17, 2017: NeuroImage
https://www.readbyqxmd.com/read/28323089/enhancement-of-erk-phosphorylation-and-photic-responses-in-vc-c1-neurons-of-a-migraine-model
#20
Suzuro Hitomi, Akiko Okada-Ogawa, Yuka Sato, Ikuko Shibuta, Masamichi Shinoda, Yoshiki Imamura, Kentaro Ono, Koichi Iwata
Although it is well known that migraine pain is enhanced by photic stimulation of the eye, the mechanisms underlying this response are not yet understood. Noxious stimulation to the dura is known to activate trigeminal spinal subnucleus caudalis and upper cervical spinal cord (Vc/C1) neurons, causing migraine pain. Intense photic stimulation to the eye is also known to activate certain Vc/C1 neurons, thus increasing migraine pain. In this study, we hypothesized that Vc/C1 neurons receiving noxious dural input would be further activated by intense photic stimulation, resulting in the enhancement of migraine pain...
March 16, 2017: Neuroscience Letters
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