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https://www.readbyqxmd.com/read/28648462/cyclic-tetrapeptide-hdac-inhibitors-as-potential-therapeutics-for-spinal-muscular-atrophy-screening-with-ipsc-derived-neuronal-cells
#1
Jiun-I Lai, Luke J Leman, Sherman Ku, Chris J Vickers, Christian A Olsen, Ana Montero, M Reza Ghadiri, Joel M Gottesfeld
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that is caused by inactivating mutations in the Survival of motor neuron 1 (SMN1) gene, resulting in decreased SMN protein expression. Humans possess a paralog gene, SMN2, which contains a splicing defect in exon 7 leading to diminished expression of full-length, fully functional SMN protein. Increasing SMN2 expression has been a focus of therapeutic development for SMA. Multiple studies have reported the efficacy of histone deacetylase inhibitors (HDACi) in this regard...
June 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28642069/chronic-choline-supplementation-improves-cognitive-and-motor-performance-via-modulating-oxidative-and-neurochemical-status-in-rats
#2
Saiqa Tabassum, Saida Haider, Saara Ahmad, Syeda Madiha, Tahira Parveen
Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes...
June 19, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28636662/differential-regulation-of-polarized-synaptic-vesicle-trafficking-and-synapse-stability-in-neural-circuit-rewiring-in-caenorhabditis-elegans
#3
Naina Kurup, Dong Yan, Karina Kono, Yishi Jin
Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28632848/effect-of-gabapentin-memantine-on-the-infantile-nystagmus-syndrome-in-the-zebrafish-model-implications-for-the-therapy-of-ocular-motor-diseases
#4
Stefan Yu Bögli, Maresa Afthinos, Melody Ying-Yu Huang
Purpose: Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28627356/aquatic-therapy-for-children-with-duchenne-muscular-dystrophy-a-pilot-feasibility-randomised-controlled-trial-and-mixed-methods-process-evaluation
#5
Daniel Hind, James Parkin, Victoria Whitworth, Saleema Rex, Tracey Young, Lisa Hampson, Jennie Sheehan, Chin Maguire, Hannah Cantrill, Elaine Scott, Heather Epps, Marion Main, Michelle Geary, Heather McMurchie, Lindsey Pallant, Daniel Woods, Jennifer Freeman, Ellen Lee, Michelle Eagle, Tracey Willis, Francesco Muntoni, Peter Baxter
BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare disease that causes the progressive loss of motor abilities such as walking. Standard treatment includes physiotherapy. No trial has evaluated whether or not adding aquatic therapy (AT) to land-based therapy (LBT) exercises helps to keep muscles strong and children independent. OBJECTIVES: To assess the feasibility of recruiting boys with DMD to a randomised trial evaluating AT (primary objective) and to collect data from them; to assess how, and how well, the intervention and trial procedures work...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28602046/exercise-interventions-for-cerebral-palsy
#6
REVIEW
Jennifer M Ryan, Elizabeth E Cassidy, Stephen G Noorduyn, Neil E O'Connell
BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder resulting from an injury to the developing brain. It is the most common form of childhood disability with prevalence rates of between 1.5 and 3.8 per 1000 births reported worldwide. The primary impairments associated with CP include reduced muscle strength and reduced cardiorespiratory fitness, resulting in difficulties performing activities such as dressing, walking and negotiating stairs.Exercise is defined as a planned, structured and repetitive activity that aims to improve fitness, and it is a commonly used intervention for people with CP...
June 11, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28600565/action-sequencing-in-the-spontaneous-swimming-behavior-of-zebrafish-larvae-implications-for-drug-development
#7
Tobias Palmér, Fredrik Ek, Olof Enqvist, Roger Olsson, Kalle Åström, Per Petersson
All motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locomotion pattern of 10 days old zebrafish larvae we have here characterized the basic organizational principles governing the swimming behavior...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588757/identification-of-neuron-selective-androgen-receptor-inhibitors
#8
Maya Otto-Duessel, Ben Yi Tew, Steven Vonderfecht, Roger Moore, Jeremy O Jones
AIM: To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHODS: Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell type-selective AR inhibitors...
May 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28587056/tolerance-of-the-brachial-plexus-to-high-dose-reirradiation
#9
Allen M Chen, Taeko Yoshizaki, Maria A Velez, Argin G Mikaeilian, Sophia Hsu, Minsong Cao
PURPOSE: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. METHODS AND MATERIALS: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure...
May 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28574926/hyposmia-symptoms-of-rapid-eye-movement-sleep-behavior-disorder-and-parkinsonian-motor-signs-suggest-prodromal-neurodegeneration-in-22q11-deletion-syndrome
#10
Ellen Buckley, Azeem Siddique, Alisdair McNeill
The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders in humans. There is an increased risk of Parkinson's disease (PD) in individuals with 22q11DS. The characteristic motor features of PD begin when more than 50% of dopaminergic neurons in the substantia nigra have degenerated. Before this, there is a prodromal period, of up to 20 years, in which nonmotor features such as hyposmia, autonomic dysfunction, rapid eye movement sleep behavior disorder, and subtle motor dysfunction can occur...
August 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28574477/utilizing-zebrafish-visual-behaviors-in-drug-screening-for-retinal-degeneration
#11
REVIEW
Logan Ganzen, Prahatha Venkatraman, Chi Pui Pang, Yuk Fai Leung, Mingzhi Zhang
Zebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo...
June 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28572817/development-of-a-novel-motor-imagery-control-technique-and-application-in-a-gaming-environment
#12
Ting Li, Jinhua Zhang, Tao Xue, Baozeng Wang
We present a methodology for a hybrid brain-computer interface (BCI) system, with the recognition of motor imagery (MI) based on EEG and blink EOG signals. We tested the BCI system in a 3D Tetris and an analogous 2D game playing environment. To enhance player's BCI control ability, the study focused on feature extraction from EEG and control strategy supporting Game-BCI system operation. We compared the numerical differences between spatial features extracted with common spatial pattern (CSP) and the proposed multifeature extraction...
2017: Computational Intelligence and Neuroscience
https://www.readbyqxmd.com/read/28570644/comparison-of-the-adolescent-and-adult-mouse-prefrontal-cortex-proteome
#13
Abigail E Agoglia, Sarah E Holstein, Amanda T Small, Marina Spanos, Brainard M Burrus, Clyde W Hodge
Adolescence is a developmental period characterized by unique behavioral phenotypes (increased novelty seeking, risk taking, sociability and impulsivity) and increased risk for destructive behaviors, impaired decision making and psychiatric illness. Adaptive and maladaptive adolescent traits have been associated with development of the medial prefrontal cortex (mPFC), a brain region that mediates regulatory control of behavior. However, the molecular changes that underlie brain development and behavioral vulnerability have not been fully characterized...
2017: PloS One
https://www.readbyqxmd.com/read/28544082/a-resource-of-potential-drug-targets-and-strategic-decision-making-for-obstructive-sleep-apnoea-pharmacotherapy
#14
REVIEW
Richard L Horner, Kevin P Grace, Andrew Wellman
There is currently no pharmacotherapy for obstructive sleep apnoea (OSA) but there is no principled a priori reason why there should not be one. This review identifies a rational decision-making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors...
May 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28541236/attention-deficit-hyperactivity-disorder-adhd-symptoms-and-cognitive-skills-of-preschool-children
#15
L Thomaidis, A Choleva, M Janikian, G Bertou, A Tsitsika, G Giannakopoulos, D C Anagnostopoulos
Attention deficit/hyperactivity disorder (ADHD) constitutes a neurobehavioral disorder which may potentially adversely affect children's wellbeing and academic achievement. The onset of symptoms is present prior to 12 years of age, and often the symptoms are evident in the preschool years. In fact, it has been suggested that screening for ADHD symptoms may be initiated as early as four years of age. Preschool children with ADHD have been shown to present with poor pre-academic skills and might be at increased risk for numerous school-related problems, including functional impairment during elementary school years and persistent poor academic performance thereafter...
January 2017: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#16
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28521116/efficacy-of-anticonvulsant-substances-in-the-6hz-seizure-test-comparison-of-two-rodent-species
#17
Elise Esneault, Guillaume Peyon, Vincent Castagné
Usually performed in the mouse, the 6Hz seizure test is used for screening potential new anticonvulsant substances against complex partial seizures. Nevertheless, advanced models of temporal lobe epilepsy (TLE) are more often performed in rats, so that possible species-related differences may complicate the development of anticonvulsant substances. The aim of the present study was to evaluate the feasibility of adapting the 6Hz test in the rat. We first compared the effects of increasing current intensities for inducing seizures in the mouse and in the rat...
May 10, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28503706/an-eye-tracker-controlled-cognitive-battery-overcoming-verbal-motor-limitations-in-als
#18
Barbara Poletti, Laura Carelli, Federica Solca, Annalisa Lafronza, Elisa Pedroli, Andrea Faini, Nicola Ticozzi, Andrea Ciammola, Paolo Meriggi, Pietro Cipresso, Dorothée Lulé, Albert C Ludolph, Giuseppe Riva, Vincenzo Silani
We assessed language, attention, executive, and social cognition abilities in a sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a recently developed cognitive battery based on oculomotor control with eye-tracking (ET) technology. Twenty-one ALS patients and 21 age- and education-matched healthy subjects underwent the ET-based cognitive assessment, together with the standard cognitive screening tools [Frontal Assessment Battery (FAB); Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]...
June 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28498739/feasibility-of-a-cardiovascular-cohort-in-a-sub-saharan-africa-community-preliminary-report-of-the-pilot-project-tahes-tanv%C3%A3-health-study-in-benin
#19
Yessito Corine Houehanou, Carmelle Mizéhoun-Adissoda, Salimanou Amidou, Iléana Désormais, Martin Houénassi, Pierre-Marie Preux, Benoit Marin, Dismand Houinato, Philippe Lacroix
BACKGROUND: Faced with the growing burden of cardiovascular disease (CVD) including atherosclerotic in Sub-Saharan Africa (SSA), the development of appropriate prediction tools, based on large cohorts, appears useful for prevention. OBJECTIVE: The objective of the pilot project TAHES (Tanvè Health Study) was to explore the feasibility of a large cohort study focused on CVD and risk factors in Benin. METHODS: We implemented a prospective cohort over 2 years...
2017: Global Health Action
https://www.readbyqxmd.com/read/28491897/longitudinal-characterization-of-biomarkers-for-spinal-muscular-atrophy
#20
Ulrike Bonati, Štefan Holiga, Nicole Hellbach, Céline Risterucci, Tobias Bergauer, Wakana Tang, Patricia Hafner, Alain Thoeni, Oliver Bieri, Irene Gerlach, Anne Marquet, Omar Khwaja, Fabio Sambataro, Alessandro Bertolino, Juergen Dukart, Arne Fischmann, Dirk Fischer, Christian Czech
OBJECTIVE: Recent advances in understanding Spinal Muscular Atrophy (SMA) etiopathogenesis prompted development of potent intervention strategies and raised need for sensitive outcome measures capable of assessing disease progression and response to treatment. Several biomarkers have been proposed; nevertheless, no general consensus has been reached on the most feasible ones. We observed a wide range of measures over 1 year to assess their ability to monitor the disease status and progression...
May 2017: Annals of Clinical and Translational Neurology
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