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Motor neuron development

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https://www.readbyqxmd.com/read/29049320/deconvolving-sequence-features-that-discriminate-between-overlapping-regulatory-annotations
#1
Akshay Kakumanu, Silvia Velasco, Esteban Mazzoni, Shaun Mahony
Genomic loci with regulatory potential can be annotated with various properties. For example, genomic sites bound by a given transcription factor (TF) can be divided according to whether they are proximal or distal to known promoters. Sites can be further labeled according to the cell types and conditions in which they are active. Given such a collection of labeled sites, it is natural to ask what sequence features are associated with each annotation label. However, discovering such label-specific sequence features is often confounded by overlaps between the labels; e...
October 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29048368/the-structure-of-human-neuromuscular-junctions-some-unanswered-molecular-questions
#2
REVIEW
Clarke R Slater
The commands that control animal movement are transmitted from motor neurons to their target muscle cells at the neuromuscular junctions (NMJs). The NMJs contain many protein species whose role in transmission depends not only on their inherent properties, but also on how they are distributed within the complex structure of the motor nerve terminal and the postsynaptic muscle membrane. These molecules mediate evoked chemical transmitter release from the nerve and the action of that transmitter on the muscle...
October 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29046314/respiratory-dysfunction-following-neonatal-sustained-hypoxia-exposure-during-a-critical-window-of-brainstem-extracellular-matrix-formation
#3
Christopher Stryker, Dominic W Camperchioli, Catherine A Mayer, Warren J Alilain, Richard John Martin, Peter M MacFarlane
The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined: 1) whether there is a critical postnatal period of ECM expression in brainstem cardio-respiratory control regions; and 2) if the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia exposure (SH, 11% O2, 24hrs/day) is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus (DMNV), the hypoglossal motor nucleus (XII), the cuneate nucleus (CN) and area postrema (AP) were immunofluorescently processed for aggrecan and Wisteria floribunda (WFA) agglutinin, a key proteoglycan of the ECM and the perineuronal net...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29038245/mitochondrial-calcium-dysregulation-contributes-to-dendrite-degeneration-mediated-by-pd-lbd-associated-lrrk2-mutants
#4
Manish Verma, Jason Callio, P Anthony Otero, Israel Sekler, Zachary P Wills
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs prior to the well-characterized phenotype of dendritic shortening...
October 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29037990/roles-for-the-vcp-co-factors-npl4-and-ufd1-in-neuronal-function-in-drosophila-melanogaster
#5
Dwayne J Byrne, Mark J Harmon, Jeremy C Simpson, Craig Blackstone, Niamh C O'Sullivan
The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by delivering ubiquitinated proteins to the proteasome for degradation. Mutations in VCP are associated with two neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), and extensive study has revealed crucial functions of VCP within neurons. By contrast, little is known about the functions of Npl4 or Ufd1 in vivo. Using neuronal-specific knockdown of Npl4 or Ufd1 in Drosophila melanogaster, we infer that Npl4 contributes to microtubule organization within developing motor neurons...
September 21, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29037065/patterns-of-symptom-development-in-patients-with-motor-neuron-disease
#6
Renée Walhout, Esther Verstraete, Martijn P Van Den Heuvel, Jan H Veldink, Leonard H Van Den Berg
OBJECTIVE: To investigate whether symptom development in motor neuron disease (MND) is a random or organized process. METHODS: Six hundred patients with amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor neuron (LMN) phenotypes were invited for a questionnaire concerning symptom development. A binomial test was used to examine distribution of symptoms from site of onset. Development of symptoms over time was evaluated by Kaplan-Meier analysis...
October 16, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29036691/nuclear-localized-c9orf72-associated-arginine-containing-dipeptides-exhibit-age-dependent-toxicity-in-c-elegans
#7
Paige Rudich, Carley Snoznik, Simon C Watkins, John Monaghan, Udai Bhan Pandey, Todd Lamitina
A hexanucleotide repeat expansion mutation in the C9orf72 gene represents a prevalent genetic cause of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Non-canonical translation of this repeat gives rise to several distinct dipeptide protein species that could play pathological roles in disease. Here, we show in the model system C. elegans that expression of the arginine-containing dipeptides, but not alanine-containing dipeptides, produces toxic phenotypes in multiple cellular contexts, including motor neurons...
September 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29036454/mirror-and-absence-of-counter-mirror-responses-to-action-sounds-measured-with-tms
#8
Luca F Ticini, Simone Schütz-Bosbach, Florian Waszak
To what extent is the mirror neuron mechanism malleable to experience? The answer to this question can help characterising its ontogeny and its role in social cognition. Some suggest that it develops through sensorimotor associations congruent with our own actions. Others argue for its extreme volatility that will encode any sensorimotor association in the environment. Here, we added to this debate by exploring the effects of short goal-directed "mirror" and "counter-mirror" trainings (a "mirror" training is defined as the first type of training encountered by the participants) on human auditory mirror motor-evoked potentials (MEPs)...
September 22, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29033893/shortcomings-in-the-current-amyotrophic-lateral-sclerosis-trials-and-potential-solutions-for-improvement
#9
REVIEW
Nakul Katyal, Raghav Govindarajan
Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29032895/cardiac-sympathetic-denervation-predicts-pd-in-at-risk-individuals
#10
David S Goldstein, Courtney Holmes, Grisel J Lopez, Tianxia Wu, Yehonatan Sharabi
INTRODUCTION: By the time a person develops the motor manifestations of Parkinson's disease (PD), substantial loss of nigrostriatal dopamine neurons has already occurred. There is great interest in identifying biomarkers that can detect pre-clinical PD. Braak's neuropathological staging concept imputes early autonomic involvement. Here we report results from a small prospective cohort study about the utility of neuroimaging evidence of cardiac sympathetic denervation in predicting PD among individuals with multiple PD risk factors...
October 5, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29030688/neurotrophic-function-of-phytochemicals-for-neuroprotection-in-aging-and-neurodegenerative-disorders-modulation-of-intracellular-signaling-and-gene-expression
#11
REVIEW
Makoto Naoi, Keiko Inaba-Hasegawa, Masayo Shamoto-Nagai, Wakako Maruyama
Bioactive compounds in food and beverages have been reported to promote health and prevent age-associated decline in cognitive, motor and sensory activities, and emotional function. Phytochemicals, a ubiquitous class of plant secondary metabolites, protect neuronal cells by interaction with cellular activities, in addition to the antioxidant and anti-inflammatory function. In aging and age-associated neurodegenerative disorders, phytochemicals protect neuronal cells by neurotrophic factor-mimic activity, in addition to suppression of apoptosis signaling in mitochondria...
October 13, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29030055/the-heart-of-pd-lewy-body-diseases-as-neurocardiologic-disorders
#12
David S Goldstein, Yehonatan Sharabi
This review provides an update about cardiac sympathetic denervation in Lewy body diseases. The family of Lewy body diseases includes Parkinson's disease (PD), pure autonomic failure (PAF), and dementia with Lewy bodies (DLB). All three feature intra-neuronal cytoplasmic deposits of the protein, alpha-synuclein. Multiple system atrophy (MSA), the parkinsonian form of which can be difficult to distinguish from PD with orthostatic hypotension, involves glial cytoplasmic inclusions that contain alpha-synuclein...
October 10, 2017: Brain Research
https://www.readbyqxmd.com/read/29028962/clinical-features-of-acute-flaccid-myelitis-temporally-associated-with-an-enterovirus-d68-outbreak-results-of-a-nationwide-survey-of-acute-flaccid-paralysis-in-japan-august-december-2015
#13
Pin Fee Chong, Ryutaro Kira, Harushi Mori, Akihisa Okumura, Hiroyuki Torisu, Sawa Yasumoto, Hiroyuki Shimizu, Tsuguto Fujimoto, Nozomu Hanaoka, Susumu Kusunoki, Toshiyuki Takahashi, Kazunori Oishi, Keiko Tanaka-Taya
Backgroud: Acute flaccid myelitis (AFM) is an acute flaccid paralysis (AFP) syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. Methods: An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens...
October 6, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29024221/dendrites-deep-learning-and-sequences-in-the-hippocampus
#14
Upinder S Bhalla
The hippocampus places us both in time and space. It does so over remarkably large spans: milliseconds to years, and centimeters to kilometers. This works for sensory representations, for memory, and for behavioral context. How does it fit in such wide ranges of time and space scales, and keep order among the many dimensions of stimulus context? A key organizing principle for a wide sweep of scales and stimulus dimensions is that of order in time, or sequences. Sequences of neuronal activity are ubiquitous in sensory processing, in motor control, in planning actions, and in memory...
October 12, 2017: Hippocampus
https://www.readbyqxmd.com/read/29023182/potential-clinical-utility-of-multiple-system-atrophy-biomarkers
#15
Kurt A Jellinger
Multiple system atrophy (MSA), an adult-onset, fatal disorder of uncertain aetiology, characterized by parkinsonism, cerebellar, autonomic and motor dysfunctions, is an α-synucleinopathy with glioneuronal degeneration involving multiple parts of the nervous system. The clinical variants correlate with the morphological phenotypes of striatonigral degeneration (MSA-P), olivoponto-cerebellar atrophy (MSA-C), and mixed type MSA. Neuropathological hallmark is the deposition of aberrant α-synuclein in glia and neurons forming cytoplasmic inclusions that cause cell dysfunction/demise...
October 12, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29021741/the-neuroprotective-role-of-protein-quality-control-in-halting-the-development-of-alpha-synuclein-pathology
#16
REVIEW
Destiny-Love Manecka, Benoît Vanderperre, Edward A Fon, Thomas M Durcan
Synucleinopathies are a family of neurodegenerative disorders that comprises Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Each of these disorders is characterized by devastating motor, cognitive, and autonomic consequences. Current treatments for synucleinopathies are not curative and are limited to improvement of quality of life for affected individuals. Although the underlying causes of these diseases are unknown, a shared pathological hallmark is the presence of proteinaceous inclusions containing the α-synuclein (α-syn) protein in brain tissue...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29021214/casein-kinase-ii-phosphorylation-of-cyclin-f-at-serine-621-regulates-the-lys48-ubiquitylation-e3-ligase-activity-of-the-scf-cyclin-f-complex
#17
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29016856/neuronal-overexpression-of-ube3a-isoform-2-causes-behavioral-impairments-and-neuroanatomical-pathology-relevant-to-15q11-2-q13-3-duplication-syndrome
#18
Nycole A Copping, Sarah G B Christian, Dylan J Ritter, M Saharul Islam, Nathalie Buscher, Dorota Zolkowska, Michael C Pride, Elizabeth L Berg, Janine M LaSalle, Jacob Ellegood, Jason P Lerch, Lawrence T Reiter, Jill L Silverman, Scott V Dindot
Maternally derived copy number gains of human chromosome 15q11.2-q13.3 (Dup15q syndrome or Dup15q) cause intellectual disability, epilepsy, developmental delay, hypotonia, speech impairments, and minor dysmorphic features. Dup15q syndrome is one of the most common and penetrant chromosomal abnormalities observed in individuals with autism spectrum disorder (ASD). Although ∼40 genes are located in the 15q11.2-q13.3 region, overexpression of the ubiquitin-protein E3A ligase (UBE3A) gene is thought to be the predominant molecular cause of the phenotypes observed in Dup15q syndrome...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29016557/future-perspectives-of-cell-therapy-for-neonatal-hypoxic-ischemic-encephalopathy
#19
REVIEW
Makoto Nabetani, Haruo Shintaku, Takashi Hamazaki
Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy. Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result in death and disability. In 1997, we reported that irreversible neuronal cell damage is induced by the elevation of intracellular Ca ion concentration that has occurred in sequence after excess accumulation of the excitatory neurotransmitter glutamate during ischemia. We also reported that hypothermia was effective in treating ischemic brain damage in rats by suppressing energy loss and raising intracellular Ca ion concentration...
October 10, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28991698/pitx3-genotype-and-risk-of-dementia-in-parkinson-s-disease-a-population-based-study
#20
David Bäckström, Magdalena Eriksson Domellöf, Gabriel Granåsen, Jan Linder, Sofia Mayans, Eva Elgh, Susanna Jakobson Mo, Lars Forsgren
Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11years with extensive investigations, including neuropsychology and DAT-imaging with (123)I FP-CIT...
October 15, 2017: Journal of the Neurological Sciences
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