WorldWideScience

Sample records for mammalian neuromuscular systems

  1. Neuromuscular disease classification system

    Science.gov (United States)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  2. Active zones of mammalian neuromuscular junctions: formation, density, and aging.

    Science.gov (United States)

    Nishimune, Hiroshi

    2012-12-01

    Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2 and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. © 2012 New York Academy of Sciences.

  3. Effect of temperature on spontaneous release of transmitter at the mammalian neuromuscular junction

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, C J; Statham, H E

    1977-01-01

    Temperature has a multifactorial effect on miniature endplate potential (MEPP) frequency at the mammalian neuromuscular junction, with a negative Q/sub 10/ at 14--28/sup 0/C. The results are explained in terms of the effect of temperature on the various factors that control (Ca/sup 2/+sub i/ at the presynaptic terminals. The temperature-sensitivity of the Ca/sup 2 +/-transport enzyme is believed to be of particular significance and accounts for the observed differences between the amphibian and mammalian neuromuscular junctions.

  4. mammalian brain system

    Directory of Open Access Journals (Sweden)

    Alan Kania

    2014-06-01

    Full Text Available Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin – a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3 was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.

  5. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

    Science.gov (United States)

    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  6. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  7. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  8. Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

    Directory of Open Access Journals (Sweden)

    Patricia Fernández

    2010-12-01

    Full Text Available This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System, a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES and, as a novelty, the myomechanic signals (MMS. In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

  9. Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

    Science.gov (United States)

    de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

    2010-01-01

    This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

  10. A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

    Science.gov (United States)

    Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

    2016-04-01

    Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

  11. Specialized Cilia in Mammalian Sensory Systems

    Directory of Open Access Journals (Sweden)

    Nathalie Falk

    2015-09-01

    Full Text Available Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies.

  12. Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

    Science.gov (United States)

    Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

    2017-01-01

    First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

  13. Regeneration of hair cells in the mammalian vestibular system.

    Science.gov (United States)

    Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

    2016-06-01

    Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

  14. Evolution and Structure of Neuromuscular Systems in Spiralian Meiofauna

    DEFF Research Database (Denmark)

    Bekkouche, Nicolas Tarik

    three taxa together forming Gnathifera). Furthermore, we could infer possible plesiomorphic states of Gnathifera such as the paired ventro-lateral nerve chords (shared with many Spiralia) as well as recover putative Gnathifera apomorphies such as the pharyngeal ganglion; all adding new information...... such as the ciliary pattern or a system of pharyngeal canals of possible importance for future comparative approaches. These different studies show that information on rare and phylogenetically isolated animals with their unique combination of neural and muscular characters are necessary to understand the evolution...

  15. Systemic inflammatory response syndrome increases immobility-induced neuromuscular weakness.

    Science.gov (United States)

    Fink, Heidrun; Helming, Marc; Unterbuchner, Christoph; Lenz, Andrea; Neff, Frauke; Martyn, J A Jeevendra; Blobner, Manfred

    2008-03-01

    Inflammation and immobility are comorbid etiological factors inducing muscle weakness in critically ill patients. This study establishes a rat model to examine the effect of inflammation and immobilization alone and in combination on muscle contraction, histology, and acetylcholine receptor regulation. Prospective, randomized, experimental study. Animal laboratory of a university hospital. Sprague-Dawley rats. To produce systemic inflammation, rats (n = 34) received three consecutive intravenous injections of Corynebacterium parvum on days 0, 4, and 8. Control rats (n = 21) received saline. Both groups were further divided to have one hind limb either immobilized by pinning of knee and ankle joints or sham-immobilized (surgical leg). The contralateral nonsurgical leg of each animal served as control (nonsurgical leg). After 12 days, body weight and muscle mass were significantly reduced in all C. parvum animals compared with saline-injected rats. Immobilization led to local muscle atrophy. Normalized to muscle mass, tetanic contraction was reduced in the surgical leg after immobilization (7.64 +/- 1.91 N/g) and after inflammation (8.71 +/- 2.0 N/g; both p < .05 vs. sham immobilization and saline injection, 11.03 +/- 2.26 N/g). Histology showed an increase in inflammatory cells in all C. parvum-injected animals. Immobilization in combination with C. parvum injection had an additive effect on inflammation. Acetylcholine receptors were increased in immobilized muscles and in all muscles of C. parvum-injected animals. The muscle weakness in critically ill patients can be replicated in our novel rat model. Inflammation and immobilization independently lead to muscle weakness.

  16. Neuromuscular and muscle-tendon system adaptations to isotonic and isokinetic eccentric exercise.

    Science.gov (United States)

    Guilhem, G; Cornu, C; Guével, A

    2010-06-01

    To present the properties of an eccentric contraction and compare neuromuscular and muscle-tendon system adaptations induced by isotonic and isokinetic eccentric trainings. An eccentric muscle contraction is characterized by the production of muscle force associated to a lengthening of the muscle-tendon system. This muscle solicitation can cause micro lesions followed by a regeneration process of the muscle-tendon system. Eccentric exercise is commonly used in functional rehabilitation for its positive effect on collagen synthesis but also for resistance training to increase muscle strength and muscle mass in athletes. Indeed, eccentric training stimulates muscle hypertrophy, increases the fascicle pennation angle, fascicles length and neural activation, thus inducing greater strength gains than concentric or isometric training programs. Eccentric exercise is commonly performed either against a constant external load (isotonic) or at constant velocity (isokinetic), inducing different mechanical constraints. These different mechanical constraints could induce structural and neural adaptive strategies specific to each type of exercise. The literature tends to show that isotonic mode leads to a greater strength gain than isokinetic mode. This observation could be explained by a greater neuromuscular activation after IT training. However, the specific muscle adaptations induced by each mode remain difficult to determine due to the lack of standardized, comparative studies. 2010 Elsevier Masson SAS. All rights reserved.

  17. Neuromuscular complications of thyrotoxicosis.

    Science.gov (United States)

    Kung, Annie W C

    2007-11-01

    Thyroid hormones exert multiple effects on the neuromuscular system and the brain, with the most important being their role in stimulating the development and differentiation of the neuromuscular system and brain in foetal and neonatal life. In the presence of hyperthyroidism, muscular and neurological symptoms may be the presenting clinical features of the disease. The frequency and severity of neuromuscular complications vary considerably and are probably related to the degree of hyperthyroidism, although in some patients the neuromuscular dysfunction is caused by associated disorders rather than by hyperthyroidism per se. This update focuses on the most common neurological and muscular disorders that occur in patients with thyrotoxicosis. It is beyond the scope of this paper to discuss thyroid eye disease and cardiac complications, in themselves separate complications of specific myocytes.

  18. Romantic love: a mammalian brain system for mate choice.

    Science.gov (United States)

    Fisher, Helen E; Aron, Arthur; Brown, Lucy L

    2006-12-29

    Mammals and birds regularly express mate preferences and make mate choices. Data on mate choice among mammals suggest that this behavioural 'attraction system' is associated with dopaminergic reward pathways in the brain. It has been proposed that intense romantic love, a human cross-cultural universal, is a developed form of this attraction system. To begin to determine the neural mechanisms associated with romantic attraction in humans, we used functional magnetic resonance imaging (fMRI) to study 17 people who were intensely 'in love'. Activation specific to the beloved occurred in the brainstem right ventral tegmental area and right postero-dorsal body of the caudate nucleus. These and other results suggest that dopaminergic reward and motivation pathways contribute to aspects of romantic love. We also used fMRI to study 15 men and women who had just been rejected in love. Preliminary analysis showed activity specific to the beloved in related regions of the reward system associated with monetary gambling for uncertain large gains and losses, and in regions of the lateral orbitofrontal cortex associated with theory of mind, obsessive/compulsive behaviours and controlling anger. These data contribute to our view that romantic love is one of the three primary brain systems that evolved in avian and mammalian species to direct reproduction. The sex drive evolved to motivate individuals to seek a range of mating partners; attraction evolved to motivate individuals to prefer and pursue specific partners; and attachment evolved to motivate individuals to remain together long enough to complete species-specific parenting duties. These three behavioural repertoires appear to be based on brain systems that are largely distinct yet interrelated, and they interact in specific ways to orchestrate reproduction, using both hormones and monoamines. Romantic attraction in humans and its antecedent in other mammalian species play a primary role: this neural mechanism motivates

  19. Mosaic serine proteases in the mammalian central nervous system.

    Science.gov (United States)

    Mitsui, Shinichi; Watanabe, Yoshihisa; Yamaguchi, Tatsuyuki; Yamaguchi, Nozomi

    2008-01-01

    We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

  20. Neuromuscular Disorders

    Science.gov (United States)

    ... lead to twitching, cramps, aches and pains, and joint and movement problems. Sometimes it also affects heart function and your ability to breathe. Examples of neuromuscular disorders include Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia ...

  1. The neuro-muscular system in continuously swimming cercariae from Belarus. I Xiphidiocercariae.

    Science.gov (United States)

    Tolstenkov, Oleg O; Akimova, Ludmila N; Terenina, Nadezhda B; Gustafsson, Margaretha K S

    2012-11-01

    The neuromuscular system (NMS) in cercariae of Neoastiotrema trituri, Plagiorchis elegans, Omphalometra flexuosa, Skrjabinoeces similis and Prosthogonimus ovatus was studied with immunocytochemical methods and confocal scanning laser microscopy. The patterns of F-actin in the musculature, 5-HT immunoreactive (IR), FMRFamide-IR neuronal elements and α-tubulin-IR sensory receptors were investigated, and they were found to be rather similar in all the cercariae studied. Four species have seven paired 5-HT-IR neurons in the body, and P. elegans has eight. N. trituri has three 5-HT-IR neurons in each brain ganglion, while the other species have four. A high degree of conformity in the structure of the NMS was observed, probably reflecting the close phylogenetic relationship and the similar strategy of host finding.

  2. Development of network-based multichannel neuromuscular electrical stimulation system for stroke rehabilitation.

    Science.gov (United States)

    Qu, Hongen; Xie, Yongji; Liu, Xiaoxuan; He, Xin; Hao, Manzhao; Bao, Yong; Xie, Qing; Lan, Ning

    2016-01-01

    Neuromuscular electrical stimulation (NMES) is a promising assistive technology for stroke rehabilitation. Here we present the design and development of a multimuscle stimulation system as an emerging therapy for people with paretic stroke. A network-based multichannel NMES system was integrated based on dual bus architecture of communication and an H-bridge current regulator with a power booster. The structure of the system was a body area network embedded with multiple stimulators and a communication protocol of controlled area network to transmit muscle stimulation parameter information to individual stimulators. A graphical user interface was designed to allow clinicians to specify temporal patterns and muscle stimulation parameters. We completed and tested a prototype of the hardware and communication software modules of the multichannel NMES system. The prototype system was first verified in nondisabled subjects for safety, and then tested in subjects with stroke for feasibility with assisting multijoint movements. Results showed that synergistic stimulation of multiple muscles in subjects with stroke improved performance of multijoint movements with more natural velocity profiles at elbow and shoulder and reduced acromion excursion due to compensatory trunk rotation. The network-based NMES system may provide an innovative solution that allows more physiological activation of multiple muscles in multijoint task training for patients with stroke.

  3. Video game-based neuromuscular electrical stimulation system for calf muscle training: a case study.

    Science.gov (United States)

    Sayenko, D G; Masani, K; Milosevic, M; Robinson, M F; Vette, A H; McConville, K M V; Popovic, M R

    2011-03-01

    A video game-based training system was designed to integrate neuromuscular electrical stimulation (NMES) and visual feedback as a means to improve strength and endurance of the lower leg muscles, and to increase the range of motion (ROM) of the ankle joints. The system allowed the participants to perform isotonic concentric and isometric contractions in both the plantarflexors and dorsiflexors using NMES. In the proposed system, the contractions were performed against exterior resistance, and the angle of the ankle joints was used as the control input to the video game. To test the practicality of the proposed system, an individual with chronic complete spinal cord injury (SCI) participated in the study. The system provided a progressive overload for the trained muscles, which is a prerequisite for successful muscle training. The participant indicated that he enjoyed the video game-based training and that he would like to continue the treatment. The results show that the training resulted in a significant improvement of the strength and endurance of the paralyzed lower leg muscles, and in an increased ROM of the ankle joints. Video game-based training programs might be effective in motivating participants to train more frequently and adhere to otherwise tedious training protocols. It is expected that such training will not only improve the properties of their muscles but also decrease the severity and frequency of secondary complications that result from SCI. Copyright © 2010 IPEM. All rights reserved.

  4. The neuro-muscular system in cercaria with different patterns of locomotion.

    Science.gov (United States)

    Tolstenkov, Oleg O; Prokofiev, Vladimir V; Terenina, Nadezhda B; Gustafsson, Margaretha K S

    2011-05-01

    The neuro-muscular system (NMS) of cercariae with different swimming patterns was studied with immunocytochemical methods and confocal scanning laser microscopy. Specimens of the continuously swimming Cercaria parvicaudata, Maritrema subdolum and Himasthla elongata were compared with specimens of the intermittently swimming Cryptocotyle lingua and the attached Podocotyle atomon. The patterns of F-actin in the musculature, 5-HT immunoreactive (-IR), FMRFamide-IR neuronal elements, α-tubulin-IR elements in the nervous and sensory systems and DAPI-stained nuclei were investigated. The general plan of the NMS was similar in all cercariae studied. No major structural differences in the patterns of muscle fibres were observed. However, in the tail of C. lingua, transverse muscle fibres connecting the bands of longitudinal muscles were found. No major structural differences in the 5-HT- or FMRFamide-IR nervous systems were observed. The number of 5-HT-IR neurones in the cercarial bodies varied between 12 and 14. The number and distribution of the α-tubulin-IR processes on the cercarial bodies and tails differed from each other. The relation between the number and structure of the α-tubulin-IR processes and the host finding strategy of the cercariae is discussed. A detailed schematic picture of the NMS in the tails of C. lingua and M. subdolum is presented.

  5. Retaining the equilibrium point hypothesis as an abstract description of the neuromuscular system.

    Science.gov (United States)

    Tresilian, J R

    1999-01-01

    The lambda version of the equilibrium point (EP) hypothesis for motor control is examined in light of recent criticisms of its various instantiations. Four important assumptions that have formed the basis for recent criticism are analyzed: First, the assumption that intact muscles possess invariant force-length characteristics (ICs). Second, that these ICs are of the same form in agonist-antagonist pairs. Third, that muscle control is monoparametric and that the control parameter, lambda, can be given a neurophysiological interpretation. Fourth, that reflex loop time delays and the known, asymmetric, nonlinear mechanical properties of muscles can be ignored. Mechanical and neurophysiological investigations of the neuromuscular system suggests that none of these assumptions is likely to be correct. This has been taken to mean that the EP hypothesis is oversimplified and a new approach is needed. It is argued that such an approach can be provided without rejecting the EP hypothesis, rather to regard it as an input-output description of muscle and associated segmental circuits. The operation of the segmental circuitry can be interpreted as having the function, at least in part, of compensating for a variety of nonlinearities and asymmetries such that the overall system implements the lambda-EP model equations.

  6. Paired Chicken and Mammalian Erythrocyte Indicator Systems for ...

    African Journals Online (AJOL)

    Three levels of erythrocytes suspensions, 1.5%, 1% and 0.5% respectively from goat and guinea pig, were compared to conventional 0.5% chicken erythrocytes, in an attempt to investigate the suitability for the two sources of mammalian erythrocytes as indicators for Newcastle disease virus haemagglutination (HA) tests.

  7. Doenças neuromusculares Neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Umbertina C. Reed

    2002-08-01

    differential diagnosis among the main neuromuscular disorders in children, that include the diseases affecting the motor unity, i.e. spinal motor neurons, peripheral nerves, neuromuscular junction and muscular fibers. Sources: the review of the clinical aspects that should be considered for a prompt differential diagnosis among several neuromuscular disorders as well as between those and the main causes of secondary muscular hypotonia due to central nervous system or systemic disturbances is based on the clinical experience acquired along the last 12 years in following-up children with Neuromuscular Disorders attended at the outpatient Service of Neuromuscular Disorders at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. In addition, it is based on Medline and on the review of the most recent numbers of Neuromuscular Disorders, the official journal of the World Muscle Society. Summary of the findings: most of neuromuscular disorders are genetic conditions in children and the most common of them are X-linked Progressive Muscular Dystrophy of Duchenne, Spinal Muscular Atrophy, Congenital Muscular Dystrophy, Myotonic Dystrophy and Congenital Myopathies. Conclusions: due to the phenomenal development in human molecular genetics the pathogenesis of several neuromuscular disorders in children has been clarified over the last decade. Nowadays many new diagnostic methods, including techniques of fetal diagnosis, and a more objective genotype-phenotype correlation as well as classification are available.

  8. Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view.

    Science.gov (United States)

    Engel, W King

    2015-04-01

    Ageing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical-pathological and clinical-pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed - our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  9. The neuroanatomy of the kisspeptin system in the mammalian brain

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Simonneaux, Valerie

    2008-01-01

    , little data are available about the localization of kisspeptin neurons in the brain, and in particular the projection patterns of kisspeptin containing axons implicated in regulation of the hypothalamo-pituitary gonadal axis. This review covers the current information about the localization of kisspeptin...... neurons in the mammalian brain and discusses the facts and artifacts of the methods of their detection. The available data suggest that kisspeptins are synthesized in neurons in the anteroventral periventricular nucleus and the arcuate nucleus. Both populations are considered to be involved in control...

  10. Next-generation mammalian genetics toward organism-level systems biology.

    Science.gov (United States)

    Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

    2017-01-01

    Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

  11. A Versatile System for USER Cloning-Based Assembly of Expression Vectors for Mammalian Cell Engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Petersen, Maja Borup Kjær

    2014-01-01

    , in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors....

  12. [Characteristics of neuromuscular scoliosis].

    Science.gov (United States)

    Putzier, M; Groß, C; Zahn, R K; Pumberger, M; Strube, P

    2016-06-01

    Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research.

  13. A versatile system for USER cloning-based assembly of expression vectors for mammalian cell engineering.

    Directory of Open Access Journals (Sweden)

    Anne Mathilde Lund

    Full Text Available A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique--USER cloning--to rapidly construct mammalian expression vectors of multiple DNA fragments and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site, cellular localization signals and epitope- and purification tags. Building blocks in the toolbox can be easily combined as they contain defined and tested Flexible Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of gene, promoter or selection marker in existing plasmids and simple construction of vectors encoding proteins, which are fused to fluorescence-, purification-, localization-, or epitope tags. The mammalian expression vector assembly platform currently allows for the assembly of up to seven fragments in a single cloning step with correct directionality and with a cloning efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors.

  14. Virtual reality and gaming systems to improve walking and mobility for people with musculoskeletal and neuromuscular conditions.

    Science.gov (United States)

    Deutsch, Judith E

    2009-01-01

    Improving walking for individuals with musculoskeletal and neuromuscular conditions is an important aspect of rehabilitation. The capabilities of clinicians who address these rehabilitation issues could be augmented with innovations such as virtual reality gaming based technologies. The chapter provides an overview of virtual reality gaming based technologies currently being developed and tested to improve motor and cognitive elements required for ambulation and mobility in different patient populations. Included as well is a detailed description of a single VR system, consisting of the rationale for development and iterative refinement of the system based on clinical science. These concepts include: neural plasticity, part-task training, whole task training, task specific training, principles of exercise and motor learning, sensorimotor integration, and visual spatial processing.

  15. Emotional Arousal and Multiple Memory Systems in the Mammalian Brain

    Directory of Open Access Journals (Sweden)

    Mark G. Packard

    2012-03-01

    Full Text Available Emotional arousal induced by stress and/or anxiety can exert complex effects on learning and memory processes in mammals. Recent studies have begun to link study of the influence of emotional arousal on memory with earlier research indicating that memory is organized in multiple systems in the brain that differ in terms of the type of memory they mediate. Specifically, these studies have examined whether emotional arousal may have a differential effect on the cognitive and stimulus-response habit memory processes subserved by the hippocampus and dorsal striatum, respectively. Evidence indicates that stress or the peripheral injection of anxiogenic drugs can bias animals and humans towards the use of striatal-dependent habit memory in dual-solution tasks in which both hippocampal and stritatal-based strategies can provide an adequate solution. A bias towards the use of habit memory can also be produced by intra-basolateral amygdala administration of anxiogenic drugs, consistent with the well documented role of efferent projections of this brain region in mediating the modulatory influence of emotional arousal on memory. In some learning situations, the bias towards the use of habit memory produced by emotional arousal appears to result from an impairing effect on hippocampus-dependent cognitive memory. Further research examining the neural mechanisms linking emotion and the relative use of multiple memory systems should prove useful in view of the potential role for maladaptive habitual behaviors in various human psychopathologies.

  16. Biological complexity and adaptability of simple mammalian olfactory memory systems.

    Science.gov (United States)

    Brennan, P; Keverne, E B

    2015-03-01

    Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  17. Structure and function of stem cell pools in mammalian cell renewal systems

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Nothdurft, W.

    1979-01-01

    Stem cells play a key-role in the maintenance of the equilibrium between cell loss and cell production in cell renewal systems as well as in the understanding of the radiation pathophysiology of mammalian organisms. The integrity of mammalian organisms with the need to maintain a constant ''millieu interior'' is depending on the normal functioning of cell renewal systems, especially those of epithelial surfaces and blood cell forming organs. All cell renewal systems of bodies have a very similar functional structure consisting of functional, proliferative - amplifying and stem cell compartments. They differ in transit and cell cycle times and in the number of amplification division - aside from the difference in their functional and biochemical make-up. The stem cell pools are providing the cells capable of differentiation without depleting their own kind. This can be achieved by symmetrical or assymmetrical stem cell division. In normal steady state, 50% of the stem cell division remain in the stem cell pool, while the other 50% leave it to differentiate, proliferate and mature, hemopoietic system is distributed throughout bodies. This is an important factor in the radiation biology of mammalian organisms since the loss of function in one area can be compensated for by more production in other areas, and locally depleted sites can be reseeded with the stem cells migrating in from blood. (Yamashita, S.)

  18. Elabela-apelin receptor signaling pathway is functional in mammalian systems.

    Science.gov (United States)

    Wang, Zhi; Yu, Daozhan; Wang, Mengqiao; Wang, Qilong; Kouznetsova, Jennifer; Yang, Rongze; Qian, Kun; Wu, Wenjun; Shuldiner, Alan; Sztalryd, Carole; Zou, Minghui; Zheng, Wei; Gong, Da-Wei

    2015-02-02

    Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.

  19. Strength Training Prior to Endurance Exercise: Impact on the Neuromuscular System, Endurance Performance and Cardiorespiratory Responses

    Directory of Open Access Journals (Sweden)

    Conceição Matheus

    2014-12-01

    Full Text Available This study aimed to investigate the acute effects of two strength-training protocols on the neuromuscular and cardiorespiratory responses during endurance exercise. Thirteen young males (23.2 ± 1.6 years old participated in this study. The hypertrophic strength-training protocol was composed of 6 sets of 8 squats at 75% of maximal dynamic strength. The plyometric strength-training protocol was composed of 6 sets of 8 jumps performed with the body weight as the workload. Endurance exercise was performed on a cycle ergometer at a power corresponding to the second ventilatory threshold until exhaustion. Before and after each protocol, a maximal voluntary contraction was performed, and the rate of force development and electromyographic parameters were assessed. After the hypertrophic strengthtraining and plyometric strength-training protocol, significant decreases were observed in the maximal voluntary contraction and rate of force development, whereas no changes were observed in the electromyographic parameters. Oxygen uptake and a heart rate during endurance exercise were not significantly different among the protocols. However, the time-to-exhaustion was significantly higher during endurance exercise alone than when performed after hypertrophic strength-training or plyometric strength-training (p <0.05. These results suggest that endurance performance may be impaired when preceded by strength-training, with no oxygen uptake or heart rate changes during the exercise.

  20. Influence of Spirulina platensis exudates on the endocrine and nervous systems of a mammalian model

    OpenAIRE

    Samah M.M. Fathy; Ashraf M.M. Essa

    2015-01-01

    Objective: To investigate the effect of intra-peritoneal injection of purified exudates of axenic Spirulina platensis on the mammalian endocrine and nervous systems. Methods: The intra-peritoneal injection of the cyanobacterial exudates in mice was applied. Sex hormonal levels of testosterone and progesterone were measured using radioimmunoassay while the follicular stimulating hormone and luteinizing hormone were evaluated by direct chemiluminescence. In addition, superoxide dismutase, ca...

  1. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems

    OpenAIRE

    Chen, Yvonne Y.; Jensen, Michael C.; Smolke, Christina D.

    2010-01-01

    RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional res...

  2. Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

    Science.gov (United States)

    Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

    2011-12-01

    Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system.

    Science.gov (United States)

    Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James

    2010-12-01

    To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.

  4. Neuromuscular control and ankle instability.

    Science.gov (United States)

    Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

    2009-04-01

    Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

  5. Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis.

    Science.gov (United States)

    Sorbara, Matthew T; Philpott, Dana J

    2011-09-01

    Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP-1-4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell-autonomous and whole-organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these diverse contexts. © 2011 John Wiley & Sons A/S.

  6. Information system for selection of conditions and equipment for the cultivation of mammalian cells

    Directory of Open Access Journals (Sweden)

    D. R. Batyrgazieva

    2017-01-01

    Full Text Available The use of mammals cells and their products wide application, so the actual problem is a creation of an information system in the field of their cultivation for the organizing and structuring of information on process experimental data. This work is devoted the analysis of mammalian cell cultivation. The main technologies of cell cultivation, necessary equipment and matrices are considered. The main stages of database design and information system is described. The justification of software products are provided and the results of the database and information system implementation are done. The detailed description of all modules of the system, as well as a comparative analysis of the results of the search are in the system to verify correct operation of the system. The scientific and practical significance of the work lies in the fact that the effective tool for presenting knowledge and data for search by specific parameters is required. The convenience of the system is that it is not necessary to address in various data sources to get and conditions of cultivation of mammalian cells, it has already been collected and structured according to parameters. With help of the system, it is possible to select conditions for the cultivation of mammalian cells at the stage of scientific researches that will significantly reduce the time and cost of work, also to rank of recommended technological and hardware solutions. The system has a functional completeness, i.e. in a specific subject area, it ensures the fulfillment of user's requirements, and allows to accumulate and process information.

  7. Accuracy of a Custom Physical Activity and Knee Angle Measurement Sensor System for Patients with Neuromuscular Disorders and Gait Abnormalities

    Directory of Open Access Journals (Sweden)

    Frank Feldhege

    2015-05-01

    Full Text Available Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.

  8. Objective neuromuscular monitoring of neuromuscular blockade in Denmark

    DEFF Research Database (Denmark)

    Söderström, C M; Eskildsen, K Z; Gätke, M R

    2017-01-01

    BACKGROUND: Neuromuscular blocking agents are commonly used during general anaesthesia but can lead to postoperative residual neuromuscular blockade and associated morbidity. With appropriate objective neuromuscular monitoring (objNMM) residual blockade can be avoided. In this survey, we investig...

  9. Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

    Science.gov (United States)

    Lyu, Zhe; Whitman, William B

    2017-01-01

    Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

  10. Neuromuscular Stress.

    Science.gov (United States)

    White, Timothy P.; Kern, Marialice

    1994-01-01

    Discusses exercise-induced stress that results from motor unit recruitment, the impact of recruitment on selected systemic support systems, and some of the environmental overlays that affect the degree of physiological stress. Adaptations to sustained changes in physical activity and muscle and myotendinous injury induced by stress are examined.…

  11. Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

    OpenAIRE

    O'Connor, Joanne; McCaughan, Dorothy; McDaid, Catriona; Booth, Alison; Fayter, Debra; Rodriguez-Lopez, Roccio; Bowers, Roy; Dyson, Lisa; Iglesias, Cynthia P; Lalor, Simon; O'Connor, Rory J; Phillips, Margaret; Ramdharry, Gita

    2016-01-01

    BACKGROUND: \\ud \\ud Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs).\\ud \\ud OBJECTIVES: \\ud \\ud To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs.\\ud \\ud METHODS: \\ud \\ud Qualitative study of views of orthoses users - a qualitative in-...

  12. A hypothesis for the minimal overall structure of the mammalian plasma membrane redox system.

    Science.gov (United States)

    de Grey, Aubrey D N J

    2003-05-01

    After a long period of frustration, many components of the mammalian plasma membrane redox system are now being identified at the molecular level. Some are apparently ubiquitous but are necessary only for a subset of electron donors or acceptors; some are present only in certain cell types; some appear to be associated with proton extrusion; some appear to be capable of superoxide production. The volume and variety of data now available have begun to allow the formulation of tentative models for the overall network of interactions of enzymes and substrates that together make up the plasma membrane redox system. Such a model is presented here. The structure discussed here is of the mammalian system, though parts of it may apply more or less accurately to fungal and plant cells too. Judging from the history of mitochondrial oxidative phosphorylation, it may be hoped that the development of models of the whole system - even if they undergo substantial revision thereafter - will markedly accelerate the pace of research in plasma membrane redox, by providing a coherent basis for the design of future experiments.

  13. [Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems]: Final report

    International Nuclear Information System (INIS)

    Friedberg, E.C.

    1987-08-01

    This study sought to exploit the use of uv radiation as a source of genomic damage. We explored the molecular mechanism of the repair of DNA damage at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian cells. Not only have observations obtained in one biological system suggested specific experimental approaches in others, but we have also learned that some biochemical pathways for DNA repair are unique to specific organisms. Our studies are summarized in terms of 4 major areas of research activity that span the past 16 years. 86 refs

  14. Radon exposure system for mammalian cells in culture: Design, operation, and dosimetry

    International Nuclear Information System (INIS)

    Seed, T.M.; Kretz, N.D.; Schlenker, R.A.

    1991-01-01

    A novel system for Rn gas exposure of mammalian cells in culture has been designed, constructed, and used to directly assess both the magnitude and the nature of chronic, low-dose Rn/Rn daughter toxicity of exposed vital lung cells isolated from normal pulmonary tissue, propagated and exposed in vitro. Direct correlations between atmospheric Rn concentrations, alpha-particle fluences, and macro- and microdoses of absorbed radiation doses by lung cells provide for a heretofore unavailable assessment of critical doses to vital cells

  15. TEACHING NEUROMUSCULAR RELAXATION.

    Science.gov (United States)

    NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

    THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

  16. How does a specific learning and memory system in the mammalian brain gain control of behavior?

    Science.gov (United States)

    McDonald, Robert J; Hong, Nancy S

    2013-11-01

    This review addresses a fundamental, yet poorly understood set of issues in systems neuroscience. The issues revolve around conceptualizations of the organization of learning and memory in the mammalian brain. One intriguing, and somewhat popular, conceptualization is the idea that there are multiple learning and memory systems in the mammalian brain and they interact in different ways to influence and/or control behavior. This approach has generated interesting empirical and theoretical work supporting this view. One issue that needs to be addressed is how these systems influence or gain control of voluntary behavior. To address this issue, we clearly specify what we mean by a learning and memory system. We then review two types of processes that might influence which memory system gains control of behavior. One set of processes are external factors that can affect which system controls behavior in a given situation including task parameters like the kind of information available to the subject, types of training experience, and amount of training. The second set of processes are brain mechanisms that might influence what memory system controls behavior in a given situation including executive functions mediated by the prefrontal cortex; switching mechanisms mediated by ascending neurotransmitter systems, the unique role of the hippocampus during learning. The issue of trait differences in control of different learning and memory systems will also be considered in which trait differences in learning and memory function are thought to potentially emerge from differences in level of prefrontal influence, differences in plasticity processes, differences in ascending neurotransmitter control, differential access to effector systems like motivational and motor systems. Finally, we present scenarios in which different mechanisms might interact. This review was conceived to become a jumping off point for new work directed at understanding these issues. The outcome of

  17. A Neuromuscular Electrical Stimulation (NMES) and robot hybrid system for multi-joint coordinated upper limb rehabilitation after stroke.

    Science.gov (United States)

    Rong, Wei; Li, Waiming; Pang, Mankit; Hu, Junyan; Wei, Xijun; Yang, Bibo; Wai, Honwah; Zheng, Xiaoxiang; Hu, Xiaoling

    2017-04-26

    It is a challenge to reduce the muscular discoordination in the paretic upper limb after stroke in the traditional rehabilitation programs. In this study, a neuromuscular electrical stimulation (NMES) and robot hybrid system was developed for multi-joint coordinated upper limb physical training. The system could assist the elbow, wrist and fingers to conduct arm reaching out, hand opening/grasping and arm withdrawing by tracking an indicative moving cursor on the screen of a computer, with the support from the joint motors and electrical stimulations on target muscles, under the voluntary intention control by electromyography (EMG). Subjects with chronic stroke (n = 11) were recruited for the investigation on the assistive capability of the NMES-robot and the evaluation of the rehabilitation effectiveness through a 20-session device assisted upper limb training. In the evaluation, the movement accuracy measured by the root mean squared error (RMSE) during the tracking was significantly improved with the support from both the robot and NMES, in comparison with those without the assistance from the system (P joint and inter-joint muscular co-contractions measured by EMG were significantly released when the NMES was applied to the agonist muscles in the different phases of the limb motion (P < 0.05). After the physical training, significant improvements (P < 0.05) were captured by the clinical scores, i.e., Modified Ashworth Score (MAS, the elbow and the wrist), Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). The EMG-driven NMES-robotic system could improve the muscular coordination at the elbow, wrist and fingers. ClinicalTrials.gov. NCT02117089 ; date of registration: April 10, 2014.

  18. Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

    Science.gov (United States)

    Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

    2017-01-31

    In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

  19. Search for biological effects of 13C-enrichment in developing mammalian systems

    International Nuclear Information System (INIS)

    Gregg, C.; Ott, D.; Deaven, L.; Spielmann, H.; Krowke, R.; Neubert, D.

    1975-01-01

    Increasing diagnostic use of stable isotopes, especially in children and pregnant women, enhances the importance of studies on the biological isotope effects in sensitive mammalian systems. Experimental data on animal systems are meager. The mouse embryos was studied at various stages and mouse limb buds were studied in organ culture. Limb bud development in vitro was unaffected by incubation with 82 mol percent 13 C-glucose as judged by either morphological or biochemical criteria. Of 271 preimplantation embryos incubated in vitro, 95.2 percent developed normally; in 13 C-enriched medium, 96.5 percent showed normal development. 13 C-Enrichment of the embryos in vitro is over 60 percent. Administration of 1.2 g glucose-U- 13 C to pregnant mice during organogenesis leads to enrichment of maternal liver glycogen to over 17 mol percent 13 C, about one-third this level in the embryo, and a lower level in maternal blood. The absolute 13 C content of the embryo continues to increase for several days after the end of isotope administration, while the enrichment in maternal tissues falls. The lipid fraction of the fetus is most highly labeled shortly after the end of isotope administration []These studies on developing mammalian systems have not yet revealed any alteration of normal development due to stable isotope enrichment. (auth)

  20. Neuromuscular complications of immune checkpoint inhibitor therapy.

    Science.gov (United States)

    Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

    2018-01-17

    Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  1. The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

    Science.gov (United States)

    Llinas, Rodolfo R.

    1988-12-01

    This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

  2. Rescue the failed half-ZFN by a sensitive mammalian cell-based luciferase reporter system.

    Directory of Open Access Journals (Sweden)

    Weifeng Zhang

    Full Text Available ZFN technology is a powerful research tool and has been used for genome editing in cells lines, animals and plants. The generation of functional ZFNs for particular targets in mammalian genome is still challenging for an average research group. The modular-assembly method is relatively fast, easy-to-practice but has a high failure rate. Some recent studies suggested that a ZFP with low binding activity might be able to form a working ZFN pair with another binding active half-ZFP. In order to unveil the potential ZFP candidates among those with low binding activities, this paper established a highly sensitive mammalian cell-based transcriptional reporter system to assess the DNA binding activities of ZFPs by inserting multiple copies of ZFN target sequence fragment (TSF of an interested gene (e. g., hPGRN or hVEGF. Our results showed that this system increased the screening sensitivity up to 50-fold and markedly amplified the differences in the binding activities between different ZFPs. We also found that the targeted chromosomal gene repair efficiency of each hPGRN or hVEGF ZFN pair was in proportion with the combination of the binding activities of the ZFL (Left zinc finger and ZFR (Right zinc finger. A hPGRN ZFR with low binding ability was able to form a biological active ZFN if combined with a hPGRN ZFL with relatively high binding ability. Lastly, site-specific genome editing by hPGRN ZFNs generated by this system was confirmed by sequencing, and the PGRN knock-out cell line showed significantly decreased cell growth compared with the control. Our system will provide a valuable tool for further optimizing the nucleases with regard to specificity and cytotoxicity.

  3. Embedded System for Prosthetic Control Using Implanted Neuromuscular Interfaces Accessed Via an Osseointegrated Implant.

    Science.gov (United States)

    Mastinu, Enzo; Doguet, Pascal; Botquin, Yohan; Hakansson, Bo; Ortiz-Catalan, Max

    2017-08-01

    Despite the technological progress in robotics achieved in the last decades, prosthetic limbs still lack functionality, reliability, and comfort. Recently, an implanted neuromusculoskeletal interface built upon osseointegration was developed and tested in humans, namely the Osseointegrated Human-Machine Gateway. Here, we present an embedded system to exploit the advantages of this technology. Our artificial limb controller allows for bioelectric signals acquisition, processing, decoding of motor intent, prosthetic control, and sensory feedback. It includes a neurostimulator to provide direct neural feedback based on sensory information. The system was validated using real-time tasks characterization, power consumption evaluation, and myoelectric pattern recognition performance. Functionality was proven in a first pilot patient from whom results of daily usage were obtained. The system was designed to be reliably used in activities of daily living, as well as a research platform to monitor prosthesis usage and training, machine-learning-based control algorithms, and neural stimulation paradigms.

  4. The neuromuscular system of Pycnophyes kielensis (Kinorhyncha: Allomalorhagida) investigated by confocal laser scanning microscopy.

    Science.gov (United States)

    Altenburger, Andreas

    2016-01-01

    Kinorhynchs are ecdysozoan animals with a phylogenetic position close to priapulids and loriciferans. To understand the nature of segmentation within Kinorhyncha and to infer a probable ancestry of segmentation within the last common ancestor of Ecdysozoa, the musculature and the nervous system of the allomalorhagid kinorhynch Pycnophyes kielensis were investigated by use of immunohistochemistry, confocal laser scanning microscopy, and 3D reconstruction software. The kinorhynch body plan comprises 11 trunk segments. Trunk musculature consists of paired ventral and dorsal longitudinal muscles in segments 1-10 as well as dorsoventral muscles in segments 1-11. Dorsal and ventral longitudinal muscles insert on apodemes of the cuticle inside the animal within each segment. Strands of longitudinal musculature extend over segment borders in segments 1-6. In segments 7-10, the trunk musculature is confined to the segments. Musculature of the digestive system comprises a strong pharyngeal bulb with attached mouth cone muscles as well as pharyngeal bulb protractors and retractors. The musculature of the digestive system shows no sign of segmentation. Judged by the size of the pharyngeal bulb protractors and retractors, the pharyngeal bulb, as well as the introvert, is moved passively by internal pressure caused by concerted action of the dorsoventral muscles. The nervous system comprises a neuropil ring anterior to the pharyngeal bulb. Associated with the neuropil ring are flask-shaped serotonergic somata extending anteriorly and posteriorly. A ventral nerve cord is connected to the neuropil ring and runs toward the anterior until an attachment point in segment 1, and from there toward the posterior with one ganglion in segment 6. Segmentation within Kinorhyncha likely evolved from an unsegmented ancestor. This conclusion is supported by continuous trunk musculature in the anterior segments 1-6, continuous pharyngeal bulb protractors and retractors throughout the anterior

  5. The neuromuscular system of Pycnophyes kielensis (Kinorhyncha: Allomalorhagida investigated by confocal laser scanning microscopy

    Directory of Open Access Journals (Sweden)

    Andreas Altenburger

    2016-11-01

    Full Text Available Abstract Background Kinorhynchs are ecdysozoan animals with a phylogenetic position close to priapulids and loriciferans. To understand the nature of segmentation within Kinorhyncha and to infer a probable ancestry of segmentation within the last common ancestor of Ecdysozoa, the musculature and the nervous system of the allomalorhagid kinorhynch Pycnophyes kielensis were investigated by use of immunohistochemistry, confocal laser scanning microscopy, and 3D reconstruction software. Results The kinorhynch body plan comprises 11 trunk segments. Trunk musculature consists of paired ventral and dorsal longitudinal muscles in segments 1–10 as well as dorsoventral muscles in segments 1–11. Dorsal and ventral longitudinal muscles insert on apodemes of the cuticle inside the animal within each segment. Strands of longitudinal musculature extend over segment borders in segments 1–6. In segments 7–10, the trunk musculature is confined to the segments. Musculature of the digestive system comprises a strong pharyngeal bulb with attached mouth cone muscles as well as pharyngeal bulb protractors and retractors. The musculature of the digestive system shows no sign of segmentation. Judged by the size of the pharyngeal bulb protractors and retractors, the pharyngeal bulb, as well as the introvert, is moved passively by internal pressure caused by concerted action of the dorsoventral muscles. The nervous system comprises a neuropil ring anterior to the pharyngeal bulb. Associated with the neuropil ring are flask-shaped serotonergic somata extending anteriorly and posteriorly. A ventral nerve cord is connected to the neuropil ring and runs toward the anterior until an attachment point in segment 1, and from there toward the posterior with one ganglion in segment 6. Conclusions Segmentation within Kinorhyncha likely evolved from an unsegmented ancestor. This conclusion is supported by continuous trunk musculature in the anterior segments 1–6, continuous

  6. A compact light-sheet microscope for the study of the mammalian central nervous system

    Science.gov (United States)

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2016-01-01

    Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca2+ signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community. PMID:27215692

  7. Understanding mammalian genetic systems: the challenge of phenotyping in the mouse.

    Directory of Open Access Journals (Sweden)

    Steve D M Brown

    2006-08-01

    Full Text Available Understanding mammalian genetic systems is predicated on the determination of the relationship between genetic variation and phenotype. Several international programmes are under way to deliver mutations in every gene in the mouse genome. The challenge for mouse geneticists is to develop approaches that will provide comprehensive phenotype datasets for these mouse mutant libraries. Several factors are critical to success in this endeavour. It will be important to catalogue assay and environment and where possible to adopt standardised procedures for phenotyping tests along with common environmental conditions to ensure comparable datasets of phenotypes. Moreover, the scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms. In addition, it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome.

  8. Sleeping to fuel the immune system: mammalian sleep and resistance to parasites

    Directory of Open Access Journals (Sweden)

    Opp Mark R

    2009-01-01

    Full Text Available Abstract Sleep is an enigma. Why animals forgo eating and reproducing, while potentially increasing their risk of predation remains unknown. Although some may question whether all animals sleep, it is clear that all living organisms possess defenses against attack by pathogens. Immune responses of humans and animals are impaired by sleep loss, and responses to immune challenge include altered sleep. Thus, sleep is hypothesized to be a component of the acute phase response to infection and to function in host defense. Examining phylogenetic relationships among sleep parameters, components of the mammalian immune system and resistance to infection may provide insight into the evolution of sleep and lead to a greater appreciation for the role of sleep in host defense.

  9. The Sensitivity of the Crayfish Reward System to Mammalian Drugs of Abuse.

    Science.gov (United States)

    Shipley, Adam T; Imeh-Nathaniel, Adebobola; Orfanakos, Vasiliki B; Wormack, Leah N; Huber, Robert; Nathaniel, Thomas I

    2017-01-01

    The idea that addiction occurs when the brain is not able to differentiate whether specific reward circuits were triggered by adaptive natural rewards or falsely activated by addictive drugs exist in several models of drug addiction. The suitability of crayfish ( Orconectes rusticus ) for drug addiction research arises from developmental variation of growth, life span, reproduction, behavior and some quantitative traits, especially among isogenic mates reared in the same environment. This broad spectrum of traits makes it easier to analyze the effect of mammalian drugs of abuse in shaping behavioral phenotype. Moreover, the broad behavioral repertoire allows the investigation of self-reinforcing circuitries involving appetitive and exploratory motor behavior, while the step-wise alteration of the phenotype by metamorphosis allows accurate longitudinal analysis of different behavioral states. This paper reviews a series of recent experimental findings that evidence the suitability of crayfish as an invertebrate model system for the study of drug addiction. Results from these studies reveal that unconditioned exposure to mammalian drugs of abuse produces a variety of stereotyped behaviors. Moreover, if presented in the context of novelty, drugs directly stimulate exploration and appetitive motor patterns along with molecular processes for drug conditioned reward. Findings from these studies indicate the existence of drug sensitive circuitry in crayfish that facilitates exploratory behavior and appetitive motor patterns via increased incentive salience of environmental stimuli or by increasing exploratory motor patterns. This work demonstrates the potential of crayfish as a model system for research into the neural mechanisms of addiction, by contributing an evolutionary, comparative context to our understanding of natural reward as an important life-sustaining process.

  10. The Sensitivity of the Crayfish Reward System to Mammalian Drugs of Abuse

    Directory of Open Access Journals (Sweden)

    Adam T. Shipley

    2017-12-01

    Full Text Available The idea that addiction occurs when the brain is not able to differentiate whether specific reward circuits were triggered by adaptive natural rewards or falsely activated by addictive drugs exist in several models of drug addiction. The suitability of crayfish (Orconectes rusticus for drug addiction research arises from developmental variation of growth, life span, reproduction, behavior and some quantitative traits, especially among isogenic mates reared in the same environment. This broad spectrum of traits makes it easier to analyze the effect of mammalian drugs of abuse in shaping behavioral phenotype. Moreover, the broad behavioral repertoire allows the investigation of self-reinforcing circuitries involving appetitive and exploratory motor behavior, while the step-wise alteration of the phenotype by metamorphosis allows accurate longitudinal analysis of different behavioral states. This paper reviews a series of recent experimental findings that evidence the suitability of crayfish as an invertebrate model system for the study of drug addiction. Results from these studies reveal that unconditioned exposure to mammalian drugs of abuse produces a variety of stereotyped behaviors. Moreover, if presented in the context of novelty, drugs directly stimulate exploration and appetitive motor patterns along with molecular processes for drug conditioned reward. Findings from these studies indicate the existence of drug sensitive circuitry in crayfish that facilitates exploratory behavior and appetitive motor patterns via increased incentive salience of environmental stimuli or by increasing exploratory motor patterns. This work demonstrates the potential of crayfish as a model system for research into the neural mechanisms of addiction, by contributing an evolutionary, comparative context to our understanding of natural reward as an important life-sustaining process.

  11. The Neuromuscular System

    NARCIS (Netherlands)

    Hosman, R.J.A.W.; Abbink, D.A.; Cardullo, F.M.

    2010-01-01

    The aim of flight simulation is to create an environment for the pilot wherein he or she can perform the piloting task in such a way that the objective of the simulation, training or research, is reached. To simulate the flight environment in a simulator models describing the aircraft dynamic

  12. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  13. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  14. Biological studies using mammalian cell lines and the current status of the microbeam irradiation system, SPICE

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: tkonishi@nirs.go.jp; Ishikawa, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Iso, H. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Yasuda, N.; Oikawa, M. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Higuchi, Y. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Kato, T. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshimaku, Tokyo 171-8501 (Japan); Hafer, K. [Department of Radiation Oncology, UCLA School of Medicine, Los Angeles, CA (United States); Kodama, K. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Neos-Tech Co. Ltd., Benten 4-11-13-202, Chuo-ku, Chiba 206-0045 (Japan); Hamano, T.; Suya, N.; Imaseki, H. [Dept. of Technical Support and Development, Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2009-06-15

    The development of SPICE (single-particle irradiation system to cell), a microbeam irradiation system, has been completed at the National Institute of Radiological Sciences (NIRS). The beam size has been improved to approximately 5 {mu}m in diameter, and the cell targeting system can irradiate up to 400-500 cells per minute. Two cell dishes have been specially designed: one a Si{sub 3}N{sub 4} plate (2.5 mm x 2.5 mm area with 1 {mu}m thickness) supported by a 7.5 mm x 7.5 mm frame of 200 {mu}m thickness, and the other a Mylar film stretched by pressing with a metal ring. Both dish types may be placed on a voice coil stage equipped on the cell targeting system, which includes a fluorescent microscope and a CCD camera for capturing cell images. This microscope system captures images of dyed cell nuclei, computes the location coordinates of individual cells, and synchronizes this with the voice coil motor stage and single-particle irradiation system consisting of a scintillation counter and a beam deflector. Irradiation of selected cells with a programmable number of protons is now automatable. We employed the simultaneous detection method for visualizing the position of mammalian cells and proton traversal through CR-39 to determine whether the targeted cells are actually irradiated. An immuno-assay was also performed against {gamma}-H2AX, to confirm the induction of DNA double-strand breaks in the target cells.

  15. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

    Science.gov (United States)

    Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  16. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2015-07-01

    Full Text Available Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1 essential branched-chain amino acids (BCAAs; (2 glutamine; (3 palmitic acid; and (4 bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER stress and drives an aimless quasi-program, which promotes aging and age-related diseases.

  17. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Science.gov (United States)

    Melnik, Bodo C.

    2015-01-01

    Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. PMID:26225961

  18. Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

    Directory of Open Access Journals (Sweden)

    Dimitrov Mitko

    2009-08-01

    Full Text Available Abstract Background N,N-Diethyl-3-methylbenzamide (deet remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. Results By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. Conclusion These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

  19. Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

    Directory of Open Access Journals (Sweden)

    Robert E. Poelmann

    2017-05-01

    Full Text Available Abstract Background Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. Results We studied embryonic stages of reptile hearts (lizard, turtle and crocodile and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard or it is vestigial (turtle. Crocodiles

  20. Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

    Science.gov (United States)

    Poelmann, Robert E; Gittenberger-de Groot, Adriana C; Biermans, Marcel W M; Dolfing, Anne I; Jagessar, Armand; van Hattum, Sam; Hoogenboom, Amanda; Wisse, Lambertus J; Vicente-Steijn, Rebecca; de Bakker, Merijn A G; Vonk, Freek J; Hirasawa, Tatsuya; Kuratani, Shigeru; Richardson, Michael K

    2017-01-01

    Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the

  1. Research highlights of partial neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Cheng ZHANG

    2014-05-01

    Full Text Available In order to understand the latest progression on neuromuscular disorders for clinicians, this review screened and systemized the papers on neuromuscular disorders which were collected by PubMed from January 2013 to February 2014. This review also introduced the clinical diagnosis and treatment hightlights on glycogen storage disease type Ⅱ (GSD Ⅱ, Duchenne muscular dystrophy (DMD, amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA. The important references will be useful for clinicians. doi: 10.3969/j.issn.1672-6731.2014.05.004

  2. Differentiation of mammalian skeletal muscle cells cultured on microcarrier beads in a rotating cell culture system

    Science.gov (United States)

    Torgan, C. E.; Burge, S. S.; Collinsworth, A. M.; Truskey, G. A.; Kraus, W. E.

    2000-01-01

    The growth and repair of adult skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. These cells are responsive to a variety of environmental cues, including mechanical stimuli. The overall goal of the research is to examine the role of mechanical signalling mechanisms in muscle growth and plasticity through utilisation of cell culture systems where other potential signalling pathways (i.e. chemical and electrical stimuli) are controlled. To explore the effects of decreased mechanical loading on muscle differentiation, mammalian myoblasts are cultured in a bioreactor (rotating cell culture system), a model that has been utilised to simulate microgravity. C2C12 murine myoblasts are cultured on microcarrier beads in a bioreactor and followed throughout differentiation as they form a network of multinucleated myotubes. In comparison with three-dimensional control cultures that consist of myoblasts cultured on microcarrier beads in teflon bags, myoblasts cultured in the bioreactor exhibit an attenuation in differentiation. This is demonstrated by reduced immunohistochemical staining for myogenin and alpha-actinin. Western analysis shows a decrease, in bioreactor cultures compared with control cultures, in levels of the contractile proteins myosin (47% decrease, p < 0.01) and tropomyosin (63% decrease, p < 0.01). Hydrodynamic measurements indicate that the decrease in differentiation may be due, at least in part, to fluid stresses acting on the myotubes. In addition, constraints on aggregate size imposed by the action of fluid forces in the bioreactor affect differentiation. These results may have implications for muscle growth and repair during spaceflight.

  3. Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle

    Science.gov (United States)

    Storella, R. J.; Schouchoff, A. L.; Fujii, M.; Hill, J.; Fletcher, J. E.; Jiang, M. S.; Smith, L. A.

    1992-01-01

    Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

  4. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts.

    Science.gov (United States)

    Blakqori, Gjon; Delhaye, Sophie; Habjan, Matthias; Blair, Carol D; Sánchez-Vargas, Irma; Olson, Ken E; Attarzadeh-Yazdi, Ghassem; Fragkoudis, Rennos; Kohl, Alain; Kalinke, Ulrich; Weiss, Siegfried; Michiels, Thomas; Staeheli, Peter; Weber, Friedemann

    2007-05-01

    La Crosse virus (LACV) is a mosquito-transmitted member of the Bunyaviridae family that causes severe encephalitis in children. For the LACV nonstructural protein NSs, previous overexpression studies with mammalian cells had suggested two different functions, namely induction of apoptosis and inhibition of RNA interference (RNAi). Here, we demonstrate that mosquito cells persistently infected with LACV do not undergo apoptosis and mount a specific RNAi response. Recombinant viruses that either express (rLACV) or lack (rLACVdelNSs) the NSs gene similarly persisted and were prone to the RNAi-mediated resistance to superinfection. Furthermore, in mosquito cells overexpressed LACV NSs was unable to inhibit RNAi against Semliki Forest virus. In mammalian cells, however, the rLACVdelNSs mutant virus strongly activated the antiviral type I interferon (IFN) system, whereas rLACV as well as overexpressed NSs suppressed IFN induction. Consequently, rLACVdelNSs was attenuated in IFN-competent mouse embryo fibroblasts and animals but not in systems lacking the type I IFN receptor. In situ analyses of mouse brains demonstrated that wild-type and mutant LACV mainly infect neuronal cells and that NSs is able to suppress IFN induction in the central nervous system. Thus, our data suggest little relevance of the NSs-induced apoptosis or RNAi inhibition for growth or pathogenesis of LACV in the mammalian host and indicate that NSs has no function in the insect vector. Since deletion of the viral NSs gene can be fully complemented by inactivation of the host's IFN system, we propose that the major biological function of NSs is suppression of the mammalian innate immune response.

  5. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  6. Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

    Science.gov (United States)

    Guthrie, O'neil W

    2017-10-01

    In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Some effects of lead at mammalian neuromuscular junction

    Energy Technology Data Exchange (ETDEWEB)

    Pickett, J.B.; Bornstein, J.C.

    1984-03-01

    The effect of lead on transmitter release was investigated in a rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode techniques. Lead reduced the number of quanta released by a nerve stimulus (m) in a dose-dependent fashion. As extracellular Ca/sup 2 +/ concentration ((Ca/sup 2 +/)/sub 0/) was varied in the absence of lead, a linear relationship between ln(m) and ln((Ca/sup 2 +/)/sub 0/) was obtained. Lead shifted the relationship between ln(m) and ln((Ca/sup 2 +/)/sub 0/) to the right without altering the slope. This suggested lead competed with Ca/sup 2 +/, which was confirmed by using a modified Lineweaver-Burk plot. Lead inhibits Ca/sup 2 +/ entry into frog sympathetic preganglionic nerve terminals, and a similar mechanism may underlie this present finding; such a mechanism, however, could not explain all the observed actions of lead. Lead increased the frequency of spontaneous quantal release in a dose-dependent manner, and 10/sup -4/ M lead doubled the magnitude of facilitation of evoked release seen with five stimuli at 60 Hz. It is suggested that these effects result from inhibition of some, or all, of the nerve terminal's Ca/sup 2 +/ sequestration mechanisms.

  8. Neuromuscular diseases: Diagnosis and management.

    Science.gov (United States)

    Mary, P; Servais, L; Vialle, R

    2018-02-01

    Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the

  9. MRI in neuromuscular disorders

    International Nuclear Information System (INIS)

    Fischmann, Arne

    2014-01-01

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  10. Influence of psychoemotional stress on the functional state of the neuromuscular system and the efficiency of sensorimotor activity of highly skilled athletes

    Directory of Open Access Journals (Sweden)

    Svitlana Fedorchuk

    2017-08-01

    Full Text Available Purpose: assessment of the influence of the level of psychoemotional stress and the effectiveness of mental self-regulation on the functional state of the neuromuscular system and the effectiveness of the sensorimotor activity of highly skilled athletes specializing in complex co-ordination sports (on the example of diving. Material & Methods: study involved 14 high-class athletes (master of sport, international master of sport, honored master of sports at the age of 15–30 years. To determine the psychophysiological properties of the nervous system of athletes, the diagnostic complex "Diagnost-1" are used. Electroneuromyography was performed on the neurodiagnostic complex "Nicolet Viking Select". For a differentiated assessment of the level of stress, the emotional state of the respondents and also for assessing the effectiveness of mental self-regulation, a technique to select colors was used. Result: interrelation between the effectiveness of mental self-regulation and adaptability, the intensity of existing stress, emotional stability and vegetative balance with electroneuromyographic characteristics, strength and functional mobility of nervous processes, the accuracy of reaction to a moving object and the ratio of the reactions of lead and lag, the efficiency of sensorimotor activity are identified. Conclusion: revealed interrelation of the effectiveness of mental self-regulation and adaptability, intensity of existing stress, emotional stability and vegetative balance with typological properties of the higher parts of the central nervous system and electroneuromyographic characteristics of athletes can have prognostic value and be used to optimize the sports development of promising young people.

  11. Morphology of the bryozoan Cinctipora elegans (Cyclostomata, Cinctiporidae) with first data on its sexual reproduction and the cyclostome neuro-muscular system.

    Science.gov (United States)

    Schwaha, Thomas F; Handschuh, Stephan; Ostrovsky, Andrew N; Wanninger, Andreas

    2018-06-14

    Cyclostome bryozoans are an ancient group of marine colonial suspension-feeders comprising approximately 700 extant species. Previous morphological studies are mainly restricted to skeletal characters whereas data on soft tissues obtained by state-of-the-art methods are still lacking. In order to contribute to issues related to cyclostome ground pattern reconstruction, we analyzed the morphology of the neuromuscular system Cinctipora elegans by means of immunocytochemical staining, confocal laser scanning microscopy, histological sections and microCT imaging. Polypides of C. elegans are located in elongated tubular skeletal cystids. Distally, the orifice leads into a prominent vestibulum which is lined by an epithelium that joins an almost complete perimetrical attachment organ, both containing radially arranged neurite bundles and muscles. Centrally, the prominent atrial sphincter separates the vestibulum from the atrium. The latter is enclosed by the tentacle sheath which contains few longitudinal muscle fibers and two principal neurite bundles. These emerge from the cerebral ganglion, which is located at the lophophoral base. Lateral ganglia are located next to the cerebral ganglion from which the visceral neurite bundles emerge that extend proximally towards the foregut. There are four tentacle neurite bundles that emerge from the ganglia and the circum-oral nerve ring, which encompasses the pharynx. The tentacles possess two striated longitudinal muscles. Short buccal dilatators are situated at the lophophoral base and short muscular sets are present at the abfrontal and frontal side of the tentacle base. The pharynx is myoepithelial and triradiate in cross-section. Oocytes are found inside the pharyngeal myoepithelium. The digestive tract contains dense circular musculature and few longitudinal muscles. The membranous sac contains regular, thin, circular and diagonal muscles and neurites in its epithelial lining. The general structure of the neuro-muscular

  12. Comparison of isometric cervical flexor and isometric cervical extensor system exercises on patients with neuromuscular imbalance and cervical crossed syndrome associated forward head posture.

    Science.gov (United States)

    Lee, Jaejin; Kim, Dohyeon; Yu, Kyunghoon; Cho, Youngki; You, Joshua H

    2018-01-01

    Isometric cervical flexor system exercise (ICF) and isometric cervical extensor system exercise (ICE) are cervical stabilization techniques that have been used to restore cervical crossed syndrome (CCS)-associated forward head posture. However, the therapeutic effects and underlying motor control mechanisms remain elusive. The purpose of present study was investigating the concurrent therapeutic effects of ICF and ICE on muscle size, muscle imbalance ratio, and muscle recruitment sequence using ultrasound imaging and electromyography. A total of 18 participants (7 females; age=24±4.0 years) with CCS associated with forward head posture underwent ICF and ICE. Paired t-test analysis was used for statistical analysis. Paired t-test analysis showed that sternocleidomastoid thickness was greater during ICF than ICE. Similarly, cross-sectional area and horizontal thickness of the longus colli were greater during ICE than ICF. The upper trapezius/lower trapezius muscle imbalance ratio and the pectoralis major/lower trapezius muscle imbalance ratio were significantly decreased during the application of ICE compared to ICF. These results provide compelling, mechanistic evidence as to how ICE is more beneficial for the restoration of neuromuscular imbalance than ICF in individuals with CCS.

  13. FUNCTIONS OF A NEUROMUSCULAR CENTRE

    Directory of Open Access Journals (Sweden)

    Janez Zidar

    2004-12-01

    Full Text Available Main functions of a neuromuscular (NM centre are making diagnosis, treatment and counselling. Some other functions, e. g. forming a register and epidemiological endeavours, could be added. All these activities are expected to be achieved by multidisciplinary approach with the idea that members use the same guidelines and share the same knowledge.NM diseases affect lower levels of the nervous system that is motor units (motor cells in the brainstem and spinal cord, nerve roots, cranial and peripheral nerves, neuromuscular junction, and muscles. There are many such diseases; a few are more common others are rare.Rational approach in making a diagnosis can be divided into several steps. The process begins with a person with clinical symptoms and signs which raise the suspicion of NM disease. The first step is the description of the predominant pattern of muscular wasting and weakness (e. g. limb-girdle, distal, ocular, facio-scapulo-humeral. Each of these syndromes require a differential diagnosis within the motor unit territory what is achieved by means of EMG and muscle biopsy. The latter is even more important to define the nature of the abnormality. Disease nature can also be determined biochemically and, as NM disorders are commonly genetically determined, at the molecular genetic level. Treatment modalities include drugs (causative and symptomatic and other measures such as promoting and maintaining good general health, preventing skeletal deformities, physiotherapy, orthoses, surgery, and prevention of respiratory and cardiac functions. Counselling is mainly by social workers that focus on the practical aspects of coping with illness and disability and by genetic counsellors who gave advise on family planning.

  14. From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes.

    Science.gov (United States)

    Corcoran, Callan C; Grady, Cameron R; Pisitkun, Trairak; Parulekar, Jaya; Knepper, Mark A

    2017-03-01

    The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database ( https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to the area of kidney physiology. In so doing, we have created an additional database ( Database of Metabolic Enzymes in Kidney Tubule Segments: https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/), mapping mRNA abundance measurements (mined from RNA-Seq studies) for all metabolic enzymes to each of 14 renal tubule segments. We carry out bioinformatics analysis of the enzyme expression pattern among renal tubule segments and mine various data sources to identify vasopressin-regulated metabolic enzymes in the renal collecting duct. Copyright © 2017 the American Physiological Society.

  15. Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial

    Directory of Open Access Journals (Sweden)

    Giannasi Lilian

    2012-05-01

    Full Text Available Abstract Background Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP, given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm and LED (= 660 nm irradiation in CP patients. Methods/design 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. Discussion This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. Trial registration The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS Descriptors Cerebral Palsy

  16. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  17. Mammalian development in space

    Science.gov (United States)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  18. Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

    Directory of Open Access Journals (Sweden)

    Martin Johnsson

    2015-05-01

    Full Text Available Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL and expression QTL (eQTL mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

  19. A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation.

    Science.gov (United States)

    Kumar, Deepesh; Das, Abhijit; Lahiri, Uttama; Dutta, Anirban

    2016-04-12

    A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

  20. A validated system for ligation-free USER™ -based assembly of expression vectors for mammalian cell engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Hansen, Bjarne Gram

    The development in the field of mammalian cell factories require fast and high-throughput methods, this means a high need for simpler and more efficient cloning techniques. For optimization of protein expression by genetic engineering and for allowing metabolic engineering in mammalian cells, a new...

  1. Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Kimberly R Hagel

    Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

  2. Neuromuscular ultrasound of cranial nerves.

    Science.gov (United States)

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  3. Functions of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, in neuromuscular system and other somatic organs.

    Science.gov (United States)

    Yamamoto, Tomoko; Shibata, Noriyuki; Saito, Yoshiaki; Osawa, Makiko; Kobayashi, Makio

    2010-06-01

    Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disease, exhibiting muscular dystrophy, and central nervous system (CNS) and ocular malformations. It is included in alpha-dystroglycanopathy, a group of muscular dystrophy showing reduced glycosylation of alpha-dystroglycan. alpha-Dystroglycan is one of the components of dystrophin-glycoprotein complex linking extracellular and intracellular proteins. The sugar chains of alpha-dystroglycan are receptors for extracellular matrix proteins such as laminin. Fukutin, a gene responsible for FCMD, is presumably related to the glycosylation of alpha-dystroglycan like other causative genes of alpha-dystroglycanopathy. The CNS lesion of FCMD is characterized by cobblestone lissencephaly, associated with decreased glycosylation of alpha-dystroglycan in the glia limitans where the basement membrane is formed. Astrocytes whose endfeet form the glia limitans seem to be greatly involved in the genesis of the CNS lesion. Fukutin is probably necessary for astrocytic function. Other components of the CNS may also need fukutin, such as migration and synaptic function in neurons. However, roles of fukutin in oligodendroglia, microglia, leptomeninges and capillaries are unknown at present. Fukutin is expressed in various somatic organs as well, and appears to work differently between epithelial cells and astrocytes. In the molecular level, since the dystrophin-glycoprotein complex is linked to cell signaling pathways involving c-src and c-jun, fukutin may be able to affect cell proliferation/survival. Fukutin was localized in the nucleus on cancer cell lines. With the consideration that mutations of fukutin give rise to wide spectrum of the clinical phenotype, more unknown functions of fukutin besides the glycosylation of alpha-dystroglycan can be suggested. Trials for novel treatments including gene therapy are in progress in muscular dystrophies. Toward effective therapies with minimal side effects, precise

  4. Applications of CRISPR/Cas9 in the Mammalian Central Nervous System.

    Science.gov (United States)

    Savell, Katherine E; Day, Jeremy J

    2017-12-01

    Within the central nervous system, gene regulatory mechanisms are crucial regulators of cellular development and function, and dysregulation of these systems is commonly observed in major neuropsychiatric and neurological disorders. However, due to a lack of tools to specifically modulate the genome and epigenome in the central nervous system, many molecular and genetic mechanisms underlying cognitive function and behavior are still unknown. Although genome editing tools have been around for decades, the recent emergence of inexpensive, straightforward, and widely accessible CRISPR/Cas9 systems has led to a revolution in gene editing. The development of the catalytically dead Cas9 (dCas9) expanded this flexibility even further by acting as an anchoring system for fused effector proteins, structural scaffolds, and RNAs. Together, these advances have enabled robust, modular approaches for specific targeting and modification of the local chromatin environment at a single gene. This review highlights these advancements and how the combination of powerful modulatory tools paired with the versatility of CRISPR-Cas9-based systems offer great potential for understanding the underlying genetic and epigenetic contributions of neuronal function, behavior, and neurobiological diseases.

  5. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F.; Wevers, C. W.; Wintzen, A. R.; Busch, H. F.; Höweler, C. J.; de Jager, A. E.; Padberg, G. W.; de Visser, M.; Wokke, J. H.

    1997-01-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  6. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F; Wevers, CWJ; Wintzen, AR; Busch, HFM; Howeler, CJ; deJager, AEJ; Padberg, GW; deVisser, M; Wokke, JHJ

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  7. Palliative care in neuromuscular diseases

    NARCIS (Netherlands)

    de Visser, Marianne; Oliver, David J.

    2017-01-01

    Purpose of review Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness. Neuromuscular disorders (NMDs) are characterized by progressive muscle weakness, leading to pronounced and incapacitating

  8. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model

    Science.gov (United States)

    Martin, François-Pierre J; Dumas, Marc-Emmanuel; Wang, Yulan; Legido-Quigley, Cristina; Yap, Ivan K S; Tang, Huiru; Zirah, Séverine; Murphy, Gerard M; Cloarec, Olivier; Lindon, John C; Sprenger, Norbert; Fay, Laurent B; Kochhar, Sunil; van Bladeren, Peter; Holmes, Elaine; Nicholson, Jeremy K

    2007-01-01

    Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography–mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level. PMID:17515922

  9. Contrast enhanced micro-computed tomography resolves the 3-dimensional morphology of the cardiac conduction system in mammalian hearts.

    Directory of Open Access Journals (Sweden)

    Robert S Stephenson

    Full Text Available The general anatomy of the cardiac conduction system (CCS has been known for 100 years, but its complex and irregular three-dimensional (3D geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I(2KI, we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart.

  10. Modeling industrial centrifugation of mammalian cell culture using a capillary based scale-down system.

    Science.gov (United States)

    Westoby, Matthew; Rogers, Jameson K; Haverstock, Ryan; Romero, Jonathan; Pieracci, John

    2011-05-01

    Continuous-flow centrifugation is widely utilized as the primary clarification step in the recovery of biopharmaceuticals from cell culture. However, it is a challenging operation to develop and characterize due to the lack of easy to use, small-scale, systems that can be used to model industrial processes. As a result, pilot-scale continuous centrifugation is typically employed to model large-scale systems requiring a significant amount of resources. In an effort to reduce resource requirements and create a system which is easy to construct and utilize, a capillary shear device, capable of producing energy dissipation rates equivalent to those present in the feed zones of industrial disk stack centrifuges, was developed and evaluated. When coupled to a bench-top, batch centrifuge, the capillary device reduced centrate turbidity prediction error from 37% to 4% compared to using a bench-top centrifuge alone. Laboratory-scale parameters that are analogous to those routinely varied during industrial-scale continuous centrifugation were identified and evaluated for their utility in emulating disk stack centrifuge performance. The resulting relationships enable bench-scale process modeling of continuous disk stack centrifuges using an easily constructed, scalable, capillary shear device coupled to a typical bench-top centrifuge. Copyright © 2010 Wiley Periodicals, Inc.

  11. Designing 3-Dimensional In Vitro Oviduct Culture Systems to Study Mammalian Fertilization and Embryo Production.

    Science.gov (United States)

    Ferraz, Marcia A M M; Henning, Heiko H W; Stout, Tom A E; Vos, Peter L A M; Gadella, Bart M

    2017-07-01

    The oviduct was long considered a largely passive conduit for gametes and embryos. However, an increasing number of studies into oviduct physiology have demonstrated that it specifically and significantly influences gamete interaction, fertilization and early embryo development. While oviduct epithelial cell (OEC) function has been examined during maintenance in conventional tissue culture dishes, cells seeded into these two-dimensional (2-D) conditions suffer a rapid loss of differentiated OEC characteristics, such as ciliation and secretory activity. Recently, three-dimensional (3-D) cell culture systems have been developed that make use of cell inserts to create basolateral and apical medium compartments with a confluent epithelial cell layer at the interface. Using such 3-D culture systems, OECs can be triggered to redevelop typical differentiated cell properties and levels of tissue organization can be developed that are not possible in a 2-D culture. 3-D culture systems can be further refined using new micro-engineering techniques (including microfluidics and 3-D printing) which can be used to produce 'organs-on-chips', i.e. live 3-D cultures that bio-mimic the oviduct. In this review, concepts for designing bio-mimic 3-D oviduct cultures are presented. The increased possibilities and concomitant challenges when trying to more closely investigate oviduct physiology, gamete activation, fertilization and embryo production are discussed.

  12. High energy fast neutrons from the Harwell variable energy cyclotron. II. Biologic studies in mammalian systems

    International Nuclear Information System (INIS)

    Berry, R.J.; Bance, D.A.; Barnes, D.W.H.; Cox, R.; Goodhead, D.T.; Sansom, J.M.; Thacker, J.

    1977-01-01

    A high energy fast neutron beam potentially suitable for radiotherapy has been described in a companion paper. Its biologic effects have been studied in the following experimental systems: clonal survival and mutation induction after irradiation in vitro in Chinese hamster cells and human diploid fibroblasts; survival of reproductive capacity in vivo of murine hemopoietic colony-forming cells and murine intestinal crypts after irradiation in vivo; survival of reproductive capacity in vivo after irradiation in vitro or in vivo of murine lymphocytic leukemia cells; acute intestinal death following total body irradiation of mice and guinea pigs; and hemopoietic death following total body irradiation of mice and guinea pigs. The relative biologic effectiveness of these high energy neutrons varied among the different biologic systems, and in several cases varied with the size of the radiation dose. The oxygen enhancement ratio was studied in murine lymphocytic leukemia cells irradiated under aerobic or hypoxic conditions in vitro and assayed for survival of reproductive capacity in vivo. Compared with x-rays, the potential therapeutic gain factor for these neutrons was about 1.5. This work represents a ''radiobiologic calibration'' program which it is suggested should be undertaken before new and unknown fast neutron spectra are used for experimental radiotherapy. The results are compared with biologic studies carried out at high energy fast neutron generators in the United States

  13. Quantitative autoradiographic characterization of GA-BAB receptors in mammalian central nervous system

    International Nuclear Information System (INIS)

    Chu, D.Chin-Mei.

    1989-01-01

    The inhibitory effects of the amino acid neurotransmitter γ-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA A and GABA B receptors. A quantitative autoradiographic method with 3 H-GABA was developed to examine the hypotheses that GABA A and GABA B sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA B receptors occur in fewer numbers and have a lower affinity for GABA than GABA A receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA B receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA B and GABA A receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA B receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons

  14. Transcriptomics as a tool for assessing the scalability of mammalian cell perfusion systems.

    Science.gov (United States)

    Jayapal, Karthik P; Goudar, Chetan T

    2014-01-01

    realized in due course when richer genomic data become available. By taking a pragmatic approach of transcriptome fingerprinting, we have demonstrated the utility of systems biology to support the comparability of laboratory and manufacturing-scale perfusion systems. Scale-down model qualification is the first step in process characterization and hence is an integral component of robust regulatory filings. Augmenting the current paradigm, which relies primarily on cell culture and product quality information, with gene expression data can help make a substantially stronger case for similarity. With continued advances in systems biology approaches, we expect them to be seamlessly integrated into bioprocess development, which can translate into more robust and high yielding processes that can ultimately reduce cost of care for patients.

  15. Cellular localization of Na(+), K(+)-ATPase in the mammalian vestibular system

    Science.gov (United States)

    Kerr, T. P.

    1984-01-01

    Two different, but complementary, procedures for cellular localization of Na+, K+-ATPase in the guinea pig vestibular system were employed. One of these techniques, devised by Stirling, depends upon the well documented ability of the specific inhibitor ouabain to bind selectively to Na+,K+-ATPase, blocking catalytic activity. Microdisected vestibular tissues are incubated with tritium-labelled (3H-) ouabain, and regions with a high concentration of Na+,K+-ATPase are subsequently identified by light microscope autoradiography. A second method, originated by Ernst, detects inorganic phosphate released from an artificial substrate (nitrophenyl phosphate) by catalytic activity of the enzyme. In the presence of strontium ion, phosphate is precipitated near regions of high activity, then converted to a product which may finally be visualized in the electron microscope. This cytochemical enzymatic reaction is inhibited by ouabain.

  16. Neuromuscular Manifestations of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    A. Arturo eLeis

    2012-03-01

    Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

  17. NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation

    International Nuclear Information System (INIS)

    Richards, T.

    1984-09-01

    NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent using a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures

  18. NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation

    Energy Technology Data Exchange (ETDEWEB)

    Richards, T.

    1984-09-01

    NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent using a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures.

  19. Elucidating the Role of Injury-Induced Electric Fields (EFs in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Matthew L Baer

    Full Text Available Injury to the vertebrate central nervous system (CNS induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  20. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Science.gov (United States)

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  1. Effectiveness of Neuromuscular Training Based on the Neuromuscular Risk Profile.

    Science.gov (United States)

    Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

    2017-07-01

    The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Controlled laboratory study. Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

  2. Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

    Science.gov (United States)

    O'Connor, Joanne; McCaughan, Dorothy; McDaid, Catriona; Booth, Alison; Fayter, Debra; Rodriguez-Lopez, Roccio; Bowers, Roy; Dyson, Lisa; Iglesias, Cynthia P; Lalor, Simon; O'Connor, Rory J; Phillips, Margaret; Ramdharry, Gita

    2016-07-01

    Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs). To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs. Qualitative study of views of orthoses users - a qualitative in-depth interview study was undertaken. Data were analysed for thematic content. A coding scheme was developed and an inductive approach was used to identify themes. Systematic review - 18 databases were searched up to November 2014: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health, EMBASE, PASCAL, Scopus, Science Citation Index, BIOSIS Previews, Physiotherapy Evidence Database, Recal Legacy, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Cochrane Central Register of Controlled Trials, Conference Proceedings Citation Index: Science, Health Management Consortium, ClinicalTrials.gov, International Clinical Trials Registry Platform and National Technical Information Service. Studies of adults using an orthosis for instability of the knee related to NMD or a CNS disorder were included. Data were extracted and quality was assessed by two researchers. Narrative synthesis was undertaken. Survey and costing analysis - a web survey of orthotists, physiotherapists and rehabilitation medicine physicians was undertaken. Telephone interviews with orthotists informed a costing analysis. Qualitative study - a total of 24 people participated. Potential for engagement in daily activities was of vital importance to patients; the extent to which their device enabled this was the yardstick by which it was measured. Patients' prime desired outcome was a reduction in pain, falls or trips, with improved balance and stability. Effectiveness

  3. A comprehensive complex systems approach to the study and analysis of mammalian cell cycle control system in the presence of DNA damage stress.

    Science.gov (United States)

    Abroudi, Ali; Samarasinghe, Sandhya; Kulasiri, Don

    2017-09-21

    Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other. This retains the functionality of the system and provides a clearer interpretation to the processes within it while reducing the complexity in comprehending these processes. To achieve this, we first update a published ODE mathematical model of cell cycle with current knowledge. Then the part of the mathematical model relevant to each sub-system is shown separately in conjunction with a diagram of the sub-system as part of this representation. The model sub-systems are Growth Factor, DNA damage, G1-S, and G2-M checkpoint signalling. To further simplify the model and better explore the function of sub-systems, they are further divided into modules. Here we also add important new modules of: chk-related rapid cell cycle arrest, p53 modules expanded to seamlessly integrate with the rapid arrest module, Tyrosine phosphatase modules that activate Cyc_Cdk complexes and play a crucial role in rapid and delay arrest at both G1-S and G2-M, Tyrosine Kinase module that is important for inactivating nuclear transport of CycB_cdk1 through Wee1 to resist M phase entry, Plk1-Related module that is crucial in activating Tyrosine phosphatases and inactivating Tyrosine kinase, and APC-Related module to show steps in CycB degradation. This multi-level systems approach incorporating all known aspects of cell cycle allowed us to (i) study, through dynamic simulation of an ODE model

  4. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

    Directory of Open Access Journals (Sweden)

    Philipp eHohenbrink

    2014-09-01

    Full Text Available The vomeronasal organ (VNO is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR genes comprise two families of chemosensory genes (V1R and V2R that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus, the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97% of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

  5. MXS-Chaining: A Highly Efficient Cloning Platform for Imaging and Flow Cytometry Approaches in Mammalian Systems.

    Directory of Open Access Journals (Sweden)

    Hanna L Sladitschek

    Full Text Available The continuous improvement of imaging technologies has driven the development of sophisticated reporters to monitor biological processes. Such constructs should ideally be assembled in a flexible enough way to allow for their optimization. Here we describe a highly reliable cloning method to efficiently assemble constructs for imaging or flow cytometry applications in mammalian cell culture systems. We bioinformatically identified a list of restriction enzymes whose sites are rarely found in human and mouse cDNA libraries. From the best candidates, we chose an enzyme combination (MluI, XhoI and SalI: MXS that enables iterative chaining of individual building blocks. The ligation scar resulting from the compatible XhoI- and SalI-sticky ends can be translated and hence enables easy in-frame cloning of coding sequences. The robustness of the MXS-chaining approach was validated by assembling constructs up to 20 kb long and comprising up to 34 individual building blocks. By assessing the success rate of 400 ligation reactions, we determined cloning efficiency to be 90% on average. Large polycistronic constructs for single-cell imaging or flow cytometry applications were generated to demonstrate the versatility of the MXS-chaining approach. We devised several constructs that fluorescently label subcellular structures, an adapted version of FUCCI (fluorescent, ubiquitination-based cell cycle indicator optimized to visualize cell cycle progression in mouse embryonic stem cells and an array of artificial promoters enabling dosage of doxycyline-inducible transgene expression. We made publicly available through the Addgene repository a comprehensive set of MXS-building blocks comprising custom vectors, a set of fluorescent proteins, constitutive promoters, polyadenylation signals, selection cassettes and tools for inducible gene expression. Finally, detailed guidelines describe how to chain together prebuilt MXS-building blocks and how to generate new

  6. [Respiratory treatments in neuromuscular disease].

    Science.gov (United States)

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  7. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  8. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  9. Identification and Simulation as Tools for Measurement of Neuromuscular Properties

    National Research Council Canada - National Science Library

    Kearney, R

    2001-01-01

    Quantitative, objective methods for the evaluation of neuromuscular properties are required for the diagnosis of neuromuscular disorders and the evaluation of the effectiveness of treatment and rehabilitation...

  10. Neuromuscular Bandage: Neurophysiological Effects and the Role of Fascias

    Directory of Open Access Journals (Sweden)

    Ximena María Villota Chicaíza

    2014-05-01

    Full Text Available During the last years, neuromuscular bandage, a therapeutic application created in 1979 by doctor Kenzo Kase has been introduced in the management of many disorders of the musculo-skeletal system and even more so in the treatment of neurological disorders; This therapeutic tool which consists of a self adhesive elastic bandage allows recovery of the injured party without diminishing its bodily function. According to the existing literature on the physiological effects of this therapeutic application in the body, you could say that there is consensus. However in this article the author wants to highlight the significant although little highlighted role played by the fas¬cias on the therapeutic effects of neuromuscular bandage, analyzing from a reflective perspective the analgesic, neuromechanical and circulatory effects, as fundamental effects of neuromuscular bandage and fascias in the same function, trying to bring a global understanding on the way they relate to all connective tissues, aspects that are of great importance for the proper evaluation of alterations and prescription of neuromuscular bandage

  11. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  12. BIOLOGY OF SOME NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Gerta Vrbova

    2004-12-01

    Full Text Available In order to understand and possibly interfere/ treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. We illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1 Duchenne muscular dystrophy (DMD, and 2 Spinal muscular atrophy (SMA.DMD is an x-linked hereditary muscle disease that leads to progressive muscle weakness. The altered gene in DMD affects dystrophin, a muscle membrane associated proteine. Attempts were made to replace the deficient or missing gene/ protein into muscles of Duchenne children. Two main strategies were explored: 1 Myoblast and stem cell transfer and 2 Gene delivery. The possible use of methods other than the introduction of the missing gene for dystrophin into muscle fibres are based on the knowledge about the adaptive potential of muscle to different functional demands and the ability of the muscle to express a new set of genes in response to such stimuli. Stretch or overload is now known to lead to changes of gene expression in normal muscle, and the success of muscle stretch in the management of Duchenne boys is most likely to be due to such adaptive changes. Electrical stimulation of muscles is also a powerful stimulus for inducing the expression of new genes and this method too has produced beneficial effects on the progress of the disease in mice and men.SMA is a heterogeneous group of hereditary neuromuscular disorders where the loss of lower motoneurones leads to progressive weakness and muscle atrophy. The disease subdivides into 3 forms according to the severity of the symptoms and age of onset. All three forms of SMA have been mapped to chromosome 5q11.2-13.2. Clinical features of all these forms of SMA include hypotonia shortly after birth, symmetrical muscle weakness and atrophy, finger tremor, areflexia or hyporeflexia and later contractures. In patients with SMA 1 and 2 the development of all parts of the motor

  13. Neuromuscular Control and Coordination during Cycling

    Science.gov (United States)

    Li, Li

    2004-01-01

    The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

  14. Kinship and interaction in neuromuscular pharmacology

    NARCIS (Netherlands)

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  15. Report on Adaptive Force, a specific neuromuscular function

    Directory of Open Access Journals (Sweden)

    Marko Hoff

    2015-08-01

    Full Text Available In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1 What is the peculiarity of this neuromuscular function, introduced as AF? 2 Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3 It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects’ option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso, the maximal isometric Adaptive Force (AFisomax and the maximal eccentric Adaptive Force (AFeccmax. Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities.

  16. Lactococcus lactis is an Efficient Expression System for Mammalian Membrane Proteins Involved in Liver Detoxification, CYP3A4, and MGST1.

    Science.gov (United States)

    Bakari, Sana; Lembrouk, Mehdi; Sourd, Laura; Ousalem, Fares; André, François; Orlowski, Stéphane; Delaforge, Marcel; Frelet-Barrand, Annie

    2016-04-01

    Despite the great importance of human membrane proteins involved in detoxification mechanisms, their wide use for biochemical approaches is still hampered by several technical difficulties considering eukaryotic protein expression in order to obtain the large amounts of protein required for functional and/or structural studies. Lactococcus lactis has emerged recently as an alternative heterologous expression system to Escherichia coli for proteins that are difficult to express. The aim of this work was to check its ability to express mammalian membrane proteins involved in liver detoxification, i.e., CYP3A4 and two isoforms of MGST1 (rat and human). Genes were cloned using two different strategies, i.e., classical or Gateway-compatible cloning, and we checked the possible influence of two affinity tags (6×-His-tag and Strep-tag II). Interestingly, all proteins could be successfully expressed in L. lactis at higher yields than those previously obtained for these proteins with classical expression systems (E. coli, Saccharomyces cerevisiae) or those of other eukaryotic membrane proteins expressed in L. lactis. In addition, rMGST1 was fairly active after expression in L. lactis. This study highlights L. lactis as an attractive system for efficient expression of mammalian detoxification membrane proteins at levels compatible with further functional and structural studies.

  17. A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.

    Directory of Open Access Journals (Sweden)

    Melissa J Caimano

    2014-03-01

    Full Text Available Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil's disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of "core" housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host

  18. Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

    Science.gov (United States)

    Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

    2018-01-15

    Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  20. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

    DEFF Research Database (Denmark)

    Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

    2017-01-01

    INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys...

  1. Neuromuscular deficits after peripheral joint injury: a neurophysiological hypothesis.

    Science.gov (United States)

    Ward, Sarah; Pearce, Alan J; Pietrosimone, Brian; Bennell, Kim; Clark, Ross; Bryant, Adam L

    2015-03-01

    In addition to biomechanical disturbances, peripheral joint injuries (PJIs) can also result in chronic neuromuscular alterations due in part to loss of mechanoreceptor-mediated afferent feedback. An emerging perspective is that PJI should be viewed as a neurophysiological dysfunction, not simply a local injury. Neurophysiological and neuroimaging studies have provided some evidence for central nervous system (CNS) reorganization at both the cortical and spinal levels after PJI. The novel hypothesis proposed is that CNS reorganization is the underlying mechanism for persisting neuromuscular deficits after injury, particularly muscle weakness. There is a lack of direct evidence to support this hypothesis, but future studies utilizing force-matching tasks with superimposed transcranial magnetic stimulation may be help clarify this notion. © 2014 Wiley Periodicals, Inc.

  2. Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

    Science.gov (United States)

    Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

    1999-06-01

    Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

  3. Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake.

    Directory of Open Access Journals (Sweden)

    Lieming Bao

    Full Text Available Polychlorinated biphenyls (PCBs are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs using the mammalian pregnane X receptor (PXR. In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL-PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants.

  4. Neuromuscular control of prey capture in frogs.

    OpenAIRE

    Nishikawa, K C

    1999-01-01

    While retaining a feeding apparatus that is surprisingly conservative morphologically, frogs as a group exhibit great variability in the biomechanics of tongue protraction during prey capture, which in turn is related to differences in neuromuscular control. In this paper, I address the following three questions. (1) How do frog tongues differ biomechanically? (2) What anatomical and physiological differences are responsible? (3) How is biomechanics related to mechanisms of neuromuscular cont...

  5. Development and aging of the Kisspeptin-GPR54 system in the mammalian brain: what are the impacts on female reproductive function?

    Directory of Open Access Journals (Sweden)

    Isabelle eFranceschini

    2013-03-01

    Full Text Available The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mammalian species including humans. Kisspeptins are very potent GnRH secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus (ARC. Within the last two years a substantial amount of data has accumulated concerning the development of these neuronal populations and their timely regulation by central and peripheral factors during fetal, neonatal and peripubertal stages of development. This review focuses on the development of the Kisspeptin-GPR54 system in the brain of female mouse, rat, sheep, monkey and humans. The notion that this system represents a major target through which signals from the environment early in life can re-program reproductive function will also be discussed.

  6. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    Science.gov (United States)

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

  7. Neuromuscular blockade in the elderly patient

    Directory of Open Access Journals (Sweden)

    Lee LA

    2016-06-01

    Full Text Available Luis A Lee, Vassilis Athanassoglou, Jaideep J Pandit Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Abstract: Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids. Other drugs (atracurium, cisatracurium have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. Keywords: anesthesia, elderly, drugs, pharmacokinetics, pharmacodynamics 

  8. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    International Nuclear Information System (INIS)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-01-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen

  9. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  10. Neuromuscular dentistry: Occlusal diseases and posture.

    Science.gov (United States)

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture.

  11. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

    Science.gov (United States)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

    2017-10-06

    Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. The e

  12. Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction.

    Science.gov (United States)

    Gerasimova, E; Lebedeva, J; Yakovlev, A; Zefirov, A; Giniatullin, R; Sitdikova, G

    2015-09-10

    Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. L-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (β-cyano-L-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca(2+)) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to

  13. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Progress is reported on the following research projects: the effects of N-ethyl-maleimide and hydroxyurea on hamster cells in culture; sensitization of synchronized human cells to x rays by N-ethylmaleimide; sensitization of hypoxic mammalian cells with a sulfhydryl inhibitor; damage interaction due to ionizing and nonionizing radiation in mammalian cells; DNA damage relative to radioinduced cell killing; spurious photolability of DNA labeled with methyl- 14 C-thymidine; radioinduced malignant transformation of cultured mouse cells; a comparison of properties of uv and near uv light relative to cell function and DNA damage; Monte Carlo simulation of DNA damage and repair mechanisms; and radiobiology of fast neutrons

  14. Stem cell route to neuromuscular therapies.

    Science.gov (United States)

    Partridge, Terence A

    2003-02-01

    As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body-wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology.

  15. Intrauterine neuromuscular blockade in fetus.

    Science.gov (United States)

    Fan, S Z; Huang, F Y; Lin, S Y; Wang, Y P; Hsieh, F J

    1990-03-01

    Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/- 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method.

  16. Protein defects in neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Vainzof M.

    2003-01-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

  17. Building the mammalian testis

    DEFF Research Database (Denmark)

    Svingen, Terje; Koopman, Peter

    2013-01-01

    Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial...

  18. Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

    Science.gov (United States)

    Sloan, Paul A; Rasul, Mazhar

    2002-01-01

    We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

  19. Computed tomography (CT) in neuromuscular disorders

    International Nuclear Information System (INIS)

    Novak, M.; Ambler, Z.

    1997-01-01

    For 24 patients with confirmed neuromuscular disorders, the clinical picture of the disease was complemented with CT examination. It is concluded, in accordance with the literature, that CT has a supplementary value as regards the extent and degree of disorder of the affected muscle groups. The basic pathological picture includes muscular atrophies, dystrophies, hypertrophies, and their combinations. The CT images are non-specific for the individual neuromuscular disorders and are of minor importance in the diagnostic process. 1 tab., 7 figs., 6 refs

  20. ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions.

    Science.gov (United States)

    Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Potluri, Srilatha; Fu, Xiu-Qing; Luo, Zhen-Ge; Nagappan, Guhan; Chan, Jia Pei; Hempstead, Barbara; Son, Young-Jin; Lu, Bai

    2013-06-12

    During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo.

  1. Gene mutation, quantitative mutagenesis, and mutagen screening in mammalian cells: study with the CHO/HGPRT system

    International Nuclear Information System (INIS)

    Hsie, A.W.

    1980-01-01

    We have employed CHO cells to develop and define a set of stringent conditions for studying mutation induction to TG resistance. Several lines of evidence support the CHO/HGPRT system as a specific-locus mutational assay. The system permits quantification of mutation at the HGPRT locus induced by various physical and chemical mutagens. The quantitative nature of the system provides a basis for the study of structure-function relationships of various classes of chemical mutagens. The intra- and interlaboratory reproducibility of this system suggests its potential for screening environmental agents for mutagenic activity

  2. Homogenization of Mammalian Cells.

    Science.gov (United States)

    de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

    2015-11-02

    Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

  3. Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes.

    Science.gov (United States)

    Zech, Astrid; Klahn, Philipp; Hoeft, Jon; zu Eulenburg, Christine; Steib, Simon

    2014-02-01

    Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular training effects on functional, dynamic and static balance measures. Thirty youth (14.9 ± 3 years) field hockey athletes were randomised to an intervention or control group. The intervention included a 20-min neuromuscular warm-up program performed twice weekly for 10 weeks. Balance assessments were performed at baseline, week three, week six and post-intervention. They included the star excursion balance test (SEBT), balance error scoring system (BESS), jump-landing time to stabilization (TTS) and center of pressure (COP) sway velocity during single-leg standing. No baseline differences were found between groups in demographic data and balance measures. Adherence was at 86%. All balance measures except the medial-lateral TTS improved significantly over time (p controls (31.8 ± 22.1%). There were no significant group by time interactions in the SEBT, TTS and COP sway velocity. Neuromuscular training was effective in improving postural control in youth team athletes. However, this effect was not reflected in all balance measures suggesting that the neuromuscular training did not influence all dimensions of postural control. Further studies are needed to confirm the potential of specific warm-up programs to improve postural control.

  4. Characterization of Genomic Deletion Efficiency Mediated by Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/Cas9 Nuclease System in Mammalian Cells*♦

    Science.gov (United States)

    Canver, Matthew C.; Bauer, Daniel E.; Dass, Abhishek; Yien, Yvette Y.; Chung, Jacky; Masuda, Takeshi; Maeda, Takahiro; Paw, Barry H.; Orkin, Stuart H.

    2014-01-01

    The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 nuclease system has provided a powerful tool for genome engineering. Double strand breaks may trigger nonhomologous end joining repair, leading to frameshift mutations, or homology-directed repair using an extrachromosomal template. Alternatively, genomic deletions may be produced by a pair of double strand breaks. The efficiency of CRISPR/Cas9-mediated genomic deletions has not been systematically explored. Here, we present a methodology for the production of deletions in mammalian cells, ranging from 1.3 kb to greater than 1 Mb. We observed a high frequency of intended genomic deletions. Nondeleted alleles are nonetheless often edited with inversions or small insertion/deletions produced at CRISPR recognition sites. Deleted alleles also typically include small insertion/deletions at predicted deletion junctions. We retrieved cells with biallelic deletion at a frequency exceeding that of probabilistic expectation. We demonstrate an inverse relationship between deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a robust system to produce a spectrum of genomic deletions to allow investigation of genes and genetic elements. PMID:24907273

  5. Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells.

    Science.gov (United States)

    Canver, Matthew C; Bauer, Daniel E; Dass, Abhishek; Yien, Yvette Y; Chung, Jacky; Masuda, Takeshi; Maeda, Takahiro; Paw, Barry H; Orkin, Stuart H

    2014-08-01

    The clustered regularly interspaced short [corrected] palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 nuclease system has provided a powerful tool for genome engineering. Double strand breaks may trigger nonhomologous end joining repair, leading to frameshift mutations, or homology-directed repair using an extrachromosomal template. Alternatively, genomic deletions may be produced by a pair of double strand breaks. The efficiency of CRISPR/Cas9-mediated genomic deletions has not been systematically explored. Here, we present a methodology for the production of deletions in mammalian cells, ranging from 1.3 kb to greater than 1 Mb. We observed a high frequency of intended genomic deletions. Nondeleted alleles are nonetheless often edited with inversions or small insertion/deletions produced at CRISPR recognition sites. Deleted alleles also typically include small insertion/deletions at predicted deletion junctions. We retrieved cells with biallelic deletion at a frequency exceeding that of probabilistic expectation. We demonstrate an inverse relationship between deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a robust system to produce a spectrum of genomic deletions to allow investigation of genes and genetic elements. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Rheotaxis guides mammalian sperm

    Science.gov (United States)

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  7. Surgical manipulation of mammalian embryos in vitro.

    Science.gov (United States)

    Naruse, I; Keino, H; Taniguchi, M

    1997-04-01

    Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

  8. Sugammadex Improves Neuromuscular Function in Patients ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... aminoglycosides), history of allergy to neuromuscular blocking agents, opioids or other drugs, and alcohol and drug dependence. Patients were divided into two ... titration microcalorimetry investigated the likelihood of the formation of complexes between sugammadex and other steroidal and nonsteroidal ...

  9. Neuromuscular transmission: new concepts and agents.

    NARCIS (Netherlands)

    Boer, H.D. de

    2009-01-01

    Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

  10. Application of three-dimensional culture systems to study mammalian spermatogenesis, with an emphasis on the rhesus monkey (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mahmoud Huleihel

    2015-01-01

    Full Text Available In vitro culture of spermatogonial stem cells (SSCs has generally been performed using two-dimensional (2D culture systems; however, such cultures have not led to the development of complete spermatogenesis. It seems that 2D systems do not replicate optimal conditions of the seminiferous tubules (including those generated by the SSC niche and necessary for spermatogenesis. Recently, one of our laboratories has been able to induce proliferation and differentiation of mouse testicular germ cells to meiotic and postmeiotic stages including generation of sperm in a 3D soft agar culture system (SACS and a 3D methylcellulose culture system (MCS. It was suggested that SACS and MCS form a special 3D microenvironment that mimics germ cell niche formation in the seminiferous tubules, and thus permits mouse spermatogenesis in vitro. In this review, we (1 provide a brief overview of the differences in spermatogenesis in rodents and primates, (2 summarize data related to attempts to generate sperm in vitro, (3 report for the first time formation of colonies/clusters of cells and differentiation of meiotic (expression of CREM-1 and postmeiotic (expression of acrosin germ cells from undifferentiated spermatogonia isolated from the testis of prepubertal rhesus monkeys and cultured in SACS and MCS, and (4 indicate research needed to optimize 3D systems for in vitroprimate spermatogenesis and for possible future application to man.

  11. Numerical calculations for diffusion effects in the well-of-the-well culture system for mammalian embryos.

    Science.gov (United States)

    Matsuura, Koji

    2014-06-01

    Recent studies suggest that the microenvironment and embryo density used during embryo culture considerably affect development to the blastocyst stage. High embryo density allows for autocrine secretions to diffuse to neighbouring embryos during group culture, with a positive effect on further development. A variation of group culture is the well-of-the-well (WOW) culture system, allowing for individual identification of embryos cultured in small holes in a microdroplet. Bovine blastocyst development is higher in the WOW culture system than in conventional group culture. To compare the concentration of chemical factors between conventional and WOW culture, a model was constructed to calculate the concentration of secreted factors based on Fick's second law of diffusion using spreadsheet software. Furthermore, model was used to determine the concentration of growth factors and waste materials adjacent to the embryo periphery. The results of these calculations suggest that the highest difference in the concentration of secreted small molecules and macromolecules was at the most two- to threefold, with the concentrations reduced more and diffusion kinetics facilitated to a greater extent in the WOW culture system. The average ratio of the concentration of secreted macromolecules (10nm diameter) around the embryos was also compared between systems with well widths of 0.1 and 0.3mm. The concentration of secreted materials surrounding embryos increased in a narrow tapered well. The findings suggest that the WOW culture system is better than conventional group culture because of the increased final concentration of autocrine factors and higher diffusion kinetics of waste materials.

  12. From Fertilisation to Implantation in Mammalian Pregnancy—Modulation of Early Human Reproduction by the Endocannabinoid System

    Directory of Open Access Journals (Sweden)

    Justin C. Konje

    2010-09-01

    Full Text Available There is an increasing recognition that the endocannabinoid system is the crucial cytokine-hormone system regulating early human pregnancy. The synchronous development of the fertilized embryo and the endometrium to ensure timely implantation has been shown to be one of the pivotal steps to successful implantation. This development is thought to be regulated by a finely balanced relationship between various components of the endocannabinoid system in the endometrium, the embryo and the Fallopian tube. In addition, this system has also been shown to be involved in the regulation of the development and maturation of the gametes prior to fertilization. In this review, we will examine the evidence from animal and human studies to support the role of the endocannabinoid system in gametogenesis, fertilization, implantation, early pregnancy maintenance, and in immunomodulation of pregnancy. We will discuss the role of the cannabinoid receptors and the enzymes involved in the synthesis and degradation of the key endocannabinoid ligands (e.g., anandamide and 2-arachinoylglycerol in early reproduction.

  13. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

    Directory of Open Access Journals (Sweden)

    Dolores L. Guzmán-Herrador

    2017-08-01

    Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  14. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [{sup 18}F]F-PEB

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shil [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: shailendra_patel@merck.com; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E. [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2007-11-15

    Binding of [{sup 18}F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([{sup 18}F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K{sub D}=0.1-0.15 nM, n{>=}3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [{sup 18}F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B{sub max}) measured using [{sup 18}F]F-PEB followed the rank order cortex{approx}caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B{sub max} being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [{sup 18}F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex{approx}caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum

  15. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB

    International Nuclear Information System (INIS)

    Patel, Shil; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E.

    2007-01-01

    Binding of [ 18 F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([ 18 F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K D =0.1-0.15 nM, n≥3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [ 18 F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B max ) measured using [ 18 F]F-PEB followed the rank order cortex∼caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B max being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [ 18 F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex∼caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum) from all three species confirmed previous in vivo

  16. Comparison of in vitro test systems using bacterial and mammalian cells for genotoxicity assessment within the "health-related indication value (HRIV) concept.

    Science.gov (United States)

    Prantl, Eva-Maria; Kramer, Meike; Schmidt, Carsten K; Knauer, Martina; Gartiser, Stefan; Shuliakevich, Aliaksandra; Milas, Julia; Glatt, Hansruedi; Meinl, Walter; Hollert, Henner

    2018-02-01

    information and may give a first indication of the mechanism of action. To check this hypothesis, various additional strains expressing specific human-relevant enzymes were investigated. It could be shown that the additional use of genetically modified tester strains can enhance the detectable substance spectrum with the bacterial genotoxicological standard procedures or increase the sensitivity. The additional use provides orienting information at this level as a lot of data can be obtained quite quickly and with little effort. These indications of the mechanism of action should be however verified with a test system that uses mammalian cells, better human cells, to check their actual relevance. The selection of appropriate additional tester strains has to be defined from case to case depending on the molecular structure and also still requires some major expertise.

  17. Reconstruction of the neuromuscular system of the swimming-type larva of Loxosomella atkinsae (Entoprocta) as inferred by fluorescence labelling and confocal microscopy

    DEFF Research Database (Denmark)

    Fuchs, Judith; Wanninger, Andreas Wilhelm Georg

    2008-01-01

    Entoprocta is one of the most enigmatic phyla of the Animal Kingdom. The morphology of their larvae has been little investigated, with details on the larval musculature lacking entirely and immunocytochemical data on the larval nervous system available for only 2 species. Here, we provide the first...

  18. Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Paulo Victor Sgobbi de Souza

    2014-12-01

    Full Text Available During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg. IVIg has been tried in a variety of immune-mediated neurological diseases, being target of widespread use in central and peripheral nervous systems diseases. Objective To give an overview of the main topics regarding the mechanism of action and different therapeutic uses of IVIg in neurological practice, mainly in neuromuscular diseases.

  19. Development of a new screening assay to identify proteratogenic substances using zebrafish danio rerio embryo combined with an exogenous mammalian metabolic activation system (mDarT).

    Science.gov (United States)

    Busquet, François; Nagel, Roland; von Landenberg, Friedrich; Mueller, Stefan O; Huebler, Nicole; Broschard, Thomas H

    2008-07-01

    The assessment of teratogenic effects of chemicals is generally performed using in vivo teratogenicity assays, for example, in rats or rabbits. We have developed an in vitro teratogenicity assay using the zebrafish Danio rerio embryo combined with an exogenous mammalian metabolic activation system (MAS), able to biotransform proteratogenic compounds. Cyclophosphamide (CPA) and ethanol were used as proteratogens to test the efficiency of this assay. Briefly, the zebrafish embryos were cocultured at 2 hpf (hours postfertilization) with the test material at varying concentrations, induced male rat liver microsomes and nicotinamide adenine dinucleotide phosphate (reduced) for 60 min at 32 degrees C under moderate agitation in Tris-buffer. The negative control (test material alone) and the MAS control (MAS alone) were incubated in parallel. For each test group, 20 eggs were used for statistical robustness. Afterward fish embryos were transferred individually into 24-well plates filled with fish medium for 48 h at 26 degrees C with a 12-h light cycle. Teratogenicity was scored after 24 and 48 hpf using morphological endpoints. No teratogenic effects were observed in fish embryos exposed to the proteratogens alone, that is, without metabolic activation. In contrast, CPA and ethanol induced abnormalities in fish embryos when coincubated with microsomes. The severity of malformations increased with increasing concentrations of the proteratogens. We conclude that the application of microsomes will improve and refine the D. rerio teratogenicity assay as a predictive and valuable alternative method to screen teratogenic substances.

  20. Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system

    International Nuclear Information System (INIS)

    Matsumae, Yoshiharu; Takahashi, Yasufumi; Ino, Kosuke; Shiku, Hitoshi; Matsue, Tomokazu

    2014-01-01

    Graphical abstract: NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells were evaluated by using the menadione–ferrocyanide double mediator system combined with scanning electrochemical microscopy (SECM). - Highlights: • NAD(P)H:quinone oxidoreductase activity of single cells were evaluated with SECM. • Fe(CN) 6 3− /menadione concentrations were optimized for long-term SECM monitoring. • Menadione affect the intracellular levels of reactive oxygen species and GSH. • At 100 μM menadione, the Fe(CN) 6 3− generation rate decreased rapidly within 30 min. - Abstract: We evaluated the intracellular NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione–ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 μM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 μM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system

  1. Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system

    Energy Technology Data Exchange (ETDEWEB)

    Matsumae, Yoshiharu [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Takahashi, Yasufumi [Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan); Ino, Kosuke [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Shiku, Hitoshi, E-mail: shiku@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Matsue, Tomokazu, E-mail: matsue@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan)

    2014-09-09

    Graphical abstract: NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells were evaluated by using the menadione–ferrocyanide double mediator system combined with scanning electrochemical microscopy (SECM). - Highlights: • NAD(P)H:quinone oxidoreductase activity of single cells were evaluated with SECM. • Fe(CN){sub 6}{sup 3−}/menadione concentrations were optimized for long-term SECM monitoring. • Menadione affect the intracellular levels of reactive oxygen species and GSH. • At 100 μM menadione, the Fe(CN){sub 6}{sup 3−} generation rate decreased rapidly within 30 min. - Abstract: We evaluated the intracellular NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione–ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 μM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 μM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system.

  2. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    OpenAIRE

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented o...

  3. Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism.

    Directory of Open Access Journals (Sweden)

    Stephen G Turney

    Full Text Available During mammalian development, neuromuscular junctions and some other postsynaptic cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons. It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territory in response to sites vacated by other axons. Here we show that soon-to-be-eliminated axons rapidly reverse fate and grow to occupy vacant sites at a neuromuscular junction after laser removal of a stronger input. This reversal supports the idea that axons take over sites that were previously vacated. Indeed, during normal development we observed withdrawal followed by takeover. The stimulus for axon growth is not postsynaptic cell inactivity because axons grow into unoccupied sites even when target cells are functionally innervated. These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity.

  4. Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism.

    Science.gov (United States)

    Turney, Stephen G; Lichtman, Jeff W

    2012-01-01

    During mammalian development, neuromuscular junctions and some other postsynaptic cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons. It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territory in response to sites vacated by other axons. Here we show that soon-to-be-eliminated axons rapidly reverse fate and grow to occupy vacant sites at a neuromuscular junction after laser removal of a stronger input. This reversal supports the idea that axons take over sites that were previously vacated. Indeed, during normal development we observed withdrawal followed by takeover. The stimulus for axon growth is not postsynaptic cell inactivity because axons grow into unoccupied sites even when target cells are functionally innervated. These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity.

  5. Divergent and convergent roles for insulin-like peptides in the worm, fly and mammalian nervous systems.

    Science.gov (United States)

    Lau, Hiu E; Chalasani, Sreekanth H

    2014-09-01

    Insulin signaling plays a critical role in coupling external changes to animal physiology and behavior. Despite remarkable conservation in the insulin signaling pathway components across species, divergence in the mechanism and function of the signal is evident. Focusing on recent findings from C. elegans, D. melanogaster and mammals, we discuss the role of insulin signaling in regulating adult neuronal function and behavior. In particular, we describe the transcription-dependent and transcription-independent aspects of insulin signaling across these three species. Interestingly, we find evidence of diverse mechanisms underlying complex networks of peptide action in modulating nervous system function.

  6. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

  7. A novel bidirectional expression system for simultaneous expression of both the protein-coding genes and short hairpin RNAs in mammalian cells

    International Nuclear Information System (INIS)

    Hung, C.-F.; Cheng, T.-L.; Wu, R.-H.; Teng, C.-F.; Chang, W.-T.

    2006-01-01

    RNA interference (RNAi) is an extremely powerful and widely used gene silencing approach for reverse functional genomics and molecular therapeutics. In mammals, the conserved poly(ADP-ribose) polymerase 2 (PARP-2)/RNase P bidirectional control promoter simultaneously expresses both the PARP-2 protein and RNase P RNA by RNA polymerase II- and III-dependent mechanisms, respectively. To explore this unique bidirectional control system in RNAi-mediated gene silencing strategy, we have constructed two novel bidirectional expression vectors, pbiHsH1 and pbiMmH1, which contained the PARP-2/RNase P bidirectional control promoters from human and mouse, for simultaneous expression of both the protein-coding genes and short hairpin RNAs. Analyses of the dual transcriptional activities indicated that these two bidirectional expression vectors could not only express enhanced green fluorescent protein as a functional reporter but also simultaneously transcribe shLuc for inhibiting the firefly luciferase expression. In addition, to extend its utility for the establishment of inherited stable clones, we have also reconstructed this bidirectional expression system with the blasticidin S deaminase gene, an effective dominant drug resistance selectable marker, and examined both the selection and inhibition efficiencies in drug resistance and gene expression. Moreover, we have further demonstrated that this bidirectional expression system could efficiently co-regulate the functionally important genes, such as overexpression of tumor suppressor protein p53 and inhibition of anti-apoptotic protein Bcl-2 at the same time. In summary, the bidirectional expression vectors, pbiHsH1 and pbiMmH1, should provide a simple, convenient, and efficient novel tool for manipulating the gene function in mammalian cells

  8. Neuromuscular blockade in children Bloqueadores neuromusculares em crianças

    Directory of Open Access Journals (Sweden)

    João Fernando Lourenço de Almeida

    2000-06-01

    Full Text Available Neuromuscular blocking agents (NMBAs have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000 and active search of articles were the mechanisms used in this review.Os bloqueadores neuromusculares têm sido amplamente utilizados para controlar pacientes que necessitem imobilidade para algum tipo de intervenção médica, desde a realização de procedimentos invasivos até a obtenção de sincronismo com a ventilação mecânica. O objetivo básico desta monografia é revisar a farmacologia dos principais bloqueadores neuromusculares, analisar as diferenças existentes na junção neuromuscular de neonatos, lactentes, pré-escolares e adultos, além de discutir suas indicações em pacientes criticamente enfermos internados em unidade de terapia intensiva pediátrica. Revisão computadorizada da literatura (Medline 1990-2000 associado a busca ativa de artigos compuseram o mecanismo de busca dos dados desta revisão.

  9. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system

    Science.gov (United States)

    Kaplan, Bernhard A.; Lansner, Anders

    2014-01-01

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin–Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian–Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian–Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures. PMID

  10. Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial.

    Science.gov (United States)

    Giannasi, Lilian Chrystiane; Matsui, Miriam Yumi; de Freitas Batista, Sandra Regina; Hardt, Camila Teixeira; Gomes, Carla Paes; Amorim, José Benedito Oliveira; de Carvalho Aguiar, Isabella; Collange, Luanda; Dos Reis Dos Santos, Israel; Dias, Ismael Souza; de Oliveira, Cláudia Santos; de Oliveira, Luis Vicente Franco; Gomes, Mônica Fernandes

    2012-05-15

    Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP), given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm) and LED (= 660 nm) irradiation in CP patients. 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS.

  11. Two Novel 30K Proteins Overexpressed in Baculovirus System and Their Antiapoptotic Effect in Insect and Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Wei Yu

    2013-01-01

    Full Text Available The 30K family of proteins is important in energy metabolism and may play a role in inhibiting cellular apoptosis in silkworms (Bombyx mori. Several 30K-family proteins have been identified. In this study, two new silkworm genes, referred to as Slp (NM 001126256 and Lsp-t (NM 001043443, were analyzed by a bioinformatics approach according to the sequences of 30K proteins previously reported in the silkworm. Both Slp and Lsp-t shared more than 41% amino acid sequence homology with the reported 30K proteins and displayed a conserved domain consistent with that of lipoprotein-11. Additionally, the cDNA sequences of both Slp and Lsp-t were obtained from the fat bodies of silkworm larvae by reverse transcription polymerase chain reaction. Both genes were expressed in BmN cells using the Bac-to-Bac system. Purified Slp and Lsp-t were added to cultured BmN and human umbilical vein endothelial cells (HUVEC that were treated with H2O2. Both Slp and Lsp-t significantly enhanced the viability and suppressed DNA fragmentation in H2O2 treated BmN and HUVEC cells. This study suggested that Slp and Lsp-t exhibit similar biological activities as their known 30K-protein counterparts and mediate an inhibitory effect against H2O2-induced apoptosis.

  12. Molecular mechanism of mutagenesis induced by olaquindox using a shuttle vector pSP189/mammalian cell system

    International Nuclear Information System (INIS)

    Hao Lihua; Chen Qian; Xiao Xilong

    2006-01-01

    Olaquindox, a quinoxaline 1,4-dioxide derivative from quindoxin, is widely used as an animal growth promoter in China. We tested olaquindox as a mutagen in a SV40-based shuttle vector pSP189 and African green kidney cell (Vero E6 cell line) system to define the safety of olaquindox as a food-additive for animals. When applied at 6.6 μg/ml, olaquindox caused 12 times higher mutation frequency in comparison to untreated controls. More than 70% of base substitutions happened at G:C base pairs featuring G:C to T:A or G:C to A:T conversions. Frequency of point mutations for in vitro modified plasmids was also dramatically increased from the spontaneous background level. Olaquindox-induced mutations did not occur randomly along the supF shuttle vector, but instead, had a hot spot at base pair no. 155 which accounts for 37% of total mutations. Olaquindox-induced mutations also showed sequence-specificity in which most point mutations occurred at site N in a 5'-NNTTNN-3' sequence while most tandem bases deletion and rearrangement were seen at the 5'-ANGGCCNAAA-3' sequence. We conclude that olaquindox induces DNA mutation, therefore, should not be used as an additive to promote animal growth

  13. The delayed rectifier potassium conductance in the sarcolemma and the transverse tubular system membranes of mammalian skeletal muscle fibers

    Science.gov (United States)

    DiFranco, Marino; Quinonez, Marbella

    2012-01-01

    A two-microelectrode voltage clamp and optical measurements of membrane potential changes at the transverse tubular system (TTS) were used to characterize delayed rectifier K currents (IKV) in murine muscle fibers stained with the potentiometric dye di-8-ANEPPS. In intact fibers, IKV displays the canonical hallmarks of KV channels: voltage-dependent delayed activation and decay in time. The voltage dependence of the peak conductance (gKV) was only accounted for by double Boltzmann fits, suggesting at least two channel contributions to IKV. Osmotically treated fibers showed significant disconnection of the TTS and displayed smaller IKV, but with similar voltage dependence and time decays to intact fibers. This suggests that inactivation may be responsible for most of the decay in IKV records. A two-channel model that faithfully simulates IKV records in osmotically treated fibers comprises a low threshold and steeply voltage-dependent channel (channel A), which contributes ∼31% of gKV, and a more abundant high threshold channel (channel B), with shallower voltage dependence. Significant expression of the IKV1.4 and IKV3.4 channels was demonstrated by immunoblotting. Rectangular depolarizing pulses elicited step-like di-8-ANEPPS transients in intact fibers rendered electrically passive. In contrast, activation of IKV resulted in time- and voltage-dependent attenuations in optical transients that coincided in time with the peaks of IKV records. Normalized peak attenuations showed the same voltage dependence as peak IKV plots. A radial cable model including channels A and B and K diffusion in the TTS was used to simulate IKV and average TTS voltage changes. Model predictions and experimental data were compared to determine what fraction of gKV in the TTS accounted simultaneously for the electrical and optical data. Best predictions suggest that KV channels are approximately equally distributed in the sarcolemma and TTS membranes; under these conditions, >70% of IKV

  14. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

    Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

    2015-01-01

    PURPOSE: To evaluate the effects of a 12-week, home-based, physiotherapist-guided neuromuscular exercise program on the knee adduction moment (an indicator of mediolateral knee load distribution) in people with a medial arthroscopic partial meniscectomy within the past 3-12 months. METHODS......: An assessor-blinded, randomised controlled trial including people aged 30-50 years with no to mild pain following medial arthroscopic partial meniscectomy was conducted. Participants were randomly allocated to either a 12-week neuromuscular exercise program that targeted neutral lower limb alignment...... or a control group with no exercise. The exercise program included eight individual sessions with one of seven physiotherapists in private clinics, together with home exercises. Primary outcomes were the peak external knee adduction moment during normal pace walking and during a one-leg sit-to-stand. Secondary...

  15. Possible mechanisms of action of Gymnodinium breve toxin at the mammalian neuromuscular junction.

    Science.gov (United States)

    Shinnick-Gallagher, P.

    1980-01-01

    1 The mechanism of action of a crude fraction of Gymnodinium breve toxin (GBTX) was investigated by intracellular recording techniques in the rat phrenic nerve diaphragm preparation. 2 GBTX (2 micrograms/ml) decreased the input resistance of the muscle membrane concomitantly with a depolarization of the resting membrane potential. 3 A low sodium solution reversed or prevented a GBTX-induced membrane depolarization. 4 Tetrodotoxin (TTX) antagonized a GBTX-induced increase in miniature endplate potential (m.e.p.p.) frequency and repolarized a GBTX-depolarized membrane. Pretreatment with TTX prevented GBTX effects. 5 GBTX reversibly reduced depolarizations produced by bath applied acetylcholine (ACh). The membrane depolarization was not responsible for the depression of ACh responses. 6 These findings suggest that GBTX increases m.e.p.p. frequency and depolarizes the resting membrane potential by increasing sodium permeability. The reduction of ACh-induced depolarizations suggests that GBTX may be acting at some site on the ACh receptor. PMID:7190452

  16. Emerging modalities in dysphagia rehabilitation: neuromuscular electrical stimulation.

    Science.gov (United States)

    Huckabee, Maggie-Lee; Doeltgen, Sebastian

    2007-10-12

    The aim of this review article is to advise the New Zealand medical community about the application of neuromuscular electrical stimulation (NMES) as a treatment for pharyngeal swallowing impairment (dysphagia). NMES in this field of rehabilitation medicine has quickly emerged as a widely used method overseas but has been accompanied by significant controversy. Basic information is provided about the physiologic background of electrical stimulation. The literature reviewed in this manuscript was derived through a computer-assisted search using the biomedical database Medline to identify all relevant articles published until from the initiation of the databases up to January 2007. The reviewers used the following search strategy: [(deglutition disorders OR dysphagia) AND (neuromuscular electrical stimulation OR NMES)]. In addition, the technique of reference tracing was used and very recently published studies known to the authors but not yet included in the database systems were included. This review elucidates not only the substantive potential benefit of this treatment, but also potential key concerns for patient safety and long term outcome. The discussion within the clinical and research communities, especially around the commercially available VitalStim stimulator, is objectively explained.

  17. Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

    Science.gov (United States)

    Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

    2017-12-01

    Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the

  18. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia...... and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel...... practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit...

  19. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

  20. Identification of minimal sequences of the Rhopalosiphum padi virus 5' untranslated region required for internal initiation of protein synthesis in mammalian, plant and insect translation systems

    DEFF Research Database (Denmark)

    Groppelli, Elisabetta; Belsham, Graham; Roberts, Lisa O.

    2007-01-01

    Rhopalosiphum padi virus (RhPV) is a member of the family Dicistroviridae. The genomes of viruses in this family contain two open reading frames, each preceded by distinct internal ribosome entry site (IRES) elements. The RhPV 5' IRES is functional in mammalian, insect and plant translation syste...

  1. Muscle mechanics and neuromuscular control

    NARCIS (Netherlands)

    Hof, AL

    The purpose of this paper is to demonstrate that the properties of the mechanical system, especially muscle elasticity and limb mass, to a large degree determine force output and movement. This makes the control demands of the central nervous system simpler and more robust. In human triceps surae, a

  2. A theoretical framework for understanding neuromuscular response to lower extremity joint injury.

    Science.gov (United States)

    Pietrosimone, Brian G; McLeod, Michelle M; Lepley, Adam S

    2012-01-01

    Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes.

  3. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an......-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x)....

  4. Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: reversal of neuromuscular block in anaesthetized Rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: At present, reversal of neuromuscular block induced by steroidal neuromuscular blocking agents (NMBAs) is achieved by administration of cholinesterase inhibitors. Chemical encapsulation of steroidal NMBAs, such as rocuronium, by a cyclodextrin is a new concept in neuromuscular block

  5. High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

    Science.gov (United States)

    Mettler, Joni A; Magee, Dillon M; Doucet, Barbara M

    2018-03-16

    Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF-) and high-frequency (HF-) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. Eleven young healthy volunteers (6 men; 5 women) received an acute bout of LF- (20 Hz) and HF- (60 Hz) NMES. Muscle biopsies were obtained from the vastus lateralis muscle prior to the first NMES treatment and 30-mins following each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin (mTOR), p70-S6 kinase 1 (S6K1), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Compared to Pre-NMES, phosphorylation of mTOR was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P 0.05). There were no differences between treatment conditions for 4E-BP1 phosphorylation (P > 0.05). An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared to LF-NMES, suggesting that HF-stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. Additionally, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

  6. Neuromuscular diseases after cardiac transplantation

    NARCIS (Netherlands)

    Mateen, Farrah J.; van de Beek, Diederik; Kremers, Walter K.; Daly, Richard C.; Edwards, Brooks S.; McGregor, Christopher G. A.; Wijdicks, Eelco F. M.

    2009-01-01

    BACKGROUND: Cardiac transplantation is a therapeutic option in end-stage heart failure. Peripheral nervous system (PNS) disease is known to occur in cardiac transplant recipients but has not been fully characterized. METHODS: This retrospective cohort review reports the PNS-related concerns of 313

  7. The Effect of Proprioceptive Neuromuscular Facilitation on Learning Fine Motor Skills: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahabi Kaseb

    2016-09-01

    Full Text Available Introduction: Preparation of neuromuscular system prior to performing motor skills affects the learning of motor skills. The present study was conducted to investigate the effects of Proprioceptive Neuromuscular Facilitation (PNF on limb coordination and accuracy in dart throwing skill. Methods: Thirty two male students were randomly selected as study sample. Based on the pretest scores, the participants were divided into three groups: experimental (proprioceptive neuromuscular facilitation, first control (without warm-up, and second control (specific warm-up. During the acquisition phase, the participants first performed the preparation training related to their own group, then all groups performed the exercise program of dart throwing consisting of 6 blocks of 9 trials in 4 training sessions. Finally, 20 days following the last exercise session, the subjects took the retention and transfer tests. Results: The results of one-way ANOVA test for coordination variable in acquisition test showed no significant difference between the groups, while there was a statistically significant difference between groups regarding coordination variable in retention and transfer tests. Furthermore, the results of one-way ANOVA for the accuracy variable in acquisition and retention tests showed no statistically significant difference between the three groups, while there was a statistically significant difference between groups for accuracy variable in transfer test. Conclusion: It seems that proprioceptive neuromuscular facilitation, as a preparation method before performance, can enhance the efficacy of training to better learn the coordination pattern of fine motor skills.

  8. Evaluation of the neuromuscular compartments in the peroneus longus muscle through electrical stimulation and accelerometry

    Directory of Open Access Journals (Sweden)

    Guillermo A. Mendez

    2013-10-01

    Full Text Available BACKGROUND: Muscles are innervated exclusively by a nerve branch and possess definite actions. However, mammalian skeletal muscles, such as the trapezius, the medial gastrocnemius, and the peroneus longus, are compartmentalized. In the peroneus longus muscle, multiple motor points, which innervate individual neuromuscular compartments (NMC, the superior (S-NMC, anteroinferior (AI-NMC, and posteroinferior (PI-NMC, have been described. The contribution of each neuromuscular compartment to the final action of the muscle is fundamental for the rehabilitation of patients afflicted by neurological and muscle dysfunctions. Interventions are often based on electrical principles that take advantage of the physiological characteristics of muscles and nerves to generate therapeutic effects. OBJECTIVE: To compare the effects of stimulating the different neuromuscular compartments (NMCs of the peroneus longus muscle on the motor threshold (MT and acceleration of the foot. METHOD: This is a cross-sectional study comprising 37 subjects. The three NMCs of the peroneus longus muscle were stimulated, and the acceleration of the foot and the motor threshold of each NMC were evaluated. A repeated measures analysis of variance with Bonferroni corrections of two intra-subjects factors was performed. RESULTS: The stimulation of the different NMCs did not result in any differences in MT (F=2.635, P=0.079. There were significant differences between the axes of acceleration caused by the stimulation of the different NMCs (F=56,233; P=0.000. The stimulation of the posteroinferior compartment resulted in the greatest acceleration in the X-axis (mean 0.614; standard deviation 0.253. CONCLUSIONS: The posteroinferior compartment primarily contributes to the eversion movement of the foot. NMCs have specific functional roles that contribute to the actions of the muscles to which they belong.

  9. Design of low-cost general purpose microcontroller based neuromuscular stimulator.

    Science.gov (United States)

    Koçer, S; Rahmi Canal, M; Güler, I

    2000-04-01

    In this study, a general purpose, low-cost, programmable, portable and high performance stimulator is designed and implemented. For this purpose, a microcontroller is used in the design of the stimulator. The duty cycle and amplitude of the designed system can be controlled using a keyboard. The performance test of the system has shown that the results are reliable. The overall system can be used as the neuromuscular stimulator under safe conditions.

  10. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2001-01-01

    The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

  11. Classification of neuromuscular blocking agents in a new neuromuscular preparation of the chick in vitro

    NARCIS (Netherlands)

    Riezen, H. van

    1968-01-01

    A neuromuscular preparation of the chick is described: 1. 1. The sciatic nerve-tibilis anterior muscle preparation of the 2–10 days old chick fulfils all criteria of an assay preparation and differentiates between curare-like and decamethonium-like agents. 2. 2. The preparation responds to

  12. Localization of two mammalian cyclin dependent kinases during mammalian meiosis

    NARCIS (Netherlands)

    Ashley, T.; Walpita, D.; de rooij, D. G.

    2001-01-01

    Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

  13. Mammalian cell biology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

  14. Cryopreservation of mammalian semen.

    Science.gov (United States)

    Curry, Mark R

    2007-01-01

    Mammalian spermatozoa were among the very first cells to be successfully cryopreserved and over the last five decades the use of frozen-thawed semen for artificial insemination has come to play an important role in domestic livestock production. More recently, semen freezing has increasingly been utilized in the establishment of genetic resource banks for endangered species. Semen is collected, most commonly either by use of an artificial vagina or by electroejaculation of an anaesthetized animal, and basic sperm parameters assessed. Semen is extended using a TEST-egg yolk-glycerol diluent, packaged in 0.25-mL plastic straws and slowly cooled to 5 degrees C over a period of 1-2 h. Cooled straws are frozen by suspending within liquid nitrogen vapor above the liquid nitrogen surface before plunging into the liquid phase. Straws are thawed briefly in air before immersing in a 35 degrees C water bath for 15 s, and often are used directly for insemination without any further processing.

  15. Neuromuscular adaptations induced by adjacent joint training.

    Science.gov (United States)

    Ema, R; Saito, I; Akagi, R

    2018-03-01

    Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training. © 2017 The Authors. Scandinavian Journal of Medicine & Science In Sports Published by John Wiley & Sons Ltd.

  16. Acute neuromuscular weakness associated with dengue infection

    Directory of Open Access Journals (Sweden)

    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  17. Medical back belt with integrated neuromuscular electrical stimulation

    NARCIS (Netherlands)

    Bottenberg, E. (Eliza); Brinks, G.J. (Ger); Hesse, J. (Jenny)

    2014-01-01

    The medical back belt with integrated neuromuscular electrical stimulation is anorthopedic device, which has two main functions. The first function is to stimulate the backmuscles by using a neuromuscular electrical stimulation device that releases regular,electrical impulses. The second function of

  18. Neuromuscular function during a forward lunge in meniscectomized patients

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Damgaard, Jacob; Roos, Ewa M.

    2012-01-01

    This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients....... Such differences may represent early changes in neuromuscular function potentially contributing to the development of knee osteoarthritis....

  19. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  20. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.Cachexia, ageing and disuse and their effects on the human and animals neuromuscular system are reviewed. Disuse induces reduction of muscle fibers (mainly II diameter with peripheral myofibrils lost; there is no core-targetoid or even reduction on myophosphorilase activity, both typical of denervation; the acetylcholine spontaneous release and trophic factors on myoneural junction are maintained; muscle fibers could change to angular shape. Ageing affects nerve and muscle by a continuous and progressive process of denervation and reinner

  1. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

    Science.gov (United States)

    Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

    2016-06-01

    Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

  2. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  3. Electrophysiological study in neuromuscular junction disorders

    Directory of Open Access Journals (Sweden)

    Ajith Cherian

    2013-01-01

    Full Text Available This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS, congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS. SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

  4. Motor neuron, nerve, and neuromuscular junction disease.

    Science.gov (United States)

    Finsterer, Josef; Papić, Lea; Auer-Grumbach, Michaela

    2011-10-01

    The aim is to review the most relevant findings published during the last year concerning clinical, genetic, pathogenic, and therapeutic advances in motor neuron disease, neuropathies, and neuromuscular junction disorders. Studies on animal and cell models have improved the understanding of how mutated survival motor neuron protein in spinal muscular atrophy governs the pathogenetic processes. New phenotypes of SOD1 mutations have been described. Moreover, animal models enhanced the insight into the pathogenetic background of sporadic and familial amyotrophic lateral sclerosis. Novel treatment options for motor neuron disease have been described in humans and animal models. Considerable progress has been achieved also in elucidating the genetic background of many forms of inherited neuropathies and high clinical and genetic heterogeneity has been demonstrated. Mutations in MuSK and GFTP1 have been shown to cause new types of congenital myasthenic syndromes. A third type of autoantibodies (Lrp4) has been detected to cause myasthenia gravis. Advances in the clinical and genetic characterization of motor neuron diseases, neuropathies, and neuromuscular transmission defects have important implications on the fundamental understanding, diagnosis, and management of these disorders. Identification of crucial steps of the pathogenetic process may provide the basis for the development of novel therapeutic strategies.

  5. EFFECT OF NEUROMUSCULAR TRAINING ON BALANCE AMONG UNIVERSITY ATHLETES

    Directory of Open Access Journals (Sweden)

    Mohansundar Sankaravel

    2016-06-01

    Full Text Available Background: Proprioceptive deficiency followed by lateral ankle sprain leads to poor balance is not uncommon. It has been linked with increased injury risk among young athletes. Introducing neuromuscular training programs for this have been believed as one of the means of injury prevention. Hence, this study was aimed to determine the effects of six weeks progressive neuromuscular training (PNM Training on static balance gains among the young athletes with a previous history of ankle sprains. Methods: This study was an experimental study design, with pre and post test method to determine the effects of PNM Training on static balance gains. All data were collected at university’s sports rehabilitation lab before and after six weeks of intervention period. There were 20 male and female volunteer young athletes (20.9 ± 0.85 years of age with a previous history of ankle sprain involving various sports were recruited from the University community. All the subjects were participated in a six week PNM Training that included stability, strength and power training. Outcome measures were collected by calculating the errors on balance error scoring system made by the athletes on static balance before and after the six weeks of intervention period. Static balance was tested in firm and foam surfaces and recorded accordingly. Results: The researchers found a significant decrease (2.40 ± 0.82 in total errors among the samples at the post test compared with their pre test (P >0.05. Conclusions: The study demonstrates that a PNM Training can improve the static balance on both the firm and foam surfaces among the young athletes with a previous history of ankle sprains.

  6. The Mammalian Cortex as a Self-Organizing Complex System: Multi-Scale Homeostatic Approaches to Criticality via Dynamical Balance of Inhibition against Excitation

    Science.gov (United States)

    Ng, Tony T.

    The mammalian cortex is a highly structured network of densely packed neurons that interact strongly with each other in very specific ways. Loosely speaking, neurons are cells that fire clicks at each other as a means of communication. Common sites of communication, known as synapses, are enabled by transmitter molecules released from presynaptic sender cells, which bind to receptors on postsynaptic receiver cells. There are two major classes of neurons - excitatory ones that prompt their downstream neighbors to fire spikes through depolarization, and inhibitory ones that suppress spike activity of their postsynaptic partners via hyperpolarization. Depolarization and hyperpolarization make membrane potential of a cell more positive and more negative, respectively. A sufficiently depolarized neuron fires a spike, which technically is called an action potential. In this thesis, we focus on the interplay between three of the cortex's most ubiquitous features and examine some of the consequences that their interactions have on cortical dynamics. One of the features, widespread projections between clusters of excitatory neurons, is topological. The two remaining features, homeostasis and balance between the amount of excitatory and inhibitory activity are dynamical. Here, homeostasis refers to the regulatory mechanism of individual cells or collections of cells that maintains constant levels of spike activity over time. Simply by varying the average homeostatic firing rate in clusters of excitatory neurons or by tuning the common homoeostatic rate of individual inhibitory neurons, we show via simulation that cluster-based activity bursts can exhibit critical dynamics and display power-law distributions with exponents that are consistent with those found in in vivo experiments of awake animals. Criticality is an idea that originated in statistical physics. At the critical point, activity levels of sites across an entire system, such as those of different cortical regions

  7. Neuromuscular blockade in cardiac surgery: An update for clinicians

    Directory of Open Access Journals (Sweden)

    Hemmerling Thomas

    2008-01-01

    Full Text Available There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

  8. Studies on the repair of damaged DNA in bacteriophage, bacterial and mammalian systems. Comprehensive report, 1 February 1981-15 September 1983

    International Nuclear Information System (INIS)

    Friedberg, E.C.

    1983-01-01

    We have explored the molecular mechanism of the repair of DNA at a number of different levels of biological organization, by investigating bacteriophage, bacterial, yeast and mammalian (including human) cells. We have demonstrated that uv endonuclease of phage T4 not only possesses pyrimidine dimer (PD)-DNA glycosylase activity but also apyrimidinic (AP) endonuclease activity. The demonstration of both activities provided an explanation for the specific endonucleosytic cleavage of DNA at sites of pyrimidine dimers catalyzed by this small protein. A new apurinic/apyrimidinic (AP) endonuclease, specific for sites of of base loss in single stranded DNA has been isolated from E. celi and presumably recognizes these lesions in single stranded regions of duplex DNA. We have partially purified this enzyme and have carried out a preliminary characterization of the activity. We treated xeroderma pigmentosum and normal cells with sodium butyrate in the hope of restoring normal levels of excision repair to the former. Although this result was not obtained, we established that all cells treated with sodium butyrate show enhanced levels of repair synthesis, thus providing a means for increasing the sensitivity of this commonly used technique for measuring DNA repair in mammalian cells in culture

  9. [The hip joint in neuromuscular disorders].

    Science.gov (United States)

    Strobl, W M

    2009-07-01

    Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

  10. Comparison of amphibian and mammalian thyroperoxidase ...

    Science.gov (United States)

    Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

  11. Mammalian Genetics and Teratology Section

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The work of the Mammalian Genetics and Teratology Section includes research in mutagenesis, basic genetics, reproductive biology, and teratogenesis involving basic studies, method development, including exploration of the biological material, and testing. The basic studies make good use of the genetic material accumulated in mutagenesis experiments of various kinds, or of the findings of mutagenesis experiments themselves. In the latter category is the finding of a repair system in the fertilized egg. The genetics of repair competency or deficiency are now under study. A linear relationship between gene dosage and level of expression of an enzyme has been demonstrated. Opportunities for the study of gene action are provided by a number of X-autosome translocations which continue to be discovered in the course of mutagenesis experiments. In these rearrangements, X-chromosome inactivation extends to neighboring autosomal loci. Considerable progress has been made in developing the skeletal mutation system, which provides information on dominants that is highly useful for risk assessment. A sensitive-indicator test is now under development which will make the screening for skeletal mutations much faster and easier. Method development has also progressed on the in vivo somatic-mutation test now being widely used as an in vivo screen for mutagens. Another method developed here is the numerical sex-chromosome anomaly (NSA) test for nondisjunction. The NSA method is being used to explore the effects of female age on chromosome loss and nondisjunction. A model for estimating the misclassification error was experimentally established for the heritable translocation test. A rapid, easy, and sensitive in vivo screening test for teratogenesis was developed. An in vitro teratogenic prescreen being developed makes use of teratocarcinoma-derived cell lines

  12. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

    Science.gov (United States)

    Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

  13. Reaction of long-lived radicals and vitamin C in γ-irradiated mammalian cells and their model system at 295 K. Tunneling reaction in biological system

    International Nuclear Information System (INIS)

    Matsumoto, Takuro; Miyazaki, Tetsuo; Kosugi, Yoshio; Kumada, Takayuki; Koyama, Sinji; Kodama, Seiji; Watanabe, Masami.

    1996-01-01

    When golden hamster embryo (GHE) cells or concentrated albumin solution (0.1 kg dm -3 ) that is a model system of cells is irradiated with γ-rays at 295 K, organic radicals produced can be observed by ESR. The organic radicals survive at both 295 K and 310 K for such a long time as 20 hr. The long-lived radicals in GHE cells and the albumin solution react with vitamin C by the rate constants of 0.007 dm 3 mol -1 s -1 and 0.014 dm 3 mol -1 s -1 , respectively. The long-lived radicals in human cells cause gene mutation, which is suppressed by addition of vitamin C. The isotope effect on the rate constant (k) for the reaction of the long-lived radicals and vitamin C has been studied in the albumin solution by use of protonated vitamin C and deuterated vitamin C. The isotope effect (k H /k D ) was more than 20-50 and was interpreted in terms of tunneling reaction. When GHE cells or the aqueous albumin solution (0.1 kg dm -3 ) is irradiated with γ-rays at 295 K, organic radicals produced survive for more than 24 hr at room temperature. Very recently we have found that vitamin C reacts with the long-lived organic radicals in the γ-irradiated albumin solution at high concentration of 0.1 kg dm -3 by the rate constant of 0.014 dm 3 mol -1 s -1 . Since most of reactions in biological systems including the reaction of vitamin C are a transfer of a hydrogen atom or a proton that has a large wave character, it is generally expected that the tunneling reaction may play an important role in biological systems at room temperature. The studies of isotope effects on reactions will give an information on the contribution of tunneling reaction. (J.P.N.)

  14. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  15. The role of proprioception and neuromuscular stability in carpal instabilities.

    Science.gov (United States)

    Hagert, E; Lluch, A; Rein, S

    2016-01-01

    Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

  16. Effects of napping on neuromuscular fatigue in myasthenia gravis.

    Science.gov (United States)

    Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

    2013-11-01

    The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

  17. Neuromuscular fatigue during high-intensity intermittent exercise in individuals with intellectual disability.

    Science.gov (United States)

    Borji, Rihab; Sahli, Sonia; Zarrouk, Nidhal; Zghal, Firas; Rebai, Haithem

    2013-12-01

    This study examined neuromuscular fatigue after high-intensity intermittent exercise in 10 men with mild intellectual disability (ID) in comparison with 10 controls. Both groups performed three maximal voluntary contractions (MVC) of knee extension with 5 min in-between. The highest level achieved was selected as reference MVC. The fatiguing exercise consists of five sets with a maximal number of flexion-extension cycles at 80% of the one maximal repetition (1RM) for the right leg at 90° with 90 s rest interval between sets. The MVC was tested again after the last set. Peak force and electromyography (EMG) signals were measured during the MVC tests. Root Mean Square (RMS) and Median Frequency (MF) were calculated. Neuromuscular efficiency (NME) was calculated as the ratio of peak force to the RMS. Before exercise, individuals with ID had a lower MVC (psport train ID individuals, they should consider this nervous system weakness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. An adaptive neuromuscular controller for assistive lower-limb exoskeletons : A preliminary study on subjects with spinal cord injury

    NARCIS (Netherlands)

    Wu, Amy R.; Dzeladini, Florin; Brug, Tycho J.H.; Tamburella, Federica; Tagliamonte, Nevio L.; Van Asseldonk, Edwin H.F.; van der Kooij, H.; Ijspeert, Auke J.

    2017-01-01

    Versatility is important for a wearable exoskeleton controller to be responsive to both the user and the environment. These characteristics are especially important for subjects with spinal cord injury (SCI), where active recruitment of their own neuromuscular system could promote motor recovery.

  19. An adaptive neuromuscular controller for assistive lower-limb exoskeletons : A preliminary study on subjects with spinal cord injury

    NARCIS (Netherlands)

    Wu, Amy R.; Dzeladini, Florin; Brug, Tycho J.H.; Tamburella, Federica; Tagliamonte, Nevio L.; Van Asseldonk, Edwin H.F.; Van Der Kooij, Herman; IJspeert, Auke Jan

    2017-01-01

    Versatility is important for a wearable exoskeleton controller to be responsive to both the user and the environment. These characteristics are especially important for subjects with spinal cord injury (SCI), where active recruitment of their own neuromuscular system could promote motor recovery.

  20. Neuromuscular fatigue and recovery profiles in individuals with intellectual disability

    OpenAIRE

    Borji , Rihab; Zghal , Firas; Zarrouk , Nidhal; Martin , Vincent; Sahli , Sonia; Rebai , Haithem

    2017-01-01

    International audience; Purpose: This study aimed to explore neuromuscular fatigue and recovery profiles in individuals with intellectual disability (ID) after exhausting submaximal contraction.Methods: Ten men with ID were compared to 10 men without ID. The evaluation of neuromuscular function consisted in brief (3 s) isometric maximal voluntary contraction (IMVC) of the knee extension superimposed with electrical nerve stimulation before, immediately after, and during 33 min after an exhaus...

  1. Reaction of long-lived radicals and vitamin C in γ-irradiated mammalian cells and their model system at 295 K. Tunneling reaction in biological system

    International Nuclear Information System (INIS)

    Matsumoto, Takuro; Kumada, Takayuki; Kodama, Seiji; Watanabe, Masami

    1997-01-01

    When golden hamster embryo (GHE) cells or concentrated albumin solution (0.1 kg dm -3 ), that is a model system of cells, is irradiated with γ-rays at 295 K, organic radicals produced can be observed by ESR. The organic radicals survive at both 295 and 310 K for as long as 20 h. The long-lived radicals in GHE cells and the albumin solution react with vitamin C by the rate constants of 0.007 dm 3 mol -1 s -1 and 0.014 dm 3 mol -1 s -1 , respectively. The long-lived radicals in human cells cause gene mutation, which is suppressed by the addition of vitamin C. The isotope effect on the rate constant (κ) for the reaction of the long-lived radicals and vitamin C has been studied in the albumin solution by use of protonated vitamin C and deuterated vitamin C. The isotope effect (κ H /κ D ) was more than 20 ∼ 50 and was interpreted in terms of tunnelling reaction. (author)

  2. Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.

    Science.gov (United States)

    Tenforde, Adam S; Shull, Pete B; Fredericson, Michael

    2012-05-01

    Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  3. The shape of mammalian phylogeny

    DEFF Research Database (Denmark)

    Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

    2011-01-01

    an assemblage, ecoregion or larger area always tends to be more unbalanced than expected from the phylogeny of species at the next more inclusive spatial scale. We conclude with a verbal model of mammalian macroevolution, which emphasizes the importance to diversification of accessing new regions...

  4. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  5. Technology of mammalian cell encapsulation

    NARCIS (Netherlands)

    Uludag, H; De Vos, P; Tresco, PA

    2000-01-01

    Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

  6. Mammalian clock output mechanisms

    NARCIS (Netherlands)

    Kalsbeek, Andries; Yi, Chun-Xia; Cailotto, Cathy; la Fleur, Susanne E.; Fliers, Eric; Buijs, Ruud M.

    2011-01-01

    In mammals many behaviours (e.g. sleep-wake, feeding) as well as physiological (e.g. body temperature, blood pressure) and endocrine (e.g. plasma corticosterone concentration) events display a 24 h rhythmicity. These 24 h rhythms are induced by a timing system that is composed of central and

  7. 2,2'-Dithiobis(N-ethyl-spermine-5-carboxamide) is a high affinity, membrane-impermeant antagonist of the mammalian polyamine transport system.

    Science.gov (United States)

    Huber, M; Pelletier, J G; Torossian, K; Dionne, P; Gamache, I; Charest-Gaudreault, R; Audette, M; Poulin, R

    1996-11-01

    We have synthesized 2,2'-dithiobis(N-ethyl-spermine-5-carboxamide) (DESC), its thiol monomer (MESC), and the mixed MESC-cysteamine disulfide (DEASC) as potential inhibitors of polyamine transport in mammalian cells. DESC was the most potent antagonist of spermine transport in ZR-75-1 human breast cancer cells, with Ki values of 5. 0 +/- 0.7, 80 +/- 31, and 16 +/- 3 microM for DESC, MESC, and DEASC, respectively. DESC also strongly blocked putrescine and spermidine uptake in ZR-75-1 cells (Ki = 1.6 +/- 0.5 and 2.7 +/- 1.1 microM, respectively). While DESC and MESC were purely competitive inhibitors of putrescine transport, DEASC was a mixed competitive/noncompetitive antagonist. Remarkably, DESC was virtually impermeant in ZR-75-1 cells despite its low Ki toward polyamine transport. The marked difference in affinity between DESC and MESC was essentially due to the tail-to-tail juxtaposition of two spermine-like structures, suggesting that dimeric ligands of the polyamine transporter might simultaneously interact with more than one binding site. While DESC strongly decreased the initial rate of [3H]spermidine transport, even a 40-fold molar excess of antagonist could not completely abolish intracellular spermidine accumulation. Moreover, as little as 0.3 microM spermidine fully restored growth in ZR-75-1 cells treated with an inhibitor of polyamine biosynthesis in the presence of 50 microM DESC, thus emphasizing the importance of uptake of trace amounts of exogenous polyamines. Thus, reducing the exogenous supply of polyamines with a potent competitive inhibitor may be kinetically inadequate to block replenishment of the polyamine pool in polyamine-depleted tumor cells that display high transport capacity. These results demonstrate that polyamine analogues cross-linked into a dimeric structure such as DESC interact with high affinity with the mammalian polyamine carrier without being used as substrates. These novel properties provide a framework for the design of

  8. Training the Antifragile Athlete: A Preliminary Analysis of Neuromuscular Training Effects on Muscle Activation Dynamics.

    Science.gov (United States)

    Kiefer, Adam W; Myer, Gregory D

    2015-10-01

    Athletic injuries typically occur when the stable, emergent coordination between behavioral processes breaks down due to external noise, or variability. A physiological system that operates at an optimal point on a spectrum of rigidity and flexibility may be better prepared to handle extreme external variability, and the purpose of the current experiment was to examine whether targeted neuromuscular training resulted in changes to the rigidity and flexibility of the gluteal muscle tonus signal as measured with electromyography prior to the landing phase of a drop vertical jump task. 10 adolescent female athletes who participated in a targeted 10-week neuromuscular training program and 6 controls participated, and their tonus dynamics were examined with recurrence quantification analysis prior to training and after the 10-week program. The dependent measures, percent laminarity (%LAM) and percent determinism (%DET) were hypothesized to decrease following training, and were submitted to a one tailed mixed-model ANOVA. The training group exhibited a decrease in %LAM and %DET after training compared to pre-training and controls. The present findings indicate increased metaflexibility (i.e., greater intermittency and an increase in internal randomness) in tonus dynamics following neuromuscular training, and have important implications for the prevention of musculoskeletal injury in sport, specifically within the context of external noise and antifragility.

  9. The Drosophila wings apart gene anchors a novel, evolutionarily conserved pathway of neuromuscular development.

    Science.gov (United States)

    Morriss, Ginny R; Jaramillo, Carmelita T; Mikolajczak, Crystal M; Duong, Sandy; Jaramillo, Maryann S; Cripps, Richard M

    2013-11-01

    wings apart (wap) is a recessive, semilethal gene located on the X chromosome in Drosophila melanogaster, which is required for normal wing-vein patterning. We show that the wap mutation also results in loss of the adult jump muscle. We use complementation mapping and gene-specific RNA interference to localize the wap locus to the proximal X chromosome. We identify the annotated gene CG14614 as the gene affected by the wap mutation, since one wap allele contains a non-sense mutation in CG14614, and a genomic fragment containing only CG14614 rescues the jump-muscle phenotypes of two wap mutant alleles. The wap gene lies centromere-proximal to touch-insensitive larva B and centromere-distal to CG14619, which is tentatively assigned as the gene affected in introverted mutants. In mutant wap animals, founder cell precursors for the jump muscle are specified early in development, but are later lost. Through tissue-specific knockdowns, we demonstrate that wap function is required in both the musculature and the nervous system for normal jump-muscle formation. wap/CG14614 is homologous to vertebrate wdr68, DDB1 and CUL4 associated factor 7, which also are expressed in neuromuscular tissues. Thus, our findings provide insight into mechanisms of neuromuscular development in higher animals and facilitate the understanding of neuromuscular diseases that may result from mis-expression of muscle-specific or neuron-specific genes.

  10. X-rays sensitive mammalian cell mutant

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1982-01-01

    A phenomenon that in x-ray-sensitive mammalian-cell mutants, cellular death due to x-ray radiation was not increased by caffeine, but on the contrary, the dead cells were resuscitated by it was discussed. The survival rate of mutant cells increased by caffein in a low concentration. This suggested that caffeine may have induced some mechanism to produce x-ray resistant mutant cells. Postirradiation treatment with caffeine increased considerably the survival rate of the mutant cells, and this suggested the existence of latent caffeine-sensitive potentially lethal damage repair system. This system, after a few hours, is thought to be substituted by caffeine-resistant repair system which is induced by caffeine, and this may be further substituted by x-ray-resistant repair system. The repair system was also induced by adenine. (Ueda, J.)

  11. The neuromuscular differential diagnosis of joint hypermobility.

    Science.gov (United States)

    Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

    2015-03-01

    Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. © 2015 Wiley Periodicals, Inc.

  12. Assessment of Motor Units in Neuromuscular Disease.

    Science.gov (United States)

    Henderson, Robert D; McCombe, Pamela A

    2017-01-01

    The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an effective biomarker for assessing disease progression and for use in clinical trials in amyotrophic lateral sclerosis has stimulated the study of methods to measure the number of motor units. Since 1970 a number of different methods, including the incremental, F-wave, multipoint, and statistical methods, have been developed but none has achieved widespread applicability. Two methods (MUNIX and the multipoint incremental method) are in current use across multiple centres and are discussed in detail in this review, together with other recently published methods. Imaging with magnetic resonance and ultrasound is increasingly being applied to this area. Motor unit number estimates have also been applied to other neuromuscular diseases such as spinal muscular atrophy, compression neuropathies, and prior poliomyelitis. The need for an objective measure for the assessment of motor units remains tantalizingly close but unfulfilled in 2016.

  13. Silent synapses in neuromuscular junction development.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Lanuza, Maria A; García, Neus; Besalduch, Nuria; Tomàs, Marta

    2011-01-01

    In the last few years, evidence has been found to suggest that some synaptic contacts become silent but can be functionally recruited before they completely retract during postnatal synapse elimination in muscle. The physiological mechanism of developmental synapse elimination may be better understood by studying this synapse recruitment. This Mini-Review collects previously published data and new results to propose a molecular mechanism for axonal disconnection. The mechanism is based on protein kinase C (PKC)-dependent inhibition of acetylcholine (ACh) release. PKC activity may be stimulated by a methoctramine-sensitive M2-type muscarinic receptor and by calcium inflow though P/Q- and L-type voltage-dependent calcium channels. In addition, tropomyosin-related tyrosine kinase B (trkB) receptor-mediated brain-derived neurotrophic factor (BDNF) activity may oppose the PKC-mediated ACh release depression. Thus, a balance between trkB and muscarinic pathways may contribute to the final functional suppression of some neuromuscular synapses during development. © 2010 Wiley-Liss, Inc.

  14. Neuromuscular Fatigue During 200 M Breaststroke

    Directory of Open Access Journals (Sweden)

    Ana Conceição

    2014-03-01

    Full Text Available The aims of this study were: i to analyze activation patterns of four upper limb muscles (duration of the active and non-active phase in each lap of 200m breaststroke, ii quantify neuromuscular fatigue, with kinematics and physiologic assessment. Surface electromyogram was collected for the biceps brachii, deltoid anterior, pectoralis major and triceps brachii of nine male swimmers performing a maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the 1st to the 3rd lap. SR increased on the 4th lap (35.91 ± 2.99 stroke·min-1. Peak blood lactate was 13.02 ± 1.72 mmol·l-1 three minutes after the maximal trial. The EMG average rectified value (ARV increased at the end of the race for all selected muscles, but the deltoid anterior and pectoralis major in the 1st lap and for biceps brachii, deltoid anterior and triceps brachii in the 4th lap. The mean frequency of the power spectral density (MNF decreased at the 4th lap for all muscles. These findings suggest the occurrence of fatigue at the beginning of the 2nd lap in the 200m breaststroke trial, characterized by changes in kinematic parameters and selective changes in upper limb muscle action. There was a trend towards a non-linear fatigue state.

  15. Mammalian Synthetic Biology: Time for Big MACs.

    Science.gov (United States)

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-10-21

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

  16. Cytometry of mammalian sperm

    Energy Technology Data Exchange (ETDEWEB)

    Gledhill, B.L.

    1983-10-11

    Male germ cells respond dramatically to a variety of insults and are important reproductive dosimeters. Semen analyses are very useful in studies on the effects of drugs, chemicals, and environmental hazards on testicular function, male fertility and heritable germinal mutations. The accessibility of male cells makes them well suited for analytical cytology. We might automate the process of determining sperm morphology but should not do so solely for increased speed. Rather, richer tangible benefits will derive from cytometric evaluation through increased sensitivity, reduced subjectivity, standardization between investigators and laboratories, enhanced archival systems, and the benefits of easily exchanged standardized data. Inroads on the standardization of assays for motility and functional integrity are being made. Flow cytometric analysis of total DNA content of individual sperm is an insensitive means to detect exposure to reproductive toxins because of the small size and low frequency of the DNA content errors. Flow cytometry can be applied to determine the proportions of X- and Y-sperm in semen samples.

  17. Mutagenesis in mammalian cells

    International Nuclear Information System (INIS)

    Burki, H.J.

    1981-01-01

    Mutagenic processes in synchronous cultures of Chinese hamster ovary cells have been studied. There is a difference in the induction of mutants by ultraviolet light during the cell cycle. There appears to be a sensitive period in the middle of the G1 stage of the cell cycle suggesting some mutagenic mechanism is present at that time. Studies indicate that mutation induction during the cell cycle is also mutagen specific since exposure to ethyl nitrosourea in the same system produces different results. Two clones have been isolated which are ultrasensitive to ultraviolet light. These cells are being used to determine if this hypermutability is cell-cycle dependent, related to cell cycle biochemistry, or to repair processes independent of cell cycle. Tritium and bromodeoxyuridine induced damage to synchronously dividing cell cultures are also being studied in relation to DNA replication. Cell killing by ionizing radiation is also related to the cell cycle. Sensitive times in the cell cycle for mutation induction by ionization radiation are identified

  18. Cytometry of mammalian sperm

    International Nuclear Information System (INIS)

    Gledhill, B.L.

    1983-01-01

    Male germ cells respond dramatically to a variety of insults and are important reproductive dosimeters. Semen analyses are very useful in studies on the effects of drugs, chemicals, and environmental hazards on testicular function, male fertility and heritable germinal mutations. The accessibility of male cells makes them well suited for analytical cytology. We might automate the process of determining sperm morphology but should not do so solely for increased speed. Rather, richer tangible benefits will derive from cytometric evaluation through increased sensitivity, reduced subjectivity, standardization between investigators and laboratories, enhanced archival systems, and the benefits of easily exchanged standardized data. Inroads on the standardization of assays for motility and functional integrity are being made. Flow cytometric analysis of total DNA content of individual sperm is an insensitive means to detect exposure to reproductive toxins because of the small size and low frequency of the DNA content errors. Flow cytometry can be applied to determine the proportions of X- and Y-sperm in semen samples

  19. Bioenergetics of mammalian sperm capacitation.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  20. Mammalian Toxicity of Munition Compounds. Phase II. Effects of Multiple Doses. Part III. 2,6-Dinitrotoluene

    Science.gov (United States)

    1976-07-01

    and the neuromuscular effects in these dogs were not due to hypocalcemia . The lowest serum calcium concen- tration in these dogs was 4.2 meq/liter...motor end plate might produce a local hypocalcemia . Such a mechanism is purely speculative. Qualitatively and quantitavely, most of the effects of 2,6...I ýNw,- -MIM I/ MIDWEST RESEARCH INS14ITUTE H0q .3L I LU -_ MAMMALIAN TOXICITY OF MUNITIONS COMPOUlNDSPHASE II: EFFECTS OF MiULTIPLE DOSES C* •PART

  1. HEMODYNAMIC AND LACTIC ACID RESPONSES TO PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION EXERCISE

    Directory of Open Access Journals (Sweden)

    Zuhal Gültekin

    2006-09-01

    Full Text Available The hemodynamic and metabolic responses to proprioceptive neuromuscular facilitation (PNF exercise were examined in 32 male university students (aged 19-28 years. Ten repetitions of PNF exercises were applied to the subjects' dominant upper extremities in the following order: as an agonist pattern flexion, adduction and external rotation; and as an antagonist pattern extension, abduction and internal rotation. Heart rate (HR, systolic blood pressure (SBP, diastolic blood pressure (DBP, double product (DP, and blood lactate concentration (La were determined before, immediately after, and at 1st, 3rd, and 5th minutes after PNF exercise. A one-way ANOVA with repeated measures indicated significant differences in HR, SBP, DBP, DP and La immediately after PNF exercise. HR increased from 81 (±10 to 108 (±15 b·min-1 (p < 0.01, SBP increased from 117 (±10 to 125 (±11 mmHg (p < 0.01, DBP increased from 71 (±10 to 75 (±8 mmHg (p < 0.01, DP increased from 96 (±16 to 135 (±24 (p < 0.01, and La increased from 0.69 (±0.31 to 3.99 (±14.63 mmol·L-1 (p < 0.01. Thus PNF exercise resulted in increased hemodynamic responses and blood lactate concentration that indicate a high strain on the cardiovascular system and anaerobic metabolism in healthy subjects

  2. Role of analgesics, sedatives, neuromuscular blockers, and delirium.

    Science.gov (United States)

    Hall, Jesse B; Schweickert, William; Kress, John P

    2009-10-01

    A major focus on critical care medicine concerns the institution of life-support therapies, such as mechanical ventilation, during periods of organ failure to permit a window of opportunity to diagnose and treat underlying disorders so that patients may be returned to their prior functional status upon recovery. With the growing success of these intensive care unit-based therapies and longer-term follow-up of patients, severe weakness involving the peripheral nervous system and muscles has been identified in many recovering patients, often confounding the time course or magnitude of recovery. Mechanical ventilation is often accompanied by pharmacologic treatments including analgesics, sedatives, and neuromuscular blockers. These drugs and the encephalopathies accompanying some forms of critical illness result in a high prevalence of delirium in mechanically ventilated patients. These drug effects likely contribute to an impaired ability to assess the magnitude of intensive care unit-acquired weakness, to additional time spent immobilized and mechanically ventilated, and to additional weakness from the patient's relative immobility and bedridden state. This review surveys recent literature documenting these relationships and identifying approaches to minimize pharmacologic contributions to intensive care unit-acquired weakness.

  3. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    Science.gov (United States)

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

    DEFF Research Database (Denmark)

    Viby-Mogensen, J.; Østergaard, D.; Donati, F.

    2000-01-01

    Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

  5. Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

  6. Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report

    Directory of Open Access Journals (Sweden)

    Parker Stephen W

    2005-02-01

    Full Text Available Abstract Background Vestibular rehabilitation (VR is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC, have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. Methods We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width, lower extremity sagittal plane mechanical energy expenditures (MEE, and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity, were measured. Results Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. Conclusion Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster

  7. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade

    DEFF Research Database (Denmark)

    Brueckmann, B; Sasaki, N; Grobara, P

    2015-01-01

    BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed...... by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual...... measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch® SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P

  8. Total hip arthroplasty in patients with neuromuscular imbalance.

    Science.gov (United States)

    Konan, S; Duncan, C P

    2018-01-01

    Patients with neuromuscular imbalance who require total hip arthroplasty (THA) present particular technical problems due to altered anatomy, abnormal bone stock, muscular imbalance and problems of rehabilitation. In this systematic review, we studied articles dealing with THA in patients with neuromuscular imbalance, published before April 2017. We recorded the demographics of the patients and the type of neuromuscular pathology, the indication for surgery, surgical approach, concomitant soft-tissue releases, the type of implant and bearing, pain and functional outcome as well as complications and survival. Recent advances in THA technology allow for successful outcomes in these patients. Our review suggests excellent benefits for pain relief and good functional outcome might be expected with a modest risk of complication. Cite this article: Bone Joint J 2018;100-B(1 Supple A):17-21. ©2018 The British Editorial Society of Bone & Joint Surgery.

  9. Surgical Space Conditions During Low-Pressure Laparoscopic Cholecystectomy with Deep Versus Moderate Neuromuscular Blockade

    DEFF Research Database (Denmark)

    Staehr-Rye, Anne K; Rasmussen, Lars S.; Rosenberg, Jacob

    2014-01-01

    : In this assessor-blinded study, 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade (rocuronium bolus plus infusion maintaining a posttetanic count 0-1) or moderate neuromuscular blockade...... (rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function). Patients received anesthesia with propofol, remifentanil, and rocuronium. The primary outcome was the proportion of procedures with optimal surgical space conditions (assessed by the surgeon...

  10. Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

    Science.gov (United States)

    Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

    2008-11-15

    We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

  11. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John

    2016-01-01

    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...

  12. New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

    Institute of Scientific and Technical Information of China (English)

    Charles H Knowles; Joanne E Martin

    2009-01-01

    Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

  13. Neuromuscular exercise as treatment of degenerative knee disease

    DEFF Research Database (Denmark)

    Ageberg, Eva; Roos, Ewa M.

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional...... instability associated with the degenerative knee disease than traditionally used training methods.SUMMARY FOR TABLE OF CONTENTS PAGECurrent data suggests that the effect from neuromuscular exercise on pain and function is comparable to the effects seen from other forms of exercise....

  14. Neuromuscular Activity and Knee Kinematics in Adolescents with Patellofemoral Pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Samani, Afshin; Olesen, Jens L

    2013-01-01

    This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS).......This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)....

  15. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  16. A mammalianized synthetic nitroreductase gene for high-level expression

    International Nuclear Information System (INIS)

    Grohmann, Maik; Paulmann, Nils; Fleischhauer, Sebastian; Vowinckel, Jakob; Priller, Josef; Walther, Diego J

    2009-01-01

    The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy. We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays. In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect. Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans

  17. Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

    Directory of Open Access Journals (Sweden)

    Stefan Hettwer

    Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

  18. Neuromuscular Structure, Evolution and Development in Meiofaunal Annelids with Special Focus on Dinophilus gyrociliatus (Dinophilidae)

    DEFF Research Database (Denmark)

    Kerbl, Alexandra

    less complex sensory structures. Yet, very little is still known on how these small brains are organized to fulfil basic functions. This study addresses the structure, evolution and development of neuromuscular systems within two exclusively meiofaunal lineages Lobatocerebridae and Dinophilidae....... RESULTS: Both families were shown to be nested within annelids in phylogenomic analyses based on transcriptomic data, which also suggest the Spiralian ancestor to be meiofaunal (Manuscript 4). The annelid affinity of the enigmatic Lobatocerebridae was further tested by detailed morphological examinations...... warranting further studies to uncover how the genetic domains influence the configuration of the brain...

  19. Enhancer evolution across 20 mammalian species

    DEFF Research Database (Denmark)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah

    2015-01-01

    The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

  20. Diagnostic value of CT scanning in neuromuscular diseases

    International Nuclear Information System (INIS)

    Bulcke, J.A.L.; Leuven Univ.; Herpels, V.

    1983-01-01

    The diagnosis of myopathies has become easier since the CT technique is available. In this article the possibilities of CT for diagnostic procedures of neuromuscular diseases are pointed out. Density measurements increase differentiation of atrophy or hypertrophy of muscles as well as other pathological changes. (orig.)

  1. Volume of the effect compartment in simulations of neuromuscular block

    NARCIS (Netherlands)

    Nigrovic, Vladimir; Proost, Johannes H.; Amann, Anton; Bhatt, Shashi B.

    2005-01-01

    Background: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. Methods: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent

  2. Neuromuscular stimulation after stroke: from technology to clinical deployment

    NARCIS (Netherlands)

    IJzerman, Maarten Joost; Renzenbrink, Gerbert J.; Geurts, Alexander C.H.

    2009-01-01

    Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades

  3. Elbow joint position sense after neuromuscular training with handheld vibration.

    Science.gov (United States)

    Tripp, Brady L; Faust, Donald; Jacobs, Patrick

    2009-01-01

    Clinicians use neuromuscular control exercises to enhance joint position sense (JPS); however, because standardizing such exercises is difficult, validations of their use are limited. To evaluate the acute effects of a neuromuscular training exercise with a handheld vibrating dumbbell on elbow JPS acuity. Crossover study. University athletic training research laboratory. Thirty-one healthy, college-aged volunteers (16 men, 15 women, age = 23 + or - 3 years, height = 173 + or - 8 cm, mass = 76 + or - 14 kg). We measured and trained elbow JPS using an electromagnetic tracking device that provided auditory and visual biofeedback. For JPS testing, participants held a dumbbell and actively identified the target elbow flexion angle (90 degrees ) using the software-generated biofeedback, followed by 3 repositioning trials without feedback. Each neuromuscular training protocol included 3 exercises during which participants held a 2.55-kg dumbbell vibrating at 15, 5, or 0 Hz and used software-generated biofeedback to locate and maintain the target elbow flexion angle for 15 seconds. We calculated absolute (accuracy) and variable (variability) errors using the differences between target and reproduced angles. Training protocols using 15-Hz vibration enhanced accuracy and decreased variability of elbow JPS (P or = .200). Our results suggest these neuromuscular control exercises, which included low-magnitude, low-frequency handheld vibration, may enhance elbow JPS. Future researchers should examine vibration of various durations and frequencies, should include injured participants and functional multijoint and multiplanar measures, and should examine long-term effects of training protocols on JPS and injury.

  4. Imaging of respiratory muscles in neuromuscular disease: A review.

    Science.gov (United States)

    Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

    2018-03-01

    Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

  5. Neuromuscular blockade for improvement of surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Scheppan, Susanne; Kissmeyer, Peter

    2015-01-01

    neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS...

  6. Alterations in neuromuscular function in girls with generalized joint hypermobility

    DEFF Research Database (Denmark)

    Jensen, Bente Rona; Melcher, Jesper Sandfeld; Melcher, Pia Grethe Sandfeld

    2016-01-01

    BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions...

  7. Influence of intense neuromuscular blockade on surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Donatsky, Anders Meller; Jensen, Bente Rona

    2015-01-01

    endotracheally intubated, mechanically ventilated, anesthetized with propofol and fentanyl, and randomized into two groups in a cross-over assessor-blinded design. Neuromuscular block was established with rocuronium. Artificial laparotomy for ileus was performed. We investigated the influence of intense...

  8. Neuromuscular function during stair descent in meniscectomized patients and controls

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Roos, Ewa M; Aagaard, Per

    2011-01-01

    The aim of this study was to identify differences in knee range of motion (ROM), movement speed, ground reaction forces (GRF) profile, neuromuscular activity, and muscle coactivation during the transition between stair descent and level walking in meniscectomized patients at high risk of knee...

  9. Roles of neuro-exocytotic proteins at the neuromuscular junction

    NARCIS (Netherlands)

    Sons-Michel, Michèle S.

    2011-01-01

    The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

  10. Comparison of the Effect of Neuromuscular Electrical Stimulation ...

    African Journals Online (AJOL)

    Children with cerebral palsy (CP) often demonstrate poor hand function due to spasticity. Thus spasticity in the wrist and finger flexors poses a great deal of functional limitations. This study was therefore designed to compare the effectiveness of Cryotherapy and Neuromuscular Electrical Stimulation (NMES) on spasticity ...

  11. Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

    Science.gov (United States)

    Ohlendieck, Kay

    2002-01-01

    This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

  12. Neuromuscular Control Deficits and the Risk of Subsequent Injury after a Concussion: A Scoping Review.

    Science.gov (United States)

    Howell, David R; Lynall, Robert C; Buckley, Thomas A; Herman, Daniel C

    2018-05-01

    An emerging area of research has identified that an increased risk of musculoskeletal injury may exist upon returning to sports after a sport-related concussion. The mechanisms underlying this recently discovered phenomenon, however, remain unknown. One theorized reason for this increased injury risk includes residual neuromuscular control deficits that remain impaired despite clinical recovery. Thus, the objectives of this review were: (1) to summarize the literature examining the relationship between concussion and risk of subsequent injury and (2) to summarize the literature for one mechanism with a theorized association with this increased injury risk, i.e., neuromuscular control deficits observed during gait after concussion under dual-task conditions. Two separate reviews were conducted consistent with both specified objectives. Studies published before 9 December, 2016 were identified using PubMed, Web of Science, and Academic Search Premier (EBSCOhost). Inclusion for the objective 1 search included dependent variables of quantitative measurements of musculoskeletal injury after concussion. Inclusion criteria for the objective 2 search included dependent variables pertaining to gait, dynamic balance control, and dual-task function. A total of 32 studies were included in the two reviews (objective 1 n = 10, objective 2 n = 22). According to a variety of study designs, athletes appear to have an increased risk of sustaining a musculoskeletal injury following a concussion. Furthermore, dual-task neuromuscular control deficits may continue to exist after patients report resolution of concussion symptoms, or perform normally on other clinical concussion tests. Therefore, musculoskeletal injury risk appears to increase following a concussion and persistent motor system and attentional deficits also seem to exist after a concussion. While not yet experimentally tested, these motor system and attentional deficits may contribute to the risk of sustaining a

  13. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  14. Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

    Science.gov (United States)

    de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

    1993-01-01

    To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

  15. Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

    Directory of Open Access Journals (Sweden)

    Alejandro Carbajal-Saucedo

    2014-01-01

    Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

  16. Stunted PFC activity during neuromuscular control under stress with obesity.

    Science.gov (United States)

    Mehta, Ranjana K

    2016-02-01

    Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

  17. Mutation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Okada, S.

    1982-01-01

    Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

  18. Interaction theory of mammalian mitochondria.

    Science.gov (United States)

    Nakada, K; Inoue, K; Hayashi, J

    2001-11-09

    We generated mice with deletion mutant mtDNA by its introduction from somatic cells into mouse zygotes. Expressions of disease phenotypes are limited to tissues expressing mitochondrial dysfunction. Considering that all these mice share the same nuclear background, these observations suggest that accumulation of the mutant mtDNA and resultant expressions of mitochondrial dysfunction are responsible for expression of disease phenotypes. On the other hand, mitochondrial dysfunction and expression of clinical abnormalities were not observed until the mutant mtDNA accumulated predominantly. This protection is due to the presence of extensive and continuous interaction between exogenous mitochondria from cybrids and recipient mitochondria from embryos. Thus, we would like to propose a new hypothesis on mitochondrial biogenesis, interaction theory of mitochondria: mammalian mitochondria exchange genetic contents, and thus lost the individuality and function as a single dynamic cellular unit. Copyright 2001 Academic Press.

  19. Producing Newborn Synchronous Mammalian Cells

    Science.gov (United States)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  20. The value transformation of health care: Impact on neuromuscular and electrodiagnostic medicine.

    Science.gov (United States)

    Narayanaswami, Pushpa; Suk, Millie; Jones, Lyell K

    2017-10-01

    Beginning in 2017, most physicians who participate in Medicare are subject to the Medicare Access and CHIP Reauthorization Act (MACRA), the milestone legislation that signals the US health care system's transition from volume-based to value-based care. Here we review emerging trends in development of value-based healthcare systems in the US. MACRA and the resulting Quality Payment Program create 2 participation pathways, the Merit-based Incentive Payment System (MIPS) and the Advanced Alternative Payment Model (AAPM) pathway. Although there are several program incentives for AAPM participation, to date there have been few AAPM options for specialists. MIPS and its widening bonus and penalty window will likely be the primary participation pathway in the early years of the program. Value-based payment has the potential to reshape health care delivery in the United States, with implications for neuromuscular and electrodiagnostic (EDX) specialists. Meaningful quality measures are required for neuromuscular and EDX specialists. Muscle Nerve 56: 679-683, 2017. © 2017 Wiley Periodicals, Inc.

  1. Mitochondrial DNA triplication and punctual mutations in patients with mitochondrial neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Mkaouar-Rebai, Emna, E-mail: emna.mkaouar@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Felhi, Rahma; Tabebi, Mouna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Alila-Fersi, Olfa; Chamkha, Imen [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Maalej, Marwa; Ammar, Marwa [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Kammoun, Fatma [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Keskes, Leila [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Hachicha, Mongia [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh02@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia)

    2016-04-29

    Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. As brain and muscle are highly dependent on OXPHOS, consequently, neurological disorders and myopathy are common features of mtDNA mutations. Mutations in mtDNA can be classified into three categories: large-scale rearrangements, point mutations in tRNA or rRNA genes and point mutations in protein coding genes. In the present report, we screened mitochondrial genes of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the second patient with mitochondrial neuromuscular disorder. - Highlights: • We reported 2 patients with mitochondrial neuromuscular disorders. • The heteroplasmic MT-ATP6 9157G>A variation was reported. • A triplication of 9 bp in the mitochondrial NC7 region was detected. • The m.14924T>C transition (S60P) in the MT-CYB gene was found.

  2. What occupant kinematics and neuromuscular responses tell us about whiplash injury.

    Science.gov (United States)

    Siegmund, Gunter P

    2011-12-01

    Literature-based review. To review the published data on occupant kinematic and neuromuscular responses during low-speed impacts and analyze how these data inform our understanding of whiplash injury. A stereotypical kinematic and neuromuscular response has been observed in human subjects exposed to rear-end impacts. Combined with various models of injury, these response data have been used to develop anti-whiplash seats that prevent whiplash injury in many, but not all, individuals exposed to a rear-end crash. Synthesis of the literature. Understanding of the occupant kinematics and neuromuscular responses, combined with data from various seat-related interventions, have shown that differential motion between the superior and inferior ends of the cervical spine is responsible for many whiplash injuries. The number of whiplash injuries not prevented by current anti-whiplash seats suggests than further work remains, possibly related to designing seats that respond dynamically to the occupant and collision properties. Neck muscles alter the head and neck kinematics during the interval in which injury likely occurs, even in initially relaxed occupants. It remains unclear whether muscle activation mitigates or exacerbates whiplash injury. If muscle activation mitigates injury, then advance warning could be used to help occupant tense their muscles before impact. Alternatively, if muscle activation exacerbates whiplash injury, then a loud preimpact sound that uncouples the startle and postural components of the muscle response could reduce peak muscle activation during a whiplash exposure. Our improved understanding of whiplash injury has led to anti-whiplash seats that have prevented many whiplash injuries. Further work remains to optimize these and possibly other systems to further reduce the number of whiplash injuries.

  3. A Comparative Study of Sagittal Balance in Patients with Neuromuscular Scoliosis

    Directory of Open Access Journals (Sweden)

    Paulo Alvim Borges

    Full Text Available OBJECTIVES: Spinopelvic alignment has been associated with improved quality of life in patients with vertebral deformities, and it helps to compensate for imbalances in gait. Although surgical treatment of scoliosis in patients with neuromuscular spinal deformities promotes correction of coronal scoliotic deformities, it remains poorly established whether this results in large changes in sagittal balance parameters in this specific population. The objective of this study is to compare these parameters before and after the current procedure under the hypothesis is that there is no significant modification. METHODS: Sampling included all records of patients with neuromuscular scoliosis with adequate radiographic records treated at Institute of Orthopedics and Traumatology of Clinics Hospital of University of São Paulo (IOT-HCFMUSP from January 2009 to December 2013. Parameters analyzed were incidence, sacral inclination, pelvic tilt, lumbar lordosis, thoracic kyphosis, spinosacral angle, spinal inclination and spinopelvic inclination obtained using the iSite-Philips digital display system with Surgimap and a validated method for digital measurements of scoliosis radiographs. Comparison between the pre- and post-operative conditions involved means and standard deviations and the t-test. RESULTS: Based on 101 medical records only, 16 patients met the inclusion criteria for this study, including 7 males and 9 females, with an age range of 9-20 and a mean age of 12.9±3.06; 14 were diagnosed with cerebral palsy. No significant differences were found between pre and postoperative parameters. CONCLUSIONS: Despite correction of coronal scoliotic deformity in patients with neuromuscular deformities, there were no changes in spinopelvic alignment parameters in the group studied.

  4. Redox homeostasis and age‐related deficits in neuromuscular integrity and function

    Science.gov (United States)

    Lightfoot, Adam P.; Earl, Kate E.; Stofanko, Martin; McDonagh, Brian

    2017-01-01

    Abstract Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness. PMID:28744984

  5. Spinal Muscular Atrophy: From Defective Chaperoning of snRNP Assembly to Neuromuscular Dysfunction

    Directory of Open Access Journals (Sweden)

    Maia Lanfranco

    2017-06-01

    Full Text Available Spinal Muscular Atrophy (SMA is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN protein. SMN is part of a multiprotein complex that also includes Gemins 2–8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5 complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs to generate small nuclear ribonucleoproteins (snRNPs, which are the operating components of the spliceosome. Molecular and structural studies have refined our knowledge of the key events taking place within the crowded environment of cells and the numerous precautions undertaken to ensure the faithful assembly of snRNPs. Nonetheless, it remains unclear whether a loss of chaperoning in snRNP assembly, considered as a “housekeeping” activity, is responsible for the selective neuromuscular phenotype in SMA. This review thus shines light on in vivo studies that point toward disturbances in snRNP assembly and the consequential transcriptome abnormalities as the primary drivers of the progressive neuromuscular degeneration underpinning the disease. Disruption of U1 snRNP or snRNP assembly factors other than SMN induces phenotypes that mirror aspects of SMN deficiency, and splicing defects, described in numerous SMA models, can lead to a DNA damage and stress response that compromises the survival of the motor system. Restoring the correct chaperoning of snRNP assembly is therefore predicted to enhance the benefit of SMA therapeutic modalities based on augmenting SMN expression.

  6. Balance improvements in female high school basketball players after a 6-week neuromuscular-training program.

    Science.gov (United States)

    McLeod, Tamara C Valovich; Armstrong, Travis; Miller, Mathew; Sauers, Jamie L

    2009-11-01

    Poor balance has been associated with increased injury risk among athletes. Neuromuscular-training programs have been advocated as a means of injury prevention, but little is known about the benefits of these programs on balance in high school athletes. To determine whether there are balance gains after participation in a neuromuscular-training program in high school athletes. Nonrandomized controlled trial. All data were collected at each participating high school before and after a 6-wk intervention or control period. 62 female high school basketball players recruited from the local high school community and assigned to a training (n = 37) or control (n = 25) group. Training-group subjects participated in a 6-wk neuromuscular-training program that included plyometric, functional-strengthening, balance, and stability-ball exercises. Data were collected for the Balance Error Scoring System (BESS) and Star Excursion Balance Test (SEBT) before and after the 6-wk intervention or control period. The authors found a significant decrease in total BESS errors in the trained group at the posttest compared with their pretest and the control group (P = .003). Trained subjects also scored significantly fewer BESS errors on the single-foam and tandem-foam conditions at the posttest than the control group and demonstrated improvements on the single-foam compared with their pretest (P = .033). The authors found improvements in reach in the lateral, anteromedial, medial, and posterior directions in the trained group at the posttest compared with the control group (P training program can increase the balance and proprioceptive capabilities of female high school basketball players and that clinical balance measures are sensitive to detect these differences.

  7. Developing maximal neuromuscular power: Part 1--biological basis of maximal power production.

    Science.gov (United States)

    Cormie, Prue; McGuigan, Michael R; Newton, Robert U

    2011-01-01

    This series of reviews focuses on the most important neuromuscular function in many sport performances, the ability to generate maximal muscular power. Part 1 focuses on the factors that affect maximal power production, while part 2, which will follow in a forthcoming edition of Sports Medicine, explores the practical application of these findings by reviewing the scientific literature relevant to the development of training programmes that most effectively enhance maximal power production. The ability of the neuromuscular system to generate maximal power is affected by a range of interrelated factors. Maximal muscular power is defined and limited by the force-velocity relationship and affected by the length-tension relationship. The ability to generate maximal power is influenced by the type of muscle action involved and, in particular, the time available to develop force, storage and utilization of elastic energy, interactions of contractile and elastic elements, potentiation of contractile and elastic filaments as well as stretch reflexes. Furthermore, maximal power production is influenced by morphological factors including fibre type contribution to whole muscle area, muscle architectural features and tendon properties as well as neural factors including motor unit recruitment, firing frequency, synchronization and inter-muscular coordination. In addition, acute changes in the muscle environment (i.e. alterations resulting from fatigue, changes in hormone milieu and muscle temperature) impact the ability to generate maximal power. Resistance training has been shown to impact each of these neuromuscular factors in quite specific ways. Therefore, an understanding of the biological basis of maximal power production is essential for developing training programmes that effectively enhance maximal power production in the human.

  8. Mammalian gastrointestinal parasites in rainforest remnants

    Indian Academy of Sciences (India)

    Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

  9. Diagnosis and management of adult hereditary cardio-neuromuscular disorders: A model for the multidisciplinary care of complex genetic disorders.

    Science.gov (United States)

    Sommerville, R Brian; Vincenti, Margherita Guzzi; Winborn, Kathleen; Casey, Anne; Stitziel, Nathan O; Connolly, Anne M; Mann, Douglas L

    2017-01-01

    Genetic disorders that disrupt the structure and function of the cardiovascular system and the peripheral nervous system are common enough to be encountered in routine cardiovascular practice. Although often these patients are diagnosed in childhood and come to the cardiologist fully characterized, some patients with hereditary neuromuscular disease may not manifest until adulthood and will present initially to the adult cardiologist for an evaluation of an abnormal ECG, unexplained syncope, LV hypertrophy, and or a dilated cardiomyopathy of unknown cause. Cardiologists are often ill-equipped to manage these patients due to lack of training and exposure as well as the complete absence of practice guidelines to aid in the diagnosis and management of these disorders. Here, we review three key neuromuscular diseases that affect the cardiovascular system in adults (myotonic dystrophy type 1, Friedreich ataxia, and Emery-Dreifuss muscular dystrophy), with an emphasis on their clinical presentation, genetic and molecular pathogenesis, and recent important research on medical and interventional treatments. We also advocate the development of interdisciplinary cardio-neuromuscular clinics to optimize the care for these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Derived (mutated)-types of TRPV6 channels elicit greater Ca²+ influx into the cells than ancestral-types of TRPV6: evidence from Xenopus oocytes and mammalian cell expression system.

    Science.gov (United States)

    Sudo, Yuka; Matsuo, Kiyotaka; Tetsuo, Tomoyuki; Tsutsumi, Satoshi; Ohkura, Masamichi; Nakai, Junichi; Uezono, Yasuhito

    2010-01-01

    The frequency of the allele containing three derived nonsynonymous SNPs (157C, 378M, 681M) of the gene encoding calcium permeable TRPV6 channels expressed in the intestine has been increased by positive selection in non-African populations. To understand the nature of these SNPs, we compared the properties of Ca²+ influx of ancestral (in African populations) and derived-TRPV6 (in non-African populations) channels with electrophysiological, Ca²+-imaging, and morphological methods using both the Xenopus oocyte and mammalian cell expression systems. Functional electrophysiological and Ca²+-imaging analyses indicated that the derived-TRPV6 elicited more Ca²+ influx than the ancestral one in TRPV6-expressing cells where both channels were equally expressed in the cells. Ca²+-inactivation properties in the ancestral- and derived-TRPV6 were almost the same. Furthermore, fluorescence resonance energy transfer (FRET) analysis showed that both channels have similar multimeric formation properties, suggesting that derived-TRPV6 itself could cause higher Ca²+ influx. These findings suggest that populations having derived-TRPV6 in non-African areas may absorb higher Ca²+ from the intestine than ancestral-TRPV6 in the African area.

  11. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  12. Is ultraviolet enhanced reactivation of mammalian virus mutagenic

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

    1981-01-01

    Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

  13. The role of patient advocacy organisations in neuromuscular disease R&D - The case of the Dutch neuromuscular disease association VSN

    NARCIS (Netherlands)

    Boon, W.P.C.; Broekgaarden, R.

    2010-01-01

    This article investigates to what extent patient advocacy organisations play a role in influencing R&D and policymaking for rare neuromuscular diseases. The Dutch neuromuscular disease organisation VSN is studied in depth. A brief history of the VSN is sketched along with the international

  14. Mammalian oocyte growth and development in vitro.

    Science.gov (United States)

    Eppig, J J; O'Brien, M; Wigglesworth, K

    1996-06-01

    This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk.

  15. Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

    Directory of Open Access Journals (Sweden)

    Galia Ramírez-Toloza

    2017-09-01

    Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host

  16. Learning disabilities in neuromuscular disorders: a springboard for adult life.

    Science.gov (United States)

    Astrea, Guja; Battini, Roberta; Lenzi, Sara; Frosini, Silvia; Bonetti, Silvia; Moretti, Elena; Perazza, Silvia; Santorelli, Filippo M; Pecini, Chiara

    2016-10-01

    Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

  17. Early appearance and possible roles of non-neuromuscular cholinesterases.

    Directory of Open Access Journals (Sweden)

    Carla eFalugi

    2012-04-01

    Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

  18. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    Science.gov (United States)

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  19. Bloqueio neuromuscular residual após o uso de rocurônio ou cisatracúrio Bloqueo neuromuscular residual después del uso de rocuronio o cisatracúrio Residual neuromuscular block after rocuronium or cisatracurium

    Directory of Open Access Journals (Sweden)

    Bruno Salomé de Morais

    2005-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio neuromuscular residual na sala de recuperação pós-anestésica (SRPA é um fenômeno que pode aumentar a morbidade pós-operatória, com incidência variando entre 0% e 93%. O objetivo deste estudo foi avaliar a incidência do bloqueio neuromuscular residual na SRPA. MÉTODO: Foram estudados 93 pacientes submetidos à cirurgia geral com o uso de cisatracúrio ou rocurônio. Após a admissão na SRPA foi realizada a monitorização objetiva da função neuromuscular (aceleromiografia - TOF GUARD. O bloqueio neuromuscular residual foi definido como SQE JUSTIFICATIVA Y OBJETIVOS: El bloqueo neuromuscular residual en la sala de recuperación posanestésica (SRPA es un fenómeno que puede aumentar la morbidez posoperatoria, con incidencia variando entre 0% y 93%. La finalidad de este estudio fue evaluar la incidencia del bloqueo neuromuscular residual en la SRPA. MÉTODO: Fueron estudiados 93 pacientes sometidos a cirugía general con el uso de cisatracúrio o rocuronio. Después de la admisión en la SRPA fue realizada la monitorización objetiva de la función neuromuscular (aceleromiografia - TOF-GUARD. El bloqueo neuromuscular residual fue definido como TOF BACKGROUND AND OBJECTIVES: Residual neuromuscular block in the post-anesthetic recovery unit (PACU may increase postoperative morbidity from 0% to 93%. This study aimed at evaluating the incidence of residual neuromuscular block in the PACU. METHODS: Participated in this study 93 patients submitted to general anesthesia with cisatracurium or rocuronium. After PACU admission, neuromuscular function was objectively monitored (acceleromyography - TOF GUARD. Residual neuromuscular block was defined as TOF < 0.9. RESULTS: From 93 patients, 53 received cisatracurium and 40 rocuronium. Demographics, procedure length and the use of antagonists were comparable between groups. Residual neuromuscular block was 32% in subgroup C (cisatracurium and 30% in subgroup R

  20. A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

    International Nuclear Information System (INIS)

    Hanley, Kathryn A.; Manlucu, Luella R.; Gilmore, Lara E.; Blaney, Joseph E.; Hanson, Christopher T.; Murphy, Brian R.; Whitehead, Stephen S.

    2003-01-01

    An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Δ30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host

  1. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    Science.gov (United States)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  2. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

  3. Ultrastructural muscle and neuro-muscular junction alterations in polymyositis

    Directory of Open Access Journals (Sweden)

    L. L. Babakova

    2012-01-01

    Full Text Available Ultrastructural analysis of 7 biopsies from m.palmaris longus and m.deltoideus in patients with confirmed polymyositis revealed alterationand degeneration of muscle fibers and anomalies of neuro-muscular junction (NMJ. The NMJ abnormalities and following denervation ofmuscle fibers in polymyositis start with subsynaptic damages. The occurance of regeneration features in muscle fibers at any stage is characteristic for PM.

  4. Neuromuscular Control of Rapid Linear Accelerations in Fish

    Science.gov (United States)

    2016-06-22

    sunfish, Lepomis macrochirus. Animals with flexible bodies, like fishes , face a tradeoff for rapid movements. To produce high forces, they must...2014 30-Apr-2015 Approved for Public Release; Distribution Unlimited Final Report: Neuromuscular Control of Rapid Linear Accelerations in Fish The...Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 swimming, acceleration, fish , muscle, stiffness REPORT DOCUMENTATION PAGE 11. SPONSOR

  5. Computed tomography of skeletal muscles in neuromuscular disease

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Kuether, G.; Muenchen Univ.

    1985-01-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions. (orig.) [de

  6. Computed tomography of skeletal muscles in neuromuscular disease

    Energy Technology Data Exchange (ETDEWEB)

    Rodiek, S.O.; Kuether, G.

    1985-06-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

  7. Use of rocuronium and sugammadex under neuromuscular transmission monitoring in a patient with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Chryssoula Staikou

    2017-01-01

    Full Text Available Multiple sclerosis (MS is a potentially disabling disease characterized by demyelinating lesions in the central nervous system. One of the anesthetic challenges encountered in surgical patients with MS is the management of neuromuscular blockade (NMB and its reversal. We report a case of a 31-year-old female patient suffering from MS, who underwent gynecological surgery under general anesthesia with sevoflurane, fentanyl, and rocuronium which was successfully reversed with sugammadex. Neuromuscular transmission (NMT monitoring was used to guide the intraoperative doses of rocuronium and also the reversal of NMB by the use of sugammadex to ensure a safe tracheal extubation. In addition, delivered volatile was titrated according to anesthetic depth monitoring (Bispectral Index while esophageal temperature was also monitored for the maintenance of normothermia. Postoperatively, a multimodal analgesic scheme offered a high-quality analgesia and sleep, minimization of anxiety, and increased patient satisfaction. At 1-month follow-up, the patient's course was uncomplicated without any MS exacerbation. We consider that the use of rocuronium and sugammadex under NMT monitoring may represent a useful and safe choice in patients with MS.

  8. Alternative NF-κB Isoforms in the Drosophila Neuromuscular Junction and Brain.

    Directory of Open Access Journals (Sweden)

    Bo Zhou

    Full Text Available The Drosophila NF-κB protein Dorsal is expressed at the larval neuromuscular junction, where its expression appears unrelated to known Dorsal functions in embryonic patterning and innate immunity. Using confocal microscopy with domain-specific antisera, we demonstrate that larval muscle expresses only the B isoform of Dorsal, which arises by intron retention. We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear translocation. We further find that the Dorsal-related immune factor Dif encodes a B isoform, reflecting a conservation of B domains across a range of insect NF-κB proteins. Carrying out mutagenesis of the Dif locus via a site-specific recombineering approach, we demonstrate that Dif B is the major, if not sole, Dif isoform in the mushroom bodies of the larval brain. The Dorsal and Dif B isoforms thus share a specific association with nervous system tissues as well as an alternative protein structure.

  9. Prolonged static stretching does not influence running economy despite changes in neuromuscular function.

    Science.gov (United States)

    Allison, Sarah J; Bailey, David M; Folland, Jonathan P

    2008-12-01

    The aim of this study was to examine the acute effects of prolonged static stretching (SS) on running economy. Ten male runners (VO2(peak) 60.1 +/- 7.3 ml x kg(-1) x min(-1)) performed 10 min of treadmill running at 70% VO2(peak) before and after SS and no stretching interventions. For the stretching intervention, each leg was stretched unilaterally for 40 s with each of eight different exercises and this was repeated three times. Respiratory gas exchange was measured throughout the running exercise with an automated gas analysis system. On a separate day, participants were tested for sit and reach range of motion, isometric strength and countermovement jump height before and after SS. The oxygen uptake, minute ventilation, energy expenditure, respiratory exchange ratio and heart rate responses to running were unaffected by the stretching intervention. This was despite a significant effect of SS on neuromuscular function (sit and reach range of motion, +2.7 +/- 0.6 cm; isometric strength, -5.6% +/- 3.4%; countermovement jump height -5.5% +/- 3.4%; all P influence running economy despite changes in neuromuscular function.

  10. Neuromuscular dose-response studies: determining sample size.

    Science.gov (United States)

    Kopman, A F; Lien, C A; Naguib, M

    2011-02-01

    Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

  11. Neuromuscular interactions around the knee in children, adults and elderly

    Science.gov (United States)

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

  12. Bilateral neuromuscular and force differences during a plyometric task.

    Science.gov (United States)

    Ball, Nick B; Scurr, Joanna C

    2009-08-01

    The purpose of this article is to compare the bilateral neuromuscular and force contribution during a plyometric bounce drop jump task and to assess the affects of nonsimultaneous foot placement. Sixteen male participants performed bounce drop jumps from a height of 0.4 m. Mean peak electromyography activity of the soleus, medial, and lateral gastrocnemius of both legs was recorded from each phase of the drop jump and normalized to a reference dynamic muscle action. Resultant ground reaction force, ground contact time, and duration of the drop jumps were recorded from each leg. Multivariate analysis of variance was used to compare bilateral electromyographic activity, resultant peak ground reaction force, and contact duration. Pearson's correlations (r) ascertained relationships between normalized electromyographic activity and contact time. Significant differences were shown between left and right triceps surae normalized electromyography during precontact and contact40ms (p 0.01). Significant differences were found between normalized soleus electromyography and both gastrocnemii for both legs during precontact (p 0.01). Weak relationships were found between normalized electromyographic activity and nonsimultaneous foot contact (r < 0.2). This study showed differences between left and right triceps surae in neuromuscular strategies engaged in the early stages of a drop jump task. Differences in contact time initiation were present; however, they are not significant enough to cause neuromuscular differences in the plantar flexor muscles.

  13. Neuromuscular signs associated with acute hypophosphatemia in a dog.

    Science.gov (United States)

    Claus, Kimberly N; Day, Thomas K; Wolf, Christina

    2015-01-01

    The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

  14. CT in neuromuscular disorders: A comparison of CT and histology

    International Nuclear Information System (INIS)

    Vliet, A.M. van der; Thijssen, H.O.M.; Merx, J.L.; Joosten, E.

    1988-01-01

    The value of CT-examination of the muscles compared to histology was studied in a retrospective analysis of 30 patients with clinical suspicion of neuromuscular disorder. In the evaluation of the CT-results descriptive criteria were used. The histologic diagnosis came from needle-biopsies taken from the quadriceps muscle. Considering the whole group of neuromuscular disorders, CT has an overall accuracy of 84.8%, a positive predictive value of 95.5% and a negative predictive value of 63.6%. This makes the use of CT as a diagnostic tool in neuromuscular disorders a reliable examination technique. In patients with a polymyositis there is even a 100% correlation between CT findings and biopsy results. Discrepancy between the biopsy results is remarkable of the quadriceps muscle and the CT findings: The number of abnormal histological findings is twice the number of abnormal CT findings. Using the more proximal gluteal region as a biopsy site would have decreased this discrepancy and would therefore have given a better correlation between CT and histology. The choice of protocol in determining the levels to be scanned is of great importance in achieving good reproducability in follow-up CT examinations. (orig.)

  15. Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2018-01-01

    Full Text Available Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

  16. Magnetic resonance imaging (MRI) in the diagnosis of neuromuscular diseases

    International Nuclear Information System (INIS)

    Schalke, B.C.G.; Rohkamm, R.; Kaiser, W.

    1990-01-01

    In the last few years imaging procedures became also important in the diagnosis of neuromuscular diseases. We examined more than 150 patients with different neuromuscular diseases with MRI. Conventional diagnostic procedures like EMG, muscle biopsy can not be replaced by imaging procedures. MRI gives the chance to get additional diagnostic informations. It is possible to determine exact distribution and intensity of pathological changes in the muscle. Inflammatory muscle diseases can be differrentiated by T1/T2 values from atrophic/dystrophic diseases. The resolving power is very high and allows the exact detection of affected areas even in a single muscle. This can help to reduce false negative muscle biopsies. This is very useful in children and young adults. MRI can be used for the early detection of genetic myopathies and neuropathies. MRI allows to examine all muscles, including the heart, bone artefacts are absent. Heart muscle involvement in neuromuscular diseases can directly be shown by this method without any risk for the patient. In addition P-spectroscopy can be done for better understanding of pathogenesis, especially if the exact distribution of pathological changes is known. (author)

  17. Recent advances in neuromuscular block during anesthesia [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Martijn Boon

    2018-02-01

    Full Text Available Muscle relaxation is a routine part of anesthesia and has important advantages. However, the lingering effects of muscle relaxants in the postoperative period have historically been associated with postoperative adverse events. Neuromuscular reversal, together with neuromuscular monitoring, is a recognized strategy to reduce the rate of postoperative residual relaxation but has only marginally improved outcome in the past few decades. Sugammadex, a novel reversal agent with unique encapsulating properties, has changed the landscape of neuromuscular reversal and opened up new opportunities to improve patient care. By quickly and completely reversing any depth of neuromuscular block, it may reduce the rate of residual relaxation and improve respiratory recovery. In addition, sugammadex has made the use of deep neuromuscular block possible during surgery. Deep neuromuscular block may improve surgical working conditions and allow for a reduction in insufflation pressures during selected laparoscopic procedures. However, whether and how this may impact outcomes is not well established.

  18. [Neurophysiology of systemic diseases].

    Science.gov (United States)

    Attarian, S

    2004-01-01

    Connective tissue diseases represent a varied and challenging group of disorders. Neuromuscular structures are highly susceptible targets for damage. In this review, the neurophysiological explorations of the neuromuscular complications are examined with particular attention to the peripheral nerve system. The most common presentations are sensorimotor polyneuropathy, mononeuritis multiplex, distal symmetric neuropathy, compression neuropathy and trigeminal sensory neuropathy.

  19. The implementation of quantitative electromyographic neuromuscular monitoring in an academic anesthesia department.

    Science.gov (United States)

    Todd, Michael M; Hindman, Bradley J; King, Brian J

    2014-08-01

    Although experts agree on the importance of quantitative neuromuscular blockade monitoring, particularly for managing reversal, such monitoring is not in widespread use. We describe the processes and results of our departmental experience with the introduction of such quantitative monitoring. In mid-2010, the senior authors became concerned about the management of nondepolarizing neuromuscular blockers (NMB) by providers within the department, based on personal observations and on a review of a departmental quality assurance/adverse event database. This review indicated the occurrence of 2 to 4 reintubations/year in the postanesthesia care unit (PACU) that were deemed to be probably or possibly related to inadequate reversal. In response, quantitative blockade equipment (Datex-Omeda ElectroSensor™ EMG system) was installed in all our main operating rooms in January 2011. This introduction was accompanied by an extensive educational effort. Adoption of the system was slow; by mid-2011, the quantitative system was being used in system. In the initial (August 2011) PACU survey of 96 patients receiving nondepolarizing NMBs, 31% had a TOF ratio of ≤0.9, 17% had a ratio of ≤0.8, and 4 patients (4%) had ratios of ≤0.5. A record review showed that the quantitative monitoring system had been used to monitor reversal in only 51% of these patients, and 23% of patients had no evidence of any monitoring, including qualitative TOF assessment. By December of 2012 (after 2 interim PACU monitoring surveys), a fourth survey showed 15% of 101 monitored patients had a TOF ratio ≤0.9, and only 5% had ratios ≤0.8. (P system was present in 83% of cases (P < 0.05 vs August 2011). A final survey in July 2013 showed nearly identical values to those from December 2012. The lowest TOF ratio observed in any patient not receiving a nondepolarizing NMB was 0.92. There were no changes in the patterns of either rocuronium or neostigmine use over the duration of the project (through

  20. The relative frequency of common neuromuscular diagnoses in a reference center

    OpenAIRE

    Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista Junior, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

    2017-01-01

    ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded confir...

  1. Neuromuscular Electrical Stimulation for Mobility Support of Elderly.

    Science.gov (United States)

    Mayr, Winfried

    2015-08-24

    The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in "compliance data storage" as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

  2. Neuromuscular electrical stimulation for mobility support of elderly

    Directory of Open Access Journals (Sweden)

    Winfried Mayr

    2015-10-01

    Full Text Available The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in “compliance data storage” as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC and maximum stimulation induced contraction (MSC were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period

  3. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  4. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.; Gadê lha, H.; Smith, D.J.; Blake, J.R.; Kirkman-Brown, J.C.

    2011-01-01

    the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian

  5. Enhancer Evolution across 20 Mammalian Species

    Science.gov (United States)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  6. Presence of abscisic acid, a phytohormone, in the mammalian brain.

    OpenAIRE

    Le Page-Degivry, M T; Bidard, J N; Rouvier, E; Bulard, C; Lazdunski, M

    1986-01-01

    This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention pr...

  7. Mottled Mice and Non-Mammalian Models of Menkes Disease

    DEFF Research Database (Denmark)

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critica......-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals....

  8. Photooxidative damage to mammalian cells and proteins by visible light

    International Nuclear Information System (INIS)

    Packer, L.; Kellogg, E.W. III

    1980-01-01

    In the present article, studies carried out in our laboratory on the effects of visible irradiation and O 2 in a variety of target systems ranging from cultured mammalian cells to purified catalase are reviewed. We will relate these studies of photooxidative damage to a scheme for the propagation of intracellular damage which traces a number of the possible pro-oxidant and anti-oxidant pathways found in the cell

  9. Endogenous peripheral neuromodulators of the mammalian taste bud.

    Science.gov (United States)

    Dando, Robin

    2010-10-01

    The sensitivity of the mammalian taste system displays a degree of plasticity based on short-term nutritional requirements. Deficiency in a particular substance may lead to a perceived increase in palatability of this substance, providing an additional drive to redress this nutritional imbalance through modification of intake. This alteration occurs not only in the brain but also, before any higher level processing has occurred, in the taste buds themselves. A brief review of recent advances is offered.

  10. Utilization of ACL Injury Biomechanical and Neuromuscular Risk Profile Analysis to Determine the Effectiveness of Neuromuscular Training.

    Science.gov (United States)

    Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

    2016-12-01

    The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).

  11. A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

    Science.gov (United States)

    Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

    2016-06-01

    We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

  12. Manejo de longo prazo em crianças com transtornos neuromusculares Long-term management of children with neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Eugen-Matthias Strehle

    2009-10-01

    inherited myopathies and neuropathies. A patient cohort (n = 200 was evaluated using descriptive statistics. SUMMARY PF THE FINDINGS: Duchenne muscular dystrophy accounted for almost half of the diagnoses, followed by spinal muscular atrophy (12%, Becker muscular dystrophy and myotonic dystrophy (7% each. Sixteen patients (9% had an unknown myopathy. CONCLUSIONS: As with other chronic illnesses, these patients should be regularly reviewed by health professionals from an early age to increase life expectancy and improve quality of life. It is useful for physicians to take a structured approach when looking after children with neuromuscular disorders and to monitor all affected organ systems.

  13. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

    2014-05-01

    Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

  14. Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2012-09-01

    Full Text Available Abstract Background Recycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ. We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD1 proteinin the Torpedo californica electric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/− NMJs. Methods Localization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/− mouse skeletal muscle. Results Endogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal muscle in vivo. EHD1−/− mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in the T. californica electric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/− mouse skeletal muscle than in wild-type skeletal muscle. Conclusion EHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/− muscle may be due to functional compensation by other EHD paralogs.

  15. Prdm9 controls activation of mammalian recombination hotspots.

    Science.gov (United States)

    Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

    2010-02-12

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

  16. Stability of resazurin in buffers and mammalian cell culture media

    DEFF Research Database (Denmark)

    Rasmussen, Eva; Nicolaisen, G.M.

    1999-01-01

    The utility of a ferricyanide/ferrocyanide system used in the AlamarBlue(TM) (Serotec, Oxford, UK) vital. dye to inhibit the reduction of resazurin by mammalian cell culture media is questioned. Resazurin was found to be relatively stable when dissolved in phosphate-buffered saline (PBS). The use...... of HEPES resulted in a huge immediate dye reduction, which was significantly enhanced by exposure to diffuse light from fluorescent tubes in the laboratory 8 h per day. The reduction of resazurin by various cell culture media was time and temperature dependent, and it was significantly enhanced......'s nutrient mixture F-10 and F-12. Fetal calf serum (5-20%) slightly decreased resazurin reduction during the first 2 days of incubation. The reduction of resazurin by mammalian cell culture media do not appear to be problematic under normal culture conditions, and it is primarily dependent upon the presence...

  17. Etiology and Recovery of Neuromuscular Fatigue following Competitive Soccer Match-Play

    Directory of Open Access Journals (Sweden)

    Callum G. Brownstein

    2017-10-01

    Full Text Available Aim: Previous research into the etiology of neuromuscular fatigue following competitive soccer match-play has primarily focused on peripheral perturbations, with limited research assessing central nervous system function in the days post-match. The aim of the present study was to examine the contribution and time-course of recovery of central and peripheral factors toward neuromuscular fatigue following competitive soccer match-play.Methods: Sixteen male semi-professional soccer players completed a 90-min soccer match. Pre-, post- and at 24, 48, and 72 h participants completed a battery of neuromuscular, physical, and perceptual tests. Maximal voluntary contraction force (MVC and twitch responses to electrical (femoral nerve and transcranial magnetic stimulation (TMS of the motor cortex during isometric knee-extension and at rest were measured to assess central nervous system (voluntary activation, VA and muscle contractile (potentiated twitch force, Qtw, pot function. Electromyography responses of the rectus femoris to single- and paired-pulse TMS were used to assess corticospinal excitability and short-interval intracortical inhibition (SICI, respectively. Fatigue and perceptions of muscle soreness were assessed via visual analog scales, and physical function was assessed through measures of jump (countermovement jump height and reactive strength index and sprint performance.Results: Competitive match-play elicited significant post-match declines in MVC force (−14%, P < 0.001 that persisted for 48 h (−4%, P = 0.01, before recovering by 72 h post-exercise. VA (motor point stimulation was reduced immediately post-match (−8%, P < 0.001, and remained depressed at 24 h (−5%, P = 0.01 before recovering by 48 h post-exercise. Qtw,pot was reduced post-match (−14%, P < 0.001, remained depressed at 24 h (−6%, P = 0.01, before recovering by 48 h post-exercise. No changes were evident in corticospinal excitability or SICI. Jump performance

  18. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  19. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  20. A hybrid mammalian cell cycle model

    Directory of Open Access Journals (Sweden)

    Vincent Noël

    2013-08-01

    Full Text Available Hybrid modeling provides an effective solution to cope with multiple time scales dynamics in systems biology. Among the applications of this method, one of the most important is the cell cycle regulation. The machinery of the cell cycle, leading to cell division and proliferation, combines slow growth, spatio-temporal re-organisation of the cell, and rapid changes of regulatory proteins concentrations induced by post-translational modifications. The advancement through the cell cycle comprises a well defined sequence of stages, separated by checkpoint transitions. The combination of continuous and discrete changes justifies hybrid modelling approaches to cell cycle dynamics. We present a piecewise-smooth version of a mammalian cell cycle model, obtained by hybridization from a smooth biochemical model. The approximate hybridization scheme, leading to simplified reaction rates and binary event location functions, is based on learning from a training set of trajectories of the smooth model. We discuss several learning strategies for the parameters of the hybrid model.

  1. A vaccine grade of yeast Saccharomyces cerevisiae expressing mammalian myostatin

    Directory of Open Access Journals (Sweden)

    Zhang Tingting

    2012-12-01

    Full Text Available Abstract Background Yeast Saccharomyces cerevisiae is a widely-used system for protein expression. We previously showed that heat-killed whole recombinant yeast vaccine expressing mammalian myostatin can modulate myostatin function in mice, resulting in increase of body weight and muscle composition in these animals. Foreign DNA introduced into yeast cells can be lost soon unless cells are continuously cultured in selection media, which usually contain antibiotics. For cost and safety concerns, it is essential to optimize conditions to produce quality food and pharmaceutical products. Results We developed a simple but effective method to engineer a yeast strain stably expressing mammalian myostatin. This method utilized high-copy-number integration of myostatin gene into the ribosomal DNA of Saccharomyces cerevisiae. In the final step, antibiotic selection marker was removed using the Cre-LoxP system to minimize any possible side-effects for animals. The resulting yeast strain can be maintained in rich culture media and stably express mammalian myostatin for two years. Oral administration of the recombinant yeast was able to induce immune response to myostatin and modulated the body weight of mice. Conclusions Establishment of such yeast strain is a step further toward transformation of yeast cells into edible vaccine to improve meat production in farm animals and treat human muscle-wasting diseases in the future.

  2. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  3. Quality of life after surgery for neuromuscular scoliosis

    Directory of Open Access Journals (Sweden)

    Peter Obid

    2013-02-01

    Full Text Available Surgery in patients with neuromuscular scoliosis is associated with a higher rate of complications. It is still controversially discussed whether the patients truly benefit from deformity correction. The purpose of this study is to investigate if the quality of life has been improved and if the patients and their caregivers are satisfied with the results of surgery. This is a retrospective clinical outcome study of 46 patients with neuromuscular scoliosis which were treated with primary stable posterior pedicle screw instrumentation and correction. To achieve fusion only autologous bone was used. Follow up was minimum 2 years and maximum 5 years with an average of 36 months. The patients and/or their caregivers received a questionnaire based on the PEDI (pediatric disability inventory and the GMFS (gross motor function score. The patients (and their caregivers were also asked if the quality of life has improved after surgery. Only 32 of 46 patients answered the questionnaire. The answers showed a high approval-rate regarding the patients satisfaction with the surgery and the improvement of quality of life. The questionnaire could be answered from 1 (I do not agree to 4 (I completely agree. The average agreement to the following statements was: i the quality of life has improved: 3.35; ii I am satisfied with surgery: 3.95; iii the operation has fulfilled my expectations: 3.76. The average age at surgery was 12.7 years. The mean pre-operative cobb-angle of the main curve was 83.1° with a correction post-operatively to a mean of 36.9° and 42.6° at final follow-up. That is an average correction of 56.9%. Although spinal fusion in neuromuscular scoliosis is associated with a higher rate of complications our results show that the patients and their caregivers are satisfied with the operation and the quality of life has improved after surgery.

  4. Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

    Science.gov (United States)

    Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

    2014-01-01

    The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

  5. Running Economy: Neuromuscular and Joint Stiffness Contributions in Trained Runners.

    Science.gov (United States)

    Tam, Nicholas; Tucker, Ross; Santos-Concejero, Jordan; Prins, Danielle; Lamberts, Robert P

    2018-05-29

    It is debated whether running biomechanics make good predictors of running economy, with little known information about the neuromuscular and joint stiffness contributions to economical running gait. The aim of this study was to understand the relationship between certain neuromuscular and spatiotemporal biomechanical factors associated with running economy. Thirty trained runners performed a 6-minute constant-speed running set at 3.3 m∙s -1 , where oxygen consumption was assessed. Overground running trials were also performed at 3.3 m∙s -1 to assess kinematics, kinetics and muscle activity. Spatiotemporal gait variables, joint stiffness, pre-activation and stance phase muscle activity (gluteus medius; rectus femoris (RF); biceps femoris(BF); peroneus longus (PL); tibialis anterior (TA); gastrocnemius lateralis and medius (LG and MG) were variables of specific interest and thus determined. Additionally, pre-activation and ground contact of agonist:antagonist co-activation were calculated. More economical runners presented with short ground contact times (r=0.639, p<0.001) and greater strides frequencies (r=-0.630, p<0.001). Lower ankle and greater knee stiffness were associated with lower oxygen consumption (r=0.527, p=0.007 & r=0.384, p=0.043, respectively). Only LG:TA co-activation during stance were associated with lower oxygen cost of transport (r=0.672, p<0.0001). Greater muscle pre-activation and bi-articular muscle activity during stance were associated with more economical runners. Consequently, trained runners who exhibit greater neuromuscular activation prior to and during ground contact, in turn optimise spatiotemporal variables and joint stiffness, will be the most economical runners.

  6. Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

    Directory of Open Access Journals (Sweden)

    Corrêa da Silva Bruno Victor

    2014-12-01

    Full Text Available The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest. Neuromuscular performance was measured by the bench press throw (BPT and vertical counter movement jump (VCMJ tests, assessed before the 1st fight (Pre and after the last one (Post. Blood lactate (LA was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05 increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post, but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post were observed. LA concentration increased significantly (p < 0.05 at Post, both in the 1st min and the 15th min of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power was observed.

  7. Oscillations-free PID control of anesthetic drug delivery in neuromuscular blockade.

    Science.gov (United States)

    Medvedev, Alexander; Zhusubaliyev, Zhanybai T; Rosén, Olov; Silva, Margarida M

    2016-07-25

    The PID-control of drug delivery or the neuromuscular blockade (NMB) in closed-loop anesthesia is considered. The NMB system dynamics portrayed by a Wiener model can exhibit sustained nonlinear oscillations under realistic PID gains and for physiologically feasible values of the model parameters. Such oscillations, also repeatedly observed in clinical trials, lead to under- and over-dosing of the administered drug and undermine patient safety. This paper proposes a tuning policy for the proportional PID gain that via bifurcation analysis ensures oscillations-free performance of the control loop. Online estimates of the Wiener model parameters are needed for the controller implementation and monitoring of the closed-loop proximity to oscillation. The nonlinear dynamics of the PID-controlled NMB system are studied by bifurcation analysis. A database of patient models estimated under PID-controlled neuromuscular blockade during general anesthesia is utilized, along with the corresponding clinical measurements. The performance of three recursive algorithms is compared in the application at hand: an extended Kalman filter, a conventional particle filter (PF), and a PF making use of an orthonormal basis to estimate the probability density function from the particle set. It is shown that with a time-varying proportional PID gain, the type of equilibria of the closed-loop system remains the same as in the case of constant controller gains. The recovery time and frequency of oscillations are also evaluated in simulation over the database of patient models. Nonlinear identification techniques based on model linearization yield biased parameter estimates and thus introduce superfluous uncertainty. The bias and variance of the estimated models are related to the computational complexity of the identification algorithms, highlighting the superiority of the PFs in this safety-critical application. The study demonstrates feasibility of the proposed oscillation-free control

  8. Diagnostics of neuromuscular diseases with the aid of computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Visser, M de; Verbeeten, Jr, B J

    1988-06-04

    In this article the diagnosis of neuromuscular diseases with the aid of computerized tomography is treated. Computerized tomography of skeletal muscles give no information which is pathognomonic for particular diseases. But the technique can be used in the following aspects: to choose a muscle for a biopsy; when it is not possible to examine the function of a muscle, a CT scan can visualize morphological deviations; in the differentiation of muscle hypertrophy and pseudo-hypertrophy. For some cases as Becker-type muscular dystrophy, facioscapulohumeral dystrophy and Kugelberg-Welander type spinal muscular atrophy computerized tomography gives characteristic images. 10 refs.; 6 figs.

  9. Diagnostics of neuromuscular diseases with the aid of computerized tomography

    International Nuclear Information System (INIS)

    Visser, M. de; Verbeeten, B.J. Jr.

    1988-01-01

    In this article the diagnosis of neuromuscular diseases with the aid of computerized tomography is treated. Computerized tomography of skeletal muscles give no information which is pathognomonic for particular diseases. But the technique can be used in the following aspects: to choose a muscle for a biopsy; when it is not possible to examine the function of a muscle, a CT scan can visualize morphological deviations; in the differentiation of muscle hypertrophy and pseudo-hypertrophy. For some cases as Becker-type muscular dystrophy, facioscapulohumeral dystrophy and Kugelberg-Welander type spinal muscular atrophy computerized tomography gives characteristic images. 10 refs.; 6 figs

  10. Cardiac involvement in children with neuro-muscular disorders

    Directory of Open Access Journals (Sweden)

    E. N. Arkhipova

    2015-01-01

    Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

  11. Schwann Cells in Neuromuscular Junction Formation and Maintenance.

    Science.gov (United States)

    Barik, Arnab; Li, Lei; Sathyamurthy, Anupama; Xiong, Wen-Cheng; Mei, Lin

    2016-09-21

    The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation. Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences

  12. Preventing Ischial Pressure Ulcers: I. Review of Neuromuscular Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Hilton M. Kaplan

    2011-01-01

    Full Text Available Objective: Pressure ulcers (PUs are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Treatment is expensive and recurrence rates are high. Pathophysiological mechanisms include reduced bulk and perfusion of chronically atrophic muscles as well as prolonged occlusion of blood flow to soft tissues from lack of voluntary postural shifting of body weight. This has suggested that PUs might be prevented by reanimating the paralyzed muscles using neuromuscular electrical stimulation (NMES. A review of the published literature over the past 2 decades is detailed.

  13. Resúmenes de los trabajos sobre las Enfermedades Neuromusculares

    OpenAIRE

    Congreso Nacional de Neurología

    2010-01-01

    Las enfermedades neuromusculares constituyen un conjunto de afectaciones que afectan las neuronas motoras periférica, las vías motoras eferentes o los efectores (músculos esqueléticos). Sus manifestaciones clínicas son muy variadas y dependen de la causa y de los niveles de afectación. En este acápite se pueden encontrar los resúmenes de trabajos relacionados con el síndrome de Guillain Barre, polineuropatía diabética, Atrofia Muscular Espinal, Distrofia miotónica y otros todos presentados en...

  14. MRI in neuromuscular disorders; MRT bei neuromuskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Fischmann, Arne [Klinik St. Anna, Luzern (Switzerland). Inst. fuer Radiologie und Nuklearmedizin; Fischer, Dirk [Kantonsspital Bruderholz (Switzerland)

    2014-03-15

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  15. Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

  16. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  17. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.

    2010-01-01

    A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs

  18. Fatigue in neuromuscular disorders: Focus on Guillain-Barré syndrome and Pompe disease

    NARCIS (Netherlands)

    J.M. de Vries (Juna); M.L.C. Hagemans (Marloes); J.B.J. Bussmann (Hans); A.T. van der Ploeg (Ans); P.A. van Doorn (Pieter)

    2010-01-01

    textabstractFatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided

  19. Mosaic evolution of the mammalian auditory periphery.

    Science.gov (United States)

    Manley, Geoffrey A

    2013-01-01

    The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

  20. Reliability of a Test Battery Designed for Quickly and Safely Assessing Diverse Indices of Neuromuscular Function

    Science.gov (United States)

    Spiering, Barry A.; Lee, Stuart M. C.; Mulavara, Ajitkumar P.; Bentley, Jason, R.; Buxton, Roxanne E.; Lawrence, Emily L.; Sinka, Joseph; Guilliams, Mark E.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

    2010-01-01

    Spaceflight affects nearly every physiological system. Spaceflight-induced alterations in physiological function translate to decrements in functional performance. Purpose: To develop a test battery for quickly and safely assessing diverse indices of neuromuscular performance. I. Quickly: Battery of tests can be completed in approx.30-40 min. II. Safely: a) No eccentric muscle actions or impact forces. b) Tests present little challenge to postural stability. III. Diverse indices: a) Strength: Excellent reliability (ICC = 0.99) b) Central activation: Very good reliability (ICC = 0.87) c) Power: Excellent reliability (ICC = 0.99) d) Endurance: Total work has excellent reliability (ICC = 0.99) e) Force steadiness: Poor reliability (ICC = 0.20 - 0.60) National

  1. Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Feingold, Brian; Mahle, William T; Auerbach, Scott; Clemens, Paula; Domenighetti, Andrea A; Jefferies, John L; Judge, Daniel P; Lal, Ashwin K; Markham, Larry W; Parks, W James; Tsuda, Takeshi; Wang, Paul J; Yoo, Shi-Joon

    2017-09-26

    For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes. © 2017 American Heart Association, Inc.

  2. Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Pilar eMartinez-Martinez

    2013-09-01

    Full Text Available Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the CNS, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand–activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.

  3. The immediate effect of neuromuscular joint facilitation on the rotation of the tibia during walking.

    Science.gov (United States)

    Li, Desheng; Huang, Qiuchen; Huo, Ming; Hiiragi, Yukinobu; Maruyama, Hitoshi

    2017-01-01

    [Purpose] The aim of this study was to investigate the change in tibial rotation during walking among young adults after neuromuscular joint facilitation therapy. [Subjects and Methods] The subjects were twelve healthy young people (6 males, 6 females). A neuromuscular joint facilitation intervention and nonintervention were performed. The interventions were performed one after the other, separated by a 1-week interval. The order of the interventions was completely randomized. The rotation of the tibia during walking was evaluated before and after treatment. [Results] The neuromuscular joint facilitation group demonstrated increased lateral rotation of the tibia in the overall gait cycle and stance phase, and decreased medial rotation of the tibia in the overall gait cycle, stance phase, and swing phase after the neuromuscular joint facilitation intervention. In the control group, there were no significant differences. [Conclusion] These results suggest neuromuscular joint facilitation intervention has an immediate effect on the rotational function of the knee.

  4. The Thoracic Lordosis Correction Improves Sacral Slope and Walking Ability in Neuromuscular Scoliosis.

    Science.gov (United States)

    Kim, Do Yeon; Moon, Eun Su; Park, Jin Oh; Chong, Hyon Su; Lee, Hwan Mo; Moon, Seong Hwan; Kim, Sung Hoon; Kim, Hak Sun

    2016-10-01

    Retrospective study. To report on neuromuscular patients with preserved walking ability, but forward bending of the body due to thoracic lordosis, and to suggest thoracic lordosis correction as the surgical treatment. It is an established fact that lumbar lordosis or pelvic parameter is directly related to thoracic sagittal balance. However, the reverse relationship has not been fully defined yet. Loss of thoracic kyphosis results in positive sagittal balance, which causes walking difficulty. Neuromuscular patients with thoracic lordosis have not been reported yet, and there have been no reports on their surgical treatments. This study analyzed 8 patients treated with thoracic lordosis correction surgery. Every patient was diagnosed with muscular dystrophy. In thoracic lordosis correction surgery, anterior release was performed in the first stage and posterior segmental instrumentation was performed in the second stage. Radiographic parameters were compared and walking ability was evaluated with gait analysis. All patients were classified according to the modified Rancho Los Amigos Hospital system preoperatively and 2 years postoperatively to evaluate functional ability. The average follow-up period was 2.9 years. Before surgery, the mean thoracic sagittal alignment was -2.1-degree lordosis, the mean Cobb angle and sacral slope increased to 36.3 and 56.6 degrees, respectively. The anterior pelvic tilt in gait analysis was 29.3 degrees. At last follow-up after surgery, the mean thoracic sagittal alignment changed to 12.6-degree kyphosis, and the Cobb angle and sacral slope decreased to 18.9 and 39.5 degrees, respectively. Lumbar lordosis and the sacral slope showed significant positive correlation (Plordosis showed a significant correlation to the preoperative flexibility of the major curve (P=0.028). The anterior pelvic tilt in gait analysis improved to 15.4 degrees. The functional ability improved in 2 (50%) of 4 patients in class 2 and maintained in remaining 6

  5. Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom.

    Science.gov (United States)

    Tribuiani, Natália; da Silva, Alexandro Mateus; Ferraz, Miriéle Cristina; Silva, Magali Glauzer; Bentes, Ana Paula Guerreiro; Graziano, Talita Signoreti; dos Santos, Marcio Galdino; Cogo, José Carlos; Varanda, Eliana Aparecida; Groppo, Francisco Carlos; Cogo, Karina; Oshima-Franco, Yoko

    2014-02-08

    Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian "cerrado" (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf's ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode's solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged from 2.5 to 5.0 mg/mL for P. aeruginosa

  6. Mammalian diversity: gametes, embryos and reproduction.

    Science.gov (United States)

    Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

    2006-01-01

    The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

  7. Factors affecting the spontaneous mutational spectra in somatic mammalian cells

    Directory of Open Access Journals (Sweden)

    О.А. Ковальова

    2006-04-01

    Full Text Available  In our survey of references we are discussed the influence of factors biological origin on the spontaneous mutation specters in mammalian. Seasonal and age components influence on the frequence of cytogenetic anomalies. The immune and endocrinous systems are take part in control of the alteration of the spontaneous mutation specters. Genetical difference of sensibility in animal and human at the alteration of factors enviroment as and  genetical differences of repair systems activity are may influence on individual variation of spontaneous destabilization characters of chromosomal apparatus.

  8. A game of thrones: neural plasticity in mammalian social hierarchies.

    Science.gov (United States)

    Mooney, Skyler J; Peragine, Diana E; Hathaway, Georgia A; Holmes, Melissa M

    2014-01-01

    Social status is a key regulator of health and reproduction in mammals, including humans. Despite this, relatively little is known about how social status influences the mammalian brain. Furthermore, the extent to which status is an independent construct, i.e., not simply acting as a psychosocial stressor, is yet to be determined. Research to date reveals several promising mechanisms and/or systems associated with social status, including monoamine systems, hypothalamic neuroendocrine axes, and the hippocampus, though whether these differences are the cause or effect of status is often unclear. We review these candidates and propose how best to approach this research question in the future.

  9. Motor unit recruitment during neuromuscular electrical stimulation: a critical appraisal.

    Science.gov (United States)

    Bickel, C Scott; Gregory, Chris M; Dean, Jesse C

    2011-10-01

    Neuromuscular electrical stimulation (NMES) is commonly used in clinical settings to activate skeletal muscle in an effort to mimic voluntary contractions and enhance the rehabilitation of human skeletal muscles. It is also used as a tool in research to assess muscle performance and/or neuromuscular activation levels. However, there are fundamental differences between voluntary- and artificial-activation of motor units that need to be appreciated before NMES protocol design can be most effective. The unique effects of NMES have been attributed to several mechanisms, most notably, a reversal of the voluntary recruitment pattern that is known to occur during voluntary muscle contractions. This review outlines the assertion that electrical stimulation recruits motor units in a nonselective, spatially fixed, and temporally synchronous pattern. Additionally, it synthesizes the evidence that supports the contention that this recruitment pattern contributes to increased muscle fatigue when compared with voluntary actions and provides some commentary on the parameters of electrical stimulation as well as emerging technologies being developed to facilitate NMES implementation. A greater understanding of how electrical stimulation recruits motor units, as well as the benefits and limitations of its use, is highly relevant when using this tool for testing and training in rehabilitation, exercise, and/or research.

  10. Ultrastructural findings in noncompaction prevail with neuromuscular disorders.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia

    2013-01-01

    Little is known about the ultrastructural abnormalities of left ventricular hypertrabeculation/noncompaction (LVHT). This literature review aimed to summarize and discuss ultrastructural abnormalities described in LVHT so far. The literature search was conducted via MEDLINE using the search terms 'non-compaction', 'noncompaction', 'left ventricular hypertrabeculation', 'spongy myocardium' in combination with the terms 'ultra-structural', or 'electron microscopy'. Altogether, 11 studies reporting ultrastructural investigations of LVHT were retrieved. In these 11 studies, data on 13 patients with LVHT were presented. Ultrastructural abnormalities found in these study patients were generally nonspecific and included an increase in the number of mitochondria (n = 3), abnormally shaped mitochondria (n = 2), distorted cristae (n = 3), sarcomeric derangement (n = 3), immature cardiomyocytes (n = 1), lipid-like inclusions (n = 1), enlarged interstitial spaces (n = 1), increased interstitial collagen (n = 1), or increased glycogen (n = 1). The morphological abnormalities were most prominent in patients with a neuromuscular disorder like Barth syndrome or mitochondrial myopathy. Only in few patients with LVHT, ultrastructural investigations have been performed so far. Ultrastructural abnormalities in LVHT are nonspecific and most prominent in patients with a neuromuscular disorder. There is a strong need to carry out thorough ultrastructural investigations of LVHT to contribute to the understanding of this still unexplained myocardial abnormality.

  11. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

    2017-06-01

    Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

  12. Toward Balance Recovery With Leg Prostheses Using Neuromuscular Model Control

    Science.gov (United States)

    Geyer, Hartmut

    2016-01-01

    Objective Lower limb amputees are at high risk of falling as current prosthetic legs provide only limited functionality for recovering balance after unexpected disturbances. For instance, the most established control method used on powered leg prostheses tracks local joint impedance functions without taking the global function of the leg in balance recovery into account. Here we explore an alternative control policy for powered transfemoral prostheses that considers the global leg function and is based on a neuromuscular model of human locomotion. Methods We adapt this model to describe and simulate an amputee walking with a powered prosthesis using the proposed control, and evaluate the gait robustness when confronted with rough ground and swing leg disturbances. We then implement and partially evaluate the resulting controller on a leg prosthesis prototype worn by a non-amputee user. Results In simulation, the proposed prosthesis control leads to gaits that are more robust than those obtained by the impedance control method. The initial hardware experiments with the prosthesis prototype show that the proposed control reproduces normal walking patterns qualitatively and effectively responds to disturbances in early and late swing. However, the response to mid-swing disturbances neither replicates human responses nor averts falls. Conclusions The neuromuscular model control is a promising alternative to existing prosthesis controls, although further research will need to improve on the initial implementation and determine how well these results transfer to amputee gait. Significance This work provides a potential avenue for future development of control policies that help improve amputee balance recovery. PMID:26315935

  13. [Six-minute walk test in children with neuromuscular disease.

    Science.gov (United States)

    Cruz-Anleu, Israel Didier; Baños-Mejía, Benjamín Omar; Galicia-Amor, Susana

    2013-01-01

    Background: neuromuscular diseases affect the motor unit. When they evolve, respiratory complications are common; the six-minute walk test plays an important role in the assessment of functional capacity. Methods: prospective, transversal, descriptive and observational study. We studied seven children with a variety of neuromuscular diseases and spontaneous ambulation. We tested their lung function, and administered a six-minute walk test and a test of respiratory muscle strength to these children. Results: the age was 9.8 ± 2.4 years. All patients were males. Forced vital capacity decreased in three patients (42.8 %), forced expiratory volume during the first second (2.04 ± 1.4 L) and peak expiratory flow (4.33 ± 3.3 L/s) were normal. The maximum strength of respiratory muscles was less than 60 % of predicted values. The distance covered in the six-minute walk test was lower when compared with healthy controls (29.9 %). Conclusions: the six-minute walk test can be a useful tool in early stages of this disease, since it is easy to perform and well tolerated by the patients.

  14. Effect of salbutamol on neuromuscular function in endurance athletes.

    Science.gov (United States)

    Decorte, Nicolas; Bachasson, Damien; Guinot, Michel; Flore, Patrice; Levy, Patrick; Verges, Samuel; Wuyam, Bernard

    2013-10-01

    The potential ergogenic effects of therapeutic inhaled salbutamol doses in endurance athletes have been controversially discussed for decades. We hypothesized that salbutamol inhalation may increase peripheral muscle contractility, reduce fatigability, and improve force recovery after a localized exercise in endurance athletes. Eleven healthy, nonasthmatic male athletes with high aerobic capacities were recruited to be compared in a double-blinded, randomized crossover study of two dose levels of salbutamol (200 and 800 μg) and a placebo administered by inhalation before a quadriceps fatigue test. Subjects performed an incremental exercise protocol consisting in sets of 10 intermittent isometric contractions starting at 20% of maximum voluntary contraction (MVC) with 10% MVC increment until exhaustion. Femoral nerve magnetic stimulation was used during and after MVC to evaluate neuromuscular fatigue after each set, at task failure, and after 10 and 30 min of recovery. Initial MVC and evoked muscular responses were not modified with salbutamol (P > 0.05). The total number of submaximal contractions until task failure significantly differed between treatments (placebo, 72 ± 7; 200 µg, 78 ± 8; and 800 µg, 82 ± 7; P 0.05). Voluntary activation was unaffected by the fatiguing task and treatments (P > 0.05). Supratherapeutic inhaled doses of β2-agonists increased quadriceps endurance during an incremental and localized fatiguing task in healthy endurance-trained athletes without significant effect on neuromuscular fatigue. Further studies are needed to clarify the underlying mechanisms.

  15. Estimating neuromuscular stimulation within the human torso with Taser stimulus.

    Science.gov (United States)

    Sun, Hongyu; Webster, John G

    2007-11-07

    Designers of electromuscular incapacitation devices need to know efficacy. Which areas of nerve and muscle are stimulated and are these areas adequate to cause incapacitation? This paper focuses on efficacy, which used a torso-sized finite element model with a mesh of about 5 mm. To estimate the neuromuscular regions stimulated by the Taser X26, calculations of electric current density and field strength values with 1 A inserted into the torso using the Utah 3D mesh were made. Field-times-duration values for given Taser stimulation were calculated. Then the region where the motor nerve was stimulated by the Taser was estimated by using a field-times-duration threshold from Reilly (1998 'Applied Bioelectricity: From Electrical Stimulation to Electropathology ' (New York: Springer)). Neuromuscular stimulation occurred up to about 19 cm away from the darts and included the spinal cord. The current density at the heart for dart separation less than 10 cm was smaller than for larger dart separation. Users of finite element computer models will find information for torso models and their creation, meshing and operation.

  16. Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

    Science.gov (United States)

    Dewan, Karuna; Vahabzadeh-Hagh, Andrew; Soofer, Donna; Chhetri, Dinesh K

    2017-07-01

    Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. In vivo canine model. In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. NA Laryngoscope, 127:1633-1638, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Acoustophoretic Synchronization of Mammalian Cells in Microchannels

    DEFF Research Database (Denmark)

    Thévoz, P.; Adams, J.D.; Shea, H.

    2010-01-01

    We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel to selec......We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel...

  18. DNA repair in non-mammalian animals

    International Nuclear Information System (INIS)

    Mitani, Hiroshi

    1984-01-01

    Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

  19. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó-Ollé, Anna; Cilleros-Mañé, Víctor; Just-Borràs, Laia

    2018-01-01

    In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR) in the mammalian neuromuscular junction (NMJ). Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally). These observations underlie the relevance of AR in the NMJ function.

  20. Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2018-04-01

    Full Text Available In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR in the mammalian neuromuscular junction (NMJ. Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally. These observations underlie the relevance of AR in the NMJ function.

  1. Repair of furocoumarin adducts in mammalian cells

    International Nuclear Information System (INIS)

    Zolan, M.E.; Smith, C.A.; Hanawalt, P.C.

    1984-01-01

    DNA repair was studied in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. A comparison was also made of repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly

  2. Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

    Science.gov (United States)

    Karten, Harvey J.

    2015-01-01

    The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

  3. Comparison of neuromuscular abnormalities between upper and lower extremities in hemiparetic stroke.

    Science.gov (United States)

    Mirbagheri, M M; AliBiglou, L; Thajchayapong, M; Lilaonitkul, T; Rymer, W Z

    2006-01-01

    We studied the neuromuscular mechanical properties of the elbow and ankle joints in chronic, hemiparetic stroke patients and healthy subjects. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joint at different joint angles. The experiments were performed for both spastic (stroke) and contralateral (control) sides of stroke patients and one side of healthy (normal) subjects. We found reflex stiffness gain (GR) was significantly larger in the stroke than the control side for both elbow and ankle joints. GR was also strongly position dependent in both joints. However, the modulation of GR with position was slightly different in two joints. GR was also larger in the control than the normal joints but the differences were significant only for the ankle joint. Intrinsic stiffness gain (K) was also significantly larger in the stroke than the control joint at elbow extended positions and at ankle dorsiflexed positions. Modulation of K with the ankle angle was similar for stroke, control and normal groups. In contrast, the position dependency of the elbow was different. K was larger in the control than normal ankle whereas it was lower in the control than normal elbow. However, the differences were not significant for any joint. The findings demonstrate that both reflex and intrinsic stiffness gain increase abnormally in both upper and lower extremities. However, the major contribution of intrinsic and reflex stiffness to the abnormalities is at the end of ROM and at the middle ROM, respectively. The results also demonstrate that the neuromuscular properties of the contralateral limb are not normal suggesting that it may not be used as a suitable control at least for the ankle study.

  4. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  5. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  6. Locomotor circuits in the mammalian spinal cord

    DEFF Research Database (Denmark)

    Kiehn, Ole

    2006-01-01

    Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network struct...

  7. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

    2014-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  8. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...

  9. Archetype, adaptation and the mammalian heart

    NARCIS (Netherlands)

    Meijler, F.L.; Meijler, T.D.

    2011-01-01

    Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural

  10. The Preparation Period in Basketball: Training Load and Neuromuscular Adaptations.

    Science.gov (United States)

    Ferioli, Davide; Bosio, Andrea; Bilsborough, Johann C; Torre, Antonio La; Tornaghi, Michele; Rampinini, Ermanno

    2018-01-18

    To investigate the 1) effect of the preparation period on the neuromuscular characteristics of 12 professional (PRO) and 16 semi-professional (SEMI-PRO) basketball players; 2) relationships between training load indices and changes in neuromuscular physical performance. Prior to and following the preparation period, players underwent a counter-movement jump (CMJ) test, followed by a repeated change of direction (COD) test consisting of 4 levels with increasing intensities. The peripheral neuromuscular functions of the knee extensors (peak torque, PT) were measured using electrical stimulations after each level (PT1, PT2, PT3 and PT4). Furthermore, PT Max (the highest value of PT) and PT Dec (PT decrement from PT Max to PT4) were calculated. Trivial-to-small (effect size, ES: -0.17 to 0.46) improvements were found in CMJ variables, regardless of the competitive levels. After the preparation period, peripheral fatigue induced by a COD test was similarly reduced in both PRO (PT Dec: from 27.8±21.3% to 11.4±13.7%, ES±90%CI= -0.71±0.30) and SEMI-PRO (PT Dec: from 26.1±21.9% to 10.2±8.2%, ES±90%CI= -0.69±0.32). Moderate-to-large relationships were found between session rating of perceived exertion training load and changes in PPO measured during the CMJs (r s ±90%CI: PPOabs, -0.46±0.26; PPOrel, -0.53±0.23) and in some PTs measured during the COD test (PT1, -0.45±0.26; PT2, -0.44±0.26; PT3, -0.40±0.27 and PT Max, -0.38±0.28). Preparation period induced minimal changes in the CMJ, while the ability to sustain repeated COD efforts was improved. Reaching high session rating of perceived exertion training loads might partially and negatively affect the ability to produce strength and power.

  11. Automated optimal coordination of multiple-DOF neuromuscular actions in feedforward neuroprostheses.

    Science.gov (United States)

    Lujan, J Luis; Crago, Patrick E

    2009-01-01

    This paper describes a new method for designing feedforward controllers for multiple-muscle, multiple-DOF, motor system neural prostheses. The design process is based on experimental measurement of the forward input/output properties of the neuromechanical system and numerical optimization of stimulation patterns to meet muscle coactivation criteria, thus resolving the muscle redundancy (i.e., overcontrol) and the coupled DOF problems inherent in neuromechanical systems. We designed feedforward controllers to control the isometric forces at the tip of the thumb in two directions during stimulation of three thumb muscles as a model system. We tested the method experimentally in ten able-bodied individuals and one patient with spinal cord injury. Good control of isometric force in both DOFs was observed, with rms errors less than 10% of the force range in seven experiments and statistically significant correlations between the actual and target forces in all ten experiments. Systematic bias and slope errors were observed in a few experiments, likely due to the neuromuscular fatigue. Overall, the tests demonstrated the ability of a general design approach to satisfy both control and coactivation criteria in multiple-muscle, multiple-axis neuromechanical systems, which is applicable to a wide range of neuromechanical systems and stimulation electrodes.

  12. Neuromuscular blockade for improvement of surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Scheppan, Susanne; Kissmeyer, Peter

    2015-01-01

    INTRODUCTION: During laparotomy, surgeons frequently experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. This issue is particularly pertinent while closing the fascia and placing the intestines into the abdominal cavity. Establishment of a deep neuromus......INTRODUCTION: During laparotomy, surgeons frequently experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. This issue is particularly pertinent while closing the fascia and placing the intestines into the abdominal cavity. Establishment of a deep...... neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS...

  13. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    Science.gov (United States)

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

  14. Neuromuscular training in construction workers: a longitudinal controlled pilot study.

    Science.gov (United States)

    Faude, Oliver; Donath, Lars; Bopp, Micha; Hofmann, Sara; Erlacher, Daniel; Zahner, Lukas

    2015-08-01

    Many accidents at construction sites are due to falls. An exercise-based workplace intervention may improve intrinsic fall risk factors. In this pilot study, we aimed at evaluating the effects of neuromuscular exercise on static and functional balance performance as well as on lower limb explosive power in construction workers. Healthy middle-aged construction workers were non-randomly assigned to an intervention [N = 20, age = 40.3 (SD 8.3) years] or a control group [N = 20, age = 41.8 (9.9) years]. The intervention group performed static and dynamic balance and strength exercises (13 weeks, 15 min each day). Before and after the intervention and after an 8-week follow-up, unilateral postural sway, backward balancing (on 3- and 4.5-cm-wide beams) as well as vertical jump height were assessed. We observed a group × time interaction for postural sway (p = 0.002) with a reduction in the intervention group and no relevant change in the control group. Similarly, the number of successful steps while walking backwards on the 3-cm beam increased only in the intervention group (p = 0.047). These effects were likely to most likely practically beneficial from pretest to posttest and to follow-up test for postural sway (+12%, standardized mean difference (SMD) = 0.65 and 17%, SMD = 0.92) and backward balancing on the 3-cm beam (+58%, SMD = 0.59 and 37%, SMD = 0.40). Fifteen minutes of neuromuscular training each day can improve balance performance in construction workers and, thus, may contribute to a decreased fall risk.

  15. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

    Directory of Open Access Journals (Sweden)

    Peter C Rowe

    Full Text Available Chronic fatigue syndrome (CFS is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04 and concentration difficulties (P = 0.02 as well as increased composite symptom scores (all P = 0.03 during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001 and for the composite symptom score (P = 0.005. During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical

  16. No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

    Science.gov (United States)

    Ritzmann, Ramona; Freyler, Kathrin; Krause, Anne; Gollhofer, Albert

    2016-10-01

    Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug's anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.

  17. The Effect of Different Repeated-High-Intensity-Effort Bouts on Subsequent Running, Skill Performance, and Neuromuscular Function.

    Science.gov (United States)

    Johnston, Rich D; Gabbett, Tim J; Jenkins, David G; Speranza, Michael J

    2016-04-01

    To assess the impact of different repeated-high-intensity-effort (RHIE) bouts on player activity profiles, skill involvements, and neuromuscular fatigue during small-sided games. 22 semiprofessional rugby league players (age 24.0 ± 1.8 y, body mass 95.6 ± 7.4 kg). During 4 testing sessions, they performed RHIE bouts that each differed in the combination of contact and running efforts, followed by a 5-min off-side small-sided game before performing a second bout of RHIE activity and another 5-min small-sided game. Global positioning system microtechnology and video recordings provided information on activity profiles and skill involvements. A countermovement jump and a plyometric push-up assessed changes in lower- and upper-body neuromuscular function after each session. After running-dominant RHIE bouts, players maintained running intensities during both games. In the contact-dominant RHIE bouts, reductions in moderate-speed activity were observed from game 1 to game 2 (ES = -0.71 to -1.06). There was also moderately lower disposal efficiency across both games after contact-dominant RHIE activity compared with running-dominant activity (ES = 0.62-1.02). Greater reductions in lower-body fatigue occurred as RHIE bouts became more running dominant (ES = -0.01 to -1.36), whereas upper-body fatigue increased as RHIE bouts became more contact dominant (ES = -0.07 to -1.55). Physical contact causes reductions in running intensity and the quality of skill involvements during game-based activities. In addition, the neuromuscular fatigue experienced by players is specific to the activities performed.

  18. Neuromuscular strain as a contributor to cognitive and other symptoms in Chronic Fatigue Syndrome: Hypothesis and conceptual model.

    Directory of Open Access Journals (Sweden)

    Peter C. Rowe

    2013-05-01

    Full Text Available Individuals with chronic fatigue syndrome (CFS have heightened sensitivity and increased symptoms following various physiologic challenges, such as orthostatic stress, physical exercise, and cognitive challenges. Similar heightened sensitivity to the same stressors in fibromyalgia (FM has led investigators to propose that these findings reflect a state of central sensitivity. A large body of evidence supports the concept of central sensitivity in FM. A more modest literature provides partial support for this model in CFS, particularly with regard to pain. Nonetheless, fatigue and cognitive dysfunction have not been explained by the central sensitivity data thus far. Peripheral factors have attracted attention recently as contributors to central sensitivity. Work by Brieg, Sunderland, and others has emphasized the ability of the nervous system to undergo accommodative changes in length in response to the range of limb and trunk movements carried out during daily activity. If that ability to elongate is impaired—due to movement restrictions in tissues adjacent to nerves, or due to swelling or adhesions within the nerve itself—the result is an increase in mechanical tension within the nerve. This adverse neural tension, also termed neurodynamic dysfunction, is thought to contribute to pain and other symptoms through a variety of mechanisms. These include mechanical sensitization and altered nociceptive signaling, altered proprioception, adverse patterns of muscle recruitment and force of muscle contraction, reduced intra-neural blood flow, and release of inflammatory neuropeptides. Because it is not possible to differentiate completely between adverse neural tension and strain in muscles, fascia, and other soft tissues, we use the more general term neuromuscular strain. In our clinical work, we have found that neuromuscular restrictions are common in CFS, and that many symptoms of CFS can be reproduced by selectively adding neuromuscular strain

  19. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    International Nuclear Information System (INIS)

    NONE

    1999-01-01

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair

  20. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-02-12

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

  1. Effect of purines on calcium-independent acetylcholine release at the mouse neuromuscular junction.

    Science.gov (United States)

    Veggetti, M; Muchnik, S; Losavio, A

    2008-07-17

    At the mouse neuromuscular junction, activation of adenosine A(1) and P2Y receptors inhibits acetylcholine release by an effect on voltage dependent calcium channels related to spontaneous and evoked secretion. However, an effect of purines upon the neurotransmitter-releasing machinery downstream of Ca(2+) influx cannot be ruled out. An excellent tool to study neurotransmitter exocytosis in a Ca(2+)-independent step is the hypertonic response. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of the specific adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) and the P2Y(12-13) agonist 2-methylthio-adenosine 5'-diphosphate (2-MeSADP) on the hypertonic response. Both purines significantly decreased such response (peak and area under the curve), and their effect was prevented by specific antagonists of A(1) and P2Y(12-13) receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N-[2-(methylthioethyl)]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with dichloromethylenebiphosphonic acid, tetrasodium salt (AR-C69931MX), respectively. Moreover, incubation of preparations only with the antagonists induced a higher response compared with controls, suggesting that endogenous ATP/ADP and adenosine are able to modulate the hypertonic response by activating their specific receptors. To search for the intracellular pathways involved in this effect, we studied the action of CCPA and 2-MeSADP in hypertonicity in the presence of inhibitors of several pathways. We found that the effect of CPPA was prevented by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) while that of 2-MeSADP was occluded by the protein kinase C antagonist chelerythrine and W-7. On the other hand, the inhibitors of protein kinase A (N-(2[pbromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide, H-89) and phosphoinositide-3 kinase (PI3K) (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran

  2. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.

    2011-01-21

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.

  3. Exposure of Mammalian Cells to Air-Pollutant Mixtures at the Air-Liquid Interface

    Science.gov (United States)

    It has been widely accepted that exposure of mammalian cells to air-pollutant mixtures at the air-liquid interface is a more realistic approach than exposing cell under submerged conditions. The VITROCELL systems, are commercially available systems for air-liquid interface expo...

  4. Dutch pediatricians' views on the use of neuromuscular blockers for dying neonates: a qualitative study

    NARCIS (Netherlands)

    ten Cate, K.; van de Vathorst, S.

    2015-01-01

    To assess Dutch pediatricians' views on neuromuscular blockers for dying neonates. Qualitative study involving in-depth interviews with 10 Dutch pediatricians working with severely ill neonates. Data were analyzed using appropriate qualitative research techniques. Participants explained their view

  5. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Science.gov (United States)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  6. Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

    Science.gov (United States)

    Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

    2015-05-01

    [Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

  7. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults

    DEFF Research Database (Denmark)

    Hristovska, Ana-Marija; Duch, Patricia; Allingstrup, Mikkel

    2017-01-01

    , and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety......, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. OBJECTIVES: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents......-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. DATA...

  8. Novel vibration-exercise instrument with dedicated adaptive filtering for electromyographic investigation of neuromuscular activation

    NARCIS (Netherlands)

    Xu, L.; Rabotti, C.; Mischi, M.

    2012-01-01

    Vibration exercise (VE) has been suggested as an effective methodology to improve muscle strength and power performance. Several studies link the effects of vibration training to enhanced neuromuscular demand, typically ascribed to involuntary reflex mechanisms. However, the underlying mechanisms

  9. A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

    NARCIS (Netherlands)

    Mullender, M.G.; Blom, N.; de Kleuver, M.; Fock, J.; Hitters, W.; Horemans, A.; Kalkman, C.; Pruijs, J.; Timmer, R.; Titarsolej, P.; van Haasteren, N.; Jager, M.V.; van Vught, A.; van Royen, B.J.

    2008-01-01

    Background: Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is

  10. Radiation effects in mammalian cells in vitro

    International Nuclear Information System (INIS)

    Hill, C.K.; Han, A.; Elkind, M.M.; Wells, R.L.; Buess, E.M.; Lin, C.M.

    1985-01-01

    The purpose of this research effort is to elucidate the mechanisms for the radiation-induced changes in mammalian cells that lead to cell death, mutation, neoplastic transformation, DNA damage, and chromosomal alterations. Of particular interest are the effects of low-dose-rate and fractionated irradiation on these end points with respect to the mechanisms whereby these effects are influenced by cellular repair processes, inhibitors, and promoters that act at the genetic or biochemical level. 17 refs

  11. Cellular and Chemical Neuroscience of Mammalian Sleep

    OpenAIRE

    Datta, Subimal

    2010-01-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

  12. Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency

    DEFF Research Database (Denmark)

    Thomsen, J L; Nielsen, C V; Palmqvist, D F

    2015-01-01

    , neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation prematurely awakened if anaesthesia had been terminated while the patient was still...... paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored...

  13. Risk of Unsuccessful Noninvasive Ventilation for Acute Respiratory Failure in Heterogeneous Neuromuscular Diseases: A Retrospective Study

    OpenAIRE

    Kataoka, Hiroshi; Nanaura, Hitoki; Kinugawa, Kaoru; Uchihara, Yuto; Ohara, Hiroya; Eura, Nobuyuki; Syobatake, Ryogo; Sawa, Nobuhiro; Takao, Kiriyama; Sugie, Kazuma; Ueno, Satoshi

    2017-01-01

    If invasive ventilation can be avoided by performing noninvasive mechanical ventilation (NIV) in patients with acute respiratory failure (ARF), the disease can be effectively managed. It is important to clarify the characteristics of patients with neuromuscular diseases in whom initial NIV is likely to be unsuccessful. We studied 27 patients in stable neuromuscular condition who initially received NIV to manage fatal ARF to identify differences in factors immediately before the onset of ARF a...

  14. Mammalian designer cells: Engineering principles and biomedical applications.

    Science.gov (United States)

    Xie, Mingqi; Fussenegger, Martin

    2015-07-01

    Biotechnology is a widely interdisciplinary field focusing on the use of living cells or organisms to solve established problems in medicine, food production and agriculture. Synthetic biology, the science of engineering complex biological systems that do not exist in nature, continues to provide the biotechnology industry with tools, technologies and intellectual property leading to improved cellular performance. One key aspect of synthetic biology is the engineering of deliberately reprogrammed designer cells whose behavior can be controlled over time and space. This review discusses the most commonly used techniques to engineer mammalian designer cells; while control elements acting on the transcriptional and translational levels of target gene expression determine the kinetic and dynamic profiles, coupling them to a variety of extracellular stimuli permits their remote control with user-defined trigger signals. Designer mammalian cells with novel or improved biological functions not only directly improve the production efficiency during biopharmaceutical manufacturing but also open the door for cell-based treatment strategies in molecular and translational medicine. In the future, the rational combination of multiple sets of designer cells could permit the construction and regulation of higher-order systems with increased complexity, thereby enabling the molecular reprogramming of tissues, organisms or even populations with highest precision. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-12-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

  16. Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives.

    Science.gov (United States)

    Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

    2018-01-01

    The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed.

  17. Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

    Science.gov (United States)

    Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

    2016-12-01

    To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Proprioceptive Neuromuscular Facilitation (PNF): Its Mechanisms and Effects on Range of Motion and Muscular Function

    Science.gov (United States)

    Hindle, Kayla B.; Whitcomb, Tyler J.; Briggs, Wyatt O.; Hong, Junggi

    2012-01-01

    Proprioceptive neuromuscular facilitation (PNF) is common practice for increasing range of motion, though little research has been done to evaluate theories behind it. The purpose of this study was to review possible mechanisms, proposed theories, and physiological changes that occur due to proprioceptive neuromuscular facilitation techniques. Four theoretical mechanisms were identified: autogenic inhibition, reciprocal inhibition, stress relaxation, and the gate control theory. The studies suggest that a combination of these four mechanisms enhance range of motion. When completed prior to exercise, proprioceptive neuromuscular facilitation decreases performance in maximal effort exercises. When this stretching technique is performed consistently and post exercise, it increases athletic performance, along with range of motion. Little investigation has been done regarding the theoretical mechanisms of proprioceptive neuromuscular facilitation, though four mechanisms were identified from the literature. As stated, the main goal of proprioceptive neuromuscular facilitation is to increase range of motion and performance. Studies found both of these to be true when completed under the correct conditions. These mechanisms were found to be plausible; however, further investigation needs to be conducted. All four mechanisms behind the stretching technique explain the reasoning behind the increase in range of motion, as well as in strength and athletic performance. Proprioceptive neuromuscular facilitation shows potential benefits if performed correctly and consistently. PMID:23487249

  19. The effect of 6-week combined agility-balance training on neuromuscular performance in basketball players.

    Science.gov (United States)

    Zemková, E; Hamar, D

    2010-09-01

    The study evaluates the effect of 6-week combined agility-balance training on neuromuscular performance in basketball players. Subjects divided into experimental (EG, n = 17) and control group (CG, n = 17) underwent a combined agility-balance training (in duration of 30 min) for a period of 6 weeks (4-5 sessions/week). Both groups performed reaction tasks similar to game-like situations, however EG on wobble boards and CG on stable surface. Prior to and after the training parameters of agility, balance, speed of step initiation, strength differentiation accuracy, and explosive power of lower limbs were evaluated. Postural stability was assessed under both static and dynamic conditions (wobble board) with eyes open and eyes closed, respectively. The velocity of the centre of pressure (COP) was registered at 100 Hz by means of posturography system FiTRO Sway check based on dynamometric platform. Using FiTRO Reaction check simple and multi-choice reaction times were measured. The same system was applied to evaluate the agility performance including reaction and movement task. Speed of step initiation was measured using FiTRO Dyne Premium. Jumping abilities were evaluated by means of FiTRO Jumper (10-seconds maximal jumps, Countermovement jump, Squat jump, Drop jump). Using the same system, the subject´s ability to match 50 % of their maximal height of the jump was evaluated. Results showed that a combined agility-balance training improved dynamic balance not only under visual control but also in eyes closed conditions. Training also increased run-out speed that likely contributed to better agility performance, reduced ground contact time during drop jump, and improved the ability to differentiate the force of muscle contraction during repeated jumps. However, such training has been found to be insufficient to improve both simple and multi-choice reaction time, and jumping performance. On the other hand, control group failed to show any significant improvement in

  20. Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes

    Directory of Open Access Journals (Sweden)

    M. Demestre

    2015-09-01

    Full Text Available Striated skeletal muscle cells from humans represent a valuable source for in vitro studies of the motoric system as well as for pathophysiological investigations in the clinical settings. Myoblasts can readily be grown from human muscle tissue. However, if muscle tissue is unavailable, myogenic cells can be generated from human induced pluripotent stem cells (hiPSCs preferably without genetic engineering. Our study aimed to optimize the generation of hiPSCs derived myogenic cells by employing selection of CD34 positive cells and followed by distinct, stepwise culture conditions. Following the expansion of CD34 positive single cells under myogenic cell culture conditions, serum deprived myoblast-like cells finally fused and formed multinucleated striated myotubes that expressed a set of key markers for muscle differentiation. In addition, these myotubes contracted upon electrical stimulation, responded to acetylcholine (Ach and were able to generate action potentials. Finally, we co-cultured motoneurons and myotubes generated from identical hiPSCs cell lines. We could observe the early aggregation of acetylcholine receptors in muscle cells of immature co-cultures. At later stages, we identified and characterised mature neuromuscular junctions (NMJs. In summary, we describe here the successful generation of an iPS cell derived functional cellular system consisting of two distinct communicating cells types. This in vitro co-culture system could therefore contribute to research on diseases in which the motoneurons and the NMJ are predominantly affected, such as in amyotrophic lateral sclerosis or spinal muscular atrophy.

  1. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth.

    Directory of Open Access Journals (Sweden)

    Deidre L Brink

    Full Text Available Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ, we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non-synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ.

  2. The combination of sugammadex and neostigmine can reduce the dosage of sugammadex during recovery from the moderate neuromuscular blockade.

    Science.gov (United States)

    Cheong, Soon Ho; Ki, Seunghee; Lee, Jiyong; Lee, Jeong Han; Kim, Myoung-Hun; Hur, Dongki; Cho, Kwangrae; Lim, Se Hun; Lee, Kun Moo; Kim, Young-Jae; Lee, Wonjin

    2015-12-01

    Sugammadex is a novel neuromuscular reversal agent, but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use. In the interest of reducing the necessary dosage of sugammadex, the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated. The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2. The subjects were randomly assigned into one of the four groups (Group S2, S1, SN, and N; n = 30 per group). The reversal agents of each groups were as follows: S2 - sugammadex 2 mg/kg, S1 - sugammadex 1 mg/kg, SN - sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg, N - neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg. The time to recovery of the train-of-four (TOF) ratio was checked in each group. The time to 90% recovery of TOF ratio was 182.6 ± 88.9, 371.1 ± 210.4, 204.3 ± 103.2, 953.2 ± 379.7 sec in group S2, S1, SN and N, respectively. Group SN showed a significantly shorter recovery time than did group S1 and N (P sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex. However, the increased incidence of systemic muscarinic side effects must be considered.

  3. Sonographically guided percutaneous muscle biopsy in diagnosis of neuromuscular disease: a useful alternative to open surgical biopsy.

    Science.gov (United States)

    O'Sullivan, Paul J; Gorman, Grainne M; Hardiman, Orla M; Farrell, Michael J; Logan, P Mark

    2006-01-01

    The purpose of this study was to evaluate the feasibility of sonographically guided percutaneous muscle biopsy in the investigation of neuromuscular disorders. Sonographically guided percutaneous needle biopsy of skeletal muscle was performed with a 14-gauge core biopsy system in 40 patients over a 24-month period. Patients were referred from the Department of Neurology under investigation for neuromuscular disorders. Sonography was used to find suitable tissue and to avoid major vascular structures. A local anesthetic was applied below skin only. A 3- to 4-mm incision was made. Three 14-gauge samples were obtained from each patient. All samples were placed on saline-dampened gauze and sent for neuropathologic analysis. As a control, we retrospectively assessed results of the 40 most recent muscle samples acquired via open surgical biopsy. With the use of sonography, 32 (80%) of 40 patients had a histologic diagnosis made via percutaneous needle biopsy. This included 26 (93%) of 28 patients with acute muscular disease and 6 (50%) of 12 patients with chronic disease. In the surgical group (all acute disease), 38 (95%) of 40 patients had diagnostic tissue attained. Sonographically guided percutaneous 14-gauge core skeletal muscle biopsy is a useful procedure, facilitating diagnosis in acute muscular disease. It provides results comparable with those of open surgical biopsy in acute muscular disease. It may also be used in chronic muscular disease but repeated or open biopsy may be needed.

  4. A Commentary on Real-Time Biofeedback to Augment Neuromuscular Training for ACL Injury Prevention in Adolescent Athletes

    Directory of Open Access Journals (Sweden)

    Adam W. Kiefer

    2015-03-01

    Full Text Available Anterior cruciate ligament injury and the associated long-term sequelae, such as immediate reductions in physical inactivity, increased adiposity and increased risk of osteoarthritis throughout adulthood, are a major health concern for adolescent athletes. Current interventions for injury prevention may have limited effectiveness, are susceptible to issues of compliance and have not achieved the widespread acceptance necessary to promote full adoption. Neuromuscular training (NMT is a well-established training intervention introduced to affect change in modifiable biomechanical risk factors to reduce the risk of injury in these athletes. Despite moderate success, neuromuscular training is still limited by its reliance on subjective feedback and after the fact (i.e., offline objective feedback techniques. The purpose of this commentary is to discuss technological tools that could be used to enhance and objectify targeted biofeedback interventions to complement NMT. Electromyography, force plates, motion sensors, and camera-based motion capture systems are innovative tools that may have realistic feasibility for integration as biofeedback into NMT programs to improve training outcomes. Improved functional deficit identification and corrective analysis may further improve and optimize athletic performance, and decrease the risk of sports-related injury during sport performance.

  5. Age related neuromuscular changes in sEMG of m. Tibialis Anterior using higher order statistics (Gaussianity & linearity test).

    Science.gov (United States)

    Siddiqi, Ariba; Arjunan, Sridhar P; Kumar, Dinesh K

    2016-08-01

    Age-associated changes in the surface electromyogram (sEMG) of Tibialis Anterior (TA) muscle can be attributable to neuromuscular alterations that precede strength loss. We have used our sEMG model of the Tibialis Anterior to interpret the age-related changes and compared with the experimental sEMG. Eighteen young (20-30 years) and 18 older (60-85 years) performed isometric dorsiflexion at 6 different percentage levels of maximum voluntary contractions (MVC), and their sEMG from the TA muscle was recorded. Six different age-related changes in the neuromuscular system were simulated using the sEMG model at the same MVCs as the experiment. The maximal power of the spectrum, Gaussianity and Linearity Test Statistics were computed from the simulated and experimental sEMG. A correlation analysis at α=0.05 was performed between the simulated and experimental age-related change in the sEMG features. The results show the loss in motor units was distinguished by the Gaussianity and Linearity test statistics; while the maximal power of the PSD distinguished between the muscular factors. The simulated condition of 40% loss of motor units with halved the number of fast fibers best correlated with the age-related change observed in the experimental sEMG higher order statistical features. The simulated aging condition found by this study corresponds with the moderate motor unit remodelling and negligible strength loss reported in literature for the cohorts aged 60-70 years.

  6. Partial neuromuscular blockade in humans enhances muscle blood flow during exercise independently of muscle oxygen uptake and acetylcholine receptor blockade

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Krustrup, Peter; Iaia, F Marcello

    2009-01-01

    This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one-legged k......This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one...... conductance during exercise, events that are not associated with either acetylcholine or an increased oxygen demand. The results do not support an essential role for acetylcholine, released form the neuromuscular junction, in exercise hyperaemia or for the enhanced blood flow during neuromuscular blockade....... The enhanced exercise hyperemia during partial neuromuscular blockade may be related to a greater recruitment of fast-twitch muscle fibres. Key words: blood flow, neuromuscular blockade, exercise, skeletal muscle....

  7. Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

    Directory of Open Access Journals (Sweden)

    Giuseppe Scapigliati

    2018-05-01

    Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

  8. Signal Peptide and Denaturing Temperature are Critical Factors for Efficient Mammalian Expression and Immunoblotting of Cannabinoid Receptors*

    Science.gov (United States)

    WANG, Chenyun; WANG, Yingying; WANG, Miao; CHEN, Jiankui; YU, Nong; SONG, Shiping; KAMINSKI, Norbert E.; ZHANG, Wei

    2013-01-01

    Summary Many researchers employed mammalian expression system to artificially express cannabinoid receptors, but immunoblot data that directly prove efficient protein expression can hardly be seen in related research reports. In present study, we demonstrated cannabinoid receptor protein was not able to be properly expressed with routine mammalian expression system. This inefficient expression was rescued by endowing an exogenous signal peptide ahead of cannabinoid receptor peptide. In addition, the artificially synthesized cannabinoid receptor was found to aggregate under routine sample denaturing temperatures (i.e., ≥95°C), forming a large molecular weight band when analyzed by immunoblotting. Only denaturing temperatures ≤75°C yielded a clear band at the predicted molecular weight. Collectively, we showed that efficient mammalian expression of cannabinoid receptors need a signal peptide sequence, and described the requirement for a low sample denaturing temperature in immunoblot analysis. These findings provide very useful information for efficient mammalian expression and immunoblotting of membrane receptors. PMID:22528237

  9. The Effects of the Gaelic Athletic Association 15 Training Program on Neuromuscular Outcomes in Gaelic Football and Hurling Players: A Randomized Cluster Trial.

    Science.gov (United States)

    OʼMalley, Edwenia; Murphy, John C; McCarthy Persson, Ulrik; Gissane, Conor; Blake, Catherine

    2017-08-01

    O'Malley, E, Murphy, JC, McCarthy Persson, U, Gissane, C, and Blake, C. The effects of the Gaelic Athletic Association 15 training program on neuromuscular outcomes in Gaelic football and hurling players: A randomized cluster trial. J Strength Cond Res 31(8): 2119-2130, 2017-Team-based neuromuscular training programs for injury prevention have been tested primarily in female and adolescent athletes in soccer, handball, and basketball with limited research in adult male field sports. This study explored whether the GAA 15, a multifaceted 8-week neuromuscular training program developed by the Gaelic Athletic Association (GAA), could improve risk factors for lower limb injury in male Gaelic footballers and hurlers. Four Gaelic sports collegiate teams were randomized into intervention or control groups. Two teams (n = 41), one football and one hurling, were allocated to the intervention, undertaking a 15 minutes program of neuromuscular training exercises at the start of team training sessions, twice weekly for 8 weeks. Two matched teams (n = 37) acted as controls, participating in usual team training. Lower extremity stability (Y-Balance test [YBT]) and jump-landing technique using the Landing Error Scoring System (LESS) were assessed preintervention and postintervention. There were moderate effect sizes in favor of the intervention for right (d = 0.59) and left (d = 0.69) composite YBT scores, with adjusted mean differences between intervention and control of 3.85 ± 0.91% and 4.34 ± 0.92% for right and left legs, respectively (p training (Cohen's d = 0.72, adjusted mean difference 2.49 ± 0.54, p jump-landing technique occurred in collegiate level Gaelic football and hurling players who adopted the GAA 15, when compared with usual training. These findings support application and evaluation of the GAA 15 in other player groups within the Gaelic games playing population.

  10. The 2013 German-Russian BION-M1 Joint Flight Project: Skeletal Muscle and Neuromuscular Changes in Mice Housed for 30 Days in a Biosatellite on Orbit

    Science.gov (United States)

    Blottner, Dieter; Shenkman, Boris; Salanova, Michele

    Exposure to microgravity results in various structural, biochemical and molecular changes of the skeletal neuromuscular system. The BION Joint Flight Proposal between the Charité Berlin Center of Space Medicine (www.zwmb.de) in Berlin, and the Institute of Biomedical Problem (IMBP) in Moscow, provided an exciting opportunity for a more detailed analysis of neuromuscular changes in mice (C57/bl6) exposed to real microgravity housed for 30 days in a BION M1 biosatellite on orbit. The mice from the BION flight group (n=5) were compared to three different on-ground control groups (Flight control, BION-ground and Vivarium, each n=5 mice). We started to analyse various skeletal muscles from the hind limbs or trunk. Apart from routine structural and biochemical analysis (fiber size and type distribution, slow/fastMyHC) we test the hypothesis for the presence of a microgravity-induced sarcolemma-cytosolic protein shift of nitric oxide synthase (NOS) and partial loss in neuromuscular synapse scaffold protein (Homer) immunoexpression known to be prone to disuse in mice or humans (hind limb unloading, bed rest) as previously shown (Sandonà D et al., PLoS One, 2012, Salanova M et al., FASEB J, 2011). National Sponsors: Federal Ministry of Economics and Technology (BMWi) via the German AeroSpace Board, DLR e.V., Bonn-Oberkassel, Germany (#50WB1121); Contract RAS-IMBP/Charité Berlin # Bion-M1/2013

  11. Direct Capture of Functional Proteins from Mammalian Plasma Membranes into Nanodiscs.

    Science.gov (United States)

    Roy, Jahnabi; Pondenis, Holly; Fan, Timothy M; Das, Aditi

    2015-10-20

    Mammalian plasma membrane proteins make up the largest class of drug targets yet are difficult to study in a cell free system because of their intransigent nature. Herein, we perform direct encapsulation of plasma membrane proteins derived from mammalian cells into a functional nanodisc library. Peptide fingerprinting was used to analyze the proteome of the incorporated proteins in nanodiscs and to further demonstrate that the lipid composition of the nanodiscs directly affects the class of protein that is incorporated. Furthermore, the functionality of the incorporated membrane proteome was evaluated by measuring the activity of membrane proteins: Na(+)/K(+)-ATPase and receptor tyrosine kinases. This work is the first report of the successful establishment and characterization of a cell free functional library of mammalian membrane proteins into nanodiscs.

  12. Expression of recombinant glycoproteins in mammalian cells: towards an integrative approach to structural biology.

    Science.gov (United States)

    Aricescu, A Radu; Owens, Raymond J

    2013-06-01

    Mammalian cells are rapidly becoming the system of choice for the production of recombinant glycoproteins for structural biology applications. Their use has enabled the structural investigation of a whole new set of targets including large, multi-domain and highly glycosylated eukaryotic cell surface receptors and their supra-molecular assemblies. We summarize the technical advances that have been made in mammalian expression technology and highlight some of the structural insights that have been obtained using these methods. Looking forward, it is clear that mammalian cell expression will provide exciting and unique opportunities for an integrative approach to the structural study of proteins, especially of human origin and medically relevant, by bridging the gap between the purified state and the cellular context. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap.

    Science.gov (United States)

    Wiest, Matheus J; Bergquist, Austin J; Schimidt, Helen L; Jones, Kelvin E; Collins, David F

    2017-04-01

    In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017. © 2016 Wiley Periodicals, Inc.

  14. Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

    Science.gov (United States)

    Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

    1998-01-01

    VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

  15. Neuromuscular factors related to success in Olympic wrestling

    Directory of Open Access Journals (Sweden)

    Alfonso Martínez-Moreno

    2011-03-01

    Full Text Available Abstract This study was undertaken to determine the relationship between maximum dynamic and isometric strength and success in male and female Olympic wrestling. Thirty-five female and thirty-seven male wrestlers were assigned into 4 groups according to their gender and competitive level: men elite (♂ ET, n = 18 and amateur (AT ♂, n = 19 and female elite (♀ ET n = 13 and amateur (AT ♀, n = 22. All subjects underwent assessments of body composition, countermovement jump, maximum dynamic strength test in full squat and bench press exercises and maximum isometric strength test of grip and hip extension. All the neuromuscular markers studied showed significantly higher values in the two elite groups compared to their respective amateur groups results, except the jump height between ♀ET y ♀AT, where no significant differences were detected. The present results suggest that the higher maximum isometric and dynamic strength values, explained in part by the differences in lean mass, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling.  Key  Words: bench press; squat; maximum dynamic strength; maximum isometric strength; combat.

  16. Neuromuscular factors related to success in Olympic wrestling

    Directory of Open Access Journals (Sweden)

    Alfonso Martínez-Moreno

    2011-03-01

    Full Text Available AbstractThis study was undertaken to determine the relationship between maximum dynamic and isometric strength and success in male and female Olympic wrestling. Thirty-five female and thirty-seven male wrestlers were assigned into 4 groups according to their gender and competitive level: men elite (♂ ET, n = 18 and amateur (AT ♂, n = 19 and female elite (♀ ET n = 13 and amateur (AT ♀, n = 22. All subjects underwent assessments of body composition, countermovement jump, maximum dynamic strength test in full squat and bench press exercises and maximum isometric strength test of grip and hip extension. All the neuromuscular markers studied showed significantly higher values in the two elite groups compared to their respective amateur groups results, except the jump height between ♀ET y ♀AT, where no significant differences were detected. The present results suggest that the higher maximum isometric and dynamic strength values, explained in part by the differences in lean mass, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling. Key  Words: bench press; squat; maximum dynamic strength; maximum isometric strength; combat.

  17. Neuromuscular adjustments of the quadriceps muscle after repeated cycling sprints.

    Directory of Open Access Journals (Sweden)

    Olivier Girard

    Full Text Available PURPOSE: This study investigated the supraspinal processes of fatigue of the quadriceps muscle in response to repeated cycling sprints. METHODS: Twelve active individuals performed 10 × 6-s "all-out" sprints on a cycle ergometer (recovery = 30 s, followed 6 min later by 5 × 6-s sprints (recovery = 30 s. Transcranial magnetic and electrical femoral nerve stimulations during brief (5-s and sustained (30-s isometric contractions of the knee extensors were performed before and 3 min post-exercise. RESULTS: Maximal strength of the knee extensors decreased during brief and sustained contractions (~11% and 9%, respectively; P0.05. While cortical voluntary activation declined (P 40% reduced (P<0.001 following exercise. CONCLUSION: The capacity of the motor cortex to optimally drive the knee extensors following a repeated-sprint test was shown in sustained, but not brief, maximal isometric contractions. Additionally, peripheral factors were largely involved in the exercise-induced impairment in neuromuscular function, while corticospinal excitability was well-preserved.

  18. Alterations in neuromuscular function in girls with generalized joint hypermobility.

    Science.gov (United States)

    Jensen, Bente Rona; Sandfeld, Jesper; Melcher, Pia Sandfeld; Johansen, Katrine Lyders; Hendriksen, Peter; Juul-Kristensen, Birgit

    2016-10-03

    Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions (90°) at 20 % Maximum Voluntary Contraction, and explosive isometric knee flexions while sitting. EMG was recorded from knee flexor and extensor muscles. Early rate of torque development was 53 % faster for GJH. Reduced hamstring muscle activation in girls with GJH was found while knee extensor and calf muscle activation did not differ between groups. Flexion-extension and medial-lateral co-activation ratio during flexions were higher for girls with GJH than NGJH girls. Girls with GJH had higher capacity to rapidly generate force than NGJH girls which may reflect motor adaptation to compensate for hypermobility. Higher medial muscle activation indicated higher levels of medial knee joint compression in girls with GJH. Increased flexion-extension co-activation ratios in GJH were explained by decreased agonist drive to the hamstrings.

  19. Long-term neuromuscular training and ankle joint position sense.

    Science.gov (United States)

    Kynsburg, A; Pánics, G; Halasi, T

    2010-06-01

    Preventive effect of proprioceptive training is proven by decreasing injury incidence, but its proprioceptive mechanism is not. Major hypothesis: the training has a positive long-term effect on ankle joint position sense in athletes of a high-risk sport (handball). Ten elite-level female handball-players represented the intervention group (training-group), 10 healthy athletes of other sports formed the control-group. Proprioceptive training was incorporated into the regular training regimen of the training-group. Ankle joint position sense function was measured with the "slope-box" test, first described by Robbins et al. Testing was performed one day before the intervention and 20 months later. Mean absolute estimate errors were processed for statistical analysis. Proprioceptive sensory function improved regarding all four directions with a high significance (pneuromuscular training has improved ankle joint position sense function in the investigated athletes. This joint position sense improvement can be one of the explanations for injury rate reduction effect of neuromuscular training.

  20. Kinematic and neuromuscular relationships between lower extremity clinical movement assessments.

    Science.gov (United States)

    Mauntel, Timothy C; Cram, Tyler R; Frank, Barnett S; Begalle, Rebecca L; Norcross, Marc F; Blackburn, J Troy; Padua, Darin A

    2018-06-01

    Lower extremity injuries have immediate and long-term consequences. Lower extremity movement assessments can assist with identifying individuals at greater injury risk and guide injury prevention interventions. Movement assessments identify similar movement characteristics and evidence suggests large magnitude kinematic relationships exist between movement patterns observed across assessments; however, the magnitude of the relationships for electromyographic (EMG) measures across movement assessments remains largely unknown. This study examined relationships between lower extremity kinematic and EMG measures during jump landings and single leg squats. Lower extremity three-dimensional kinematic and EMG data were sampled from healthy adults (males = 20, females = 20) during the movement assessments. Pearson correlations examined the relationships of the kinematic and EMG measures and paired samples t-tests compared mean kinematic and EMG measures between the assessments. Overall, significant moderate correlations were observed for lower extremity kinematic (r avg  = 0.41, r range  = 0.10-0.61) and EMG (r avg  = 0.47, r range  = 0.32-0.80) measures across assessments. Kinematic and EMG measures were greater during the jump landings. Jump landings and single leg squats place different demands on the body and necessitate different kinematic and EMG patterns, such that these measures are not highly correlated between assessments. Clinicians should, therefore, use multiple assessments to identify aberrant movement and neuromuscular control patterns so that comprehensive interventions can be implemented.

  1. Validity of the Neuromuscular Recovery Scale: a measurement model approach.

    Science.gov (United States)

    Velozo, Craig; Moorhouse, Michael; Ardolino, Elizabeth; Lorenz, Doug; Suter, Sarah; Basso, D Michele; Behrman, Andrea L

    2015-08-01

    To determine how well the Neuromuscular Recovery Scale (NRS) items fit the Rasch, 1-parameter, partial-credit measurement model. Confirmatory factor analysis (CFA) and principal components analysis (PCA) of residuals were used to determine dimensionality. The Rasch, 1-parameter, partial-credit rating scale model was used to determine rating scale structure, person/item fit, point-measure item correlations, item discrimination, and measurement precision. Seven NeuroRecovery Network clinical sites. Outpatients (N=188) with spinal cord injury. Not applicable. NRS. While the NRS met 1 of 3 CFA criteria, the PCA revealed that the Rasch measurement dimension explained 76.9% of the variance. Ten of 11 items and 91% of the patients fit the Rasch model, with 9 of 11 items showing high discrimination. Sixty-nine percent of the ratings met criteria. The items showed a logical item-difficulty order, with Stand retraining as the easiest item and Walking as the most challenging item. The NRS showed no ceiling or floor effects and separated the sample into almost 5 statistically distinct strata; individuals with an American Spinal Injury Association Impairment Scale (AIS) D classification showed the most ability, and those with an AIS A classification showed the least ability. Items not meeting the rating scale criteria appear to be related to the low frequency counts. The NRS met many of the Rasch model criteria for construct validity. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. The rapid evolution of molecular genetic diagnostics in neuromuscular diseases.

    Science.gov (United States)

    Volk, Alexander E; Kubisch, Christian

    2017-10-01

    The development of massively parallel sequencing (MPS) has revolutionized molecular genetic diagnostics in monogenic disorders. The present review gives a brief overview of different MPS-based approaches used in clinical diagnostics of neuromuscular disorders (NMDs) and highlights their advantages and limitations. MPS-based approaches like gene panel sequencing, (whole) exome sequencing, (whole) genome sequencing, and RNA sequencing have been used to identify the genetic cause in NMDs. Although gene panel sequencing has evolved as a standard test for heterogeneous diseases, it is still debated, mainly because of financial issues and unsolved problems of variant interpretation, whether genome sequencing (and to a lesser extent also exome sequencing) of single patients can already be regarded as routine diagnostics. However, it has been shown that the inclusion of parents and additional family members often leads to a substantial increase in the diagnostic yield in exome-wide/genome-wide MPS approaches. In addition, MPS-based RNA sequencing just enters the research and diagnostic scene. Next-generation sequencing increasingly enables the detection of the genetic cause in highly heterogeneous diseases like NMDs in an efficient and affordable way. Gene panel sequencing and family-based exome sequencing have been proven as potent and cost-efficient diagnostic tools. Although clinical validation and interpretation of genome sequencing is still challenging, diagnostic RNA sequencing represents a promising tool to bypass some hurdles of diagnostics using genomic DNA.

  3. Neurologic and neuromuscular functional disorders of the pharynx and esophagus

    International Nuclear Information System (INIS)

    Wuttge-Hannig, A.; Hannig, C.

    2007-01-01

    Neurologic swallowing disorders are an increasing diagnostic problem in our overaged population. Undiagnosed chronic aspiration pneumonia is the cause of death in 20-40% of all inhabitants of nursing homes. In neurologic diseases of the pharynx, the physiologic interaction of pharyngeal contraction, closure of the pharynx, and esophageal motility are frequently disturbed. This may be due to cortical, bulbar, or cerebellar brain damage of ischemic or traumatic origin. Furthermore diseases or peripheral nerves, muscles, and synapses cause disturbances. The most life-threatening complication of these disturbances is tracheal aspiration, which requires an iso-osmolar contrast medium for imaging studies that cause no or minimal pulmonary problems. Utilizing fast dynamic documentation we can analyze the swallowing act in 35 images within the passage time of 0.7 s. This requires digital frame sequences from 15-50 images/s, which can be provided by DSI or videofluoroscopy. Neurologic and neuromuscular patterns are demonstrated with and without tracheal aspiration. The differentiation of aspiration in a so-called pre-, intra-, and postdeglutitive form is possible. We distinguish four grades of severity of aspiration, which is also of great clinical impact for the differential rehabilitation therapy. The efficiency of the rehabilitation protocol can be assessed by the dynamic swallowing studies. (orig.) [de

  4. Peripheral neuromuscular dysfunction and falls in an elderly cohort.

    Science.gov (United States)

    Sorock, G S; Labiner, D M

    1992-09-01

    In a prospective study of 169 tenants of senior citizen housing in New Jersey in 1986-1987, the relations between tests of peripheral sensory and motor functions in the lower extremities and the rate of first falls were evaluated. The mean age of the cohort was 79.8 years. Fifty-seven persons fell at least once during the follow-up period (mean, 5.6 months). After adjustment for history of stroke, heart failure, emphysema, and use of a walker or cane, rate ratios for first falls were elevated in subjects with reduced toe joint position sense (rate ratio (RR) = 2.2) and sharp-dull discrimination (RR = 2.0), but to a lesser extent for reduced ankle strength (RR = 1.5). Presence of one or more of these three deficits was defined as a peripheral neuromuscular dysfunction and was associated with first falls after adjustment for multiple covariates (RR = 2.4, 95% confidence interval 1.3-4.5). Having two or all three sensory or motor deficits increased the rate of falling 3.9 times (95% confidence interval 2.1-7.0) compared with persons without these deficits. These data suggest that impaired sensory and motor function of the lower extremities plays an important role in falls in the elderly.

  5. Applications of Shape Memory Alloys for Neurology and Neuromuscular Rehabilitation

    Directory of Open Access Journals (Sweden)

    Simone Pittaccio

    2015-05-01

    Full Text Available Shape memory alloys (SMAs are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE, shape memory effect (SME and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous.

  6. Noninvasive Respiratory Management of Patients With Neuromuscular Disease.

    Science.gov (United States)

    Bach, John R

    2017-08-01

    This review article describes definitive noninvasive respiratory management of respiratory muscle dysfunction to eliminate need to resort to tracheotomy. In 2010 clinicians from 22 centers in 18 countries reported 1,623 spinal muscular atrophy type 1 (SMA1), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis users of noninvasive ventilatory support (NVS) of whom 760 required it continuously (CNVS). The CNVS sustained their lives by over 3,000 patient-years without resort to indwelling tracheostomy tubes. These centers have now extubated at least 74 consecutive ventilator unweanable patients with DMD, over 95% of CNVS-dependent patients with SMA1, and hundreds of others with advanced neuromuscular disorders (NMDs) without resort to tracheotomy. Two centers reported a 99% success rate at extubating 258 ventilator unweanable patients without resort to tracheotomy. Patients with myopathic or lower motor neuron disorders can be managed noninvasively by up to CNVS, indefinitely, despite having little or no measurable vital capacity, with the use of physical medicine respiratory muscle aids. Ventilator-dependent patients can be decannulated of their tracheostomy tubes.

  7. Effect of calcium on excitatory neuromuscular transmission in the crayfish

    Science.gov (United States)

    Bracho, H.; Orkand, R. K.

    1970-01-01

    1. The effects of varying the external Ca concentration from 1·8 to 30 mM/l. (⅛-2 times normal) have been studied at the in vitro crayfish excitatory neuromuscular junction. Electrophysiological techniques were used to record transmembrane junctional potentials from muscle fibres and extracellular junctional currents from the vicinity of nerve terminals. 2. The excitatory junctional potential amplitude was proportional to [Ca]0n, where n varied between 0·68 and 0·94 (mean 0·82) when [Ca]0 was varied from 1·8 to 15 mM/l. 3. The increase in junctional potential amplitude on raising [Ca]0 resulted primarily from an increase in the average number of quanta of excitatory transmitter released from the presynaptic nerve terminal by the nerve impulse. 4. The size of the quanta, synaptic delay, presynaptic potential and electrical properties of the muscle membrane were little affected by changes in calcium concentration in the range studied. PMID:5498460

  8. Evaluation of ventilators for mouthpiece ventilation in neuromuscular disease.

    Science.gov (United States)

    Khirani, Sonia; Ramirez, Adriana; Delord, Vincent; Leroux, Karl; Lofaso, Frédéric; Hautot, Solène; Toussaint, Michel; Orlikowski, David; Louis, Bruno; Fauroux, Brigitte

    2014-09-01

    Daytime mouthpiece ventilation is a useful adjunct to nocturnal noninvasive ventilation (NIV) in patients with neuromuscular disease. The aims of the study were to analyze the practice of mouthpiece ventilation and to evaluate the performance of ventilators for mouthpiece ventilation. Practice of mouthpiece ventilation was assessed by a questionnaire, and the performance of 6 home ventilators with mouthpiece ventilation was assessed in a bench test using 24 different conditions per ventilator: 3 mouthpieces, a child and an adult patient profile, and 4 ventilatory modes. Questionnaires were obtained from 30 subjects (mean age 33 ± 11 y) using NIV for 12 ± 7 y. Fifteen subjects used NIV for > 20 h/day, and 11 were totally ventilator-dependent. The subject-reported benefits of mouthpiece ventilation were a reduction in dyspnea (73%) and fatigue (93%) and an improvement in speech (43%) and eating (27%). The bench study showed that none of the ventilators, even those with mouthpiece ventilation software, were able to deliver mouthpiece ventilation without alarms and/or autotriggering in each condition. Alarms and/or ineffective triggering or autotriggering were observed in 135 of the 198 conditions. The occurrence of alarms was more common with a large mouthpiece without a filter compared to a small mouthpiece with a filter (P ventilator. Subjects are satisfied with mouthpiece ventilation. Alarms are common with home ventilators, although less common in those with mouthpiece ventilation software. Improvements in home ventilators are needed to facilitate the expansion of mouthpiece ventilation. Copyright © 2014 by Daedalus Enterprises.

  9. Supervised neuromuscular exercise prior to hip and knee replacement

    DEFF Research Database (Denmark)

    Fernandes, Linda; Roos, Ewa M; Overgaard, Søren

    2017-01-01

    was analysed to estimate the probability for the intervention being cost effective for a range of threshold values. A health care sector perspective was applied. RESULTS: HOOS/KOOS quality of life [8.25 (95% CI, 0.42 to 16.10)] and QALYs [0.04 (95% CI, 0.01 to 0.07)] were statistically significantly improved....... Effect-sizes ranged between 0.09-0.59 for HOOS/KOOS subscales. Despite including an intervention cost of €326 per patient, there was no difference in total cost between groups [€132 (95% CI -3942 to 3679)]. At a threshold of €40,000, preoperative exercise was found to be cost effective at 84% probability....... CONCLUSION: Preoperative supervised neuromuscular exercise for 8 weeks was found to be cost-effective in patients scheduled for THR and TKR surgery at conventional thresholds for willingness to pay. One-year clinical effects were small to moderate and favoured the intervention group, but only statistically...

  10. Lower Limb Neuromuscular Asymmetry in Volleyball and Basketball Players.

    Science.gov (United States)

    Fort-Vanmeerhaeghe, Azahara; Gual, Gabriel; Romero-Rodriguez, Daniel; Unnitha, Viswanath

    2016-04-01

    The primary objective of the present study was to evaluate the agreement between the dominant leg (DL) (determined subjectively) and the stronger leg (SL) (determined via a functional test) in a group of basketball and volleyball players. The secondary objective was to calculate lower limb neuromuscular asymmetry when comparing the DL vs the non-dominant leg (NDL) and the SL vs the weaker (WL) leg in the whole group and when differentiating by sex. Seventy-nine male and female volleyball and basketball players (age: 23.7 ± 4.5 years) performed three single-leg vertical countermovement jumps (SLVCJ) on a contact mat. Vertical jump height and an inter-limb asymmetry index (ASI) were determined. Only 32 (40%) of the subjects had a concordance between the perception of their dominant leg and the limb reaching the highest jump height. Using the DL as the discriminating variable, significant (pjump performance. Vertical jump asymmetry of 10-15% exists and this can be considered as a reference value for male and female basketball and volleyball players.

  11. An examination of neuromuscular and metabolic fatigue thresholds

    International Nuclear Information System (INIS)

    Bergstrom, Haley C; Housh, Terry J; Cochrane, Kristen C; Jenkins, Nathaniel D M; Lewis, Robert W Jr; Traylor, Daniel A; Schmidt, Richard J; Johnson, Glen O; Cramer, Joel T; Zuniga, Jorge M

    2013-01-01

    This study examined the relationships among the physical working capacity at the fatigue threshold (PWC FT ), the power outputs associated with the gas exchange threshold (PGET) and the respiratory compensation point (PRCP), and critical power (CP) to identify possible physiological mechanisms underlying the onset of neuromuscular fatigue. Ten participants (mean ± SD age: 20 ± 1 years) performed a maximal incremental cycle ergometer test to determine the PWC FT , PGET, and PRCP. CP was determined from the 3 min all-out test. The PWC FT (197 ± 55 W), PRCP (212 ± 50 W), and CP (208 ± 63 W) were significantly greater than the PGET (168 ± 40 W), but there were no significant differences among the PWC FT , PRCP, and CP. All thresholds were significantly inter-4 (r = 0.794–0.958). The 17% greater estimates for the PWC FT than PGET were likely related to differences in the physiological mechanisms that underlie these fatigue thresholds, while the non-significant difference and high correlation between the PWC FT and the PRCP suggested that hyperkalemia may underlie both thresholds. Furthermore, it is possible that the 5% lower estimate of the PWC FT than CP could more accurately reflect the demarcation of the heavy from severe exercise intensity domains. (paper)

  12. A family of neuromuscular stimulators with optical transcutaneous control.

    Science.gov (United States)

    Jarvis, J C; Salmons, S

    1991-01-01

    A family of miniature implantable neuromuscular stimulators has been developed using surface-mounted Philips 4000-series integrated circuits. The electronic components are mounted by hand on printed circuits (platinum/gold on alumina) and the electrical connections are made by reflow soldering. The plastic integrated-circuit packages, ceramic resistors and metal interconnections are protected from the body fluids by a coating of biocompatible silicone rubber. This simple technology provides reliable function for at least 4 months under implanted conditions. The circuits have in common a single lithium cell power-supply (3.2 V) and an optical sensor which can be used to detect light flashes through the skin after the device has been implanted. This information channel may be used to switch the output of a device on or off, or to cycle through a series of pre-set programs. The devices are currently finding application in studies which provide an experimental basis for the clinical exploitation of electrically stimulated skeletal muscle in cardiac assistance, sphincter reconstruction or functional electrical stimulation of paralysed limbs.

  13. Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

    Science.gov (United States)

    Pallarés, J G; López-Samanes, Á; Fernández-Elías, V E; Aguado-Jiménez, R; Ortega, J F; Gómez, C; Ventura, R; Segura, J; Mora-Rodríguez, R

    2015-12-01

    This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  15. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  16. Application of recombinant fluorescent mammalian cells as a toxicity biosensor.

    Science.gov (United States)

    Kim, E J; Lee, Y; Lee, J E; Gu, M B

    2002-01-01

    With respect to developing a more sensitive biosensor, a recombinant fluorescent Chinese Hamster Ovary cell line was used for the monitoring of various toxicants. Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively. They were characterized with mitomycin C and gamma-ray as genotoxicants and bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs. When compared to each other, the response of KFC-A10 was generally more informative and sensitive. Compared to typical bacterial biosensor systems, these cell lines offered a sensitivity of 2- to 50-fold greater for the tested chemicals. Based on these results, the use of mammalian cells offers a sensitive biosensor system that is not only fast, cheap and reproducible but also capable of monitoring the endocrine-like characteristics of environmental toxicants.

  17. Mammalian developmental genetics in the twentieth century.

    Science.gov (United States)

    Artzt, Karen

    2012-12-01

    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.

  18. Nutrient acquisition strategies of mammalian cells.

    Science.gov (United States)

    Palm, Wilhelm; Thompson, Craig B

    2017-06-07

    Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

  19. Preservation of mammalian germ plasm by freezing

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, P.

    1978-01-01

    Embryos of several mammalian species can be frozen to -196/sup 0/C (or below) by procedures that result in the thawed embryos being indistinguishable from their unfrozen counterparts. The survival often exceeds 90%, and in liquid nitrogen it should remain at that high level for centuries. Sublethal biochemical changes are also precluded at -196/sup 0/C. No developmental abnormalities have been detected in mouse offspring derived from frozen-thawed embryos, and, since all the manipulations are carried out on the preimplantation stages, none would be expected.

  20. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    Science.gov (United States)

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years.

  1. Mammalian Gravity Receptors: Structure and Metabolism

    Science.gov (United States)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  2. Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives

    Directory of Open Access Journals (Sweden)

    Carron M

    2017-12-01

    Full Text Available Michele Carron, Francesco Bertoncello, Giovanna Ieppariello Department of Medicine, Anesthesiology, and Intensive Care, University of Padova, Padua, Italy Abstract: The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed. Keywords: sugammadex, aging, elderly, neuromuscular blockade, rocuronium, anesthesia, safety

  3. Characterization of cervical neuromuscular response to head-neck perturbation in active young adults.

    Science.gov (United States)

    Alsalaheen, Bara; Bean, Ryan; Almeida, Andrea; Eckner, James; Lorincz, Matthew

    2018-04-01

    The majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response. Nineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: (1) Anticipated perturbation with no preload (A-NP), (2) Unanticipated perturbation with no preload (U-NP), (3) Anticipated perturbation with preload (A-P), and (4) Unanticipated perturbation with preload (U-P). None of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM. The findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Neuromodulation of activity-dependent synaptic enhancement at crayfish neuromuscular junction.

    Science.gov (United States)

    Qian, S M; Delaney, K R

    1997-10-17

    Action potential-evoked transmitter release is enhanced for many seconds after moderate-frequency stimulation (e.g. 15 Hz for 30 s) at the excitor motorneuron synapse of the crayfish dactyl opener muscle. Beginning about 1.5 s after a train, activity-dependent synaptic enhancement (ADSE) is dominated by a process termed augmentation (G.D. Bittner, D.A. Baxter, Synaptic plasticity at crayfish neuromuscular junctions: facilitation and augmentation, Synapse 7 (1991) 235-243'[4]; K.L. Magleby, Short-term changes in synaptic efficacy, in: G.M. Edelman, L.E. Gall, C.W. Maxwell (Eds.), Synaptic Function, John Wiley and Sons, New York, 1987, pp. 21-56; K.L. Magleby; J.E. Zengel, Augmentation: a process that acts to increase transmitter release at the frog neuromuscular junction, J. Physiol. (Lond.) 257 (1976) 449-470) which decays approximately exponentially with a time constant of about 10 s at 16 degrees C, reflecting the removal of Ca2+ which accumulates during the train in presynaptic terminals (K.R. Delaney, D.W. Tank, R.S. Zucker, Serotonin-mediated enhancement of transmission at crayfish neuromuscular junction is independent of changes in calcium, J. Neurosci. 11 (1991) 2631-2643). Serotonin (5-HT, 1 microM) increases evoked and spontaneous transmitter release several-fold (D. Dixon, H.L. Atwood, Crayfish motor nerve terminal's response to serotonin examined by intracellular microelectrode, J. Neurobiol. 16 (1985) 409-424; J. Dudel, Modulation of quantal synaptic release by serotonin and forskolin in crayfish motor nerve terminals, in: Modulation of Synaptic Transmission and Plasticity in Nervous Systems, G. Hertting, H.-C. Spatz (Eds.), Springer-Verlag, Berlin, 1988; S. Glusman, E.A. Kravitz. The action of serotonin on excitatory nerve terminals in lobster nerve-muscle preparations, J. Physiol. (Lond.) 325 (1982) 223-241). We found that ADSE persists about 2-3 times longer after moderate-frequency presynaptic stimulation in the presence of 5-HT. This slowing of the

  5. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

    Science.gov (United States)

    Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

    2018-02-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

  6. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

    Science.gov (United States)

    Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

    2018-01-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

  7. Sport-Specific Assessment of the Effectiveness of Neuromuscular Training in Young Athletes.

    Science.gov (United States)

    Zemková, Erika; Hamar, Dušan

    2018-01-01

    Neuromuscular training in young athletes improves performance and decreases the risk of injuries during sports activities. These effects are primarily ascribed to the enhancement of muscle strength and power but also balance, speed and agility. However, most studies have failed to demonstrate significant improvement in these abilities. This is probably due to the fact that traditional tests do not reflect training methods (e.g., plyometric training vs. isometric or isokinetic strength testing, dynamic balance training vs. static balance testing). The protocols utilized in laboratories only partially fulfill the current needs for testing under sport-specific conditions. Moreover, laboratory testing usually requires skilled staff and a well equipped and costly infrastructure. Nevertheless, experience demonstrates that high-technology and expensive testing is not the only way to proceed. A number of physical fitness field tests are available today. However, the low reliability and limited number of parameters retrieved from simple equipment used also limit their application in competitive sports. Thus, there is a need to develop and validate a functional assessment platform based on portable computerized systems. Variables obtained should be directly linked to specific features of particular sports and capture their complexity. This is essential for revealing weak and strong components of athlete performance and design of individually-tailored exercise programs. Therefore, identifying the drawbacks associated with the assessment of athlete performance under sport-specific conditions would provide a basis for the formation of an innovative approach to their long-term systematic testing. This study aims (i) to review the testing methods used for the evaluation of the effect of neuromuscular training on sport-specific performance in young athletes, (ii) to introduce stages within the Sport Longlife Diagnostic Model, and (iii) to propose future research in this topic

  8. Sport-Specific Assessment of the Effectiveness of Neuromuscular Training in Young Athletes

    Science.gov (United States)

    Zemková, Erika; Hamar, Dušan

    2018-01-01

    Neuromuscular training in young athletes improves performance and decreases the risk of injuries during sports activities. These effects are primarily ascribed to the enhancement of muscle strength and power but also balance, speed and agility. However, most studies have failed to demonstrate significant improvement in these abilities. This is probably due to the fact that traditional tests do not reflect training methods (e.g., plyometric training vs. isometric or isokinetic strength testing, dynamic balance training vs. static balance testing). The protocols utilized in laboratories only partially fulfill the current needs for testing under sport-specific conditions. Moreover, laboratory testing usually requires skilled staff and a well equipped and costly infrastructure. Nevertheless, experience demonstrates that high-technology and expensive testing is not the only way to proceed. A number of physical fitness field tests are available today. However, the low reliability and limited number of parameters retrieved from simple equipment used also limit their application in competitive sports. Thus, there is a need to develop and validate a functional assessment platform based on portable computerized systems. Variables obtained should be directly linked to specific features of particular sports and capture their complexity. This is essential for revealing weak and strong components of athlete performance and design of individually-tailored exercise programs. Therefore, identifying the drawbacks associated with the assessment of athlete performance under sport-specific conditions would provide a basis for the formation of an innovative approach to their long-term systematic testing. This study aims (i) to review the testing methods used for the evaluation of the effect of neuromuscular training on sport-specific performance in young athletes, (ii) to introduce stages within the Sport Longlife Diagnostic Model, and (iii) to propose future research in this topic

  9. Pilates and Proprioceptive Neuromuscular Facilitation Methods Induce Similar Strength Gains but Different Neuromuscular Adaptations in Elderly Women.

    Science.gov (United States)

    Teixeira de Carvalho, Fabiana; de Andrade Mesquita, Laiana Sepúlveda; Pereira, Rafael; Neto, Osmar Pinto; Amaro Zangaro, Renato

    2017-01-01

    Background/Study Context: The aging process is associated with a decline in muscle mass, strength, and conditioning. Two training methods that may be useful to improve muscle function are Pilates and proprioceptive neuromuscular facilitation (PNF). Thus, the present study aimed to compare the influence of training programs using Pilates and PNF methods with elderly women. Sixty healthy elderly women were randomly divided into three groups: Pilates group, PNF group, and control group. Pilates and PNF groups underwent 1-month training programs with Pilates and PNF methods, respectively. The control group received no intervention during the 1 month. The maximal isometric force levels from knee extension and flexion, as well as the electromyography (EMG) signals from quadriceps and biceps femoris, were recorded before and after the 1-month intervention period. A two-way analysis of variance revealed that the Pilates and PNF methods induced similar strength gains from knee flexors and extensors, but Pilates exhibited greater low-gamma drive (i.e., oscillations in 30-60 Hz) in the EMG power spectrum after the training period. These results support use of both Pilates and PNF methods to enhance lower limb muscle strength in older groups, which is very important for gait, postural stability, and performance of daily life activities.

  10. Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

    Science.gov (United States)

    Jenkins, F A; Crompton, A W; Downs, W R

    1983-12-16

    Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

  11. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  12. Ecology and evolution of mammalian biodiversity.

    Science.gov (United States)

    Jones, Kate E; Safi, Kamran

    2011-09-12

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future.

  13. The mammalian ovary from genesis to revelation.

    Science.gov (United States)

    Edson, Mark A; Nagaraja, Ankur K; Matzuk, Martin M

    2009-10-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

  14. Ecology and evolution of mammalian biodiversity

    Science.gov (United States)

    Jones, Kate E.; Safi, Kamran

    2011-01-01

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

  15. Focusing on RISC assembly in mammalian cells.

    Science.gov (United States)

    Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  16. Focusing on RISC assembly in mammalian cells

    International Nuclear Information System (INIS)

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

    2008-01-01

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

  17. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  18. Classification of EMG signals using PSO optimized SVM for diagnosis of neuromuscular disorders.

    Science.gov (United States)

    Subasi, Abdulhamit

    2013-06-01

    Support vector machine (SVM) is an extensively used machine learning method with many biomedical signal classification applications. In this study, a novel PSO-SVM model has been proposed that hybridized the particle swarm optimization (PSO) and SVM to improve the EMG signal classification accuracy. This optimization mechanism involves kernel parameter setting in the SVM training procedure, which significantly influences the classification accuracy. The experiments were conducted on the basis of EMG signal to classify into normal, neurogenic or myopathic. In the proposed method the EMG signals were decomposed into the frequency sub-bands using discrete wavelet transform (DWT) and a set of statistical features were extracted from these sub-bands to represent the distribution of wavelet coefficients. The obtained results obviously validate the superiority of the SVM method compared to conventional machine learning methods, and suggest that further significant enhancements in terms of classification accuracy can be achieved by the proposed PSO-SVM classification system. The PSO-SVM yielded an overall accuracy of 97.41% on 1200 EMG signals selected from 27 subject records against 96.75%, 95.17% and 94.08% for the SVM, the k-NN and the RBF classifiers, respectively. PSO-SVM is developed as an efficient tool so that various SVMs can be used conveniently as the core of PSO-SVM for diagnosis of neuromuscular disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Neuromuscular interfacing: establishing an EMG-driven model for the human elbow joint.

    Science.gov (United States)

    Pau, James W L; Xie, Shane S Q; Pullan, Andrew J

    2012-09-01

    Assistive devices aim to mitigate the effects of physical disability by aiding users to move their limbs or by rehabilitating through therapy. These devices are commonly embodied by robotic or exoskeletal systems that are still in development and use the electromyographic (EMG) signal to determine user intent. Not much focus has been placed on developing a neuromuscular interface (NI) that solely relies on the EMG signal, and does not require modifications to the end user's state to enhance the signal (such as adding weights). This paper presents the development of a flexible, physiological model for the elbow joint that is leading toward the implementation of an NI, which predicts joint motion from EMG signals for both able-bodied and less-abled users. The approach uses musculotendon models to determine muscle contraction forces, a proposed musculoskeletal model to determine total joint torque, and a kinematic model to determine joint rotational kinematics. After a sensitivity analysis and tuning using genetic algorithms, subject trials yielded an average root-mean-square error of 6.53° and 22.4° for a single cycle and random cycles of movement of the elbow joint, respectively. This helps us to validate the elbow model and paves the way toward the development of an NI.

  20. In vivo imaging of the developing neuromuscular junction in neonatal mice.

    Science.gov (United States)

    Turney, Stephen G; Walsh, Mark K; Lichtman, Jeff W

    2012-11-01

    Although fluorescently labeled structures can be analyzed more easily at high resolution in fixed-tissue preparations than in living animals, some biological questions can only be answered by time-lapse imaging. Changes in nervous system wiring during development cannot be determined reliably by taking tissue from different animals at staggered time points. Rather, the same cells and connections must be viewed repeatedly. To study developmental synapse elimination, we image muscles in transgenic mice that express fluorescent proteins in motor neurons and follow the same neuromuscular junctions (NMJs) over multiple days. This protocol describes the use of confocal microscopy for in vivo imaging of developing NMJs in transgenic neonatal mice expressing cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP). The sternomastoid, a flat, accessible neck muscle with large junctions, is imaged. A principal advantage of confocal microscopy is the ability to acquire multiple fluorescence channels simultaneously. If the channels are acquired sequentially, there is inevitably misalignment because of movement. Moreover, the total imaging time scales linearly with the number of channels. With simultaneous acquisition, only a single scan may be required. With perfect alignment between channels, irrespective of movement that might occur during a scan, color differences can be used to study interactions between axons over time. A limitation of this technique is that axons must be brightly labeled and at the muscle surface. NMJs that are more than one muscle fiber deep may be difficult to scan because of index of refraction changes that cause image blurring.