Impediment in upper airway stabilizing forces assessed by phrenic nerve stimulation in sleep apnea patients

BACKGROUND: The forces developed during inspiration play a key role in determining upper airway stability and the occurrence of nocturnal breathing disorders. Phrenic nerve stimulation applied during wakefulness is a unique tool to assess Upper airway dynamic properties and to measure the overall mechanical effects of the inspiratory process on UA stability. OBJECTIVES: To compare the flow/pressure responses to inspiratory and expiratory twitches between sleep apnea subjects and normal subjects. METHODS: Inspiratory and expiratory twitches using magnetic nerve stimulation completed in eleven untreated sleep apnea subjects and ten normal subjects. RESULTS: In both groups, higher flow and pressure were reached during inspiratory twitches. The two groups showed no differences in expiratory twitch parameters. During inspiration, the pressure at which flow-limitation occurred was more negative in normals than in apneic subjects, but not reaching significance (p = 0.07). The relationship between pharyngeal pressure and flow adequately fitted with a polynomial regression model providing a measurement of upper airway critical pressure during twitch. This pressure significantly decreased in normals from expiratory to inspiratory twitches (-11.1 ± 1.6 and -15.7 ± 1.0 cm H(2)O respectively, 95% CI 1.6–7.6, p < 0.01), with no significant difference between the two measurements in apneic subjects. The inspiratory/expiratory difference in critical pressure was significantly correlated with the frequency of nocturnal breathing disorders. CONCLUSION: Inspiratory-related upper airway dilating forces are impeded in sleep apnea patients

Binocular interactions underlying the classic optomotor responses of flying flies.

In response to imposed course deviations, the optomotor reactions of animals reduce motion blur and facilitate the maintenance of stable body posture. In flies, many anatomical and electrophysiological studies suggest that disparate motion cues stimulating the left and right eyes are not processed in isolation but rather are integrated in the brain to produce a cohesive panoramic percept. To investigate the strength of such inter-ocular interactions and their role in compensatory sensory-motor transformations, we utilize a virtual reality flight simulator to record wing and head optomotor reactions by tethered flying flies in response to imposed binocular rotation and monocular front-to-back and back-to-front motion. Within a narrow range of stimulus parameters that generates large contrast insensitive optomotor responses to binocular rotation, we find that responses to monocular front-to-back motion are larger than those to panoramic rotation, but are contrast sensitive. Conversely, responses to monocular back-to-front motion are slower than those to rotation and peak at the lowest tested contrast. Together our results suggest that optomotor responses to binocular rotation result from the influence of non-additive contralateral inhibitory as well as excitatory circuit interactions that serve to confer contrast insensitivity to flight behaviors influenced by rotatory optic flow

Aerospace medicine and biology. A continuing bibliography with indexes, supplement 206, May 1980

This bibliography lists 169 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1980

Locomotion Behaviour

By far the most characteristic traits of nematodes are their extremely narrow streamlined body and undulatory style of locomotion, useful in their common burrowing habit. These traits have enabled them to be successful in an amazingly wide range of free-living and parasitic environments that is without parallel in other meiofauna. This review examines what is known of the mechanism of this locomotion and its adaptations to various environments in the light of their unique body architecture and neuromuscular system

Human Skeletal myopathy myosin mutations disrupt myosin head sequestration

Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle, and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyse the effects of common MYH7 and MYH2 mutations in the light meromyosin region of myosin (LMM). Analyses of expressed and purified MYH7 and MYH2 LMM mutant proteins combined with in-silico modelling showed that myosin coiled-coil structure and packing of filaments in vitro are commonly disrupted. Using muscle biopsies from patients, and Mant-ATP chase protocols to estimate the proportion of myosin heads that were super-relaxed, together with X-ray diffraction measurements to estimate myosin head order we found that basal myosin ATP consumption was increased and the myosin super-relaxed state was decreased in vivo. In addition, myofibre mechanics experiments to investigate contractile function showed myofibre contractility was not affected. These findings indicate that the structural remodelling associated with LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help design future therapies for myosinopathies

Gait Analysis for Early Neurodegenerative Diseases Classification through the Kinematic Theory of Rapid Human Movements

Neurodegenerative diseases are particular diseases whose decline can partially or completely compromise the normal course of life of a human being. In order to increase the quality of patient's life, a timely diagnosis plays a major role. The analysis of neurodegenerative diseases, and their stage, is also carried out by means of gait analysis. Performing early stage neurodegenerative disease assessment is still an open problem. In this paper, the focus is on modeling the human gait movement pattern by using the kinematic theory of rapid human movements and its sigma-lognormal model. The hypothesis is that the kinematic theory of rapid human movements, originally developed to describe handwriting patterns, and used in conjunction with other spatio-temporal features, can discriminate neurodegenerative diseases patterns, especially in early stages, while analyzing human gait with 2D cameras. The thesis empirically demonstrates its effectiveness in describing neurodegenerative patterns, when used in conjunction with state-of-the-art pose estimation and feature extraction techniques. The solution developed achieved 99.1% of accuracy using velocity-based, angle-based and sigma-lognormal features and left walk orientation

"Role of the neuronal protein Cap23 in the maturation and maintenance of dendritic arbors in-vivo"

Dendrites in the central nervous system are the postsynaptic counterparts in the neural circuitry, and the principal sites of excitatory synaptic inputs. Little is known about the genetic elements regulating the specification, formation, development, and maintenance of these structures. They are formed early in development, and barring small changes in structure, remain essentially unchanged throughout life. More than 90% of the synapses in the brain are located on the heads and necks of dendritic protuberances called spines. Since synapses are the functional units of brain function, a detailed study of their anatomical and morphological features is important for understanding the functioning of the brain, both in health and disease. But the high density and the structural complexity of neurons, and the small size of the spines in the brain impedes a detailed examination of spine morphology and synaptic structure. We used a line of transgenic mice expressing membrane targeted GFP (m-GFP) under the Thy-1 promoter to study dendritic morphology. These lines of mice express GFP in a subset of neurons, and lights up their entire arbor, enabling visualization of the proverbial “tree from the forest”. Expression of GFP in the membrane gets rid of all artifacts associated with volume and intensity, and enables visualization of fine structure of dendrites with an unprecedented clarity and resolution. Using deconvolution confocal microscopy, we are able to detect dendritic structures hitherto visible only in electron micrographs, and are able to resolve spines that are below the theoretical limit of resolution of a light microscope. This line of mice has the potential to become an invaluable assay tool for detecting early onset defects in neuropsychiatric disorders, as it is increasingly becoming apparent that changes in synapses (i.e. spines) are the first markers of all neural diseases. We next used the increased clarity offered by the m-GFP mice to address the role of the neuronal protein Cap23 in the maintenance of dendrites. Cap23 is a major cortical-cytoskeleton associated and calmodulin protein binding protein that is widely and abundantly expressed during development, maintained in selected brain regions in adults, and re-induced during nerve regeneration. Mice deficient in Cap23 start out having normal dendritic structure and arborization, but subsequently start decreasing in their arborization from around the time corresponding to synapse elimination in the CNS. This decrease in branching is progressive in nature, and correlates with the levels of the protein expressed. Since dendrites are normal to start with, but decrease in their arborization subsequently and in a steady manner, we refer to this novel phenomenon as “Dendritic Atrophy”, and implicate Cap23 in the maintenance of dendrites. The atrophy starts in the higher-order branches and proceeds towards the lower-order ones, and the remaining branches develop ‘complex spines’. Deficiency of Cap23 leads to the misregulation of a number of important genes in the proteome of the brain, but not in the transcriptome, suggesting the role of Cap23 in regulating dendritic structure by modulating the levels of several important dendritic proteins. Interestingly, in the background of a deficiency of Cap23, the transcriptome of the brain shows the predominant upregulation of a number of non-coding RNAs of unknown function that show important similarities with microRNAs. At least one miRNA (miR-128) is starkly downregulated in Cap23 mutants. This leads to the interesting possibility that Cap23 might be involved in the maintenance of dendrites through miRNA mediated regulation of protein levels. Since defects in dendritic structure and arborization is a hallmark of all neuronal diseases, it becomes interesting to speculate whether aberrations in RNA mediated control is a general mechanism underlying neuropsychiatric diseases in general