Human motor control is a complex process involving both central and peripheral components of the nervous system. Type Ia afferent input contributes to both motor unit recruitment and firing frequency, however, whether maximal force production is dependent on this input is unclear. Therefore, chapter 2 examined maximal and explosive force production of the knee extensors following prolonged infrapatellar tendon vibration; designed to attenuate the efficacy of the homonymous Ia afferent-α-motoneuron pathway. Despite a marked decrease in H-reflex amplitude, indicating an attenuated efficacy of the Ia afferent-α-motoneuron pathway, both maximal and explosive force production were unaffected after vibration. This suggested that maximal and explosive isometric quadriceps force production was not dependent upon Ia afferent input to the homonymous motor unit pool. Voluntary movements are linked with various modulations in ongoing neural oscillations within the supraspinal sensorimotor system. Despite considerable interest in the oscillatory responses to movements per se, the influence of the motor parameters that define these movements is poorly understood. Subsequently, chapters 3 and 4 investigated how the motor parameters of voluntary contractions modulated the oscillatory amplitude. Chapter 3 recorded electroencephalography from the leg area of the primary sensorimotor cortex in order to investigate the oscillatory responses to isometric unilateral contractions of the knee-extensors at four torque levels (15, 30, 45 and 60% max.). An increase in movement-related gamma (30-50 Hz) activity was observed with increments in knee-extension torque, whereas oscillatory power within the delta (0.5-3 Hz), theta (3-7 Hz), alpha (7-13 Hz) and beta (13-30 Hz) bands were unaffected. Chapter 4 examined the link between the motor parameters of voluntary contraction and modulations in beta (15-30 Hz) oscillations; specifically, movement-related beta decrease (MRBD) and post-movement beta rebound (PMBR). Magnetoencephalography (MEG) was recorded during isometric ramp and constant-force wrist-flexor contractions at distinct rates of force development (10.4, 28.9 and 86.7% max./s) and force output (5, 15, 35 and 60%max.), respectively. MRBD was unaffected by RFD or force output, whereas systematic modulation of PMBR by both contraction force and RFD was identified for the first time. Specifically, increments in isometric contraction force increased PMBR amplitude, and increments in RFD increased PMBR amplitude but decreased PMBR duration. Physical fatigue arises not only from peripheral processes within the active skeletal muscles but also from supraspinal mechanisms within the brain. However, exactly how cortical activity is modulated during fatigue has received a paucity of attention. Chapter 5 investigated whether oscillatory activity within the primary sensorimotor cortex was modulated when contractions were performed in a state of physical fatigue. MEG was recorded during submaximal isometric contractions of the wrist-flexors performed both before and after a fatiguing series of isometric wrist-flexions or a time matched control intervention. Physical fatigue offset the attenuation in MRBD observed during the control trial, whereas PMBR was increased when submaximal contractions were performed in a fatigued state.

The chicken ductus arteriosi (DA) are two embryonic blood vessels that shunt blood away from the non-ventilated lungs and towards the body and chorioallantoic membrane. I show that prostaglandins have a diminished role in maintaining chicken DA patency and nitric oxide inhibits oxygen induced contraction of the day 19 proximal DA in a time dependent manner. The pathways governing oxygen induced contraction in the chicken DA are similar to those found in mammals and include contributions from ROS, Kv channels, L-type Ca2+ channels, and the Rho kinase pathway. Longer exposure to high oxygen generates increased oxygen induced constriction of the day 19 DA that may be mediated through the Rho kinase pathway.

O complexo troponina-tropomiosina regula a contração muscular esquelética e cardíaca. A ligação do cálcio nos sítios regulatórios localizados no domínio N-terminal da troponina C (TnC) induz uma mudança conformacional que remove a ação inibitória da troponina I (TnI) e inicia a contração muscular. Nós usamos fragmentos recombinantes da TnI e uma série de mutantes da TnC para estudar as interações estruturais e regulatórias das diferentes regiões da TnI com os domínios da TnC, TnT e actina-tropomiosina. Nossos resultados indicam que a TnI é organizada em regiões que apresentam funções estruturais e regulatórias e que se ligam de modo antiparalelo com os correspondentes domínios estruturais e regulatórios da TnC. Estudos funcionais mostram que a região inibitória (aminoácidos 103-116) em combinação com a região C-terminal da TnI (TnI103-182) pode regular a atividade ATPásica da acto-miosina de maneira dependente de Ca2+. A regulação não é observada com a região inibitória em combinação com a região N-terminal (TnI116) Estudos de ligação mostram que a região N-terminal da TnI (TnI1-98) interage com o domínio C-terminal da TnC na presença e na ausência de Ca2+ e também interage com a TnT. A região inibitória/C-terminal da TnI (TnI103-182) interage com o domínio N-terminal da TnC de maneira dependente de Ca2+. Baseados nestes resultados, propomos um modelo para a mudança conformacional induzida pelo Ca2+. Neste modelo, a região N-terminal da TnI está ligada fortemente com o domínio C-terminal da TnC na presença ou na ausência de Ca2+. As regiões inibitórias e C-terminal da TnI ligam-se à actina-tropomiosina na ausência de Ca2+ e nos domínios N-terminal e C-terminal da TnC na presença de Ca2+. / The troponin-tropomyosin complex regulates skeletal and cardiac muscle contraction. Calcium binding to the regulatory sites in the N-terminal domain of troponin C (TnC). induces a conformational change which removes the inhibitory action of troponin I (TnI) and initiates muscular contraction. We used recombinant TnI fragments and a series of TnC mutants to study the structural and regulatory interactions between different TnI regions and the domains of TnC, TnT and actin-tropomyosin. Our results indicate that TnI is organized into regions with distinct structural and regulatory functions which bind, in an antiparallel manner, with the corresponding structural and regulatory domains of TnC. Functional studies show that a fragment containing the inhibitory and C-terminal regions of TnI (TnIl03-182) can regulate the actomyosin ATPase in a Ca2+- dependent manner. Regulation was not observed with a fragment containing the N-terminal and inhibitory regions (TnIl-116). Binding studies show that the N-terminal region of TnI (TnI1-98) interacts with the C-terminal domain of TnC in the presence of Ca2+ or Mg2+. The inhibitory/C-terminal region of TnI (TnI103-182) binds to the N-terminal domain of TnC in a Ca2+-dependent manner. Based on these results, we propose a model for the Ca2+ -induced conformational change. In this model the N-terminal region of TnI is bound strongly to the C-terminal domain of TnC in the presence or absence of Ca2+. The inhibitory and C-terminal regions of TnI bind to actin-tropomyosin in the absence of Ca2+ and to tne N- and C-terminal domains of TnC in the presence of Ca2+.

No description available.

The purpose of the present study was to test the use of visually displayed EMG biofeedback as a means for training hearing impaired adolescents to reduce anterior temporalis or frontalis muscle tension . Five male and four female hearing impaired students between the ages of 13 and 15 were chosen from the California School for the Deaf, Fremont, CA to serve as participants. Each participant was randomly assigned to either an experimental or control condition. Participants in the experimental groups were given five 15 minute EMG biofeedback training sessions. An additional group of 4 adolescents with normal hearing from Marshall Junior High School, Stockton, CA served as a hearing control group. The dependent measure was a 5 minute pretest and post-test measurement of muscle tension (in microvolts). Split-plot analyses were performed to determine if there were significant differences between a ) the .hearing impaired experimental and the hearing impaired control groups, b) the hearing impaired control and the hearing control groups, and c) the hearing impaired experimental group and the hearing control group. Results of the analyses showed that at post-test both the hearing impaired experimental group and the hearing control group showed a significant decrease in muscle tension F(1,7)=5.85 p< .05. The interaction was nonsignificant. Comparison of the two control groups showed that at post-test the two groups were not significantly different in levels of muscle tension. The comparison between the hearing impaired experimental and the hearing control groups resulted in a significant interaction (Group X Time of Testing) F( 1,6)=9.47, p=.02, and the main effect for time of testing approached significance.

Background: Pelvic floor muscle (PFM) training is recommended as first line conservative management for stress urinary incontinence (SUI). The fundamental issue of how to optimally contract the PFM has not previously been investigated. An effective voluntary PFM contraction is known to positively influence the bladder neck and urethra which are urethrovesical (UV) structures associated with continence. The PFM may be globally or selectively contracted according to cue to instruction. The main research question was to investigate which cue to instruction for a PFM contraction has the potential to optimise position of UVSs following a brief period of practice in continent nulliparous pre-menopausal women (aiming to provide normative data) and parous menopausal women with previously unreported SUI. Hypotheses: Posterior or combined cues for instruction of PFM contraction are more influential in optimising UV position (UVP) during PFMC following brief practice than an anterior cue. Posterior or combined cues are equally influential in altering UVP. Aims: Preliminary aim was to investigate the reliability and suitability of 2-DRTUS and angle of urethral inclination (AUI) for imaging of selective contraction of the PFM and ease of reading images by a non diagnostic imaging researcher. Principal aim was to investigate if there is an optimal cue to instruction for a PFM contraction in two groups of women. Study 1: pre menopausal nulliparous continent women (to provide normative data) and Study 2: post menopausal parous stress incontinent women. Secondary aims were investigation of posture; ability to selectively contract the PFM contraction; and cue preference. Method: Study 1: Twenty women who were able to effectively and selectively contract were taught the following cues: anterior; posterior; anterior and posterior combined. Following 4 weeks of practice, perineal 2-D RTUS images of three PFMC for each cue were captured in supine and standing twice (for repeatability analysis) five minutes apart. Two raters measured AUI. Data analysis was undertaken using a Customized General Linear Model (GLM) ANOVA with Bonferroni correction for interactions between all variables; subject, cue, posture and test. Seventeen data sets were available for analysis. Study 2: Methodology was based on Study 1. Twenty-one women were taught the study cues, followed the practice protocol and underwent data collection in the supine position. Twenty-one sets of data were available for analysis. Results: Reliability: ICC [1,3] for intra rater reliability was 0.957 [CI 95%: 0.946 to 0.967 p=0.000], inter rater reliability [2,1] 0.820 [CI 95%: 0.768 to 0.861] and for repeatability [1,3] 0.781 [CI 95%: 0.690 to 0.849 p=0.000] (continent) and 0.954 [CI 95%:0.931 to 0.971 p=0.000] (incontinent). Principal results Study 1: anterior vs posterior cues (difference) 3.979˚ (CI 95%: [0.503 to 7.455 p=0.021]); anterior vs combined 3.777˚ (CI 95%: [-0.099 to 6.853 p= 0.059]) posterior vs combined cues -0.602˚ (CI 95%: [-2.874- 4.078 p=1.00]). Aggregated data from tests 1 and 2: anterior vs posterior 4.240° (CI 95%: [1.213 to 7.267 p=0.003]); anterior vs posterior 3.756° (95%CI: [0.729 to 6.783 p=0.009]); posterior vs combined-6.48° (95% CI: [-3.511 to 2.542 p=1.000]). Principal results Study 2: anterior vs posterior 3.936˚ (95%CI: [0.863 to 7.008p=0.008]; 4.946˚ anterior vs combined (95%CI: [1.873 to 8.018 p=0.001]); posterior vs combined 1.010° (95%CI: -[2.062 to 4.082 p=1.000]). Aggregated analysis was anterior vs posterior 3.703˚ (95%CI: [1.639 to 5.761 p=0.000]); anterior vs combined 5.089˚ (95%CI: [3.0287 to 7.1503 p=0.000]) and posterior and combined 1.389° (95%CI: [-0.672 to 3.450 p=0.309]). Secondary results: 2-D RTUS and the AUI were found to be suitable for investigating selective PFM contraction. Posture: supine vs standing (difference) 9.496˚ (p=0.000); (posture did not affect absolute AUI). Three continent (13%) and 2 incontinent (7%) subjects were unable to selectively contract the PFM. Cue preference in both studies was posterior or combined. Conclusions: AUI was significantly narrower/optimal when instruction for PFM contraction included a posterior cue, in both continent and stress incontinent women. This is proposed to be due to optimal recruitment of puborectalis. Puborectalis may be more important in urinary continence than widely recognized. This study has provided seminal information with respect to optimal cue to contraction for a PFM contraction and will change practice. Investigation of the potential impact of these findings clinically is required. It is proposed that further understanding will lead to standardisation of PFM instruction, ease of comparability between PFM research studies, and will clarify PFM instructions for the media and lay public.

Increased airway smooth muscle (ASM) mass contributes to airway hyperresponsiveness (AHR) in asthma and is orchestrated by growth factors, cytokines and chemokines. Airway contractile responses are influenced by neuromediators, such as acetylcholine, and glutamate released by parasympathetic and sympathetic airway nerves. Hyperactivity of these neural elements, termed neurogenic inflammation, is linked with hypercontractility and AHR. Glutamate is a non-essential amino acid derivative, and its physiological role is traditionally considered with respect to its being the primary excitatory neurotransmitter in brain, and regulation of neuronal development and memory. In allergic inflammation, immune cells including dendritic cells, neutrophils and eosinophils, constitutively synthesize and release glutamate, which signals through activation of glutamate receptors, most important among which are ionotrophic N-methyl D-aspartate receptors (NMDA-R). We hypothesized that glutamatergic signaling mediated through NMDA-Rs plays an important role in inducing functional Ca2+ responses in human (H) ASM cells that can underpin airway hypercontractility. We investigated the expression and function of NMDA-Rs in HASM cells, and assessed the effects of pro-inflammatory cytokines on NMDA-R expression and functional responses. Moreover, we measured airway responses to NMDA in mice, murine thin cut lung slice preparations, and floating collagen gels seeded with HASMs. Our data reveal that airway myocytes express multi-subunit NMDA-R complexes that function as receptor-operated calcium channels (ROCCs), mobilizing intracellular Ca2+ in ASM in vitro and airway contraction ex vivo. Individual airway myocytes treated with NMDA-R agonist exhibit disparate temporal patterns of intercellular Ca2+ flux that can be partitioned into four discrete function sub-groups. Further we show that tumor necrosis factor (TNF) exposure modulates NMDA-R subunit expression, and these changes are associated with a shift in the distribution of myocytes in individual Ca2+-mobilization sub-groups in vitro. Further, post-TNF exposure, NMDA-R agonists’ treatment induced Ca2+-dependent airway dilation in murine lung slice preparations, an effect that was prevented by co-treatment with inhibitors of nitric oxide synthase (NOS) or cyclooxygenase (COX). Taken together, we conclude that NMDA-R regulate HASM-mediated airway contraction and their role can be affected upon exposure to asthma-associated inflammatory mediators. Thus, NMDA-Rs are of relevance to mechanisms that determine airway narrowing and AHR associated with chronic respiratory diseases. / October 2015

Os sinais de eletromiografia de agulha podem ser modelados por um sistema linear invariante no tempo (SLIT). A pergunta é: Quantos coeficientes são necessários para tal? O presente mestrado estuda, para sinais de eletromiografia de agulha gravados sob as mesmas condições experimentais, como varia o número ótimo de coeficientes autorregressivos com o comprimento das épocas e com a força de contração muscular concomitantemente. O estudo foi realizado tendo como base sinais de 10%, 25%, 50% e 80% da máxima contração voluntária (MCV) e tendo épocas de 500ms, 250ms, 100ms, 50ms e 25ms de seis indivíduos normais. Desta forma, uma função densidade de probabilidade é sugerida para a ordem do modelo autorregressivo que melhor descreva o sinal de eletromiografia obtido a uma força de contração específica e que tenha uma duração de época definida. / Needle electromyography signals (EMG) can be modeled by a linear time invariant system (LTI). The posed question is How many coefficients are needed for an adequate modeling? This Masters dissertation studies how the optimal number of autoregressive coefficients changes concomitantly with the epoch length and the muscle contraction force for needle electromyography signals recorded under the same experimental conditions. The study was conducted on signals from six normal individuals at 10%, 25%, 50% and 80% of the maximum voluntary contraction and epoch lengths of 500ms, 250ms, 100ms, 50ms and 25ms. Thus, a probability density function is suggested for the autoregressive model order that best describes the electromyographic signal obtained at a specific \"contraction force\" and has a defined \"epoch length\".

A troponina (Tn) regula a contração do músculo estriado esquelético de vertebrados. Ela é composta de três subunidades: troponina I (TnI), troponina C (TnC) e troponina T (TnT). A TnI tem a função inibitória que é neutralizada pela ligação de Ca2+ nos sítios regulatórios do N-domínio da TnC, e a TnT posiciona o complexo no filamento fino. Para monitorar o sinal do Ca2+ sendo transmitido da TnC para a TnI as propriedades espectrais únicas do 5-hidroxitriptofano (5HW) foram utilizadas. O 5HW foi incorporado em mutantes pontuais de TnI com um único códon para triptofano. Foram identificadas duas sondas espectrais intrínsecas na TnI capazes de detectar a ligação de Ca2+ na Tn: as TnIs com 5HW nas posições 100 e 121. Complexos troponina reconstituídos com estes mutantes fluorescentes de TnI, Tn-TnIF100HW e Tn-TnIM121HW, apresentaram respectivamente 12 e 70 % de aumento na intensidade do espectro de emissão devido à ligação de Ca2+ na TnC. Nos complexos binários (TnC-TnI) as TnIs com 5HW nas posições 106 e 121 também captam a ligação do Ca2+ na TnC. A análise da fluorescência destas sondas demonstrou que: 1) as regiões da TnI que respondem ao N-domínio regulatório da TnC ocupado com Ca2+ são a região inibitória da TnI, resíduos 96 até 116, e a região vizinha que inclui a posição 121 da TnI; 2) mutações pontuais e a incorporação de 5HW na TnI podem afetar tanto a afinidade como a cooperatividade da ligação de Ca2+ na TnC, confirmando o papel da TnI em modular a afinidade da TnC por Ca2+; 3) as constantes de dissociação de Ca2+ surpreendentemente altas, Kd ~ 10-8 M, calculadas a partir dos sinais das sondas na região inibitória da TnI, sugerem a possibilidade de que os sítios do domínio N-terminal da TnC sejam os sítios de ligação de Ca2+ de maior afinidade no complexo troponina. / Vertebrate striated muscle contraction is regulated by troponin (Tn). Tn is composed of three subunits: troponin I (TnI), troponin C (TnC) and troponin T (TnT). TnI has an inhibitory role that is neutralized by calcium binding to the regulatory sites in the N-domain of TnC, and TnT positions the troponin complex on the thin filament. In order to follow the Ca2+ induced conformational change that is transmitted from TnC to TnI, the unique spectral properties of 5-hydroxytryptophan (5HW) incorporated as point-mutants of TnI were used. It was possible to identify two new TnI intrinsic spectral probes sensitive to Ca2+ binding to Tn: TnI with single 5HW at positions 100 and 121. Trimeric troponin complexes reconstituted with two fluorescent mutants of TnI, Tn-TnIF100HW and Tn-TnIM121HW, showed respectively 12 and 70 % increase in the emission spectra when Ca2+ bound to TnC. In the binary complexes (TnC-TnI) two TnIs with 5HW at positions 106 and 121 were also sensitive to Ca2+ binding to TnC. Fluorescence analysis of these probes showed: 1) the regions in TnI that respond to Ca2+ binding to the regulatory N-domain of TnC are the inhibitory region of TnI (residues 96 to 116), and a neighbor region that includes position 121; 2) point mutations and incorporation of 5HW in TnI can affect both the affinity and the cooperativity of Ca2+ binding to TnC, confirming the role of TnI as a modulator of the Ca2+ affinity of TnC; 3) the high dissociation constant for sites in the N-terminal domain of TnC (Kd ~ 10-8 M), derived from data using probes in the inhibitory region of TnI suggested the possibility that these sites are the high affinity Ca2+ binding sites in the troponin complex.

Os sinais de eletromiografia de agulha podem ser modelados por um sistema linear invariante no tempo (SLIT). A pergunta é: Quantos coeficientes são necessários para tal? O presente mestrado estuda, para sinais de eletromiografia de agulha gravados sob as mesmas condições experimentais, como varia o número ótimo de coeficientes autorregressivos com o comprimento das épocas e com a força de contração muscular concomitantemente. O estudo foi realizado tendo como base sinais de 10%, 25%, 50% e 80% da máxima contração voluntária (MCV) e tendo épocas de 500ms, 250ms, 100ms, 50ms e 25ms de seis indivíduos normais. Desta forma, uma função densidade de probabilidade é sugerida para a ordem do modelo autorregressivo que melhor descreva o sinal de eletromiografia obtido a uma força de contração específica e que tenha uma duração de época definida. / Needle electromyography signals (EMG) can be modeled by a linear time invariant system (LTI). The posed question is How many coefficients are needed for an adequate modeling? This Masters dissertation studies how the optimal number of autoregressive coefficients changes concomitantly with the epoch length and the muscle contraction force for needle electromyography signals recorded under the same experimental conditions. The study was conducted on signals from six normal individuals at 10%, 25%, 50% and 80% of the maximum voluntary contraction and epoch lengths of 500ms, 250ms, 100ms, 50ms and 25ms. Thus, a probability density function is suggested for the autoregressive model order that best describes the electromyographic signal obtained at a specific \"contraction force\" and has a defined \"epoch length\".