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Biomedical subjects

David A Green

Publications and source records attributed to David A Green.

6 recordsLinked to original sources

Neuromuscular and biomechanical coupling in human cycling: modulation of cutaneous reflex responses to sural nerve stimulation.

This study tested the hypothesis that the modulation of cutaneous reflexes during human cycling would be dependent on muscle biomechanical function and phase of leg movement. The coupling between neuromuscular (electromyographic, EMG), kinetic and kinematic responses to brief innocuous (75% of the pain threshold PnT) and noxious (125% PnT) sural nerve stimulation were studied. Stimuli were delivered pseudorandomly at eight equidistant (45 degrees) positions of the crank cycle. Peak ipsilateral middle latency EMG reflex responses were calculated between 70 and 130 ms post stimulus in Biceps Femoris (BF), Rectus Femoris (RF), Tibialis Anterior (TA) and Soleus (SOL). Peak torque, knee and ankle joint angle changes were calculated between 140 and 220 ms post stimulus to quantify net kinetic and kinematic reflex modulation. Reflex responses were predominately suppressive during early activation of all muscles and facilitatory during BF and TA muscle inactivation. EMG reflex responses in monoarticular lower leg muscles TA and SOL were well correlated with ankle angle in dorsi/plantaflexion, whereas the correlation between reflex modulation in biarticular upper leg muscles (BF and RF) and knee angle changes in flexion/extension was weaker. Stimulation provoked significant ankle eversion over the whole crank cycle for both stimulus intensities, which was correlated with TA and BF EMG reflex responses. Torque modulation followed EMG and kinematic changes in a movement phase-dependent manner. Reflex magnitude was stimulation intensity-dependent. Supplementary nociceptive activation may contribute for this increase. We conclude that sural nerve stimulation during human cycling evokes distinct reflex responses in muscles operating around the knee (BF and RF) and the ankle (TA and SOL). These reflexes are modulated in a phase-dependent manner depending on muscle biomechanical function to generate energy for limb and crank propulsion during a specific region in the cycle. This modulation contributed to a specific adaptation of joint motion and force production in order to maintain task performance.

Adult↗

Krh1p and Krh2p act downstream of the Gpa2p G(alpha) subunit to negatively regulate haploid invasive growth.

The yeast G(alpha) subunit Gpa2p and its coupled receptor Gpr1p function in a signaling pathway that is required for the transition to pseudohyphal and invasive growth. A two-hybrid screen using a constitutively active allele of GPA2 identified the KRH1 gene as encoding a potential binding partner of Gpa2p. Strains containing deletions of KRH1 and its homolog KRH2 were hyper-invasive and displayed a high level of expression of FLO11, a gene involved in pseudohyphal and invasive growth. Therefore, KRH1 and KRH2 encode negative regulators of the invasive growth pathway. Cells containing krh1Delta krh2Delta mutations also displayed increased sensitivity to heat shock and decreased sporulation efficiency, indicating that Krh1p and Krh2p regulate multiple processes controlled by the cAMP/PKA pathway. The krh1Delta krh2Delta mutations suppressed the effect of a gpa2Delta mutation on FLO11 expression and eliminated the effect of a constitutively active GPA2 allele on induction of FLO11 and heat shock sensitivity, suggesting that Krh1p and Krh2p act downstream of Gpa2p. The Sch9p kinase was not required for the signal generated by deletion of KRH1 and KRH2; however, the cAMP-dependent kinase Tpk2p was required for generation of this signal. These results support a model in which activation of Gpa2p relieves the inhibition exerted by Krh1p and Krh2p on components of the cAMP/PKA signaling pathway.

Adaptor Proteins, Signal Transducing↗