Medullary expiratory activity: influence of intercostal tendon organs and muscle spindle endings

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary expiratory activity in decerebrate cats. Impeded intercostal muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate intercostal TOs without MSEs. Impeded contractions of the intercostal muscles augmented expiratory laryngeal motoneuron activity, and either had no effect on or reduced the activity of bulbospinal expiratory neurons. Vibration was used to stimulate intercostal MSEs. Intercostal MSEs had no effect on medullary expiratory neuron activity. It is concluded that both external and internal intercostal TOs have an excitatory effect on expiratory laryngeal motoneuron activity and an inhibitory effect on a subpopulation of expiratory neurons driving intercostal and/or abdominal muscles, and intercostal MSEs have no direct influence on medullary expiratory activity.     

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome

Background  

Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network.     

Fictive cough in the cat.

Experiments were performed to determine whether cough could be elicited in paralyzed cats ventilated on a respiratory cycle-triggered pump. Midcollicular decerebrate cats were paralyzed and artificially ventilated on a phrenic-triggered pump. Phrenic and cranial iliohypogastric nerve efferent activities were recorded. Cough was elicited by electrical stimulation of the superior laryngeal nerve (SLN) or probing the intrathoracic trachea. Fictive coughs induced by electrical stimulation of the SLN or mechanical stimulation of the intrathoracic trachea consisted of large-amplitude bursts in phrenic discharge immediately followed by large bursts in cranial iliohypogastric discharge. During fictive cough, phrenic postinspiratory discharge was reduced relative to control cycles. Codeine (0.03-1 mg/kg iv) decreased both SLN- and probe-induced fictive cough. I conclude that fictive cough can be produced in paralyzed cats ventilated on a phrenic-triggered pump. Furthermore, fictive cough can be produced in the absence of afferent feedback associated with active expiration.     

Volume-timing relationships during cough and resistive loading in the cat.

The relationship between pulmonary volume-related feedback and inspiratory (CTI) and expiratory (CTE) phase durations during cough was determined. Cough was produced in anesthetized cats by mechanical stimulation of the intrathoracic tracheal lumen. During eupnea, the animals were exposed to single-breath inspiratory and expiratory resistive loads. Cough was associated with large increases in inspiratory volume (VI) and expiratory volume (VE) but no change in phase durations compared with eupnea. There was no relationship between VI and CTI during coughing. A linear relationship with a negative slope existed between VI and eupneic inspiratory time during control and inspiratory resistive loading trials. There was no relationship between VE and CTE during all coughs. However, when the first cough in a series or a single cough was analyzed, the VE/CTE relationship had a positive slope. A linear relationship with a negative slope existed between VE and eupneic expiratory time during control and expiratory resistive loading trials. These results support separate ventilatory pattern regulation during cough that does not include modulation of phase durations by pulmonary volume-related feedback.     

Medullary inspiratory activity: influence of intercostal tendon organs and muscle spindle endings

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary inspiratory activity in decerebrate and allobarbital-anesthetized cats. Impeded muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate external and internal intercostal TOs without MSEs. Impeded contractions of either the external or internal intercostal muscles reduced phrenic and medullary inspiratory neuronal activities. Vibration was used to selectively stimulate external or internal intercostal MSEs (90 and 40 micron amplitude, respectively). Selective stimulation of either external or internal intercostal MSEs did not change phrenic or medullary inspiratory neuronal activities. It is concluded that both external and internal intercostal TOs have a generalized inhibitory effect on medullary inspiratory activity and intercostal MSEs have no effect on medullary inspiratory activity.     

Inspiratory and expiratory patterns of the pectoralis major muscle during pulmonary defensive reflexes

Experiments wereconducted to determine the discharge pattern of the pectoralis majormuscle during pulmonary defensive reflexes in anesthetized cats(n = 15). Coughs andexpiration reflexes were elicited by mechanical stimulation of theintrathoracic trachea or larynx. Augmented breaths occurredspontaneously or were evoked by the same mechanical stimuli.Electromyograms (EMGs) were recorded from the diaphragm, rectusabdominis, and pectoralis major muscles. During augmented breaths, thepectoralis major had inspiratory EMG activity similar to that of thediaphragm, but during expiration reflexes the pectoralis major also hadpurely expiratory EMG activity similar to the rectus abdominis. Duringtracheobronchial cough, the pectoralis major had an inspiratory patternsimilar to that of the diaphragm in 10 animals, an expiratory patternsimilar to that of the rectus abdominis in 3 animals, and a biphasicpattern in 2 animals. The pectoralis major was active during both the inspiratory and expiratory phases during laryngeal cough. We conclude that, in contrast to the diaphragm or rectus abdominis muscles, thepectoralis major is active during both inspiratory and expiratory pulmonary defensive reflexes.

     

Comparative interactomics analysis of protein family interaction networks using PSIMAP (protein structural interactome map)

MOTIVATION: Many genomes have been completely sequenced. However, detecting and analyzing their protein-protein interactions by experimental methods such as co-immunoprecipitation, tandem affinity purification and Y2H is not as fast as genome sequencing. Therefore, a computational prediction method based on the known protein structural interactions will be useful to analyze large-scale protein-protein interaction rules within and among complete genomes. RESULTS: We confirmed that all the predicted protein family interactomes (the full set of protein family interactions within a proteome) of 146 species are scale-free networks, and they share a small core network comprising 36 protein families related to indispensable cellular functions. We found two fundamental differences among prokaryotic and eukaryotic interactomes: (1) eukarya had significantly more hub families than archaea and bacteria and (2) certain special hub families determined the topology of the eukaryotic interactomes. Our comparative analysis suggests that a very small number of expansive protein families led to the evolution of interactomes and seemed to have played a key role in species diversification. SUPPLEMENTARY INFORMATION: http://interactomics.org.     

A protein domain interaction interface database: InterPare

Background  

Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently.     

Large-scale co-evolution analysis of protein structural interlogues using the global protein structural interactome map (PSIMAP)

MOTIVATION: Interacting pairs of proteins should co-evolve to maintain functional and structural complementarity. Consequently, such a pair of protein families shows similarity between their phylogenetic trees. Although the tendency of co-evolution has been known for various ligand-receptor pairs, it has not been studied systematically in the widest possible scope. We investigated the degree of co-evolution for more than 900 family pairs in a global protein structural interactome map (PSIMAP--a map of all the structural domain-domain interactions in the PDB). RESULTS: There was significant correlation in 45% of the total SCOPs Family level pairs, rising to 78% in 454 reliable family interactions. Expectedly, the intra-molecular interactions between protein families showed stronger co-evolution than inter-molecular interactions. However, both types of interaction have a fundamentally similar pattern of co-evolution except for cases where different interfaces are involved. These results validate the use of co-evolution analysis with predictive methods such as PSIMAP to improve the accuracy of prediction based on "homologous interaction". The tendency of co-evolution enabled a nearly 5-fold enrichment in the identification of true interactions among the potential interlogues in PSIMAP. The estimated sensitivity was 79.2%, and the specificity was 78.6%. AVAILABILITY: The results of co-evolution analysis are available online at http://www.biointeraction.org