the cellular prion protein regulate morphological development of Streptomyces by secreting peptidases and their associated inhibitors

Moreover, Streptomyces has become an important production host for heterologous expression of recombinant proteins due to its excellent secretion capacity, which makes the downstream processing much simpler. Therefore, understanding of the mechanism of its protein export systems is extremely important for the economical application of Streptomyces. Protein transport across the bacterial membrane is mediated by different translocation systems, of which the general protein secretion system plays a prominent role in protein export and membrane insertion. The Sec translocation machinery is a protein complex comprised of SecYEG, the ATPase SecA, and the accessory factor SecDF. The roles of the Sec pathway components have been extensively studied, but the function of the SecDF complex in protein secretion is still poorly understood. The SecDF complex has been shown to be involved in the cycling of SecA and the release of the translocated protein from the translocation channel. Recently, the SecDF complex was proposed to be a membrane integrated chaperone that uses proton motive force to complete protein translocation through the SecYEG channel via the control of SecA cycling. Chronic heart failure, which affects over 5 million people in the US, is associated with increased incidence of sudden death primary from ventricular tachycardia degenerating to ventricular fibrillation. A FTY720 morning surge in sudden deaths and ventricular arrhythmias have been demonstrated in patients with CHF. The onset of other cardiovascular events such as heart attack, stroke and chest pain is also increased in the morning. The underlying mechanisms are poorly understood, in part due to a lack of characterization of heart rate dynamics, autonomic oscillation and nonlinear dynamics in time-of-day-dependent adverse cardiac events in large animal CHF models. Moreover most studies to date have been done primarily in HF patients and have been limited and influenced by concurrent medication use. Time-of-day-dependent variations in heart rate dynamics, autonomic nervous system and nonlinear dynamics are associated with the morning surge in cardiovascular events. Heart rate variability can assess the regulation of arrhythmogenic substrate in CHF of the failing heart. Traditional linear HRV is analyzed in the time and frequency domain, and markers include SDNN, CV, and rMSSD, spectral power in different frequency range, etc. HRV has been shown to have important prognostic implications. Heart rate fluctuations have been recognized as complex dynamical behaviors originating from nonlinear processes. Despite knowledge of HRV parameters in patients with CHF which are associated with a morning surge in ventricular arrhythmias, the underlying mechanisms contributing to these important observations have remained elusive. We have recently developed a novel arrhythmogenic large animal model of CHF in the canine heart that exhibits decreased LV function and spontaneous ventricular arrhythmia that are initiated and maintained by a focal nonreentrant mechanism. The purpose of the present study was to assess whether there is a morning surge in premature ventricular complexes and VT in our new irreversible arrhythmogenic canine CHF model.

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