Chronic oscillatory strain induces MLCK associated rapid recovery from acute stretch in airway smooth muscle cells

A deep inspiration (DI) temporarily relaxes agonist-constricted airways in normal subjects, but in asthma airways are refractory and may rapidly renarrow, possibly due to changes in the structure and function of airway smooth muscle (ASM). Chronic largely uniaxial cyclic strain of ASM cells in culture causes several structural and functional changes in ASM similar to that in asthma, including increases in contractility, MLCK content, shortening velocity, and shortening capacity. However, changes in recovery from acute stretch similar to a DI have not been measured. We have therefore measured the response and recovery to large stretches of cells modified by chronic stretching and investigated the role of MLCK. Chronic, 10% uniaxial cyclic stretch, with or without a strain gradient, was administered for up to 11 days to cultured cells grown on Silastic membranes. Single cells were then removed from the membrane and subjected to 1 Hz oscillatory stretches up to 10% of the in situ cell length. These oscillations reduced stiffness by 66% in all groups (P < 0.05). Chronically strained cells recovered stiffness three times more rapidly than unstrained cells, while the strain gradient had no effect. The stiffness recovery in unstrained cells was completely inhibited by the MLCK inhibitor ML-7, but recovery in strained cells exhibiting increased MLCK was slightly inhibited. These data suggest that chronic strain leads to enhanced recovery from acute stretch, which may be attributable to the strain-induced increases in MLCK. This may also explain in part the more rapid renarrowing of activated airways following DI in asthma.     

Internet-based CBT for depression with and without telephone tracking in a national helpline: randomised controlled trial

Background

Telephone helplines are frequently and repeatedly used by individuals with chronic mental health problems and web interventions may be an effective tool for reducing depression in this population.

Aim

To evaluate the effectiveness of a 6 week, web-based cognitive behaviour therapy (CBT) intervention with and without proactive weekly telephone tracking in the reduction of depression in callers to a helpline service.

Method

155 callers to a national helpline service with moderate to high psychological distress were recruited and randomised to receive either Internet CBT plus weekly telephone follow-up; Internet CBT only; weekly telephone follow-up only; or treatment as usual.

Results

Depression was lower in participants in the web intervention conditions both with and without telephone tracking compared to the treatment as usual condition both at post intervention and at 6 month follow-up. Telephone tracking provided by a lay telephone counsellor did not confer any additional advantage in terms of symptom reduction or adherence.

Conclusions

A web-based CBT program is effective both with and without telephone tracking for reducing depression in callers to a national helpline.

Trial Registration

Controlled-Trials.com ISRCTN93903959     

C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes

BACKGROUND: Mammalian integrin-linked kinase (ILK) was identified in a yeast two-hybrid screen for proteins binding the integrin beta(1) subunit cytoplasmic domain. ILK has been implicated in integrin-mediated signaling and is also an adaptor within integrin-associated cytoskeletal complexes. RESULTS: We identified the C. elegans pat-4 gene in previous genetic screens for mutants unable to assemble integrin-mediated muscle cell attachments. Here, we report that pat-4 encodes the sole C. elegans homolog of ILK. In pat-4 null mutants, embryonic muscle cells form integrin foci, but the subsequent recruitment of vinculin and UNC-89 as well as actin and myosin filaments to these in vivo focal adhesion analogs is blocked. Conversely, PAT-4/ILK requires the ECM component UNC-52/perlecan, the transmembrane protein integrin, and the novel cytoplasmic attachment protein UNC-112 to be properly recruited to nascent attachments. Transgenically expressed "kinase-dead" ILK fully rescues pat-4 loss-of-function mutants. We also identify UNC-112 as a new binding partner for ILK. CONCLUSIONS: Our data strengthens the emerging view that ILK functions primarily as an adaptor protein within integrin adhesion complexes and identifies UNC-112 as a new ILK binding partner.     

The effects of mosquito transmission and population bottlenecking on virulence, multiplication rate and rosetting in rodent malaria

Malaria parasites vary in virulence, but the effects of mosquito transmission on virulence phenotypes have not been systematically analysed. Using six lines of malaria parasite that varied widely in virulence, three of which had been serially blood-stage passaged many times, we found that mosquito transmission led to a general reduction in malaria virulence. Despite that, the between-line variation in virulence remained. Forcing serially passaged lines through extreme population bottlenecks (<5 parasites) reduced virulence in only one of two lines. That reduction was to a level intermediate between that of the virulent parental and avirulent ancestral line. Mosquito transmission did not reverse the increased parasite replication rates that had accrued during serial passage, but it did increase rosetting frequencies. Re-setting of asexual stage genes during the sexual stages of the life cycle, coupled with stochastic sampling of parasites with variable virulence during population bottlenecks, could account for the virulence reductions and increased rosetting induced by mosquito transmission.     

New developments in developmental biology

A report on the 15th International Society of Developmental Biologists Congress, Sydney, Australia, 3-7 September 2005.     

Outcome following implantation of a peripheral nerve stimulator in patients with chronic nerve pain

This study evaluated the usefulness of the implanted peripheral nerve stimulator in patients with pain following injury to a peripheral nerve. The patient sample (n = 17) consisted of 7 men and 10 women with a mean age of 48 years (SD = 18 years). The mean follow-up time since implantation of the stimulator was 21 months (SD = 15 months). Workers' compensation and/or litigation were involved in 11 cases. Peripheral nerve stimulators were placed in the upper extremity in 12 patients and in the lower extremity in 5 patients. Pain relief following implantation was rated as excellent by five patients, good by six patients, fair by four patients, and poor by two patients. A statistically significant decrease in reported pain level was found postoperatively (p < 0.0003). There was no statistically significant difference in postoperative pain level between men and women (p = 0.30), between cases involving workers' compensation or litigation and those not involving these issues (p = 1.0), or between patients who received an upper-extremity implant and those who received a lower-extremity implant (p = 0.56). Of the 12 patients who were unable to work before the operation, 6 returned to work after the operation. In conclusion, peripheral nerve stimulators can be useful in decreasing pain in carefully selected patients with severe neurogenic pain.