Dataset Information

Frequency and relative prevalence of calcium blips and puffs in a model of small IP?R clusters.

ABSTRACT: In this work, we model the local calcium release from clusters with a few inositol 1,4,5-trisphosphate receptor (IP3R) channels, focusing on the stochastic process in which an open channel either triggers other channels to open (as a puff) or fails to cause any channel to open (as a blip). We show that there are linear relations for the interevent interval (including blips and puffs) and the first event latency against the inverse cluster size. However, nonlinearity is found for the interpuff interval and the first puff latency against the inverse cluster size. Furthermore, the simulations indicate that the blip fraction among all release events and the blip frequency are increasing with larger basal [Ca(2+)], with blips in turn giving a growing contribution to basal [Ca(2+)]. This result suggests that blips are not just lapses to trigger puffs, but they may also possess a biological function to contribute to the initiation of calcium waves by a preceding increase of basal [Ca(2+)] in cells that have small IP3R clusters.

SUBMITTER: Qi H

PROVIDER: S-EPMC4052235 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Frequency and relative prevalence of calcium blips and puffs in a model of small IP₃R clusters.

Qi Hong H Huang Yandong Y Rüdiger Sten S Shuai Jianwei J

Biophysical journal 20140601 11

In this work, we model the local calcium release from clusters with a few inositol 1,4,5-trisphosphate receptor (IP3R) channels, focusing on the stochastic process in which an open channel either triggers other channels to open (as a puff) or fails to cause any channel to open (as a blip). We show that there are linear relations for the interevent interval (including blips and puffs) and the first event latency against the inverse cluster size. However, nonlinearity is found for the interpuff in ...[more]

PMID: 24896114

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Project description:Colorectal cancer (CRC) has high incidence and is associated with high case fatality. In France, the 5-year survival, pooled across all cancer stages at diagnosis, ranges from 57% in men to 60% in women. About one third of patients diagnosed with CRC will develop a metachronous recurrence during the following years. It is of paramount importance to accurately identify factors associated with the increased risk of progression and death, in order to develop effective follow-up and treatment strategies. However, to accurately assess the role of patients’ specific characteristics in the progression of cancer several methodological challenges need to be overcome. One difficulty, common to prognostic studies of cancer, concerns the need to separate the effects of prognostic factors on different clinical endpoints, such as disease recurrence vs recurrence-free death. Another difficulty, encountered in prognostic studies, is that the cause of death is not available or not accurately coded. Yet, some patients are likely to die of causes not related to the disease of primary interest, especially in cancers with longer survival and in those that affect older subjects. Until recently, the existing statistical methodology was not able to simultaneously, deal with both difficulties, i.e. to account for (i) possibly different effects of prognostic factors on death vs recurrence, and (ii) unknown causes of death. However, this challenge has been addressed by the recent development of the Markov relative survival model (MRS) , which extends the Markov multi-state model to incorporate relative survival modelling. Simulations demonstrate that MRS is able to accurately estimate different effects of prognostic factors on the risk of each of several events, including separate effects on disease-specific vs other causes of death. To date, the MRS had not been applied in clinical or epidemiological studies. The aim of this study was to assess the potential advantages of the new multi-state relative survival model (MRS), proposed by Huszti et al. (2012), in a prognostic cancer study. To this end, we compared the MRS results with those obtained with two more conventional analyses, based on Cox’s proportional hazards model, and the multi-state Markov model proposed by Alioum and Commenges (2001). The three models were applied to explore the impact of prognostic factors on cancer-specific mortality and recurrence, in a large population-based French registry of colorectal cancer, with up to 25 years of follow-up.

Dataset Information

Frequency and relative prevalence of calcium blips and puffs in a model of small IP?R clusters.

Publications

Frequency and relative prevalence of calcium blips and puffs in a model of small IP₃R clusters.

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