Lobe specific Ca2+-calmodulin nano-domain in neuronal spines: a single molecule level analysis.

Calmodulin (CaM) is a ubiquitous Ca(2+) buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca(2+)-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca(2+)-CaM-dependent enzymes: Ca(2+)/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca(2+) and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca(2+) ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca(2+) and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca(2+) signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca(2+)-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca(2+) channels, and to the microscopic injection rate of Ca(2+) ions. We also demonstrate that Ca(2+) saturation takes place via two different pathways depending on the Ca(2+) injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca(2+) sensors that can differentially transduce Ca(2+) influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca(2+)-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity.

Corporate decision-making: A case study of decision support systems and financial performance in health care organizations

The purpose of this study was twofold: (1) To describe the relation of the intensity of DSS implementation to financial performance as an empirical exploration of improved performance at the organizational level. (2) To describe the relation of the intensity of DSS implementation to the type of organizational decision culture. A multiple case study design was utilized to compare three groups of paired cases. A pattern matching strategy was applied in this study. Four predictions were specified and compared to the empirical data. A progressively upward trend in the scores was predicted for the following theoretical relationships. (1) The greater the number of DSSs, the higher the sophistication index. (2) The greater the number of DSSs, the higher the financial ratios. (3) The greater the number of DSSs, the higher the culture score. (4) The higher the culture score, the higher the financial ratios. The data did not support any of the predicted trends except the relation between the number of DSSs and the financial ratios. The Income/Revenue ratio indicates the efficiency of a company's operations. One would expect that this ratio would be most affected by the operational and financial decision support systems. The majority of the systems measured in the study supported decisions tangential to the patient service areas. The evidence suggested that the type and number of decision support systems affects the bottom line. ^