Overproduction of PDR3 Suppresses Mitochondrial Import Defects Associated with a TOM70 Null Mutation by Increasing the Expression of TOM72 in Saccharomyces cerevisiae

Most mitochondrial proteins are synthesized with cleavable amino-terminal targeting signals that interact with the mitochondrial import machinery to facilitate their import from the cytosol. We previously reported that the presequence of the F1-ATPase beta subunit precursor (pre-F1beta ) acts as an intramolecular chaperone that maintains the precursor in an import-competent conformation prior to import (P. Hajek, J. Y. Koh, L. Jones, and D. M. Bedwell, Mol. Cell. Biol. 17:7169-7177, 1997). We also found that a mutant form of pre-F1beta with a minimal targeting signal (Delta 1,2 pre-F1beta) is inefficiently imported into mitochondria because it rapidly folds into an import-incompetent conformation. We have now analyzed the consequences of reducing the pre-F1beta targeting signal to a minimal unit in more detail. We found that Delta 1,2 pre-F1beta is more dependent upon the Tom70p receptor for import than WT pre-F1beta is, resulting in a growth defect on a nonfermentable carbon source at 15°C. Experiments using an in vitro mitochondrial protein import system suggest that Tom70p functions to maintain a precursor containing the Delta 1,2 pre-F1beta import signal in an import-competent conformation. We also identified PDR3, a transcriptional regulator of the pleiotropic drug resistance network, as a multicopy suppressor of the mitochondrial import defects associated with Delta 1,2 pre-F1beta in a tom70Delta strain. The overproduction of PDR3 mediated this effect by increasing the import of Delta 1,2 pre-F1beta into mitochondria. This increased the mitochondrial ATP synthase activity to the extent that growth of the mutant strain was restored under the selective conditions. Analysis of the transcription patterns of components of the mitochondrial outer membrane import machinery demonstrated that PDR3 overproduction increased the expression of TOM72, a little studied TOM70 homologue. These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis

Softer perspectives on enhancing the patient experience using IS/IT

Purpose – This paper aims to argue that the implementation of the Choose and Book system has failed due to the inability of project sponsors to appreciate the complex and far-reaching softer implications of the implementation, especially in a complex organisation such as the NHS, which has multifarious stakeholders. Design/methodology/approach – The authors use practice-oriented research to try and isolate key parameters. These parameters are compared with existing conventional thinking in a number of focused areas. Findings – Like many previous NHS initiatives, the focus of this system is in its obvious link to patients. However we find that although this project has cultural, social and organisational implications, programme managers and champions of the Connecting for Health programme emphasised the technical domains to IS/IT adoption. Research limitations/implications – This paper has been written in advance of a fully implemented Choose and Book system. Practical implications – The paper requests that more attention be paid to the softer side of IS/IT delivery, implementation, introduction and adoption. Originality/value – The paper shows that patient experience within the UK healthcare sector is still well below what is desired

Induction of Continuous Stimulus-Response Relations

The present research investigates the mental processes involved in inducing continuous stimulus response relations. A simple perceptual-motor learning task was used in which subjects learned to produce a continuous variable (response duration) accurately for values chosen from another continuous dimension (stimulus length). Subjects were trained on several "practice" pairs, for which they received feedback about the correct responses. Trials involving practice pairs were intermixed with trials involving "transfer" pairs, for which no feedback was given. The correct responses and stimuli were related by simple mathematical functions: a power (Experiment 1); alogarithmic (Experiment 2); and a linear function with a positive intercept (Experiment 3).Experiment 1 demonstrated that people can learn a power function rapidly and use it to perform as well for transfer pairs as for practice pairs. Experiments 2 and 3 revealed a systematic pattern of bias during early learning, consistent with the hypothesis that people have a predisposition toward inducing a power function. However, the biases decreased in magnitude with practice.We propose an account for induction of continuous stimulus-response relations called the"adaptive-regression" model. According to it, people are initially biased to induce a power function, but the bias is gradually weakened through experience, so that other stimulus-response relations can be learned with sufficient practice. The present results support the adaptive regression model

The effect of cotton-based collection methods on eosinophil cationic protein (ECP) concentrations detected in saliva

Teck Yee Wong, David Koh, Andrew Wee, Vivian Ng, Yong Tat Koh, Zhenjie Sum, Gerald KohDepartment of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeBackground: Salivary eosinophil cationic protein (ECP) level has the potential to be an assessment tool for asthma. Its measurement is not well-established and needs standardization. We studied how passive drool (PD) and two commercial devices, Salivette® (cotton-based device) and Sorbette® (cellulose–cotton-based-device), may affect ECP levels during collection among healthy subjects.Methods: Study I (n = 10) involved direct sampling of healthy adult subjects with Salivette® and Sorbette®. Study II (n = 33) involved ‘indirect’ sampling of previously collected PD by both devices.Results: In study I, ECP levels were detected in all PD samples but only in three with Sorbette® and none with Salivette® (collection order: PD, Sorbette® and Salivette®). We changed the order of collection (Salivette®, Sorbette®, PD) and the results were similar (ECP levels detected in all PD samples, three with Sorbette® and only one with Salivette®). In study II, ECP levels in saliva collected by PD was 12.8 μg/L (median) and using Sorbette® and Salivette® were < 2.0 μg/L and 3.4 μg/L respectively (p < 0.01). ECP levels in PD correlated with Sorbette® (rs = 0.79, p < 0.01) and Salivette® (rs = 0.62, p 0.01).Conclusion: Compared to PD, saliva collected using cotton or cellulose-based collection devices resulted in lower measurable ECP levels.Keywords: salivary ECP, collection method

Multi-view Temporal Ensemble for Classification of Non-Stationary Signals

In the classification of non-stationary time series data such as sounds, it is often tedious and expensive to get a training set that is representative of the target concept. To alleviate this problem, the proposed method treats the outputs of a number of deep learning sub-models as the views of the same target concept that can be linearly combined according to their complementarity. It is proposed that the view’s complementarity be the contribution of the view to the global view, chosen in this work to be the Laplacian eigenmap of the combined data. Complementarity is computed by alternate optimization, a process that involves the cost function of the Laplacian eigenmap and the weights of the linear combination. By blending the views in this way, a more complete view of the underlying phenomenon can be made available to the final classifier. Better generalization is obtained, as the consensus between the views reduces the variance while the increase in the discriminatory information reduces the bias. Data experiment with artificial views of environment sounds formed by deep learning structures of different configurations shows that the proposed method can improve the classification performance