Precise Regulation of Gene Expression Dynamics Favors Complex Promoter Architectures

Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure

ICAR: endoscopic skull‐base surgery

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Kinetics of long-distance ruthenium-to-copper electron transfer in [pentaammineruthenium histidine-83]azurin

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Effect of a Biopsychosocial Approach on Patient Satisfaction and Patterns of Care

BACKGROUND: There is a growing tendency to include in medical curricula teaching programs that promote a biopsychosocial (BPS) approach to patient care. However, we know of no attempts to assess their effect on patterns of care and health care expenditures. OBJECTIVE: To determine whether 1) a teaching intervention aiming to promote a BPS approach to care affects the duration of the doctor-patient encounter, health expenditures, and patient satisfaction with care, and 2) the teaching method employed affects these outcomes. METHODS: We compared two teaching methods. The first one (didactic) consisted of reading assignments, lectures, and group discussions. The second (interactive) consisted of reading assignments, small group discussions, Balint groups, and role-playing exercises. We videotaped patient encounters 1 month before and 6 months after the teaching interventions, and recorded the duration of the videotaped encounters and whether the doctor had prescribed medications, ordered tests, and referred the patient to consultants. Patient satisfaction was measured by a structured questionnaire. RESULTS: Both teaching interventions were followed by a reduction in medications prescribed and by improved patient satisfaction. Compared to the didactic group, the interactive group prescribed even fewer medications, ordered fewer laboratory examinations, and elicited higher scores of patient satisfaction. The average duration of the encounters after the didactic and interactive teaching interventions was longer than that before by 36 and 42 seconds, respectively. CONCLUSIONS: A BPS teaching intervention may reduce health care expenditures and enhance patients' satisfaction, without changing markedly the duration of the encounter. An interactive method of instruction was more effective in achieving these objectives than a didactic one

Biochemical characterisation of the esterase activities of wine lactic acid bacteria

The original publication can be found at www.springerlink.comEsters are an important group of volatile compounds that can contribute to wine flavour. Wine lactic acid bacteria (LAB) have been shown to produce esterases capable of hydrolysing ester substrates. This study aims to characterise the esterase activities of nine LAB strains under important wine conditions, namely, acidic conditions, low temperature (to 10°C) and in the presence of ethanol (2–18% v/v). Esterase substrate specificity was also examined using seven different ester substrates. The bacteria were generally found to have a broad pH activity range, with the majority of strains showing maximum activity close to pH 6.0. Exceptions included an Oenococcus oeni strain that retained most activity even down to a pH of 4.0. Most strains exhibited highest activity across the range 30–40°C. Increasing ethanol concentration stimulated activity in some of the strains. In particular, O. oeni showed an increase in activity up to a maximum ethanol concentration of around 16%. Generally, strains were found to have greater activity towards short-chained esters (C2–C8) compared to long-chained esters (C10–C18). Even though the optimal physicochemical conditions for enzyme activity differed from those found in wine, these findings are of potential importance to oenology because significant activities remained under wine-like conditions.Angela Matthews, Paul R. Grbin and Vladimir Jirane