Quantifying redox transcription factor dynamics as a tool to investigate redox signalling

\ua9 2024 The Authors. A critical feature of the cellular antioxidant response is the induction of gene expression by redox-sensitive transcription factors. In many cells, activating these transcription factors is a dynamic process involving multiple redox steps, but it is unclear how these dynamics should be measured. Here, we show how the dynamic profile of the Schizosaccharomyces pombe Pap1 transcription factor is quantifiable by three parameters: signal amplitude, signal time and signal duration. In response to increasing hydrogen peroxide concentrations, the Pap1 amplitude decreased while the signal time and duration showed saturable increases. In co-response plots, these parameters showed a complex, non-linear relationship to the mRNA levels of four Pap1-regulated genes. We also demonstrate that hydrogen peroxide and tert-butyl hydroperoxide trigger quantifiably distinct Pap1 activation profiles and transcriptional responses. Based on these findings, we propose that different oxidants and oxidant concentrations modulate the Pap1 dynamic profile, leading to specific transcriptional responses. We further show how the effect of combination and pre-exposure stresses on Pap1 activation dynamics can be quantified using this approach. This method is therefore a valuable addition to the redox signalling toolbox that may illuminate the role of dynamics in determining appropriate responses to oxidative stress

A Quantitative Analysis of Flight Feather Replacement in the Moustached Tree Swift Hemiprocne mystacea, a Tropical Aerial Forager

The functional life span of feathers is always much less than the potential life span of birds, so feathers must be renewed regularly. But feather renewal entails important energetic, time and performance costs that must be integrated into the annual cycle. Across species the time required to replace flight feather increases disproportionately with body size, resulting in complex, multiple waves of feather replacement in the primaries of many large birds. We describe the rules of flight feather replacement for Hemiprocne mystacea, a small, 60g tree swift from the New Guinea region. This species breeds and molts in all months of the year, and flight feather molt occurs during breeding in some individuals. H. mystacea is one to be the smallest species for which stepwise replacement of the primaries and secondaries has been documented; yet, primary replacement is extremely slow in this aerial forager, requiring more than 300 days if molt is not interrupted. We used growth bands to show that primaries grow at an average rate of 2.86 mm/d. The 10 primaries are a single molt series, while the 11 secondaries and five rectrices are each broken into two molt series. In large birds stepwise replacement of the primaries serves to increase the rate of primary replacement while minimizing gaps in the wing. But stepwise replacement of the wing quills in H. mystacea proceeds so slowly that it may be a consequence of the ontogeny of stepwise molting, rather than an adaptation, because the average number of growing primaries is probably lower than 1.14 feathers per wing

Baptist home missions in North America

In a volume lettered: China and the Chinese: a collection of pamphlets relating thereto. Volume 63

Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF), rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison

Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli

Despite extensive study of individual enzymes and their organization into pathways, the means by which enzyme networks control metabolite concentrations and fluxes in cells remains incompletely understood. Here, we examine the integrated regulation of central nitrogen metabolism in Escherichia coli through metabolomics and ordinary-differential-equation-based modeling. Metabolome changes triggered by modulating extracellular ammonium centered around two key intermediates in nitrogen assimilation, α-ketoglutarate and glutamine. Many other compounds retained concentration homeostasis, indicating isolation of concentration changes within a subset of the metabolome closely linked to the nutrient perturbation. In contrast to the view that saturated enzymes are insensitive to substrate concentration, competition for the active sites of saturated enzymes was found to be a key determinant of enzyme fluxes. Combined with covalent modification reactions controlling glutamine synthetase activity, such active-site competition was sufficient to explain and predict the complex dynamic response patterns of central nitrogen metabolites

Decoration supplementation and male–male competition in the great bowerbird (Ptilonorhynchus nuchalis): a test of the social control hypothesis

Many animals use signals to communicate their social status to conspecifics, and the social control hypothesis suggests that social interactions maintain the evolutionary stability of status signals: low-quality individuals signal at a low level to prevent high-quality individuals from “punishing” them. I examined whether the numbers of decorations at bowers are socially controlled in the great bowerbird (Ptilonorhynchus nuchalis). In two populations, I supplemented males with decorations to determine whether they (a) rejected supplemental decorations and (b) experienced increased bower destruction from rivals. In contrast to the social control hypothesis, males in both populations accepted most supplemental decorations. Though the mean destruction rate did not increase during supplementation in either population, one of the study populations (Townsville) exhibited a negative correlation between the numbers of decorations naturally displayed at bowers and the change in destruction rate during the experiment. Townsville males that naturally had few decorations at their bowers also had more decorations stolen by other males during supplementation than males that naturally had many decorations. These results suggest that the numbers of decorations at bowers are an honest signal of the male's ability to defend his display site from rivals in at least one population of the great bowerbird (Townsville), but they do not support the social control hypothesis because males at both sites failed to limit signal expression. I discuss how the external nature of bower decorations and their availability in the environment may influence the costs and benefits of decoration theft and social control

Individual Facial Coloration in Male Eulemur fulvus rufus: A Condition-dependent Ornament?

Researchers studying individual variation in conspicuous skin coloration in primates have suggested that color indicates male quality. Although primate fur color can also be flamboyant, the potential condition dependence and thus signaling function of fur remains poorly studied. We studied sources of variation in sexually dichromatic facial hair coloration in red-fronted lemurs (Eulemur fulvus rufus). We collected data on 13 adult males in Kirindy Forest, Madagascar, during two study periods in 2006 and 2007, to determine whether variation in facial hair coloration correlates with male age, rank, androgen status, and reproductive success. We quantified facial hair coloration via standardized digital photographs of each male, assessed androgen status using fecal hormone measurements, and obtained data on reproductive success through genetic paternity analyses. Male facial hair coloration showed high individual variation, and baseline coloration was related to individual androgen status but not to any other parameter tested. Color did not reflect rapid androgen changes during the mating season. However, pronounced long-term changes in androgen levels between years were accompanied by changes in facial hair coloration. Our data suggest that facial hair coloration in red-fronted lemur males is under proximate control of androgens and may provide some information about male quality, but it does not correlate with dominance rank or male reproductive success

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency

<p>Abstract</p> <p>Background</p> <p>The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.</p> <p>Results</p> <p>We show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed <it>in vivo </it>in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.</p> <p>Conclusion</p> <p><it>in silico </it>experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.</p