Modeling spinal locomotor circuits for movements in developing zebrafish

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the ‘‘time of diagnosis’’ phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation

Adjusting VMI settings for overlapping successive models, with stock-dependent demand and cannibalization: A case study in consumer electronics retailing in Germany

This thesis develops a method to optimize the inventory-related performance of a VMI (Vendor Managed Inventory) in retailing environments, for two successive products with overlapping lifecycles, under stock-dependent demand. The study refers to existing research in different fields, such as inventory policies and VMIs, retailing of substitutable products, stock-dependent demands and product lifecycle management. However, no study encompassing all these research streams could be found, and thus an abductive approach is developed, aiming at building new theory. The thesis draws upon a case study at Sony Germany, which has started an ambitious VMI initiative with the largest retailer of consumer electronics products in Germany. First, stock and sales data available, along with insights collected among employees, is used to understand the key profit-drivers when lifecycles of the two products overlap, and a set of indicators is propounded to measure them. The pattern of sales in relation to inventories of the two products is studied, and results in the validation of the stock-dependent demand assumption, with demand following a Poisson distribution of parameter λ [on-hand stock]. Demand for the new product is also found to be negatively affected by stock levels of the old product, in an exponential way. Second, a model is built and a scenario- based simulation embedding the patterns previously established is performed to evaluate different strategies to steer the stock levels in the VMI. Scenarios are evaluated against the proposed set of indicators, but no scenario is found to over perform consistently the others. Nevertheless interesting patterns emerge and it is possible to relate the performance observed to specificities of scenarios and product contexts. Using the patterns identified, a set of guidelines is suggested, along with proposals for practical implementation

Body mass dependence of oxidative phosphorylation efficiency in liver mitochondria from mammals

International audienceIn eukaryotes, the performances of an organism are dependent on body mass and chemically supported by the mitochondrial production of ATP. Although the relationship between body mass and mitochondrial oxygen consumption is well described, the allometry of the transduction efficiency from oxygen to ATP production (ATP/O) is still poorly understood. Using a comparative approach, we investigated the oxygen consumption and ATP production of liver mitochondria from twelve species of mammals ranging from 5 g to 600 kg. We found that both oxygen consumption and ATP production are mass dependent but not the ATP/O at the maximal phosphorylating state. The results also showed that for sub-maximal phosphorylating states the ATP/O value positively correlated with body mass, irrespective of the metabolic intensity. This result contrasts with previous data obtained in mammalian muscles, suggesting a tissue-dependence of the body mass effect on mitochondrial efficiency

SiliFish: A desktop application to model swimming behavior in developing zebrafish (Danio rerio)

Summary: SiliFish is an open-source desktop application to model and study zebrafish swimming. Here, we explain how to define the general parameters of the model, define cell populations, place them within the spinal cord, and define their projections. We explain how to run a simulation and how to visualize the network output and single-cell activity. The choice of C# as the programming language allows higher speed performance, simulating models with larger spinal circuits in less time.For complete details on the use and execution of this protocol, please refer to Roussel et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Data from: Allometry of mitochondrial efficiency is set by metabolic intensity

Metabolic activity sets the rates of individual resource uptake from the environment and resource allocations. For this reason, relationship with body size has been heavily documented from ecosystems to cells. Until now, most of the studies used the fluxes of oxygen as proxy of energy output without knowledge of the efficiency of biological systems to convert oxygen into ATP. The aim of this study was to examine the allometry of coupling efficiency (ATP/O) of skeletal muscle mitochondria isolated from twelve mammal species ranging from 6 g to 550 kg. Mitochondrial efficiencies were measured at different steady states of phosphorylation. The efficiencies increased sharply at higher metabolic rates. We have shown that body mass dependence of mitochondrial efficiency depends on metabolic intensity in skeletal muscles of mammals. Mitochondrial efficiency positively depends on body mass when mitochondria are close to the basal metabolic rate, however the efficiency is independent of body mass at the maximum metabolic rate. As a result, it follows that large mammals exhibit a faster dynamic increase in ATP/O than small species when mitochondria shift from basal to maximal activities. Finally, the invariant value of maximal coupling efficiency across mammal species could partly explain why scaling exponent values are very close to 1 at maximal metabolic rates

Mean data set (Boel et al 2019)

Mean values of mitochondrial bioenergetics parameters for all of the species shown in the manuscript

David and Goliath: a mitochondrial coupling problem?

An organism's size, known to affect biological structures and processes from cellular metabolism to population dynamics, depends upon the duration and rate of growth. However, it is still poorly understood how mitochondrial function affects the energetic basis of growth, especially in ectotherms, which represent a huge majority of animal biodiversity. Here, we present an intraspecies comparison of neighboring populations of frogs (Rana temporaria) that have large differences in body mass even at the same age. By investigating liver mitochondrial bioenergetics, we find that frogs with high growth rates and large body sizes exhibit higher ATP synthesis rates and more efficient oxidative phosphorylation compared to the smaller frogs with low growth rates. This higher energy transduction efficiency is not associated with significant increased oxidative capacity or membrane potential values, but instead may rely on a higher mitochondrial phosphorylation system activity in combination with a lower inner membrane proton leakage. Overall, the present study introduces the mitochondrial energy transduction system as an important mechanism for balancing physiological and ecological trade-offs associated with body size. Whether phenotype differences in mitochondrial function result from local ecological constraints or reflect a natural genetic variability within wild populations of common frogs remains an open question. However, our findings highlight the need for closer consideration of all aspects of mitochondrial metabolism for a better understanding of the physiological basis of the link between size, metabolism, and energy production in wild-dwelling organisms

Algebraic synthesis of dependable logic controllers

International audienceThis paper presents an algebraic method to synthesize control laws for logical system controllers. The starting point is a set of functional and dependable requirements expressed with algebraic relations or state models. We propose to synthesize control laws by solving a Boolean equation which represents all the requirements. The mathematical results that we have obtained allow to establish the exact form of the solutions if this equation has solutions. The first step of this method is the formalization of each requirement with Boolean relations between Boolean functions. Under this formulation, the requirements can be assembled and their coherence can be analyzed. This step consists in verifying if the Boolean equation, which represents all the requirements, has solutions. The third step is the synthesis of the control laws by solving this equation. At the end of this step, a parametric formulation of all the possible solutions is given. The fourth step of the method is the choice of a particular solution. This choice is made by the designer from heuristics. This method is illustrated with an example