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News Article | May 4, 2017
Site: www.eurekalert.org

Biologists from UNIGE have discovered how this organ adapts to the cycles of feeding and fasting, and the alternation of day and night In mammals, the liver plays a pivotal role in metabolism and the elimination of toxins, and reaches its maximum efficiency when they are active and feed. Biologists from the University of Geneva (UNIGE), Switzerland, have discovered how this organ adapts to the cycles of feeding and fasting, and the alternation of day and night within 24 hours. The researchers showed in mice that the size of the liver increases by almost half before returning to its initial dimensions, according to the phases of activity and rest. Published in the journal Cell, their study describes the cellular mechanisms of this fluctuation, which disappears when the normal biological rhythm is reversed. The disruption of our circadian clock due to professional constraints or private habits therefore probably has important repercussions on our liver functions. Mammals have adapted to diurnal and nocturnal rhythms using a central clock located in the brain. The latter, which is resettled every day by the light, synchronizes the subordinate clocks present in most of our cells. In the liver, more than 350 genes involved in metabolism and detoxification are expressed in a circadian fashion, with a biological rhythm of 24 hours. "Many of them are also influenced by the rhythm of food intake and physical activity, and we wanted to understand how the liver adapts to these fluctuations", says Ueli Schibler, professor emeritus at the Department of Molecular Biology of the UNIGE Faculty of Science. The liver oscillates, but not the other organs The mice forage and feed at night, while the day is spent resting. "In rodents following a usual circadian rhythm, we observed that the liver gradually increases during the active phase to reach a peak of more than 40% at the end of the night, and that it returns to its initial size during the day", notes Flore Sinturel, researcher of the Geneva group and first author of the study. The cellular mechanisms of this adaptation were discovered in collaboration with scientists from the Nestlé Institute of Health Sciences (NIHS) and the University of Lausanne (UNIL) in Switzerland. Researchers have shown that the size of liver cells and their protein content oscillate in a daily manner. The number of ribosomes, the organelles responsible for producing the proteins required for the various functions of the liver, fluctuates together with the size of the cell. "The latter adapts the production and assembly of new ribosomes to ensure a peak of protein production during the night. The components of ribosomes produced in excess are then identified, labeled, and degraded during the resting phase", explains Flore Sinturel. The amplitude of the variations observed by the biologists depends on the cycles of feeding and fasting, as well as diurnal and nocturnal phases. Indeed, the fluctuations disappear when the phases of feeding no longer correspond to the biological clock, which evolved in the course of hundreds of millions of years: "the size of the liver and the hepatocytes, as well as their contents in ribosomes and proteins, remain nearly stable when mice are fed during the day. Yet, these animals ingest similar amounts of food, irrespective of whether they are fed during the night or during the day", points out Frédéric Gachon of the NIHS, who co-directed the study. Many human subjects no longer live according to the rhythm of their circadian clock, due to night work hours, alternating schedules or frequent international travels. A previous study (Leung et al., Journal of Hepatology, 1986) determining the volume of the human liver during six hours using methods based on ultrasound, suggests that this organ also oscillates within us. If mechanisms similar to those found in mice exist in humans, which is likely to be the case, the deregulation of our biological rhythms would have a considerable influence on hepatic functions.


News Article | May 8, 2017
Site: www.medicalnewstoday.com

In mammals, the liver plays a pivotal role in metabolism and the elimination of toxins, and reaches its maximum efficiency when they are active and feed. Biologists from the University of Geneva (UNIGE), Switzerland, have discovered how this organ adapts to the cycles of feeding and fasting, and the alternation of day and night within 24 hours. The researchers showed in mice that the size of the liver increases by almost half before returning to its initial dimensions, according to the phases of activity and rest. Published in the journal Cell, their study describes the cellular mechanisms of this fluctuation, which disappears when the normal biological rhythm is reversed. The disruption of our circadian clock due to professional constraints or private habits therefore probably has important repercussions on our liver functions. Mammals have adapted to diurnal and nocturnal rhythms using a central clock located in the brain. The latter, which is resettled every day by the light, synchronizes the subordinate clocks present in most of our cells. In the liver, more than 350 genes involved in metabolism and detoxification are expressed in a circadian fashion, with a biological rhythm of 24 hours. "Many of them are also influenced by the rhythm of food intake and physical activity, and we wanted to understand how the liver adapts to these fluctuations", says Ueli Schibler, professor emeritus at the Department of Molecular Biology of the UNIGE Faculty of Science. The mice forage and feed at night, while the day is spent resting. "In rodents following a usual circadian rhythm, we observed that the liver gradually increases during the active phase to reach a peak of more than 40% at the end of the night, and that it returns to its initial size during the day", notes Flore Sinturel, researcher of the Geneva group and first author of the study. The cellular mechanisms of this adaptation were discovered in collaboration with scientists from the Nestlé Institute of Health Sciences (NIHS) and the University of Lausanne (UNIL) in Switzerland. Researchers have shown that the size of liver cells and their protein content oscillate in a daily manner. The number of ribosomes, the organelles responsible for producing the proteins required for the various functions of the liver, fluctuates together with the size of the cell. "The latter adapts the production and assembly of new ribosomes to ensure a peak of protein production during the night. The components of ribosomes produced in excess are then identified, labeled, and degraded during the resting phase", explains Flore Sinturel. The amplitude of the variations observed by the biologists depends on the cycles of feeding and fasting, as well as diurnal and nocturnal phases. Indeed, the fluctuations disappear when the phases of feeding no longer correspond to the biological clock, which evolved in the course of hundreds of millions of years: "the size of the liver and the hepatocytes, as well as their contents in ribosomes and proteins, remain nearly stable when mice are fed during the day. Yet, these animals ingest similar amounts of food, irrespective of whether they are fed during the night or during the day", points out Frédéric Gachon of the NIHS, who co-directed the study. Many human subjects no longer live according to the rhythm of their circadian clock, due to night work hours, alternating schedules or frequent international travels. A previous study (Leung et al., Journal of Hepatology, 1986) determining the volume of the human liver during six hours using methods based on ultrasound, suggests that this organ also oscillates within us. If mechanisms similar to those found in mice exist in humans, which is likely to be the case, the deregulation of our biological rhythms would have a considerable influence on hepatic functions. Article: Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles, Ueli Schibler et al., Cell, doi: 10.1016/j.cell.2017.04.015, published 4 May 2017.


News Article | March 11, 2016
Site: www.biosciencetechnology.com

Innovative software tools allowed the scientists to construct accurate "maps" of gene networks for about 400 different human cell and tissue types, ranging from immune cells to brain tissues, whereas previous studies were limited to just one or few tissues. Each of these networks describes hundreds of thousands of regulatory interactions among thousands of genes, giving the first global view of the "control system" of diverse cells and tissues. The team found that genetic variants disrupt components of these networks in disease-specific tissues, giving new insights on disease mechanisms which may lead to targeted treatments that are more effective and have fewer side-effects for the patient. The project was spearheaded by researchers from the newly formed Department of Computational Biology (DCB) at the University of Lausanne (UNIL) and the SIB Swiss Institute of Bioinformatics, in collaboration with researchers from the University Hospital of Lausanne (CHUV) and the Broad Institute of MIT and Harvard. Advances in genome-sequencing and related technologies have given rise to large studies that compare genetic variants between healthy people and people with a given condition. These studies have successfully identified thousands of genetic variants that are linked to different diseases. However, the mechanisms by which these variants influence disease processes remain mostly unknown, which is currently hindering progress to developing better diagnostic tests and personalized treatments for patients. Daniel Marbach, David Lamparter and Prof. Sven Bergmann (SIB, UNIL), in collaboration with Prof. Zoltán Kutalik (SIB, CHUV, UNIL) and Prof. Manolis Kellis (MIT), have now mapped networks of interacting genes that are perturbed by disease variants with unprecedented resolution across hundreds of human cell types and tissues. "The challenge is that over 90% of disease variants lie outside of genes, in regions of the genome that are still poorly understood" Marbach says. "These regions can have regulatory functions, which are sometimes disrupted by genetic variants. Things get even more complicated as the regulatory relationships may vary between different tissue types. For example, a certain gene may activate another one in the liver, but not in the heart." The team thus tackled the ambitious task of creating accurate "maps" of the regulatory networks that control the activity of genes in a given tissue. Data from an international research consortium (FANTOM) coupled with novel analysis techniques allowed them to create the largest collection of such networks to date, describing the regulatory interactions among over 19,000 genes in close to 400 human cell types and tissues. The study thus gives the first comprehensive view of the regulatory systems across a broad range of cells and tissues. The underlying hypothesis was that genetic variants may impact genes that are connected within regulatory networks of tissues that are specific to certain diseases. To test their hypothesis, the researchers employed techniques similar to those applied to social networks to gain information about users on the basis of their interconnections. But in this case, they used biological networks to gain information about genes that can lead to diseases. In a large study including genetic data for diverse neurodegenerative, psychiatric, immune-related, cardiovascular and metabolic disorders, the researchers found that disease variants often affect groups of genes that were densely interconnected within regulatory networks, confirming their hypothesis. Moreover, these affected network components pinpointed with remarkable precision cell types or tissues that are implicated in disease processes. "For example, people with schizophrenia were found to have genetic variants that perturb interacting genes in brain tissues that are responsible for cognitive and emotional behavior, while genetic variants associated with obesity impact genes that interact in tissues of the intestinal system" Marbach says. "Our work shows that accurate maps of gene networks for different tissues will be of tremendous value to advance our understanding of how diseases start and progress, which is essential to design targeted treatments and to identify patient groups that respond to these treatments in a personalized medicine setting," concludes Prof. Bergmann.


Menichelli E.,Nofima Materials AS | Menichelli E.,Norwegian University of Life Sciences | Olsen N.V.,Nofima Materials AS | Meyer C.,Unil | Naes T.,Nofima Materials AS
Food Quality and Preference | Year: 2012

This paper proposes a methodology for combining extrinsic and intrinsic attributes in consumer testing of food products. The paper attempts to focalize on the main sensory drivers of liking or choice probability and their interaction with additional information, and to investigate effects related to the population as well as how consumers differ in their assessments. Two different data analysis approaches are considered and compared on choice probability data from a consumer study of orange juice. One of the methods is based on mixed model ANOVA of individual differences, the other approach is based on fuzzy clustering related to regression residuals. The main results show that extrinsic consumer attributes are easily and efficiently related to the sensory properties of products, allowing for interactions. The methodology estimates population or segment means and gives an overview of individual differences in choice intent or liking. © 2011 Elsevier Ltd.


Neves P.,UNIL | Neuffer N.,Service des Urgences | Yersin B.,Service des Urgences
Revue Medicale Suisse | Year: 2011

Alcohol abuse causes numerous medical and social problems. In spite of the decrease of the global consumption of alcohol per capita in Switzerland during the last years, the cases of massive alcoholic poisoning seem increasing in emergency departments. Very few data is available at the moment on this phenomenon. The present article focuses on this problem within the framework of the emergency department of the CHUV. It aims at bringing to light on the sociodemographic and medical characteristics, as well as on the characteristics of the stay of these patients who are admitted with such a problem, to have a global vision of this phenomenon.


Lunati I.,UNIL | Lee S.H.,Chevron
14th European Conference on the Mathematics of Oil Recovery 2014, ECMOR 2014 | Year: 2014

Flow through fractured nanoporous shale formations is complicated by a hierarchy of structural features (ranging from nanopores to microseismic and hydraulic fractures) and by several gas-transport mechanisms that differ from standard viscous flow used in reservoir modeling. In small pores, self-diffusion becomes more important than advection, and slippage effects and Knudsen diffusion might become relevant at relatively low densities. We derive a nonlinear effective diffusion coefficient that describes the main transport mechanisms. In its dimensionless form, this coefficient only depends on a geometric factor (or dimensionless permeability) and on the kinetic model that describes the gas. To simplify the description of the complex structure of fractured shale formations, we observe that the production rate is controlled by the flow from the shale matrix (which has the largest storage capacity but the lowest diffusivity) into the fracture network, which is assumed to produce instantaneously. Therefore, we propose to model the flow in the shale matrix and estimate the production rate with a simple bundle of tube. Each tube is characterized by two diameters (conductive diameter and storage diameter), which idealizes gas pathways formed by bulbs and throats and permit to model slow recovery of large gas volumes. To construct a Bundle-of-Dual-Tube Model (BoDTM) a reliable estimate of the joint statistics of the matrix-porosity parameters is needed. This can be either inferred from core measurements or postulate on the basis of some a-priori assumption if not enough information is available. By means of simplified distributions we investigate the effects the variability and correlation of bundle-parameters on the production rate. The BoDTM, which can be easily extended to obtain bundles with a more complex statistics, entails enough flexibility to describe complex production rate from shale formations.


Lee S.H.,Chevron | Jensen C.L.,Chevron | Lunati I.,UNIL
Society of Petroleum Engineers - SPE Reservoir Simulation Symposium 2015 | Year: 2015

Gas flow through fractured nano-porous shale formations is complicated by a hierarchy of structural features and fluid transport mechanisms. Structural features include tight porous rock with a variety of fractures. Gas transport mechanisms include self diffusion, Knudsen diffusion, advection, gas expansion, adsorption, and slippage effects at the pore walls. In nanopores, as encountered in tight shale gas reservoirs, the effects of diffusion can overcome advection and should be included in reservoir flow calculations. As the permeability of shale is very low, conventional reservoir simulation modeling and production estimation methods, which are designed for fluid-flow processes dominated by viscous forces, may not be reliable to predict the reservoir production rate. We present a pore-based mechanistic model (the Bundle of Dual-Tube Model, BoDTM), which includes complex gas dynamics in fractured nano- porous shale formations. The pore-based model provides a quick and reliable means for modeling tight rock gas flow that includes known and uncertain reservoir properties, such as rock permeability, diffusion, pore volume, pore throat size, rock tortuosity and fracture characteristics. Gas flow is modeled in the shale matrix and production rate is estimated with a simple bundle of dual-tubes. Each dual-tube idealizes a gas pathway formed by pore bulbs and throats and is characterized by two diameters (a conductive diameter and a storage diameter) and one length. The two diameters permit modeling slow recovery of large gas volumes; the tube length takes into account the pathway length from the matrix into the fracture network, which is the length that controls the travel time and the production rate. To construct the BoDTM, a statistical estimate of the fracture-network and shale-matrix parameters is necessary. Production rate is controlled by flow from the tight shale rock matrix (which has the largest storage capacity but the lowest diffusivity) into the fracture network, and we assume that gas in the fractures is produced instantaneously. Applying statistical distribution functions, we examine the effect of model input properties on gas production. By applying the BoDTM to field data from the Bamett and Fayetteville Plays, we demonstrate that the model provides a means to quickly assess gas production rates from shale formations. Copyright © 2015 Society of Petroleum Engineers.


Olsen N.V.,430 As | Menichelli E.,430 As | Menichelli E.,Norwegian University of Life Sciences | Meyer C.,Unil | Naes T.,430 As
Appetite | Year: 2011

The objective of this article is to compare product quality and brand choice for private labels (PL) and national brands (NB). Over the past two decades, PL have gained larger and larger share of grocery sales, and nowadays PL play a crucial part in the European food retail sector. Since it is stated that most PL have moved on from being mostly low cost me-too products to become also premium products, we want to investigate if objective and perceived quality of PL fits the quality of NB. Four hypotheses are stated and tested on orange juice data from Norway. A trained sensory panel and consumers (n= 105) evaluated six juice samples that vary according to three factors. These factors were (1) Brand (PL and NB), (2) Treatment (Gentle heat treatment and Pasteurized) and (3) Pulp (with and without). Principal component analysis, two-way ANOVA, and PLS regression were conducted, and the results indicate that variation in quality exists both among PL and NB, there is a large discrepancy between blind liking and brand choice, and that consumers with a positive attitude towards PL are more likely to choose a PL instead of a NB. © 2011 Elsevier Ltd.


News Article | February 17, 2017
Site: www.rdmag.com

Researchers at EPFL and UNIL have discovered a faster and more efficient gait, never observed in nature, for six-legged robots walking on flat ground. Bio-inspired gaits – less efficient for robots – are used by real insects since they have adhesive pads to walk in three dimensions. The results provide novel approaches for roboticists and new information to biologists. When vertebrates run, their legs exhibit minimal contact with the ground. But insects are different. These six-legged creatures run fastest using a three-legged, or “tripod” gait where they have three legs on the ground at all times – two on one side of their body and one on the other. The tripod gait has long inspired engineers who design six-legged robots, but is it necessarily the fastest and most efficient way for bio-inspired robots to move on the ground? Researchers at EPFL and UNIL revealed that there is in fact a faster way for robots to locomote on flat ground, provided they don’t have the adhesive pads used by insects to climb walls and ceilings. This suggests designers of insect-inspired robots should make a break with the tripod-gait paradigm and instead consider other possibilities including a new locomotor strategy denoted as the “bipod” gait. The researchers’ findings are published in Nature Communications. The scientists carried out a host of computer simulations, tests on robots and experiments on Drosophila melanogaster – the most commonly studied insect in biology. “We wanted to determine why insects use a tripod gait and identify whether it is, indeed, the fastest way for six-legged animals and robots to walk,” said Pavan Ramdya, co-lead and corresponding author of the study. To test the various combinations, the researchers used an evolutionary-like algorithm to optimize the walking speed of a simulated insect model based on Drosophila. Step-by-step, this algorithm sifted through many different possible gaits, eliminating the slowest and shortlisting the fastest. Adhesive pads The findings shed new light on problems for biologists and robotics engineers alike. The researchers found that the common insect tripod gait did emerge when they optimized their insect model to climb vertical surfaces with adhesion on the tips of its legs. By contrast, simulations of ground-walking without the adhesiveness of insects’ legs revealed that bipod gaits, where only two legs are on the ground at any given time, are faster and more efficient – although in nature no insects actually walk this way. “Our findings support the idea that insects use a tripod gait to most effectively walk on surfaces in three dimensions, and because their legs have adhesive properties. This confirms a long-standing biological hypothesis,” said Ramdya. “Ground robots should therefore break free from only using the tripod gait”. Polymer boots The researchers then built a six-legged robot capable of employing either the tripod or bipod gait. The bipod gait was again demonstrated to be faster, corroborating the simulation algorithms’ results. Finally, the experimenters examined real insects. To see if leg adhesion might also play a role in the walking coordination of real flies, they put polymer drops on the flies’ legs to cover their claws and adhesive pads – as if the flies were wearing boots – and watched what happened. The flies quickly began to use bipod-like leg coordination similar to the one discovered in the simulation. “This result shows that, unlike most robots, animals can adapt to find new ways of walking under new circumstances,” said Robin Thandiackal, a co-lead author of the study. “There is a natural dialogue between robotics and biology: Many robot designers are inspired by nature and biologists can use robots to better understand the behavior of animal species. We believe that our work represents an important contribution to the study of animal and robotic locomotion.”


News Article | February 17, 2017
Site: www.eurekalert.org

When vertebrates run, their legs exhibit minimal contact with the ground. But insects are different. These six-legged creatures run fastest using a three-legged, or "tripod" gait where they have three legs on the ground at all times - two on one side of their body and one on the other. The tripod gait has long inspired engineers who design six-legged robots, but is it necessarily the fastest and most efficient way for bio-inspired robots to move on the ground? Researchers at EPFL and UNIL revealed that there is in fact a faster way for robots to locomote on flat ground, provided they don't have the adhesive pads used by insects to climb walls and ceilings. This suggests designers of insect-inspired robots should make a break with the tripod-gait paradigm and instead consider other possibilities including a new locomotor strategy denoted as the "bipod" gait. The researchers' findings are published in Nature Communications. The scientists carried out a host of computer simulations, tests on robots and experiments on Drosophila melanogaster - the most commonly studied insect in biology. "We wanted to determine why insects use a tripod gait and identify whether it is, indeed, the fastest way for six-legged animals and robots to walk," said Pavan Ramdya, co-lead and corresponding author of the study. To test the various combinations, the researchers used an evolutionary-like algorithm to optimize the walking speed of a simulated insect model based on Drosophila. Step-by-step, this algorithm sifted through many different possible gaits, eliminating the slowest and shortlisting the fastest. The findings shed new light on problems for biologists and robotics engineers alike. The researchers found that the common insect tripod gait did emerge when they optimized their insect model to climb vertical surfaces with adhesion on the tips of its legs. By contrast, simulations of ground-walking without the adhesiveness of insects' legs revealed that bipod gaits, where only two legs are on the ground at any given time, are faster and more efficient - although in nature no insects actually walk this way. "Our findings support the idea that insects use a tripod gait to most effectively walk on surfaces in three dimensions, and because their legs have adhesive properties. This confirms a long-standing biological hypothesis," said Ramdya. "Ground robots should therefore break free from only using the tripod gait". The researchers then built a six-legged robot capable of employing either the tripod or bipod gait. The bipod gait was again demonstrated to be faster, corroborating the simulation algorithms' results. Finally, the experimenters examined real insects. To see if leg adhesion might also play a role in the walking coordination of real flies, they put polymer drops on the flies' legs to cover their claws and adhesive pads - as if the flies were wearing boots - and watched what happened. The flies quickly began to use bipod-like leg coordination similar to the one discovered in the simulation. "This result shows that, unlike most robots, animals can adapt to find new ways of walking under new circumstances," said Robin Thandiackal, a co-lead author of the study. "There is a natural dialogue between robotics and biology: Many robot designers are inspired by nature and biologists can use robots to better understand the behavior of animal species. We believe that our work represents an important contribution to the study of animal and robotic locomotion."

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