Mechanics of the cellular actin cortex: from signalling to shape change

The actin cortex is a thin layer of actin, myosin, and actin binding proteins that underlies the membrane of most animal cells. It is highly dynamic and can undergo remodelling on time-scales of tens of seconds thanks to protein turnover and myosin-mediated contractions. The cortex enables cells to resist external mechanical stresses, controls cell shape, and allows cells to exert forces on their neighbours. Thus, its mechanical properties are key to its physiological function. Here, we give an overview of how cortex composition, structure, and dynamics control cortex mechanics and cell shape. We use mitosis as an example to illustrate how global and local regulation of cortex mechanics give rise to a complex series of cell shape changes.Comment: Revie

Ornamental colors reveal age in the king penguin

We investigated whether delayed plumage maturation occurred in king penguins (Aptenodytes patagonicus). Therefore we examined the relationships between age and sex on spectral properties and size of two colored plumage patches and a UV-reflective beak spot, using known-age cohorts. Unlike the colored patch on the breast, we found age differences in ear and beak coloration. These results suggest that head ornaments in king penguins could signal sexual maturity or social status. No sex differences were found in the intensity of colored ornaments, which can result from mutual mate choice or genetic correlation between sexes. Size of colored patches did not relate to age or sex

Cryptic speciation in gentoo penguins is driven by geographic isolation and regional marine conditions: Unforeseen vulnerabilities to global change

The conservation of biodiversity is hampered by data deficiencies, with many new species and subspecies awaiting description or reclassification. Population genomics and ecological niche modelling offer complementary new tools for un-covering functional units of phylogenetic diversity. We hypothesize that phyloge-netically delineated lineages of gentoo penguins (Pygoscelis papua) distributed across Antarctica and sub-Antarctic Islands are subject to spatially explicit ecological con-ditions that have limited gene flow, facilitating genetic differentiation, and thereby speciation processes

Evidence of pathogen-induced immunogenetic selection across the large geographic range of a wild seabird

Over evolutionary time,pathogen challenge shapes theimmunephenotype of the host tobetterrespondtoanincipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation becauseof its circumpolardistributionover a large latitudinal range, with littleornoadmixturebetweendifferent clades. Inthis study,we examine thediversity ina key family of innateimmunegenes-theToll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7.We present evidence of positive selection in TLR4 and TLR5,which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments.Fil: Levy, Hila. University of Oxford; Reino UnidoFil: Fiddaman, Steven R.. University of Oxford; Reino UnidoFil: Vianna, Juliana A.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Noll, Daly. Pontificia Universidad Católica de Chile; Chile. Universidad de Chile; ChileFil: Clucas, Gemma V.. Cornell University; Estados UnidosFil: Sidhu, Jasmine K.H.. University of Oxford; Reino UnidoFil: Polito, Michael J.. Louisiana State University; Estados UnidosFil: Bost, Charles A.. Centre D'etudes Biologiques de Chizé; FranciaFil: Phillips, Richard A.. British Antarctic Survey; Reino UnidoFil: Crofts, Sarah. Falklands Conservation; Reino UnidoFil: Miller, Gary D.. University of Western Australia; AustraliaFil: Pistorius, Pierre. Nelson Mandela University; SudáfricaFil: Bonnadonna, Francesco. Université de Montpellier; FranciaFil: Le Bohec, Celine. Université de Strasbourg; FranciaFil: Barbosa, Andres. Consejo Superior de Investigaciones Científicas. Museo Nacional de Ciencias Naturales; EspañaFil: Trathan, Phil. British Antarctic Survey; Reino UnidoFil: Raya Rey, Andrea Nélida. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Frantz, Laurent A.F.. University of London; Reino UnidoFil: Hart, Tom. University of Oxford; Reino UnidoFil: Smith, Adrian L.. University of Oxford; Reino Unid

Single-cell transcriptomics reveals shared immunosuppressive landscapes of mouse and human neuroblastoma

BACKGROUND High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key component of the tumor ecosystem the complexity of which has to be accurately understood to define selective targeting opportunities, including immune-based therapies. METHODS We combined various approaches including single-cell transcriptomics to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of 10 biopsies from neuroblastoma patients, either at diagnosis or at relapse. Features of related cells were validated by multicolor flow cytometry and functional assays. RESULTS We show that the immune microenvironment of MYCN-driven mouse neuroblastoma is characterized by a low content of T cells, several phenotypes of macrophages and a population of cells expressing signatures of myeloid-derived suppressor cells (MDSCs) that are molecularly distinct from the various macrophage subsets. We document two cancer-associated fibroblasts (CAFs) subsets, one of which corresponding to CAF-S1, known to have immunosuppressive functions. Our data unravel a complex content in myeloid cells in patient tumors and further document a striking correspondence of the microenvironment populations between both mouse and human tumors. We show that mouse intratumor T cells exhibit increased expression of inhibitory receptors at the protein level. Consistently, T cells from patients are characterized by features of exhaustion, expressing inhibitory receptors and showing low expression of effector cytokines. We further functionally demonstrate that MDSCs isolated from mouse neuroblastoma have immunosuppressive properties, impairing the proliferation of T lymphocytes. CONCLUSIONS Our study demonstrates that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T cells and accumulation of immunosuppressive cells. Our work provides a new and precious data resource to better understand the neuroblastoma ecosystem and suggest novel therapeutic strategies, targeting both tumor cells and components of the microenvironment

Étude du comportement hors-équilibre du cortex cellulaire

By consuming energy from the hydrolysis of ATP, cells are able to exert forces that stem from biochemical reactions. A central element of cells is the cytoskeleton, which is mainly composed of microtubules and actin filaments and accounts for the architecture and most of the mechanical properties of the cells. It is made of crosslinked polymers and, in terms of rheology, has a viscoelastic behavior. Within the cytoskeleton, processes such as actin or microtubule polymerization can exert forces. Proteins from the molecular motor family have the specific role of converting the energy stored in chemical form into mechanical energy. The out-of-equilibrium mechanical activity of the cell is directly related to these forces of biochemical origin. In this work, we studied the statistical distribution of biochemical forces exerted on a micrometer-sized bead attached to the actin cortex through cell adhesion receptors: integrins. The study of the forces of biological origin is inseparable from knowledge of the forces of thermal origin because, at this microscopic scale, the contribution of thermal forces is not negligible. The forces acting on the probe have two possible origins: biological or thermal. Our experimental approach is based on the combination of two microrheology techniques, active and passive, which allows us to calculate the temporal autocorrelation function of the forces exerted on a probe attached to the cortical actin and compare it to the autocorrelation function of the estimated thermal forces via the fluctuation-dissipation theorem. The difference between these two spectra gives us an idea of the contribution of the forces of biological origin to the movement of the bead and a measure of the deviation of the system from thermodynamic equilibrium. To further investigate this system, i.e. a bead undergoing forces from the cortical actin, we studied the effect of varying the ligand coating density on the bead. The question that has driven us throughout this work is the origin of these biological forces or, more precisely the nature of the component of the cytoskeleton that exerts these athermal forces. Initially, we studied the influence of temperature on these biological forces. We then studied the effect of depletion of ATP in the cell, of the depolymerization of actin and of the inhibition of molecular motors of the myosin family.La cellule est capable, en consommant l'énergie issue de l'hydrolyse de l'ATP, d'exercer des forces qui prennent leurs origines dans des réactions biochimiques. Un élément important de la cellule est le cytosquelette, composé principalement de microtubules et de filaments d'actine, il en constitue l'architecture et lui donne l'essentiel de ses propriétés mécaniques. Il est composé de polymères réticulés et, du point de vue de la rhéologie, a un comportement viscoélastique. Au sein du cytosquelette, des processus tels que la polymérisation de l'actine ou des microtubules permettent d'exercer des forces. Des protéines, de la famille des moteurs moléculaires, ont pour rôle spécifique de convertir l'énergie stockée sous forme chimique en énergie mécanique. L'activité mécanique hors-équilibre de la cellule est donc directement reliée à ces forces d'origine biochimique. Dans ce travail, nous avons étudié la distribution statistique des forces d'origine biochimique s'exerçant sur une bille de taille micrométrique attachée au cortex d'actine par l'intermédiaire de récepteurs de l'adhésion cellulaire : les intégrines. L'étude des forces d'origine biologique est inséparable de la connaissance des forces d'origine thermique car à cette échelle microscopique la contribution des forces thermiques n'est pas négligeable. Les forces s'exerçant sur la sonde ont deux origines possibles : biologique ou thermique. Notre approche expérimentale est basée sur la combinaison de deux techniques de microrhéologie, active et passive, ce qui nous permet de calculer la fonction d'autocorrélation temporelle des forces exercées sur une sonde accrochée à l'actine corticale et de la comparer à la fonction d'autocorrélation des forces thermiques estimée via le théorème de fluctuation-dissipation. La différence entre ces deux spectres nous donne une idée de la contribution des forces d'origine biologique au mouvement de la bille et une mesure de l'écart du système à l'équilibre thermodynamique. Afin d'étudier plus en détail ce système de bille subissant des forces de la part de l'actine corticale, nous avons étudié l'effet de la variation de la densité de ligand recouvrant la bille. La question qui nous a animés tout au long de ce travail est l'origine de ces forces biologiques ou plus exactement la nature du composant du cytosquelette qui exerce ces forces athermiques. Dans un premier temps, nous avons étudié l'influence de la température sur ces forces biologiques. Nous avons ensuite étudié l'effet de la déplétion de l'ATP dans la cellule, de la dépolymérisation de l'actine et de l'inhibition des moteurs moléculaires de la famille des myosines

Étude du comportement hors-équilibre du cortex cellulaire

By consuming energy from the hydrolysis of ATP, cells are able to exert forces that stem from biochemical reactions. A central element of cells is the cytoskeleton, which is mainly composed of microtubules and actin filaments and accounts for the architecture and most of the mechanical properties of the cells. It is made of crosslinked polymers and, in terms of rheology, has a viscoelastic behavior. Within the cytoskeleton, processes such as actin or microtubule polymerization can exert forces. Proteins from the molecular motor family have the specific role of converting the energy stored in chemical form into mechanical energy. The out-of-equilibrium mechanical activity of the cell is directly related to these forces of biochemical origin. In this work, we studied the statistical distribution of biochemical forces exerted on a micrometer-sized bead attached to the actin cortex through cell adhesion receptors: integrins. The study of the forces of biological origin is inseparable from knowledge of the forces of thermal origin because, at this microscopic scale, the contribution of thermal forces is not negligible. The forces acting on the probe have two possible origins: biological or thermal. Our experimental approach is based on the combination of two microrheology techniques, active and passive, which allows us to calculate the temporal autocorrelation function of the forces exerted on a probe attached to the cortical actin and compare it to the autocorrelation function of the estimated thermal forces via the fluctuation-dissipation theorem. The difference between these two spectra gives us an idea of the contribution of the forces of biological origin to the movement of the bead and a measure of the deviation of the system from thermodynamic equilibrium. To further investigate this system, i.e. a bead undergoing forces from the cortical actin, we studied the effect of varying the ligand coating density on the bead. The question that has driven us throughout this work is the origin of these biological forces or, more precisely the nature of the component of the cytoskeleton that exerts these athermal forces. Initially, we studied the influence of temperature on these biological forces. We then studied the effect of depletion of ATP in the cell, of the depolymerization of actin and of the inhibition of molecular motors of the myosin family.La cellule est capable, en consommant l'énergie issue de l'hydrolyse de l'ATP, d'exercer des forces qui prennent leurs origines dans des réactions biochimiques. Un élément important de la cellule est le cytosquelette, composé principalement de microtubules et de filaments d'actine, il en constitue l'architecture et lui donne l'essentiel de ses propriétés mécaniques. Il est composé de polymères réticulés et, du point de vue de la rhéologie, a un comportement viscoélastique. Au sein du cytosquelette, des processus tels que la polymérisation de l'actine ou des microtubules permettent d'exercer des forces. Des protéines, de la famille des moteurs moléculaires, ont pour rôle spécifique de convertir l'énergie stockée sous forme chimique en énergie mécanique. L'activité mécanique hors-équilibre de la cellule est donc directement reliée à ces forces d'origine biochimique. Dans ce travail, nous avons étudié la distribution statistique des forces d'origine biochimique s'exerçant sur une bille de taille micrométrique attachée au cortex d'actine par l'intermédiaire de récepteurs de l'adhésion cellulaire : les intégrines. L'étude des forces d'origine biologique est inséparable de la connaissance des forces d'origine thermique car à cette échelle microscopique la contribution des forces thermiques n'est pas négligeable. Les forces s'exerçant sur la sonde ont deux origines possibles : biologique ou thermique. Notre approche expérimentale est basée sur la combinaison de deux techniques de microrhéologie, active et passive, ce qui nous permet de calculer la fonction d'autocorrélation temporelle des forces exercées sur une sonde accrochée à l'actine corticale et de la comparer à la fonction d'autocorrélation des forces thermiques estimée via le théorème de fluctuation-dissipation. La différence entre ces deux spectres nous donne une idée de la contribution des forces d'origine biologique au mouvement de la bille et une mesure de l'écart du système à l'équilibre thermodynamique. Afin d'étudier plus en détail ce système de bille subissant des forces de la part de l'actine corticale, nous avons étudié l'effet de la variation de la densité de ligand recouvrant la bille. La question qui nous a animés tout au long de ce travail est l'origine de ces forces biologiques ou plus exactement la nature du composant du cytosquelette qui exerce ces forces athermiques. Dans un premier temps, nous avons étudié l'influence de la température sur ces forces biologiques. Nous avons ensuite étudié l'effet de la déplétion de l'ATP dans la cellule, de la dépolymérisation de l'actine et de l'inhibition des moteurs moléculaires de la famille des myosines

Etude du comportement hors-équilibre du cortex cellulaire

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Cinétiques de décontamination en milieu contrôlé de moules toxiques (Diarrheic Shellfish Poison). Premiers résultats

Laboratory assays have been performed, using mussels contamined with Dinophysis, in order to assess potential depurations kinetics. Mussels samples from Seine bay, Douarnenez bay and Vilaine bay have been tested . From these assays, which are to be performed in 1989; two main results are stressed : 1) when the toxicity level is near 0,5 MU/g of hepatopancreas*, depuration is undedectable during twelve days, 2) when the toxicity level exceeds 1 MU/g,depuration is important during the first eight days. *(quarantine level used by Japanese authorities) .Afin de mieux appréhender les cinétiques de décontamination de moules de bouchots contaminées par la toxine diarrhéique secrétée par Dinophysis (DSP), des essais en laboratoire ont été effectués à partir de moules provenant de la baie de Seine, de la baie de Douarnenez et de la baie de Vilaine. A partir de ces essais qui seront poursuivis en 1989 il se dégage deux cas : 1) quand la toxicité des moules est située autour de 0,5 US/gramme d ' hépatopancréas (seuil de salubrité défini par les Japonais) la décontamination est non décelable sur 12 jours, 2) quand la toxicité est supérieure à 1 US, la décontamination est importante les huit premiers jour