The Actin Cortex: A Bridge between Cell Shape and Function

The cortical actin network controls many animal cell shape changes by locally modulating cortical tension. Recent work has provided insight into cortex components and regulators. However, how the network is reorganized in response to cellular signaling, and the role reorganization may play during cell state changes, remain to be determined

Viscoelastic properties of differentiating blood cells are fate- and function-dependent

This is the final version of the article. Available from the publisher via the DOI in this record.Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies.Funding: The authors acknowledge financial support by the Cambridge Commonwealth Trust (to AEE; http://www.cambridgetrusts.org), the Medical Research Council (to KC and JG; grant number: 94185; http://www.mrc.ac.uk), the Human Frontier Science Program (to GW and JG; grant number: RGP0015/2009-C; http:// www.hfsp.org) and the European Research Council (to JG; grant number: 282060; http://erc.europa.eu)

Nuclear mechanotransduction in stem cells.

In development and in homeostatic maintenance of tissues, stem cells and progenitor cells are constantly subjected to forces. These forces can lead to significant changes in gene expression and function of stem cells, mediating self-renewal, lineage specification, and even loss of function. One of the ways that has been proposed to mediate these functional changes in stem cells is nuclear mechanotransduction - the process by which forces are converted to signals in the nucleus. The purpose of this review is to discuss the means by which mechanical signals are transduced into the nucleus, through the linker of nucleoskeleton and cytoskeleton (LINC) complex and other nuclear envelope transmembrane (NET) proteins, which connect the cytoskeleton to the nucleus. We discuss how LINC/NETs confers tissue-specific mechanosensitivity to cells and further elucidate how LINC/NETs acts as a control center for nuclear mechanical signals, regulating both gene expression and chromatin organization. Throughout, we primarily focus on stem cell-specific examples, notwithstanding that this is a nascent field. We conclude by highlighting open questions and pointing the way to enhanced research efforts to understand the role nuclear mechanotransduction plays in cell fate choice

Identification of a stable complex between a [NiFe]‐hydrogenase catalytic subunit and its maturation protease

Salmonella enterica serovar Typhimurium has the ability to use molecular hydrogen as a respiratory electron donor. This is facilitated by three [NiFe]‐hydrogenases termed Hyd‐1, Hyd‐2, and Hyd‐5. Hyd‐1 and Hyd‐5 are homologous oxygen‐tolerant [NiFe]‐hydrogenases. A critical step in the biosynthesis of a [NiFe]‐hydrogenase is the proteolytic processing of the catalytic subunit. In this work, the role of the maturation protease encoded within the Hyd‐5 operon, HydD, was found to be partially complemented by the maturation protease encoded in the Hyd‐1 operon, HyaD. In addition, both maturation proteases were shown to form stable complexes, in vivo and in vitro, with the catalytic subunit of Hyd‐5. The protein–protein interactions were not detectable in a strain that could not make the enzyme metallocofactor

Les déficits cognitifs chez les individus présentant un trouble de la personnalité comorbide à la schizophrénie : une étude de la portée

Essai présenté en vue de l’obtention du grade de doctorat en psychologie (D.Psy), option Neuropsychologie cliniqueObjectif : Il est estimé qu'environ 40 % des personnes diagnostiquées avec la schizophrénie répondent également aux critères diagnostiques d'un trouble de la personnalité. Cette comorbidité est associée à un pronostic défavorable de la maladie. La cognition étant le meilleur prédicteur du rétablissement, la présente étude vise à caractériser le profil cognitif des individus présentant un trouble de la personnalité comorbide à la schizophrénie en revisitant la littérature des 24 dernières années. Nous cherchions à déterminer si la cognition de ces individus diffère de celle des personnes présentant uniquement un diagnostic de schizophrénie, et à caractériser ces différences. Méthode : Les articles ont été recueillis à partir de PubMed, Google Scholar, Web of Science, PsychInfo, PsychNet, MedLine et EMBASE. Ils ont été sélectionnés selon les critères d'inclusion suivants : (a) utilisation de mesures neuropsychologiques ou de cognition sociale, (b) diagnostic explicite des troubles mentaux établi à l'aide d'outils diagnostiques validés, (c) participants présentant un trouble de la personnalité comorbide à un diagnostic de schizophrénie, et (d) résultats de mesures neuropsychologiques spécifiques pour les participants présentant ce type de comorbidité. Résultats : Au total, 11 articles ont été retenus pour l'analyse des données. Parmi eux, six ont établi cliniquement un diagnostic de trouble de la personnalité, tandis que cinq ont mesuré les traits associés à divers troubles de la personnalité. En raison de l'hétérogénéité des méthodologies propres à chaque article, aucune conclusion statistique n'a pu être tirée. Cependant, des différences semblent se dessiner au niveau des fonctions exécutives et de la cognition sociale entre les individus ayant un trouble de la personnalité comorbide à la schizophrénie et ceux ayant uniquement un diagnostic de schizophrénie. Les traits de personnalité du cluster B semblent associés à plus de déficits cognitifs, tandis qu'une prévalence élevée des traits de personnalité antisociale semble liée à de meilleures compétences métacognitives. Conclusion : Cette étude soulève des pistes de recherche pour l'avenir. Elle offre également des recommandations tant pour les clinicien.es que pour les chercheur.es

The Characterization of the Magdalene in the Gospels according to John, Thomas, Philip and Mary

The recent interest in the figure of Mary Magdalene in pop culture has seemingly generated a fascination in studying the Magdalene academically. As a figure who is negatively and often wrongly characterized as a sinner, a prostitute and sexual partner to Jesus, the Magdalene is also a significant literary character who symbolizes the power of the feminine and the feminine right to salvation. Using both diachronic and synchronic methodologies we can begin to understand the power and influence of the Magdalene in both the canonical gospels and other Christian texts at Nag Hammadi. The character of the Magdalene is examined in the Gospels according to John, Thomas, Philip and Mary where her character advances the plot and aids the reader in understanding the theological message of each gospel. Within these selected texts, the relationship that the Magdalene has with Jesus and the competition that exists between Mary and Peter is emphasized. The texts are examined using a gender-critical approach to illustrate the role that gender and sex play in the development, as well as in the reception of the text. Using a combination of diachronic, synchronic as well as a gender-critical approach we are able to understand how the Magdalene highlights the unity in Christ and gives empowerment to female literary characters

Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy

Refractive index imaging is a label-free technique that enables long-term monitoring of the internal structures and molecular composition in living cells with minimal perturbation. Existing tomographic methods for the refractive index imaging lack 3-D resolution and result in artifacts that prevent accurate refractive index quantification. To overcome these limitations without compromising the capability to observe a sample in its most native condition, we have developed a regularized tomographic phase microscope (RTPM) enabling accurate refractive index imaging of organelles inside intact cells. With the enhanced accuracy, we quantify the mass of chromosomes in intact living cells, and differentiate two human colon cancer lines, HT-29 and T84 cells, solely based on the non-aqueous (dry) mass of chromosomes. In addition, we demonstrate chromosomal imaging using a dual-wavelength RTPM, which shows its potential to determine the molecular composition of cellular organelles in live cells.National Institute of Biomedical Imaging and Bioengineering (U.S.) (9P41EB015871-26A1

Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a b-cateninmediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate

Three-dimensional geometry controls division symmetry in stem cell colonies.

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell-cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry. This article has an associated First Person interview with the first author of the paper