Dense active matter model of motion patterns in confluent cell monolayers

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations. We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. Simulations and normal mode analysis perfectly match when tissue-level reorganisation occurs on times longer than the persistence time of cell motility. Our analytical model quantitatively matches measured velocity correlation functions over more than a decade with a single fitting parameter.Comment: updated version accepted for publication in Nat. Com

A socio-psychological perspective on the phenomenon of infant rapes in South Africa

In the context of much social violence South Africa has recently witnessed an increase in the reported cases of rape of young children and even infants. In this article the author wishes to move away from an individual focus on the dynamics underlying the rapist but rather wants to present a socio-psychological perspective on this phenomenon. It will be argued that the rape of infants must firstly be understood within the context of rape as whole. Emphasis will also be given to specific social and political factors present in South African society which may place children at risk of abuse and sexual violence. The interpersonal relationships which may be typical of families of victims will also be explored. Finally intervention and management strategies for mental health professionals working with victims and their families will be suggested.S Afr Psychiatry Rev 2003;6:6-1

Family murder in post-apartheid South Africa: reflections for mental health professionals

In the late eighties the phenomenon of family murder was closely linked to Afrikaans-speaking families faced with political change and uncertainty. A large study carried out by the Human Sciences Research Council (HSRC) at the time disputed this overly simplistic explanation and proposed a complex interplay of interpersonal and intrapsychic factors reflecting a phenomenon which took place under all population groups. Recent cases of family murder reported in the media have once again posed serious questions regarding possible etiological explanations for this phenomenon in post-apartheid South Africa. In this article the reviews the original HSRC findings as well as exploring social and psychological factors, which may be relevant in present day South Africa. A social constructionist perspective is used as a theoretical framework for understanding the wider context of this type of violence. In conclusion possible interventions, which move beyond the simplistic but focus rather on the social responsibility of mental health professionals are proposed. In die laat 1980s het die opvatting ontstaan dat daar 'n noue verband bestaan tussen gesinsmoord en Afrikaansprekende gesinne wat met politieke veranderinge en onsekerheid gekonfronteer word. 'n Omvattende studie wat op dié stadium deur die Raad vir Geesteswetenskaplike Navorsing (RGN) uitgevoer was, het hierdie oorsimplistiese standpunt bevraagteken. 'n Komplekse wisselwerking tussen interpersoonlike en intrapsigiese faktore, as 'n refleksie van 'n verskynsel wat onder alle bevolkingsgroepe voorkom, is as alternatief voorgestel. Onlangse gevalle van gesinsmoord wat in die media geraporteer is, het opnuut ernstige vrae oor moontlike etiologiese verklarings vir hierdie verskynsel in post-apartheid Suid-Afrika na vore gebring. Die skrywer neem in hierdie artikel opnuut die oorspronklike RGN-bevindinge in oënskou, terwyl sosiale en sielkundige faktore in post-apartheid Suid-Afrika, wat ook 'n impak hierop kan hê, ondersoek word. 'n Sosiaal-konstruksionistiese perspektief is as teoretiese raamwerk vir 'n beter begrip van die breër konteks van hierdie tipe geweld gebruik. Ten slotte word moontlike intervensies voorgestel wat verder as simplistiese verklarings kyk, en eerder op die sosiale verantwoordelikeheid van geestesgesondheidswerkers fokus. Key words: Family murder, Family violence, Violent crime, Mental health care, Psychological services (Health SA Gesondheid: 2003 8(2): 83-91

Cellular Contraction and Polarization Drive Collective Cellular Motion

Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity

Decreased STARD10 expression is associated with defective insulin secretion in humans and mice

Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell

Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues.

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal - "isogonal" - deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit y embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Lepton flavour violation in the MSSM

We derive new constraints on the quantities delta_{XY}^{ij}, X,Y=L,R, which parametrise the flavour-off-diagonal terms of the charged slepton mass matrix in the MSSM. Considering mass and anomalous magnetic moment of the electron we obtain the bound |delta^{13}_{LL} delta^{13}_{RR}|<0.1 for tan beta=50, which involves the poorly constrained element delta^{13}_{RR}. We improve the predictions for the decays tau -> mu gamma, tau -> e gamma and mu -> e gamma by including two-loop corrections which are enhanced if tan beta is large. The finite renormalisation of the PMNS matrix from soft SUSY-breaking terms is derived and applied to the charged-Higgs-lepton vertex. We find that the experimental bound on BR(tau -> e gamma) severely limits the size of the MSSM loop correction to the PMNS element U_{e3}, which is important for the proper interpretation of a future U_{e3} measurement. Subsequently we confront our new values for delta^{ij}_{LL} with a GUT analysis. Further, we include the effects of dimension-5 Yukawa terms, which are needed to fix the Yukawa unification of the first two generations. If universal supersymmetry breaking occurs above the GUT scale, we find the flavour structure of the dimension-5 Yukawa couplings tightly constrained by mu -> e gamma.Comment: 37 pages, 15 figures; typo in Equation (35) and (49) correcte

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