A Computational Study of the Development of Epithelial Acini: I. Sufficient Conditions for the Formation of a Hollow Structure

Normal hollow epithelial acini are 3-dimensional culture structures that resemble the architecture and functions of normal breast glands and lobules. This experimental model enables in vitro investigations of genotypic and molecular abnormalities associated with epithelial cancers. However, the way in which the acinar structure is formed is not yet completely understood. Gaining more information about consecutive stages of acini development—starting from a single cell that gives rise to a cluster of randomly oriented cells, followed by cell differentiation that leads to a layer of polarised cells enclosing the hollow lumen—will provide insight into the transformations of eukaryotic cells that are necessary for their successful arrangement into an epithelium. In this paper, we introduce a two-dimensional single-cell-based model representing the cross section of a typical acinus. Using this model, we investigate mechanisms that lead to the unpolarised cell growth, cell polarisation, stabilisation of the acinar structure and maintenance of the hollow lumen and discuss the sufficient conditions for each stage of acinar formation. In the follow-up paper (Rejniak and Anderson, A computational study of the development of epithelial acini. II. Necessary conditions for structure and lumen stability), we investigate what morphological changes are observable in the growing acini when some assumptions of this model are relaxed.     

Comparison of techniques for the assessment of polymorphonuclear leukocyte polarisation in suspension

Summry— Polarisation of polymorphonuclear leukocytes (PMN) is suspension was assessed using three techniques: 1) visual classification; 2) computerized morphometry; and 3) flow cytometry. While visual classification detected the formation, polarisation and type of cytoplasmic extensions produced by PMN, morphometry and flow cytometry detected only the formation of extensions. The area, perimeter and ellipticity were, in general, statistically different for each subtype of PMN-shape identified by visual classification. Furthermore, the magnitude and direction of changes detected by flow cytometry were affected by the use of erythrocyte lysis (during isolation of the cells) and the fixative used prior to analysis. The findings of this study demonstrate that visual classification is a more sensitive, reliable and appropriate assay of PMN polarisation than current morphometric and flow cytometric methods.     

A 'polarisation sun-dial' dictates the optimal time of day for dispersal by flying aquatic insects

1. Daily changes in the flight activity of aquatic insects have been investigated in only a few water beetles and bugs. The diel flight periodicity of aquatic insects and the environmental factors governing it are poorly understood. 2. We found that primary aquatic insects belonging to 99 taxa (78 Coleoptera, 21 Heteroptera) fly predominantly in mid‐morning, and/or around noon and/or at nightfall. There appears to be at least four different types of diurnal flight activity rhythm in aquatic insects, characterised by peak(s): (i) in mid‐morning; (ii) in the evening; (iii) both in mid‐morning and the evening; (iv) around noon and again in the evening. These activity maxima are quite general and cannot be explained exclusively by daily fluctuations of air temperature, humidity, wind speed and risks of predation, which are all somewhat stochastic. 3. We found experimental evidence that the proportion (%) P(θ) of reflecting surfaces detectable polarotactically as ‘water’ is always maximal at the lowest (dawn and dusk) and highest (noon) angles of solar elevation (θ) for dark reflectors while P(θ) is maximal at dawn and dusk (low solar elevations) for bright reflectors under clear or partly cloudy skies. 4. From the temporal coincidence between peaks in the diel flight activity of primary aquatic insects and the polarotactic detectability P(θ) of water surfaces we conclude that the optimal times of day for aquatic insects to disperse are the periods of low and high solar elevations θ. The θ‐dependent reflection–polarisation patterns, combined with an appropriate air temperature, clearly explain why polarotactic aquatic insects disperse to new habitats in mid‐morning, and/or around noon and/or at dusk. We call this phenomenon the ‘polarisation sun‐dial’ of dispersing aquatic insects.     

Daughter B cells are not created equal: Asymmetric segregation of antigen during B cell division

Comment on: Thaunat O, et al. Science 2012; 335:475-9.     

Visfatin aggravates transverse aortic constriction-induced cardiac remodelling by enhancing macrophage-mediated oxidative stress in mice

Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.     

Quantifying structural changes and stoichiometry of protein interactions using size and density profiling

Summary The use of Dual Polarisation Interferometry, and emerging analytical biophysical technique, is described for the determination of the optogeometrical properties (thickness and density) at high resolution of adsorbed protein layers at the solid-liquid interface. The technique has been used to quantify, in real time and at subatomic resolution, the structural changes occurring in two well-characterised protein interaction systems, an antibody-antigen interaction and the biotin-streptavidin interaction. The realtime data obtained on structural changes during the interactions is in excellent agreement with previously reported X-ray crystallography and neutron reflection data. The precision of the measurements taken was of the order of 0.01 nm with respect to protein size. The dual-parameter approach also allowed the stoichiometry of both of these interactions to be calculated, giving values that confirm the current understanding of the interactions. This approach provides detailed insights into the inherent and subtle link between structural change and function in proteins, to a degree not previously possible through mass change measurements alone. The technique is expected to find utility in the increasingly important study of protein structure and function.