Functions of p120ctn isoforms in cell-cell adhesion and intracellular signaling

The functions of many organs depend on the generation of an epithelium. The transition from a set of loosely connected nonpolarized cells to organized sheets of closely associated polarized epithelial cells requires the assembly of specialized cell junctions. In vertebrates, three major types of junctions are responsible for epithelial integrity: adherens junctions, tight junctions, and desmosomes. p120 catenin (p120ctn) is an Armadillo family member and a component of the cadherin-catenin complex in the adherens junction. It fulfils pleiotropic functions according to its subcellular localization: modulating the turnover rate of membrane-bound cadherins, regulating the activation of small RhoGTPases in the cytoplasm, and modulating nuclear transcription. Over the last two decades, knowledge of p120ctn obtained from in vitro experiments has been confirmed and extended by using different animal models. It has become clear that p120ctn is essential for normal development and homeostasis, at least in frog and mammals. p120ctn is a Src substrate that can be phosphorylated at different tyrosine, serine and threonine residues and can dock various kinases and phosphatases. Thereby, p120ctn regulates the phosphorylation status and the junctional stability of the cadherin-catenin complex. Multiple p120ctn isoforms are generated by alternative splicing, which allows the translation to be initiated from four start codons and enables the inclusion of four alternatively used exons. We will discuss the effects of different p120ctn isoforms on cadherin turnover and intracellular signaling, in particular RhoGTPase activity and phosphorylation events

Editorial: Membrane lipids in T cell functions

Plasma membrane lipids play essential roles in regulating T cell signaling, differentiation, and effector functions. The major lipid species in the plasma membrane are glycerophospholipids, sphingolipids, and sterol lipids. TCR and costimulatory molecules lead to profound changes in the composition, distribution, and dynamic of plasma membrane lipids. For instance, cholesterol, sphingomyelin, and saturated phosphocholine are enriched at the contact zone between T cells and antigen-presenting cells during peptide/MHC complexes recognition, where they constitute a platform of lipid domains essential for optimal T cell signaling. Glycerophospholipid provide docking sites for binding pivotal signaling proteins as well as for their conformation, portioning, and mobility. Finally, plasma membrane lipids also act as second messengers with important immune-regulatory functions. This Research Topic contains seven articles that review the current understanding of the mechanisms and molecules involved in the metabolism and function of membrane lipids and how differences in their content may affect T cell functional properties

Proliferation versus Differentiation: Redefining Retinoic Acids Role.

Retinoic acid is commonly used in culture to differentiate stem cells into neurons and has established neural differentiation functions in vivo in developing and adult organisms. In this issue of Stem Cell Reports, Mishra et al. (2018) broaden its role in stem cell functions, showing that retinoic acid is necessary for stem and progenitor cell proliferation in the adult brain

A Nystr\"om-based finite element method on polygonal elements

We consider families of finite elements on polygonal meshes, that are defined implicitly on each mesh cell as solutions of local Poisson problems with polynomial data. Functions in the local space on each mesh cell are evaluated via Nystr\"om discretizations of associated integral equations, allowing for curvilinear polygons and non-polynomial boundary data. Several experiments demonstrate the approximation quality of interpolated functions in these spaces

Structure and functions of fungal cell surfaces

A review with 24 references on the biochemistry, molecular structure, and function of cell surfaces of fungi, especially dermatophytes: the chemistry and structure of the cell wall, the effect of polyene antibiotics on the morphology and function of cytoplasmic membranes, and the chemical structure and function of pigments produced by various fungi are discussed

A versatile sensor interface for programmable vision systems-on-chip

This paper describes an optical sensor interface designed for a programmable mixed-signal vision chip. This chip has been designed and manufactured in a standard 0.35μm n-well CMOS technology with one poly layer and five metal layers. It contains a digital shell for control and data interchange, and a central array of 128 × 128 identical cells, each cell corresponding to a pixel. Die size is 11.885 × 12.230mm2 and cell size is 75.7μm × 73.3μm. Each cell contains 198 transistors dedicated to functions like processing, storage, and sensing. The system is oriented to real-time, single-chip image acquisition and processing. Since each pixel performs the basic functions of sensing, processing and storage, data transferences are fully parallel (image-wide). The programmability of the processing functions enables the realization of complex image processing functions based on the sequential application of simpler operations. This paper provides a general overview of the system architecture and functionality, with special emphasis on the optical interface.European Commission IST-1999-19007Office of Naval Research (USA) N00014021088

Towards visualisation of central-cell-effects in scanning-tunnelling-microscope images of subsurface dopant qubits in silicon

Atomic-scale understanding of phosphorous donor wave functions underpins the design and optimisation of silicon based quantum devices. The accuracy of large-scale theoretical methods to compute donor wave functions is dependent on descriptions of central-cell-corrections, which are empirically fitted to match experimental binding energies, or other quantities associated with the global properties of the wave function. Direct approaches to understanding such effects in donor wave functions are of great interest. Here, we apply a comprehensive atomistic theoretical framework to compute scanning tunnelling microscopy (STM) images of subsurface donor wave functions with two central-cell-correction formalisms previously employed in the literature. The comparison between central-cell models based on real-space image features and the Fourier transform profiles indicate that the central-cell effects are visible in the simulated STM images up to ten monolayers below the silicon surface. Our study motivates a future experimental investigation of the central-cell effects via STM imaging technique with potential of fine tuning theoretical models, which could play a vital role in the design of donor-based quantum systems in scalable quantum computer architectures.Comment: Nanoscale 201

Intertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death.

Timely sister chromatid separation, promoted by separase, is essential for faithful chromosome segregation. Separase is a member of the CD clan of cysteine proteases, which also includes the pro-apoptotic enzymes known as caspases. We report a role for the C. elegans separase SEP-1, primarily known for its essential activity in cell division and cortical granule exocytosis, in developmentally programmed cell death when the predominant pro-apoptotic caspase CED-3 is compromised. Loss of SEP-1 results in extra surviving cells in a weak ced-3(-) mutant, and suppresses the embryonic lethality of a mutant defective for the apoptotic suppressor ced-9/Bcl-2 implicating SEP-1 in execution of apoptosis. We also report apparent non-apoptotic roles for CED-3 in promoting germ cell proliferation, meiotic chromosome disjunction, egg shell formation, and the normal rate of embryonic development. Moreover, loss of the soma-specific (CSP-3) and germline-specific (CSP-2) caspase inhibitors result in CED-3-dependent suppression of embryonic lethality and meiotic chromosome non-disjunction respectively, when separase function is compromised. Thus, while caspases and separases have evolved different substrate specificities associated with their specialized functions in apoptosis and cell division respectively, they appear to have retained the residual ability to participate in both processes, supporting the view that co-option of components in cell division may have led to the innovation of programmed cell suicide early in metazoan evolution

FHL2 regulates hematopoietic stem cell functions under stress conditions.

FHL2, a member of the four and one half LIM domain protein family, is a critical transcriptional modulator. Here, we identify FHL2 as a critical regulator of hematopoietic stem cells (HSCs) that is essential for maintaining HSC self-renewal under regenerative stress. We find that Fhl2 loss has limited effects on hematopoiesis under homeostatic conditions. In contrast, Fhl2-null chimeric mice reconstituted with Fhl2-null bone marrow cells developed abnormal hematopoiesis with significantly reduced numbers of HSCs, hematopoietic progenitor cells (HPCs), red blood cells and platelets as well as hemoglobin levels. In addition, HSCs displayed a significantly reduced self-renewal capacity and were skewed toward myeloid lineage differentiation. We find that Fhl2 loss reduces both HSC quiescence and survival in response to regenerative stress, probably as a consequence of Fhl2-loss-mediated downregulation of cyclin-dependent kinase-inhibitors, including p21(Cip) and p27(Kip1). Interestingly, FHL2 is regulated under the control of a tissue-specific promoter in hematopoietic cells and it is downregulated by DNA hypermethylation in the leukemia cell line and primary leukemia cells. Furthermore, we find that downregulation of FHL2 frequently occurs in myelodysplastic syndrome and acute myeloid leukemia patients, raising a possibility that FHL2 downregulation has a role in the pathogenesis of myeloid malignancies

Tracking Cell Signals in Fluorescent Images

In this paper we present the techniques for tracking cell signal in GFP (Green Fluorescent Protein) images of growing cell colonies. We use such tracking for both data extraction and dynamic modeling of intracellular processes. The techniques are based on optimization of energy functions, which simultaneously determines cell correspondences, while estimating the mapping functions. In addition to spatial mappings such as affine and Thin-Plate Spline mapping, the cell growth and cell division histories must be estimated as well. Different levels of joint optimization are discussed. The most unusual tracking feature addressed in this paper is the possibility of one-to-two correspondences caused by cell division. A novel extended softassign algorithm for solutions of one-to-many correspondences is detailed in this paper. The techniques are demonstrated on three sets of data: growing bacillus Subtillus and e-coli colonies and a developing plant shoot apical meristem. The techniques are currently used by biologists for data extraction and hypothesis formation