Flow-distributed spikes for Schnakenberg kinetics

This is the post-print version of the final published paper. The final publication is available at link.springer.com by following the link below. Copyright @ 2011 Springer-Verlag.We study a system of reaction–diffusion–convection equations which combine a reaction–diffusion system with Schnakenberg kinetics and the convective flow equations. It serves as a simple model for flow-distributed pattern formation. We show how the choice of boundary conditions and the size of the flow influence the positions of the emerging spiky patterns and give conditions when they are shifted to the right or to the left. Further, we analyze the shape and prove the stability of the spikes. This paper is the first providing a rigorous analysis of spiky patterns for reaction-diffusion systems coupled with convective flow. The importance of these results for biological applications, in particular the formation of left–right asymmetry in the mouse, is indicated.RGC of Hong Kon

Transplanting intact donor tissue enhances dopamine cell survival and the predictability of motor improvements in a rat model of Parkinson's disease

Primary cell transplantation is currently the gold standard for cell replacement in Parkinson's disease. However, the number of donors needed to treat a single patient is high, and the functional outcome is sometimes variable. The present work explores the possibility of enhancing the viability and/or functionality of small amounts of ventral mesencephalic (VM) donor tissue by reducing its perturbation during preparation and implantation. Briefly, unilaterally lesioned rats received either: (1) an intact piece of half an embryonic day 13 (E13) rat VM; (2) dissociated cells from half an E13 rat VM; or (3) no transplant. D-amphetamine- induced rotations revealed that animals receiving pieces of VM tissue or dissociated cells showed significant improvement in ipsilateral rotation 4 weeks post transplantation. By 6 weeks post transplantation, animals receiving pieces of VM tissue showed a trend for further improvement, while those receiving dissociated cells remained at their 4 week scores. Postmortem cell counts showed that the number of dopaminergic neurons in dissociated cell transplants was significantly lower than that surviving in transplants of intact tissue. When assessing the correlation between the number of dopamine cells in each transplant, and the improvement in rotation bias in experimental animals, it was shown that transplants of whole pieces of VM tissue offered greater predictability of graft function based on their dopamine cell content. Such results suggest that maintaining the integrity of VM tissue during implantation improves dopamine cell content, and that the dopamine cell content of whole tissue grafts offers a more predictable outcome of graft function in an animal model of Parkinson's disease

ciliaFA : a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software

Background: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. Methods: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. Results: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. Conclusions: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use

The potential roles of hepatocyte growth factor (HGF)-MET pathway inhibitors in cancer treatment

MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepa-tocyte growth factor (HGF) receptor, a member of the receptor tyrosine kinase (RTK) family. HGF, also known as scatter factor (SF), is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis), mobility (motogenesis), and differentiation (morphogenesis); it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development. © 2014 Parikh et al

Functional analysis of altered Tenascin isoform expression in breast cancer

Background: Cellular interactions with the extracellular matrix (ECM) control many aspects of cell function. The complex ECM protein Tenascin-C (TN), which exists as multiple isoforms, is upregulated in breast cancer. We previously have identified a change in the TN isoform profile in breast cancer, with detection of two additional isoforms — TN16 and TN14/16 — not seen in normal breast [1]. The purpose of this study was to investigate directly the effects of these tumour-associated TNC isoforms on breast cancer cell behaviour

Arthroscopic treatment of a medial meniscal cyst using a posterior trans-septal approach: a case report

Arthroscopic partial menisectomy followed by cyst decompression is currently recommended for treatment of a meniscal cyst. However, it is doubtful whether partial menisectomy should be performed on cysts communicating with the joint in cases without a meniscal tear on its surface since meniscal function will be sacrificed. In this report, a meniscal cyst arising from the posterior horn of the medial meniscus without meniscal tear on its surface was resected using an arthroscopic posterior trans-septal approach. A 59 year-old male presented to our hospital with popliteal pain when standing up after squatting down. Magnetic resonance imaging revealed a multilobulated meniscal cyst arising from the posterior horn of the medial meniscus extending to the posterior septum with a grade 2 meniscal tear by Mink's classification. The medial meniscus was intact on the surface on arthroscopic examination. The meniscal cyst and posterior septum were successfully resected using a posterior trans-septal approach without harming the meniscus. This is the first report on a meniscal cyst being resected using an arthroscopic posterior trans-septal approach with a 9-month follow-up period

GABAergic neurons comprise a major cell type in rodent visual relay nuclei: an immunocytochemical study of pretectal and accessory optic nuclei.

The enzyme glutamic acid decarboxylase (GAD) has been localized in sections of rodent brains (gerbil, rat) using conventional immunocytochemical techniques. Our findings demonstrate that large numbers of GAD-positive neurons and axon terminals (puncta) are present in the visual relay nuclei of the pretectum and the accessory optic system. The areas of highest density of these neurons are in the nucleus of the optic tract (NOT) of the pretectum, the dorsal and lateral terminal accessory optic nuclei (DTN, LTN), the ventral and dorsal subdivisions of the medial terminal accessory optic nucleus (MTNv, MTNd), and the interstitial nucleus of the posterior fibers of the superior fasciculus (inSFp). The findings indicate that 27% of the NOT neurons are GAD-positive and that these neurons are distributed over all of the NOT except the most superficial portion of the NOT caudally. The GAD-positive neurons of the NOT are statistically smaller (65.9 microns2) than the total population of neurons of the NOT (84.3 microns2) but are otherwise indistinguishable in shape from the total neuron population. The other visual relay nuclei that have been analyzed (DTN, LTN, MTNv, MTNd, inSFp) are similar in that from 21% to 31% of their neurons are GAD-positive; these neurons are smaller in diameter and are more spherical than the total populations of neurons. The data further show that a large proportion of the neurons in these visual relay nuclei are contacted by GAD-positive axon terminals. It is estimated that approximately one-half of the neurons of the NOT and the terminal accessory optic nuclei receive a strong GABAergic input and have been called "GAD-recipient neurons". Further, the morphology of the GAD-positive neurons combined with their similar distribution to the GAD-recipient neurons suggest that many of these neurons are acting as GABAergic, local circuit neurons. On the other hand, the large number of GAD-positive neurons in the NOT and MTN (20-30%) in relation to estimates of projection neurons (75%) presents the possibility that some may in fact be projection neurons. The overall findings provide morphological evidence which supports the general conclusion that GABAergic neurons play a significant role in modulating the output of the visually related NOT and terminal accessory optic nuclei

Factorizations of Elements in Noncommutative Rings: A Survey

We survey results on factorizations of non zero-divisors into atoms (irreducible elements) in noncommutative rings. The point of view in this survey is motivated by the commutative theory of non-unique factorizations. Topics covered include unique factorization up to order and similarity, 2-firs, and modular LCM domains, as well as UFRs and UFDs in the sense of Chatters and Jordan and generalizations thereof. We recall arithmetical invariants for the study of non-unique factorizations, and give transfer results for arithmetical invariants in matrix rings, rings of triangular matrices, and classical maximal orders as well as classical hereditary orders in central simple algebras over global fields.Comment: 50 pages, comments welcom

The Extremes of Thermonuclear Supernovae

The majority of thermonuclear explosions in the Universe seem to proceed in a rather standardised way, as explosions of carbon-oxygen (CO) white dwarfs in binary systems, leading to 'normal' Type Ia supernovae (SNe Ia). However, over the years a number of objects have been found which deviate from normal SNe Ia in their observational properties, and which require different and not seldom more extreme progenitor systems. While the 'traditional' classes of peculiar SNe Ia - luminous '91T-like' and faint '91bg-like' objects - have been known since the early 1990s, other classes of even more unusual transients have only been established 20 years later, fostered by the advent of new wide-field SN surveys such as the Palomar Transient Factory. These include the faint but slowly declining '02es-like' SNe, 'Ca-rich' transients residing in the luminosity gap between classical novae and supernovae, extremely short-lived, fast-declining transients, and the very luminous so-called 'super-Chandrasekhar' SNe Ia. Not all of them are necessarily thermonuclear explosions, but there are good arguments in favour of a thermonuclear origin for most of them. The aim of this chapter is to provide an overview of the zoo of potentially thermonuclear transients, reviewing their observational characteristics and discussing possible explosion scenarios.Comment: Author version of a chapter for the 'Handbook of Supernovae', edited by A. Alsabti and P. Murdin, Springer. 50 pages, 7 figure