Understanding cisplatin resistance using cellular models

Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF-CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7-fold with a treatment dose of 1.6 microg/ml. Cisplatin resistance in these cells correlated with increases in the antioxidant glutathione, yet treatment with buthionine sulphoximine, an inhibitor of glutathione synthesis, had no effect on resistance, suggesting that the increase in glutathione was not directly involved in cisplatin resistance. Two models were developed from H69 SCLC cells, H69-CP and H69CIS200 using 100 ng/ml or 200 ng/ml cisplatin respectively. Both cell models were 2-4 fold resistant to cisplatin, and have decreased expression of p21 which may increase the cell's ability to progress through the cell cycle in the presence of DNA damage. Both the H69-CP and H69CIS200 cells showed no decrease in cellular cisplatin accumulation. However, the H69-CP cells have increased levels of cellular glutathione and are cross resistant to radiation whereas the H69CIS200 cells have neither of these changes. This suggests that increases in glutathione may contribute to cross-resistance to other drugs and radiation, but not directly to cisplatin resistance. There are multiple resistance mechanisms induced by cisplatin treatment, even in the same cell type. How then should cisplatin-resistant cancers be treated? Cisplatin-resistant cell lines are often more sensitive to another chemotherapeutic drug paclitaxel (H69CIS200), or are able to be sensitized to cisplatin with paclitaxel pre-treatment (H69-CP). The understanding of this sensitization by paclitaxel using cell models of cisplatin resistance will lead to improvements in the clinical treatment of cisplatin resistant tumours

Reducing the risk of cardiovascular disease in older women

Cardiovascular disease (CVD) is the leading cause of death in women older than 50 years. Risk factors for CVD differ in some aspects from those in men. The prevention of CVD in women has undergone a reappraisal with the publication of studies looking at the use of menopausal hormone therapy for both primary and secondary prevention. Although these studies concluded that there was no place for the use of hormone therapy for prevention of CVD, recent data suggests that the issue is still not resolved as regards the younger woman in early menopause. Until more data is available in this regard, the main focus of prevention should be on interventions to decrease risk factors for cardiovascular disease. South African Family Practice Vol. 49 (5) 2007: pp. 32-3

Evolving spiking neural networks for temporal pattern recognition in the presence of noise

Creative Commons - Attribution-NonCommercial-NoDerivs 3.0 United StatesNervous systems of biological organisms use temporal patterns of spikes to encode sensory input, but the mechanisms that underlie the recognition of such patterns are unclear. In the present work, we explore how networks of spiking neurons can be evolved to recognize temporal input patterns without being able to adjust signal conduction delays. We evolve the networks with GReaNs, an artificial life platform that encodes the topology of the network (and the weights of connections) in a fashion inspired by the encoding of gene regulatory networks in biological genomes. The number of computational nodes or connections is not limited in GReaNs, but here we limit the size of the networks to analyze the functioning of the networks and the effect of network size on the evolvability of robustness to noise. Our results show that even very small networks of spiking neurons can perform temporal pattern recognition in the presence of input noiseFinal Published versio

The Coronal Analysis of SHocks and Waves (CASHeW) Framework

Coronal Bright Fronts (CBF) are large-scale wavelike disturbances in the solar corona, related to solar eruptions. They are observed in extreme ultraviolet (EUV) light as transient bright fronts of finite width, propagating away from the eruption source. Recent studies of individual solar eruptive events have used EUV observations of CBFs and metric radio type II burst observations to show the intimate connection between low coronal waves and coronal mass ejection (CME)-driven shocks. EUV imaging with the Atmospheric Imaging Assembly(AIA) instrument on the Solar Dynamics Observatory (SDO) has proven particularly useful for detecting CBFs, which, combined with radio and in situ observations, holds great promise for early CME-driven shock characterization capability. This characterization can further be automated, and related to models of particle acceleration to produce estimates of particle fluxes in the corona and in the near Earth environment early in events. We present a framework for the Coronal Analysis of SHocks and Waves (CASHeW). It combines analysis of NASA Heliophysics System Observatory data products and relevant data-driven models, into an automated system for the characterization of off-limb coronal waves and shocks and the evaluation of their capability to accelerate solar energetic particles (SEPs). The system utilizes EUV observations and models written in the Interactive Data Language (IDL). In addition, it leverages analysis tools from the SolarSoft package of libraries, as well as third party libraries. We have tested the CASHeW framework on a representative list of coronal bright front events. Here we present its features, as well as initial results. With this framework, we hope to contribute to the overall understanding of coronal shock waves, their importance for energetic particle acceleration, as well as to the better ability to forecast SEP events fluxes.Comment: Accepted for publication in the Journal of Space Weather and Space Climate (SWSC

The Isolation and Purification of a Fluorescent Compound from Pseudomonas

Fluorescence in certain land snails has been found to arise from a bacteria carried by the snails. The bacteria, a genus of Pseudomonas, produce a pigment complex in iron-deficient media. The pigment complex consists of both fluorescent and non-fluorescent pigments. One of the fluorescent compounds was isolated and purified by paper chromatography using several different solvent systems. Absorption and fluorescent spectra of the compound at a number of pH values were measured and the changes with pH of both the intensity and the color of the fluorescence were observed. The purified compound was ninhydrin negative but after acid hydrolysis several amino acids were identified and were thought to occur in peptide bonds. The amino acids identified were: serine, glutamic acids, aspartic acid, cystine, threonine, lysine, and alanine. A comparison with other fluorescent compounds isolated from the Pseudomonas pigment complex showed the compound to be one which had not been previously isolated. Suggestions on a more efficient method of purification and precautions necessary during isolation are given

The Isolation and Purification of a Fluorescent Compound from Pseudomonas

Fluorescence in certain land snails has been found to arise from a bacteria carried by the snails. The bacteria, a genus of Pseudomonas, produce a pigment complex in iron-deficient media. The pigment complex consists of both fluorescent and non-fluorescent pigments. One of the fluorescent compounds was isolated and purified by paper chromatography using several different solvent systems. Absorption and fluorescent spectra of the compound at a number of pH values were measured and the changes with pH of both the intensity and the color of the fluorescence were observed. The purified compound was ninhydrin negative but after acid hydrolysis several amino acids were identified and were thought to occur in peptide bonds. The amino acids identified were: serine, glutamic acids, aspartic acid, cystine, threonine, lysine, and alanine. A comparison with other fluorescent compounds isolated from the Pseudomonas pigment complex showed the compound to be one which had not been previously isolated. Suggestions on a more efficient method of purification and precautions necessary during isolation are given

Information theoretical analysis of differences in information transmission in cerebellar Purkinje cells across species

Abstract from the 23rd Annual Computational Neuroscience Meeting CNS 2014. © 2014 Kidd et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThe dendrite of the cerebellar Purkinje cell is one of the most complex structures in the mammalian brain, receiving more than 150,000 synaptic inputs. It is also one of the most extensively modelled neurons in the mammalian brain, with theoretical analysis of the input-output relationships in its dendrite extending back 40 years. While most of this experimental and modelling work has been conducted using mammalian neurons, it has also often been noted that overall cerebellar structure as well as the general morphology of Purkinje cells has been highly conserved in all vertebrate species. The work described here seeks to identify conserved features of Purkinje cell function by examining the relationship between structure and function in a range of vertebrate species from fish to mammalsPeer reviewedFinal Published versio