Non-synonymous single nucleotide polymorphisms in the P2X receptor genes: Association with diseases, impact on receptor functions and potential use as diagnosis biomarkers

P2X receptors are Ca2+-permeable cationic channels in the cell membranes, where they play an important role in mediating a diversity of physiological and pathophysiological functions of extracellular ATP. Mammalian cells express seven P2X receptor genes. Single nucleotide polymorphisms (SNPs) are widespread in the P2RX genes encoding the human P2X receptors, particularly the human P2X7 receptor. This article will provide anoverview of the non-synonymous SNPs (NS-SNPs) that have been associated with or implicated in altering the susceptibility to pathologies or disease conditions, and discuss the consequences of the mutations resulting from such NS-SNPs on the receptor functions. Disease-associated NS-SNPs in the P2RXgenes have been valuable in understanding the disease etiology and the receptor function, and are promising as biomarkers to be used for the diagnosis and development of stratified therapeutics. © 2014 by the authors; licensee MDPI, Basel, Switzerland

Fast automatic quantitative cell replication with fluorescent live cell imaging

Hoffmann N, Keck M, Neuweger H, et al. Combining peak- and chromatogram-based retention time alignment algorithms for multiple chromatography-mass spectrometry datasets. BMC Bioinformatics. 2012;13(1): 21.Background Modern analytical methods in biology and chemistry use separation techniques coupled to sensitive detectors, such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These hyphenated methods provide high-dimensional data. Comparing such data manually to find corresponding signals is a laborious task, as each experiment usually consists of thousands of individual scans, each containing hundreds or even thousands of distinct signals. In order to allow for successful identification of metabolites or proteins within such data, especially in the context of metabolomics and proteomics, an accurate alignment and matching of corresponding features between two or more experiments is required. Such a matching algorithm should capture fluctuations in the chromatographic system which lead to non-linear distortions on the time axis, as well as systematic changes in recorded intensities. Many different algorithms for the retention time alignment of GC-MS and LC-MS data have been proposed and published, but all of them focus either on aligning previously extracted peak features or on aligning and comparing the complete raw data containing all available features. Results In this paper we introduce two algorithms for retention time alignment of multiple GC-MS datasets: multiple alignment by bidirectional best hits peak assignment and cluster extension (BIPACE) and center-star multiple alignment by pairwise partitioned dynamic time warping (CEMAPP-DTW). We show how the similarity-based peak group matching method BIPACE may be used for multiple alignment calculation individually and how it can be used as a preprocessing step for the pairwise alignments performed by CEMAPP-DTW. We evaluate the algorithms individually and in combination on a previously published small GC-MS dataset studying the Leishmania parasite and on a larger GC-MS dataset studying grains of wheat (Triticum aestivum). Conclusions We have shown that BIPACE achieves very high precision and recall and a very low number of false positive peak assignments on both evaluation datasets. CEMAPP-DTW finds a high number of true positives when executed on its own, but achieves even better results when BIPACE is used to constrain its search space. The source code of both algorithms is included in the OpenSource software framework Maltcms, which is available from http://maltcms.sf.net webcite. The evaluation scripts of the present study are available from the same source

Belonging, social connection and non-clinical care: Experiences of HIV peer support among recently diagnosed people living with HIV in Australia

Effective HIV treatments have transformed the medical needs of people living with HIV (PLHIV) to a chronic condition. However, stigma, poorer mental health outcomes and social isolation remain significant challenges for many PLHIV. HIV peer support programs have assisted PLHIV in navigating the clinical, emotional and social aspects of living with HIV. We draw on semi-structured interviews with 26 recently diagnosed PLHIV in Australia to explore experiences of HIV peer support services. Our thematic analysis identified three overarching themes. First, participants commonly reported that peer support programs offered a sense of belonging and connection to a broader HIV community. This established a network, sometimes separate to their existing social networks, of other PLHIV with whom to share experiences of HIV. Second, peer-based programs provided an opportunity for participants to hear firsthand, non-clinical perspectives on living with HIV. While participants valued the clinical care they received, the perspectives of peers gave participants insights into how others had managed aspects of living with HIV such as disclosure, sex and relationships. Finally, participants highlighted important considerations around ensuring referrals were made to socially and culturally appropriate support programs. Peer support programs fill an important gap in HIV care, working alongside and extending the work of the clinical management of HIV. Incorporating formal referrals to peer support services as part of the HIV diagnosis process could assist recently diagnosed PLHIV in adjusting to a positive diagnosis

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Modeling Checkpoint-Based Movement with the Earth Mover's Distance

Movement data comes in various forms, including trajectory data and checkpoint data. While trajectories give detailed information about the movement of individual entities, checkpoint data in its simplest form does not give identities, just counts at checkpoints. However, checkpoint data is of increasing interest since it is readily available due to privacy reasons and as a by-product of other data collection. In this paper we propose to use the Earth Mover’s Distance as a versatile tool to reconstruct individual movements or flow based on checkpoint counts at different times. We analyze the modeling possibilities and provide experiments that validate model predictions, based on coarse-grained aggregations of data about actual movements of couriers in London, UK. While we cannot expect to reconstruct precise individual movements from highly granular checkpoint data, the evaluation does show that the approach can generate meaningful estimates of object movements. B. Speckmann and K. Verbeek are supported by the Netherlands Organisation for Scientific Research (NWO) under project nos. 639.023.208 and 639.021.541, respectively. This paper arose from work initiated at Dagstuhl seminar 12512 “Representation, analysis and visualization of moving objects”, December 2012. The authors gratefully acknowledge Schloss Dagstuhl for their support

Thermodynamics of deformed AdS5_5 model with a positive/negative quadratic correction in graviton-dilaton system

By solving the Einstein equations of the graviton coupling with a real scalar dilaton field, we establish a general framework to self-consistently solve the geometric background with black-hole for any given phenomenological holographic models. In this framwork, we solve the black-hole background, the corresponding dilaon field and the dilaton potential for the deformed AdS$_5$ model with a positive/negative quadratic correction. We systematically investigate the thermodynamical properties of the deformed AdS$_5$ model with a positive and negative quadratic correction, respectively, and compare with lattice QCD on the results of the equation of state, the heavy quark potential, the Polyakov loop and the spatial Wilson loop. We find that the bulk thermodynamical properties are not sensitive to the sign of the quadratic correction, and the results of both deformed holographic QCD models agree well with lattice QCD result for pure SU(3) gauge theory. However, the results from loop operators favor a positive quadratic correction, which agree well with lattice QCD result. Especially, the result from the Polyakov loop excludes the model with a negative quadratic correction in the warp factor of ${\rm AdS}_5$.Comment: 26 figures,36 pages,V.3: an appendix,more equations and references added,figures corrected,published versio

Evolutionary Map of the Universe: Tracing Clusters to High Redshift

The Australian SKA Pathfinder (ASKAP) is a new radio-telescope being built in Western Australia. One of the key surveys for which it is being built is EMU (Evolutionary Map of the Universe), which will make a deep (~10 {\mu}Jy/bm rms) radio continuum survey covering the entire sky as far North as +30\circ. EMU may be compared to the NRAO VLA Sky Survey (NVSS), except that it will have about 45 times the sensitivity, and five times the resolution. EMU will also have much better sensitivity to diffuse emission than previous large surveys, and is expected to produce a large catalogue of relics, tailed galaxies, and haloes, and will increase the number of known clusters by a significant factor. Here we describe the EMU project and its impact on the astrophysics of clusters.Comment: Accepted by J. Astrophys. Ast

Quantifying Morphological Evolution from Low to High Redshifts

Establishing the morphological history of ordinary galaxies was one of the original goals for the Hubble Space Telescope, and remarkable progress toward achieving this this goal has been made. How much of this progress has been at the expense of the Hubble sequence? As we probe further out in redshift space, it seems time to re-examine the underlying significance of Hubble's tuning fork in light of the the spectacular and often bizarre morphological characteristics of high redshift galaxies. The aim of this review is to build a morphological bridge between high-redshift and low-redshift galaxy populations, by using quantitative morphological measures to determine the maximum redshift for which the Hubble sequence provides a meaningful description of the galaxy population. I will outline the various techniques used to quantify high-redshift galaxy morphology, highlight the aspects of the Hubble sequence being probed by these techniques, and indicate what is getting left behind. I will argue that at higher redshifts new techniques (and new ideas) that place less emphasis on classical morphology and more emphasis on the link between morphology and resolved stellar populations are needed in order to probe the evolutionary history of high-redshift galaxies

Parameters influencing the size of chitosan-TPP nano- and microparticles

Chitosan nanoparticles, produced by ionic gelation, are among the most intensely studied nanosystems for drug delivery. However, a lack of inter-laboratory reproducibility and a poor physicochemical understanding of the process of particle formation have been slowing their potential market applications. To address these shortcomings, the current study presents a systematic analysis of the main polymer factors affecting the nanoparticle formation driven by an initial screening using systematic statistical Design of Experiments (DoE). In summary, we found that for a given chitosan to TPP molar ratio, the average hydrodynamic diameter of the particles formed is strongly dependent on the initial chitosan concentration. The degree of acetylation of the chitosan was found to be the second most important factor involved in the system's ability to form particles. Interestingly, viscosimetry studies indicated that the particle formation and the average hydrodynamic diameter of the particles formed were highly dependent on the presence or absence of salts in the medium. In conclusion, we found that by controlling two simple factors of the polymer solution, namely its initial concentration and its solvent environment, it is feasible to control in a reproducible manner the production and characteristics of chitosan particles ranging in size from nano- to micrometres

Targeting DNA-PKcs and ATM with miR-101 Sensitizes Tumors to Radiation

Radiotherapy kills tumor-cells by inducing DNA double strand breaks (DSBs). However, the efficient repair of tumors frequently prevents successful treatment. Therefore, identifying new practical sensitizers is an essential step towards successful radiotherapy. In this study, we tested the new hypothesis: identifying the miRNAs to target DNA DSB repair genes could be a new way for sensitizing tumors to ionizing radiation.HERE, WE CHOSE TWO GENES: DNA-PKcs (an essential factor for non-homologous end-joining repair) and ATM (an important checkpoint regulator for promoting homologous recombination repair) as the targets to search their regulating miRNAs. By combining the database search and the bench work, we picked out miR-101. We identified that miR-101 could efficiently target DNA-PKcs and ATM via binding to the 3'- UTR of DNA-PKcs or ATM mRNA. Up-regulating miR-101 efficiently reduced the protein levels of DNA-PKcs and ATM in these tumor cells and most importantly, sensitized the tumor cells to radiation in vitro and in vivo.These data demonstrate for the first time that miRNAs could be used to target DNA repair genes and thus sensitize tumors to radiation. These results provide a new way for improving tumor radiotherapy