Alpha 2 macroglobulin activity in rats infected with Trypanosoma lewisi and treated with cyclophosphamide and its effect on the malignancy of the disease

Background & objectives: Trypanosoma lewisi is a common, flagellated parasite of the rat. Ourprevious study showed that rabbits injected with serum collected from rats infected with Trypanosomalewisi and treated with cyclophosphamide (CyI) produced high levels of antibodies against a newprotein in the CyI rat serum.Results: In the present study, this protein was characterised as α2 macroglobulin (α2M) and thekinetics of its production and its influence on the malignancy of the disease were determined. In ratsinfected with T. lewisi, α2M was first demonstrated and peaked on the second day post-infection(972 μg/ml) and then reduced gradually, reaching a level of 32 μg/ml on the eighth day post-infection.However, in the CyI rats the level of α2M was gradually increased as the disease progressed,reaching a level of 890 μg/ml on the eighth day post-infection. Injection of both crude and purifiedα2M into rats infected with T. lewisi led to increased parasitaemia.Interpretation & conclusion: The present study suggests that increased levels of α2M in the CyI ratscontribute to the malignancy of the disease

A multidimensional systems biology analysis of cellular senescence in aging and disease.

BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence

Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system–based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases

A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

<p>Abstract</p> <p>Background</p> <p>The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes), for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties.</p> <p>Results</p> <p>The main patterns discovered by the classification methods are as follows: (a) the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b) the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO) annotations; (c) GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d) interaction with the XRCC5 (Ku80) protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e) DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related.</p> <p>Conclusions</p> <p>The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.</p

A genetic analysis of nitric oxide-mediated signaling during chronological aging in the yeast

In mammals, NO•, a signaling molecule is implicated in the regulation of vasodilation, neurotransmission and immune response. It is believed that NO• is a signaling molecule also in unicellular organism like yeast and may be involved in the regulation of apoptosis and sporulation. It has been reported that NO• is produced during chronological aging (CA) leading to an increase of the superoxide level, which in turn mediates apoptosis. Since this conclusion was based on indirect measurements of NO• by the Griess reaction, the role of NO• signaling during CA in the yeast remains uncertain. We investigated this issue more precisely using different genetic and biochemical methodologies. We used cells lacking the factors influencing nitrosative stress response like flavohemoglobin metabolizing NO•, S-nitrosoglutathione reductase metabolizing S-nitrosoglutathione and the transcription factor Fzf1p mediating NO• response. We measured the standard parameters describing CA and found an elevation in the superoxide level, percentage of death cells, the level of TUNEL positive cells and a decrease in proliferating potential. These observations showed no significant differences between wild type cells and the disruptants except for a small elevation of the superoxide level in the Δsfa1 mutant. The intracellular NO• level and flavohemoglobin expression decreased rather than increased during CA. Products of general nitrogen metabolism and protein tyrosine nitration were slightly decreased during CA, the magnitude of changes showing no differences between the wild type and the mutant yeast. Altogether, our data indicate that apoptosis during yeast CA is mediated by superoxide signaling rather than NO• signaling

ECOLOGICAL AND MICROTOPOGRAPHICAL IMPACT OF MESSOR EBENINUS AND MESSOR ARENARIUS ANTS ON ARID LOESS RANGELANDS OF THE NORTHERN NEGEV

Improper land management, such as over-grazing in arid areas, has negative effects on the local ecosystems for both the short and the long term time periods. An effective rehabilitation scheme requires human interference by introducing ecosystem engineering organisms together with activities that encourage the spreading and the reproduction of the local plant and animal species. Most of the former studies in arid lands focused on shrubs as engineering species, and much less on other organisms. The major focus of this study was on assessing the impact of Messor ebeninus and M. arenarius on the micro-topographic patterns of arid areas using unique spatial statistical tools designed solely for this purpose. As a case study, the nests’ sizes and their distribution were compared between two adjacent shrublands with similar geographic outlines during 2008 and 2015.One of the shrublands was moderately grazed for the last 20 years (at the far past it was exposed to over-grazing), while the other one is still exposed to over-grazing. The results collected in 2014 at the shrublands and at the adjacent loess area demonstrate the spatial ecosystem ability of the Messor sp. to engineer and beneficially modify their environment by enlarging the water conserving area, increasing the soil fertility and vegetative productivity, and finally accelerating the whole area rehabilitation

High accuracy calibration and use of power analysers for measurement of solid-state lighting devices

One of the key parameters in the photometry of solid-state lighting is the measurement of the luminous efficacy of the device under test. This parameter requires not only accurate photometric measurements, but also accurate measurement of the electrical parameters of the device. It has become apparent that high-accuracy electrical measurements of lighting devices and solid-state lighting devices, in particular, are subject to much greater errors when the current waveform departs from a pure sinusoidal waveform. Key aspects influencing this are the calibration of the power analyser used for the measurement and the wiring arrangement used during the measurement. This paper describes a method of waveform-specific calibration for power analysers, and a simple, common error used in the wiring setup, which can result in significant errors