ATP-dependent and independent functions of Rad54 in genome maintenance

Rad54’s ATPase activity does not affect accumulation of homologous recombination proteins in repair foci, but influences its dissociation and that of Rad51

Impact of Aspergillus fumigatus in allergic airway diseases

For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA), known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF). The goal of this review is to discuss new understandings of host-pathogen interactions in the genesis of allergic airway diseases caused by A. fumigatus. Host and pathogen related factors that participate in triggering the inflammatory cycle leading to pulmonary exacerbations in ABPA are discussed

Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae?

The purpose of this review-hypothesis is to discuss the literature which had proposed the concept that the mechanisms by which infectious and inflammatory processes induce cell and tissue injury, in vivo, might paradoxically involve a deleterious synergistic ‘cross-talk’, among microbial- and host-derived pro-inflammatory agonists. This argument is based on studies of the mechanisms of tissue damage caused by catalase-negative group A hemolytic streptococci and also on a large body of evidence describing synergistic interactions among a multiplicity of agonists leading to cell and tissue damage in inflammatory and infectious processes. A very rapid cell damage (necrosis), accompanied by the release of large amounts of arachidonic acid and metabolites, could be induced when subtoxic amounts of oxidants (superoxide, oxidants generated by xanthine-xanthine oxidase, HOCl, NO), synergized with subtoxic amounts of a large series of membrane-perforating agents (streptococcal and other bacterial-derived hemolysins, phospholipases A 2 and C, lysophosphatides, cationic proteins, fatty acids, xenobiotics, the attack complex of complement and certain cytokines). Subtoxic amounts of proteinases (elastase, cathepsin G, plasmin, trypsin) very dramatically further enhanced cell damage induced by combinations between oxidants and the membrane perforators. Thus, irrespective of the source of agonists, whether derived from microorganisms or from the hosts, a triad comprised of an oxidant, a membrane perforator, and a proteinase constitutes a potent cytolytic cocktail the activity of which may be further enhanced by certain cytokines. The role played by non-biodegradable microbial cell wall components (lipopolysaccharide, lipoteichoic acid, peptidoglycan) released following polycation- and antibiotic-induced bacteriolysis in the activation of macrophages to release oxidants, cytolytic cytokines and NO is also discussed in relation to the pathophysiology of granulomatous inflammation and sepsis. The recent failures to prevent septic shock by the administration of only single antagonists is disconcerting. It suggests, however, that since tissue damage in post-infectious syndromes is caused by synergistic interactions among a multiplicity of agents, only cocktails of appropriate antagonists, if administered at the early phase of infection and to patients at high risk, might prevent the development of post-infectious syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72535/1/j.1574-695X.1999.tb01357.x.pd

Varying aggregate sizes, plasticizers, and supplementary cementitious materials to efficiently use Portland clinker in concrete

Mitigating greenhouse gas (GHG) emissions from the production of concrete, a critical infrastructure material around the world, has been highlighted as necessary to meet climate change goals. Concrete is made of water, aggregates (e.g. crushed rocks), and Portland cement (PC), a hydraulic binder. PC is the primary source of GHG emissions from concrete, a function of the emissions derived from the production of its clinker, a kilned, quenched material composed of calcium silicates that, by mass, makes up the majority of PC. While considerable attention has been given to reducing the GHG emissions from PC manufacture, better utilization of other resources used in concrete can lower the demand for the level of clinker necessary in any given mixture. In this work, we examine how changing the size of aggregates, the use of a superplasticizer (SP), and the use of supplementary cementitious materials (SCMs) can lower GHG emissions from concrete. We derive a system of equations based fundamentally on standard mixture proportioning guidelines to determine the most efficient use of PC in a concrete mixture for specified strength and workability, and we quantify GHG emissions using life cycle assessment methods. Findings show that the use of reactive SCMs can contribute to reduced GHG emissions, as can the use of a higher maximum aggregate diameter and higher SP dosage. Our models also suggest that a concrete producer could follow standard mixture proportioning guidelines and yield a mixture that has over 2 times the PC content needed. The efficient use of PC within concrete mixtures by appropriately selecting other constituents can lower GHG emissions, contributing to climate change goals

Amplifying reflective thinking in musical performance

In this paper we report on the development of tools that encourage both a creative and reflective approach to music-making and musical skill development. A theoretical approach to musical skill development is outlined and previous work in the area of music visualisation is discussed. In addition the characterisation of music performance as a type of design problem is discussed and the implications of this position for the design of tools for musicians are outlined. Prototype tools, the design of which is informed by the theories and previous work, are described and some preliminary evaluation of their effectiveness is discussed. Future directions are outlined. Copyright 2005 ACM

Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4

Joshua Runtuwene,1,2 Kai-Chun Cheng,1 Akihiro Asakawa,1 Haruka Amitani,1 Marie Amitani,1 Akinori Morinaga,1 Yoshiyuki Takimoto,3 Bernabas Harold Ralph Kairupan,2 Akio Inui1 1Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; 2Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia; 3Department of Biomedical Ethics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Background: Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes.Methods: Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis.Results: RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.Conclusion: RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression. Keywords: diabetes mellitus, STZ, HFD, HOMA-IR, PEPCK, GLUT