Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip((R)) microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc.

Genetic covariance between indices of body condition and immunocompetence in a passerine bird

Background: Condition-dependence is a ubiquitous feature of animal life histories and has important implications for both natural and sexual selection. Mate choice, for instance, is typically based on condition-dependent signals. Theory predicts that one reason why condition-dependent signals may be special is that they allow females to scan for genes that confer high parasite resistance. Such explanations require a genetic link between immunocompetence and body condition, but existing evidence is limited to phenotypic associations. It remains unknown, therefore, whether females selecting males with good body condition simply obtain a healthy mate, or if they acquire genes for their offspring that confer high immunocompetence. Results: Here we use a cross-foster experimental design to partition the phenotypic covariance in indices of body condition and immunocompetence into genetic, maternal and environmental effects in a passerine bird, the zebra finch Taeniopygia guttata. We show that there is significant positive additive genetic covariance between an index of body condition and an index of cell-mediated immune response. In this case, genetic variance in the index of immune response explained 56% of the additive genetic variance in the index of body condition. Conclusion: Our results suggest that, in the context of sexual selection, females that assess males on the basis of condition-dependent signals may gain genes that confer high immunocompetence for their offspring. More generally, a genetic correlation between indices of body condition and imuunocompetence supports the hypothesis that parasite resistance may be an important target of natural selection. Additional work is now required to test whether genetic covariance exists among other aspects of both condition and immunocompetence.

The effects of air pollution on hospitalizations for cardiovascular disease in elderly people in Australian and New Zealand cities

OBJECTIVE: The goal of this study was to estimate the associations between outdoor air pollution and cardiovascular hospital admissions for the elderly. DESIGN: Associations were assessed using the case-crossover method for seven cities: Auckland and Christchurch, New Zealand; and Brisbane, Canberra, Melbourne, Perth, and Sydney Australia. Results were combined across cities using a random-effects meta-analysis and stratified for two adult age groups: 15-64 years and >= 65 years of age (elderly). Pollutants considered were nitrogen dioxide, carbon monoxide, daily measures of particulate matter (PM) and ozone. Where multiple pollutant associations were found, a matched case-control analysis was used to identify the most consistent association. RESULTS: In the elderly, all pollutants except 03 were significantly associated with five categories or cardiovascular disease admissions. No associations were found for arrhythmia and stroke. For a 0.9-ppm increase in CO, there were significant increases in elderly hospital admissions for total cardiovascular disease (2.2%), all cardiac disease (2.8%), cardiac failure (6.0%), ischemic heart disease (2.3%), and myocardial infarction (2.9%). There was some heterogeneity between cities, possibly due to differences in humidity and the percentage of elderly people. In matched analyses, CO had the most consistent association. CONCLUSIONS. The results suggest that air pollution arising from common emission sources for CO, NO2, and PM (e.g., motor vehicle exhausts) has significant associations with adult cardiovascular hospital admissions, especially in the elderly, at air pollution concentrations below normal health guidelines. RELEVANCE TO CLINICAL AND PROFESSIONAL PRACTICE: Elderly populations in Australia need to be protected from air pollution arising from outdoor sources to reduce cardiovascular disease.

Can occupational therapy intervention play a part in maintaining independence and quality of life in older people? A randomised controlled trial Jeannine Liddle 1 , 2 , Lyn March 3 , Barbara Carfrae 4 , Terence Finnegan 5 , Jane Druce 6 , Jennifer Schwarz 7 Peter Brooks

The main objective of this study was to see if older people could maintain their quality of life and independence after their homes had been modified and they were using community services as recommended by an occupational therapist. There were 167 study participants aged 69 to 94 years from the Northern Sydney Area, After being assessed at home by an occupational therapist, 105 were randomly allocated to one of two groups, to either have or not have the occupational therapist's recommendations carried out, They were assessed again after six months, A third group did not require any intervention, This group was followed up by telephone and postal questionnaire at six months. The main outcome measures used were the Sickness Impact Profile, the Philadelphia Geriatric Center Morale Scale, the Life Satisfaction Index, assessment of Activities of Daily Living, the Health Assessment Questionnaire and change in residence. After six months there were no difference in outcomes among the three groups. Most study participants remained at a satisfactory level on each measure. Three people had died, One had moved to hostel care and one had moved to a nursing home. A further 14 from the group having no intervention had withdrawn from the study, A secondary objective of this study was to indicate the responsiveness of these outcome measures to change in the short term (over six months) in an elderly population. Twelve-month assessments are in progress and may indicate what to expect from these outcome measures in the medium term.

Recovery of poly-3-hydroxybutyrate from recombinant Escherichia coli by homogenization and centrifugation

Poly-3-hydroxybutyrate from recombinant E. coli was recovered using homogenization and continuous centrifugation with a purity of 94%. Final protein and DNA concentrations were 1.0% w/w and 1.9% w/w, respectively, when a hypochlorite treatment was employed prior to centrifugation. High fractional cell debris removal (94%) was achieved with two centrifugation steps.