Mutation as a stress response and the regulation of evolvability.

Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes.

Adaptive amplification.

Modern techniques are revealing that repetition of segments of the genome, called amplification or gene amplification, is very common. Amplification is found in all domains of life, and occurs under conditions where enhanced expression of the amplified genes is advantageous. Amplification extends the range of gene expression beyond that which is achieved by control systems.

The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing.

Study Objective: Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR.

Design: Interventional, cross-over clinical study.

Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia.

Cells from patients with Fanconi anemia (FA), an inherited disorder that includes bone marrow failure and cancer predisposition, have increased sensitivity to oxidative stress through an unknown mechanism. We demonstrate that the FA group G (FANCG) protein is found in mitochondria. Wild-type but not G546R mutant FANCG physically interacts with the mitochondrial peroxidase peroxiredoxin-3 (PRDX3).

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

Background: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown.

Aim: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF.

Guiding health promotion efforts with urban Inuit: a community-specific perspective on health information sources and dissemination strategies.

Objective: To develop a community-specific perspective of health information sources and dissemination strategies of urban Inuit to better guide health promotion efforts.

Methods: Through a collaborative partnership with the Tungasuvvingat Inuit Family Resource Centre, a series of key informant interviews and focus groups were conducted to gather information on specific sources of health information, strategies of health information dissemination, and overall themes in health information processes.

Findings: Distinct patterns of health information sources and dissemination strategies emerged from the data.

Botswana's Tebelopele voluntary HIV counseling and testing network: use and client risk factors for HIV infection, 2000-2004.

Background: : HIV services, including voluntary counseling and testing (VCT) and antiretroviral (ARV) therapy, expanded rapidly in Botswana from 2000 through 2004.

Methods: : Client data from Botswana's Tebelopele VCT network were analyzed to describe clients, factors associated with HIV infection, and trends in VCT use.

Results: : Tebelopele provided free, anonymous, same-day HIV tests for 117,234 clients from 2000 through 2004.

On the mechanism of gene amplification induced under stress in Escherichia coli.

Gene amplification is a collection of processes whereby a DNA segment is reiterated to multiple copies per genome. It is important in carcinogenesis and resistance to chemotherapeutic agents, and can underlie adaptive evolution via increased expression of an amplified gene, evolution of new gene functions, and genome evolution. Though first described in the model organism Escherichia coli in the early 1960s, only scant information on the mechanism(s) of amplification in this system has been obtained, and many models for mechanism(s) were possible.

Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients.

The symptom burden resulting from sleep-disordered breathing (SDB) in patients with mild-to-moderate congestive heart failure (CHF) is unclear. The current authors monitored 24-h activity levels and compared subjective and objective measures of daytime sleepiness in 39 CHF patients, New York Heart Association class 2-3, on optimal medication. A total of 22 patients were classified as SDB (apnoea/hypopnoea index (AHI) median (range) 22.

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF.

Trapping Phyllophaga spp. (Coleoptera: Scarabaeidae: Melolonthinae) in the United States and Canada using sex attractants.

The sex pheromone of the scarab beetle, Phyllophaga anxia, is a blend of the methyl esters of two amino acids, L-valine and L-isoleucine. A field trapping study was conducted, deploying different blends of the two compounds at 59 locations in the United States and Canada. More than 57,000 males of 61 Phyllophaga species (Coleoptera: Scarabaeidae: Melolonthinae) were captured and identified.

A role for topoisomerase III in a recombination pathway alternative to RuvABC.

The physiological role of topoisomerase III is unclear for any organism. We show here that the removal of topoisomerase III in temperature sensitive topoisomerase IV mutants in Escherichia coli results in inviability at the permissive temperature. The removal of topoisomerase III has no effect on the accumulation of catenated intermediates of DNA replication, even when topoisomerase IV activity is removed.

Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms.

"Adaptive mutation" denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac(-)Escherichia coli cells on lactose medium induces Lac(+)revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele.

Antibiotic-induced lateral transfer of antibiotic resistance.

As do many temperate bacteriophages, integrating conjugative elements (ICEs) recruit the SOS DNA damage response to mobilize themselves from the bacterial chromosome and infect other cells. This transfers resistance to multiple antibiotics. Several commonly used antibiotics induce the SOS response, potentially hastening genetic change and the evolution to resistance of pathogenic populations.

Protemblemaria perla, a new species of tube blenny (Perciformes: Chaenopsidae) from the tropical eastern Pacific.

Protemblemaria perla, from Isla del Rey, Islas Perlas, Panama, is distinctive in having a long unbranched cirrus on the posterior nostril, a U-shaped fleshy ridge bearing fleshy flaps and a pair of papillae on the nape, a relatively high number (18) of segmented dorsal-fin rays, and small rust-colored spots on the dorsal fin. Protemblemaria perla and P. punctata, from the southern Caribbean, share several morphological features and form a transisthmian species pair.

Longitudinal relations between child vagal tone and parenting behavior: 2 to 4 years.

The longitudinal relations between physiological markers of child emotion regulation and maternal parenting practices were examined from 2 to 4 years of age. At Time 1, cardiac vagal tone was assessed for one hundred four 2-year-olds (54 females); their mothers completed an assessment of parenting styles. Two years later, at Time 2, 84 of the original participants were reassessed on measures of cardiac vagal tone and parenting style.

Adaptive mutation and amplification in Escherichia coli: two pathways of genome adaptation under stress.

The neo-Darwinists suggested that evolution is constant and gradual, and thus that genetic changes that drive evolution should be too. However, more recent understanding of phenomena called adaptive mutation in microbes indicates that mutation rates can be elevated in response to stress, producing beneficial and other mutations. We review evidence that, in Escherichia coli, two separate mechanisms of stress-induced genetic change occur that revert a lac frameshift allele allowing growth on lactose medium.

Predicting preschoolers' externalizing behaviors from toddler temperament, conflict, and maternal negativity.

Rarely have researchers elucidated early childhood precursors of externalizing behaviors for boys and girls from a normative sample. Toddlers (N = 104; 52 girls) were observed interacting with a same-sex peer and their mothers, and indices of conflict-aggression, emotion and behavior dysregulation, parenting, and child externalizing problems were obtained. Results indicated that boys initiated more conflictual-aggressive interactions as toddlers and had more externalizing difficulties 2 years later, yet girls' (not boys') conflict-aggressive initiations at age 2 were related to subsequent externalizing problems.