Evidence for a single, ancient origin of a genus-wide alternative life history strategy.

Understanding the evolutionary origins and factors maintaining alternative life history strategies (ALHS) within species is a major goal of evolutionary research. While alternative alleles causing discrete ALHS are expected to purge or fix over time, one-third of the ~90 species of butterflies are polymorphic for a female-limited ALHS called Alba. Whether Alba arose once, evolved in parallel, or has been exchanged among taxa is currently unknown.

Improving the quality of healthcare: a cross-sectional study of the features of successful clinical networks.

Objectives: Networks of clinical experts are being established internationally to help embed evidence based care in health systems. There is emerging evidence that these clinical networks can drive quality improvement programs, but the features that distinguish successful networks are largely unknown. We examined the factors that make clinical networks effective at improving quality of care and facilitating system-wide changes.

Selection of epitopes from self-antigens for eliciting Th2 or Th1 activity in the treatment of autoimmune disease or cancer.

Vaccines have been valuable tools in the prevention of infectious diseases, and the rapid development of new vectors against constantly mutating foreign antigens in viruses such as influenza has become a regular, seasonal exercise. Harnessing the immune response against self-antigens is not necessarily analogous or as achievable by iterative processes, and since the desired outcome includes leaving the targeted organism intact, requires some precision engineering. In vaccine-based treatment of autoimmunity and cancer, the proper selection of antigens and generation of the desired antigen-specific therapeutic immunity has been challenging.

Feasibility Study: Colombian Caribbean Folk Dances to Increase Physical Fitness and Health-Related Quality of Life in Older Women.

The objectives of the study were to describe the feasibility of an intervention in older women based on folk dances of the Colombian Caribbean region, and to analyze the effects of the intervention on physical fitness and health-related quality of life (HRQoL). A pilot study was conducted in a sample of 27 participants, 15 in the intervention group (IG) and 12 in the comparison group (CG). Caribbean Colombian dance rhythms were introduced as an intervention that lasted 12 weeks.

Th1 epitope selection for clinically effective cancer vaccines.

New cancer immunotherapies mark progress in our understanding of tumor biology and harnessing the immune system's management of self. However, protein- and peptide-based vaccines are not yet consistently efficacious. Recent work uncovers principles governing the genesis of T helper type-restrictive immunity to self-antigens elicited by vaccine epitopes, enabling vaccines to skew the balance from tolerogenic Type II (Th2) to inflammatory Type I (Th1) T cells, and invigorating this cancer immunotherapeutic approach.

Hybrid incompatibility arises in a sequence-based bioenergetic model of transcription factor binding.

Postzygotic isolation between incipient species results from the accumulation of incompatibilities that arise as a consequence of genetic divergence. When phenotypes are determined by regulatory interactions, hybrid incompatibility can evolve even as a consequence of parallel adaptation in parental populations because interacting genes can produce the same phenotype through incompatible allelic combinations. We explore the evolutionary conditions that promote and constrain hybrid incompatibility in regulatory networks using a bioenergetic model (combining thermodynamics and kinetics) of transcriptional regulation, considering the bioenergetic basis of molecular interactions between transcription factors (TFs) and their binding sites.

Specific-gene studies of evolutionary mechanisms in an age of genome-wide surveying.

The molecular tools of genomics have great power to reveal patterns of genetic difference within or among species, but must be complemented by the mechanistic study of the genetic variants found if these variants' evolutionary meaning is to be well understood. Central to this purpose is knowledge of the organisms' genotype-phenotype-environment interactions, which embody biological adaptation and constraint and thus drive natural selection. The history of this approach is briefly reviewed.

A genetic polymorphism evolving in parallel in two cell compartments and in two clades.

Background: The enzyme phosphoenolpyruvate carboxykinase, PEPCK, occurs in its guanosine-nucleotide-using form in animals and a few prokaryotes. We study its natural genetic variation in Colias (Lepidoptera, Pieridae). PEPCK offers a route, alternative to pyruvate kinase, for carbon skeletons to move between cytosolic glycolysis and mitochondrial Krebs cycle reactions.

Evolutionary genomics of Colias Phosphoglucose Isomerase (PGI) introns.

Little is known of intron sequences' variation in cases where eukaryotic gene coding regions undergo strong balancing selection. Phosphoglucose isomerase, PGI, of Colias butterflies offers such a case. Its 11 introns include many point mutations, insertions, and deletions.

Kinetic and structural characterization of caspase-3 and caspase-8 inhibition by a novel class of irreversible inhibitors.

Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of information linking their functions to diseases. Through a structure-based drug design approach, a number of novel beta-strand peptidomimetic compounds were synthesized.

Emergence of complex haplotypes from microevolutionary variation in sequence and structure of Colias phosphoglucose isomerase.

A molecular evolutionary explanation of natural genetic variation requires analysis of specific variants' evolutionary dynamics. To pursue this for phosphoglucose isomerase (PGI) of Colias butterflies, whose polymorphism is maintained by strong natural selection, we assembled a large data set of wild haplotypes, highly variable at the amino acid and DNA levels. The most common electrophoretic, i.

A mitochondrial-DNA-based phylogeny for some evolutionary-genetic model species of Colias butterflies (Lepidoptera, Pieridae).

We study the phylogenetic relationships among some North American Colias ("sulfur") butterflies, using mitochondrial gene sequences (ribosomal RNA, cytochrome oxidase I+II) totaling about 20% of the mitochondrial genome. We find that (1) the lowland species complex shows a branching order different from earlier views; (2) several montane and northern taxa may be more distinct than in earlier views; (3) one morphologically conservative Holarctic assemblage, C. hecla, is differentiated at the molecular-genetic level into at least three taxa which occupy distinct positions in the phylogeny and are sisters to diverse other taxa.

Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy.

To study effects of mitochondrial complex I (CI, NADH:ubiquinone oxidoreductase) deficiency, we inactivated the Ndufs4 gene, which encodes an 18 kDa subunit of the 45-protein CI complex. Although small, Ndufs4 knockout (KO) mice appeared healthy until approximately 5 weeks of age, when ataxic signs began, progressing to death at approximately 7 weeks. KO mice manifested encephalomyopathy including a retarded growth rate, lethargy, loss of motor skill, blindness, and elevated serum lactate.

Prostate cancer detection in men with an initial diagnosis of atypical small acinar proliferation.

Objective: To determine the subsequent prostatic adenocarcinoma detection rate amongst men with an initial diagnosis of atypical small acinar proliferation (ASAP).

Patients And Methods: We reviewed the Illawarra Prostate Pathology Database over a 10-year period (January 1994 to January 2004) for specimens diagnosed as ASAP. These specimens were re-reviewed and clinical data obtained.

Trace metal levels in sediments deposited in urban stormwater management facilities.

Characteristics of solids recovered from stormwater best management practice (BMP) facilities, including stormwater ponds, constructed wetlands, an infiltration basin, a biofilter, a stormwater treatment clarifier, and three-chamber oil and grit separators were described with respect to their metal chemistry. The reported trace metal concentrations in BMP sediments were assessed against the Ontario Sediment Quality Guidelines. Between 80 to 100% of all samples were marginally-to-intermediately polluted by Cd, Cr, Cu, Fe, Pb, Mn, Ni and Zn.

From DNA to fitness differences: sequences and structures of adaptive variants of Colias phosphoglucose isomerase (PGI).

Colias eurytheme butterflies display extensive allozyme polymorphism in the enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness effects of these genotypes found evidence of strong natural selection maintaining this polymorphism in the wild. Here we analyze the molecular features of this polymorphism by sequencing multiple alleles and modeling their structures.

Odorant stimulation enhances survival of olfactory sensory neurons via MAPK and CREB.

Olfactory sensory neurons (OSNs) can be sensitized to odorants by repeated exposure, suggesting that an animal's responsiveness to olfactory cues can be enhanced at the initial stage of detection. However, because OSNs undergo a regular cycle of apoptosis and replacement by ostensibly naive, precursor-derived neurons, the advantage of sensitization would be lost in the absence of a mechanism for odorant-enhanced survival of OSNs. Using recombinant adenoviruses in conjunction with surgical and electrophysiological techniques, we monitored OSN survival and function in vivo and find that odorant exposure selectively rescues populations of OSNs from apoptosis.

Winter operation of an on-stream stormwater management pond.

The winter operation of an on-stream stormwater management pond in Kingston, Canada is characterised. The pond froze over in late November. Ice thickness varied from 0.

Urban drainage and highway runoff in cold climates: conference overview.

This overview of research findings presented at the conference on urban drainage and highway runoff in cold climates starts with generation of urban runoff and snowmelt, followed by snowmelt and winter runoff quality, best management practices for urban snowmelt and winter runoff, and snow management in urban areas. Research on the urban hydrological cycle is lagging behind the needs in this field, particularly in terms of data availability. The current studies of winter urban runoff quality focus on road salts in the urban environment and their environmental effects.

The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones.

The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 microg/mL for the most potent congeners).

Observations on the relationship between triazines and mycobacteria in metal removal fluids.

The purpose of the study was to determine whether hexahydrotriazine ("triazine") bactericides increase the likelihood of elevated mycobacteria growth in metal removal fluids (MRFs). In reaction to an outbreak of hypersensitivity pneumonitis (HP) at a transmission manufacturing facility, machining plants of a large automobile manufacturer were directed to increase the testing of MRF, especially testing for mycobacteria. A working hypothesis was developed that triazine bactericides cause an increase in mycobacteria contamination, which in turn may lead to an increased risk of HP for workers exposed to MRF aerosols.

Urbanization, land use, and water quality in Shanghai. 1947-1996.

The paper undertakes a preliminary investigation into the relationship between water quality and urbanization as well as the changing patterns of land use within Shanghai. Longitudinal changes to water quality at various points along the course of the Huangpu River are analysed and compared to changes in the rates of urbanization and changes in land uses. The results reveal that rapid urbanization corresponds with rapid degradation of water quality.