CAG Repeat Variants in the POLG1 Gene Encoding mtDNA Polymerase-Gamma and Risk of Breast Cancer in African-American Women

The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49–6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies

Calculation of the relative metastabilities of proteins using the CHNOSZ software package

<p>Abstract</p> <p>Background</p> <p>Proteins of various compositions are required by organisms inhabiting different environments. The energetic demands for protein formation are a function of the compositions of proteins as well as geochemical variables including temperature, pressure, oxygen fugacity and pH. The purpose of this study was to explore the dependence of metastable equilibrium states of protein systems on changes in the geochemical variables.</p> <p>Results</p> <p>A software package called CHNOSZ implementing the revised Helgeson-Kirkham-Flowers (HKF) equations of state and group additivity for ionized unfolded aqueous proteins was developed. The program can be used to calculate standard molal Gibbs energies and other thermodynamic properties of reactions and to make chemical speciation and predominance diagrams that represent the metastable equilibrium distributions of proteins. The approach takes account of the chemical affinities of reactions in open systems characterized by the chemical potentials of basis species. The thermodynamic database included with the package permits application of the software to mineral and other inorganic systems as well as systems of proteins or other biomolecules.</p> <p>Conclusion</p> <p>Metastable equilibrium activity diagrams were generated for model cell-surface proteins from archaea and bacteria adapted to growth in environments that differ in temperature and chemical conditions. The predicted metastable equilibrium distributions of the proteins can be compared with the optimal growth temperatures of the organisms and with geochemical variables. The results suggest that a thermodynamic assessment of protein metastability may be useful for integrating bio- and geochemical observations.</p

Do Fish Perceive Anaesthetics as Aversive?

<div><p>This study addresses a fundamental question in fish welfare: are the anaesthetics used for fish aversive? Despite years of routine general use of many agents, within both scientific research and aquaculture, there is a paucity of information regarding their tolerance and associated behavioural responses by fish. This study examined nine of the most commonly used fish anaesthetic agents, and performed preference tests using adult mixed sex zebrafish (<i>Danio rerio</i>), the most commonly held laboratory fish. Video tracking software quantified swimming behaviour related to aversion for each anaesthetic at 50% of its standard recommended dose compared with clean water in a flow-through chemotaxic choice chamber. Results suggest that several commonly used anaesthetics were aversive, including two of the most commonly recommended and used: MS222 (ethyl 3-aminobenzoate methanesulphate) and benzocaine. For ethical best practice, it is recommended that compounds that are aversive, even at low concentration, should no longer be used routinely for anaesthesia or indeed the first step of humane euthanasia of adult zebrafish. Two agents were found not to induce aversive behavioural responses: etomidate and 2,2,2 tribromoethanol. For the millions of adult zebrafish used in laboratories and breeding worldwide, etomidate appears best suited for future routine humane use.</p></div

Pre-sedation and transport of Rhamdia quelen in water containing essential oil of Lippia alba: metabolic and physiological responses

The effects of transporting silver catfish (Rhamdia quelen) for 6 h in plastic bags containing 0 (control), 30 or 40 A mu L/L of essential oil (EO) from Lippia alba leaves were investigated. Prior to transport, the fish in the two experimental groups were sedated with 200 A mu L/L of EO for 3 min. After transport, dissolved oxygen, carbon dioxide, alkalinity, water hardness, pH, temperature and un-ionized ammonia levels in the transport water did not differ significantly among the groups. However, total ammonia nitrogen levels and net Na+, Cl- and K+ effluxes were significantly lower in the groups transported with EO of L. alba than those in the control group. PvO(2), PvCO(2) and HCO3 (-) were higher after transporting fish in 40 A mu L/L of EO of L. alba, but there were no significant differences between groups regarding blood pH or hematocrit. Cortisol levels were significantly higher in fish transported in 30 A mu L/L of EO of L. alba compared to those of the control group. The metabolic parameters (glycogen, lactate, total amino acid, total ammonia and total protein) showed different responses after adding EO to the transport water. In conclusion, while the EO of L. alba is recommended for fish transport in the conditions tested in the present study because it was effective in reducing waterborne total ammonia levels and net ion loss, the higher hepatic oxidative stress in this species with the same EO concentrations reported by a previous study led us to conclude that the 10-20 A mu L/L concentration range of EO and lack of pre-sedation before transport are more effective

Microbial legacies alter decomposition in response to simulated global change.

Terrestrial ecosystem models assume that microbial communities respond instantaneously, or are immediately resilient, to environmental change. Here we tested this assumption by quantifying the resilience of a leaf litter community to changes in precipitation or nitrogen availability. By manipulating composition within a global change experiment, we decoupled the legacies of abiotic parameters versus that of the microbial community itself. After one rainy season, more variation in fungal composition could be explained by the original microbial inoculum than the litterbag environment (18% versus 5.5% of total variation). This compositional legacy persisted for 3 years, when 6% of the variability in fungal composition was still explained by the microbial origin. In contrast, bacterial composition was generally more resilient than fungal composition. Microbial functioning (measured as decomposition rate) was not immediately resilient to the global change manipulations; decomposition depended on both the contemporary environment and rainfall the year prior. Finally, using metagenomic sequencing, we showed that changes in precipitation, but not nitrogen availability, altered the potential for bacterial carbohydrate degradation, suggesting why the functional consequences of the two experiments may have differed. Predictions of how terrestrial ecosystem processes respond to environmental change may thus be improved by considering the legacies of microbial communities