Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows

Many studies have demonstrated that male aggression is regulated by testosterone. The conversion of testosterone to estradiol by brain aromatase is also known to regulate male aggression in the breeding season. Male song sparrows (Melospiza melodia morphna) are territorial not only in the breeding season, but also in the nonbreeding season, when plasma testosterone and estradiol levels are basal. Castration has no effect on nonbreeding aggression. In contrast, chronic (10 day) aromatase inhibitor (fadrozole) treatment decreases nonbreeding aggression, indicating a role for estrogens. Here, we show that acute (1 day) fadrozole treatment decreases nonbreeding territoriality, suggesting relatively rapid estrogen effects. In spring, fadrozole decreases brain aromatase activity, but acute and chronic fadrozole treatments do not significantly decrease aggression, although trends for some behaviors approach significance. In gonadally intact birds, fadrozole may be less effective at reducing aggression in the spring. This might occur because fadrozole causes a large increase in plasma testosterone in intact breeding males. Alternatively, estradiol may be more important for territoriality in winter than spring. We hypothesize that sex steroids regulate male aggression in spring and winter, but the endocrine mechanisms vary seasonally.     

The Influence of Age and Gender on Skin-Associated Microbial Communities in Urban and Rural Human Populations

Differences in the bacterial community structure associated with 7 skin sites in 71 healthy people over five days showed significant correlations with age, gender, physical skin parameters, and whether participants lived in urban or rural locations in the same city. While body site explained the majority of the variance in bacterial community structure, the composition of the skin-associated bacterial communities were predominantly influenced by whether the participants were living in an urban or rural environment, with a significantly greater relative abundance of Trabulsiella in urban populations. Adults maintained greater overall microbial diversity than adolescents or the elderly, while the intragroup variation among the elderly and rural populations was significantly greater. Skin-associated bacterial community structure and composition could predict whether a sample came from an urban or a rural resident ~5x greater than random.     

Membrane composition and ion-permeability in extremophiles

Abstract: Protons and sodium ions are the only used coupling ions in energy transduction in Bacteria and Archaea. At their growth temperature, the permeability of the cytoplasmic membrane of thermophilic bacteria to protons is high as compared to sodium ions. In some thermophiles, therefore, sodium is the sole energy coupling ion. Comparison of the proton- and sodium permeability of the membranes of variety of bacterial and archaeal species that differ in their optimal growth temperature reveals that the permeation processes of protons and sodium ions must occur by different mechanisms. The proton permeability increases with the temperature, and has a comparable value for most species at their respective growth temperatures. The sodium permeability is lower than the proton permeability and increases also with the temperature, but is lipid independent. Therefore, it appears that for most bacteria the physical properties of the cytoplasmic membrane are optimised to ensure a low proton permeability at the respective growth temperature.     

North and South: Exploring isotopic analysis of bone carbonates and collagen to understand post-medieval diets in London and northern England

Objectives

We evaluate the potential of paired isotopic analysis of bone carbonate and collagen to examine the diet of post-medieval human and animal populations from England (17th–19th c.), including, for the first time, manufacturing towns in northern England. The potential for identifying C₄ crop consumption is explored alongside regional and local patterning in diet by sex and socioeconomic status.

Materials and Methods

Humans (n = 216) and animals (n = 168) were analyzed from sites in London and northern England for both carbon and nitrogen isotopes of bone collagen (𝛿¹³C_coll, 𝛿¹⁵N_coll). Isotopic analysis of bone carbonates (𝛿¹³C_carb, 𝛿¹⁸O_carb) was carried out on all humans and 27 animals, using Fourier transform infrared spectroscopy–attenuated total reflectance to assess diagenesis.

Results

Variations in diet were observed between and within different populations by geographical location and socioeconomic status. Three pigs and one cow consumed C₄ resources, indicating the availability of C₄-fed animal protein. Londoners consumed more animal and marine protein and C₄ resources. Middle- and upper-class populations from both London and northern populations also had greater access to these foods compared to those of lower status in the same regions.

Discussion

This substantial multi-isotope dataset deriving from bone carbonate and collagen combined from diverse post-medieval urban communities enabled, for the first time, the biomolecular identification of the dynamics of C₄ consumption (cane sugar/maize) in England, providing insight into the dynamics of food globalization during this period. We also add substantially to the animal dataset for post-medieval England, providing further insight into animal management during a key moment of agricultural change.

     

ATM regulates cell fate choice upon p53 activation by modulating mitochondrial turnover and ROS levels

Despite extensive study, the mechanisms of cell fate choice upon p53 activation remain poorly understood. Using genome-wide shRNA screening, we recently identified the ATM kinase as synthetic lethal with Nutlin-3, an MDM2 inhibitor that leads to non-genotoxic p53 activation. Here, we demonstrate that while this synthetic lethal interaction relies upon components of both the intrinsic and extrinsic apoptotic pathways (e.g., BAX and BID), it is not due to significant ATM effects on the expression of p53 target genes. Instead, loss of ATM activity results in increased mitochondria and reactive oxygen species that drive apoptosis. Finally, we provide evidence that pharmacologic inhibition of ATM blocks autophagy in direct opposition to p53, which activates this process, and that inhibition of autophagy is sufficient to elicit an apoptotic response when combined with Nutlin-3.     

Thyroxine suppresses thrombocytopoiesis and stimulates erythropoiesis in mice.

Thyroxine has been shown in vitro to stimulate erythropoiesis by two mechanisms: a direct, beta 2-adrenergic receptor-mediated stimulation of red cell precursors, and an indirect, erythropoietin-mediated mechanism. Clinical reports have suggested that excess thyroxine also exerts depressive effects on thrombocytopoiesis, but the most sensitive methods of assessing platelet production, i.e., percentage of 35S incorporation into platelets and determination of megakaryocyte size and number, are not appropriate for analysis of platelet production in human patients. The purpose of this study was to use a mouse model to investigate the effects of the hyperthyroid state on erythropoiesis and thrombocytopoiesis, and to assess in vivo the two mechanisms by which thyroxine has been described to stimulate erythropoiesis in vitro. We found that thyroxine administration significantly depressed platelet production and stimulated erythropoiesis in mice. Both the D- and L-isomers of thyroxine in appropriate doses produced this depression of thrombocytopoiesis, and the effect was dose dependent for both isomers. Daily administration of thyroxine:increased blood volume; decreased the peripheral platelet count, total circulating platelet count and mass, percentage of 35S incorporation into platelets, and megakaryocyte number and size; and concurrently increased indices of red cell production (packed cell volume, red blood cell count, total circulating red blood cell count and mass, and reticulocyte count). Additionally, propranolol, a nonspecific beta-blocker, partially reversed the suppression of platelet production by L-thyroxine, lending credence to the assertion that the direct, beta 2-adrenergic receptor-mediated stimulation of the erythroid cell line by thyroxine reported to exist in vitro may also be important in vivo.     

GST among issues raised during CMA workshop on political lobbying

A recent CMA-sponsored workshop on political lobbying attracted many more physicians than anticipated. Dr. Bill Acker, chair of the Political Action Committee, said this is a sign of physicians'' growing interest in lobbying and politics.