The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice

<p>Abstract</p> <p>Background</p> <p>Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions <it>in vivo </it>using model genetic systems.</p> <p>Methods</p> <p>Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the Apc^Minmodel of intestinal carcinoma.</p> <p>Results</p> <p>En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in Apc^Minanimals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.</p> <p>Conclusion</p> <p>Our findings provide <it>in vivo </it>evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.</p

Molecular diagnosis of bird-mediated pest consumption in tropical farmland

Biodiversity loss will likely have surprising and dramatic consequences for human wellbeing. Identifying species that benefit society represents a critical first step towards predicting the consequences of biodiversity loss. Though natural predators prevent billions of dollars in agricultural pest damage annually, characterizing which predators consume pests has proven challenging. Emerging molecular techniques may illuminate these interactions. In the countryside of Costa Rica, we identified avian predators of coffee’s most damaging insect pest, the coffee berry borer beetle (Coleoptera:Scolytidae Hypothenemus hampeii), by assaying 1430 fecal samples of 108 bird species for borer DNA. While feeding trials confirmed the efficacy of our approach, detection rates were low. Nevertheless, we identified six species that consume the borer. These species had narrow diet breadths, thin bills, and short wings; traits shared with borer predators in other systems. Borer predators were not threatened; therefore, safeguarding pest control necessitates managing species beyond those at risk of regional extinction by maintaining populations in farmland habitats. Generally, our results demonstrate potential for pairing molecular methods with ecological analyses to yield novel insights into species interactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-630) contains supplementary material, which is available to authorized users

Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis

Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors (GABAARs). The impact of changes in steady state Cl− gradient is relatively straightforward to understand, but how dynamic interplay between Cl− influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl− load on a fast time scale, whereas Cl−extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl− gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABAAR-mediated inhibition, but increasing GABAAR input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl−. Furthermore, if spiking persisted despite the presence of GABAAR input, Cl− accumulation became accelerated because of the large Cl− driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl− and pH regulation. Several model predictions were tested and confirmed by [Cl−]i imaging experiments. Our study has thus uncovered how Cl− regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K− accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention

Following the genes: a framework for animal modeling of psychiatric disorders

The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Molecular scatology and high-throughput sequencing reveal predominately herbivorous insects in the diets of adult and nestling Western Bluebirds (Sialia mexicana) in California vineyards

Determining the ecosystem function of high-order predators is critical for evaluation of food web interactions. Insectivorous birds are abundant predators in many ecosystems yet because they forage upon small taxa, it remains largely unknown whether birds are providing ecosystem services in the form of pest control or disservices by preying upon predaceous arthropod species. We extracted DNA from noninvasive fecal samples of adult and nestling Western Bluebirds (Sialia mexicana) in California vineyards. Using universal arthropod-specific primers, we sequenced prey items via massively parallel sequencing on the Illumina MiSeq platform. Bluebirds consumed a broad diet comprising 66 unique arthropod species from 6 orders and 28 families. Aedes sp. (mosquitoes: Culicidae), a previously unknown prey, was the most common item recovered, occurring in 49.5% of the fecal samples. Ectoparasitic bird blowfly (Protocalliphora) DNA was found in 7% of adult and 11% of nestling samples, presenting clear evidence of active feeding by the avian hosts on adult or larval ectoparasites. Herbivorous insects, primarily from the orders Hemiptera and Lepidoptera, represented over half (56%) of the prey items in bluebird diets. Intraguild predation (consumption of predator or parasitoid arthropods) represented only 3% of adult and nestling dietary items. Diets of adults were significantly different from nestlings as were diets from birds sampled in different vineyard blocks. Sex, date, number of young, and individual bird (based on resampled individuals) were all insignificant factors that did not explain diet variability. Nestling age was a significant factor in explaining a small amount of the variability in dietary components. In addition, our analysis of subsampling larger fecal samples and processing them independently revealed highly dissimilar results in all 10 trials and we recommend avoiding this common methodology. Molecular scatology offers powerfully informative techniques that can reveal the ecosystem function and services provided by abundant yet cryptic avian foragers

Molecular tools reveal diets of insectivorous birds from predator fecal matter

The emerging field of molecular scatology enables critical testing of food web theory. The non-invasive application of molecular tools allows for sequencing of prey DNA from predator fecal matter, evaluating diet breadth and foraging guild. While insectivorous bats are obscure foragers compared to most insectivorous birds, more is known about which arthropod species bats consume because molecular techniques have been optimized for mammalian systems, not avian physiology. Our research objective was to use molecular tools to detect arthropod prey in the fecal matter of an insectivorous avian predator. We used Western Bluebird (Sialia mexicana) as a model predator due to its generalist foraging strategy. We compared two fecal DNA extraction kits: (1) Qiagen's DNA stool mini kits, used widely in dietary studies on bats and (2) Zymo's Soil/Fecal DNA MiniPrep kits, not currently cited in the molecular scatology literature. We successfully extracted DNA only with the Zymo kit, amplified mitochondrial cytochrome oxidase c subunit I genes, sequenced, and identified the arthropod prey. A spiked PCR experiment showed evidence of possible inhibitors remaining in the Qiagen kit extractions. Overall, arthropod prey from seven different orders and five different classes were identified. We discuss the ecological implications of these data and suggest areas of future research applying molecular techniques to avian fecal matter. Consistent methodological advancement will enable molecular scatology to identify ecosystem services provided by insectivorous birds, develop ecological theory, and inform predator conservation efforts. © 2013 Springer Science+Business Media Dordrecht