Thermodynamic properties and structural stability of thorium dioxide

Using density functional theory (DFT) calculations, we have systematically investigated the thermodynamic properties and structural stabilities of thorium dioxide (ThO$_2$). Based on the calculated phonon dispersion curves, we calculate the thermal expansion coefficient, bulk modulus, and heat capacities at different temperatures for ThO$_2$ under the quasi-harmonic approximation. All the results are in good agreement with corresponding experiments proving the validity of our methods. Our theoretical studies can help people more clearly understand the thermodynamic behaviors of ThO$_2$ at different temperatures. In addition, we have also studied possible defect formations and diffusion behaviors of helium in ThO$_2$, to discuss its structural stability. It is found that in intrinsic ThO$_2$ without any Fermi energy shifts, the interstitial Th$_i^{4+}$ defect other than oxygen or thorium vacancies, interstitial oxygen, and any kinds of Frenkel pairs, is most probable to form with an energy release of 1.74 eV. However, after upshifting the Fermi energy, the formation of the other defects also becomes possible. For helium diffusion, we find that only through the thorium vacancy can it happen with the small energy barrier of 0.52 eV. Otherwise, helium atoms can hardly incorporate or diffuse in ThO$_2$. Our results indicate that people should prevent upshifts of the Fermi energy of ThO$_2$ to avoid the formation of thorium vacancies and so as to prevent helium caused damages.Comment: 11 pages, 11 figure

Many Microbe Microarrays Database: uniformly normalized Affymetrix compendia with structured experimental metadata

Many Microbe Microarrays Database (M3D) is designed to facilitate the analysis and visualization of expression data in compendia compiled from multiple laboratories. M3D contains over a thousand Affymetrix microarrays for Escherichia coli, Saccharomyces cerevisiae and Shewanella oneidensis. The expression data is uniformly normalized to make the data generated by different laboratories and researchers more comparable. To facilitate computational analyses, M3D provides raw data (CEL file) and normalized data downloads of each compendium. In addition, web-based construction, visualization and download of custom datasets are provided to facilitate efficient interrogation of the compendium for more focused analyses. The experimental condition metadata in M3D is human curated with each chemical and growth attribute stored as a structured and computable set of experimental features with consistent naming conventions and units. All versions of the normalized compendia constructed for each species are maintained and accessible in perpetuity to facilitate the future interpretation and comparison of results published on M3D data. M3D is accessible at http://m3d.bu.edu/

Many Microbe Microarrays Database: uniformly normalized Affymetrix compendia with structured experimental metadata

Many Microbe Microarrays Database (M3D) is designed to facilitate the analysis and visualization of expression data in compendia compiled from multiple laboratories. M3D contains over a thousand Affymetrix microarrays for Escherichia coli, Saccharomyces cerevisiae and Shewanella oneidensis. The expression data is uniformly normalized to make the data generated by different laboratories and researchers more comparable. To facilitate computational analyses, M3D provides raw data (CEL file) and normalized data downloads of each compendium. In addition, web-based construction, visualization and download of custom datasets are provided to facilitate efficient interrogation of the compendium for more focused analyses. The experimental condition metadata in M3D is human curated with each chemical and growth attribute stored as a structured and computable set of experimental features with consistent naming conventions and units. All versions of the normalized compendia constructed for each species are maintained and accessible in perpetuity to facilitate the future interpretation and comparison of results published on M3D data. M3D is accessible at http://m3d.bu.edu/

Semaphorin-1a Is Required for Aedes aegypti Embryonic Nerve Cord Development

Although mosquito genome projects have uncovered orthologues of many known developmental regulatory genes, extremely little is known about mosquito development. In this study, the role of semaphorin-1a (sema1a) was investigated during vector mosquito embryonic ventral nerve cord development. Expression of sema1a and the plexin A (plexA) receptor are detected in the embryonic ventral nerve cords of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector), suggesting that Sema1a signaling may regulate mosquito nervous system development. Analysis of sema1a function was investigated through siRNA-mediated knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti development results in a number of nerve cord phenotypes, including thinning, breakage, and occasional fusion of the longitudinal connectives, thin or absent commissures, and general distortion of the nerve cord. Although analysis of Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar phenotypes, aspects of the longitudinal phenotypes differed between D. melanogaster and A. aegypti. The results of this investigation suggest that Sema1a is required for development of the insect ventral nerve cord, but that the developmental roles of this guidance molecule have diverged in dipteran insects

Mouse Middle Ear Ion Homeostasis Channels and Intercellular Junctions

The middle ear contains homeostatic mechanisms that control the movement of ions and fluids similar to those present in the inner ear, and are altered during inflammation.The normal middle ear cavity is fluid-free and air-filled to allow for effective sound transmission. Within the inner ear, the regulation of fluid and ion movement is essential for normal auditory and vestibular function. The same ion and fluid channels active in the inner ear may have similar roles with fluid regulation in the middle ear.Middle and inner ears from BALB/c mice were processed for immunohistochemistry of 10 specific ion homeostasis factors to determine if similar transport and barrier mechanisms are present in the tympanic cavity. Examination also was made of BALB/c mice middle ears after transtympanic injection with heat-killed Haemophilus influenza to determine if these channels are impacted by inflammation.The most prominent ion channels in the middle ear included aquaporins 1, 4 and 5, claudin 3, ENaC and Na(+),K(+)-ATPase. Moderate staining was found for GJB2, KCNJ10 and KCNQ1. The inflamed middle ear epithelium showed increased staining due to expected cellular hypertrophy. Localization of ion channels was preserved within the inflamed middle ear epithelium.The middle ear epithelium is a dynamic environment with intrinsic mechanisms for the control of ion and water transport to keep the middle ear clear of fluids. Compromise of these processes during middle ear disease may underlie the accumulation of effusions and suggests they may be a therapeutic target for effusion control

siRNA-Mediated Gene Targeting in Aedes aegypti Embryos Reveals That Frazzled Regulates Vector Mosquito CNS Development

Although mosquito genome projects uncovered orthologues of many known developmental regulatory genes, extremely little is known about the development of vector mosquitoes. Here, we investigate the role of the Netrin receptor frazzled (fra) during embryonic nerve cord development of two vector mosquito species. Fra expression is detected in neurons just prior to and during axonogenesis in the embryonic ventral nerve cord of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector). Analysis of fra function was investigated through siRNA-mediated knockdown in Ae. aegypti embryos. Confirmation of fra knockdown, which was maintained throughout embryogenesis, indicated that microinjection of siRNA is an effective method for studying gene function in Ae. aegypti embryos. Loss of fra during Ae. aegypti development results in thin and missing commissural axons. These defects are qualitatively similar to those observed in Dr. melanogaster fra null mutants. However, the Aa. aegypti knockdown phenotype is stronger and bears resemblance to the Drosophila commissureless mutant phenotype. The results of this investigation, the first targeted knockdown of a gene during vector mosquito embryogenesis, suggest that although Fra plays a critical role during development of the Ae. aegypti ventral nerve cord, mechanisms regulating embryonic commissural axon guidance have evolved in distantly related insects

Na+/K+-ATPase α1 Identified as an Abundant Protein in the Blood-Labyrinth Barrier That Plays an Essential Role in the Barrier Integrity

BACKGROUND:The endothelial-blood/tissue barrier is critical for maintaining tissue homeostasis. The ear harbors a unique endothelial-blood/tissue barrier which we term "blood-labyrinth-barrier". This barrier is critical for maintaining inner ear homeostasis. Disruption of the blood-labyrinth-barrier is closely associated with a number of hearing disorders. Many proteins of the blood-brain-barrier and blood-retinal-barrier have been identified, leading to significant advances in understanding their tissue specific functions. In contrast, capillaries in the ear are small in volume and anatomically complex. This presents a challenge for protein analysis studies, which has resulted in limited knowledge of the molecular and functional components of the blood-labyrinth-barrier. In this study, we developed a novel method for isolation of the stria vascularis capillary from CBA/CaJ mouse cochlea and provided the first database of protein components in the blood-labyrinth barrier as well as evidence that the interaction of Na(+)/K(+)-ATPase α1 (ATP1A1) with protein kinase C eta (PKCη) and occludin is one of the mechanisms of loud sound-induced vascular permeability increase. METHODOLOGY/PRINCIPAL FINDINGS:Using a mass-spectrometry, shotgun-proteomics approach combined with a novel "sandwich-dissociation" method, more than 600 proteins from isolated stria vascularis capillaries were identified from adult CBA/CaJ mouse cochlea. The ion transporter ATP1A1 was the most abundant protein in the blood-labyrinth barrier. Pharmacological inhibition of ATP1A1 activity resulted in hyperphosphorylation of tight junction proteins such as occludin which increased the blood-labyrinth-barrier permeability. PKCη directly interacted with ATP1A1 and was an essential mediator of ATP1A1-initiated occludin phosphorylation. Moreover, this identified signaling pathway was involved in the breakdown of the blood-labyrinth-barrier resulting from loud sound trauma. CONCLUSIONS/SIGNIFICANCE:The results presented here provide a novel method for capillary isolation from the inner ear and the first database on protein components in the blood-labyrinth-barrier. Additionally, we found that ATP1A1 interaction with PKCη and occludin was involved in the integrity of the blood-labyrinth-barrier

The Phylogenetic Origin of oskar Coincided with the Origin of Maternally Provisioned Germ Plasm and Pole Cells at the Base of the Holometabola

The establishment of the germline is a critical, yet surprisingly evolutionarily labile, event in the development of sexually reproducing animals. In the fly Drosophila, germ cells acquire their fate early during development through the inheritance of the germ plasm, a specialized maternal cytoplasm localized at the posterior pole of the oocyte. The gene oskar (osk) is both necessary and sufficient for assembling this substance. Both maternal germ plasm and oskar are evolutionary novelties within the insects, as the germline is specified by zygotic induction in basally branching insects, and osk has until now only been detected in dipterans. In order to understand the origin of these evolutionary novelties, we used comparative genomics, parental RNAi, and gene expression analyses in multiple insect species. We have found that the origin of osk and its role in specifying the germline coincided with the innovation of maternal germ plasm and pole cells at the base of the holometabolous insects and that losses of osk are correlated with changes in germline determination strategies within the Holometabola. Our results indicate that the invention of the novel gene osk was a key innovation that allowed the transition from the ancestral late zygotic mode of germline induction to a maternally controlled establishment of the germline found in many holometabolous insect species. We propose that the ancestral role of osk was to connect an upstream network ancestrally involved in mRNA localization and translational control to a downstream regulatory network ancestrally involved in executing the germ cell program

Topography-driven isolation, speciation and a global increase of endemism with elevation

Aim: Higher-elevation areas on islands and continental mountains tend to be separated by longer distances, predicting higher endemism at higher elevations; our study is the first to test the generality of the predicted pattern. We also compare it empirically with contrasting expectations from hypotheses invoking higher speciation with area, temperature and species richness. Location: Thirty-two insular and 18 continental elevational gradients from around the world. Methods: We compiled entire floras with elevation-specific occurrence information, and calculated the proportion of native species that are endemic (‘percent endemism’) in 100-m bands, for each of the 50 elevational gradients. Using generalized linear models, we tested the relationships between percent endemism and elevation, isolation, temperature, area and species richness. Results: Percent endemism consistently increased monotonically with elevation, globally. This was independent of richness–elevation relationships, which had varying shapes but decreased with elevation at high elevations. The endemism–elevation relationships were consistent with isolation-related predictions, but inconsistent with hypotheses related to area, richness and temperature. Main conclusions: Higher per-species speciation rates caused by increasing isolation with elevation are the most plausible and parsimonious explanation for the globally consistent pattern of higher endemism at higher elevations that we identify. We suggest that topography-driven isolation increases speciation rates in mountainous areas, across all elevations and increasingly towards the equator. If so, it represents a mechanism that may contribute to generating latitudinal diversity gradients in a way that is consistent with both present-day and palaeontological evidence

Transcription Regulation of Sex-Biased Genes during Ontogeny in the Malaria Vector Anopheles gambiae

In Anopheles gambiae, sex-regulated genes are responsible for controlling gender dimorphism and are therefore crucial in determining the ability of female mosquitoes to transmit human malaria. The identification and functional characterization of these genes will shed light on the sexual development and maturation of mosquitoes and provide useful targets for genetic control measures aimed at reducing mosquito fertility and/or distorting the sex ratio