The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected ...model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.
Significant increases to the atmospheric radiation environment are recorded by a network of ground level neutron monitors as ground level enhancements (GLEs). These space weather phenomena pose a ...risk to aviation via single event effects in aircraft electronics and ionizing dose to passengers and crew. Under the UK Space Weather Instrumentation, Measurement, Modeling and Risk programme, we have developed a new model to provide nowcasts of the aviation radiation environment, including both the galactic cosmic ray (GCR) background and during GLE events. The Model for Atmospheric Ionising Radiation Effects (MAIRE+) uses multiple data sources to characterize primary GCR and GLE particle spectra and combines these with precalculated geomagnetic and atmospheric response matrices to predict particle fluxes from ground level to 20 km altitude across the entire globe. Two European neutron monitors (located at Oulu in Finland and Dourbes in Belgium) are used as the primary indicators of GLE intensity in order to maximize accuracy over UK airspace. Outputs from MAIRE+ for the historical GLEs in September and October 1989 are compared to recalibrated empirical data from a solid‐state detector that was carried on Concorde in that period. The model will be hosted in the UK and will provide additional capability to the Met Office Space Weather Operations Center (MOSWOC).
Plain Language Summary
Ionizing radiation in the atmosphere is primarily caused by galactic cosmic rays (GCR) interacting with the upper atmosphere, creating showers of secondary radiation. At aviation altitudes the radiation environment is hundreds of times more intense than that experienced at the ground level. This relatively stable background level of radiation is punctuated by space weather events called ground level enhancements (GLEs), when energetic solar protons arrive at Earth and lead to elevated atmospheric radiation levels that can be orders of magnitude greater than background levels. Under the UK Space Weather Instrumentation, Measurement, Modeling and Risk programme, we have developed a new model to provide nowcasts of the aviation radiation environment, including both the GCR background and during GLE events. Through our Model for Atmospheric Ionising Radiation Effects, we show how data from ground level neutron monitors can be used to characterize the atmospheric radiation environment from ground level to 20 km altitude across the entire globe.
Key Points
The new Model for Atmospheric Ionising Radiation Effects (MAIRE+) is presented
MAIRE+ uses neutron monitor data, sunspot number, Kp, and geostationary proton flux to nowcast the aviation radiation environment
Model outputs are compared to data from a solid‐state detector carried on board Concorde during ground level enhancements in 1989
Exploration of chemical composition and structural configuration space is the central problem in crystal structure prediction. Even in limiting structure space to a single structure type, many ...different compositions and configurations are possible. In this work, we attempt to address this problem using an extension to the existing ChemDASH code in which variable compositions can be explored. We show that ChemDASH is an efficient method for exploring a fixed-composition space of spinel structures and build upon this to include variable compositions in the Mn-Fe-Zn-O spinel phase field. This work presents the first basin-hopping crystal structure prediction method that can explore variable compositions.
The vc-ChemDASH methodology allows for the simultaneous evolution of composition and configuration of a system to find stable solid solutions.
Edwardsiella ictaluri is the cause of extensive mortalities and economic losses to the channel catfish industry of the southeast United States. Here we report the complete genome of Edwardsiella ...ictaluri 93-146. Whole-genome sequence analysis of E. ictaluri provides a tool for understanding the genomic regions specific to the species and the Edwardsiella genus.
Osteosarcoma is the most common cancer of bone occurring mostly in teenagers. Despite rapid advances in our knowledge of the genetics and cell biology of osteosarcoma, significant improvements in ...patient survival have not been observed. The identification of effective therapeutics has been largely empirically based. The identification of new therapies and therapeutic targets are urgently needed to enable improved outcomes for osteosarcoma patients.
We have used genetically engineered murine models of human osteosarcoma in a systematic, genome-wide screen to identify new candidate therapeutic targets. We performed a genome-wide siRNA screen, with or without doxorubicin. In parallel, a screen of therapeutically relevant small molecules was conducted on primary murine- and primary human osteosarcoma-derived cell cultures. All results were validated across independent cell cultures and across human and mouse osteosarcoma.
The results from the genetic and chemical screens significantly overlapped, with a profound enrichment of pathways regulated by PI3K and mTOR pathways. Drugs that concurrently target both PI3K and mTOR were effective at inducing apoptosis in primary osteosarcoma cell cultures in vitro in both human and mouse osteosarcoma, whereas specific PI3K or mTOR inhibitors were not effective. The results were confirmed with siRNA and small molecule approaches. Rationale combinations of specific PI3K and mTOR inhibitors could recapitulate the effect on osteosarcoma cell cultures.
The approaches described here have identified dual inhibition of the PI3K-mTOR pathway as a sensitive, druggable target in osteosarcoma, and provide rationale for translational studies with these agents.
The progress on developing models of the radiation environment since the 1960s is reviewed with emphasis on models that can be applied to predicting the performance of microelectronics used in ...spacecraft and instruments. Space, atmospheric, and ground environments are included. It is shown that models must be adapted continually to account for increased understanding of the dynamics of the radiation environment and the changes in microelectronics technology. The IEEE Nuclear and Space Radiation Effects Conference is a vital forum to report model progress to the radiation effects research community.
Females in almost all animal groups copulate with multiple males,. This behaviour allows different males to compete for fertilization and gives females the opportunity to mediate this competition. In ...many animals and most insects, the second male to copulate with a female typically sires most of her offspring,,. In Drosophila melanogaster, this second-male sperm precedence has long been studied but, as in most species, its mechanism has remained unknown. Here we show, using labelled sperm in doubly mated females, that males can both physically displace andincapacitate stored sperm from earlier-mating males. Displacement occurs only if the second male transfers sperm to the female, and in only one of her three sperm-storage organs. Incapacitation can be caused by either fertile or spermless second males, but requires extended intervals between matings. Sperm from different males are not 'stratified' in the storage organs but mix freely. Many animal species may have multiple mechanisms of sperm competition like those observed here, and revealing these mechanisms is necessary to understand the genetic and evolutionary basis of second-male sperm precedence in animals.
The objectives, instrumentation, methods and data leading up to launch of the NASA Living With a Star (LWS) Space Environment Testbed (SET) payload onboard the Air Force Research Laboratory ...Demonstration and Science Experiments (DSX) spacecraft are described. The experiments characterize the space radiation environment and how it affects hardware performance. The payload consists of a compact space weather instrument and a carrier containing four board experiments.
Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to ...stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia – with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan. The presence of sex and stress steroid receptors in the hippocampus provides a point of influence for these variables to drive changes in cognitive function. Here, we used a rodent model of chronic adolescent stress (CAS) to determine the extent to which CAS modifies glutamatergic signaling resulting in cognitive dysfunction. Male and female Wistar rats born in-house remained non-stressed (NS), unmanipulated aside from standard cage cleaning, or were exposed to either physical restraint (60 min) or social defeat (CAS) each day (6 trials each), along with social isolation, throughout the adolescent period (PND 35–47). Cognition was assessed in adult (PND 80–130) male and female rats (n = 10–12) using the Barnes Maze task and the Attention Set-Shift task. Whole hippocampi were extracted from a second cohort of male and female rats (NS and CAS; n = 9–10) and processed for RNA sequencing. Brain tissue from the first cohort (n = 6) was processed for density of glutamatergic synaptic markers (GluA1, NMDA1a, and synaptophysin) or whole-cell patch clamping (n = 4) to determine glutamatergic activity in the hippocampus. Females with a history of chronic stress had shorter latencies to locate the goal box than NS controls during acquisition learning but showed an increased latency to locate the new goal box during reversal learning. This reversal deficit persisted across domains as females with a history of stress required more trials to reach criterion during the reversal phases of the Attention Set-Shift task compared to controls. Ovariectomy resulted in greater performance variability overall during reversal learning with CAS females showing worse performance. Males showed no effects of CAS history on learning or memory performance. Bioinformatic prediction using gene ontology categorization indicated that in females, postsynaptic membrane gene clusters, specifically genes related to glutamatergic synapse remodeling, were enriched with a history of stress. Structural analysis indicated that CAS did not alter glutamate receptor density in females. However, functionally, CAS females had a decreased AMPA/NMDA-dependent current ratio compared to controls indicating a weakening in synaptic strength in the hippocampus. Males showed only a slight change in density of NMDA1a labeling in the CA3 region with a history of stress. The data observed here suggest that females are at risk for impaired cognitive flexibility following a history of adolescent stress, possibly driven by changes in glutamatergic signaling.
Ensembl 2007 Hubbard, T J P; Aken, B L; Beal, K ...
Nucleic acids research,
01/2007, Letnik:
35, Številka:
1
Journal Article
Recenzirano
The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from ...Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.
PDF
