Fragile X Mental Retardation 1 and Filamin A Interact Genetically in Drosophila Long-Term Memory

The last decade has witnessed the identification of single-gene defects associated with an impressive number of mental retardation syndromes. Fragile X syndrome, the most common cause of mental retardation for instance, results from disruption of the FMR1 gene. Similarly, Periventricular Nodular Heterotopia, which includes cerebral malformation, epilepsy and cognitive disabilities, derives from disruption of the Filamin A gene. While it remains unclear whether defects in common molecular pathways may underlie the cognitive dysfunction of these various syndromes, defects in cytoskeletal structure nonetheless appear to be common to several mental retardation syndromes. FMR1 is known to interact with Rac, profilin, PAK and Ras, which are associated with dendritic spine defects. In Drosophila, disruptions of the dFmr1 gene impair long-term memory (LTM), and the Filamin A homolog (cheerio) was identified in a behavioral screen for LTM mutants. Thus, we investigated the possible interaction between cheerio and dFmr1 during LTM formation in Drosophila. We show that LTM specifically is defective in dFmr1/cheerio double heterozygotes, while it is normal in single heterozygotes for either dFmr1 or cheerio. In dFmr1 mutants, Filamin (Cheerio) levels are lower than normal after spaced training. These observations support the notion that decreased actin cross-linking may underlie the persistence of long and thin dendritic spines in Fragile X patients and animal models. More generally, our results represent the first demonstration of a genetic interaction between mental retardation genes in an in vivo model system of memory formation

GeneSeer: A sage for gene names and genomic resources

BACKGROUND: Independent identification of genes in different organisms and assays has led to a multitude of names for each gene. This balkanization makes it difficult to use gene names to locate genomic resources, homologs in other species and relevant publications. METHODS: We solve the naming problem by collecting data from a variety of sources and building a name-translation database. We have also built a table of homologs across several model organisms: H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, S. cerevisiae, S. pombe and A. thaliana. This allows GeneSeer to draw phylogenetic trees and identify the closest homologs. This, in turn, allows the use of names from one species to identify homologous genes in another species. A website is connected to the database to allow user-friendly access to our tools and external genomic resources using familiar gene names. CONCLUSION: GeneSeer allows access to gene information through common names and can map sequences to names. GeneSeer also allows identification of homologs and paralogs for a given gene. A variety of genomic data such as sequences, SNPs, splice variants, expression patterns and others can be accessed through the GeneSeer interface. It is freely available over the web and can be incorporated in other tools through an http-based software interface described on the website. It is currently used as the search engine in the RNAi codex resource, which is a portal for short hairpin RNA (shRNA) gene-silencing constructs

Molecular cloning of linotte in Drosophila: A novel gene that functions in adults during associative learning

AbstractThe linotte (lio) gene was identified in a screen for mutations that disrupted 3 hr memory after olfactory associative learning, without affecting the perception of odors or electroschock. The mutagenesis yielded a transposon-tagged gene disruption, which allowed rapid cloning of genomic DNA. The lio transcription unit was identified via rescue of the lio1 learning/memory defect by induced expression of a lio+ transgene in adults. The perception of odors or electroshock remained normal when the lio+ transgene was expressed in these lio1 flies. Learning/memory remained normal when the lio+ transgene was expressed in wild-type (lio+) flies. The lio gene produces only one transcript, the level of expression of which varies throughout development. Sequence analysis indicates that lio encodes a novel protein

An assay for social interaction in Drosophila fragile X mutants

We developed a novel assay to examine social interactions in Drosophila and, as a first attempt, apply it here at examining the behavior of Drosophila Fragile X Mental Retardation gene (dfmr1) mutants. Fragile X syndrome is the most common cause of single gene intellectual disability (ID) and is frequently associated with autism. Our results suggest that dfmr1 mutants are less active than wild-type flies and interact with each other less often. In addition, mutants for one allele of dfmr1, dfmr1B55, are more likely to come in close contact with a wild-type fly than another dfmr1B55 mutant. Our results raise the possibility of defective social expression with preserved receptive abilities. We further suggest that the assay may be applied in a general strategy of examining endophenoypes of complex human neurological disorders in Drosophila, and specifically in order to understand the genetic basis of social interaction defects linked with ID

Prevalence, Nature, Severity and Risk Factors for Prescribing Errors in Hospital Inpatients : Prospective Study in 20 UK Hospitals

Funding This study was funded by the General Medical Council (GMC). The study funders had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of this manuscript or in the decision to submit the article for publication. Acknowledgements The EQUIP team would like to thank the following people: Members of the Expert Reference Group (Graham Buckley, Gary Cook, Dianne Parker, Lesley Pugsley and Mike Scott); Members of the Error Validation Group (Lindsay Harper, Katy Mellor, Steven Williams, Keith Harkins, Steve McGlynn, Ray George, Tim Dornan, Penny Lewis); Tribal Consulting Ltd. (Heather Heathfield, Emma Carter) for database design; Study co-ordinators at hospitals (Linda Aldred, Deborah Armstrong, Isam Badhawi, Kathryn Ball, Neil Caldwell, Vanya Fidling, Nicholas Fong, Heather Ford, Andrea Gill, Lindsay Harper, Jean Holmes, Sally James, Christopher Poole, Sally Shaw, Heather Smith, Julie Street, Atia Rifat, David Thornton, Tracey Thornton, Jane Warren, Steven Williams), and all pharmacists at the study sites who collected data for this study.Peer reviewedPublisher PD

Quality standards for digital forensics : learning from experience in England & Wales

The Forensic Science Regulator has the role of setting quality standards for forensic science in the Criminal Justice System (CJS) in England and Wales. The current requirement is for organisations carrying out digital forensics to gain accreditation to the international standard ISO/IEC 17025 and the Forensic Science Regulator's Codes of Practice and Conduct. The aim of this requirement is to embed a systematic approach to quality, including understanding methods, validating software and systems, understanding risks, ensuring that all involved in the crime scene to court process have the skills and competence they need and the appropriate equipment and environment for the work, and providing ongoing assurance of quality through audit and proficiency tests. However, the challenge of implementing the standards in digital forensics should not be underestimated, particularly in an environment where there is insufficient capacity to meet a growing demand for services in an area of increasing complexity and fragmented delivery. It is therefore timely to review available data to determine the extent to which accreditation to ISO/IEC 17025 is addressing quality issues in digital forensics and consider what changes and resources could be made available to assist with implementation of quality systems

N-body simulations of the Magellanic Stream

A suite of high-resolution N-body simulations of the Magellanic Clouds -- Milky Way system are presented and compared directly with newly available data from the HI Parkes All-Sky Survey (HIPASS). We show that the interaction between Small and Large Magellanic Clouds results in both a spatial and kinematical bifurcation of both the Stream and the Leading Arm. The spatial bifurcation of the Stream is readily apparent in the HIPASS data, and the kinematical bifurcation is also tentatively identified. This bifurcation provides strong support for the tidal disruption origin for the Magellanic Stream. A fiducial model for the Magellanic Clouds is presented upon completion of an extensive parameter survey of the potential orbital configurations of the Magellanic Clouds and the viable initial boundary conditions for the disc of the Small Magellanic Cloud. The impact of the choice of these critical parameters upon the final configurations of the Stream and Leading Arm is detailed.Comment: Accepted by MNRAS, 07 Jun 2006. 14 pages, 14 figures, 3 tables. LaTeX (mn2e.sty). File with decent resolution images (strongly recommended) available at http://astronomy.swin.edu.au/~tconnors/publications/ . References added; distance and HI-LOres difference figures added; clearer figures; discussion added to, but conclusions unchange

Segregation of Odor Identity and Intensity during Odor Discrimination in Drosophila Mushroom Body

Molecular and cellular studies have begun to unravel a neurobiological basis of olfactory processing, which appears conserved among vertebrate and invertebrate species. Studies have shown clearly that experience-dependent coding of odor identity occurs in “associative” olfactory centers (the piriform cortex in mammals and the mushroom body [MB] in insects). What remains unclear, however, is whether associative centers also mediate innate (spontaneous) odor discrimination and how ongoing experience modifies odor discrimination. Here we show in naïve flies that Gαq-mediated signaling in MB modulates spontaneous discrimination of odor identity but not odor intensity (concentration). In contrast, experience-dependent modification (conditioning) of both odor identity and intensity occurs in MB exclusively via Gαs-mediated signaling. Our data suggest that spontaneous responses to odor identity and odor intensity discrimination are segregated at the MB level, and neural activity from MB further modulates olfactory processing by experience-independent Gαq-dependent encoding of odor identity and by experience-induced Gαs-dependent encoding of odor intensity and identity

Bulge n and B/T in High Mass Galaxies: Constraints on the Origin of Bulges in Hierarchical Models

We use the bulge Sersic index n and bulge-to-total ratio (B/T) to explore the fundamental question of how bulges form. We perform 2D bulge-disk-bar decomposition on H-band images of 143 bright, high stellar mass (>1.0e10 solar masses) low-to-moderately inclined (i<70 degrees) spirals. Our results are: (1) Our H-band bar fraction (~58%) is consistent with that from ellipse fits. (2) 70% of the stellar mass is in disks, 10% in bars, and 20% in bulges. (3) A large fraction (~69%) of bright spirals have B/T<0.2, and ~76% have low n<2 bulges. These bulges exist in barred and unbarred galaxies across a wide range of Hubble types. (4) About 65% (68%) of bright spirals with n<2 (B/T<0.2) bulges host bars, suggesting a possible link between bars and bulges. (5) We compare the results with predictions from a set of LCDM models. In the models, a high mass spiral can have a bulge with a present-day low B/T<0.2 only if it did not undergo a major merger since z<2. The predicted fraction (~1.6%) of high mass spirals, which have undergone a major merger since z<4 and host a bulge with a present-day low B/T<0.2, is a factor of over thirty smaller than the observed fraction (~66%) of high mass spirals with B/T<0.2. Thus, contrary to common perception, bulges built via major mergers since z<4 seriously fail to account for the bulges present in ~66% of high mass spirals. Most of these present-day low B/T<0.2 bulges are likely to have been built by a combination of minor mergers and/or secular processes since z<4.Comment: Accepted by the Astrophysical Journal. 42 pages of text, 27 figures, 12 table

Olfactory Jump Reflex Habituation in Drosophila and Effects of Classical Conditioning Mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity