Software and methods for oligonucleotide and cDNA array data analysis.

Two HTML-based programs were developed to analyze and filter gene-expression data: 'Bullfrog' for Affymetrix oligonucleotide arrays and 'Spot' for custom cDNA arrays. The programs provide intuitive data-filtering tools through an easy-to-use interface. A background subtraction and normalization program for cDNA arrays was also built that provides an informative summary report with data-quality assessments. These programs are freeware to aid in the analysis of gene-expression results and facilitate the search for genes responsible for interesting biological processes and phenotypes

Species delimitation and phylogeny of a New Zealand plant species radiation

<p>Abstract</p> <p>Background</p> <p>Delimiting species boundaries and reconstructing the evolutionary relationships of late Tertiary and Quaternary species radiations is difficult. One recent approach emphasizes the use of genome-wide molecular markers, such as amplified fragment length polymorphisms (AFLPs) and single nucleotide polymorphisms (SNPs), to identify distinct metapopulation lineages as taxonomic species. Here we investigate the properties of AFLP data, and the usefulness of tree-based and non-tree-based clustering methods to delimit species and reconstruct evolutionary relationships among high-elevation <it>Ourisia </it>species (Plantaginaceae) in the New Zealand archipelago.</p> <p>Results</p> <p>New Zealand <it>Ourisia </it>are shown to comprise a geologically recent species radiation based on molecular dating analyses of ITS sequences (0.4–1.3 MY). Supernetwork analyses indicate that separate tree-based clustering analyses of four independent AFLP primer combinations and 193 individuals of <it>Ourisia </it>produced similar trees. When combined and analysed using tree building methods, 15 distinct metapopulations could be identified. These clusters corresponded very closely to species and subspecies identified on the basis of diagnostic morphological characters. In contrast, Structure and PCO-MC analyses of the same data identified a maximum of 12 and 8 metapopulations, respectively. All approaches resolved a large-leaved group and a small-leaved group, as well as a lineage of three alpine species within the small-leaved group. We were unable to further resolve relationships within these groups as corrected and uncorrected distances derived from AFLP profiles had limited tree-like properties.</p> <p>Conclusion</p> <p><it>Ourisia </it>radiated into a range of alpine and subalpine habitats in New Zealand during the Pleistocene, resulting in 13 morphologically and ecologically distinct species, including one reinstated from subspecies rank. Analyses of AFLP identified distinct metapopulations consistent with morphological characters allowing species boundaries to be delimited in <it>Ourisia</it>. Importantly, Structure analyses suggest some degree of admixture with most species, which may also explain why the AFLP data do not exhibit sufficient tree-like properties necessary for reconstructing some species relationships. We discuss this feature and highlight the importance of improving models for phylogenetic analyses of species radiations using AFLP and SNP data.</p

Antarctic macrobenthic communities: a compilation of circumpolar information

Comprehensive information on Antarctic macrobenthic community structure has been publicly available since the 1960s. It stems from trawl, dredge, grab, and corer samples as well as from direct and camera observations (Table 1–2). The quality of this information varies considerably; it consists of pure descriptions, figures for presence (absence) and abundance of some key taxa or proxies for such parameters, e.g. sea-floor cover. Some data sets even cover a defined and complete proportion of the macrobenthos with further analyses on diversity and zoogeography. As a consequence the acquisition of data from approximately 90 different campaigns assembled here was not standardised. Nevertheless, it was possible to classify this broad variety of known macrobenthic assemblages to the best of expert knowledge (Gutt 2007; Fig. 1). This overview does not replace statistically sound community and diversity analyses. However, it shows from where which kind of information is available and it acts as an example of the feasibility and power of such data collections. The data set provides unique georeferenced biological basic information for the planning of future coordinated research activities, e.g. under the umbrella of the biology program “Antarctic Thresholds - Ecosystem Resilience and Adaptation” (AnT-ERA) of the Scientific Committee on Antarctic Research (SCAR) and especially for actual conservation issues, e.g. the planning of Marine Protected Areas (MPAs) by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR)

HST/WFC3 Observations of an Off-Nuclear Superbubble in Arp 220

We present a high spatial resolution optical and infrared study of the circumnuclear region in Arp 220, a late-stage galaxy merger. Narrowband imaging using HST/WFC3 has resolved the previously observed peak in H$\alpha$+[NII] emission into a bubble-shaped feature. This feature measures 1.6" in diameter, or 600 pc, and is only 1" northwest of the western nucleus. The bubble is aligned with the western nucleus and the large-scale outflow axis seen in X-rays. We explore several possibilities for the bubble origin, including a jet or outflow from a hidden active galactic nucleus (AGN), outflows from high levels of star formation within the few hundred pc nuclear gas disk, or an ultraluminous X-ray source. An obscured AGN or high levels of star formation within the inner $\sim$100 pc of the nuclei are favored based on the alignment of the bubble and energetics arguments.Comment: Accepted for publication in ApJ. 12 pages, 10 figure

Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest.

The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estimates for the three clonal C.&nbsp;gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole-genome sequencing of 134 C.&nbsp;gattii isolates and using Bayesian evolutionary analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate for each lineage (1.59 × 10-8, 1.59 × 10-8, and 2.70 × 10-8, respectively) to be an order of magnitude higher than common neutral fungal mutation rates (2.0 × 10-9), indicating a microevolutionary rate (e.g., successive clonal generations in a laboratory) in comparison to a species' slower, macroevolutionary rate (e.g., when using fossil records). The clonal nature of the PNW C.&nbsp;gattii emergence over a narrow number of years would therefore possibly explain our higher mutation rates. Our results suggest that the mean time to most recent common ancestor for all three sublineages occurred within the last 60 to 100&nbsp;years. While the cause of C.&nbsp;gattii dispersal to the PNW is still unclear, our research estimates that the arrival is neither ancient nor very recent (i.e., &lt;25 years ago), making a strong case for an anthropogenic introduction. IMPORTANCE The recent emergence of the pathogenic fungus Cryptococcus gattii in the Pacific Northwest (PNW) resulted in numerous investigations into the epidemiological and enzootic impacts, as well as multiple genomic explorations of the three primary molecular subtypes of the fungus that were discovered. These studies lead to the general conclusion that the subtypes identified likely emerged out of Brazil. Here, we conducted genomic dating analyses to determine the ages of the various lineages seen in the PNW and propose hypothetical causes for the dispersal events. Bayesian evolutionary analysis strongly suggests that these independent fungal populations in the PNW are all 60 to 100 years old, providing a timing that is subsequent to the opening of the Panama Canal, which allowed for more direct shipping between Brazil and the western North American coastline, a possible driving event for these fungal translocation events

Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

UnlabelledMigalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.Trial registrationClinicalTrials.gov NCT01196871

DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies

BACKGROUND: Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies. RESULTS: Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements. CONCLUSION: Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest

Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study

Objective To quantify the change in prescribing of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis, and any concurrent change in the incidence of infective endocarditis, following introduction of a clinical guideline from the National Institute for Health and Clinical Excellence (NICE) in March 2008 recommending the cessation of antibiotic prophylaxis in the United Kingdom

Mechanisms of aging in senescence-accelerated mice

BACKGROUND: Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). RESULTS: The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. CONCLUSION: We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases