Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Pneumonia and meningitis in a Beagle Dog caused by Actinomyces bowdenii

A 5-year-old female Beagle Dog was euthanized following ten days of inappetence, lethargy, and pain in the left cervical region that was not responsive to steroids or antibiotics. At necropsy, there were multiple soft dark red to tan nodules throughout all lung lobes, abundant purulent subdural exudate over the right temporal lobe of the brain, and minimally enlarged submandibular and tracheobronchial lymph nodes. Impression smear of the subdural pus and histologic section of the lung and meninges demonstrated small aggregates of rod-shaped to filamentous bacteria often surrounded by Splendori-Hoeppli material. Aerobic culture of the subdural exudate yielded pure growth of Actinomyces bowdenii. To our knowledge, this is the first report of central nervous disease or pneumonia associated with Actinomyces bowdenii

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Poster 2 Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Project Plan Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Midterm Report Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Poster 1 Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Abstract Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste

Edutainment (semester?), IPRO 329: Edutainment IPRO 329 Final Report Sp05

This semester IPRO 329, Edutainment, turns its complete efforts toward an educational computer gaming suite targeted at fourth-grade students and the subjects these students struggle with most in school. It is tentatively entitled Scholars of the Lost Exhibit. Work on this project began last semester as the team completed their award-winning game College Pursuit. During this semester, we will focus on the design, development, testing, and marketing of Scholars of the Lost Exhibit.Deliverables for IPRO 329: Edutainment for the Spring 2005 semeste