Whole genome sequencing reveals a 7 base-pair deletion in DMD exon 42 in a dog with muscular dystrophy

Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on the X-chromosome. Truncating mutations in the DMD gene cause loss of dystrophin and the classical DMD clinical syndrome. Spontaneous DMD gene mutations and associated phenotypes occur in several other species. The mdx mouse model and the golden retriever muscular dystrophy (GRMD) canine model have been used extensively to study DMD disease pathogenesis and show efficacy and side effects of putative treatments. Certain DMD gene mutations in high-risk, the so-called hot spot areas can be particularly helpful in modeling molecular therapies. Identification of specific mutations has been greatly enhanced by new genomic methods. Whole genome, next generation sequencing (WGS) has been recently used to define DMD patient mutations, but has not been used in dystrophic dogs. A dystrophin-deficient Cavalier King Charles Spaniel (CKCS) dog was evaluated at the functional, histopathological, biochemical, and molecular level. The affected dog’s phenotype was compared to the previously reported canine dystrophinopathies. WGS was then used to detect a 7 base pair deletion in DMD exon 42 (c.6051-6057delTCTCAAT mRNA), predicting a frameshift in gene transcription and truncation of dystrophin protein translation. The deletion was confirmed with conventional PCR and Sanger sequencing. This mutation is in a secondary DMD gene hotspot area distinct from the one identified earlier at the 5′ donor splice site of intron 50 in the CKCS breed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-016-9675-2) contains supplementary material, which is available to authorized users

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

mTor, acting mainly via mTORC1, controls dystrophin transcription in a raptor- and rictor-independent mechanism

Who teaches writing?

Who Teaches Writing is an open teaching and learning resource being used in English Composition classes at Oklahoma State University. It was authored by contributors from Oklahoma State University and also includes invited chapters from other institutions both inside and outside of Oklahoma. Contributors include faculty from various departments, contingent faculty and staff, and graduate instructors. One purpose of the resource is to provide short, relatively jargon-free chapters geared toward undergraduate students taking First-Year Composition. Support for this project was provided in part by OpenOKState and Oklahoma State University Libraries.OpenOKStateOklahoma State University LibrariesLibraryEnglis

Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

A Comparison of Quality of Life between Intense and Non-Intense Treatment for Patients with Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome

Acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) are hematologic malignancies that occur most frequently in the sixth and seventh decades of life. Both disorders are associated with a poor prognosis, with median survival of one year or less. An overall five-year survival rate for both disorders, regardless of treatment, is less than 10%. A primary goal of treatment is to improve quality of life (QOL) because cure is improbable. The purpose of this longitudinal cohort study was to compare QOL between groups, intensive, non-intensive therapy, and supportive care. The sample consisted of 85 patients with high risk MDS and AML recruited from Moffitt Cancer Center. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure QOL. The aims for the study were to: 1) To compare the difference in QOL scores measured by the Functional Assessment of Cancer Therapy –Leukemia version for intensive chemotherapy, non-intensive therapy and supportive care within 7 days of new treatment and one month after initiation of treatment; 2) To determine QOL predictors of AML and high risk MDS from age, comorbidity, fatigue, and diagnosis; 3) To test the moderating effect of treatment with age, comorbidity, and fatigue on QOL. The first aim was analyzed with repeated measures analysis of variance (ANOVA). The supportive care group was not included in the analysis because of low accrual. Results indicated that there was a significant group by time interaction (with p=.040). Follow up tests revealed that the intensive treatment group had a significant improvement in their QOL scores at 1 month post treatment (p=.020). The second aim was conducted using Pearson’s correlations with age, comorbidity, fatigue, and diagnosis with significant correlations found between fatigue and QOL (r=-.693, p\u3c .001). These findings identify an important relationship between fatigue and QOL. This was a negative correlation, showing that as fatigue increases QOL decreases. The third aim was explored using regression with Hayes (2013) application for moderation analysis. Scores for QOL for age, comorbidity, and fatigue were not moderated by treatment. These findings suggest that the most intensive treatment approach improves QOL. In addition, fatigue is a significant predictor of QOL. As fatigue increases, QOL scores decrease. Additional studies with a larger, more diverse sample is needed to explore the relationship between treatment approaches and QOL. In addition, intervention studies can be developed in AML and high risk MDS focused on fatigue management. It is anticipated that the results of this study will be used to inform patients and health care providers when making decisions concerning treatment based on QOL outcomes

Acquired immunity protects against helminth infection in a natural host population: long-term field and laboratory evidence

Long-term records of parasite infection are rare for individuals in wild host populations. This study, on an introduced population of Xenopus laevis in Wales, demonstrates powerful control by acquired immunity of the monogenean, Protopolystoma xenopodis. Field evidence was based on a 10 year dataset for 619 individually-marked hosts screened at each capture for patent (egg-producing) infection. The adult parasite population occurred predominantly in juvenile hosts. Invasion began rapidly ‘post-birth' (in early tadpoles). Longitudinal records for animals aged ⩾15 years showed that, after loss of this primary infection, most hosts had strong resistance to re-infection. For ca. 80% of the population, no infections were recorded during adult life; for ca. 15%, there were isolated brief episodes of patent infection; for ca. 5%, parasites persisted as repeated short-term or chronic long-term infections. Acquired immunity was confirmed by laboratory challenge infection of wild-caught X. laevis: in 30/32 exposures, no parasites survived to maturity; in the two infected, development was retarded. Parasite persistence depends principally on host recruitment generating naïve young (as in human measles). In some hosts, retarded parasite development delays reproduction for several years: these infections show ‘Typhoid Mary' characteristics, persisting in ‘latent' form with potential to initiate epidemics in naïve cohorts

Creating Fiscal Space for Poverty Reduction in Ecuador: A Fiscal Management and Public Expenditure Review

The last Public Expenditure Review for Ecuador (PER) was produced in 1993. More than a decade later, the purpose of this report is to provide the Ecuadorian authorities with the World Bank's and Inter-American Development Bank's joint comprehensive account of their diagnoses and recommendations in the area of fiscal management and public expenditure. This report consists of two volumes. This first volume examines whether, and how, the core goals of public expenditure management, i.e., balanced fiscal aggregates, resource allocations to strategic sectors, and equity and microeconomic efficiency of public spending are met in Ecuador. Volume II presents sector studies on fiscal sustainability, the fiscal rules, education, health, pensions, the results of a national teachers' tracking survey, water and sanitation, electricity, telecommunications and oil.