The Physical Activity and Alzheimer's disease (PAAD) study: Cognitive outcomes

Background: Alzheimer’s disease is a progressive disease that degrades cognitive functioning and ultimately results in death. Currently, there is no cure for Alzheimer’s disease and, hence, the identification of preventative strategies is important. Physical activity (PA) is a behavioral intervention that holds promise with respect to delaying the onset of Alzheimer’s disease. Purpose: The purpose of this study was to explore the differential cognitive benefits achieved in response to PA as a function of a person’s genetic risk for AD. Methods: Older cognitively normal adults (50–65 years) with a family history of AD (FHxAD) participated in an 8-month PA program. Cognitive performance was measured at baseline, pretest, midtest, and posttest and changes over time were assessed as a function of apolipoprotein E (APOE) status (carriers: 1–2 copies of the ?4 allele; noncarriers: 0 copies of the ?4 allele). Results: Improvements in memory were associated with PA participation irrespective of APOE ?4 carrier status. Conclusions: Future experimental studies are needed to confirm that PA causes improvements to cognitive performance in older cognitively normal adults with a FHxAD and that these improvements are equivalent for cognitively normal APOE ?4 carriers and noncarriers

Investigating Risk Factors Predictive of Problem Outcomes Experienced by First Year Drinking and Non-Drinking Collegiate Student-Athletes

This study examined risk factors for problem outcomes experienced by drinking and non-drinking first year collegiate student-athletes. Freshman and transfer student-athletes (N=2956) reported their alcohol use, problems experienced and demographic/sport-related data via an online survey. We hypothesized extreme drinking, male, out-of-season, team sport and Division III would significantly predict experiencing more alcohol, sport and other-related problem outcomes. Results suggest that out-of-season, team sport and light, heavy or extreme drinking (versus non-drinking) student-athletes were more likely to report alcohol-related problems. Female and in-season student-athletes were more likely to experience sport-related problems. Other problem outcomes were more likely to be experienced by heavy and extreme drinkers but not light drinkers. Findings should guide prevention programming that targets high-risk student-athlete groups

Proteomics of canine lymphoma identifies potential cancer-specific protein markers

Purpose: Early diagnosis of cancer is crucial for the success of treatment of the disease, and there is a need for markers whose differential expression between disease and normal tissue could be used as a diagnostic tool. Spontaneously occurring malignancies in pets provide a logical tool for translational research for human oncology. Lymphoma, one of the most common neoplasms in dogs, is similar to human non-Hodgkin's lymphoma and could serve as an experimental model system. Experimental Design: Thirteen lymph nodes from normal dogs and 11 lymph nodes from dogs with B-cell lymphoma were subjected to proteomic analysis using two-dimensional PAGE separation and matrix-assisted laser desorption/ionization time-of-flight analysis. Results: A total of 93 differentially expressed spots was subjected to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry analysis, and several proteins that showed differential expression were identified. Of these, prolidase (proline dipeptidase), triosephosphate isomerase, and glutathione S-transferase were down-regulated in lymphoma samples, whereas macrophage capping protein was up-regulated in the lymphoma samples. Conclusions: These proteins represent potential markers for the diagnosis of lymphoma and should be further investigated in human samples for validation of their utility as diagnostic markers

Innovative Research Exploring the Effects of Physical Activity and Genetics on Cognitive Performance in Community-Based Older Adults

Physical activity is predictive of better cognitive performance and lower risk of Alzheimer’s disease (AD). The apolipoprotein E gene (APOE) is a susceptibility gene for AD with the e4 allele being associated with a greater risk of AD. Cross-sectional and prospective research shows that physical activity is predictive of better cognitive performance for those at greater genetic risk for AD. However, the moderating role of APOE on the effects of a physical activity intervention on cognitive performance has not been examined. The purpose of this manuscript is to justify the need for such research and to describe the design, methods, and recruitment tactics used in the conductance of a study designed to provide insight as to the extent to which cognitive benefits resulting from an 8-month physical activity program are differentiated by APOE e4 status. The effectiveness of the recruitment strategies and the feasibility of recruiting APOE e4 carriers are discussed

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

NAA10 polyadenylation signal variants cause syndromic microphthalmia

Background A single variant in NAA10 (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.Methods Three families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in NAA10 were evaluated using quantitative PCR and RNAseq.Results Genetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included NAA10. Exome sequencing identified a hemizygous NAA10 polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c.*43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct NAA10 PAS variants, chrX:g.153,195,401T>C, c.*39A>G and chrX:g.153,195,400T>C, c.*40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced NAA10 mRNA levels and abnormal 3′ UTRs in affected individuals. Targeted sequencing of NAA10 in 376 additional affected individuals failed to identify variants in the PAS.Conclusion These data show that PAS variants are the most common variant type in NAA10-associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that NAA10 harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yi

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Quantification of codon selection for comparative bacterial genomics

<p>Abstract</p> <p>Background</p> <p>Statistics measuring codon selection seek to compare genes by their sensitivity to selection for translational efficiency, but existing statistics lack a model for testing the significance of differences between genes. Here, we introduce a new statistic for measuring codon selection, the Adaptive Codon Enrichment (ACE).</p> <p>Results</p> <p>This statistic represents codon usage bias in terms of a probabilistic distribution, quantifying the extent that preferred codons are over-represented in the gene of interest relative to the mean and variance that would result from stochastic sampling of codons. Expected codon frequencies are derived from the observed codon usage frequencies of a broad set of genes, such that they are likely to reflect nonselective, genome wide influences on codon usage (<it>e.g</it>. mutational biases). The relative adaptiveness of synonymous codons is deduced from the frequency of codon usage in a pre-selected set of genes relative to the expected frequency. The ACE can predict both transcript abundance during rapid growth and the rate of synonymous substitutions, with accuracy comparable to or greater than existing metrics. We further examine how the composition of reference gene sets affects the accuracy of the statistic, and suggest methods for selecting appropriate reference sets for any genome, including bacteriophages. Finally, we demonstrate that the ACE may naturally be extended to quantify the genome-wide influence of codon selection in a manner that is sensitive to a large fraction of codons in the genome. This reveals substantial variation among genomes, correlated with the tRNA gene number, even among groups of bacteria where previously proposed whole-genome measures show little variation.</p> <p>Conclusions</p> <p>The statistical framework of the ACE allows rigorous comparison of the level of codon selection acting on genes, both within a genome and between genomes.</p

Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis

BACKGROUND: Whether overweight or obese end stage renal disease (ESRD) patients are suitable for renal transplantation (RT) is often debated. The objective of this review and meta-analysis was to systematically investigate the outcome of low versus high BMI recipients after RT. METHODS: Comprehensive searches were conducted in MEDLINE OvidSP, Web of Science, Google Scholar, Embase, and CENTRAL (the Cochrane Library 2014, issue 8). We reviewed four major guidelines that are available regarding (potential) RT recipients. The methodology was in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and written based on the PRISMA statement. The quality assessment of studies was performed by using the GRADE tool. A meta-analysis was performed using Review Manager 5.3. Random-effects models were used. RESULTS: After identifying 5,526 studies addressing this topic, 56 studies were included. We extracted data for 37 outcome measures (including data of more than 209,000 RT recipients), of which 26 could be meta-analysed. The following outcome measures demonstrated significant differences in favour of low BMI (<30) recipients: mortality (RR = 1.52), delayed graft function (RR = 1.52), acute rejection (RR = 1.17), 1-, 2-, and 3-year graft survival (RR = 0.97, 0.95, and 0.97), 1-, 2-, and 3-year patient survival (RR = 0.99, 0.99, and 0.99), wound infection and dehiscence (RR = 3.13 and 4.85), NODAT (RR = 2.24), length of hospital stay (2.31 days), operation duration (0.77 hours), hypertension (RR = 1.35), and incisional hernia (RR = 2.72). However, patient survival expressed in hazard ratios was in significant favour of high BMI recipients. Differences in other outcome parameters were not significant. CONCLUSIONS: Several of the pooled outcome measurements show significant benefits for ‘low’ BMI (<30) recipients. Therefore, we postulate that ESRD patients with a BMI >30 preferably should lose weight prior to RT. If this cannot be achieved with common measures, in morbidly obese RT candidates, bariatric surgery could be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0340-5) contains supplementary material, which is available to authorized users

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies