1,720,981 research outputs found
The Intersection of Type 2 Diabetes and Cognitive Impairment in Mexican Americans: Insights from the Mitochondria
Get PDFMitochondrial dysfunction is common in numerous complex age-related diseases. The role of mitochondrial dysfunction in cognitive impairment has yet to be studied in Mexican American populations. This population serves as a group of interest due to their high prevalence of type 2 diabetes (T2D). T2D is known to be associated with cognitive impairment (CI), suggesting that Mexican American populations may be at greater risk for CI. In this study, mtDNA copy number (mtDNACN), cell-free mtDNA (CFmtDNA) levels and mitochondrial gene expression was assessed. MtDNACN was found to be decreased in CI, while CFmtDNA was found to be elevated in T2D. Cross-condition comparisons of mitochondrial expression elucidated characteristic expression profiles perhaps associated with the co-occurrence of T2D and CI pathology
Transcriptomic Signatures of Cognitive Impairment
Get PDFThe dramatic shift in population demographics and rapid growth of the aging population has resulted in a drastic increase in the prevalence of complex age-related diseases. Of the most common age-related complex diseases, Alzheimer's disease (AD) remains the primary cause of dementia. The increased prevalence of this disease presents a major burden on our healthcare system and caregivers. Among the many pathophysiological hallmarks, there is a substantial amount of literature implicating mitochondrial dysfunction as an important signature of early AD pathophysiology. Use of 'omics' technologies and system-based approaches have become increasingly more common for studying AD. Though each data type (i.e. genomics, transcriptomics and proteomics) has advantages and disadvantages, transcriptomics serves as a cost-efficient method for obtaining a snapshot of functional molecular changes underlying the disease. Here we detail two distinct and innovative studies of the transcriptome using different analytical strategies to investigate the underlying molecular signatures of cognitive impairment in its varying forms. We report the first study of differential gene expression in mild cognitively impaired Mexican Americans. This study revealed 30 differentially expressed transcripts that were enriched for a number of biological processes previously implicated in AD pathophysiology. The second study is also the first of its kind (in the context of this phenotype) examining posttranscriptional methylation at functionally important sites within the mitochondrial transcriptome of individuals diagnosed with AD, progressive supranuclear palsy (PSP) or pathological aging(PA). We observed similar hypermethylation at these key sites in individuals diagnosed with tauopathies such as AD or PSP. Several nuclear-encoded genes were identified as associated and the expression of 5300 nuclear-encoded transcripts was correlated with this hypermethylation. These correlated transcripts were enriched for a number of biological and molecular processes. Though these studies are quite distinct in methodology, we observed overlap in the enriched processes identified in each respective study (i.e. mitochondrial dysfunction, chromatin binding/remodeling, protein degradation pathways, autophagy); many of these processes have been previously implicated in AD. Replication of these findings in larger cohorts and different racial/ethnic populations will be vital for gaining a more complete understanding of the molecular dysfunction that underlies cognitive impairment phenotypes
Mitochondrial RNA Sequencing Variation in Age-Related Pathologies
No full textBackground. Mitochondrial function has been implicated in a number of age-related disease pathologies, and post-transcriptional sequence modifications in mitochondrial RNA (mtRNA) have been correlated with variation in the mitochondrial function. One of the most significant modifications is methylation of mitochondrial transfer RNAs (tRNA) at their 9th position (termed “p9 sites”). Post-transcriptional modifications to these tRNAs are known to alter efficiency of translation and protein synthesis, affecting downstream mitochondrial function. The impact that these modifications to the mitochondrial transcriptome have on risk for age-related disease has not been previously explored.
Purpose. The purpose of this study was to determine if altered post-transcriptional modification rates to mitochondrial p9 tRNA sites is associated with risk for age-related disease pathologies.
Methods. RNA sequencing and genotyping data was analyzed from cerebellar tissue of 275 Caucasian subjects consisting of elderly controls, and individuals with diagnosed AD, progressive supranuclear palsy or pathological aging. Data were obtained through the Synapse data repository and were collected by the Mayo RNAseq study, led by Dr. Nilüfer Ertekin-Taner, Mayo Clinic, Jacksonville, FL as part of the multi-PI U01 AG046139 (MPIs Golde, Ertekin-Taner, Younkin, Price). Heteroplasmy in mtRNA was measured using the VarScan software tool. Variants in the nuclear-encoded gene MRPP3 were analyzed for association with altered p9 methylation rates.
Results. Average number and rate of heteroplasmy at the 13 sites were compared across control and case groups. A higher rate of heteroplasmy was observed at the p9 sites, indicating the presence of methylation within these tRNAs.
Concluding Remarks. Post-transcriptional modification of mtRNA occurs under normal, non-pathologic states; alteration of methylation rate at the p9 site of mitochondrial tRNAs may be associated with aging pathology. The rate of p9 methylation has been associated with genetic factors encoded in the nuclear DNA (Hodgkinson et al., 2014). Targeting methylation of mitochondrial tRNA could prove to be a viable therapeutic approach for deficits in mitochondrial function
Influence of Nitrogen Deficiency on Ureide Mediated Stress Resistance in Arabidopsis thaliana
No full textThe relationship between nitrogen availability and presence of heavy metal stress appear to affect development and growth of Arabidopsis thaliana plants. In this work, Arabidopsis thaliana seedlings were exposed to media containing varying concentrations of nitrogen in form of NH4NO3 or KNO3 and cadmium in the form of CdCl2. When exposed to increasing cadmium stress, aln mutant lines, lacking a functional allantoinase enzyme, displayed enhanced growth and development when compared to wild type, most likely due to their high allantoin content. Increasing nitrogen concentrations appeared to decrease the amount of senescing tissue caused by exposure to cadmium stress. Growth appeared to be slightly increased in both wild type and aln mutant lines grown in media containing KNO3 as the nitrogen source, thereby supporting the importance of nitrogen source on plant growth
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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