1,720,986 research outputs found
Comparative interactome mapping of Tau‐protein in classical and rapidly progressive Alzheimer's disease identifies subtype‐specific pathways
Abstract
Aims
Tau is a key player in Alzheimer's disease (AD) and other Tauopathies. Tau pathology in the brain directly correlates with neurodegeneration in AD. The recent identification of a rapid variant of AD demands an urgent need to uncover underlying mechanisms leading to differential progression in AD. Accordingly, we aimed to dissect the underlying differential mechanisms of toxicity associated with the Tau protein in AD subtypes and to find out subtype‐dependent biomarkers and therapeutic targets.
Methods
To identify and characterise subtype‐specific Tau‐associated mechanisms of pathology, we performed comparative interactome mapping of Tau protein in classical AD (cAD) and rapidly progressive AD (rpAD) cases using co‐immunoprecipitation coupled with quantitative mass spectrometry. The mass spectrometry data were extensively analysed using several bioinformatics approaches.
Results
The comparative interactome mapping of Tau protein revealed distinct and unique interactors (DPYSL4, ARHGEF2, TUBA4A and UQCRC2) in subtypes of AD. Interestingly, an analysis of the Tau‐interacting proteins indicated enrichment of mitochondrial organisation processes, including negative regulation of mitochondrion organisation, mitochondrial outer membrane permeabilisation involved in programmed cell death, regulation of autophagy of mitochondrion and necroptotic processes, specifically in the rpAD interactome. While, in cAD, the top enriched processes were related to oxidation–reduction process, transport and monocarboxylic acid metabolism.
Conclusions
Overall, our results provide a comprehensive map of Tau‐interacting protein networks in a subtype‐dependent manner and shed light on differential functions/pathways in AD subtypes. This comprehensive map of the Tau‐interactome has provided subsets of disease‐related proteins that can serve as novel biomarkers/biomarker panels and new drug targets
Amplified fragment length polymorphism (AFLP) analysis of genetic variability in Phalaenopsis
Amplified fragment length polymorphism (AFLP) markers allow a rapid assessment of the level of genetic variation that would be difficult to evaluate using a limited number of morphological markers. AFLP was used to assess the level of genetic variation among 16 different Phalaenopsis species and hybrids. Ten AFLP primer combinations were used for genetic analysis of these Phalaenopsis and 95% of polymorphism in 16 Phalaenopsis species and hybrids was detected. The genetic similarity among Phalaenopsis species and hybrids ranged from 0.298 to 0.774 based on Dice coefficient. The dendrogram derived by UPGMA analysis clustered into two main groups. A significant linear relationship (r² = 0.524, P < 0.0001) was observed between known pedigrees and AFLP-derived genetic similarity for 136 pairwise comparisons of Phalaenopsis species and hybrids. The results indicate that there is an abundance of genetic diversity among within Phalaenopsis and that AFLP can be used to distinguish morphologically similar genotypes.
In a second study, the effect of gametophytic selection on genetic diversity in Phalaenopsis was examined by AFLP analysis. Sixteen F1 seedlings resulting from cross-pollination that occurred within high (30 ºC) and low (14 ºC) temperature incubators between two hybrid Phalaenopsis [P. (Taisoco Windian à Sogo Yukidian) by P. hybrid unknown], were subjected to genetic analysis by AFLP. A total of 651 fragments ranging in size from 100 to 350 bp were detected using six primer combinations, of which 387 (59.4%) were polymorphic. Seedlings derived from different temperature treatments exhibited 25.5% to 35.9% polymorphism. The genetic similarity among 16 F1 seedlings ranged from 0.825 to 0.946 based on the Dice coefficient. A dendrogram based on 387 polymorphic markers was derived by UPGMA analysis resulting in three major groups and one subgroup. The dendrogram analysis showed clear clustering in Phalaenopsis hybrids pollinated under different temperature treatments, suggesting that several loci may have been selected during the divergent temperature stress treatments during pollination and early pollen tube growth.Master of Scienc
Use of RAPD markers in plant varietal development
DNA based molecular markers have played an important role in plant varietal development. With the discovery of polymerase chain reaction (PCR), very low or single copy sequences can act as molecular markers because during the PCR, DNA is multiplied to such an extent that it can be easily visualized on an agarose gel. With the new technique of random amplification of genomic DNA, there is no need to know the target DNA sequence, and specific primers and ample polymorphism can be revealed.Rye (Secale cereale L.) contains agronomically important genes that have been transferred to wheat through chromosomal translocations. Extensive polymorphisms were observed among six varieties of rye, Balboa, Blanco, Chaupon, Imperial, Insave and Musketeer by random amplified polymorphic DNA (RAPD) markers. In addition to the varieties, amplification patterns of individual plants were also studied.Rye chromosome 1RS containing wheat lines were studied by random primers to find markers specific for rye translocation. Hexaploid wheat lines carrying 1RS.1BL translocation in Chisholm and Arkan background, 1RS.1AL translocations and 1RS.1BL translocations in tetraploid wheat were analyzed. Two 1RS specific markers, OPR19\sb{1350} and OPJ07\sb{1200} were established. The two markers had no sequence homology to each other. The presence of 1RS specific OPJ07\sb{1200} was confirmed by two specific primers and hybridization studies.RAPD markers have the potential to identify plant varieties, species and hybrids. Species specific amplification profiles for 17 rhododendron species, hybrids and varieties were produced. The amplification patterns were stable among clonally propagated rhododendron species, but when F2 plants of two hybrids were studied with RAPDs, extensive polymorphisms were observed among individual F2 plants. The stability of RAPD profiles among clonally propagated rhododendrons and polymorphisms among F2 hybrids describes their usefulness in plant identification and genetic studies.Amplification profiles of thirteen rhododendron hybrids, species and varieties were analyzed to study their genetic relationship. In the cluster analysis, the hybrids with common parents grouped together and showed a close association as compared to the others. The overall genetic relationship revealed by cluster analysis was consistent with their known pedigrees.Made available in DSpace on 2011-05-07T13:38:38Z (GMT). No. of bitstreams: 2
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Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Assessment of Genetic Variation of Acer rubrum L. and Liriodendron tulipifera L. Populations in Unmanaged Forests of the Southeast United States
Acer rubrum L. and Liriodendron tulipifera L. are prolific throughout their ranges in the Southeastern U.S. and also have increasingly important roles in forestry and wood products in this region. The relatively low density and intermediate strength of the wood makes them versatile for use in many different wood products. Exploring the genetic structure of these species could provide a foundation for further genetic and breeding exploration with these economically important trees. This study utilizes amplified fragment length polymorphism to determine the level of genetic diversity of these species in contrasting physiographic provinces. AFLP was performed using five primer combinations on samples collected from six unmanaged populations of each species in the Mountains and Coastal Plain of the Southeastern U.S. Wood density was determined using an X-ray densitometer. A. rubrum lacked strong genetic structure while L. tulipifera showed differentiation between physiographic provinces. Genetic diversity of A. rubrum was lower within the Mountain populations (He: 0.327) than the Coastal Plain populations (He: 0.365). The average wood density for A. rubrum is lower in the Mountains (539.00 kg/m^3) than in the Coastal Plain (575.43 kg/m^3). Genetic diversity of L. tulipifera was higher overall (He: 0.289) than within the Mountain populations (He: 0.281) or the Coastal Plain populations (He: 0.271). The average wood density for L. tulipifera is greater in the Mountains (445.45 kg/m^3) than in the Coastal Plain (441.67 kg/m^3).Master of Scienc
Variations on the Author
“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
We 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
We 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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