1,720,953 research outputs found
Studies On The Role Of Mitochondrial Dysfunction In Amyloid- β Mediated Neurodegeneration
Full text linkAlzheimer’s disease (AD) is one of the major causes of dementia worldwide. AD is
characterized clinically by progressive cognitive decline, and pathologically by the presence of
extracellular senile plaques composed primarily of amyloid-β peptide (Aβ) and intracellular
neurofibrillary tangles made up mainly of hyper phosphorylated tau.AD is a progressive disease
and may takes more than twenty years to develop prominent clinical symptoms such as memory
loss. It is important to unfold early molecular mechanisms that contribute to development of the
disease.Aberrant accumulation of amyloid-β (Aβ) in brain is the major trigger for pathogenesis
in AD. It is hence essential to understand how Aβ attains such toxic levels in the brain
parenchyma. Aging is one of the major risk factors of AD. DNA damage plays an important role
both in aging and AD. We studied the effect of both toxic and sub lethal dose of DNA damage
on neurons. Treating differentiated SH-SY5Y cells with a toxic dose of Camptothecin(CPT)
induced ROS, mitochondrial dysfunction and apoptosis. Increased expression of BID which is a
BH3-only pro-apoptotic protein was observed under similar treatment. Down regulation of BID
provided transient protection from toxic dose of CPT in neurons.
Next we shifted our focus to study the stress response in neuron induced by sub lethal dose of
DNA damaging agent CPT and Doxorubicin (Dox) without inducing cell death.We detected that
a very subtle and tolerable amount of DNA damage, related to aging, increased intraneuronal
Aβ1-42 production both in cultured neuron and in the cortex of rodent brain.Strikingly, we also
observed elevated levels of mitochondrial fusion and of its major driver protein, MFN2.
Hyperfusion of mitochondria may be seen as an adaptive stress response resulting from the
induction of ER stress since we detected upregulated phosphorylation of both PERK, an
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important arm of unfolded protein response and an ER-stress marker, and its substrate eukaryotic
initiation factor 2 α (eIF2α), together constituting a signaling responsible for protective
mitochondrial remodeling. This adaptive remodeling of mitochondria resulted in an increase in
mitochondrial oxygen consumption rate and ATP production. At later time points this elongated
structure of mitochondria shifts towards fission. Mitochondrial fission is observed in AD brain
but the phenomenon that is leading to this shift is not well studied in the disease model. Reports
suggest that eIF2α phosphorylation can increase BACE1 activity, the rate limiting enzyme in Aβ
production. In our model, we show that inhibiting PERK, decreased Aβ1-42 level while direct
BACE1 inhibition, reduced the mitochondrial fusion.Moreover, we found increased MFN2
expression in younger 5xFAD transgenic mice when Aβ plaques and neurodegeneration were
absent. Down regulation of MFN2 decreased CPT induced increase in Aβ1-42in neuron. Thus, this
study indicates that mild DNA damage leads to increased Aβ1-42 production via ER stress and
may also direct mitochondrial elongation as an initial adaptive/protective response. We propose
that age-related subtle genomic DNA damage may trigger enhanced intraneuronal Aβ1-
42 production in an apparently healthy neuron way before the appearance of clinical symptoms in
AD.
Mitochondrial genome can bear signatures for AD. Mutation in mitochondrial genome can
compromise its function and also can be considered as biomarker for early diagnosis of the
disease. In the next part of our work we have analysed point mutations in mtDNA from AD
patient’s whole blood. We identified SNPs which are common and unique to all the samples. The
nature and distribution of mutations were also studied. To our surprise the mutations were not
due to oxidation, but it was due to replication error. The SNPs were dispersed in coding region
not in D loop of mtDNA. Defective replication of mtDNA could be a result of ineffective
replication carried by POLG. Further work in this direction will help to understand the reason of
developing these mutations in AD patients’ whole blood.
Altogether this work explores an unconventional role of mitochondria in AD. The connection of
mitochondria in subtle DNA damage associated stress response and increase in Aβ1-42 production
in neuronsis a novel finding and may lead to better understanding of the pathogenesis of AD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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