1,720,955 research outputs found
Age-related changes at the Caenorhabditis elegans neuromuscular junction
No full textThe ageing population is an important problem for society as it predisposes individuals towards disease. Cognitive decline, dementia and frailty are associated with ageing, and much evidence supports a central role of synapses. However, the mechanisms by which aged synapses are compromised remain unclear. This thesis describes a functional analysis of the C. elegans neuromuscular system across ageing to model the effects of ageing on synaptic physiology. Motility assays were used to give an insight into the integrity of the neuromuscular system. Aldicarb and levamisole-induced whole worm contraction assays were used to give a more detailed insight into the integrity of presynaptic and postsynaptic loci. Patch clamp analysis of miniature postsynaptic currents (mPSCs) was used to characterise neurotransmission across ageing. Lastly, different genetic backgrounds were used to investigate the contribution of longevity and synaptic pathways to NMJ function across age. C. elegans has a median lifespan of 14 17 days and becomes progressively immotile with age, with swimming frequency decreasing from 110±3 to 71±12 beats per minute from day 1 to day 5 of adulthood. Counter intuitively, this was coincident with an increase in NMJ efficacy identified using aldicarb and levamisole contraction assays. Patch clamp analysis of neuromuscular transmission also revealed increased mPSC frequency and amplitude from 9±3 to 33±7 Hz and 15±1 to 27±4 pA between day 1 and 5 of adulthood. As animals progress from early ageing to later ages on day 10 and 16 of adulthood, NMJ efficacy decreases, but not to levels lower than that seen on day 1 of adulthood. Patch clamp analysis revealed increased in mPSC frequency and amplitude from 9±3 to 22±9 Hz and 15±1 to 19±4 pA between day 1 and 10 of adulthood, indicating more neurotransmitter release and preserved sensitivity in aged, immotile worms. The contraction assays indicate that even very aged, immotile worms on day 16 of adulthood had functional muscle cells. daf-2(e1370) worms have reduced insulin signalling and show extended lifespan and motility across ageing. Aldicarb assays in daf- 2 worms indicate insulin signalling is required for increased neurotransmitter release during early ageing. dnj-1 (tm3223) worms lack the homologue of a synaptic co chaperone, CSP. Lifespan, swimming, contraction and patch clamp analysis of neuromuscular function in dnj-14 worms revealed no defects compared to wild type across lifespan. In summary, there is an increase in NMJ efficacy during early ageing that is dependent on insulin signalling, a conserved longevity and synaptic physiology regulator. During later ageing, C.elegans NMJs remain functional. In contrast to conclusions from previous morphological studies, muscle function is largely preserved across the C. elegans lifespan, indicating additional determinates including the motor circuit may play a role in age-related immotility. This study resonates with emerging evidence in mammalian systems that defective signalling in neuronal circuits is a key mechanism for age-related impairment of the nervous system, in which changes in synaptic function may play a role
Synthesis and properties of triplex-forming oligonucleotides containing 2'-O-(2-methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine
No full text2'-O-(2-Methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine phosphoramidite (MEPU) has been synthesized from d-ribose and 5-iodouracil and incorporated into triplex-forming oligonucleotides (TFOs) by automated solid-phase oligonucleotide synthesis. The TFOs gave very high triplex stability with their target duplexes as measured by ultraviolet/fluorescence melting and DNase I footprinting. The incorporation of MEPU into TFOs renders them resistant to degradation by serum nucleases.<br/
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
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
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