4 results
34380 Cadherin complexes recruit PIWIL2 to suppress transposons and pro-tumorigenic transformation
- Alyssa Risner, Joyce Nair-Menon, Colin McDowell, Vamsi Gangaraju, Antonis Kourtidis
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 12
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- Article
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- Open access
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ABSTRACT IMPACT: This study has uncovered a novel surprising mechanism involving the epithelial adherens junctions and transposon regulation that can deepen our understanding of tumorigenesis. OBJECTIVES/GOALS: Recent studies show that genomic instability in 50% of tumors can be attributed to increased transposon activity, but the the reasons for this activity are unknown. We have evidence of a novel mechanism linking adherens junctions with transposon regulation. We hypothesize that adherens junctions suppress transposons to maintain genomic integrity. METHODS/STUDY POPULATION: We observed co-localization of PIWIL2 with adherens junction components of well differentiated epithelial breast, kidney and colon cell lines MCF10A, MDCK and CACO2, respectively, through immunofluorescence staining, confocal microscopy, and co-immunoprecipitation studies. Breast cancer cell lines MCF7 and MDA-231 were also observed using immunofluorescence to determine the localization of PIWIL2 in cancer cell lines. shRNA knockdown of PIWIL2 in MCF10A cells, followed by western blot, immunofluorescence, and qRT-PCR was performed to confirm the knockdown, observe if transposons were upregulated, and determine the extent of DNA damage to the genome by the marker gamma-H2AX. RNA-seq will be performed to determine piRNA sequences and possible targets of PIWIL2. RESULTS/ANTICIPATED RESULTS: Our data have revealed an interaction of E-cadherin and p120 catenin, core components of adherens junctions, with PIWIL2, a member of the Argonaute family of proteins and a key component of the piRNA processing pathway that is responsible for transposon silencing. piRNAs (PIWI-interacting RNAs) are a distinct class of small RNAs that bind to PIWI proteins, and aid in transposon degradation. We found co-localization of PIWIL2 with E-cadherin and p120 catenin at adherens junctions of well-differentiated epithelial cells, whereas this association was lost in cancer cells. Furthermore, our data show that E-cadherin depletion results in mis-localization of PIWIL2 and TDRD1, another member of the PIWI complex. E-cadherin depletion also results in upregulation of transposons and ?-H2AX, an indicator of DNA damage. DISCUSSION/SIGNIFICANCE OF FINDINGS: Since both loss of junctional integrity and increased transposon activity are universal events in cancer, this study has the potential to further our understanding of the causes of tumorigenesis. Understanding the mechanisms of transposon regulation has the potential to lead to a therapeutic target in the future.
7 - Yeats and Abstraction: From Berkeley to Zen
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- By Colin McDowell, Australian Public Service
- Edited by Matthew Gibson, Neil Mann
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- Book:
- Yeats, Philosophy, and the Occult
- Published by:
- Liverpool University Press
- Published online:
- 04 July 2017
- Print publication:
- 31 December 2016, pp 251-288
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Summary
My imagination was for a time haunted by figures that, muttering “The great systems,” held out to me the sundried skeletons of birds, and it seemed to me that this image was meant to turn my thoughts to the living bird. That bird signifies truth when it eats, evacuates, builds its nest, engenders, feeds its young; do not all intelligible truths lie in its passage from egg to dust? (CW14 158; AVB 214).
It seems to me that I have found what I wanted. When I try to put all into a phrase I say, “Man can embody truth but he cannot know it.” I must embody it in the completion of my life. The abstract is not life and everywhere draws out its contradictions. You can refute Hegel but not the Saint or the Song of Sixpence…. (CL InteLex 7362; L 922)
As a poet who thought in concrete terms, Yeats was unhappy when he found himself amongst abstract things; yet, despite his natural inclination, he knew he needed abstraction to set his experience in order (CW13104; AVA 129). A Vision is, of course, Yeats's most sustained abstraction, but, once A Vision was published, he also engaged in extended study of several major philosophers. Foremost of these was George Berkeley.
Some Yeats scholars have been less than kind about their subject's ability to comprehend philosophy in general and Berkeley in particular. W. J. Mc Cormack is severe on Yeats in most matters, and takes particular delight in using an unsourced statement to the effect that the eminent Berkeley scholar A. A. Luce, being “[a]n astringent personality, … had no time for Yeats as an amateur philosopher at best and a very questionable protestant.” It is not my intention here or elsewhere to devote much time to Yeats's Protestantism or otherwise, but I do wish to reiterate what Donald Torchiana had said about Luce on Yeats's philosophizing well before Mc Cormack took up the case. I shall then continue with other matters, which were studiously avoided by Mc Cormack in his rush to judgment.
Mc Cormack avers that “The advance by scholarship of Berkeley's claims to the modern reader's attention occurred in stated rejection of the Yeatsian exposition” (WIE4).
Shifting Sands: Dancing the Horoscope in the Vision Papers
- Edited by Neil Mann, Matthew Gibson, Claire Nally
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- Book:
- W. B. Yeats's 'A Vision'
- Published by:
- Liverpool University Press
- Published online:
- 04 July 2017
- Print publication:
- 31 December 2012, pp 194-216
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Summary
Felkin told me thathe had seen a Dervish dance a horoscope. He went round and round on the sand and then circle to centre. He whirled round at the planets making round whorls in the sand by doing so. He then danced the connecting lines between planets and fell in trance. This is what I saw in dream or vision years ago.
W. B. Yeats, June 1909It was one of W. B. Yeats's idler fantasies that A Vision might found a new Irish heresy, as disciples studied it and applied its doctrines (L712). In fact, even as he wrote this, he knew how few readers his work could realistically expect. In A Vision A, he had confined his audience, somewhat pessimistically, to his “old fellow students” in the Golden Dawn, and suggested that “if they will master what is most abstract there and make it the foundation of their visions, a curtain may ring up on a new drama” (CW13 lv; AVA xii). Later, when he came to write A Vision B, he had resigned himself to finding a solitary satisfaction; the symbols, he said, helped him “to hold in a single thought reality and justice” (AVB25).
Generally speaking, readers have been content to allow Yeats his petty triumph. Literary critics continue to read the book as Yeats gave them license to do, as “metaphors for poetry” (AVB8). So far, the only people who have taken up the challenge of applying the doctrines of A Vision have been astrologers seeking to enlarge their art. I shall briefly examine some of these later, but in order properly to assess the use to which these epigones have put A Vision, one first needs to see some of the ways in which the Yeatses tried to integrate astrology into the system with a possible view towards extending astrology's capabilities.
There are few traces of traditional astrology in the finished work, especially as concerns the individual. Several passages extant in A Vision B mention how the natal horoscope can twist, or rather enrich and complicate, the natural character of a person's phase (AVB 153, 176).
Nutritional ecology of elephants in Kibale National Park, Uganda, and its relationship with crop-raiding behaviour
- Karyn D. Rode, Patrick I. Chiyo, Colin A. Chapman, Lee R. McDowell
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- Journal:
- Journal of Tropical Ecology / Volume 22 / Issue 4 / July 2006
- Published online by Cambridge University Press:
- 10 July 2006, pp. 441-449
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This study investigated the nutritional ecology of forest elephants in Kibale National Park, Uganda relative to crop-raiding behaviour, and examined nutritional differences between crops and food consumed by wild elephants. An index of dietary nutrient concentration was determined by quantifying the species and parts of plants consumed along feeding trails, collecting food items, and analysing foods for energy, fibre, protein, minerals and secondary compounds. Frequency of crop raiding was quantified over 13 mo. Energy and protein concentration was within suggested levels, but concentrations of several minerals, particularly sodium, were low relative to requirements based on captive elephants and values reported for other wild populations. The very low sodium concentrations of Kibale elephant diets and low availability of alternative sodium sources, such as soil or water, suggest that sodium drive is very likely in this population. Crops consumed by Kibale elephants had higher Na concentrations and lower concentrations of fibre and secondary compounds than wild diets. The known attraction of elephants to mineral sources throughout their range and the low mineral concentration of leaves, fruits, bark, and stems consumed by forest elephant in this study suggest that mineral nutrition is likely to be an important factor driving elephant behaviour and patterns of habitat use.
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