164,561 research outputs found
ALT 2014 AGM Calling Notice and Trustee and Vice-Chair Nomination Form
No full textThe calling notice for the ALT 2014 AGM to be held on 2 September 2014, and the nomination form for: 1) Vice-Chair of the Association (who becomes Chair, then President in successive years) to serve three years; 2) Trustees to serve three years (two vacancies). All nominations should be marked "Nominations" and sent to arrive by 5pm on Friday 6 June 2014. Items may be submitted by post, to Maren Deepwell, Chief Executive, ALT, Gipsy Lane, Headington, Oxford OX3 0BP, UK, or by fax to +44 (0)1865 484165, or email to [email protected]
Joint response to the Royal Society’s call for views: Vision for science and mathematics education 5-19
No full textThis response has been prepared by a consortium of the leading Technology Enhanced Learning (TEL) research labs in the UK, in collaboration with the UK’s Technology Enhanced Learning research programme and the Association for Learning Technology (ALT)
HIRA protects ALT telomeres from aberrant R-loop accumulation
No full textThe Alternative Lengthening of Telomeres (ALT) pathway is a homology-directed repair (HDR) mechanism of telomere extension that enables the proliferation of several aggressive cancers. Recurrent mutations inactivate the ATRX (alpha-thalassemia/mental retardation, X-linked)–DAXX (death domain associated protein) chromatin remodeling complex, which coordinates histone H3.3 deposition at telomeres. Recently, we showed that HIRA, the remaining H3.3 chaperone, adapts to compensate for ATRX loss by maintaining telomeric chromatin to sustain ALT cancer cell survival. However, the specific mechanisms underlying HIRA's ability to rescue ALT telomeres from the repercussions of ATRX loss remain unclear.
Here, we demonstrate that the HIRA-UBN1/2 complex mediates new H3.3 deposition, limiting the accumulation of unchromatinized, single-stranded DNA (ssDNA) presence at telomeres following ALT-associated HDR. HIRA adapts to maintain H3.3 levels but cannot entirely prevent R-loops, leading to collisions between RNA polymerase II and the ALT replisome and unwarranted replication stress. Furthermore, we show that Chk1-mediated H3.3 S31 phosphorylation is crucial for suppressing aberrant ssDNA accumulation and maintaining the integrity of telomeric chromatin. These studies suggest that the deposition of new histone H3.3 maintains productive ALT, and HIRA ensures ALT cell survival by limiting TERRA R-loop formation. This implicates HIRA in TERRA R-loop homeostasis, which we propose is essential in ensuring ALT cancer cell survival following ATRX loss
On the Benthic Invertebrate Megafauna at the Mid-Atlantic Ridge, in the Vicinity of the Charlie-Gibbs Fracture Zone
No full textLittle is known about the fauna that inhabits non-chemosynthetic environments associated with mid-ocean ridges. This thesis investigates a ridge and fracture zone system to assess its influence as a barrier to faunal dispersal, and as a unique bathyal habitat. It also describes the ecology of megabenthic communities inhabiting a ridge. Sites were chosen on the Mid-Atlantic Ridge in the vicinity of the Charlie-Gibbs Fracture Zone, at a target depth of 2,500 m. Four superstations were chosen north and south of the Fracture Zone, on either side of the ridge. Different productivity levels and hydrographic features were characteristic for the northern and southern sites. In order to characterise the benthic megafauna 50 ha were trawled and 32,000 m2 of seafloor were sampled with HD video footage, targeting both flat and 10 ? sloped habitats. Holothurians were the most abundant megafauna. In order to assess their evolutionary relationship 43 holothurian specimens were genetically studied by modelling five of their genes (16S, 18S, 28S, COI, H3) in a phylogenetic analysis. All four sites exhibited noticeably different faunal characteristics. The biomass was highest at the SE, and lowest at the NW site. Body sizes differed between sites for most taxa, that were sufficient in numbers to be compared between sites, most likely as a result of different adaptations to food supply. Differences in species richness were observed between the sampling methods, with the highest richness at the SE site in trawl samples, and highest at the NW and SW sites in the video survey. Species densities were highest at the northern sites with both methods. Differences in diversity were also observed, with trawl samples providing a higher taxonomic resolution than the video survey and showing highest diversity at the SE site and lowest at the NE site. Community composition was significantly different between sites. Variations in the composition of megabenthic assemblages were observed between flat and 10 ? sloped habitats, although the effect of slope appears to be site dependent. The genetic analyses revealed a close relationship between individuals from different families. The extent to which the Ridge acts as a faunal barrier was unclear as the southern sites lacked an obvious difference in community composition. Faunal differences to the north and south of the Fracture Zone, however, suggest that this feature is a barrier to dispersal. The contrasting megafaunal assemblages of the sites probably reflect a combination of environmental drivers including sediment type, phytodetrital quality, hydrography, and habitat complexity
ALT-C 2011 Proceedings Papers: 0136 Learning Through Online Discussion: A Framework Evidenced in Learners' Interactions.
No full textThe Reactionary Web: Digital Media and the Reconstitution of White Supremacist Networks after the Alt-Right
No full textMy dissertation is a digital-rhetorical criticism of U.S. American reactionary networks in the aftermath of the Alt-Right, between the August 2017 “Unite the Right” rally in Charlottesville, Virginia, the January 2021 storming of the United States Capitol, and the Covid-19 pandemic. The Alt-Right was a loose coalition of far-right, white supremacist, and misogynistic digital communities. Emboldened by the successful campaign of President Donald Trump, the Alt-Right sought to “mainstream” white nationalism through digital media tactics, most infamously the circulation of memes, to facilitate online-offline radicalization. The Alt-Right’s meteoric rise is accredited to its sense of strategy within a digital media environment amenable to polarization, conspiracy, and disinformation. Yet even as these dynamics worsened in the years following Unite the Right, the Alt-Right failed to survive as a meaningful symbol for reactionary political affinity, evidenced by its absence on January 6th, because its key figures were publicly exposed throughout a “regulatory turn” within platform governance. After the Alt-Right, how have U.S. white supremacist online communities reproduced their influence throughout the regulatory turn? I approach the question through materialist criticism which investigates the productive purchase of rhetorical practices, particularly in the constitution and defense of racial regimes. Therefore, I situate the Alt-Right within the platformization, or the digital reproduction of racial capitalism. My central argument is that the Alt-Right’s failure masks a violent relation within, toward, and against publicity that is endemic to the exchange of Internetworked media under racial capitalism. I commence with an event-based analysis of the Alt-Right’s decline (2) before analyzing collective posting habits (3), platform interfaces (4), and platform policy (5), that afford productive capacity to its successors. My chapters establish empirical, ideological, and infrastructural links between the Alt-Right’s decline in the United States and the atmospheric quality of white masculine violence on and of digital media. I conclude by speculating an abolitionist posture against the Internet
Effects of BRCA2 deficiency on telomere recombination in non-ALT and ALT cells
No full textThis article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Sapir et al.Background: Recent studies suggest that BRCA2 affects telomere maintenance. Interestingly, anti cancer treatments that involve BRCA2 and telomerase individually are currently being explored. In the light of the above recent studies their combinatorial targeting may be justified in the development of future treatments. In order to investigate effects of BRCA2 that can be explored for this combinatorial targeting we focused on the analysis of recombination rates at telomeres by monitoring T-SCEs (Telomere Sister Chromatid Exchanges). Results: We observed a significant increase in T-SCE frequencies in four BRCA2 defective human cell lines thus suggesting that BRCA2 suppresses recombination at telomeres. To test this hypothesis further we analyzed T-SCE frequencies in a set of Chinese hamster cell lines with or without functional BRCA2. Our results indicate that introduction of functional BRCA2 normalizes frequencies of T-SCEs thus supporting the notion that BRCA2 suppresses recombination at telomeres. Given that ALT (Alternative Lengthening of Telomeres) positive cells maintain telomeres by recombination we investigated the effect of BRCA2 depletion in these cells. Our results show that this depletion causes a dramatic reduction in T-SCE frequencies in ALT positive cells, but not in non-ALT cells. Conclusion: BRCA2 suppresses recombination at telomeres in cells that maintain them by conventional mechanisms. Furthermore, BRCA2 depletion in ALT positive cells reduces high levels of T-SCEs normally found in these cells. Our results could be potentially important for refining telomerase-based anti-cancer therapies.This work is supported in part by grants from European Commission RISC-RAD contract FI6RCT2003-508842 and British Counci
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