2,945 research outputs found
NF-κB regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes
Get PDFNF-κB is involved in immune responses, inflammation, oncogenesis, cell proliferation and apoptosis. Even though NF-κB can be activated by DNA damage via Ataxia telangiectasia-mutated (ATM) signalling, little was known about an involvement in DNA repair. In this work, we dissected distinct DNA double-strand break (DSB) repair mechanisms revealing a stimulatory role of NF-κB in homologous recombination (HR). This effect was independent of chromatin context, cell cycle distribution or cross-talk with p53. It was not mediated by the transcriptional NF-κB targets Bcl2, BAX or Ku70, known for their dual roles in apoptosis and DSB repair. A contribution by Bcl-xL was abrogated when caspases were inhibited. Notably, HR induction by NF-κB required the targets ATM and BRCA2. Additionally, we provide evidence that NF-κB interacts with CtIP-BRCA1 complexes and promotes BRCA1 stabilization, and thereby contributes to HR induction. Immunofluorescence analysis revealed accelerated formation of replication protein A (RPA) and Rad51 foci upon NF-κB activation indicating HR stimulation through DSB resection by the interacting CtIP-BRCA1 complex and Rad51 filament formation. Taken together, these results define multiple NF-κB-dependent mechanisms regulating HR induction, and thereby providing a novel intriguing explanation for both NF-κB-mediated resistance to chemo- and radiotherapies as well as for the sensitization by pharmaceutical intervention of NF-κB activatio
Interleukin-18 is expressed in rat testis and may promote germ cell growth
No full textMona-Lisa Strand, Aida Wahlgren, Konstantin Svechnikov, Cecilia Zetterstroma, Brian P. Setchell, Olle Sode
Sex differences in Cognitive Abilities Test scores: a UK national picture
Get PDFBackground and aims. There is uncertainty about the extent or even existence of sex differences in the mean and variability of reasoning test scores ( Jensen, 1998; Lynn, 1994, ; Mackintosh, 1996). This paper analyses the Cognitive Abilities Test (CAT) scores of a large and representative sample of UK pupils to determine the extent of any sex differences.
Sample. A nationally representative UK sample of over 320,000 school pupils aged 11-12 years was assessed on the CAT (third edition) between September 2001 and August 2003. The CAT includes separate nationally standardized tests for verbal, quantitative, and non-verbal reasoning. The size and recency of the sample is unprecedented in research on this issue.
Methods. The sheer size of the sample ensures that any sex difference will achieve statistical significance. Therefore, effect sizes (d) and variance ratios (VR) are employed to evaluate the magnitude of sex differences in mean scores and in score variability, respectively.
Results. The mean verbal reasoning score for girls was 2.2 standard score points higher than the mean for boys, but only 0.3 standard points in favour of girls for non-verbal reasoning (NVR), and 0.7 points in favour of boys for quantitative reasoning (QR). However, for all three tests there were substantial sex differences in the standard deviation of scores, with greater variance among boys. Boys were over represented relative to girls at both the top and the bottom extremes for all tests, with the exception of the top 10% in verbal reasoning.
Conclusions. Given the small differences in means, explanations for sex differences in wider domains such examination attainment at age 16 need to look beyond conceptions of `ability'. Boys tend to be both the lowest and the highest performers in terms of their reasoning abilities, which warns against the danger of stereotyping boys as low achievers
Nation
No full textThe state of civic participation in the U.S. is the subject of much hand-wringing. The lament is generally that citizens are withdrawn - that civic life is less vibrant than it once was and should be. This book review welcomes Downsizing Democracy: How America Sidelined its Citizens and Privatized its Public, by Matthew Crenson & Benjamin Ginsburg (2002), as an alternative to the tendency to blame citizens for the current malaise. Crenson & Ginsburg make the case that the government itself has disinvited civic participation in several key ways. The author observes that, notwithstanding this lack of invitation, citizens can and should still take on themselves the responsibility for civic action - not just in traditional political spheres, but in the myriad venues of our everyday lives.525-2927
Diversity in the Norwegian Viking Age: an osteobiographical approach
Get PDFSammendrag
Denne doktorgradsavhandlingen undersøker sosial organisasjon under norsk vikingtid (ca. 750–1050 e.Kr.) gjennom et bioarkeologisk og postkolonialt teoretisk perspektiv, med særlig vekt på mobilitet, kosthold, vold og sosial makt. Målet har vært å avdekke regionale og nasjonale mønstre knyttet til sentrale sider ved vikingtidens sosiale organisering, inkludert kjønnet handlingsrom og etnisitet, og å bidra til en bredere diskusjon om samfunnsstruktur og maktutøvelse.
Avhandlingen bygger på tre hovedmål. Først analyseres mobilitet og kosthold basert på resultater fra isotopanalyser for å identifisere regionale forskjeller i Norge under vikingtiden. Deretter undersøkes forholdet mellom voldsnivå og sentralmaktens styrke, med særlig fokus på forskjeller mellom Norge og Danmark. Til slutt utforskes den sosiale kompleksiteten i det multietniske samfunnet i Norge under Vikingtiden, sett i lys av at landet hadde en relativt svak sentralmakt i denne perioden.
Gjennom en biografisk tilnærming og tverrfaglig metodebruk, som kombinerer DNA, isotopdata, osteologiske analyser og arkeologi, utfordres tradisjonelle narrativ. Funnene viser blant annet gruppe- eller familiebaserte reiser. Det avdekkes også tydelige regionale forskjeller i kosthold og voldsnivå. Det økte nivået av vold i Norge tolkes i sammenheng med mer flytende og desentraliserte sosiale strukturer enn i Danmark.
Avhandlingen aktualiserer også samiske grupper, kvinner og barn som samtidige og handlende aktører i vikingtidens samfunn. Gravpraksiser og mobilitetsmønstre blant samiske individer utfordrer etablerte forestillinger. Samlet viser forskningen at den sosiale organiseringen i norsk vikingtid var mer mangfoldig og kompleks enn tidligere antatt, og åpner for nye perspektiver og forskningsspor.
Summary
This doctoral thesis investigates social organisation in the Norwegian Viking Age (c. 750–1050 CE) through a bioarchaeological and post-colonial lens, with a particular focus on mobility, diet, violence, and social power. The objective has been to uncover both regional and national patterns in social structure and gendered agency, including considerations of ethnicity and the broader dynamics of social climate and power.
Three central aims guided this work. First, the study explored mobility and diet using multi-isotopic analysis and archaeological data to evaluate regional variation and gender dynamics in these practices. Second, it examined the interplay between violence and the strength of central governance, comparing Norway with Denmark to assess how levels of interpersonal violence relate to broader political structures. Third, the thesis investigated agency and interaction within Norway’s multi-ethnic Viking Age society—particularly among the Sámi, women, and children—in the context of weak central governance.
Using osteobiographical methods and an interdisciplinary approach combining ancient DNA, multi-isotope data, osteology, and archaeology, the study challenges longstanding Norse-centric and male-focused narratives. Findings suggest that long-distance mobility was common to both sexes and often established in childhood, hinting at group or familial travel. Regional dietary patterns and elevated violence levels—especially in Norway—further reflect the complexity of social hierarchies. The thesis foregrounds the Sámi as contemporaneous actors and reveals burial practices that defy conventional categorisation. Overall, the research presents a more nuanced and diversified picture of social organisation in the Norwegian Viking Age and proposes new directions for future research
MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA
Get PDFTopoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 5'-phosphotyrosyl bond. These intermediate complexes can become cytotoxic protein-DNA adducts and DSB repair at these lesions requires removal of topoisomerase II. To analyse removal of topoisomerase II from genomic DNA we adapted the trapped in agarose DNA immunostaining assay. Recombinant MRE11 from 2 sources removed topoisomerase IIalpha from genomic DNA in vitro, as did MRE11 immunoprecipitates isolated from A-TLD or K562 cells. Basal topoisomerase II complex levels were very high in A-TLD cells lacking full-length wild type MRE11, suggesting that MRE11 facilitates the processing of topoisomerase complexes that arise as part of normal cellular metabolism. In K562 cells inhibition of MRE11, PARP or replication increased topoisomerase IIalpha and beta complex levels formed in the absence of an anti-topoisomerase II dru
Strand separation establishes a sustained lock at the Tus-Ter replication fork barrier
No full textThe bidirectional replication of a circular chromosome by many bacteria necessitates proper termination to avoid the head-on collision of the opposing replisomes. In Escherichia coli, replisome progression beyond the termination site is prevented by Tus proteins bound to asymmetric Ter sites. Structural evidence indicates that strand separation on the blocking (nonpermissive) side of Tus-Ter triggers roadblock formation, but biochemical evidence also suggests roles for protein-protein interactions. Here DNA unzipping experiments demonstrate that nonpermissively oriented Tus-Ter forms a tight lock in the absence of replicative proteins, whereas permissively oriented Tus-Ter allows nearly unhindered strand separation. Quantifying the lock strength reveals the existence of several intermediate lock states that are impacted by mutations in the lock domain but not by mutations in the DNA-binding domain. Lock formation is highly specific and exceeds reported in vivo efficiencies. We postulate that protein-protein interactions may actually hinder, rather than promote, proper lock formation.Accepted Author ManuscriptBN/Nynke Dekker LabBN/Cees Dekker LabBN/Martin Depken La
idX Information Design Exchange. What information designers know and can do
No full textStrand, Lennart (2007). Co-author: idX Information Design Exchange. What information designers know and can do. "Development of International Core Competencies and Student and Faculty Exchange in Information Design" within the EU/US Cooperation Programme in Higher Education and Vocational Education and Training Outcome. Developed in co-operation with International Institute for Information Design, http://www.iiid.net/</p
An Observation of the Strand Theater
Get PDFThis article provides a history of The Strand Theater in downtown Binghamton NY based on fire insurance maps and the author\u27s observations
A self-conscious Kurt Vonnegut: an analysis of Cat's Cradle, Slaughterhouse-Five and Breakfast of Champions
No full textThe works of Kurt Vonnegut stand as seminal in the American literary canon. Looking at three of his most influential novels, namely Cat's Cradle, Slaughterhouse-Five and Breakfast of Champions, this study aims to better understand the mechanisms which inform his fiction. Working chronologically through the novels, the study examines historical context, narrative technique, theoretical underpinnings and the social critique of each novel. Guided by an idea of the postmodern novel the study examines how these elements interact, concluding that by way of what may be considered "simple" yet self-conscious metafiction and prose as well as variations in narrative technique, Vonnegut is able to more accurately convey his opinions on the American situation as well as demonstrate his stance on the role of fiction and the writer in contemporary society. The study also considers closely the role of the reader and the author/reader/text relationship
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