12 research outputs found
A positive Living-in-History effect: the case of the fall of the Berlin Wall
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Research has shown that individuals use a combination of cultural life script events and historical events when dating personal memories, providing evidence for a cultural life script effect and Living-in-History (LiH) effect on the temporal organisation of autobiographical memory. Yet, in contrast to life script events, the LiH effect has only been found for negative events such as war or natural disasters. Therefore, this study tested whether a positive historical event, here the fall of the Berlin Fall, also elicits a LiH effect and whether this effect would differ due to the subsequent changes in life. Comparing West and East Germans, we found a moderate LiH effect for the fall of the Berlin Wall in East Germans but not in West Germans. Yet, the LiH effect in East Germans did not relate to the perceived change in life or the valence of the historical event. Additionally, this study replicated the finding that life script events serve as temporal landmarks when navigating through oneâs autobiographical timeline
Adhesion enhancement of cribellate capture threads by epicuticular waxes of the insect prey sheds new light on spider web evolution
Single puffs of the capture thread of U. plumipes peel off the elytra of C. maculatus. Sped up 2.4 times
Supplementary material from Adhesion enhancement of cribellate capture threads by epicuticular waxes of the insect prey sheds new light on spider web evolution
Document includes figure S1, S2 and S3 as well as table S1 and S
Movie S1 from Adhesion enhancement of cribellate capture threads by epicuticular waxes of the insect prey sheds new light on spider web evolution
Fluid matrix consisting of cuticular waxes propagates from the prey (here: elytra of C. maculatus) through the cribellate capture thread (here: U. plumipes). Sped up 8 time
A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance
To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA AâPLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage
Genomic heterogeneity at baseline is associated with T790M resistance mutations in EGFRâmutated lung cancer treated with the firstâ/secondâgeneration tyrosine kinase inhibitors
Abstract This study analyzed whether extended molecular profiling can predict the development of epidermal growth factor receptor (EGFR) gene T790M mutation, which is the most frequent resistance alteration in nonâsmall cell lung cancer (NSCLC) after treatment with the firstâ/secondâgeneration (1G/2G) EGFR inhibitors (tyrosine kinase inhibitors [TKIs]), but only weakly associated with clinical characteristics. Whole exome sequencing (WES) was performed on pretreatment tumor tissue with matched normal samples from NSCLC patients with (nâ=â25, detected in tissue or blood rebiopsies) or without (nâ=â14, negative tissue rebiopsies only) subsequent EGFR p.T790M mutation after treatment with 1G/2G EGFR TKI. Several complex genetic biomarkers were assessed using bioinformatic methods. After treatment with firstâline afatinib (44%) or erlotinib/gefitinib (56%), median progressionâfree survival and overall survival were 12.1 and 33.7âmonths, respectively. Clinical and tumor genetic characteristics, including age (median, 66âyears), sex (74% female), smoking (69% never/light smokers), EGFR mutation type (72% exon 19 deletions), and TP53 mutations (41%) were not significantly associated with T790M mutation (pâ>â0.05). By contrast, complex biomarkers including tumor mutational burden, the clockâlike mutation signature SBS1â+â5, tumor ploidy, and markers of subclonality including mutantâallele tumor heterogeneity, subclonal copy number changes, and median tumorâadjusted variant allele frequency were significantly higher at baseline in tumors with subsequent T790M mutation (all pâ<â0.05). Each marker alone could predict subsequent development of T790M with an area under the curve (AUC) of 0.72â0.77, but the small number of cases did not allow confirmation of better performance for biomarker combinations in leaveâoneâout crossâvalidated logistic regression (AUC 0.69, 95% confidence interval: 0.50â0.87). Extended molecular profiling with WES at initial diagnosis reveals several complex biomarkers associated with subsequent development of T790M resistance mutation in NSCLC patients receiving firstâ/secondâgeneration TKIs as the firstâline therapy. Larger prospective studies will be necessary to define a forecasting model