Refine
Has Fulltext
- yes (12)
Is part of the Bibliography
- yes (12)
Document Type
- Journal article (11)
- Review (1)
Language
- English (12)
Keywords
- land-use change (2)
- Bombus Spp. Hymenoptera (1)
- CRC (1)
- CX5461 (1)
- Disease gene prioritization (1)
- EMMA (1)
- Festkörperphysik (1)
- MIZ1 (1)
- MYC (1)
- Mexican coffee plantations (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (5)
- Physikalisches Institut (2)
- Comprehensive Cancer Center Mainfranken (1)
- Institut für Molekulare Infektionsbiologie (1)
- Institut für Theoretische Physik und Astrophysik (1)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (1)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (1)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (1)
- Pathologisches Institut (1)
- Rudolf-Virchow-Zentrum (1)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 212372 (1)
MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.
Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases
(2016)
Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.