• (Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level.

      Fan, Xing-Xing; Yao, Xiao-Jun; Xu, Su-Wei; Wong, Vincent K-W.; He, Jian-Xing; Ding, Jian; Xue, Wei-Wei; Mujtaba, Tahira; Michelangeli, Francesco; Huang, Min; et al. (Nature Publishing Group, 2015-11-06)
      Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.
    • Zoo-housed mammals do not avoid giving birth on weekends

      Hosey, Geoff; Ward, Samantha J; Ferguson, Amanda; Jenkins, Hannah; Hill, Sonya P; University of Bolton; Nottingham Trent University; ZSL London Zoo; North of England Zoological Society; University of Chester
      There is evidence that zoo visitor presence can influence the behavior and, in some cases, adrenal response of zoo animals, and can sometimes compromise animal welfare. In some laboratory studies, significantly more primate births have been reported on weekends, when fewer people are working there, compared with weekdays when staffing levels are at their highest. Here we investigate whether there is evidence of a “weekend effect” on births in zoo animals as a result of visitor numbers. Unlike laboratories, zoos are typically busier with visitors on weekends than on weekdays, although staffing levels remain fairly consistent across days of the week. If zoo animal parturition is sensitive to human presence, then fewer births would be expected on weekends compared with weekdays. We tested this using birth data and visitor numbers on the entrance gate from zoo records across 16 species representing artiodactyls, perissodactyls, carnivores and primates at four British zoos, to see whether there is an association between mean daily birth rates and average visitor numbers. We predict that, if there is a visitor effect, daily births should be lower on weekends than weekdays and should correlate with mean daily visitor numbers. Results showed that births for all 16 species were randomly distributed through the week, and there was no significant decline in births on weekends. We conclude that the ‘weekend effect’, if such a thing exists, does not appear to be a feature of zoo births, suggesting that elevated weekend visitor numbers are not sufficiently stressful to trigger delayed parturition.
    • Zooarchaeology through the lens of collagen fingerprinting at Denisova Cave

      Brown, Samantha; Wang, Naihui; Oertle, Annette; Kozlikin, Maxim B.; Shunkov, Michael V.; Derevianko, Anatoly P.; Comeskey, Daniel; Jope-Street, Blair; Harvey, Virginia L.; Chowdhury, Manasij Pal; et al. (Nature Research, 2021-07-29)
      Denisova Cave, a Pleistocene site in the Altai Mountains of Russian Siberia, has yielded significant fossil and lithic evidence for the Pleistocene in Northern Asia. Abundant animal and human bones have been discovered at the site, however, these tend to be highly fragmented, necessitating new approaches to identifying important hominin and faunal fossils. Here we report the results for 8253 bone fragments using ZooMS. Through the integration of this new ZooMS-based data with the previously published macroscopically-identified fauna we aim to create a holistic picture of the zooarchaeological record of the site. We identify trends associated with climate variability throughout the Middle and Upper Pleistocene as well as patterns explaining the process of bone fragmentation. Where morphological analysis of bones from the site have identified a high proportion of carnivore bones (30.2%), we find that these account for only 7.6% of the ZooMS assemblage, with large mammals between 3 and 5 more abundant overall. Our analysis suggests a cyclical pattern in fragmentation of bones which sees initial fragmentation by hominins using percussive tools and secondary carnivore action, such as gnawing and digestion, likely furthering the initial human-induced fragmentation.