Mistletoe lectin dissociates into catalytic and binding subunits before translocation across the membrane to the cytoplasm

AbstractHybridomas producing monoclonal antibodies (mAbs) against the mistletoe lectin A-chain (MLA) were obtained to investigate the intracellular routing and translocation of ribosome-inactivating proteins. Anti-MLA mAb MNA5 did not bind the holotoxin but interacted with isolated MLA. This epitope was not recognized upon MLA denaturation or conjugation of MLA with the ricin binding subunit (RTB). Furthermore, the mAbs did not appreciably react with a panel of MLA synthetic octapeptides linked to the surface of polyethylene pins. A study of the cytotoxicity of mistletoe lectin, ricin, and chimeric toxin MLA/RTB for the hybridomas revealed that interchain disulfide bond reduction and subunit dissociation are required for cytotoxic activity of mistletoe lectin

Lake surface temperature [in “State of the Climate in 2017”]

Observed lake surface water temperature anomalies in 2017 are placed in the context of the recent warming observed in global surface air temperature by collating long-term in situ lake surface temperature observations from some of the world’s best-studied lakes and a satellite-derived global lake surface water temperature dataset. The period 1996–2015, 20 years for which satellite-derived lake temperatures are available, is used as the base period for all lake temperature anomaly calculations

Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis

Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma. Electronic supplementary material The online version of this article (doi:10.1007/s10495-013-0935-2) contains supplementary material, which is available to authorized users

De flora en vegetatie van lijnvormige beplantingen in Nederland

Climate change effects on freshwater biogeochemistry and riverine loads of biogenic elements to the Baltic Sea are not straight forward and are difficult to distinguish from other human drivers such as atmospheric deposition, forest and wetland management , eutrophication and hydrological alterations. Eutrophication is by far the most well-known factor affecting the biogeochemistry of the receiving waters in the various sub-basins of the Baltic Sea. However, the present literature review reveals that climate change is a compounding factor for all major drivers of freshwater biogeochemistry discussed here, although evidence is still often based on short-term and/or small-scale studies

NotCal04; comparison/ calibration 14C records 26-50 cal kyr BP

Author Posting. © Arizona Board of Regents on behalf of the University of Arizona, 2004. This article is posted here by permission of Dept. of Geosciences, University of Arizona for personal use, not for redistribution. The definitive version was published in Radiocarbon 46 (2004): 1225-1238.The radiocarbon calibration curve IntCal04 extends back to 26 cal kyr BP. While several high-resolution records exist beyond this limit, these data sets exhibit discrepancies of up to several millennia. As a result, no calibration curve for the time range 26–50 cal kyr BP can be recommended as yet, but in this paper the IntCal04 working group compares the available data sets and offers a discussion of the information that they hold

IntCal04 terrestrial radiocarbon age calibration, 0-26 cal kyr BP

Author Posting. © Arizona Board of Regents on behalf of the University of Arizona, 2004. This article is posted here by permission of Dept. of Geosciences, University of Arizona for personal use, not for redistribution. The definitive version was published in Radiocarbon 46 (2004): 1029-1058.A new calibration curve for the conversion of radiocarbon ages to calibrated (cal) ages has been constructed and internationally ratified to replace IntCal98, which extended from 0–24 cal kyr BP (Before Present, 0 cal BP = AD 1950). The new calibration data set for terrestrial samples extends from 0–26 cal kyr BP, but with much higher resolution beyond 11.4 cal kyr BP than IntCal98. Dendrochronologically-dated tree-ring samples cover the period from 0–12.4 cal kyr BP. Beyond the end of the tree rings, data from marine records (corals and foraminifera) are converted to the atmospheric equivalent with a site-specific marine reservoir correction to provide terrestrial calibration from 12.4–26.0 cal kyr BP. A substantial enhancement relative to IntCal98 is the introduction of a coherent statistical approach based on a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The tree-ring data sets, sources of uncertainty, and regional offsets are discussed here. The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed in brief, but details are presented in Hughen et al. (this issue a). We do not make a recommendation for calibration beyond 26 cal kyr BP at this time; however, potential calibration data sets are compared in another paper (van der Plicht et al., this issue)