Endocytosis of the ASGP receptor H1 is reduced by mutation of tyrosine-5 but still occurs via coated pits

The clustering of plasma membrane receptors in clathrin-coated pits depends on determinants within their cytoplasmic domains. In several cases, individual tyrosine residues were shown to be necessary for rapid internalization. We have mutated the single tyrosine at position 5 in the cytoplasmic domain of the major subunit H1 of the asialoglycoprotein receptor to alanine. Expressed in fibroblasts cells, the mutant protein was accumulated in the plasma membrane, and its rate of internalization was reduced by a factor of four. The residual rate of endocytosis, however, was still significantly higher than that of resident plasma membrane proteins. Upon acidification of the cytoplasm, which specifically inhibits the formation of clathrin-coated vesicles but not uptake of the fluid phase marker Lucifer yellow, residual endocytosis was blocked. By immunoelectron microscopy mutant H1 could be directly demonstrated in coated pits. The fraction of wild-type and mutant H1 present in coated pits as determined by immunogold localization correlated well with the respective rates of internalization. Thus, mutation of tyrosine-5 only partially inactivates recognition of H1 for incorporation into coated pits

LSE continental breakfast 1: what can we expect from Brexit negotiations?

In the first of LSE’s Continental Breakfasts – held under Chatham House rules, so participants can speak as freely as they wish – a roundtable discussed the immediate challenges facing the UK as it triggers Article 50. Robert van Geffen distills some of the key points

Would Brexit be the final straw for financial services in the UK?

Nearly 2.2m people work in financial services in Britain, which is a global centre of excellence in the industry. What impact would leaving the EU have on the sector? Robert van Geffen looks at whether UK banks would continue to be able to ‘passport’ services across the EU and, if not, how they might get around the problem. Even assuming they were able to do that, he writes, the UK would no longer be able to influence EU financial regulation. Furthermore, it is unlikely to cut back on regulation as a result of Brexit

Analysis of healthy sitting behavior: Interface pressure distribution and subcutaneous tissue oxygenation

Pressure ulcers are a large problem in individuals who use a wheelchair for their mobility and have limited trunk stability and motor function. Because no relation between interface pressure and pressure ulcer development has been established and no clinical threshold for pressure ulcer development can be given, looking at the sitting behavior of nondisabled individuals is important. Nondisabled individuals do not develop pressure ulcers because they continuously shift posture. We analyzed the sitting behavior of 25 nondisabled male subjects by using a combination of interface pressure measurement and subcutaneous tissue oxygenation measurement by means of the Oxygen to See. These subjects shifted posture on average 7.8 +/- 5.2 times an hour. These posture shifts were merely a combination of posture shifts in the frontal and sagittal plane. Subcutaneous oxygen saturation increased on average 2.2% with each posture adjustment, indicating a positive effect of posture shifts on tissue viability. The results of this study can be used as a reference for seating interventions aimed at preventing pressure ulcers. Changing the sitting load at least every 8 minutes is recommended for wheelchair users

A TROPOMI- and GLM-Based Estimate of NOx Production by Lightning over the U.S.

Lightning produces NO because the extreme temperatures (>20000 K) in lightning channels dissociate molecular O2 and molecular N2, which then combine to form NOx which quickly reacts with O3 to form NO2. Lightning is responsible for 10-15% of NOx emissions globally. This is 2 8 Tg N a-1 [Schumann and Huntrieser, 2007] or 100 to 400 mol per flash. Much of the uncertainty stems from limited knowledge of lightning NOx production per flash (LNOx PE) or per unit flash length. Most LNOx is injected into mid- and upper-troposphere where away from deep convection its lifetime is longer relative to lower troposphere NOx. NOx in this region enhances the concentrations of upper tropospheric NOy, OH, and O3 and contributes to positive radiative forcing by O3 and negative forcing by CH4. We have previously used OMI NO2 to obtain estimates of LNOx production per flash over the Gulf of Mexico (Pickering et al., 2016, JGR), in convective events during NASAs TC4 field program (Bucsela et al., 2010, JGR), and over broad regions of the tropics (Allen et al., 2019, JGR) and midlatitudes (Bucsela et al., 2019, JGR). In the latter studies, we obtained PE values of 170 100 mol flash and 180 100 mol flash, respectively