Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction

Regulation of chromatin structure involves histone posttranslational modifications that can modulate intrinsic properties of the chromatin fiber to change the chromatin state. We used chemically defined nucleosome arrays to demonstrate that H2B ubiquitylation (uH2B), a modification associated with transcription, interferes with chromatin compaction and leads to an open and biochemically accessible fiber conformation. Notably, these effects were specific for ubiquitin, as compaction of chromatin modified with a similar ubiquitin-sized protein, Hub1, was only weakly affected. Applying a fluorescence-based method, we found that uH2B acts through a mechanism distinct from H4 tail acetylation, a modification known to disrupt chromatin folding. Finally, incorporation of both uH2B and acetylated H4 resulted in synergistic inhibition of higher-order chromatin structure formation, possibly a result of their distinct modes of action

The Ca(2+)-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate

Transient receptor potential (TRP) channel, melastatin subfamily (TRPM)4 is a Ca(2+)-activated monovalent cation channel that depolarizes the plasma membrane and thereby modulates Ca(2+) influx through Ca(2+)-permeable pathways. A typical feature of TRPM4 is its rapid desensitization to intracellular Ca(2+) ([Ca(2+)](i)). Here we show that phosphatidylinositol 4,5-biphosphate (PIP(2)) counteracts desensitization to [Ca(2+)](i) in inside-out patches and rundown of TRPM4 currents in whole-cell patch-clamp experiments. PIP(2) shifted the voltage dependence of TRPM4 activation towards negative potentials and increased the channel's Ca(2+) sensitivity 100-fold. Conversely, activation of the phospholipase C (PLC)-coupled M1 muscarinic receptor or pharmacological depletion of cellular PIP(2) potently inhibited currents through TRPM4. Neutralization of basic residues in a C-terminal pleckstrin homology (PH) domain accelerated TRPM4 current desensitization and strongly attenuated the effect of PIP(2), whereas mutations to the C-terminal TRP box and TRP domain had no effect on the PIP(2) sensitivity. Our data demonstrate that PIP(2) is a strong positive modulator of TRPM4, and implicate the C-terminal PH domain in PIP(2) action. PLC-mediated PIP(2) breakdown may constitute a physiologically important brake on TRPM4 activity

Inactivation of TRPM7 kinase in mice results in enlarged spleens, reduced T-cell proliferation and diminished store-operated calcium entry

Abstract T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca2+ in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell proliferation on external Ca2+ and Mg2+ concentrations. At a fixed [Mg2+ o] of ~0.4 mM, Ca2+ o stimulated proliferation with a steep concentration dependence and vice versa, at a fixed [Ca2+ o] of ~0.4 mM, Mg2+ o positively regulated proliferation but with a shallower dependence. Proliferation was significantly lower in KD mouse than in wildtype at all Ca2+ and Mg2+ concentrations. Ca2+ elevations elicited by anti-CD3 antibody were diminished in KD mutant T cells and SOCE measured in activated KD splenocytes was reduced. These results demonstrate that a functional TRPM7 kinase supports robust SOCE, blastogenesis and proliferation, whereas its inactivation suppresses these cellular events