The remarkable power of enzymes to undertake catalysis frequently stems from their grouping of multiple, complementary chemical units within close proximity around the enzyme active site. Motivated by this, we report here a bioinspired surfactant catalyst that incorporates a variety of chemical functionalities common to hydrolytic enzymes. The textbook hydrolase active site, the catalytic triad, is modeled by positioning the three groups of the triad (-OH, -imidazole, and -CO2H) on a single, trifunctional surfactant molecule. To support this, we recreate the hydrogen bond donating arrangement of the oxyanion hole by imparting surfactant functionality to a guanidinium headgroup. Self-assembly of these amphiphiles in solution drives the collection of functional headgroups into close proximity around a hydrophobic nano-environment, affording hydrolysis of a model ester at rates that challenge α-chymotrypsin. Structural assessment via NMR and XRD, paired with MD simulation and QM calculation, reveals marked similarities of the co-micelle catalyst to native enzymes. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species. We show that RAVs exist as distinct, highly dynamic structures separate from the intact ER reticular architecture that interact with mitochondria via direct intermembrane contacts. These findings describe a new ER subcompartment within cells. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).The cave bear is one of the best known extinct large mammals that inhabited Europe during the "Ice Age," becoming extinct ≈24,000 years ago along with other members of the Pleistocene megafauna. Long-standing hypotheses speculate that many cave bears died during their long hibernation periods, which were necessary to overcome the severe and prolonged winters of the Last Glacial. Here, we investigate how long hibernation periods in cave bears would have directly affected their feeding biomechanics using CT-based biomechanical simulations of skulls of cave and extant bears. Our results demonstrate that although large paranasal sinuses were necessary for, and consistent with, long hibernation periods, trade-offs in sinus-associated cranial biomechanical traits restricted cave bears to feed exclusively on low energetic vegetal resources during the predormancy period. This biomechanical trade-off constitutes a new key factor to mechanistically explain the demise of this dominant Pleistocene megafaunal species as a direct consequence of climate cooling. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Is the media biased against conservatives? Although a dominant majority of journalists identify as liberals/Democrats and many Americans and public officials frequently decry supposedly high and increasing levels of media bias, little compelling evidence exists as to (i) the ideological or partisan leanings of the many journalists who fail to answer surveys and/or identify as independents and (ii) whether journalists' political leanings bleed into the choice of which stories to cover that Americans ultimately consume. Using a unique combination of a large-scale survey of political journalists, data from journalists' Twitter networks, election returns, a large-scale correspondence experiment, and a conjoint survey experiment, we show definitively that the media exhibits no bias against conservatives (or liberals for that matter) in what news that they choose to cover. This shows that journalists' individual ideological leanings have unexpectedly little effect on the vitally important, but, up to this point, unexplored, early stage of political news generation.  https://www.selleckchem.com/products/idf-11774.html  Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).Mechanical forces play important roles in development, physiology, and diseases, but how force is transduced into gene transcription remains elusive. Here, we show that transcription of transgene DHFR or endogenous genes egr-1 and Cav1 is rapidly up-regulated in response to cyclic forces applied via integrins at low frequencies but not at 100 Hz. Gene up-regulation does not follow the weak power law with force frequency. Force-induced transcription up-regulation at the nuclear interior is associated with demethylation of histone H3 lysine-9 trimethylation (H3K9me3), whereas no transcription up-regulation near the nuclear periphery is associated with H3K9me3 that inhibits Pol II recruitment to the promoter site. H3K9me3 demethylation induces Pol II recruitment and increases force-induced transcription of egr-1 and Cav1 at the nuclear interior and activates mechano-nonresponsive gene FKBP5 near the nuclear periphery, whereas H3K9me3 hypermethylation has opposite effects. Our findings demonstrate that rapid up-regulation of endogenous mechanoresponsive genes depends on H3K9me3 demethylation. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).