G protein-independent, arrestin-dependent signaling is a paradigm that broadens the signaling scope of G protein-coupled receptors (GPCRs) beyond G proteins for numerous biological processes. However, arrestin signaling in the collective absence of functional G proteins has never been demonstrated. Here we achieve a state of "zero functional G" at the cellular level using HEK293 cells depleted by CRISPR/Cas9 technology of the Gs/q/12 families of Gα proteins, along with pertussis toxin-mediated inactivation of Gi/o. Together with HEK293 cells lacking β-arrestins ("zero arrestin"), we systematically dissect G protein- from arrestin-driven signaling outcomes for a broad set of GPCRs. We use biochemical, biophysical, label-free whole-cell biosensing and ERK phosphorylation to identify four salient features for all receptors at "zero functional G": arrestin recruitment and internalization, but-unexpectedly-complete failure to activate ERK and whole-cell responses. These findings change our understanding of how GPCRs function and in particular of how they activate ERK1/2.
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http://dx.doi.org/10.1038/s41467-017-02661-3 | DOI Listing |
Introduction: During centrifuge-simulated suborbital spaceplane flights, launch and re-entry frequently cause visual symptoms, and G-induced loss of consciousness can occur. G-related effects may be more prominent during re-entry from microgravity on actual flights. A modified anti-G maneuver that does not involve a breath strain and is suitable for members of the public may be effective against these effects.
View Article and Find Full Text PDFThe degree of immunological compatibility between donors and recipients greatly impacts allograft survival. In the United States kidney allocation system, HLA antigen-level matching has been shown to cause ethnic disparities and thus, has been de-emphasised. However, priority points are still awarded for antigen-level zero-ABDR matching, zero-DR matching and one-DR matching.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
In pursuit of high- hydride superconductors, the molecular hydrides have attracted less attention because the hydrogen quasimolecules are usually inactive for superconductivity. Here, we report on the successful synthesis of a novel bismuth hydride superconductor 2/-BiH at pressures around 170-180 GPa. Its structure comprises bismuth atoms and elongated hydrogen molecules with a H-H bond length of 0.
View Article and Find Full Text PDFJ Gerontol B Psychol Sci Soc Sci
December 2024
School of Psychology, Georgia Institute of Technology, Atlanta, GA, USA.
Objectives: Mindfulness interventions are consistently associated with beneficial effects in younger adults. In this meta-analysis, we seek to quantify the effectiveness of mindfulness interventions for the mental health and well-being of older adults.
Method: We include 46 studies that implemented a mindfulness intervention (MBSR = 20; MBCT = 9; ad hoc protocol = 17) with older adults (samples with an average age of 60 or older; healthy adults = 20; adults with underlying symptoms = 26), examining a wide range of outcome measures (e.
J Environ Manage
December 2024
Fujian Key Laboratory of Pollution Control and Resource Reuse, School of Environmental and Resource Sciences, Fujian Normal University, Fuzhou, 350117, Fujian Province, China. Electronic address:
Carbon-encapsulated nanoscale zero-valent-iron (C@Fe) derived from plant-based extracts has been the subject of growing interest due to its environmental friendliness. However, the effects of various pyrolysis atmospheres on the structure-function connections of C@Fe are still unclear. In this study, three pyrolytic atmospheres, namely Air, N, and 5% H/Ar were selected to fabricate X-C@Fe (X represented as A, N, H) for removing 2,4,6-Trichlorophenol (TCP), and the relationships between their structures and functions were demonstrated.
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