ACS Central Science最新文献

The nanogeoscientist aims to uncover how planets formed and evolved.

Protein N-glycosylation is a cotranslational modification that takes place in the endoplasmic reticulum (ER). Disruption of this process can result in accumulation of misfolded proteins, known as ER stress. In response, the unfolded protein response (UPR) restores proteostasis or responds by controlling cellular fate, including increased expression of activating transcription factor 4 (ATF4) that can lead to apoptosis. The ability to control and manipulate such a stress pathway could find use in relevant therapeutic areas, such as in treating cancerous states in which the native ER stress response is often already perturbed. The first committed step in the N-glycosylation pathway is therefore a target for potential ER stress modulation. Here, using structure-based design, the scaffold of the natural product tunicamycin allows construction of a panel capable of graduated inhibition of DPAGT1 through lipid-substituent-modulated interaction. The development of a quantitative, high-content, cellular immunofluorescence assay allowed precise determination of downstream mechanistic consequences (through the nuclear localization of key proxy transcription factor ATF4 as a readout of resulting ER stress). Only the most potent inhibition of DPAGT1 generates an ER stress response. This suggests that even low-level "background" biosynthetic flux toward protein glycosylation is sufficient to prevent response to ER stress. "Tuned" inhibitors of DPAGT1 also now seemingly successfully decouple protein glycosylation from apoptotic response to ER stress, thereby potentially allowing access to cellular states that operate at the extremes of normal ER stress.

Protein N-glycosylation is a cotranslational modification that takes place in the endoplasmic reticulum (ER). Disruption of this process can result in accumulation of misfolded proteins, known as ER stress. In response, the unfolded protein response (UPR) restores proteostasis or responds by controlling cellular fate, including increased expression of activating transcription factor 4 (ATF4) that can lead to apoptosis. The ability to control and manipulate such a stress pathway could find use in relevant therapeutic areas, such as in treating cancerous states in which the native ER stress response is often already perturbed. The first committed step in the N-glycosylation pathway is therefore a target for potential ER stress modulation. Here, using structure-based design, the scaffold of the natural product tunicamycin allows construction of a panel capable of graduated inhibition of DPAGT1 through lipid-substituent-modulated interaction. The development of a quantitative, high-content, cellular immunofluorescence assay allowed precise determination of downstream mechanistic consequences (through the nuclear localization of key proxy transcription factor ATF4 as a readout of resulting ER stress). Only the most potent inhibition of DPAGT1 generates an ER stress response. This suggests that even low-level “background” biosynthetic flux toward protein glycosylation is sufficient to prevent response to ER stress. “Tuned” inhibitors of DPAGT1 also now seemingly successfully decouple protein glycosylation from apoptotic response to ER stress, thereby potentially allowing access to cellular states that operate at the extremes of normal ER stress.

Editing of the archetypal tunicamycin scaffold creates novel intracellular protein glycosylation inhibitors with altered stress induction potential.

Inelastic photoelectron scattering (IPES) by gas molecules, a critical phenomenon observed in ambient pressure X-ray photoelectron spectroscopy (APXPS), complicates spectral interpretation due to kinetic energy loss in the primary spectrum and the appearance of additional features at higher binding energies. In this study, we systematically investigate IPES in various gas environments using APXPS, providing detailed insights into interactions between photoelectrons emitted from solid surfaces and surrounding gas molecules. Core-level XPS spectra of Au, Ag, Zn, and Cu metals were recorded over a wide kinetic energy range in the presence of CO₂, N₂, Ar, and H₂ gases, demonstrating the universal nature of IPES across different systems. Additionally, we analyzed spectra of scattering effects induced by gas-phase interactions without metal solids. In two reported CO₂-reduction systems (p-GaN/Au/Cu and p-Si/TaO_x/Cu), we elucidated that IPES is independent of the composition, structure, or size of the solid materials. Using metal foil platforms, we further developed an analytical model to extract electron excitation cross sections of gas molecules. These findings enhance our understanding of IPES mechanisms and enable the predictions of IPES structures in other solid–gas systems, providing a valuable reference for future APXPS studies and improving the accuracy of spectral analysis in gas-rich catalytic interfaces.

Inelastic photoelectron scattering by gas molecules is comprehensively studied for ambient pressure X-ray photoelectron spectroscopy analyses, advancing spectral interpretation in gas-rich interfaces.

Inelastic photoelectron scattering (IPES) by gas molecules, a critical phenomenon observed in ambient pressure X-ray photoelectron spectroscopy (APXPS), complicates spectral interpretation due to kinetic energy loss in the primary spectrum and the appearance of additional features at higher binding energies. In this study, we systematically investigate IPES in various gas environments using APXPS, providing detailed insights into interactions between photoelectrons emitted from solid surfaces and surrounding gas molecules. Core-level XPS spectra of Au, Ag, Zn, and Cu metals were recorded over a wide kinetic energy range in the presence of CO₂, N₂, Ar, and H₂ gases, demonstrating the universal nature of IPES across different systems. Additionally, we analyzed spectra of scattering effects induced by gas-phase interactions without metal solids. In two reported CO₂-reduction systems (p-GaN/Au/Cu and p-Si/TaO _x /Cu), we elucidated that IPES is independent of the composition, structure, or size of the solid materials. Using metal foil platforms, we further developed an analytical model to extract electron excitation cross sections of gas molecules. These findings enhance our understanding of IPES mechanisms and enable the predictions of IPES structures in other solid-gas systems, providing a valuable reference for future APXPS studies and improving the accuracy of spectral analysis in gas-rich catalytic interfaces.

To track changes in the colors of eucalyptus, this Ngugi researcher gathers knowledge in Aboriginal communities as well as in the lab.