chemical modulation
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Author(s):  
Gustavo Manuel Segovia ◽  
Juan A Allegretto ◽  
Elisa Bindini ◽  
Lucía Belén Pizarro ◽  
Tanja Lüdtke ◽  
...  

We hereby report on thermodynamic and kinetic aspects of ZIF-8 MOF synthesis from methanolic solutions of precursors and 3-mercaptopropionic acid (MPA) acting as chemical modifying agent. MPA bears great interest...


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Daichi Oka ◽  
Yasushi Hirose ◽  
Shoichiro Nakao ◽  
Tomoteru Fukumura ◽  
Tetsuya Hasegawa

AbstractAnderson localization derived from randomness plays a crucial role in various kinds of phase transitions. Although treated as a free variable parameter in theory, randomness in electronic materials is hard to control experimentally owing to the coexisting Coulomb interaction. Here we demonstrate that the intrinsic anion disorder in a mixed-anion system of SrNbO2N induces a significant random potential that overwhelms the Coulomb potential while maintaining the lattice structure. A metal-to-insulator transition is triggered by a chemical modulation of the electron density where the critical electron density is more than three orders of magnitude greater than that predicted by the well-known Mott criterion. The localized electrons show characteristic electrical properties such as temperature-dependent multiple crossovers of conduction mechanisms and a positive magnetoresistance above 50% at low temperature. The large magnetoresistance is attributed to wave-function shrinkage of the localized states and clearly visualizes the anisotropy in the band structure, which indicates a compatibility of the periodicity and randomness.


2021 ◽  
Vol 143 (40) ◽  
pp. 16458-16469
Author(s):  
Shuntaro Takahashi ◽  
Anita Kotar ◽  
Hisae Tateishi-Karimata ◽  
Sudipta Bhowmik ◽  
Zi-Fu Wang ◽  
...  

2021 ◽  
pp. 167183
Author(s):  
Christopher B. Ryder ◽  
Hannah C. Kondolf ◽  
Meghan E. O'Keefe ◽  
Bowen Zhou ◽  
Derek W. Abbott

2021 ◽  
pp. 2882-2890
Author(s):  
Muhammad Mominur Rahman ◽  
Scott McGuigan ◽  
Shaofeng Li ◽  
Lina Gao ◽  
Dong Hou ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Constantin Cretu ◽  
Patricia Gee ◽  
Xiang Liu ◽  
Anant Agrawal ◽  
Tuong-Vi Nguyen ◽  
...  

AbstractIntron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning the selection of branch and 3′ splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.


2021 ◽  
Vol 7 (29) ◽  
pp. eabf5620
Author(s):  
Thomas Pfeffer ◽  
Adrian Ponce-Alvarez ◽  
Konstantinos Tsetsos ◽  
Thomas Meindertsma ◽  
Christoffer Julius Gahnström ◽  
...  

Influential theories postulate distinct roles of catecholamines and acetylcholine in cognition and behavior. However, previous physiological work reported similar effects of these neuromodulators on the response properties (specifically, the gain) of individual cortical neurons. Here, we show a double dissociation between the effects of catecholamines and acetylcholine at the level of large-scale interactions between cortical areas in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. An acetylcholine boost decreased interactions during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly increased by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted noisier decision-making, which we confirmed for both perceptual and value-based choice behavior. Our work highlights specific circuit mechanisms for shaping cortical network interactions and behavioral variability by key neuromodulatory systems.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3975
Author(s):  
Simone Gastaldi ◽  
Valentina Boscaro ◽  
Eleonora Gianquinto ◽  
Christina F. Sandall ◽  
Marta Giorgis ◽  
...  

In the search for new chemical scaffolds able to afford NLRP3 inflammasome inhibitors, we used a pharmacophore-hybridization strategy by combining the structure of the acrylic acid derivative INF39 with the 1-(piperidin-4-yl)1,3-dihydro-2H-benzo[d]imidazole-2-one substructure present in HS203873, a recently identified NLRP3 binder. A series of differently modulated benzo[d]imidazole-2-one derivatives were designed and synthesised. The obtained compounds were screened in vitro to test their ability to inhibit NLRP3-dependent pyroptosis and IL-1β release in PMA-differentiated THP-1 cells stimulated with LPS/ATP. The selected compounds were evaluated for their ability to reduce the ATPase activity of human recombinant NLRP3 using a newly developed assay. From this screening, compounds 9, 13 and 18, able to concentration-dependently inhibit IL-1β release in LPS/ATP-stimulated human macrophages, emerged as the most promising NLRP3 inhibitors of the series. Computational simulations were applied for building the first complete model of the NLRP3 inactive state and for identifying possible binding sites available to the tested compounds. The analyses led us to suggest a mechanism of protein–ligand binding that might explain the activity of the compounds.


2021 ◽  
Author(s):  
Ling Lan ◽  
Ying-Jie Sun ◽  
Xiao-Yang Jin ◽  
Li-Jun Xie ◽  
Li Liu ◽  
...  

Author(s):  
Ling Lan ◽  
Ying-Jie Sun ◽  
Xiao-Yang Jin ◽  
Li-Jun Xie ◽  
Li Liu ◽  
...  

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