Single molecules that act as light-energy transducers (e.g., converting the energy of a photon into atomic-level mechanical motion) are examples of minimal molecular devices. Here, we focus on a molecular switch designed by merging a conformationally locked diarylidene skeleton with a retinal-like Schiff base and capable of mimicking, in solution, different aspects of the transduction of the visual pigment Rhodopsin. Complementary ab initio multiconfigurational quantum chemistry-based computations and time-resolved spectroscopy are used to follow the light-induced isomerization of the switch in methanol. The results show that, similar to rhodopsin, the isomerization occurs on a 0.3-ps time scale and is followed by <10-ps cooling and solvation. The entire (2-photon-powered) switch cycle was traced by following the evolution of its infrared spectrum. These measurements indicate that a full cycle can be completed within 20 ps.
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http://dx.doi.org/10.1073/pnas.0802376105 | DOI Listing |
CNS Drugs
January 2025
Innovative Medicines and Global Clinical Development, Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA.
Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:
Proto-oncogene RET is overexpressed in many cancers, and its expression level is positively related to the size and malignancy of the tumors. Effective inhibition of its overexpression can be used to potentially treat cancers. A guanine-rich GC-boxes (I-V) sequence in its promoter region folds into noncanonical G-quadruplex (G4) DNA structures, negatively regulating its expression by interactions with small molecules.
View Article and Find Full Text PDFCell
January 2025
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands. Electronic address:
Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Hematology, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China.
SPT5 exhibits versatile functions in RNA Pol II promoter proximal pausing, pause release, and elongation in metazoans. However, the mechanism underlying the functional switch of SPT5 during early elongation has not been fully understood. Here, we report that the phosphorylation site-rich domain (PRD)/CTR1 and the prion-like domain (PLD)/CTR2, which are situated adjacent to each other within the C-terminal repeat (CTR) in SPT5, play pivotal roles in Pol II pausing and elongation, respectively.
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