Article
Biochemistry & Molecular Biology
Lin Yuan, Wanying Yi, Changyu Sun, Shuangshuang Ma, Jiali Wang, Saijuan Liu, Yijing Chen, Yuewen Chen, Yu Chen
Summary: Dendritic spines, the postsynaptic structures in neural circuitry, are regulated by EphB2 signaling, which involves the activation of CREB to modulate the expression of Annexin A1, ultimately impacting dendritic spine morphology.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jyothi Mahadevan, Asmita Jha, Johannes Rudolph, Samuel Bowerman, Domenic Narducci, Anders S. Hansen, Karolin Luger
Summary: PARP1 contributes to genome architecture and DNA damage repair through its dynamic association with chromatin. PARP1/2 recognize damaged DNA and recruit the DNA repair machinery. Single-molecule microscopy in live cells revealed two classes of freely diffusing PARP1/2 and two classes of bound PARP1/2. Majority of PARP1/2 diffuse freely in both undamaged and damaged nuclei, while a small fraction becomes transiently bound upon laser-induced DNA damage. Treatment with PARP1/2 inhibitors in the presence of DNA damage causes subtle changes in the dynamics of bound PARP1/2, suggesting potential for targeted therapy.
Article
Multidisciplinary Sciences
Jing Gao, Hongru Li, Haijiao Xu, Yong Liu, Mingjun Cai, Yan Shi, Jingrui Zhang, Hongda Wang
Summary: Using dSTORM imaging, nanoscale GCGR clusters were observed on HepG2 cell membranes, and high glucose promoted GCGR expression and the formation of more and larger clusters. Glucagon stimulation under high glucose did not inhibit GCGR levels as significantly as that under low glucose, and did not increase the downstream cAMP-PKA signal, indicating high glucose-induced glucagon resistance. Furthermore, high glucose induced stronger glucagon resistance in hepatoma cells compared with hepatic cells.
Article
Multidisciplinary Sciences
Meenakshi Sharma, Eva de Alba
Summary: This study investigates the association and dissociation rates of the AIM2-DNA complex at the single molecule level using optical traps and confocal fluorescence microscopy. The results reveal distinct mechanisms for the growth of AIM2 oligomers and show that the size of the oligomers can increase fourfold within seconds. Additionally, it is found that single AIM2 molecules do not diffuse/scan along the DNA, suggesting that oligomerization depends on stochastic encounters with DNA and/or DNA-bound AIM2.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Sahar Foroutannejad, Lydia L. L. Good, Changfan Lin, Zachariah I. I. Carter, Mahlet G. G. Tadesse, Aaron L. L. Lucius, Brian R. R. Crane, Rodrigo A. A. Maillard
Summary: Characterizing folding pathways of large proteins that bind complex cofactors is challenging. The authors use optical tweezers to study the folding mechanism of dCRY and identify the role of FAD moieties in folding. They show that FAD binds to unfolded intermediates and drives the folding process, but not all FAD moieties are necessary for complete folding.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Hongxia Fu, Yan Jiang, Wesley P. Wong, Timothy A. Springer
Summary: Von Willebrand factor (VWF) is an important ultra-long concatemeric protein in hemostasis and thrombosis. Self-association of VWF molecules in flow is reversible and has a self-limiting mechanism. The tension in tethered VWF plays a crucial role in mediating association between VWF molecules.
Article
Multidisciplinary Sciences
Inna Armandari, Walderik W. Zomerman, Sabine L. A. Plasschaert, Marlinde J. Smit, Tosca E. Martini, Eduardo S. de Camargo Magalhaes, Shanna M. Hogeling, Geesina C. Rozema-Huizinga, Harm J. Lourens, Tiny G. J. Meeuwsen-de Boer, Frank J. G. Scherpen, Eveline S. J. M. de Bont, Sophia W. M. Bruggeman
Summary: The study found that phosphorylation of the transcription factor CREB correlates strongly with survival in medulloblastoma patients and differentiation phenotype. During normal cerebellar development, phosphorylated CREB is selectively expressed in differentiating cerebellar granule neuron progenitor cells. Inducing CREB activation via PKA-mediated signaling enhances sensitivity of medulloblastoma cells to chemotherapy.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Kanta Kawai, Tasuku Hirayama, Haruka Imai, Takanori Murakami, Masatoshi Inden, Isao Hozumi, Hideko Nagasawa
Summary: In this study, we developed an activity-based fluorescence probe H-FluNox for monitoring the fluctuations of labile heme (LH) in cells. The probe exhibited high selectivity towards LH, enabling the discrimination of LH from labile Fe(II). By using this probe, we observed the acute release of LH upon NO stimulation and the accumulation of LH by inhibiting the heme exporter. Furthermore, the imaging studies using the probe provided insights into the heme-export activity of ATP-binding cassette subfamily G member 2 (ABCG2), the LH pooling ability of G-quadruplex, and the involvement of LH in ferroptosis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Linyu Zuo, Jiawei Ding, Zhi Qi
Summary: The article discusses the importance of fusion genes in tumors, as well as the mechanism of action of the EWS-FLI1 fusion gene in Ewing sarcoma, including the formation of biomolecular condensates to enhance gene transcription. The DNA Curtains method can be used to visualize the assembly process of EWS-FLI1 condensates.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Multidisciplinary Sciences
Nikolas L. Jorstad, Janet H. T. Song, David Exposito-Alonso, Hamsini Suresh, Nathan Castro-Pacheco, Fenna M. Krienen, Anna Marie Yanny, Jennie Close, Emily Gelfand, Brian Long, Stephanie C. Seeman, Kyle J. Travaglini, Soumyadeep Basu, Marc Beaudin, Darren Bertagnolli, Megan Crow, Song-Lin Ding, Jeroen Eggermont, Alexandra Glandon, Jeff Goldy, Katelyn Kiick, Thomas Kroes, Delissa Mcmillen, Trangthanh Pham, Christine Rimorin, Kimberly Siletti, Saroja Somasundaram, Michael Tieu, Amy Torkelson, Guoping Feng, William D. Hopkins, Thomas Hollt, C. Dirk Keene, Sten Linnarsson, Steven A. Mccarroll, Boudewijn P. Lelieveldt, Chet C. Sherwood, Kimberly Smith, Christopher A. Walsh, Alexander Dobin, Jesse Gillis, Ed S. Lein, Rebecca D. Hodge, Trygve E. Bakken
Summary: Our study used snRNA-seq to analyze the transcriptome of the cerebral cortex in humans and four nonhuman primate species. We found that cell types in the cerebral cortex are highly conserved among great apes, with marmosets showing some unique cell type proportions. Profiling gorillas allowed us to identify expression differences between humans and chimpanzees that are specialized in humans. We also discovered that neuronal gene expression has evolved faster on the human lineage, while glial expression changes have occurred rapidly in all species. Human-specific DEGs are enriched near adaptive genomic changes and may contribute to specialized cortical function.
Article
Biology
Takeshi Otsuka, Yasuo Kawaguchi
Summary: The study shows that manipulation of specific pyramidal cell subtypes in the motor cortex has a significant impact on cortical network activity, with PT cell-dependent oscillatory activity playing an important role in motor learning.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sangwoo Park, Giovanni B. Brandani, Taekjip Ha, Gregory D. Bowman
Summary: Chromatin remodelers use a helicase-type ATPase motor to shift DNA and exhibit a sequence-dependent bias in nucleosome positioning, which is influenced by local DNA perturbations throughout the nucleosome footprint.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Duo Xu, Mingyuan Dong, Yuxi Chen, Angel M. Delgado, Natasha C. Hughes, Linghua Zhang, Daniel H. O'Connor
Summary: The brain can generate complex sequences of movements and adjust them based on behavioral context or real-time sensory feedback. In this study, researchers developed a task called "sequence licking" and found that mice could rapidly branch the sequence based on tactile feedback. Through optogenetics and electrophysiology, they also identified key cortical regions involved in encoding and controlling tongue movements.
Article
Biochemistry & Molecular Biology
Tobias Buchborn, Taylor Lyons, Chenchen Song, Amanda Feilding, Thomas Knoepfel
Summary: By using cell type-specific voltage imaging in awake mice, researchers have found that shaking behavior is preceded by high-frequency oscillations and overlaps with low-frequency oscillations in the motor cortex. These oscillations mirror the rhythmics of shaking behavior and reflect the activity of layer 2/3 pyramidal cells. The results provide insights into the cortical fingerprint of serotonin-2A receptor-mediated shaking behavior and offer a promising methodological avenue for studying cell-type specific brain dynamics related to cross-mammalian psychedelic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Weitao Fu, Hao Yang, Chenxian Hu, Jianing Liao, Zhou Gong, Minkui Zhang, Shangxiang Ye, Shuai Yang, Yixuan Lei, Rong Sheng, Zhiguo Zhang, Xiaojun Yao, Chun Tang, Dan Li, Tingjun Hou
Summary: Using molecular dynamics simulation, structure-based virtual screening, structure-activity relationship exploration, and bioassays, we identified small-molecule antagonists targeting a prospective pocket on the androgen receptor (AR) dimer interface. The first-in-class antagonist, M17-B15, effectively disrupts AR self-association and suppresses AR signaling, demonstrating its extraordinary anti-prostate cancer efficacy in vitro and in mouse xenograft tumor models. Targeting the dimer interface pocket (DIP) is a novel and valid strategy against prostate cancer.
ACS CENTRAL SCIENCE
(2023)