Article
Plant Sciences
Jawad Ahmed, Yasar Sajjad, Aasia Latif, Mohammad Saeed Lodhi, Muhammad Huzafa, Chen Situ, Raza Ahmad, Muhammad Maroof Shah, Amjad Hassan
Summary: This study reveals the potential role of CrWAK genes in the biosynthesis of MIAs in Catharanthus roseus, providing a basis for further functional characterization and mechanistic explanation.
JOURNAL OF PLANT RESEARCH
(2023)
Article
Plant Sciences
Joana G. Guedes, Rogerio Ribeiro, Ines Carqueijeiro, Ana Luisa Guimaraes, Claudia Bispo, John Archer, Herlander Azevedo, Nuno A. Fonseca, Mariana Sottomayor
Summary: The mesophyll idioblasts of Catharanthus roseus are a hotspot for alkaloid accumulation and have a distinctive transcriptomic profile associated with stress responses. The transcriptome of idioblasts may hold the key to understanding the MIA pathway and increasing the levels of anticancer drugs.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Biochemistry & Molecular Biology
Sara Rosendahl, Rima Sulniute, Michaela Eklund, Cecilia Koskinen Holm, Marcus J. O. Johansson, Elin Kindstedt, Susanne Lindquist, Pernilla Lundberg
Summary: CCR3 deficiency influences osteoblast and osteoclast differentiation, leading to thinner cortical bone in adult male mice.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Chino C. Cabalteja, Shivani Sachdev, Ross W. Cheloha
Summary: This study presents a cross-linking platform that utilizes a synthetic peptide epitope and a single domain antibody pair to rapidly and specifically form covalent linkages. The system exhibits fast kinetics and can be used to label live cells expressing receptor-nanobody fusions.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Neurosciences
Justin L. Bollinger, David T. Dadosky, James K. Flurer, Ivanka L. Rainer, Samuel C. Woodburn, Eric S. Wohleb
Summary: Chronic unpredictable stress (CUS) leads to microglia-mediated neuronal remodeling and synapse loss in the prefrontal cortex (PFC), affecting cognition and behavior. Purinergic signaling, specifically through the P2Y12 receptor, plays a critical role in guiding microglia-neuron interactions. Deletion or blockade of P2Y12 prevents stress-induced alterations in microglial properties, attenuates synapse loss in the PFC, and improves behavioral deficits.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Su Hui Yang, Daulat Bikram Khadka, Jinhe Han, Soon-Young Na, Minsang Shin, Don-Kyu Kim, Byung-Chul Oh, Eun Young Kim, Hueng-Sik Choi, Won-Jea Cho
Summary: ERR gamma is an orphan nuclear receptor similar to estrogen receptors, but its endogenous ligand is unknown. Only stilbene and flavonol molecules have been found to modulate its transcriptional activity, but without selectivity. Therefore, virtual screening identified a novel ERR gamma inverse agonist, pyrazolamide 7, and its optimized derivative, pyrazolamide 19, showed potent and selective inverse agonistic activity towards ERR gamma. Pyrazolamide 19 exhibited strong affinity towards ERR gamma and inhibited the expression of hepcidin, fibrinogen, and gluconeogenic genes, suggesting potential antimicrobial, anti-coagulant, and antidiabetic activities.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Alessandro Nicoli, Verena Weber, Carlotta Bon, Alexandra Steuer, Stefano Gustincich, Raul R. Gainetdinov, Roman Lang, Stefano Espinoza, Antonella Di Pizio
Summary: This study discovered four novel TAAR5 antagonists through high-throughput screening and developed a computational strategy for identifying TAAR5 ligands. Despite lacking an experimental structure, the TAAR5 binding site was accurately modeled by integrating comparative sequence- and structure-based analyses. These newly discovered TAAR5 antagonists could serve as potential treatments for depression, anxiety, and neurodegenerative diseases.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Cell Biology
Lina M. Gallego-Paez, William J. S. Edwards, Manasa Chanduri, Yanyu Guo, Thijs Koorman, Chieh-Yu Lee, Nina Grexa, Patrick Derksen, Jie Yan, Martin A. Schwartz, Jan Mauer, Benjamin Thomas Goult
Summary: This study identified a previously unannotated cassette exon, referred to as exon 17b, in the TLN1 gene. The presence of this exon alters the function of the TLN1 protein in the mechanosensitive adapter system and affects cell adhesion dynamics and motility. This novel exon is detectable in multiple healthy tissues and significantly enriched in certain cancer subtypes.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Xueying Wang, Shuguang Yuan, H. C. Stephen Chan
Summary: This study performed molecular dynamics simulations to illustrate the energy barriers of Na+ transfer in the transmembrane helix bundle of beta 2AR. It found that the translocation of allosteric Na+ into the intracellular side is significantly difficult, which suggests that the translocation direction could be specific to the receptor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biology
Ralf Schmauder, Thomas Eick, Eckhard Schulz, Guenther Sammler, Elmar Voigt, Guenter Mayer, Holger Ginter, Guenter Ditze, Klaus Benndorf
Summary: By using a microfluidic chip-based technique, we have developed a method for studying ion currents and fluorescence signals in order to measure the kinetics of channel activation and deactivation, as well as ligand binding and unbinding. This approach allows for the rapid generation of concentration-activation relationships and activation kinetics, while minimizing the effects of interference.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Huong T. Vu, Zhechun Zhang, Riina Tehver, D. Thirumalai
Summary: This study reveals the structural basis of kinesin stepping directionality and its correlation with the plus end of microtubules. It also explains the effects of microtubules on a key step in the catalytic cycle of kinesin.
Article
Chemistry, Medicinal
Qimeng Yang, Weizhong Tang, Lidan Sun, Zhiming Yan, Chunli Tang, Yongliang Yuan, Huan Zhou, Feng Zhou, Siyuan Zhou, Qingqing Wu, Peng Song, Ting Fang, Ronglian Xu, Jing Han, Neng Jiang
Summary: symbolscript GLP-1R/Y2R dual agonists have potential to treat obesity and type 2 diabetes. They show better effects on long-term glycemic control and weight reduction compared to monoagonist counterparts. In mice with obesity and nonalcoholic steatohepatitis, symbolscript treatment significantly reduces hepatic triglyceride and total cholesterol levels and reverses hepatic steatosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Geng Chen, Xiankun Wang, Qiwen Liao, Yunjun Ge, Haizhan Jiao, Qiang Chen, Yezhou Liu, Wenping Lyu, Lizhe Zhu, Gydo C. P. van Zundert, Michael J. Robertson, Georgios Skiniotis, Yang Du, Hongli Hu, Richard D. Ye
Summary: The formyl peptide receptor 1 (FPR1) plays a critical role in detecting short peptides characteristic of protein synthesis in bacteria and mitochondria, and is important in phagocyte migration and activation during bacterial infection, tissue injury and inflammation. This study reveals the structural basis of FPR1 recognition of bacteria-derived chemotactic peptides, providing insights for developing FPR1-targeting agents.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Celine Ortega-Ferreira, Perrine Soret, Gautier Robin, Silvia Speca, Sandra Hubert, Marianne Le Gall, Emiko Desvaux, Manel Jendoubi, Julie Saint-Paul, Loubna Chadli, Agnes Chomel, Sylvie Berger, Emmanuel Nony, Beatrice Neau, Benjamin Fould, Anne Licznar, Franck Levasseur, Thomas Guerrier, Sahar Elouej, Sophie Courtade-Gaiani, Nicolas Provost, The Quyen Nguyen, Julien Verdier, David Launay, Frederic De Ceuninck
Summary: Systemic sclerosis (SSc) is a disease with limited treatment options, and galectin-3 (Gal-3) has been implicated in its pathology. This study shows that Gal-3 and its interactants are associated with disease severity and various pathological processes in SSc patients. The researchers developed Gal-3 neutralizing monoclonal antibodies (mAb) and demonstrated their therapeutic potential in a mouse model of SSc, reducing skin and lung lesions.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Shu-Hsien Sheu, Srigokul Upadhyayula, Vincent Dupuy, Song Pang, Fei Deng, Jinxia Wan, Deepika Walpita, H. Amalia Pasolli, Justin Houser, Silvia Sanchez-Martinez, Sebastian E. Brauchi, Sambashiva Banala, Melanie Freeman, C. Shan Xu, Tom Kirchhausen, Harald F. Hess, Luke Lavis, Yulong Li, Severine Chaumont-Dubel, David E. Clapham
Summary: This study discovers the existence of synapses between axons and primary cilia and reveals their role in neuronal communication. The cilia are enriched in serotonin receptors and can be stimulated by serotonin released from axons, altering the epigenetic state of the postsynaptic neuron.