Editorial Material
Biochemistry & Molecular Biology
Clint A. Stalnecker, Channing J. Der
Summary: In this study, Shui et al. use a systems biology approach to elucidate the paradoxical role of microRNA in regulating gene and protein expression in oncogenic KrasG12D.
Article
Cell Biology
Jie-Ning Li, Hui-Lung Sun, Ming-Yang Wang, Pai-Sheng Chen
Summary: MicroRNAs (miRNAs) are small non-coding RNAs that play a role in regulating pathophysiological processes by suppressing target gene expression post-transcriptionally. The function of miRNAs is regulated by a conserved biogenesis machinery involving processing steps and the formation of a miRNA-induced silencing complex (miRISC). This study discovered a novel regulatory mechanism involving the post-translational modification of AGO2 by E-cadherin, leading to enhanced miRISC activity on gene silencing.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Michael J. Chrusch, Selena Fu, Simon C. Spanswick, Haley A. Vecchiarelli, Payal P. Patel, Matthew N. Hill, Richard H. Dyck
Summary: Zinc plays a role in modulating synaptic plasticity, particularly in the hippocampal dentate gyrus. This study aimed to determine if vesicular zinc is important for modulating adult hippocampal neurogenesis and behavior in an experience-dependent manner. The results show that vesicular zinc is essential for enhancing adult hippocampal neurogenesis and behavior following enrichment, supporting the role of zincergic neurons in experience-dependent plasticity in the hippocampus.
Article
Multidisciplinary Sciences
Derek K. Cheng, Tobiloba E. Oni, Jennifer S. Thalappillil, Youngkyu Park, Hsiu-Chi Ting, Brinda Alagesan, Nadia V. Prasad, Kenneth Addison, Keith D. Rivera, Darryl J. Pappin, Linda Van Aelst, David A. Tuveson
Summary: The study identified protein interactors of active KRAS in PDAC cells using proximity labeling, revealing that RSK1 selectively interacts with membrane-bound KRASG12D through NF1 and SPRED2. It was found that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS in PDAC, highlighting the role of WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Jean Ching-Yi Tien, Seema Chugh, Andrew E. Goodrum, Yunhui Cheng, Rahul Mannan, Yuping Zhang, Lisha Wang, Vijaya L. Dommeti, Xiaoming Wang, Alice Xu, Jennifer Hon, Carson Kenum, Fengyun Su, Rui Wang, Xuhong Cao, Sunita Shankar, Arul M. Chinnaiyan
Summary: The study demonstrates a pathogenic role for AGO2 in KRAS-dependent non-small cell lung cancer, suggesting that its knockout may help inhibit tumor growth and improve pathological grade.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Extensive studies have shown that misregulation of individual miRNAs is associated with cancer. Recently, it has been discovered that mutations in the miRNA biogenesis and processing machinery are also involved in several malignancies. These mutations can cause global miRNA misregulation and contribute to cancer development. Additionally, it has been found that mutant KRAS can affect the activity of miRNA regulatory pathway members, further promoting tumorigenesis. Targeting both mutant KRAS and the miRNA core machinery may present a potential strategy for cancer treatment.
Article
Pharmacology & Pharmacy
Prakash Lingasamy, Kristina Posnograjeva, Sergei Kopanchuk, Allan Tobi, Ago Rinken, Ignacio J. General, Eliana K. Asciutto, Tambet Teesalu
Summary: The study elucidates the binding dynamics of the PL1 peptide with its receptors, as well as the process of binding and internalization of PL1 nanoparticles in vitro. Results indicate that the engagement of PL1 peptide with FN-EDB and TNC-C is primarily driven by electrostatic interactions, and PL1-functionalized nanoparticles can deposit on the target ECM and induce cellular uptake.
Article
Cell Biology
Sergio Crespo-Garcia, Pamela R. Tsuruda, Agnieszka Dejda, Rathi D. Ryan, Frederik Fournier, Shawnta Y. Chaney, Frederique Pilon, Taner Dogan, Gael Cagnone, Priyanka Patel, Manuel Buscarlet, Sonali Dasgupta, Gabrielle Girouard, Surabhi R. Rao, Ariel M. Wilson, Robert O'Brien, Rachel Juneau, Vera Guber, Alexandre Dubrac, Christian Beausejour, Scott Armstrong, Frederick A. Mallette, Christopher B. Yohn, Jean-Sebastien Joyal, Dan Marquess, Pedro J. Beltran, Przemyslaw Sapieha
Summary: The study reveals that pathological blood vessels engage pathways of cellular senescence, while healthy blood vessels do not. Eliminating p16(INK4A)-expressing cells or inhibiting the anti-apoptotic protein BCL-xL can suppress pathological angiogenesis, promoting physiological vascular repair in the retina. These findings suggest that BCL-xL inhibitors may hold potential as treatments for neovascular retinal diseases.
Article
Biotechnology & Applied Microbiology
Mireia Uribe-Herranz, Silvia Beghi, Marco Ruella, Kalpana Parvathaneni, Silvano Salaris, Nektarios Kostopoulos, Subin S. George, Stefano Pierini, Elisavet Krimitza, Francesca Costabile, Guido Ghilardi, Kimberly Amelsberg, Yong Gu Lee, Raymone Pajarillo, Caroline Markmann, Bevin McGettigan-Croce, Divyansh Agarwal, Noelle Frey, Simon F. Lacey, John Scholler, Khatuna Gabunia, Gary Wu, Elise Chong, David L. Porter, Carl H. June, Stephen J. Schuster, Vijaj Bhoj, Andrea Facciabene
Summary: Several studies have shown that commensal microbes can influence T cell function in cancer immunotherapy. This study investigated the effects of vancomycin-induced gut microbiota dysbiosis on chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models and clinical data. The results showed that vancomycin combined with CAR T cell therapy improved tumor control and tumor-associated antigen cross-presentation. Fecal microbiota transplant from healthy donors also replicated these results. These findings highlight the importance of gut microbiota modulation in improving outcomes of CAR T cell therapy.
Article
Multidisciplinary Sciences
Christopher J. Schulze, Kyle J. Seamon, Yulei Zhao, Yu C. Yang, Jim Cregg, Dongsung Kim, Aidan Tomlinson, Tiffany J. Choy, Zhican Wang, Ben Sang, Yasin Pourfarjam, Jessica Lucas, Antonio Cuevas-Navarro, Carlos Ayala-Santos, Alberto Vides, Chuanchuan Li, Abby Marquez, Mengqi Zhong, Vidyasiri Vemulapalli, Caroline Weller, Andrea Gould, Daniel M. Whalen, Anthony Salvador, Anthony Milin, Mae Saldajeno-Concar, Nuntana Dinglasan, Anqi Chen, Jim Evans, John E. Knox, Elena S. Koltun, Mallika Singh, Robert Nichols, David Wildes, Adrian L. Gill, Jacqueline A. M. Smith, Piro Lito
Summary: Researchers have designed a small molecule that has high affinity and selectivity for the active form of mutant KRAS, a difficult-to-target oncogene. This small molecule remodels the surface of a protein and inhibits oncogenic signaling, leading to tumor regressions in cancer models. This inhibitory strategy can be applied to other undruggable cancer drivers.
Article
Biotechnology & Applied Microbiology
Jia Hu, Shengqiang Zou, Juanjuan Huang, Xuhui Huan, Xia Jin, Lieding Zhou, Kai Zhao, Youzhi Han, Shengji Wang
Summary: In this study, a R2R3-MYB transcription factor, PagMYB151, was cloned from Populus alba x P. glandulosa. The expression of PagMYB151 was found to enhance the growth and physiological indexes of poplar under salt stress conditions. Additionally, 6 salt stress-induced transcription factors that co-expressed with PagMYB151 were identified.
Article
Gastroenterology & Hepatology
Ashley Velez-Delgado, Katelyn L. Donahue, Kristee L. Brown, Wenting Du, Valerie Irizarry-Negron, Rosa E. Menjivar, Emily L. Lasse Opsahl, Nina G. Steele, Stephanie The, Jenny Lazarus, Veerin R. Sirihorachai, Wei Yan, Samantha B. Kemp, Samuel A. Kerk, Murali Bollampally, Sion Yang, Michael K. Scales, Faith R. Avritt, Fatima Lima, Costas A. Lyssiotis, Arvind Rao, Howard C. Crawford, Filip Bednar, Timothy L. Frankel, Benjamin L. Allen, Yaqing Zhang, Marina Pasca di Magliano
Summary: This study reveals that non-cell autonomous oncogenic KRAS signaling can reprogram pancreatic fibroblasts, leading to an inflammatory response and affecting the tumor microenvironment, thereby promoting tumor development.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Neurosciences
Meiyan Wang, Fred H. Gage, Simon T. Schafer
Summary: Human brain organoids generated from pluripotent stem cells recapitulate early developing human brain features but lack functional vasculature and non-neuronal cells. Recent progress in intracerebral transplantation approaches has demonstrated successful vascularization and neurodifferentiation of brain organoids. Ethical considerations in the field of brain organoid transplantation are also discussed.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Environmental Sciences
Lena Roelfer, David J. Abson, Maria Manez Costa, Sergio Rosendo, Timothy F. Smith, Louis Celliers
Summary: This study presents an approach for assessing governance performance in complex social-ecological systems (SES) and identifying leverage points to enhance climate resilience. The results suggest that improving support from the provincial government, prioritizing climate change in development plans, increasing collaboration, and allocating funding to climate change actions are key leverage points for improving governance performance and climate resilience.
Article
Multidisciplinary Sciences
Long Li, Romain Durand-de Cuttoli, Antonio V. Aubry, C. Joseph Burnett, Flurin Cathomas, Lyonna F. Parise, Kenny L. Chan, Carole Morel, Chongzhen Yuan, Yusuke Shimo, Hsiao-yun Lin, Jun Wang, Scott J. Russo
Summary: Traumatic social experiences in humans can lead to psychiatric disorders. In rodents, little is known about the impact of social trauma on social reward. A study on the chronic social defeat stress (CSDS) model in mice suggests that previously rewarding social targets are perceived as threats in susceptible mice.
Article
Zoology
Claudia A. Grillo, Mande Holford, Nils G. Walter
Summary: This article proposes using agent-based models to define general rules for interactions across biological systems and evolutionary time, and speculates on the possibility of simulating self-organizing systems and deciphering universal principles that govern biological interactions. It aims to explore further advancements in biosciences in the 21st century.
INTEGRATIVE AND COMPARATIVE BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rajeev Yadav, Julia R. Widom, Adrien Chauvier, Nils G. Walter
Summary: This study used single molecule fluorescence technology to reveal three dynamically interconverting conformations of the fluoride riboswitch. Specifically, the fluoride ion snap-locks the conformation through its interaction with magnesium-induced RNA, and a long-range base pair plays a crucial role in the process. Additionally, the proximally paused RNA polymerase further promotes riboswitch docking. Finally, the study found that fluoride binding at short RNA lengths is an early step towards folding into the docked conformation.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Arathi Mohan, Kent A. Grif, Fulei Wuchu, David B. Zhen, Chandan Kumar-Sinha, Oxana Crysler, David Hsiehchen, Thomas Enzler, Dominique Dippman, Valerie Gunchick, Abhinav Achreja, Olamide Animasahun, Srinadh Choppara, Minal Nenwani, Arul M. Chinnaiyan, Deepak Nagrath, Mark M. Zalupski, Vaibhav Sahai
Summary: This study investigated the effect of the novel inhibitor, Devimistat, in patients with advanced biliary tract cancer. The results showed that Devimistat in combination with Gemcitabine and Cisplatin had a synergistic effect on cells and significantly decreased oxygen consumption rate. In the clinical trial, the combination therapy of Devimistat with Gemcitabine and Cisplatin demonstrated good safety and efficacy.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
John T. Randolph, Matthew J. O'Connor, Fei Han, Charles W. Hutchins, Y. Amy Siu, Min Cho, Yunan Zheng, Jonathan A. Hickson, Jana L. Markley, Vlasios Manaves, Mikkel Algire, Kenton A. Baker, Alex M. Chapman, Sujatha M. Gopalakrishnan, Sanjay C. Panchal, Kelly Foster-Duke, DeAnne F. Stolarik, Anita Kempf-Grote, Darby Dammeier, Stacey Fossey, Qi Sun, Chaohong Sun, Yu Shen, Michael J. Dart, Warren M. Kati, Albert Lai, Ari J. Firestone, Michael E. Kort
Summary: Compounds that inhibit glutathione peroxidase 4 (GPX4) have potential as cancer therapeutics, but our research found that the tested compound 24, a structural analog of the GPX4 inhibitor RSL3, did not effectively inhibit tumor growth in a mouse model. However, partial target engagement was observed in tumor homogenate, suggesting further investigation is warranted.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Adrien Chauvier, Jason C. C. Porta, Indrajit Deb, Emily Ellinger, Katarina Meze, Aaron T. T. Frank, Melanie D. D. Ohi, Nils G. G. Walter
Summary: This study investigates the interaction between RNA polymerase and nascent transcripts during transcription. It is found that the transcription process of a preQ(1) riboswitch can be modulated by the RNA polymerase and the conformation of the nascent RNA. Ligand binding to the riboswitch leads to the release of RNA polymerase pause and the continuation of transcription. The mechanism by which riboswitch folding modulates pausing is revealed through cryo-electron microscopy reconstructions.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Elizabeth Duran, Andreas Schmidt, Robb Welty, Ameya P. Jalihal, Sethuramasundaram Pitchiaya, Nils G. Walter
Summary: Cellular machineries that drive gene expression and regulate it rely on the assembly and interactions of proteins and RNA called ribonucleoprotein complexes (RNPs). Recreating these cellular machines and understanding their mechanisms is challenging. Single molecule fluorescence microscopy studies within crude or recombinantly supplemented cell extracts can provide insights into the behavior of specific biomolecules within RNPs in native cellular environments. This review discusses the methods and strategies used in dissecting RNP-driven processes, with a focus on pre-mRNA splicing and transcription regulation.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Pharmacology & Pharmacy
Emily Ellinger, Adrien Chauvier, Rosa A. Romero, Yichen Liu, Sujay Ray, Nils G. Walter
Summary: This review examines the potential of riboswitches as novel antibacterial drug targets. The limited mechanisms of action of currently available antibiotics are summarized, followed by a delineation of the functional mechanisms of riboswitches. The potential for developing novel approaches that target paradigmatic riboswitches in the context of their bacterial gene expression machinery is discussed.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Chemistry, Physical
Guoming Gao, Nils G. Walter
Summary: Biomolecular condensates are membraneless cellular compartments formed by phase separation, which play crucial roles in regulating cellular functions. Live-cell single particle tracking has revealed the mesoscopic organization and biological functions of condensates. However, there is a lack of quantitative benchmarking and objective comparison of boundary detection methods for condensates. In this study, synthetic data with defined ground truth is used to evaluate the most commonly used methods for condensate boundary detection, providing guidance for selecting optimal methods in imaging-based studies of condensates.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Genetics & Heredity
Juilee Rege, Sascha Bandulik, Kazutaka Nanba, Carla Kosmann, Amy R. Blinder, Allein Plain, Pankaj Vats, Chandan Kumar-Sinha, Antonio M. Lerario, Tobias Else, Yuto Yamazaki, Fumitoshi Satoh, Hironobu Sasano, Thomas J. Giordano, Tracy Ann Williams, Martin Reincke, Adina F. Turcu, Aaron M. Udager, Richard Warth, William E. Rainey
Summary: This study identified mutations in the SLC30A1 gene associated with PA. The mutations are located near the zinc-binding site in the coding region of SLC30A1 and may cause abnormal ion transport. PA cases with SLC30A1 mutations showed male dominance and increased levels of aldosterone and 18-oxocortisol.
Article
Nanoscience & Nanotechnology
Mathias Centola, Erik Poppleton, Sujay Ray, Martin Centola, Robb Welty, Julian Valero, Nils G. Walter, Petr Sulc, Michael Famulok
Summary: Molecular engineering aims to design nanoassemblies for complex tasks, but efficient chemical-fuel-driven nanoscale driver-follower systems have not been realized. In this study, a DNA nanomachine driven by the chemical energy of DNA-templated RNA-transcription-consuming nucleoside triphosphates was developed, generating rhythmic pulsating motion and successfully coupling with a passive follower.
NATURE NANOTECHNOLOGY
(2023)
Review
Urology & Nephrology
Guoming Gao, Emily S. Sumrall, Sethuramasundaram Pitchiaya, Markus Bitzer, Simon Alberti, Nils G. Walter
Summary: The regulation of solute microenvironments is crucial for cellular homeostasis. In the kidney, biomolecular condensates formed through hyperosmotic phase separation play important roles in kidney physiology and disease.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qian Hou, Surajit Chatterjee, Paul E. Lund, Krishna C. Suddala, Nils G. Walter
Summary: This study investigates the thermodynamic and kinetic folding properties of two riboswitches from different bacteria and the effects of urea and trimethylamine N-oxide (TMAO) on their folding. The results show that the riboswitch from a thermophilic bacterium is more thermotolerant and that urea destabilizes their folded structure while TMAO counteracts urea denaturation. These findings shed light on how subtle sequence adaptations in a thermophilic bacterium can stabilize a common RNA structure.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Chandan Kumar-Sinha, Pankaj Vats, Nguyen Tran, Dan R. Robinson, Valerie Gunchick, Yi-Mi Wu, Xuhong Cao, Yu Ning, Rui Wang, Erica Rabban, Janice Bell, Sunita Shankar, Rahul Mannan, Yuping Zhang, Mark M. Zalupski, Arul M. Chinnaiyan, Vaibhav Sahai
Summary: In this study, integrative clinical sequencing was performed on advanced biliary tract cancer (BTC) tumors. The results revealed actionable and potentially actionable genomic alterations in a significant portion of the patients, and those who received matched targeted therapy showed improved overall survival. The study also identified recurrent mutations in FGFR2 and a novel association between KRAS and BRAF mutations with high expression of immune modulatory protein NT5E (CD73).
Article
Cell Biology
Rebecca T. Perelman, Andreas Schmidt, Umar Khan, Nils G. Walter
Summary: This study investigates the spatial localization and diffusion of mRNA in cellular ribonucleoprotein (RNP) granules. The results show that mRNA molecules are often localized at the boundaries of these granules, potentially due to intermolecular interactions.
Article
Oncology
Aki Morikawa, Jinju Li, Peter Ulintz, Xu Cheng, Athena Apfel, Dan Robinson, Alex Hopkins, Chandan Kumar-Sinha, Yi-Mi Wu, Habib Serhan, Kait Verbal, Dafydd Thomas, Daniel F. Hayes, Arul M. Chinnaiyan, Veerabhadran Baladandayuthapani, Jason Heth, Matthew B. Soellner, Sofia D. Merajver, Nathan Merrill
Summary: The development of novel therapies for brain metastases is an unmet need, and the unique molecular features of brain metastases may serve as potential therapeutic targets. In this study, molecular profiles of breast cancer brain metastases were evaluated, and patient-derived xenografts (PDXs) were used as a drug screening platform. The PI3K pathway alterations were found to be the most predictive for drug efficacy in PDXs, and histone deacetylase and proteasome inhibitors showed high sensitivity.
CANCER RESEARCH COMMUNICATIONS
(2023)
