Article
Food Science & Technology
Tingting Shan, Jianping Wei, Yuan Wang, Xubo Zhao, Yuyao Zhao, Qian Ge, Yahong Yuan, Tianli Yue
Summary: Pesticides have different effects on the quality of kiwifruit, with reasonable use improving taste, weight, and nutrient content. Different pesticides may be more suitable for different varieties of kiwifruit, and the study's findings could ultimately help enhance the sensory quality of kiwifruit for farmers.
JOURNAL OF FOOD SCIENCE
(2021)
Review
Immunology
Junna Jiao, Zhuangwei Lv, Yurong Wang, Liye Fan, Angang Yang
Summary: Activation-induced cytidine deaminase (AID) plays a crucial role in promoting B cell diversification through somatic hypermutation (SHM) and class switch recombination (CSR). Apart from its physiological function of humoral immune response, AID has been linked to the initiation and progression of lymphomas. This review proposes an alternative role for AID and explores its off-target effects in regulating tumorigenesis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Xiaolong Cheng, Zexu Li, Ruocheng Shan, Zihan Li, Shengnan Wang, Wenchang Zhao, Han Zhang, Lumen Chao, Jian Peng, Teng Fei, Wei Li
Summary: A major challenge in the application of the CRISPR-Cas13d system is accurately predicting its guide-dependent on-target and off-target effects. In this study, researchers used CRISPR-Cas13d proliferation screens and developed a deep learning model called DeepCas13 to predict on-target activity based on guide sequences and secondary structures. DeepCas13 outperformed existing methods in predicting the efficiency of guides targeting both protein-coding and non-coding RNAs.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Anna Dimoula, Dimitrios Fotellis, Evmorfia Aivalioti, Dimitrios Delialis, Alexia Polissidis, Raphael Patras, Nikolaos Kokras, Kimon Stamatelopoulos
Summary: Depression is considered a risk factor for cardiovascular disease, and successful antidepressant treatment may reduce the risk of cardiovascular events. Selective serotonin reuptake inhibitors (SSRIs) have been shown to have beneficial effects on vascular inflammation, endothelial function, and arterial stiffening. However, it is challenging to distinguish the direct beneficial effects of antidepressants on endothelial health from the overall improvement in depression in clinical studies.
Article
Multidisciplinary Sciences
Melissa R. Pitman, Alexander C. Lewis, Lorena T. Davies, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Jason A. Powell, Stuart M. Pitson
Summary: The study found that JTE-013 has broad off-target effects on sphingolipid metabolism, increasing cellular levels of ceramides, dihydroceramides, sphingosine, and dihydrosphingosine. Additionally, the study revealed that JTE-013 inhibits the activity of several sphingolipid metabolic enzymes.
SCIENTIFIC REPORTS
(2022)
Review
Clinical Neurology
Jason Charles Ray, Mahima Kapoor, Richard J. Stark, Shuu-Jiun Wang, Lars Bendtsen, Manjit Matharu, Elspeth Jane Hutton
Summary: Migraine is the second largest cause of years lost to disability globally, with limited therapeutics specifically developed for its treatment. After 30 years of research, CGRP inhibitors have emerged as a promising tool for migraine prevention. However, with limited real-world experience, the systemic actions of CGRP need to be considered for potential side effects.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Felix P. Mayer, Marco Niello, Daniela Cintulova, Spyridon Sideromenos, Julian Maier, Yang Li, Simon Bulling, Oliver Kudlacek, Klaus Schicker, Hideki Iwamoto, Fei Deng, Jinxia Wan, Marion Holy, Rania Katamish, Walter Sandtner, Yulong Li, Daniela D. Pollak, Randy D. Blakely, Marko D. Mihovilovic, Michael H. Baumann, Harald H. Sitte
Summary: Increasing extracellular levels of serotonin can ameliorate symptoms of depression and anxiety-related disorders. The study found that certain ring-substituted cathinones show preference for the release of serotonin and exert 5-HT-associated effects in behavioral models. These compounds have low abuse liability and potential for adverse events.
MOLECULAR PSYCHIATRY
(2023)
Review
Biotechnology & Applied Microbiology
Congting Guo, Xiaoteng Ma, Fei Gao, Yuxuan Guo
Summary: Gene editing involves precise changes to specific nucleic acid sequences. The CRISPR/Cas9 system has revolutionized gene editing, making it efficient, convenient, and programmable. However, off-target effects remain a major concern, leading to unexpected alterations in the genome. Various methods have been developed to detect and mitigate these off-target effects, advancing the precision of CRISPR/Cas9 derivatives. This review summarizes these technological advancements and discusses the challenges in managing off-target effects for future gene therapy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elisa Baldelli, Mahalakshmi Subramanian, Abduljalil M. Alsubaie, Guy Oldaker, Maria Emelianenko, Emna El Gazzah, Sara Baglivo, Kimberley A. Hodge, Fortunato Bianconi, Vienna Ludovini, Lucio Crino, Emanuel F. Petricoin, Mariaelena Pierobon
Summary: Targetable alterations in cancer provide new opportunities for drug discovery, but pre-clinical testing often involves solubilization of drugs in DMSO. A study found that DMSO had heterogeneous effects on signaling proteins at different concentrations and exposure times across various cell lines. It is important to carefully evaluate these off-target effects in pre-clinical drug screening and testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Xianxian Yao, Danyang Chen, Bin Zhao, Binru Yang, Zhaokui Jin, Mingjian Fan, Geru Tao, Shucun Qin, Wuli Yang, Qianjun He
Summary: The development of stimuli-responsively degradable porous carriers for controlled drug release is important for clinical translation. In this study, a new type of Fe-MOF nanocrystals is engineered as an acid-degradable drug carrier and hydrogen donor. Fe-MOF nanocrystals exhibit acid-responsive degradation for H-2 generation and simultaneous drug release, and can effectively inhibit cancer metastasis and sensitize MDR cancer cells for enhanced chemotherapy. The high anti-MDR/antimetastasis efficacies and biocompatibility make Fe-MOF nanocrystals and Fe-MOF-based nanomedicine highly promising for clinical translation.
Article
Biochemical Research Methods
Christian Anthon, Giulia Ilaria Corsi, Jan Gorodkin
Summary: The effectiveness of CRISPR/Cas9-mediated genome editing experiments relies on the careful selection of guide RNA (gRNA) for target recognition and cleavage activation. This study presents a user-friendly webserver that incorporates both on- and off-target prediction tools, CRISPRon and CRISPRoff, to facilitate gRNA selection.
Article
Biochemical Research Methods
Wei-Xin Hu, Yu Rong, Yan Guo, Feng Jiang, Wen Tian, Hao Chen, Shan-Shan Dong, Tie-Lin Yang
Summary: Research shows that designing sgRNAs with on-target mismatches can improve binding activity and reduce off-target effects. A web tool named ExsgRNA is provided for optimizing sgRNA design.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Immunology
Prisca Benedicto-Matambo, Julie E. Bines, Chikondi Malamba-Banda, Isaac T. Shawa, Kayla Barnes, Arox W. Kamng'ona, Daniel Hungerford, Kondwani C. Jambo, Miren Iturriza-Gomara, Nigel A. Cunliffe, Katie L. Flanagan, Khuzwayo C. Jere
Summary: Live-attenuated vaccines have been shown to reduce deaths and hospitalizations associated with diarrhea in children and may provide protection against other infections as well. The off-target effects of vaccination are thought to be mediated by modified innate and adaptive immunity. However, it remains unclear whether rotavirus vaccines can also reduce non targeted gastrointestinal infections.
Article
Chemistry, Medicinal
Sebastian Schieferdecker, Esther Vock
Summary: Toxicity, particularly off-target effects, is a major reason for the failure in pharmaceutical development. This study focuses on identifying the key amino acid residues in the active site of 5-HT2B receptor through molecular dynamics simulations. Pharmacophore models were developed and their performance was evaluated on in-house data and a diverse subset of Enamine REAL. Machine learning was used to label the subset for 5-HT2B activity. These models can serve as filters for early detection of compounds with potential 5-HT2B off-target liabilities.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Blessie Elizabeth Nelson, Jacob J. Adashek, Steven H. Lin, Vivek Subbiah
Summary: With the development of immune-based therapies, the abscopal phenomenon has gained significant attention. Collaboration among radiation oncologists, oncologists and immunologists has increased, leading to exploration of various methods to induce the abscopal effect. However, further prospective studies and data analysis are needed to determine the appropriate candidates and cancer types.
Article
Cell Biology
Rachel M. Schaefer, Lydia R. Heasley, David J. Odde, Michael A. McMurray
Article
Cell Biology
Galo Garcia, Gregory C. Finnigan, Lydia R. Heasley, Sarah M. Sterling, Adeeti Aggarwal, Chad G. Pearson, Eva Nogales, Michael A. McMurray, Jeremy Thorner
JOURNAL OF CELL BIOLOGY
(2016)
Article
Cell Biology
Lydia R. Heasley, Michael A. McMurray
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Biology
Andrew Weems, Michael McMurray
Article
Cell Biology
Gaurav Barve, Shreyas Sridhar, Amol Aher, Mayurbhai H. Sahani, Sarika Chinchwadkar, Sunaina Singh, K. N. Lakshmeesha, Michael A. McMurray, Ravi Manjithaya
JOURNAL OF CELL SCIENCE
(2018)
Editorial Material
Cell Biology
Michael A. McMurray
JOURNAL OF CELL BIOLOGY
(2019)
Article
Cell Biology
Michael A. McMurray, Jeremy Thorner
Article
Biology
Courtney R. Johnson, Marc G. Steingesser, Andrew D. Weems, Anum Khan, Amy Gladfelter, Aurelie Bertin, Michael A. McMurray
Article
Cell Biology
Elias T. Spiliotis, Michael A. McMurray
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Biochemistry & Molecular Biology
Lydia R. Heasley, Emily Singer, Benjamin J. Cooperman, Michael A. McMurray
Summary: Studies have shown that Saccharomyces cerevisiae spores are born prepolarized to outgrow, away from interspore bridges, challenging the traditional assumption that spores break symmetry and polarize at random locations. The findings also highlight the need for further investigation into polarity establishment mechanisms and local cell wall digestion, as well as the historically overlooked key steps in the Saccharomyces life cycle.
Article
Genetics & Heredity
Ashley S. Denney, Andrew D. Weems, Michael A. McMurray
Summary: Life necessitates the oligomerization of individual proteins into higher-order assemblies with the help of molecular chaperones. Missense mutations can disrupt protein folding and lead to disease, but some mutations are kinetically delayed to prevent interference with wild-type function. The involvement of chaperones, kinetic folding delays, and oligomerization dynamics were further explored in tumor-derived mutants of the tumor suppressor p53, with findings suggesting temperature sensitivity and Hsp90 regulation.
G3-GENES GENOMES GENETICS
(2021)
Article
Genetics & Heredity
Daniel S. Hassell, Marc G. Steingesser, Ashley S. Denney, Courtney R. Johnson, Michael A. McMurray
Summary: Intracellular proteins rely not only on amino acid sequences, but also on the concentrations of small molecules, which vary widely between organisms, metabolic states, and environmental conditions. Natural small molecules have the potential to rescue gene mutants through complex mechanisms, influencing protein function and potentially driving evolution.
G3-GENES GENOMES GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Randi Yeager, G. Guy Bushkin, Emily Singer, Rui Fu, Benjamin Cooperman, Michael McMurray
Summary: Researchers found that dormant yeast spores of each mating type contain transcripts representing mating pheromones and receptors, with translation of these components being repressed until germination. Additionally, a rare yeast gene Mata1 was found to be enriched in a spores of mating type a, with its transcripts remaining mostly unspliced.
Article
Cell Biology
Daniel Hassell, Ashley Denney, Emily Singer, Aleyna Benson, Andrew Roth, Julia Ceglowski, Marc Steingesser, Michael McMurray
Summary: Polymers of septin protein complexes are essential for the cytoskeletal function in eukaryotic cells. The folding and assembly of septins require assistance from chaperones, and different septins have distinct requirements for chaperone assistance. Our findings suggest that translation elongation rates of different septins may play a role in directing the stepwise assembly pathway with the help of cytosolic chaperones.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Cell Biology
Aleyna Benson, Michael McMurray
Summary: Septin proteins in budding yeast localize almost exclusively at the future site of cytokinesis, possibly through interactions with specific phospholipids and curvature-sensitive mechanisms. Overexpression of two tagged septins leads to uniform plasma membrane localization and perturbation of endogenous septin function. These findings shed light on the mechanisms restricting septin localization to specific membranes.