Article
Multidisciplinary Sciences
Preksha Bhagchandani, Charles A. Chang, Weichen Zhao, Luiza Ghila, Pedro L. Herrera, Simona Chera, Seung K. Kim
Summary: This study introduces a new model of experimental diabetes, the B6 RIP-DTR mouse, which can efficiently induce diabetes and be used for islet transplantation. The model has reliable diabetes induction and the rejection response of transplanted islets can be monitored through blood glucose and histology. Different immune cells can be distinguished using flow cytometry in this model.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Eric M. Brown, Hugo Arellano-Santoyo, Emily R. Temple, Zachary A. Costliow, Matthieu Pichaud, A. Brantley Hall, Kai Liu, Michael A. Durney, Xiebin Gu, Damian R. Plichta, Clary A. Clish, Jeffrey A. Porter, Hera Vlamakis, Ramnik J. Xavier
Summary: ADPRTs are widely present in the human gut microbiome, not limited to pathogens, and can impact pathogenesis by modifying host proteins. The ADPRT Bxa in Bacteroides exhibits enzymatic activity at the cellular level, altering the cell cytoskeleton and inducing the secretion of specific substances. Strains of Bacteroides encoding Bxa colonize the gut in significantly larger quantities than mutants lacking bxa, correlating with increased inosine concentrations in feces and tissues.
CELL HOST & MICROBE
(2021)
Article
Biochemistry & Molecular Biology
Andrea Hlousek-Kasun, Petra Mikolcevic, Johannes Gregor Matthias Rack, Callum Tromans-Coia, Marion Schuller, Gytis Jankevicius, Marija Matkovic, Branimir Bertosa, Ivan Ahel, Andreja Mikoc
Summary: ADP-ribosylation is an important covalent modification that plays critical roles in various biological processes. The toxin/antitoxin pair DarT/DarG has been discovered, where DarT modifies DNA and DarG reverses this modification. The homologue SCO6735 is highly conserved and associated with antibiotic production in bacteria, and it can also reverse the ADP-ribosylation catalyzed by DarT.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Petra Mikolcevic, Andrea Hlousek-Kasun, Ivan Ahel, Andreja Mikoc
Summary: ADP-ribosylation is an ancient posttranslational modification present in all kingdoms of life, with crucial roles in eukaryotes but still with limited understanding in bacteria and viruses. Research on this system may provide a fighting advantage in the search for therapeutic targets in the future. The relevance of this subject is highlighted by the current world pandemic caused by a virus dependent on a representative of such a system.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Physical
Mohsen Sadeghi, Frank Noe
Summary: Biomembrane remodeling is crucial for cellular trafficking, with membrane-binding proteins being key players. A coarse-grained model parametrized to reflect local curvatures and lateral dynamics of proteins was developed to study the formation and breakup of protein clusters on the membrane surface, demonstrating the role of protein flexibility and concentration in aggregation behavior.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Genetics & Heredity
Xing Zhang, Benjamin W. Harding, Dina Aggad, Damien Courtine, Jia-Xuan Chen, Nathalie Pujol, Jonathan J. Ewbank
Summary: The study reveals that different fungal enterotoxins have varying effects on the immune defense and biology of the nematode C. elegans, highlighting the complex and potentially antagonistic mechanisms in the interaction between co-evolved hosts and pathogens.
Article
Biotechnology & Applied Microbiology
Hunseok Choi, Seonghyeon Son, Donghyun Lee, Jonghyun Bae, Eunyoung Seo, Dong Wook Kim, Eun Jin Kim
Summary: The study constructed new genes that can trigger the expression of TCP and CT in Vibrio cholerae, and induce antibody responses against TCP in animal models. However, the cholera toxin produced by these strains is secreted into the culture medium. To potentially apply in oral cholera vaccines, the researchers constructed V. cholerae strains that can express intracellular CTB under the control of the toxT-139F allele.
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemical Research Methods
Stephanie C. Luthi, Anna Howald, Kathrin Nowak, Robert Graage, Giody Bartolomei, Christine Neupert, Xaver Sidler, Deena Leslie Pedrioli, Michael O. Hottiger
Summary: Plasma phosphodiesterases and/or ADP-ribosylhydrolases were found to rapidly remove post-translational modifications in vitro ADP-ribosylated proteins. Mass spectrometry identified a total of 60 ADP-ribosylated proteins, with 17 of them being ADP-ribosylated plasma proteins. This new protocol marks an important advancement in the field of ADP-ribosylation and provides insights into ADP-ribosylomes in blood and plasma under different conditions.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Madison Turner, Kayla A. Heney, A. Rod Merrill
Summary: The study demonstrated the importance of the N-terminus of C3larvinA in its structure and function, with residues Asp(23), Ala(31), and Lys(36) playing critical roles in enzymatic activity. Analysis revealed these residues participated in a series of interactions, with Ala(31) and Lys(36) associating with a structural network of previously identified residues and Asp(23) forming novel interactions. Furthermore, the membrane translocation activity of each variant into host target cells was assessed, suggesting a potential relationship between protein dipole and target cell entry.
BIOSCIENCE REPORTS
(2021)
Article
Biophysics
Yonghwan Kim, Dongtak Lee, Youngjun Seo, Hyo Gi Jung, Jae Won Jang, Dongsung Park, Insu Kim, Jaeheung Kim, Gyudo Lee, Kyo Seon Hwang, Seung-Hyun Kim, Sang Won Lee, Jeong Hoon, Dae Sung Yoon
Summary: In this study, an electrochemical biosensor based on cell membrane was developed, inspired by the pathological process of cholera toxin. The biosensor exhibited excellent detection performance, selectivity, and long-term stability. Overall, it has great potential for clinical application and cost-effective detection of cholera toxin in developing countries.
BIOSENSORS & BIOELECTRONICS
(2023)
Review
Cell Biology
Yujie Gan, Huanhuan Sha, Renrui Zou, Miao Xu, Yuan Zhang, Jifeng Feng, Jianzhong Wu
Summary: This review provides an update on methodological advances in the study of ADP-ribosylation and discusses the function and therapeutic potential of mono-ADP-ribosylation in cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Laura Kevorkian, Salome C. Vilchez Larrea, Silvia H. Fernandez Villamil
Summary: This study identifies the nuclear localization of TcPARP and its enrichment in the nucleolus of Trypanosoma cruzi. The study also reveals the presence of TcPARP in a thread-like structure connecting two dividing nuclei, and the detection of ADP-ribose polymers in this structure during mitosis. These findings shed light on new potential functions of TcPARP inside the nucleus and contribute to our understanding of its role in trypanosomatids beyond the well-described DNA damage response.
Review
Pharmacology & Pharmacy
Marie Eggers, Felix Ruehl, Friedrich Haag, Friedrich Koch-Nolte
Summary: Nanobodies, the single variable immunoglobulin domains of heavy chain antibodies naturally occurring in camelids, have a hydrophilic surface area which makes them highly soluble, robust in harsh environments, and exceptionally easy to format into bispecific reagents. The unique properties of nanobodies have been utilized in modulating purinergic signaling, with examples targeting P2X7, CD38, and ARTC2.2.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Micaela A. Reeves, Joshua M. Royal, David A. Morris, Jessica M. Jurkiewicz, Nobuyuki Matoba, Krystal T. Hamorsky
Summary: EPT, a recombinant variant of cholera toxin B subunit, shows promise for ulcerative colitis treatment. A solid oral formulation of EPT has been developed to prevent degradation in gastric acid, demonstrating therapeutic efficacy in mouse colitis models without the need for gastric acid neutralization pretreatment.
Article
Food Science & Technology
Katharina Ernst
Summary: Pertussis, also known as whooping cough, is a respiratory disease caused by infection with Bordetella pertussis. Despite available vaccination, case numbers are increasing globally and there is currently no causative treatment for the symptoms of pertussis. The AB-type protein toxin PT, a virulence factor, is identified as a potential drug target for developing novel therapeutic strategies.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)