Article
Microbiology
Xiaoyu Liu, Zhe Chen, Xuyao Jiao, Xukai Jiang, Jicheng Qiu, Fuping You, Hongan Long, Hongzhi Cao, Casey C. Fowler, Xiang Gao
Summary: This study reveals how the human-adapted bacterial pathogen Salmonella enterica serovar Typhi produces two distinct versions of typhoid toxin and explores the differences in structure and receptor specificity between these two toxins. The study also shows that the two toxins have different glycan-binding properties, resulting in distinct functional traits.
Article
Microbiology
Xiaoyu Liu, Zhe Chen, Xuyao Jiao, Xukai Jiang, Jicheng Qiu, Fuping You, Hongan Long, Hongzhi Cao, Casey C. Fowler, Xiang Gao
Summary: This study reveals that typhoid toxin has different versions, PltB and PltC are unable to form heteromeric delivery complexes and therefore form separate toxins, PltC exhibits stronger electrostatic interactions with PltA, enabling it to outcompete PltB in toxin assembly, and PltB and PltC exhibit significant differences in glycan binding specificity.
Article
Medicine, Research & Experimental
Joseph H. Lubin, Christopher Markosian, D. Balamurugan, Minh T. Ma, Chih-Hsiung Chen, Dongfang Liu, Renata Pasqualini, Wadih Arap, Stephen K. Burley, Sagar D. Khare
Summary: In this study, a structure-based pipeline was developed to analyze protein-protein interactions and immune evasion of SARS-CoV-2 variants. The results showed changes in interfacial interactions and weakened therapeutic antibody binding, providing insights into the molecular basis of immune evasion.
Article
Infectious Diseases
Gillian A. M. Tarr, Joshua Rounds, Madhura S. Vachon, Kirk Smith, Carlota Medus, Craig W. Hedberg
Summary: This study examines the incidence and risk factors of different serogroups of STEC infections in Minnesota. The results indicate variations in transmission routes and risk factors among different serogroups, suggesting the need for serogroup-specific disease control strategies.
JOURNAL OF INFECTION
(2023)
Article
Chemistry, Multidisciplinary
Guang-Lei Ma, Hoa Thi Tran, Zhen Jie Low, Hartono Candra, Li Mei Pang, Qing Wei Cheang, Mingliang Fang, Zhao-Xun Liang
Summary: In this study, the researchers identified the sungeidine pathway as a degenerative pathway for AQE biosynthesis, and by retrofitting this pathway with genes from the dynemicin pathway, they were able to synthesize the AQE skeleton and various novel compounds. This study sheds light on the surprising biosynthetic steps involved in the formation of AQEs and provides insights into the biosynthetic enzymes involved in this process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biology
Fenghui Zhao, Chao Zhang, Qingtong Zhou, Kaini Hang, Xinyu Zou, Yan Chen, Fan Wu, Qidi Rao, Antao Dai, Wanchao Yin, Dan-Dan Shen, Yan Zhang, Tian Xia, Raymond C. Stevens, H. Eric Xu, Dehua Yang, Lihua Zhao, Ming-Wei Wang
Summary: This study presents the cryo-EM structure of human GIPR in complex with GIP and a G(s) trimer, revealing a structural framework of hormone recognition and GIPR activation. It shows the specific interactions between GIP and GIPR that contribute to their metabolic functions.
Article
Multidisciplinary Sciences
Linda Hernandez Duran, David Thomas Wilson, Mohamed Salih, Tasmin Lee Rymer
Summary: Australian funnel-web spiders, known for their venomous bites, have the potential to provide therapeutics and natural bioinsecticides. This study investigates the relationships between behaviors and morphophysiological variables that may affect venom composition in these spiders. The results suggest that venom components are associated with heart rate and defensiveness in some species, but not in others, highlighting species-specific associations. Overall, this study contributes to a broader understanding of the function and evolution of venoms in funnel-web spiders.
Article
Biochemistry & Molecular Biology
Xiaojing Cong, Damien Maurel, Helene Demene, Ieva Vasiliauskaite-Brooks, Joanna Hagelberger, Fanny Peysson, Julie Saint-Paul, Jerome Golebiowski, Sebastien Granier, Remy Sounier
Summary: GPCR functional selectivity presents new opportunities for designing safer drugs. Through a combination of functional assays, solution NMR spectroscopy, and molecular dynamic simulations, our study has identified specific mu OR conformations induced by G protein-biased agonists, shedding light on the dynamic mechanism enabling opioid ligands to preferentially activate the G protein pathway.
Review
Biotechnology & Applied Microbiology
Chenyi An, Xiaohuan Wang, Fan Song, Jinglei Hu, Long Li
Summary: Cell-cell communication plays a crucial role in cells' ability to sense and adapt to their environment. This review focuses on the regulatory effects of protein-membrane interaction, biomechanical force, and bioelectric microenvironment on intercellular receptor-ligand binding kinetics. Understanding these regulatory factors can have significant implications for drug design and biomedical research.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yi Zhou, Panayiotis E. Stevis, Jing Cao, Kei Saotome, Jiaxi Wu, Arielle Glatman Zaretsky, Sokol Haxhinasto, George D. Yancopoulos, Andrew J. Murphy, Mark W. Sleeman, William C. Olson, Matthew C. Franklin
Summary: This article presents the cryo-electron microscopy structures of five signaling complexes of the IL-6 family cytokines, revealing their assembly and molecular interactions. The structures provide insights for therapeutic targeting of gp130-mediated signaling.
Article
Multidisciplinary Sciences
Jun Xu, Qinggong Wang, Harald Huebner, Yunfei Hu, Xiaogang Niu, Haoqing Wang, Shoji Maeda, Asuka Inoue, Yuyong Tao, Peter Gmeiner, Yang Du, Changwen Jin, Brian K. Kobilka
Summary: In this study, the authors used cryo-EM and NMR to investigate the mechanisms underlying the signaling versatility of M2R. They found that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, and LY2119620 modulates agonist efficacy in G-protein and beta-arrestin pathways differently. These findings highlight the importance of conformational dynamics in the complex signaling behavior of GPCRs.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Graca Pinto, Marta Sampaio, Oscar Dias, Carina Almeida, Joana Azeredo, Hugo Oliveira
Summary: This study analyzed 179 complete genomes of Shiga toxin-producing Escherichia coli (STEC) in terms of serotypes, prophage coding regions, and stx gene variants, revealing a high genetic diversity and the prevalence of non-O157 serotypes. Most STEC genomes contain a single stx gene, with some strains harboring two, three, or four stx genes, and stx2 being the most common variant. The study also identified four clusters, three subclusters, and one singleton of Stx phages, showing a diverse genetic structure with a strong selective pressure to maintain the location of stx genes close to lytic cassettes.
Review
Chemistry, Inorganic & Nuclear
Utsab Manna, Gopal Das, Md Alamgir Hossain
Summary: This review provides a comprehensive assessment of examples of neutral receptors binding fluoride, focusing on the structural aspects. It discusses the selective solid-state capture of fluoride by various receptors and also briefly mentions the fluoride selective sensing in solution state.
COORDINATION CHEMISTRY REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Jeong Joo Kim, Ryan E. Hibbs
Summary: GABAA receptors are important in mediating fast neuronal inhibition in the brain and have rich pharmacology. Recent efforts in structural biology have provided insights into how important drug classes and natural products interact with these receptors, laying a foundation for drug design. The focus has been on subunit assemblies of the receptor found at synapses.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Brian P. Cary, Elliot J. Gerrard, Matthew J. Belousoff, Madeleine M. Fletcher, Yan Jiang, Isabella C. Russell, Sarah J. Piper, Denise Wootten, Patrick M. Sexton
Summary: This study describes the cryo-EM structures of PTH1R in complex with different agonists, such as PTH, PTH-related protein, abaloparatide, long-acting PTH, and truncated peptide M-PTH(1-14). The N terminus of each agonist engages the transmembrane bundle in a similar way, leading to Gas activation. The full-length peptides induce subtle differences in the orientation of the extracellular domain, while in the structure bound to M-PTH, the extracellular domain remains unresolved, indicating its high dynamic nature in the absence of peptides. Water molecules near peptide and G protein binding sites were also identified. These results provide insights into the mechanism of action of orthosteric agonists of PTH1R.
Article
Chemistry, Multidisciplinary
Anujan Ramesh, Sahana Kumar, Anthony Brouillard, Dipika Nandi, Ashish Kulkarni
ADVANCED MATERIALS
(2020)
Review
Pharmacology & Pharmacy
Sahana Kumar, Anujan Ramesh, Ashish Kulkarni
EXPERT OPINION ON DRUG DISCOVERY
(2020)
Article
Multidisciplinary Sciences
Anh Nguyen, Anujan Ramesh, Sahana Kumar, Dipika Nandi, Anthony Brouillard, Alexandria Wells, Leonid Pobezinsky, Barbara Osborne, Ashish A. Kulkarni
Review
Engineering, Biomedical
Anthony Brouillard, Nilesh Deshpande, Ashish A. Kulkarni
Summary: Innovations in cancer immunotherapy, particularly utilizing engineered multifunctional nanomaterials and biological materials, have the potential to improve anti-cancer efficacy by enhancing immune responses. This review explores various strategies and platforms that target and activate different aspects of the immune system for a more comprehensive and effective approach to cancer treatment. The goal is to pave the way for diverse and strategic regression of tumors by eliciting responses from both the adaptive and innate immune systems concurrently.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Nanoscience & Nanotechnology
Dipika Nandi, Manisha Shivrayan, Jingjing Gao, Jithu Krishna, Ritam Das, Bin Liu, S. Thayumanavan, Ashish Kulkarni
Summary: Designer nanomaterials capable of delivering immunomodulators to specific immune cells have been extensively studied, but certain nanomaterials can nonspecifically activate NLRP3 inflammasomes, leading to unwanted effects. Core hydrophobicity strongly activates NLRP3 assembly compared to other nanoparticle attributes. Different signaling pathways and kinetics are observed with varying core hydrophobicity patterns.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Instruments & Instrumentation
Anujan Ramesh, Vaishali Malik, Hayat Anu Ranjani, Harriet Smith, Ashish A. Kulkarni
Summary: Immune checkpoint inhibitors have revolutionized cancer immunotherapy, with macrophages playing a significant role in the tumor microenvironment. However, challenges exist in modulating macrophage functions to initiate an anti-tumor response.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Article
Engineering, Biomedical
Anujan Ramesh, Vaishali Malik, Anthony Brouillard, Ashish Kulkarni
Summary: Tumor-associated macrophages (TAMs) can be reprogrammed metabolically from a pro-tumorigenic M2 phenotype to an antitumorigenic M1 phenotype. Recent developments have shown that distinct metabolic signatures accompany macrophages based on their polarization states. In this study, supramolecular nanoparticle system was used to deliver drugs and effectively rewired macrophage metabolism, leading to reduced tumor growth.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2022)
Article
Chemistry, Multidisciplinary
Dipika Nandi, James Forster, Anujan Ramesh, Anh Nguyen, Hariharan Bharadwaj, Ashish Kulkarni
Summary: Inflammasome activation is associated with inflammatory diseases, but current methods have limited understanding of its kinetics and early detection of treatment efficacy. Researchers developed lipid-based nanoparticles, including a reporter nanoparticle and a theranostic nanoparticle, to monitor inflammasome activation and track treatment efficacy. The biocompatible platform enhanced probe circulation and provided in vitro and in vivo monitoring. By delivering an inflammasome-inhibiting drug with the reporter probe, real-time tracking of treatment efficacy was achieved. These findings establish novel nanotools for non-invasive evaluation of inflammasome-targeted immunotherapy.
Review
Chemistry, Physical
Anh Nguyen, Sahana Kumar, Ashish A. Kulkarni
Summary: Despite advancements in cancer immunotherapy, the heterogeneity in tumor response poses obstacles to successful treatments and accurate prognosis. Existing imaging techniques have limitations in early assessment of immune response. Engineered nanomaterials play a significant role in overcoming these challenges by improving drug delivery and dynamic imaging techniques.
Article
Chemistry, Multidisciplinary
Anujan Ramesh, Nilesh Deshpande, Vaishali Malik, Anh Nguyen, Mehak Malhotra, Maharshi Debnath, Anthony Brouillard, Ashish Kulkarni
Summary: Conventional diagnostic techniques lack sensitivity and specificity for early detection of inflammatory diseases. Detection of macrophage phenotypes can predict the prognosis of various diseases. Activatable nanoreporters have been engineered to detect M1 and M2 macrophage markers in real-time, enabling early detection of breast cancer and monitoring of inflammatory responses and wound healing in muscle injury models.
Article
Biochemical Research Methods
Maharshi Debnath, James Forster, Anujan Ramesh, Ashish Kulkarni
Summary: This study investigates the interaction between lipid nanoparticles (LNPs) and serum proteins, and how it affects immune responses and cellular uptake. The presence of a protein corona on LNPs reduces inflammasome activation and cellular uptake in macrophages. The lipid formulation of LNPs plays a critical role in determining their endocytic pathways.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Nanoscience & Nanotechnology
Dipika Nandi, James Forster III, Anujan Ramesh, Anh Nguyen, Hariharan Bharadwaj, Ashish Kulkarni
Summary: This study developed a liposomal nanoreporter platform for the spatiotemporal delivery of imaging probe and inhibitor, enabling the monitoring and regulation of inflammasome activation. It exhibited the ability to detect and reduce inflammasome activation in vitro and in vivo, and alleviated inflammation. This novel tool has high potential for the real-time monitoring and treatment of inflammasome-mediated diseases.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Materials Science, Biomaterials
James Forster, Dipika Nandi, Ashish Kulkarni
Summary: In recent years, significant progress has been made in the engineering of mRNA lipid nanoparticle vaccines, but there is still limited understanding of their immunogenicity. A design-driven approach is needed to determine the biophysical characteristics that drive nanoparticle immunogenicity. This study investigated the activation of NLRP3 inflammasomes by different lipid compositions in mRNA lipid nanoparticles and found that specific combinations of lipid types significantly influenced their activation.
BIOMATERIALS SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Vaishali Malik, Anujan Ramesh, Ashish A. Kulkarni
Summary: The engineered nanoparticle can efficiently repolarize M2 macrophages to M1 phenotype and simultaneously block CD47-SIRPa interactions, enhancing the efficacy of macrophage immunotherapy.
ADVANCED THERAPEUTICS
(2021)
Article
Nanoscience & Nanotechnology
Anujan Ramesh, Anthony Brouillard, Ashish Kulkarni
Summary: Tumor-associated macrophages play critical roles in tumor progression and can switch their phenotype and function, making them ideal therapeutic targets. Recent efforts in designing nanotherapeutics for macrophage immunotherapy offer new avenues for cancer immunotherapy by repolarizing tumor-associated macrophages.
ACS APPLIED BIO MATERIALS
(2021)