Article
Biochemistry & Molecular Biology
Ilona Turek, Lubna Freihat, Jignesh Vyas, Janet Wheeler, Victor Muleya, David T. Manallack, Chris Gehring, Helen Irving
Summary: Recent discoveries have identified low-activity guanylate cyclase (GC) catalytic centers within kinase domains in plants, which generate cGMP essential for intramolecular and downstream signaling. Researchers have explored the existence of such cryptic GCs in human proteome and found 18 candidates, including the neurotropic receptor tyrosine kinase 1 (NTRK1). In vitro studies revealed that the embedded NTRK1 GC is functional and exhibits a preference for Mn2+ over Mg2+. These findings suggest previously unsuspected roles of cGMP in intramolecular and downstream signaling of NTRK1, as well as its involvement in NTRK1-dependent growth and neoplasia.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Calvin K. Lee, William C. Schmidt, Shanice S. Webster, Jonathan W. Chen, George A. O'Toole, Gerard C. L. Wong
Summary: This study reveals that changes in c-di-GMP levels in bacterial biofilms are not the sole factor determining surface commitment, as oscillations in c-di-GMP levels can propagate across generations. Additionally, the study demonstrates that modulation of c-di-GMP signals and cooperative surface commitment can be influenced by varying the interaction strength between PilO and SadC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Jingchao Zhang, Huijun Wu, Di Wang, Lanxin Wang, Yifan Cui, Chenxi Zhang, Kun Zhao, Luyan Ma, Gerald Pier
Summary: Biofilm formation is a major cause of persistent infections. The intracellular glycosyl hydrolase PslG plays a crucial role in the synthesis of the exopolysaccharide PSL, which is essential for biofilm matrix formation in the opportunistic pathogen Pseudomonas aeruginosa. Lack of PslG or its hydrolytic activity enhances PSL signaling, affects cyclic-di-GMP levels during cell division, and alters the localization of PSL, resulting in the formation of long chains of bacterial cells and fast-forming biofilm microcolonies.
Article
Microbiology
Courtney N. Dial, Lauren Speare, Garrett C. Sharpe, Scott M. Gifford, Alecia N. Septer, Karen L. Visick
Summary: Vibrio fischeri efficiently colonizes its squid host by producing a transient biofilm dependent on symbiosis polysaccharide. Yeast extract inhibits biofilm formation, while omitting it and adding vitamin pABA and calcium can induce biofilm formation. pABA increases the concentration of c-di-GMP, which plays a crucial role in inducing biofilm formation.
Article
Biochemical Research Methods
Charles Elliot Serpellone Nash, Natalicia J. Antunes, Weverton C. Coelho-Silva, Rafael Campos, Gilberto De Nucci
Summary: This study reports an improved method for determining cAMP and cGMP concentrations in washed platelet supernatants by combining LC-MS/MS technology. The method showed high precision, the lowest limit of quantification, and quantified the effect of a novel catecholamine on cyclic nucleotide levels.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Victor W. Mak, Akash M. Patel, Rose Yen, Jennifer Hanisak, Yeon-Hee Lim, Jianming Bao, Rong Zheng, W. Michael Seganish, Yang Yu, David R. Healy, Aimie Ogawa, Zhao Ren, Aileen Soriano, Grigori P. Ermakov, Maribel Beaumont, Essam Metwally, Alan C. Cheng, Andreas Verras, Thierry Fischmann, Matthias Zebisch, H. Leonardo Silvestre, Paul A. McEwan, John Barker, Paul Rearden, Thomas J. Greshock
Summary: Activation of PKG1 alpha is a promising approach for treating cardiovascular diseases, as it induces various beneficial effects such as smooth muscle relaxation and prevention of platelet aggregation. In this study, small molecule activators were optimized and shown to have anti-proliferative effects in human pulmonary arterial smooth muscle cells. Mechanistic studies revealed that the activators work through a similar mechanism as cGMP and bind to an allosteric pocket in close proximity to the cyclic nucleotide-binding domain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Jie Su, Pierre Coleman, Angeliki Ntorla, Rhys Anderson, Michael J. Shattock, Joseph R. Burgoyne
Summary: This study demonstrates that the cytosolic DNA sensor cGAS can activate PKGI directly through the generation of cGAMP, showing a link between inflammation and blood pressure regulation.
Article
Pharmacology & Pharmacy
Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones
Summary: Praliciguat treatment showed metabolic effects of increasing energy utilization, improving insulin sensitivity, and reducing plasma triglycerides in diet-induced obesity (DIO) mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Hari Prasad, John Kandam Kulathu Mathew, Sandhya S. Visweswariah
Summary: This review highlights the importance of Receptor Guanylyl Cyclase C (GC-C) in regulating intestinal fluid and ion homeostasis, and its causal link to intestinal inflammation, dysbiosis, and tumorigenesis. The GC-C signaling pathway plays a role in extra gastrointestinal functions such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has also uncovered the involvement of GC-C in the ion-microbiome-immune axis in inflammatory bowel disease and suggests potential therapeutic strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biology
Adrina Kalasho Kuzmiszyn, Anders Lund Selli, Markus Furuholmen, Natalia Smaglyukova, Timofei Kondratiev, Ole-Martin Fuskevag, Georg Sager, Erik Sveberg Dietrichs
Summary: The effects of differential temperatures on cAMP levels and elimination of cAMP and cGMP in embryonic H9c2 cardiac cells were studied. The results showed that intracellular cAMP significantly increased at 30 degrees Celsius but not at 20 degrees Celsius. Elimination of cAMP and cGMP through ABC transport proteins and PDE enzymes showed temperature dependent reduction.
Article
Biochemistry & Molecular Biology
Maryam Alapa, Chuanlong Cui, Ping Shu, Hong Li, Vlad Kholodovych, Annie Beuve
Summary: The study found that redox modifications play a crucial role in NO activation of GC1, with NO-stimulated GC1 containing more bound Cys, potentially disulfide bonds. Mass spectrometry identified ten oxidized and two reduced Cys in NO-stimulated GC1, and computational modeling narrowed down potential Cys candidates involved in disulfide bonds to Cys489 and Cys571. Mutational studies confirmed the involvement of Cys489 and Cys571 in GC1's response to NO, potentially as a thiol/disulfide switch.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Cunguo Chen, Murong Hu, Yunyun Cao, Binbin Zhu, Jiashe Chen, Yashi Li, Junyi Shao, Sen Zhou, Pengfei Shan, Chen Zheng, Zhongyu Li, Zhiming Li
Summary: In this study, a combined immunotherapy strategy was developed based on immune agonists and photothermal therapy, which can effectively improve the biological efficacy of immunotherapy, transform the immunosuppressive tumor microenvironment into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells.
Article
Chemistry, Multidisciplinary
Shikha S. Chauhan, Nick J. Marotta, Anna C. Karls, Emily E. Weinert
Summary: The levels of 2',3'-cNMPs can modulate bacterial phenotypes by rapidly affecting translation.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Shikha S. Chauhan, Nick J. Marotta, Anna C. Karls, Emily E. Weinert
Summary: 2',3'-cNMPs levels can modulate bacterial phenotypes by affecting gene expression and inhibiting translation. This study identified Escherichia coli proteins that bind 2',3'-cNMPs and demonstrated their inhibitory effect on translation. It also developed a tool to increase cellular 2',3'-cNMP levels and showed a decrease in E. coli growth rates as a result. These findings suggest a mechanism for rapid modulation of bacterial phenotypes by 2',3'-cNMPs.
ACS CENTRAL SCIENCE
(2022)
Article
Polymer Science
Akesh Babu Kakarla, Ing Kong, Cin Kong, Helen Irving
Summary: A novel hydrogel-based ink composed of Alg reinforced with f-BNNTs was developed in this study, showing good structural stability and improved thermal stability when f-BNNTs were incorporated into the scaffolds. Cell viability experiments indicated a slight effect on toxicity with higher concentrations of BNNTs in the scaffolds.
Article
Materials Science, Multidisciplinary
Akesh B. Kakarla, Ing Kong, Ilona Turek, Cin Kong, Helen Irving
Summary: A novel printable hydrogel-based ink solution comprised of gelatin-alginate (GA) reinforced by boron nitride nanotubes (BNNTs) was developed for 3D bioprinting and tissue engineering applications. The research showed that increasing the concentration of BNNTs improved printability and printing accuracy, but also affected the swelling rate of the scaffold. The study suggests that BNNTs reinforced GA scaffold could be a potential ink solution for tissue engineering applications through 3D bioprinting processes.
MATERIALS & DESIGN
(2022)
Review
Biotechnology & Applied Microbiology
Neha Tanwar, Sagar S. Arya, James E. Rookes, David M. Cahill, Sangram K. Lenka, Kailash C. Bansal
Summary: Chloroplast genome engineering is a promising approach for enhancing the nutritional value of food crops by increasing the levels of existing metabolites, restoring lost metabolites during crop domestication, and introducing novel nutritional compounds.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Nandini Bhattacharya, David M. Cahill, Wenrong Yang, Mandira Kochar
Summary: Graphene, with its unique properties, has great potential as a nano-delivery system in both biomedicine and agriculture. Its large surface area, chemical and mechanical stability, tunable surface chemistry and low toxicity make it a promising material for agricultural delivery systems. Recent research has shown success in using graphene as a delivery vehicle for plant nutrients and crop protection agents in agriculture.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Yichao Wang, Ali Zavabeti, Qifeng Yao, Thi Linh Chi Tran, Wenrong Yang, Lingxue Kong, David Cahill
Summary: Nanobionics-driven synthesis is an environmentally friendly approach for designing and synthesizing functional materials on a nanoscale. In this work, plasmonic HxMoO3 was synthesized using a green nanobionics approach by interacting chloroplasts with MoO3 nanoflakes. The synthesized plasmonic materials showed tunable plasmon resonances and high photocatalytic activities.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Multidisciplinary Sciences
Bhaskar Sharma, Luis O. B. Afonso, Manoj Pratap Singh, Udit Soni, David M. Cahill
Summary: The continuous use of nitrogen fertilizer has been linked to climate change and biodiversity reduction. Sustainable methods are needed in the agricultural sector to maintain high crop yields. This study synthesized zinc and magnesium doped and undoped hydroxyapatite nanoparticles and their urea nanohybrids to deliver nitrogen to wheat sustainably. Results showed that the nanohybrids significantly boosted wheat growth and yield and improved nutrient uptake and grain protein levels. The multi-nutrient complexes demonstrated the potential to reduce nitrogen inputs while maintaining wheat plant growth and nitrogen uptake.
SCIENTIFIC REPORTS
(2022)
Correction
Physiology
Lachlan Van Schaik, Christine Kettle, Rod Green, Daniel Wundersitz, Brett Gordon, Helen R. Irving, Joseph A. Rathner
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Development Studies
Muneer Ahmad Magry, David Cahill, James Rookes, Sapna A. Narula
Summary: Our study investigates the impact of climate change on non-timber forest products in Khunti district, India. Through questionnaires, interviews, and data analysis, we found that changing climate has significantly decreased the yield and quality of these products, leading to lower sale prices and affecting livelihoods. Respondents also identified infrastructure development and forest cover loss as key factors contributing to these climate change impacts.
CLIMATE AND DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Ilona Turek, Trang H. Nguyen, Charles Galea, Isaiah Abad, Lubna Freihat, David T. Manallack, Tony Velkov, Helen Irving
Summary: Interleukin-1 receptor-associated kinase 3 (IRAK3) regulates cellular responses to IL-1Rs and TLRs, leading to decreased pro-inflammatory cytokines and suppressed inflammation. The mechanism of IRAK3's action is unknown, but it functions as a guanylate cyclase and its cGMP product inhibits NF-κB activity. By mutagenesis and analysis, we identified residues in and near the catalytic center of IRAK3 that affect NF-κB activity and subcellular localization in HEK293T cells. Mutant IRAK3 variants with reduced cGMP generation capacity and altered NF-κB activity fail to rescue IRAK3 function in LPS-stimulated THP-1 monocytes unless a cGMP analog is present.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Santosh T. R. B. Rao, Ilona Turek, Julian Ratcliffe, Simone Beckham, Cassandra Cianciarulo, Siti S. B. M. Y. Adil, Christine Kettle, Donna R. Whelan, Helen R. Irving
Summary: This study investigated the distribution of 5-HT3 receptor subunits in intracellular and cell-free mitochondria. A and E subunits were found to be localized on the inner membrane of the mitochondria and could form heteromeric complexes. Cell-free mitochondria colocalized with the fluorescent signal for A subunits. The presence of A and E subunits affected changes in membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin, which were inhibited by pre-treatment with ondansetron. It is likely that the 5-HT3 receptors on mitochondria directly impact mitochondrial function and may have therapeutic implications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Santosh T. R. B. Rao, Ilona Turek, Helen R. Irving
Summary: 5-HT3 receptors are widely distributed in animals from different phyla, with the Chordata phylum being the most abundant. Through multiple sequence alignment of receptor protein sequences, common critical amino acid residues in the ligand binding region were discovered. This finding is significant for understanding the evolutionary patterns of 5-HT3 receptors and their potential effects on parasitic and other species in ecosystems.
Review
Agriculture, Multidisciplinary
Ananya Padmakumar, Chowdary Pavani, Kalyani Eswar, Lingxue Kong, Wenrong Yang, Subramanium Gopalakrishnan, David Miles Cahill, Aravind Kumar Rengan
Summary: The use of bacterial biocontrol agents (BBCAs) in plant protection has increased due to the rising awareness of chemical risks and the need for sustainable agriculture. Nanotechnology has facilitated the development of efficient and ecologically sound nanoformulations, such as bacteria premised nanobiopesticides (B-NBPs). These B-NBPs are synthesized using nanomaterials with amended properties at the nanoscale. This article provides an overview of BBCAs and their antagonistic mechanisms, focusing on the significance of BNPs in plant infection management and addressing concerns related to the efficacy of B-NBPs.
ACS AGRICULTURAL SCIENCE & TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Siti Saleha Binte Mohamed Yakob Adil, Mwila Kabwe, Cassandra Cianciarulo, Trang Hong Nguyen, Helen Irving, Joseph Tucci
Summary: Microbial resistance to antibiotics is a significant challenge, and bacteriophages may serve as an alternative or adjunct to traditional antibiotics. This study investigates the immune effects of bacteriophage FNU1 on immune cells, particularly its modulation through IRAK3. The findings suggest that IRAK3 regulates immune responses to endotoxins and impurities in bacteriophage preparations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Thi Linh Chi Tran, Albert Guirguis, Thanojan Jeyachandran, Yichao Wang, David M. Cahill
Summary: Nanoparticles have been shown to enhance plant growth and development, and improve crop production, especially under adverse environmental conditions like drought. Silicon dioxide nanoparticles have been found to be taken up by plants and have the potential to improve tolerance to abiotic stress.
FUNCTIONAL PLANT BIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Anamika Pal, Pawan Kaur, Neeraj Dwivedi, Jim Rookes, Himadri B. Bohidar, Wenrong Yang, David Miles Cahill, Palash Kumar Manna
Summary: Clay-nanocomposite materials have been widely used for drug delivery systems, but their application in agriculture is less explored. The combination of nanoclay and active ingredients can create a biocompatible and environmentally friendly delivery vehicle for micronutrients, pesticides, etc., improving crop growth. This review provides an overview of the synthesis and application of clay-based nanocomposites in agriculture, addressing issues related to the delivery of active ingredients and biological macromolecules for crop protection and sustainability.
ACS AGRICULTURAL SCIENCE & TECHNOLOGY
(2023)