Article
Plant Sciences
Pao-Yuan Hsiao, Cyong-Yu Zeng, Ming-Che Shih
Summary: The study found that three BdERFVIIs genes are involved in a feedback regulatory loop to mediate downstream responses in the submergence stress response. The same regulatory loop was also found in rice, involving the orthologue of BdERF961. These findings offer new perspectives for the development of submergence-tolerant crops.
Article
Neurosciences
Panagiotis Mastorakos, Nicole Mihelson, Marie Luby, Scott R. Burks, Kory Johnson, Amie W. Hsia, Jaclyn Witko, Joseph A. Frank, Lawrence Latour, Dorian B. McGavern
Summary: Positive vascular recanalization after endovascular thrombectomy may lead to cerebral edema and worsened clinical outcomes, especially in patients with hemorrhagic transformation. Resident microglia initially stabilize damaged vessels, followed by an influx of myelomonocytic cells causing severe edema. Prolonged blockade of myeloid cell recruitment can prevent severe edema but also interfere with vascular repair.
NATURE NEUROSCIENCE
(2021)
Review
Cell Biology
Ming-Hsiang Hong, I-Chun Weng, Fang-Yen Li, Wei-Han Lin, Fu-Tong Liu
Summary: Galectins are animal lectins that recognize carbohydrates and play important roles in cellular homeostasis. Recent studies have shown that galectins accumulate around damaged endocytic vesicles and control cellular responses by interacting with cellular proteins, such as autophagy. The differential regulatory effects among galectins are also highlighted in this review.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Biology
Xiaojie Yu, Sonya James, James H. Felce, Blanka Kellermayer, David A. Johnston, H. T. Claude Chan, Christine A. Penfold, Jinny Kim, Tatyana Inzhelevskaya, C. Ian Mockridge, Yasunori Watanabe, Max Crispin, Ruth R. French, Patrick J. Duriez, Leon R. Douglas, Martin J. Glennie, Mark S. Cragg
Summary: The study demonstrated that agonists with greater activity induced higher density receptor clustering and specific super-structures as opposed to simply larger receptor clusters.
COMMUNICATIONS BIOLOGY
(2021)
Review
Immunology
Natasha M. Kafai, Michael S. Diamond, Julie M. Fox
Summary: Alphaviruses are a group of emerging and reemerging viruses that can cause a range of diseases, from debilitating arthritis to potentially fatal encephalitis. The differences in immune responses contribute to the varying disease progression and outcomes.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Article
Immunology
Fernando Bandeira Sulczewski, Raul A. Maqueda-Alfaro, Marcela Alcantara-Hernandez, Oriana A. Perez, Sanjana Saravanan, Tae Jin Yun, David Seong, Rebeca Arroyo Hornero, Hayley M. Raquer-McKay, Eduardo Esteva, Zachary R. Lanzar, Rebecca A. Leylek, Nicholas M. Adams, Annesa Das, Adeeb H. Rahman, Andres Gottfried-Blackmore, Boris Reizis, Juliana Idoyaga
Summary: This study investigates the role of transitional dendritic cells (tDCs) in antiviral immune responses and reveals their distinct features compared to other dendritic cell subsets. The authors show that tDCs share bone marrow progenitors with plasmacytoid DCs (pDCs) and contribute to the development of ESAM(+) type 2 DCs (DC2s). Unlike other DC subsets, tDCs exhibit characteristics of differentiated DCs, including antigen capture, response to stimuli, and activation of antigen-specific naive T cells. Moreover, viral sensing by tDCs leads to IL-1β secretion and fatal immune pathology. Overall, tDCs are a unique pDC-related subset with a DC2 differentiation potential and a special proinflammatory function during viral infections.
Article
Genetics & Heredity
Stuart D. Woodcock, Karl Syson, Richard H. Little, Danny Ward, Despoina Sifouna, James K. M. Brown, Stephen Bornemann, Jacob G. Malone
Summary: The study reveals the close connection between trehalose metabolism and branched alpha-glucan biosynthesis in the human pathogen Pseudomonas aeruginosa, highlighting their distinct roles in mediating responses to different environmental stresses.
Article
Immunology
Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain, Jenny E. Hernandez-Davies, Rafael de Assis, Zachary W. Wagoner, Andrew M. Sorn, Mahina Tabassum Mitul, Aviv I. Benchorin, Elizabeth Levendosky, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Jacob Boeckmann, Rie Nakajima, Algimantas Jasinskas, Naresha Saligrama, D. Huw Davies, Lisa E. Wagar
Summary: This study investigated the effects of different antigen formats on mucosal adaptive immune responses using a human tonsil organoid model. The results showed significant differences in the B and T cell responses elicited by different antigen formats, which led to changes in the corresponding antibody response. The ability of antigen formats to recruit naive and memory B and T cells to the response was identified as a major source of variability.
Article
Biochemistry & Molecular Biology
Sarah J. Taleb, Jianxin Wei, Rachel K. Mialki, Su Dong, Yanhui Li, Jing Zhao, Yutong Zhao
Summary: This study demonstrates that disrupting the interaction between LPA1 and Nedd4L with peptide P1 increases the stability of LPA1 and enhances LPA/LPA1 signaling, leading to increased cell migration and specific gene expression in lung epithelial cells.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Immunology
Nardhy Gomez-Lopez, Roberto Romero, Li Tao, Meyer Gershater, Yaozhu Leng, Chengrui Zou, Marcelo Farias-Jofre, Jose Galaz, Derek Miller, Adi L. Tarca, Marcia Arenas-Hernandez, Gaurav Bhatti, Valeria Garcia-Flores, Zhenjie Liu, Robert Para, Tomi Kanninen, Ola Hadaya, Carmen Paredes, Yi Xu
Summary: Pregnant women infected with SARS-CoV-2 may face increased risks of adverse outcomes, and pregnancy-specific immune responses can modulate susceptibility to microbial infection. Studies on cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women reveal differential in vitro responses compared to nonpregnant women, shedding light on immune mechanisms involved in coronavirus disease in pregnancy.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Nardhy Gomez-Lopez, Roberto Romero, Li Tao, Meyer Gershater, Yaozhu Leng, Chengrui Zou, Marcelo Farias-Jofre, Jose Galaz, Derek Miller, Adi L. Tarca, Marcia Arenas-Hernandez, Gaurav Bhatti, Valeria Garcia-Flores, Zhenjie Liu, Robert Para, Tomi Kanninen, Ola Hadaya, Carmen Paredes, Yi Xu
Summary: Pregnant women exhibit different cellular immune responses to SARS-CoV-2 compared to nonpregnant women, highlighting the importance of understanding the immune mechanisms involved in coronavirus disease 2019 during pregnancy.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Renee M. van der Sluis, Lamin B. Cham, Albert Gris-Oliver, Kristine R. Gammelgaard, Jesper G. Pedersen, Manja Idorn, Ulvi Ahmadov, Sabina Sanches Hernandez, Ena Cemalovic, Stine H. Godsk, Jacob Thyrsted, Jesper D. Gunst, Silke D. Nielsen, Janni J. Jorgensen, Tobias Wang Bjerg, Anders Laustsen, Line S. Reinert, David Olagnier, Rasmus O. Bak, Mads Kjolby, Christian K. Holm, Martin Tolstrup, Soren R. Paludan, Lasse S. Kristensen, Ole S. Sogaard, Martin R. Jakobsen
Summary: Understanding the molecular pathways involved in the antiviral and inflammatory response to SARS-CoV-2 infection is crucial for treating severe COVID-19. Circulating plasmacytoid dendritic cells (pDCs) decrease in COVID-19 patients early after symptom onset and this is associated with disease severity. pDCs sense the virus and produce antiviral and inflammatory cytokines to protect epithelial cells from SARS-CoV-2 infection. TLR7-MyD88 signaling is important for antiviral interferon production, while TLR2 is responsible for the inflammatory IL-6 response. SARS-CoV-2 interacts with neuropilin-1 on pDCs to dampen the antiviral interferon response.
Article
Chemistry, Analytical
Michael R. Stoneman, Valerica Raicu
Summary: This study investigated the impact of the interaction between a GPCR and its agonist ligand on the dielectric properties of the plasma membrane in living yeast cells using radiofrequency dielectric spectroscopy. The results showed a significant increase in plasma membrane permittivity after exposure to the agonist ligand, while cells lacking the ability to express the specific receptor showed no change. Interestingly, the electrical properties of the cellular interior also underwent a large change after the addition of the agonist, regardless of Ste2 expression.
Article
Multidisciplinary Sciences
Valentina Palmerini, Silvia Monzani, Quentin Laurichesse, Rihab Loudhaief, Sara Mari, Valentina Cecatiello, Vincent Olieric, Sebastiano Pasqualato, Julien Colombani, Ditte S. Andersen, Marina Mapelli
Summary: The Drosophila tumour necrosis factor (TNF) system consists of a single ligand, Eiger (Egr), and two receptors. The crystallographic structure of Egr in complex with the extracellular domain of the receptor Grindelwald suggests that distinct affinities of TNF ligand for its receptors mediate non-redundant functions.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kazune Tamura, Guillaume Dejean, Filip Van Petegem, Harry Brumer
Summary: The study examined the significant role of complex glycans in feeding the human gut microbiota and the prevalence of Bacteroidetes in the gut microbiota worldwide. It also investigated the role of cell-surface glycan-binding proteins in the polysaccharide utilization loci and provided insights into the structural specificities of three bacterial species.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Rob Hill, Meritxell Canals
Summary: Morphine and other opioids are widely used for pain treatment, but their side effects limit their use. Developing opioids with fewer side effects is a major research focus, but translating promising candidates from the lab to the clinic remains challenging.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Gastroenterology & Hepatology
Jesse J. DiCello, Simona E. Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Celine Valant, Daniel P. Poole
Summary: This study investigates the modulation of delta opioid receptor in the enteric nervous system using allosteric modulators, demonstrating the potential of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling and suppress colonic motility. The findings suggest that allosteric modulation of opioid receptor signaling could be a therapeutic strategy for conditions such as irritable bowel syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Biochemical Research Methods
Jacob Neumann, Yen Ting Lin, Abhishek Mallela, Ely F. Miller, Joshua Colvin, Abell T. Duprat, Ye Chen, William S. Hlavacek, Richard G. Posner
Summary: This article presents the implementation of a practical MCMC method in PyBioNetFit for parameterization of mathematical models in biological systems. The new MCMC method, am, incorporates an adaptive move proposal distribution and has been successfully applied to real-world Bayesian inference problems, including forecasting of new Coronavirus Disease 2019 case detection with Bayesian quantification of forecast uncertainty.
Article
Biochemistry & Molecular Biology
Christopher J. Lupton, Charles Bayly-Jones, Laura D'Andrea, Cheng Huang, Ralf B. Schittenhelm, Hari Venugopal, James C. Whisstock, Michelle L. Halls, Andrew M. Ellisdon
Summary: NF1 mutations cause neurofibromatosis type 1 and various cancers. This study reveals the structure of NF1 homodimer and provides insights into its role in cellular proliferation and cancer, potentially offering new therapeutic opportunities for modulating the RAS pathway.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Virology
Abhishek Mallela, Jacob Neumann, Ely F. Miller, Ye Chen, Richard G. Posner, Yen Ting Lin, William S. Hlavacek
Summary: Although many individuals in the US have acquired immunity against COVID-19, the ongoing transmission of the disease poses a threat to those who are not immune. By calculating the population-specific basic reproduction number R0, which represents the expected number of secondary cases generated by an infected person in the absence of interventions, we can estimate when sustained disease transmission will end. Our state-level R0 estimates obtained using Bayesian inference show significant variations in disease transmission across states, making it more challenging to achieve herd immunity in certain states. Based on adjusted herd immunity thresholds, vaccination data, and seroprevalence survey data, no state had achieved herd immunity as of September 20, 2021.
Article
Pharmacology & Pharmacy
Rob Hill, Andrew C. Kruegel, Jonathan A. Javitch, J. Robert Lane, Meritxell Canals
Summary: The study found differential effects of Mitragynine and its metabolite, 7-OH Mitragynine, on mouse respiration and anti-nociception. Mitragynine showed a ceiling effect on respiratory depression, while 7-OH Mitragynine had dose-dependent effects. Inhibition of CYP3A reduced the respiratory depressant effects and anti-nociception induced by Mitragynine, but had no effect on the effects of 7-OH Mitragynine. These findings suggest that metabolic saturation may contribute to the improved safety profile of Mitragynine.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Iman Lohraseb, Peter McCarthy, Genevieve Secker, Ceilidh Marchant, Jianmin Wu, Naveid Ali, Sharad Kumar, Roger J. Daly, Natasha L. Harvey, Hiroshi Kawabe, Oded Kleifeld, Sophie Wiszniak, Quenten Schwarz
Summary: This study uncovers the important role of NEDD4-mediated ubiquitination in neural crest cell development, regulating the ubiquitination and turnover of Profilin 1 to modulate actin polymerization.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Rani Zananiri, Sivasubramanyan Mangapuram Venkata, Vera Gaydar, Dan Yahalom, Omri Malik, Sergei Rudnizky, Oded Kleifeld, Ariel Kaplan, Arnon Henn
Summary: RecBCD helicase has additional non-catalytic ATP binding sites that enhance ATP flux to catalytic sites and enable fast unwinding even when ATP is scarce. The importance and functionality of these auxiliary binding sites are demonstrated by their impact on E.coli survival after exposure to damage-inducing radiation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Hsin-Yung Yen, Idlir Liko, Wanling Song, Parth Kapoor, Fernando Almeida, Joanna Toporowska, Karolina Gherbi, Jonathan T. S. Hopper, Steven J. Charlton, Argyris Politis, Mark S. P. Sansom, Ali Jazayeri, Carol Robinson
Summary: This study presents a mass spectrometry-based approach to investigate the biased signaling and allosteric modulation of the beta(1)-adrenergic receptor in response to different ligands. The researchers discovered that isoprenaline can act as a biased agonist and that endogenous zinc ions enhance the binding between the receptor and G(s) proteins.
Article
Microbiology
Sheila Roitman, Andrey Rozenberg, Tali Lavy, Corina P. D. Brussaard, Oded Kleifeld, Oded Beja
Summary: Isolation and characterization of a virophage-like element, Gezel-14T, that co-infects a polar algae, Phaeocystis globosa, with a partner virus, PgV-14T, is reported. This co-infection reduces the fitness of the viral host by decreasing burst sizes of PgV-14T. Genomic screens reveal the integration of Gezel-14T-like elements into Phaeocystis genomes, suggesting the capability of these widespread viruses to integrate into cellular host genomes.
NATURE MICROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Anh T. N. Nguyen, Diep T. N. Nguyen, Huan Yee Koh, Jason Toskov, William MacLean, Andrew Xu, Daokun Zhang, Geoffrey I. Webb, Lauren T. May, Michelle L. Halls
Summary: The application of artificial intelligence in drug discovery for G protein-coupled receptors (GPCRs) is expanding rapidly. It can assist in understanding the actions of GPCRs, discovering new ligand-GPCR interactions, and predicting clinical responses. This article provides an overview of artificial intelligence concepts and its applications in different stages of GPCR drug discovery. The benefits and limitations of artificial intelligence are discussed, along with the potential for further development in assisting GPCR drug discovery.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Rob Hill, Julie Sanchez, Laura Lemel, Mirjana Antonijevic, Yselkla Hosking, Shailesh N. Mistry, Andrew C. Kruegel, Jonathan A. Javitch, J. Robert Lane, Meritxell Canals
Summary: This study evaluated the effects of three novel opioids on respiratory depression and analgesia, and compared these measurements with their in vitro efficacy. The results showed that these opioids can induce respiratory depression and analgesia at certain doses, but there are differences in potency and duration of effect among the novel opioids.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Bianca Maria Casella, James P. P. Farmer, Desislava N. N. Nesheva, Huw E. L. Williams, Steven J. J. Charlton, Nicholas D. D. Holliday, Charles A. A. Laughton, Shailesh N. N. Mistry
Summary: Inhibition of CXCR2 is a potential strategy for the treatment of pulmonary diseases and cancers. This study reports the design and synthesis of fluorescent NAMs that selectively bind to CXCR2, enabling the measurement and evaluation of their pharmacological properties. These NAMs can be used as alternative compounds for targeting these receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Quynh N. Mai, Priyank Shenoy, Tim Quach, Jeffri S. Retamal, Arisbel B. Gondin, Holly R. Yeatman, Luigi Aurelio, Joshua W. Conner, Daniel P. Poole, Meritxell Canals, Cameron J. Nowell, Bim Graham, Thomas P. Davis, Stephen J. Briddon, Stephen J. Hill, Christopher J. H. Porter, Nigel W. Bunnett, Michelle L. Halls, Nicholas A. Veldhuis
Summary: The study found that the NK1R antagonist Span-Chol has a prolonged analgesic effect mechanism: increasing local concentration at membranes, sustained decrease in NK1R endocytosis, and persistent inhibition of signaling from endosomes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)