More Like this

1. Multi-label activity recognition using activity-specific features and activity correlations

   https://doi.org/10.1109/CVPR46437.2021.01439  

   Zhang Y, Li X (June 2021, 2021 IEEE/CVF Conference on Computer Vision and Pattern Recognition)
2. Exploration of the Fusidic Acid Structure Activity Space for Antibiotic Activity

   https://doi.org/10.3390/molecules30030465  

   Kang, Yoon-Suk; Silva, Simone C; Smith, Kenneth; Sumida, Krissty; Wang, Yuhan; Chiaraviglio, Lucius; Donthiri, Ramachandra Reddy; Aljahdali, Alhanouf Z; Kirby, James E; O’Doherty, George A (February 2025, Molecules)

   Fusidic acid is a translation inhibitor with activity against major Gram-positive bacterial pathogens such as S. aureus. However, its activity against Gram-negatives is poor based on an inability to access its cytoplasmic target in these organisms. Opportunities for functionalization of the fusidic acid scaffold to enhance activity against Gram-negative pathogens have not been explored. Using an activity-guided synthetic strategy, the tolerance of the tetracyclic natural product to derivatization at the A- and C-rings and its carboxylic acid side chain was explored with the goal of enhancing its activity spectrum and pharmacological properties. All side-chain carboxylic acid esters were inactive. Oxidation of the C-ring alcohol and oxime were not tolerated either. A number of esters of the A-ring alcohol retained modest activity against Gram-positive bacteria and were informative for future activity-guided studies. For the A-ring esters, differences in antibacterial activity relative to inhibitory activity in a ribosome in vitro translation assay suggested the possibility of a pro-druglike effect for the fusidic acid pyrazine-2-carboxylate. This study furthers the understanding of the activity of the fusidic acid scaffold against Gram-positive bacteria. These results suggest promise for future modification of the A-ring alcohol of fusidic acid in the advancement of its antibiotic properties. 

   more » « less
3. Synthesis and Antibacterial Activity of Ficuseptine and Its Derivatives: Determination of Structure–Activity Relationships

   https://doi.org/10.1055/a-2490-2986  

   Hoang, Nghia_L T; Nsereko, Nina_N P; Sheetz, Sydney A; Tasker, Sarah Z (April 2025, Synlett)

   Abstract The indolizinium natural product ficuseptine, produced by the tropical fig tree Ficus septica, has been reported to have antibacterial properties. Herein, the synthesis of ficuseptine, ten analogues with differing aryl substituents, and two aryl regioisomers is reported. Despite several previous total syntheses, synthetically prepared ficuseptine has not been subjected to biological testing to confirm its activity. In our hands, ficuseptine was moderately active in Gram-positive B. spizizenii, with an MIC of 32 μg/mL, which was maintained for most aryl substituents. The position of the aryl rings was crucial, however, since regioisomeric ficuseptine analogues, mimicking related natural products, were found to be inactive. Finally, all ficuseptine derivatives were inactive (MIC >128 μg/mL) against Gram-negative E. coli. Understanding these structure–activity relationships (SAR) is helpful for future studies to understand the molecule’s mechanism of action or further develop its antibacterial properties. 

   more » « less
4. Protecting activity of desiccated enzymes

   https://doi.org/10.1002/pro.3604  

   Piszkiewicz, Samantha; Gunn, Kathryn H.; Warmuth, Owen; Propst, Ashlee; Mehta, Aakash; Nguyen, Kenny H.; Kuhlman, Elizabeth; Guseman, Alex J.; Stadmiller, Samantha S.; Boothby, Thomas C.; et al (March 2019, Protein Science)

   Abstract Protein‐based biological drugs and many industrial enzymes are unstable, making them prohibitively expensive. Some can be stabilized by formulation with excipients, but most still require low temperature storage. In search of new, more robust excipients, we turned to the tardigrade, a microscopic animal that synthesizes cytosolic abundant heat soluble (CAHS) proteins to protect its cellular components during desiccation. We find that CAHS proteins protect the test enzymes lactate dehydrogenase and lipoprotein lipase against desiccation‐, freezing‐, and lyophilization‐induced deactivation. Our data also show that a variety of globular and disordered protein controls, with no known link to desiccation tolerance, protect our test enzymes. Protection of lactate dehydrogenase correlates, albeit imperfectly, with the charge density of the protein additive, suggesting an approach to tune protection by modifying charge. Our results support the potential use of CAHS proteins as stabilizing excipients in formulations and suggest that other proteins may have similar potential. 

   more » « less
5. Spatial representability of neuronal activity

   https://doi.org/10.1038/s41598-021-00281-y  

   Akhtiamov, D.; Cohn, A. G.; Dabaghian, Y. (October 2021, Scientific Reports)

   Abstract A common approach to interpreting spiking activity is based on identifying the firing fields—regions in physical or configuration spaces that elicit responses of neurons. Common examples include hippocampal place cells that fire at preferred locations in the navigated environment, head direction cells that fire at preferred orientations of the animal’s head, view cells that respond to preferred spots in the visual field, etc. In all these cases, firing fields were discovered empirically, by trial and error. We argue that the existence and a number of properties of the firing fields can be established theoretically, through topological analyses of the neuronal spiking activity. In particular, we use Leray criterion powered by persistent homology theory, Eckhoff conditions and Region Connection Calculus to verify consistency of neuronal responses with a single coherent representation of space. 

   more » « less