Catálogo de publicaciones - revistas

<jats:p>Cure strategies are confounded by basic reservoir biology</jats:p>

<jats:p>Autoantibodies influence a wide range of conditions beyond autoimmune diseases</jats:p>

<jats:p>Plants commandeer a pathogen’s virulence factor to bolster immunity</jats:p>

<jats:p>A political scientist urges readers to embrace the chaos and complexity of life</jats:p>

<jats:p>How B cells assess risk in the intestine</jats:p>

<jats:p>Epitope editing can empower targeted cancer immunotherapies</jats:p>

<jats:p> We report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of <jats:italic>Staphylococcus aureus</jats:italic> , <jats:italic>Escherichia coli</jats:italic> , and <jats:italic>Pseudomonas aeruginosa</jats:italic> . We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory–calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail. </jats:p>

<jats:p>The global ocean’s oxygen inventory is declining in response to global warming, but the future of the low-oxygen tropics is uncertain. We report new evidence for tropical oxygenation during the Paleocene-Eocene Thermal Maximum (PETM), a warming event that serves as a geologic analog to anthropogenic warming. Foraminifera-bound nitrogen isotopes indicate that the tropical North Pacific oxygen-deficient zone contracted during the PETM. A concomitant increase in foraminifera size implies that oxygen availability rose in the shallow subsurface throughout the tropical North Pacific. These changes are consistent with ocean model simulations of warming, in which a decline in biological productivity allows tropical subsurface oxygen to rise even as global ocean oxygen declines. The tropical oxygen increase may have helped avoid a mass extinction during the PETM.</jats:p>

<jats:p> Polygalacturonase-inhibiting proteins (PGIPs) interact with pathogen-derived polygalacturonases to inhibit their virulence-associated plant cell wall–degrading activity but stimulate immunity-inducing oligogalacturonide production. Here we show that interaction between <jats:italic>Phaseolus vulgaris</jats:italic> PGIP2 (PvPGIP2) and <jats:italic>Fusarium phyllophilum</jats:italic> polygalacturonase (FpPG) enhances substrate binding, resulting in inhibition of the enzyme activity of FpPG. This interaction promotes FpPG-catalyzed production of long-chain immunoactive oligogalacturonides, while diminishing immunosuppressive short oligogalacturonides. PvPGIP2 binding creates a substrate binding site on PvPGIP2-FpPG, forming a new polygalacturonase with boosted substrate binding activity and altered substrate preference. Structure-based engineering converts a putative PGIP that initially lacks FpPG-binding activity into an effective FpPG-interacting protein. These findings unveil a mechanism for plants to transform pathogen virulence activity into a defense trigger and provide proof of principle for engineering PGIPs with broader specificity. </jats:p>