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Synaptotagmin (syt) 1, a Ca²⁺sensor for synaptic vesicle exocytosis, functions in vivo as a multimer. Syt1 senses Ca²⁺via tandem C2-domains that are connected to a single transmembrane domain via a juxtamembrane linker. Here, we show that this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS). Interestingly, condensate formation negatively regulates the Ca²⁺-sensitivity of syt1. Moreover, Ca²⁺and anionic phospholipids facilitate the observed phase separation, and increases in [Ca²⁺]_ipromote the fusion of syt1 droplets in living cells. Together, these observations suggest a condensate-mediated feedback loop that serves to fine-tune the ability of syt1 to trigger release, via alterations in Ca²⁺binding activity and potentially through the impact of LLPS on membrane curvature during fusion reactions. In summary, the juxtamembrane linker of syt1 emerges as a regulator of syt1 function by driving self-association via LLPS.

The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, is fueling a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and site-specific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction, involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the photocatalytic diselenide contraction transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21^stamino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.

A cobalt silylene (Co=Si) linkage enables a distinct metal/ligand cooperative activation of an organic azide, where nitrene transfer occurs to and from the Co⋅⋅⋅Si linkage without ligand dissociation from the 18‐electron cobalt center. This process utilizes the orthogonal binding affinities of the silicon and cobalt sites to avoid CO poisoning that would otherwise inhibit reactivity, leading to significantly improved catalytic isocyanate generation compared with related systems. The dual‐site approach demonstrates the potential of metal/main‐group bonds to access new and efficient catalytic pathways.

A cobalt silylene (Co=Si) linkage enables a distinct metal/ligand cooperative activation of an organic azide, where nitrene transfer occurs to and from the Co⋅⋅⋅Si linkage without ligand dissociation from the 18‐electron cobalt center. This process utilizes the orthogonal binding affinities of the silicon and cobalt sites to avoid CO poisoning that would otherwise inhibit reactivity, leading to significantly improved catalytic isocyanate generation compared with related systems. The dual‐site approach demonstrates the potential of metal/main‐group bonds to access new and efficient catalytic pathways.

Cool- and warm-season precipitation totals have been reconstructed on a gridded basis for North America using 439 tree-ring chronologies correlated with December–April totals and 547 different chronologies correlated with May–July totals. These discrete seasonal chronologies are not significantly correlated with the alternate season; the December–April reconstructions are skillful over most of the southern and western United States and north-central Mexico, and the May–July estimates have skill over most of the United States, southwestern Canada, and northeastern Mexico. Both the strong continent-wide El Niño–Southern Oscillation (ENSO) signal embedded in the cool-season reconstructions and the Arctic Oscillation signal registered by the warm-season estimates faithfully reproduce the sign, intensity, and spatial patterns of these ocean–atmospheric influences on North American precipitation as recorded with instrumental data. The reconstructions are included in the North American Seasonal Precipitation Atlas (NASPA) and provide insight into decadal droughts and pluvials. They indicate that the sixteenth-century megadrought, the most severe and sustained North American drought of the past 500 years, was the combined result of three distinct seasonal droughts, each bearing unique spatial patterns potentially associated with seasonal forcing from ENSO, the Arctic Oscillation, and the Atlantic multidecadal oscillation. Significant 200–500-yr-long trends toward increased precipitation have been detected in the cool- and warm-season reconstructions for eastern North America. These seasonal precipitation changes appear to be part of the positive moisture trend measured in other paleoclimate proxies for the eastern area that began as a result of natural forcing before the industrial revolution and may have recently been enhanced by anthropogenic climate change.