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There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π‐stacking and H‐bonding) between from the biaryl side‐chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure‐activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (K_ddetermined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H‐bonding interactions that modulate the potency of solithromycin analogs.

Phylogenetic studies ofCarexL. (Cyperaceae) have consistently demonstrated that most subgenera and sections are para‐ or polyphyletic. Yet, taxonomists continue to use subgenera and sections inCarexclassification. Why? The GlobalCarexGroup (GCG) here takes the position that the historical and continued use of subgenera and sections serves to (i) organize our understanding of lineages inCarex, (ii) create an identification mechanism to break the ~2000 species ofCarexinto manageable groups and stimulate its study, and (iii) provide a framework to recognize morphologically diagnosable lineages withinCarex. Unfortunately, the current understanding of phylogenetic relationships inCarexis not yet sufficient for a global reclassification of the genus within a Linnean infrageneric (sectional) framework. Rather than leavingCarexclassification in its current state, which is misleading and confusing, we here take the intermediate steps of implementing the recently revised subgeneric classification and using a combination of informally named clades and formally named sections to reflect the current state of our knowledge. This hybrid classification framework is presented in an order corresponding to a linear arrangement of the clades on a ladderized phylogeny, largely based on the recent phylogenies published by the GCG. It organizesCarexinto six subgenera, which are, in turn, subdivided into 62 formally named Linnean sections plus 49 informal groups. This framework will serve as a roadmap for research onCarexphylogeny, enabling further development of a complete reclassification by presenting relevant morphological and geographical information on clades where possible and standardizing the use of formal sectional names.

The megadiverse genusCarex(c. 2000 species, Cyperaceae) has a nearly cosmopolitan distribution, displaying an inverted latitudinal richness gradient with higher species diversity in cold‐temperate areas of the Northern Hemisphere. Despite great expansion in our knowledge of the phylogenetic history of the genus and many molecular studies focusing on the biogeography of particular groups during the last few decades, a global analysis ofCarexbiogeography and diversification is still lacking. For this purpose, we built the hitherto most comprehensiveCarex‐dated phylogeny based on three markers (ETS–ITS–matK), using a previous phylogenomic Hyb‐Seq framework, and a sampling of two‐thirds of its species and all recognized sections. Ancestral area reconstruction, biogeographic stochastic mapping, and diversification rate analyses were conducted to elucidate macroevolutionary biogeographic and diversification patterns. Our results reveal thatCarexoriginated in the late Eocene in E Asia, where it probably remained until the synchronous diversification of its main subgeneric lineages during the late Oligocene. E Asia is supported as the cradle ofCarexdiversification, as well as a “museum” of extant species diversity. Subsequent “out‐of‐Asia” colonization patterns feature multiple asymmetric dispersals clustered toward present times among the Northern Hemisphere regions, with major regions acting both as source and sink (especially Asia and North America), as well as several independent colonization events of the Southern Hemisphere. We detected 13 notable diversification rate shifts during the last 10 My, including remarkable radiations in North America and New Zealand, which occurred concurrently with the late Neogene global cooling, which suggests that diversification involved the colonization of new areas and expansion into novel areas of niche space.