DNA mismatch repair (MMR) identifies and corrects errors made during replication. In all organisms except those expressing MutH, interactions between a DNA mismatch, MutS, MutL, and the replication processivity factor (β-clamp or PCNA) activate the latent MutL endonuclease to nick the error-containing daughter strand. This nick provides an entry point...

Epithelial (E)-cadherin-mediated cell−cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in...

The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to...

BPI-inducible protein A (BipA) is a member of the family of ribosome-dependent translational GTPase (trGTPase) factors along with elongation factors G and 4 (EF-G and EF4). Despite being highly conserved in bacteria and playing a critical role in coordinating cellular responses to environmental changes, its structures (isolated and ribosome bound)...

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors,...

Bacterial growth and morphogenesis are intimately coupled to expansion of peptidoglycan (PG), an extensively cross-linked macromolecule that forms a protective mesh-like sacculus around the cytoplasmic membrane. Growth of the PG sacculus is a dynamic event requiring the concerted action of hydrolases that cleave the cross-links for insertion of new material...

Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K+/Na+ selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in...

Criegee intermediates are thought to play a role in atmospheric chemistry, in particular, the oxidation of SO2, which produces SO3 and subsequently H2SO4, an important constituent of aerosols and acid rain. However, the impact of such oxidation reactions is affected by the reactions of Criegee intermediates with water vapor, because...

The high-valent state of the diheme enzyme MauG exhibits charge–resonance (CR) stabilization in which the major species is a bis-FeIV state with one heme present as FeIV=O and the other as FeIV with axial heme ligands provided by His and Tyr side chains. In the absence of its substrate, the...

Living organisms have adapted to atmospheric dioxygen by exploiting its oxidizing power while protecting themselves against toxic side effects. Reactive oxygen and nitrogen species formed during oxidative stress, as well as high-potential reactive intermediates formed during enzymatic catalysis, could rapidly and irreversibly damage polypeptides were protective mechanisms not available. Chains...

The C-terminal transmembrane domain (TMD) of viral fusion proteins such as HIV gp41 and influenza hemagglutinin (HA) is traditionally viewed as a passive α-helical anchor of the protein to the virus envelope during its merger with the cell membrane. The conformation, dynamics, and lipid interaction of these fusion protein TMDs...

Pacific salmon are a dominant component of the northeast Pacific ecosystem. Their status is of concern because salmon abundance is highly variable—including protected stocks, a recently closed fishery, and actively managed fisheries that provide substantial ecosystem services. Variable ocean conditions, such as the Pacific Decadal Oscillation (PDO), have influenced these...

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here...

What are the ecological causes and consequences of variation in phytochemical diversity within and between plant taxa? Despite decades of natural products discovery by organic chemists and research by chemical ecologists, our understanding of phytochemically mediated ecological processes in natural communities has been restricted to studies of either broad classes...

Soft, inflatable segments are the active elements responsible for the actuation of soft machines and robots. Although current designs of fluidic actuators achieve motion with large amplitudes, they require large amounts of supplied volume, limiting their speed and compactness. To circumvent these limitations, here we embrace instabilities and show that...

Marine ammonia-oxidizing archaea (AOA) are among the most abundant of marine microorganisms, spanning nearly the entire water column of diverse oceanic provinces. Historical patterns of abundance are preserved in sediments in the form of their distinctive glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids. The correlation between the composition of GDGTs...

The early diversification of angiosperms in diverse ecological niches is poorly understood. Some have proposed an origin in a darkened forest habitat and others an open aquatic or near aquatic habitat. The research presented here centers on Montsechia vidalii, first recovered from lithographic limestone deposits in the Pyrenees of Spain...

The Asteraceae (sunflowers and daisies) are the most diverse family of flowering plants. Despite their prominent role in extant terrestrial ecosystems, the early evolutionary history of this family remains poorly understood. Here we report the discovery of a number of fossil pollen grains preserved in dinosaur-bearing deposits from the Late...

Melanoma is difficult to treat once it becomes metastatic. However, the precise ancestral relationship between primary tumors and their metastases is not well understood. We performed whole-exome sequencing of primary melanomas and multiple matched metastases from eight patients to elucidate their phylogenetic relationships. In six of eight patients, we found...

Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control...