In PNAS, Hansen et al. (1) document an observed planet-wide increase in the frequency of extremely hot months and a decrease in the frequency of extremely cold months, consistent with earlier studies (2). This analysis is achieved through aggregation of gridded monthly temperature measurements from all over the planet. Such...

Stone et al. (1) find that their analysis is unable to show a causal relation of local temperature anomalies, such as in Texas in 2011, with global warming. It was because of limitations in such local analyses that we reframed the problem in our report (2), separating the task of...

TorsinA is a membrane-associated AAA+ (ATPases associated with a variety of cellular activities) ATPase implicated in primary dystonia, an autosomal-dominant movement disorder. We reconstituted TorsinA and its cofactors in vitro and show that TorsinA does not display ATPase activity in isolation; ATP hydrolysis is induced upon association with LAP1 and...

Affinity improvement of proteins, including antibodies, by computational chemistry broadly relies on physics-based energy functions coupled with refinement. However, achieving significant enhancement of binding affinity (>10-fold) remains a challenging exercise, particularly for cross-reactive antibodies. We describe here an empirical approach that captures key physicochemical features common to antigen–antibody interfaces to...

G-protein–coupled receptor (GPCR) activity gradients evoke important cell behavior but there is a dearth of methods to induce such asymmetric signaling in a cell. Here we achieved reversible, rapidly switchable patterns of spatiotemporally restricted GPCR activity in a single cell. We recruited properties of nonrhodopsin opsins—rapid deactivation, distinct spectral tuning,...

There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune...

Nuclear pore complexes (NPCs) mediate the exchange of macromolecules between the cytoplasm and the nucleoplasm. Soluble nuclear transport receptors bind signal-dependent cargos to form transport complexes that diffuse through the NPC and are then disassembled. Although transport receptors enable the NPC's permeability barrier to be overcome, directionality is established by...

The complexity and depth of the relationships between the three domains of life challenge the reliability of phylogenetic methods, encouraging the use of alternative analytical tools. We reconstructed a gene similarity network comprising the proteomes of 14 eukaryotes, 104 prokaryotes, 2,389 viruses and 1,044 plasmids. This network contains multiple signatures...

TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than...

The herpesvirus virion is a multilayered structure consisting of a DNA-filled capsid, tegument, and envelope. Detailed reconstructions of the capsid are possible based on its icosahedral symmetry, but the surrounding tegument and envelope layers lack regular architecture. To circumvent limitations of symmetry-based ultrastructural reconstruction methods, a fluorescence approach was developed...

Bacillus subtilis is a plant-beneficial Gram-positive bacterium widely used as a biofertilizer. However, relatively little is known regarding the molecular processes underlying this bacterium's ability to colonize roots. In contrast, much is known about how this bacterium forms matrix-enclosed multicellular communities (biofilms) in vitro. Here, we show that, when B....

Targeted disruption of RIIβ-protein kinase A (PKA) in mice leads to a lean phenotype, increased nocturnal locomotor activity, and activation of brown adipose tissue. Because RIIβ is abundantly expressed in both white and brown adipose tissue as well as the brain, the contribution of neuronal vs. peripheral PKA to these...

Recent global proteomic and genomic studies have determined that lysine acetylation is a highly abundant posttranslational modification. The next challenge is connecting lysine acetyltransferases (KATs) to their cellular targets. We hypothesize that proteins that physically interact with KATs may not only predict the cellular function of the KATs but may...

The evolution of 13- and 17-y periodical cicadas (Magicicada) is enigmatic because at any given location, up to three distinct species groups (Decim, Cassini, Decula) with synchronized life cycles are involved. Each species group is divided into one 13- and one 17-y species with the exception of the Decim group,...

Compelling evidence from many animal taxa indicates that male genitalia are often under postcopulatory sexual selection for characteristics that increase a male’s relative fertilization success. There could, however, also be direct precopulatory female mate choice based on male genital traits. Before clothing, the nonretractable human penis would have been conspicuous...

Changes in genome architecture often have a significant effect on ecological specialization and speciation. This effect may be further enhanced by involvement of sex chromosomes playing a disproportionate role in reproductive isolation. We have physically mapped the Z chromosome of the major pome fruit pest, the codling moth, Cydia pomonella...

Rising atmospheric carbon dioxide (CO2) conditions are driving unprecedented changes in seawater chemistry, resulting in reduced pH and carbonate ion concentrations in the Earth’s oceans. This ocean acidification has negative but variable impacts on individual performance in many marine species. However, little is known about the adaptive capacity of species...

The intraflagellar transport (IFT) complex is an integral component of the cilium, a quintessential organelle of the eukaryotic cell. The IFT system consists of three subcomplexes [i.e., intraflagellar transport (IFT)-A, IFT-B, and the BBSome], which together transport proteins and other molecules along the cilium. IFT dysfunction results in diseases collectively...

Gene expression is controlled by coordinated action of many epigenetic mechanisms including covalent histone modifications. Although numerous recurrent patterns of colocalized histone modifications have been associated with specific gene expression states, interrelationships between individual modifications are largely unknown. Here, we analyze quantitative relationships between colocalized histone marks during embryonic stem...

The T helper type 2 (Th2) cytokine genes Il4, Il5, and Il13 are contained within a 140-kb region of mouse chromosome 11 and their expression is controlled by a locus control region (LCR) embedded within this locus. The LCR is composed of a number of DNase I–hypersensitive sites (HSs), which...