Browse Articles

Promoter identity shapes splicing outcomes and fidelity

Pair living emerged early in placental mammals

It is widely assumed that the first placental mammals were solitary. Here, we tested this assumption and which ecological and life history factors are related to mammalian social organization. We compiled a comprehensive database by reviewing over 14,000 primary peer-reviewed publications on the social organization of the 5,390 extant placental mammal species. We found empirical data for 726 species across 1,473 populations: 353 populations were primarily solitary, 250 populations pair living, and 870 populations group living. Notably, 367 species (51%) and 583 populations (40%) exhibited intraspecific variation in social organization. Using a Bayesian phylogenetic framework that incorporates intraspecific variation, we show that the ancestral placental mammal was mainly but not exclusively solitary, displaying intraspecific variation. Pair living was estimated to account for approximately 26% of ancestral social organization. Phylogeny explained most of the variation between species, while life history and ecology were less important. Our analysis found that the ecology and life history of extant solitary and pair-living mammals is very similar and different from those of group-living mammals. Our results revise prevailing theories of mammalian social evolution, revealing that pair living emerged early, shifting the focus of studying mammalian social evolution from the origins of pair living to the origins of group living.

Single-cell profiling decodes patagium development in gliding mammal

Science for America’s next 250 years

All-fiber random Kerr optical frequency combs

Proteolytic activation of c-MYC facilitated by DOT1L

c-MYC is a key regulator of growth and metabolism. Functional and molecular cooperation between the H3K79 methyltransferase DOT1L and c-MYC has been reported in several human cancer types, but the nature of their interaction remains undefined. We demonstrate that DOT1L and MYC [Myc and Mondo-like (MML-1) in Caenorhabditis elegans ] coregulate genes in the nematode model and mammalian cancer cells. Moreover, both c-MYC and MML-1 exhibit cleavage products facilitated by DOT1L function. Surprisingly, we found a similarity between a conserved sequence in DOT1 proteins and the DDI-family protease catalytic motif. We characterize a c-MYC sequence preceding the DNA-binding domain as a site of nuclear proteolytic cleavage, demonstrate its importance for transcription activation by c-MYC, and propose that c-MYC is activated by a protease, as previously reported for Nuclear factor erythroid 2-related factor (NRF) and SREBP transcription factors. Our results suggest that DOT1L may activate c-MYC and other transcription factors in the nucleus by acting as a protease.

Enhancing the longevity of lithium-manganese-rich layered oxides by promoting oxygen redox reversibility

Psychological inoculation against climate doom

Individuals encounter “climate doom,” extreme portrayals of climate change, on social media. While climate doom may be intended to motivate action, it may also be perceived as manipulative or elicit hopelessness. Yet, no research has examined whether psychological inoculation helps to improve recognition of climate doom or influences engagement with it on social media. In this preregistered study ( n = 521), we tested whether inoculation improves discernment of climate doom and influences engagement with it by collecting behavioral data using a social media simulator. We find that inoculation substantially improves discernment of climate doom and that this is due to increased perceived manipulation of doom messaging specifically ( d = 0.68). There was no interaction between the inoculation condition and political leaning and while higher perceived manipulation of doom content predicted lower behavioral intentions, inoculation did not moderate this relationship. Inoculation increased engagement, particularly disliking and flagging of doom content, and decreased sharing. Overall, our results should lead climate communicators to reconsider doom messaging as a mobilization strategy and demonstrate that inoculation is an effective tool for increasing recognition of, and critical engagement with, climate doom across the political spectrum.

A Lactate–H4K12la–HDAC1 epigenetic axis governs microglial state transitions during experimental autoimmune encephalomyelitis in female mice

Hypermutability of integrated sequences of viral origin in a chlorarachniophyte

Mutations provide the raw material for evolution, but mutation rates are not uniform across genomes. Using a mutation accumulation experiment in the marine phytoplankton Bigelowiella natans , we found extreme local variation in mutation rate: over 1,000-fold differences across its nuclear genome. While the baseline single-nucleotide mutation rate is approximately 3.5 × 10 –10 per site per generation, a common value for unicellular species, two genomic regions derived from integrated viruses exhibit strikingly elevated rates of about 6 × 10 –7 . These two regions show a distinctive mutational signature with almost exclusively T/A→C/G transitions, a pattern also found in other non-eukaryote-derived sequences in B. natans , contrary to the usual GC to AT mutation bias. Notably, hypermutation occurs only on TpA dinucleotides, and only in a subset of experimental lines, suggesting a regulated process rather than random genomic instability. We propose that B. natans targets invading DNA through localized hypermutation, reminiscent of deamination-based antiviral defense systems in animals. This prompts the idea of genome editing as a recurring immune strategy in eukaryotes.

Human wastewater contamination drives the emergence of multidrug-resistant bacteria in the Galápagos marine ecosystem

The human hippocampus can pattern separate memories by meaning

Hippocampal pattern separation is a neural operation supporting mnemonic discrimination of highly similar memories by orthogonalizing neural inputs into nonoverlapping representations. In humans, pattern separation is thought to support the specificity of episodic memories. Recent neuroimaging studies suggest that the hippocampus can also access and manipulate semantic information. However, it is unclear whether the hippocampus can pattern separate highly similar semantic representations. Here, we tested multiple neural and behavioral signatures of pattern separation using high-resolution functional MRI during a well-established memory discrimination task where we manipulated semantic similarity in a multidimensional conceptual space using word-embeddings. Thirty young adults (Mage = 21.1, 16 females) saw adjective-noun phrases (e.g., “exotic zoo”) that were later repeated exactly as before or modified with semantically similar adjectives (e.g., “strange zoo”). Crucially, we presented exact and modified repeats both during an incidental encoding and a two-choice recognition phase, where mnemonic discrimination was assessed. Consistent with pattern separation, we found attenuated repetition suppression for modified repeats in repetition sensitive clusters of the hippocampal head, which was evident at both high and low levels of similarity with no difference between two a priori defined similarity bins. In addition, within participants, the neural signature of pattern separation was associated with mnemonic discrimination at recognition. Finally, clusters sensitive to repetitions during encoding differentiated lures from foils at recognition. These results suggest that hippocampal pattern separation is triggered by fine-grained differences in meaning and supports the creation of highly specific representations of memories overlapping in semantic memory.

Linking long-range surface-induced mobility enhancement and intrinsic fragility of polymer glasses

Distinct repair processes produce APOBEC-induced deletions, tandem substitutions, and complex mutations in yeast and human cells

APOBEC3A (A3A) and APOBEC3B (A3B) induce single base substitution signatures SBS2 and SBS13, which are composed of C>T and C>G mutations, respectively, at T C W sequences in >50% of sequenced tumors. However, few driver mutations have been attributed to APOBEC-induced SBS mutations. Although SBS2 and SBS13 have been associated with additional mutation types, the contribution of APOBECs to non-SBS mutations and the mechanisms that generate noncanonical APOBEC-induced mutations are uncharacterized. Here, we show that A3A expression generates non-SBS mutations including C deletions within TT C motifs, CC>TT and T C >AT/CT/GT dinucleotide variants (DNVs), distinct classes of paired SNV-SNV events, and complex insertion-SBS mutations in a yeast model system. Furthermore, we found that endogenous APOBEC expression in breast cancer cell lines is a significant driver of all these mutation types. In addition, we show that C deletions and complex insertion-SBS mutations within TT C motifs occur primarily by strand slippage during translesion synthesis (TLS) bypass of APOBEC-induced, UNG-dependent, abasic sites. Additionally, we found that CC>TT and T C >AT/CT/GT DNVs, which comprise the APOBEC-associated DBS11 signature, are generated by dU templating and TLS bypass of APOBEC-induced abasic sites, respectively. We also present data indicating that phased APOBEC-induced SNV-SNV mutations are produced during abasic site bypass by TLS. Analysis of WGS data from cultured human cells and tumors indicates that similar mechanisms generate these noncanonical APOBEC-induced mutations in human cancers, providing additional means by which APOBECs could contribute to carcinogenesis and therapeutic resistance.

Transitions between persistent climate–carbon regimes coincide with elevated Phanerozoic biosphere vulnerability

Abstract Linking abiotic forcing to coherent biotic responses over Phanerozoic time remains difficult to quantify because both environmental drivers and biological dynamics are heterogeneous, irregularly sampled, and affected by proxy and geochronological uncertainty. Here we introduce a regime-based description of the climate–carbon system in which Phanerozoic evolution is organized into a small number of recurring, long-lived mega-climate states separated by relatively sharp transitions. Using recurrence diagnostics on paired carbon and oxygen stable isotope records, together with complementary early-warning indicators, we identify five persistent regimes and their boundaries. We interpret the resulting structure with a conceptual climate–carbon cycle model that admits multiple coexisting equilibria, providing a mechanistic basis for state changes that switch between stable attractors under changing environmental forcings and perturbations. We connect these results to a biosphere vulnerability metric that incorporates biotic turnover with sample-standardized global diversity to show that vulnerability is systematically elevated near major regime transitions. These results suggest that transitions between persistent climate–carbon attractors provide a dynamical context for why some perturbation intervals coincide with heightened biospheric stress, beyond what is expected from more gradual background environmental changes alone.

Anterior and posterior retrosplenial cortex employ distinct strategies for egocentric–allocentric transformation in spatial coding

The transformation from egocentric to allocentric spatial coordinates is a critical process in neural spatial computation. The retrosplenial cortex (RSC) is hypothesized to serve as a central hub for this conversion, bridging egocentric perceptual inputs with allocentric representations in hippocampal and parahippocampal circuits. However, the regional and projection-specific organization of this function within the RSC remains poorly defined. In this study, we employed two-photon calcium imaging in freely navigating mice to dissect RSC spatial coding. We identified functional differences along the anteroposterior axis: the anterior RSC (aRSC) was predominantly characterized by egocentric boundary vector (EBV) coding, whereas the posterior RSC (pRSC) exhibited enhanced allocentric boundary representation. And it reveals that egocentric boundary vector cells (EBVCs) in the pRSC possess broader egocentric tuning than those in the aRSC. Despite this, pRSC shows tighter integration of allocentric head direction information, which converges specifically onto specialized conjunctive cells, resulting in a more selective boundary representation. Crucially, this work identifies functional differences along the RSC, where spatial coding transforms from more egocentric in aRSC to more allocentric in pRSC. Furthermore, it defines a specialized RSC to medial entorhinal cortex (MEC) projection pathway that is enriched for these global-tuned, conjunctive neurons, providing the MEC with a highly integrated, world-referenced spatial signal for constructing cognitive maps. Our findings elucidate a functional variance and projection-specific circuitry within the RSC, providing experimental evidence for models of hierarchical spatial processing.

Vibrio cholerae-synthesized tryptophan activates innate immune signaling in enteroendocrine cells via phosphorylation of the nuclear receptor ultraspiracle

The global demand and potential public health impact of oral antiviral treatment stockpile for influenza pandemics

Antiviral drugs are among the few countermeasures available during the critical interval between the emergence of a novel influenza pandemic and vaccine availability. Antiviral stockpiling is a key pandemic preparedness measure, yet existing stockpiling estimates vary widely and rest on outdated assumptions about healthcare-seeking behavior and drug-specific effectiveness—limitations that the COVID-19 pandemic and recent clinical trial evidence have made untenable. We developed a multiscale transmission model incorporating heterogeneous healthcare-seeking behavior and direct clinical estimates of antiviral transmission risk reduction to estimate country-specific demand and mortality impact across four pandemic scenarios in 186 countries. We find that baloxavir marboxil (BXM), due to its transmission-reducing potential, could avert 37 to 68% of mean pandemic deaths in the first epidemic wave, approximately double the impact of oseltamivir, while requiring a mean stockpile approximately 5 to 10% smaller (7 to 34% of the population, compared to 28 to 36% for oseltamivir). Uncertainty in viral load dynamics and transmission reduction benefits from clinical trials means that BXM’s impact could vary, but sensitivity analyses consistently suggest that BXM is likely to be more effective than oseltamivir. Under limited drug availability, priority should be given to treatment over postexposure prophylaxis. Although drug rationing for high-mortality populations (e.g., elderly) can substantially reduce BXM demand, doing so leads to greater total pandemic deaths. Critically, each week of delay in initiating antiviral distribution erodes impact by up to 3% of averted deaths, meaning that antiviral stockpiles must be accompanied by rapid deployment infrastructure to deliver their potential impact.

Plastron-mediated direct H2O2 synthesis

Abstract Gas-liquid-solid catalytic reactions are ubiquitous in the chemical industry and environmental chemistry. The efficacy of these reactions is constrained by the inherently low solubility of gases in liquids and poor mass transfer of reactants/products to/from the catalyst surface. We show that a gas layer trapped on a hydrophobic catalyst (plastron) substantially enriches local gas concentration, alleviating mass-transfer limitations and accelerating reaction rates. Using gold-palladium catalyst for direct hydrogen peroxide synthesis as a model, hydrogen/air plastrons on hydrophobic organosilica yield up to a 20-fold rate enhancement without sub-ambient temperatures, high pressures, or alcohol co-solvents. Combined with selective adsorption of butanethiol on gold-palladium nanoparticles, plastrons further inhibit undesirable decomposition pathways of hydrogen peroxide by repelling water from the catalytic center, eliminating the need for acid and halide promoters. This strategy serves as a new class of heterogeneous catalysts for gas-liquid-solid reactions, offering a route to chemical processes with reduced cost and carbon footprint.

The cortical scene processing network emerges in infancy, prior to independent navigation experience

Sighted people rely on vision to recognize and navigate the local environment. By adulthood, human cortex contains at least three regions that respond selectively to visual scene information, but it remains unknown when or how these regions develop. One hypothesis is that development of scene selectivity depends on passive exposure to the low-level visual statistics of scenes. Another hypothesis is that development depends on active experience using scene information to plan and guide navigation. Using ecological momentary assessment, we measured the quantity of forward-facing ego-motion and active navigation that infants experienced in the first months of life. By age 5 mo, infants cumulatively experienced around 340 h of forward facing ego-motion, almost exclusively passive. Next we used functional MRI in infants aged 2 to 9 mo to measure neural responses to scenes. Awake infants watched videos of ego-motion through real-world scenes, as well as videos of faces, objects, and scrambled videos. We found stronger responses to scenes than control conditions in the location of all three cortical scene regions. Responses in infant scene regions a) were dissociable from those in nearby face and object regions; b) could not be fully explained by low-level visual features; and c) were found even in subsamples of infants with no locomotor experience. Thus, the basic signature of scene selectivity emerges prior to independent navigation and with limited passive visual exposure to the diagnostic visual statistics of scenes.