Browse Articles

Small CAG Repeat RNA Forms a Duplex Structure with Sticky Ends That Promote RNA Condensation

Escalation of genome defense capacity enables control of an expanding meiotic driver

From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via innovation of specificity factors. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to specificity factor innovations, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the genome defense capacity to control a recently expanded selfish gene in Drosophila melanogaster . Through a targeted RNAi screen for repressors of Stellate —a recently evolved meiotic driver—we identified a defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to elevate Aub and AGO3 expression, thereby escalating the silencing capacity of piRNA pathway to tame expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life, we envision that augmenting the defense capacity to quantitatively match selfish genes is a repeatedly employed defense strategy in evolution.

A synapse-specific refractory period for plasticity at individual dendritic spines

How newly formed memories are preserved while brain plasticity is ongoing has been a source of debate. One idea is that synapses which experienced recent plasticity become resistant to further plasticity, a type of metaplasticity often referred to as saturation. Here, we probe the local dendritic mechanisms that limit plasticity at recently potentiated synapses. We show that recently potentiated individual synapses exhibit a synapse-specific refractory period for further potentiation. We further found that the refractory period is associated with reduced postsynaptic CaMKII signaling; however, stronger synaptic activation fully restored CaMKII signaling but only partially restored the ability for further plasticity. Importantly, the refractory period is released after one hour, a timing that coincides with the enrichment of several postsynaptic proteins to preplasticity levels. Notably, increasing the level of the postsynaptic scaffolding protein, PSD95, but not of PSD93, overcomes the refractory period. Our results support a model in which potentiation at a single synapse is sufficient to initiate a synapse-specific refractory period that persists until key postsynaptic proteins regain their steady-state synaptic levels.

Molecular dynamics-guided reaction discovery reveals endoperoxide-to-alkoxy radical isomerization as key branching point in α-pinene ozonolysis

Funding rules that promote equity in climate adaptation outcomes

Many climate policies adopt improving equity as a key objective. A key challenge is that policies often conceive of equity in terms of individuals but introduce strategies that focus on spatially coarse administrative areas. For example, the Justice40 Initiative in the United States requires 518 diverse federal programs to prioritize funds for “disadvantaged” census tracts. This strategy is largely untested and contrasts with the federal government’s definition of equity as the “consistent and systematic fair, just and impartial treatment of all individuals (Executive Office of the President, Federal Register, 2021).” How well does the Justice40 approach improve equity in climate adaptation outcomes across individuals ? We analyze this question using a case study of a municipality that faces repetitive flooding and struggles to effectively manage these risks due to limited resources and public investment. We find that the way the Federal Emergency Management Agency implements the Justice40 Initiative can be an obstacle to promoting equity in household flood-risk outcomes. For example, in this case study, ensuring the majority of benefits accrue in “Justice40 Communities” does not reduce risk for the most burdened households, does not reduce risk-burden inequality, and produces net costs. In contrast, we design simple funding rules based on household risk burden that cost-effectively target the most burdened households, reduce risk-burden inequality, and accrue large net benefits. Our findings suggest that “disadvantaged community” indicators defined at coarse spatial scales face the risk of poorly capturing many climate risks and can be ineffective for meeting equity promises about climate-related investments.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants

The magnitude of legal wildlife trade and implications for species survival

The unsustainable use of wildlife is a primary driver of global biodiversity loss. No comprehensive global dataset exists on what species are in trade, their geographic origins, and trade’s ultimate impacts, which limits our ability to sustainably manage trade. The United States is one of the world’s largest importers of wildlife, with trade data compiled in the US Law Enforcement Management Information System (LEMIS). The LEMIS provides the most comprehensive publicly accessible wildlife trade database of non-the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) listed species. In total, 21,097 species and over 2.85 billion individuals were traded over the past 22 y (2000-2022). When LEMIS data are combined with CITES records, the United States imported over 29,445 wild species, including over 50% of all globally described species in some taxonomic groups. For most taxa, around half of the individuals are declared as sourced from the wild. Although the LEMIS provides the only means to assess trade volumes for many taxa, without any associated data on most wild populations, it is impossible to assess the impact on biodiversity, sustainability of trade, or any potential risk of pest or pathogen spread. These insights underscore the considerable underestimation of trade and the urgent need for other countries to adopt similar mechanisms to accurately record trade.

Large Language Models lack essential metacognition for reliable medical reasoning

Individualized temporal patterns drive human sleep spindle timing

Sleep spindles are cortical electrical oscillations considered critical for memory consolidation and sleep stability. The timing and pattern of sleep spindles are likely to be important in driving synaptic plasticity during sleep as well as preventing disruption of sleep by sensory and internal stimuli. However, the relative importance of factors such as sleep depth, cortical up/down-state, and temporal clustering in governing sleep spindle dynamics remains poorly understood. Here, we analyze sleep data from 1,025 participants, statistically modeling the simultaneous influences of multiple factors on moment-to-moment spindle production using a point process-generalized linear model framework. Results reveal fingerprint-like timing patterns, characterized by a refractory period followed by a period of increased spindle activity, which are highly individualized yet consistent night-to-night, with increased variability with age. Strikingly, short-term (<15 s) temporal patterns of past spindle history are the main determinant of spindle timing, accounting for over 70% of the statistical deviance—surpassing the contribution of factors such as cortical up/down-state (slow oscillation phase), sleep depth, and long-term history (15 to 90 s, including ~50 s infraslow activity). Short-term history has a statistically significant influence in over 98% of the population, suggesting it is a near-universal feature of spindle activity. Short-term history and slow oscillation phase exert independent effects on spindle timing. Our results establish a robust statistical framework to examine abnormalities in sleep spindle timing observed in neurological disorders and aging, as well as the relationship between individualized sleep spindle timing, cognition, and sleep stability.

Recent changes in ENSO’s impacts on the summertime circumglobal teleconnection and mid-latitude extremes

Reconciling Archean organic-rich mudrocks with low primary productivity before the Great Oxygenation Event

The organic carbon content of ancient rocks provides a fundamental record of the biosphere on early Earth. For over 50 y, the high organic content of Archean (>2.5 Ga) mudrocks has puzzled geologists and evolutionary biologists, because high biological primary productivity was unexpected for the nascent biosphere before the rise of O 2 . Here, we took a different approach to resolve this apparent paradox, by studying the accumulation rates of Archean organic-rich mudrocks. We evaluated the sedimentation rates of three sections of the Mount McRae Shale and Jeerinah Formation (2.68 to 2.48 Ga, Pilbara Craton, Australia) with new and recently published U–Pb zircon ages from intraformational ash beds. For comparison, we compiled Phanerozoic (<500 Ma) data from comparable depositional settings and developed an idealized model that considers the sedimentation rates for predicting rock organic content. We found that organic-rich Archean mudrocks were deposited under exceptionally low sedimentation rates (~1 m/Ma), in sharp contrast to organic-rich rocks from the Phanerozoic Eon (10 to 100 m/Ma). Constrained by observations, model results indicated that the Archean data reflect low primary productivity (~100-fold lower than during the Phanerozoic) and enhanced preservation under anoxic conditions, with the principal control on organic carbon content provided by dilution with inorganic sediment. Thus, the high organic carbon content which is typically attributed to high productivity instead reflects slow accumulation, high preservation, and minimal inorganic dilution—reconciling the geological evidence with a slow carbon cycle cadence during Archean time.

Interplay of p23 with FKBP51 and their chaperone complex in regulating tau aggregation

Abstract The pathological deposition of tau and amyloid-beta into insoluble amyloid fibrils are pathological hallmarks of Alzheimer’s disease. Molecular chaperones are important cellular factors contributing to the regulation of tau misfolding and aggregation. Here we reveal an Hsp90-independent mechanism by which the co-chaperone p23 as well as a molecular complex formed by two co-chaperones, p23 and FKBP51, modulates tau aggregation. Integrating NMR spectroscopy, SAXS, molecular docking, and site-directed mutagenesis we reveal the structural basis of the p23-FKBP51 complex. We show that p23 specifically recognizes the TPR domain of FKBP51 and interacts with tau through its C-terminal disordered tail. We further show that the p23-FKBP51 complex binds tau to form a dynamic p23-FKBP51-tau trimeric complex that delays tau aggregation and thus may counteract Hsp90-FKBP51 mediated toxicity. Taken together, our findings reveal a co-chaperone mediated Hsp90-independent chaperoning of tau protein.

Human and primate categorical understanding of color

Selective utilization of medicinal polysaccharides by human gut Bacteroides and Parabacteroides species

The value of returning a sample of the Martian atmosphere

The elemental and isotopic abundances of major species in the Martian atmosphere have been determined, but analyses often lack sufficient precision, and those of minor and trace species are frequently not well known. Many important questions about the evolution and current state of Mars require the kind of knowledge that can be gained from analysis of a returned sample of the Martian atmosphere. Key target species include the noble gases, nitrogen, and various species containing carbon, hydrogen, and oxygen, such as methane. More detailed analyses will no doubt provide measurements of other species that will allow insights of their own. These volatiles can constrain the origin of the Martian atmosphere, exchange of volatiles between the surface and interior, polar processes, and (in the case of methane) the possibility of extant biology on Mars.

Potential plant extinctions with the loss of the Pleistocene mammoth steppe

Abstract During the Pleistocene-Holocene transition, the dominant mammoth steppe ecosystem across northern Eurasia vanished, in parallel with megafauna extinctions. However, plant extinction patterns are rarely detected due to lack of identifiable fossil records. Here, we introduce a method for detection of plant taxa loss at regional (extirpation) to potentially global scale (extinction) and their causes, as determined from ancient plant DNA metabarcoding in sediment cores (sedaDNA) from lakes in Siberia and Alaska over the past 28,000 years. Overall, potential plant extinctions track changes in temperature, in vegetation, and in megafauna extinctions at the Pleistocene-Holocene transition. Estimated potential plant extinction rates were 1.7–5.9 extinctions per million species years (E/MSY), above background extinction rates but below modern estimates. Major potential plant extinction events were detected around 17,000 and 9000 years ago which lag maximum vegetation turnover. Our results indicate that herbaceous taxa and taxa contributing less to beta diversity are more vulnerable to extinction. While the robustness of the estimates will increase as DNA reference libraries and ancient sedaDNA data expand, the available data support that plants are more resilient to environmental changes than mammals.

Parameter study of a 5G array antenna at 28 GHz

Characterizing progenitor cells in developing and injured spinal cord: Insights from single-nucleus transcriptomics and lineage tracing

Various mature tissue-resident cells exhibit progenitor characteristics following injury. However, the existence of endogenous stem cells with multiple lineage potentials in the adult spinal cord remains a compelling area of research. In this study, we present a cross-species investigation that extends from development to injury. We used single-nucleus transcriptomic sequencing and genetic lineage tracing to characterize neural cells in the spinal cord. Our findings show that ciliated ependymal cells lose neural progenitor gene signatures and proliferation ability following the differentiation of NPCs within the ventricular zone. By combining single-nucleus transcriptome datasets from the rhesus macaque spinal cord injury (SCI) model with developmental human spinal cord datasets, we revealed that ciliated ependymal cells respond minimally to injury and cannot revert to a developmental progenitor state. Intriguingly, we observed astrocytes transdifferentiating into mature oligodendrocytes postinjury through lineage tracing experiments. Further analysis identifies an intermediate-state glial cell population expressing both astrocyte and oligodendrocyte feature genes in adult spinal cords. The transition ratio from astrocytes into oligodendrocytes increased after remodeling injury microenvironment by functional scaffolds. Overall, our results highlight the remarkable multilineage potential of astrocytes in the adult spinal cord.

A multi-model study to inform the United States’ 2035 NDC

Chemical signatures of social information in Barbary macaques

Abstract Primates are well-known for their complex social lives and intricate social relationships, which requires them to obtain and update social knowledge about conspecifics. The sense of smell may provide access to social information that is unavailable in other sensory domains or enhance the precision and reliability of other sensory cues. However, the cognition of social information in catarrhine primates has been studied primarily in the visual and auditory domain. We assessed the social information content of body odor in a catarrhine primate, the Barbary macaque ( Macaca sylvanus ), in three semi-free ranging groups at Affenberg Salem, Germany. In particular, we related socially relevant attributes (identity, genetic relatedness, rank, sex, age, group membership) to chemical profiles of body odor. We applied non-invasive active sampling via thermal desorption tubes and analyzed samples by gas chromatography–mass spectrometry. We found robust evidence for individual odor signatures and limited support for kin signatures. Chemical profiles were also related to group membership, but little to rank, sex or age. The detected associations between chemical profiles and socially relevant attributes form the theoretical foundations for olfactory information transfer, highlighting the potential of body odor to provide valuable social information in this highly visually oriented primate.