Crop pathogens often lack exclusive access to their host and must interact with plants concurrently engaged with numerous other symbionts. Here, we demonstrate that the colonization of hosts by plant-mutualistic mycorrhizal fungi can indirectly induce transcriptional responses of a major plant parasite, the nematode Globodera pallida, via a modified host resource profile. A shift in the resource profile

Neutrophils are the most abundant circulating leukocyte population that play critical roles in neuroinflammation following central nervous system (CNS) injury. CD177, a glycoprotein on neutrophils, is emerging as an important immune regulator which can fundamentally affect multiple human inflammatory diseases. However, the role and regulatory mechanism of CD177 glycobiology of neutrophils in neuroinflammation

Mechanical snapping instabilities are leveraged by natural systems, metamaterials, and devices for rapid sensing, actuation, and shape changes, as well as to absorb impact. In all current forms of snapping, shapes deform in the same direction as the exerted forces, even though there is no physical law that dictates this. Here, we realize countersnapping mechanical structures that respond in the opposite

Elevated brain levels of the essential metals manganese (Mn), copper, or iron induce motor disease. However, mechanisms of metal-induced motor disease are unclear and treatments are lacking. Elucidating the mechanisms of Mn-induced motor disease is particularly important because occupational and environmental Mn overexposure is a global public health problem. To address this, here we combined unbiased

Mitochondrial DNA (mtDNA) replication requires a steady supply of deoxyribonucleotides (dNTPs), synthesized de novo by ribonucleotide reductase (RNR). In nondividing cells, RNR consists of RRM1 and RRM2B subunits. Mutations in RRM2B cause mtDNA depletion syndrome, linked to muscle weakness, neurological decline, and early mortality. The impact of RRM2B deficiency on dNTP pools in nondividing tissues

Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have been used extensively to control some major crop pests, but their benefits decrease when pests evolve resistance. Better understanding of the genetic basis of resistance is needed to effectively monitor, manage, and counter pest resistance to Bt crops. Resistance to Bt proteins in at least

Forming and forgetting memories shape our self-awareness and help us face future challenges. Therefore, understanding how memories are formed and how different memories interact in the brain is important. Previous studies have shown that thirsty flies sense humidity through ionotropic receptors, which help them locate water sources. Here, we showed that thirsty flies can be trained to associate specific

Ischemic retinal diseases are major causes of blindness worldwide and are characterized by pathological angiogenesis. Epigenetic alterations in response to metabolic shifts in endothelial cells (ECs) suffice to underlie excessive angiogenesis. Lactate accumulation and its subsequent histone lactylation in ECs contribute to vascular disorders. However, the regulatory mechanism of establishing and sustaining

Although cochlear implants (CIs) provide valuable auditory information to more than one million profoundly deaf patients, these devices remain inadequate in conveying fine timing cues. Early deaf patients in particular struggle to use interaural time differences (ITDs) for spatial hearing and auditory scene analysis. Why CI patients experience these limitations remains controversial. One possible explanation

Cellular signaling processes can elicit powerful responses and may need to be amplified to be efficient or dampened to prevent overstimulation. Therefore, they often involve autoregulatory feedbacks. Receptor kinase signaling pathways are abundant in plants, where they convey the presence of both exogenous and endogenous ligands. Among them, endogenous CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide

Awareness of the threats of climate change is causing distress in increasingly documented ways, with youth particularly affected. Experiences such as climate distress and eco-anxiety have implications for the health and well-being of societies and economies, including individuals' mental health and future planning, as well as their agency beliefs. Here, we show in a large sample of US youth (n = 2

Bedaquiline is the cornerstone of a new regimen for the treatment of drug-resistant tuberculosis. However, its clinical use is threatened by the emergence of bedaquiline-resistant strains of Mycobacterium tuberculosis. Bedaquiline targets mycobacterial ATP synthase but the predominant route to clinical bedaquiline resistance is via upregulation of the MmpS5L5 efflux pump due to mutations that inactivate

There is broad consensus that AI presents risks, but considerable disagreement about the nature of those risks. These differing viewpoints can be understood as distinct narratives, each offering a specific interpretation of AI's potential dangers. One narrative focuses on doomsday predictions of AI posing long-term existential risks for humanity. Another narrative prioritizes immediate concerns that

The 2024 Nobel Prize in Physics recognizes breakthroughs contributing to the emergence of a new understanding of the computations that underlie human intelligence, with profound implications for artificially intelligent systems. John Hopfield and Geoffrey Hinton played seminal roles in these breakthroughs. I begin by characterizing the scientific context in which the new understanding of intelligence

Herpesviruses encode conserved protein kinases (CHPKs) that target cellular cyclin-dependent kinase (CDK) phosphorylation sites; thus, they are termed viral CDK-like kinases. Tyrosine 15 in the GxGxxG motifs of CDK1 and CDK2, whose phosphorylation down-regulates their catalytic activities, is conserved in the corresponding motifs of CHPKs. We found that CHPK UL13, the corresponding Tyr-162 in herpes

Mimicking the interconvertible carbon allotropes of 2-dimensional (2D) graphene and 1-dimensional (1D) carbon nanotubes (CNTs), herein we report the in situ transformation of 2D π-conjugated covalent organic frameworks (COFs) sheet into 1D nanotubular structures via self-assembly the sheets at solvent interfaces. The facile “roll-sheets” self-assembly resulted in coaxial nanotubes with uniform cross-sectional

Various pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connections during early development. Animal models of ASD exhibit an abundance of synapses in different brain regions, which is strongly linked to the appearance of ASD behaviors. Overexpression of CD47 on neurons

Maternal separation (MS), a chronic stress event in early life, impairs myelination in the prefrontal cortex (PFC) and leads to PFC cognitive disorders. It remains largely unclear how such deficits are mediated. Here, we show that peripheral CD4 + T cells play an essential role in mediating the destructive effects of MS on medial prefrontal cortical (mPFC) myelination and cognitive functions in mice

Mitochondrial DNA (mtDNA) stability, essential for cellular energy production, relies on DNA polymerase gamma (POLγ). Here, we show that the POLγ Y951N disease-causing mutation induces replication stalling and severe mtDNA depletion. However, unlike other POLγ disease-causing mutations, Y951N does not directly impair exonuclease activity and only mildly affects polymerase activity. Instead, we found

Most bioorthogonal photouncaging reactions preferentially occur in polar environments to accommodate biological applications in the aqueous cellular milieu. However, they are not precisely designed to chemically adapt to the diverse microenvironments of the cell. Herein, we report a hydrophobic photouncaging reaction with tailored photolytic kinetics toward solvent polarity. Structural modulations

Biobanks advance biomedical and clinical research by collecting and offering data and biological samples for numerous studies. However, the impact of these repositories varies greatly due to differences in their purpose, scope, governance, and data collected. Here, we computationally identified 2,663 biobanks and their textual mentions in 228,761 scientific articles, 16,210 grants, 15,469 patents,

Many enteric viruses benefit from the microbiota. In mice, microbiota depletion reduces infection by noroviruses and picornaviruses. However, Reovirales viruses are outliers among enteric viruses. Rotavirus infection is inhibited by bacteria, and we determined that several reovirus strains have enhanced replication following microbiota depletion. Here, we focused on an isogenic pair of reoviruses that

CXCR3 is a chemokine receptor for three ligands: CXCL9, CXCL10, and CXCL11. Accumulating evidence, including data presented here, suggests that the interaction between CXCL9/CXCL10 and CXCR3 not only attracts CXCR3+ T cells but also promotes the induction of IFNγ- high effector/cytotoxic CD4+ and CD8+ T cells, establishing a CXCL9/10-CXCR3-IFNγ self-amplifying cycle that promotes efficient cancer cell

Human ClpP protease contributes to mitochondrial protein quality control by degrading misfolded proteins. ClpP is overexpressed in cancers such as acute myeloid leukemia (AML), where its inhibition leads to the accumulation of damaged respiratory chain subunits and cell death. Conversely, hyperactivating ClpP with small-molecule activators, such as the recently discovered ONC201, disrupts mitochondrial

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naïve to H5

Trait regression and loss have occurred repeatedly in numerous lineages in response to environmental changes. In parasitoid wasps, a megadiverse group of hymenopteran insects, yolk protein reduction or loss has been observed in many species, likely linked to the transition from ectoparasitism to endoparasitism. However, the genetic basis of this trait and the impact of its loss on genome evolution

Theory predicts that well-adapted populations may evolve mechanisms to counteract the inevitable influx of deleterious mutations. While mutational robustness can be directly selected in the laboratory, evidence for its spontaneous evolution during general adaptation is mixed. Moreover, whether robustness evolves to include pleiotropic effects remains largely unexplored. Here, we studied the effects

The concept that proteins are selected to fold into a well-defined native state has been effectively addressed within the framework of energy landscapes, underpinning the recent successes of structure prediction tools like AlphaFold. The amyloid fold, however, does not represent a unique minimum for a given single sequence. While the cross- β hydrogen-bonding pattern is common to all amyloids, other

CD20 is a four-transmembrane protein expressed at the surface of B cells from late pro-B cells to memory B cells, with the exception of plasma cells. Its expression pattern makes it an attractive therapeutic target for different B cell malignancies and autoimmune diseases. Despite the clinical success of CD20-targeting antibodies, the biology of the CD20 protein is still not well understood. We investigated

Translational research suggests that the basolateral part of the amygdala (BLA) computes some of the core processes underlying social preferences, but its precise role in prosocial choice remains unclear. We hypothesize that the human BLA is not necessary for prosocial behavior per se, but fine-tunes the degree of prosociality as a function of the social distance between actor and recipient of a prosocial

Enchondromas are common bone tumors composed of chondrocytes originating from growth plate cells which can progress to malignant chondrosarcoma. Mutations in the genes encoding isocitrate dehydrogenase (IDH1 and IDH2) are identified in a large proportion of these tumors. IDH enzymes convert isocitrate to alpha-ketoglutarate (α-KG), an essential component of the citric acid cycle. While mutant IDH enzymes

As in many diploid organisms with genetic sex determination, haploid-dominant organisms have also evolved sex chromosomes or extensive genomic regions that lack genetic recombination. An understanding of sex chromosome evolution should explain the causes and consequences of such regions in both diploids and haploids. However, haploids have been little studied, even though differences from sex chromosomes

Definitions of sustainability commonly stress both systemic continuity and equality over time. However, the degree to which these two sides of sustainability might be related has not been systematically investigated. Recent theoretical and methodological insights have provided archaeologists with new tools for investigating sustainability in premodern societies. Here, we use Gini coefficients on residence

Indoor residual spraying (IRS) is one of the core vector control interventions available to malaria control programs. Normative and scientific guidance has long held that very high IRS coverage (at least 80 to 85% houses sprayed) is necessary to provide community protection, but there is little evidence backing these recommendations, in large part due to the operational and ethical concerns that conducting

The urethra is considered a passive conduit for urine. Here, we reveal a surprising multicellular signaling pathway guiding the urethra’s dynamic response to an invading pathogen. Using a genetic approach in female mice, we deposited uropathogenic Escherichia coli into the distal urethra to establish a model of ascending urinary tract infection that progresses to the bladder within 4 h. We show that

Here, we assess the extent to which land use relating to food acquisition (farming, herding, foraging) and associated value regimes shaped past economic inequality. We consider the hypothesis that land-use systems in which production was limited by heritable material wealth (such as land) sustained higher levels of inequality than those limited by (free) human labor. We address this hypothesis using

From Rousseau onward, scholars have identified the transition to sedentary agriculture as crucial to the history of wealth inequality. Here, using the GINI project’s global database on disparities in residential size, we examine the effects of important innovations in plant cultivation, animal husbandry, and traction on wealth inequality. Over a series of regional case studies, we find no evidence

Defining wealth broadly to include wealth in people, relational connections, and material possessions, we examine the prehistory of wealth inequality at the level of the residential units using the consistent proxy of Gini coefficients calculated across areas of contemporaneous residential units. In a sample of >1,100 sites and > 47,000 residential units spanning >10,000 y, persistent wealth inequality

The Gini coefficient is a statistical measure commonly used to characterize distributions of socioeconomic quantities. Archaeologists and social scientists have recently adopted this method to analyze ancient inequality by targeting specific proxy variables (e.g., residential unit size, burial data, etc.). Variations in the Gini are then examined in relation to key factors such as time, geography,

Scholars are divided over the long-term effects that war has had on inequality. Some have argued that conflict grows the gap between rich and poor. Others counter that violence levels out wealth differences. The GINI Project Database is a large global sample of archaeological data on house sizes created to investigate what factors influenced economic inequality over long periods of time, including

Renal ischemia–reperfusion injury (IRI) is a common complication in several clinical scenarios including kidney transplantation. Mannan-binding lectin-associated serine proteinase (MASP)-2 is essential for activation of the complement lectin pathway, which has been implicated in the pathogenesis of renal IRI and therefore represents a potential therapeutic target. We developed a new, affinity-enhanced

The structure of the environment includes more horizontal and vertical (i.e. cardinal) orientations than oblique orientations, meaning that edges tend to be aligned with or perpendicular to the direction of gravity. This bias in the visual scene is associated with a bias in visual sensitivity in adults. Although infants must learn to function in this biased environment, their immature motor control

Marine heatwaves are extreme climatic events consisting of persistent periods of warm ocean waters that have profound impacts on marine life. These episodes are becoming more intense, longer, and more frequent in response to anthropogenic global warming. Here, we provide a comprehensive and quantitative assessment on the role of global warming on marine heatwaves. To do so, we construct a counterfactual

Specialized metabolism plays a central role in how plants cope with both biotic and abiotic stresses in order to survive and reproduce within dynamic and challenging environments. One recently described class of plant-specific, ribosomally synthesized, and posttranslationally modified peptides are the burpitides, which are characterized by the installation of distinct sidechain macrocycles by enzymes

Humans often live in neighborhoods, nested socio-spatial clusters within settlements of varying size and population density. In today’s cities, neighborhoods are often characterized as relatively homogenous and may exhibit segregation along various socioeconomic dimensions. However, even within neighborhoods of similar social or economic status, there is often residential disparity, which in turn impacts

We address three basic issues regarding the long-term dynamics of inequality in society. First, we consider the interpretation of residence sizes in socioeconomic terms by comparing statistical patterns extracted from the Global Dynamics of Inequality (GINI) Project database with those from the 21st-century United States. Second, we examine the degree to which the size and productivity of human networks

Understanding the relationship between inequality and economic growth is a critical science problem that hinders sustainable development. In 1955, Simon Kuznets hypothesized that rising economic growth raises inequality, which levels off as that growth continues. Kuznets’ “curve,” which is a cornerstone of development economics, was based on data from a small sample of rich capitalist economies. Here

Long-entrenched grand narratives have tied inequality in large human aggregations to generally linear trends, a direct outcome of domestication, then fostered by population growth and/or stepped scalar transitions in the hierarchical complexity of human institutions. This general pattern has been argued to short-circuit or reverse only in the context of cataclysmic disasters or societal breakdowns

CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptides have emerged as key regulators of plant–microbe interactions, including arbuscular mycorrhizal (AM) symbiosis. Here, we identify Medicago truncatula CLE16 as a positive regulator of AM symbiosis. MtCLE16 is expressed in root cells colonized by AM fungi (AMF) and its overexpression within colonized tissues increases arbuscule abundance by finetuning

Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ). Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis. Here, we report the molecular design

Antibody–drug conjugates (ADCs) are a rapidly developing therapeutic approach in cancer treatment that has shown remarkable efficacy in breast cancer. Despite the promising efficacy of anti-HER2 ADCs, many patients are still experiencing disease progression under treatment. Here, by analyzing the transcriptome data from patient-derived organoid models, I-SPY2 trial, and resistant cell lines, we identified

Montane ecosystems are crucial for maintaining global biodiversity and function that sustain life on our planet. Yet, these ecosystems are highly vulnerable to changing temperatures and may undergo critical transitions under ongoing climate change. What we do not know is to what extent montane biodiversity and ecosystem services will respond to local temperature variations in a gradual versus abrupt

Major depressive disorder (MDD) is a leading cause of disability worldwide. Risk for MDD is heritable, and the genetic structure of founder populations enables investigation of rare susceptibility alleles with large effect. In an extended Old Order Mennonite family cohort, we identified a rare missense variant in GPR156 (c.1599G>T, p.Glu533Asp) associated with a two-fold increase in the relative risk