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Proceedings Of The National Academy Of Sciences Of The United States Of America[JOURNAL]

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Neural tissues and chondrostean traits in a Carboniferous actinopterygian.

Caron AM, Tietjen K, Coates MI

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372151 · Publisher ↗

Ray-finned fishes (Actinopterygii) represent over half of extant vertebrate species, but their early evolutionary history is largely unresolved. Current phylogenetic estimates, corroborated by discoveries of preserved ne... Ray-finned fishes (Actinopterygii) represent over half of extant vertebrate species, but their early evolutionary history is largely unresolved. Current phylogenetic estimates, corroborated by discoveries of preserved neural tissues, place most Palaeozoic actinopterygians outside the crown group and leave the deep roots of major extant divisions depauperate. Moreover, apparent fossil brains in early fishes are minuscule relative to endocranial chamber space, implying that endocasts are poor indicators of neuroanatomical gross morphology. Here, through X-ray micro-computed tomography of the early actinopterygian we show unexpected neurocranial and neural soft tissue morphology indicative of a large brain fitting snugly within the endocranium. We find internal ventricular structures, present a model of neural tissue preservation, identify neuroanatomical characters, and demonstrate that endocasts capture phylogenetically and ecologically informative signal. These data suggest that bridges the gap between early actinopterygians and modern Chondrostei, thereby offering an alternative framework for understanding early actinopterygian neural evolution that departs radically from current phylogenetic hypotheses.

Assessment of diverse deep brain stimulation targets uncovers a common neural pathway for instantaneous antidepressant effects in rats.

Qian P, Bo B, Li M … +5 more , Li G, Liu Y, Liang Z, Sun H, Duan X

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372150 · Publisher ↗

Deep brain stimulation (DBS) is a promising therapeutic modality for managing treatment-resistant depression. Most DBS research has focused on single brain regions resulting in unclear optimal stimulation targets and vag... Deep brain stimulation (DBS) is a promising therapeutic modality for managing treatment-resistant depression. Most DBS research has focused on single brain regions resulting in unclear optimal stimulation targets and vague mechanisms. Here, we introduce an experimental paradigm in which multiple graphene fiber stimulating electrodes were implanted in various brain regions of the same depressive animal for behavioral testing and DBS-functional MRI studies. We observed an instantaneous alleviation of depressive-like symptoms with a high response rate in Wistar-Kyoto rats following DBS at the medial forebrain bundle (MFB), lateral habenula (LHb), ventral tegmental area (VTA), and dorsal raphe nucleus (DRN), with a highly similar blood-oxygenation-level-dependent (BOLD) activation pattern, engaging the cortical areas, limbic, serotonin, and dopamine system where the BOLD activation levels in the medial prefrontal cortex (mPFC) and cingulate cortex showed strongest correlation with the degree of depression alleviation. No antidepressant effects were observed in DBS at the mPFC or nucleus accumbens. Lesion of VTA dopaminergic neurons resulted in a decrease in the extent of depression alleviation and BOLD activation levels. These results indicate that DBS targeting the MFB, LHb, VTA, and DRN might represent a rapid-acting antidepressant therapy by activating a highly overlapping dopamine-related neural network.

A nucleic acid labeling chemistry reveals surface DNA on exosomes.

Bošković F, Dutta Gupta P, Zhang J … +2 more , Krishnan Y, Szostak JW

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372149 · Publisher ↗

Chemical labeling of nucleic acids is essential to pinpoint the structure, localization, and function of RNA and DNA. Yet, reversible sequence-independent chemistries that can label native RNA and DNA remain poorly devel... Chemical labeling of nucleic acids is essential to pinpoint the structure, localization, and function of RNA and DNA. Yet, reversible sequence-independent chemistries that can label native RNA and DNA remain poorly developed. Here, we describe Reversible Uridine Nitrilium-mediated Addition (RUNA), a reversible covalent chemistry that selectively modifies uridine and thymidine residues via N3 deprotonation and reaction with a nitrilium ion intermediate generated from an aldehyde and an isonitrile. The reaction forms a stable N3 adduct that can be quantitatively reversed by hydrolysis. By using reagents that are either membrane permeable or impermeable, we demonstrate the localization and function of DNA on exosomes. Although exosomes harbor nucleic acids, whether the latter are encapsulated in the exosome lumen or are surface-adhered is unknown. RUNA revealed that exosomes display DNA on their outer surface. The abundance of such surface DNA increases upon DNA-damage accumulation in cancer cells that are treated with a PARP inhibitor. This surface DNA drives exosome uptake by M2-polarized macrophages through scavenger receptors and triggers a shift toward an M1-like proinflammatory state. The selective labeling of surface DNA revealed an unexpected mechanism by which exosomes engage innate immune cells. RUNA is a versatile tool to analyze the nucleic acid content and functionality of extracellular vesicles in health and disease.

Proteostasis and unfolded protein response dynamics in human neuron/mouse glia co-cultures reveal a cell-specific maturation response.

Barny LA, Garcia SK, Houcek AJ … +4 more , Uzay B, Kim M, Kavalali ET, Plate L

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372148 · Publisher ↗

Proteostasis, or protein homeostasis, is a tightly regulated network of cellular pathways essential for maintaining proper protein folding, trafficking, and degradation. Neurons are particularly vulnerable to proteostasi... Proteostasis, or protein homeostasis, is a tightly regulated network of cellular pathways essential for maintaining proper protein folding, trafficking, and degradation. Neurons are particularly vulnerable to proteostasis collapse due to their postmitotic and long-lived nature and thus represent a unique cell type to understand the dynamics of proteostasis throughout development and maturation. Here, we utilized a dual-species co-culture model of human excitatory neurons and mouse glia to recapitulate and investigate cell type-specific, maturation-related changes in the proteostasis network using data-independent acquisition LC-MS/MS proteomics. We quantified branch-specific unfolded protein response (UPR) activation by monitoring curated effector proteins downstream of the ATF6, IRE1/XBP1s, and PERK pathways, enabling a comprehensive, unbiased evaluation of UPR dynamics during in vitro neuronal maturation between 30 d and 60 d. Species-specific analysis revealed that mature neurons largely preserved proteostasis, although they showed some signs of collapse, primarily in endoplasmic reticulum (ER)-to-Golgi transport mechanisms. However, these changes were accompanied by upregulation of proteostasis-related machinery and activation of the ATF6 branch, as well as maintenance of the XBP1s and PERK branches of the UPR over time. In contrast, glia exhibited broad downregulation of proteostasis factors and UPR components, independent of neuronal presence. Furthermore, we quantified stimulus-specific modulation of select UPR branches in matured neurons exposed to pharmacologic ER stressors. These findings highlight distinct, cell-type-specific stress adaptations during in vitro maturation and provide a valuable proteomic resource for dissecting proteostasis and UPR regulation in human neurons.

The dynamic genomes of reshape our understanding of fern chromosome evolution.

Rizzieri YC, Limpanasittichai P, Hernández F … +9 more , Mendez-Reneau JI, Holt SD, Sutherland B, Mandáková T, Beck JB, Kuo LY, Kooyers NJ, Li FW, Sigel EM

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372147 · Publisher ↗

Ferns are well known for their exceptionally large genomes and high chromosome numbers, which may be in part due to whole genome duplications (WGDs) followed by slow diploidization. To better understand the mode of fern... Ferns are well known for their exceptionally large genomes and high chromosome numbers, which may be in part due to whole genome duplications (WGDs) followed by slow diploidization. To better understand the mode of fern genome evolution, we focus on the heterosporous fern genus which exhibits striking variation in genome size and chromosome number. We generated chromosome-level genome assemblies for the fern with the smallest genome, and a globally invasive species widely thought to be an allopentaploid. Surprisingly, we found that is in fact a diploid hybrid and that , despite having a genome ten times smaller than , has substantially more chromosomes. Both species lack any recent WGDs and their highly variable genomes were predominately shaped by transposable element proliferation and chromosome rearrangements. The complete decoupling of chromosome number and genome size in sharply contrasts the typical pattern in ferns, which are mostly homosporous and produce only one type of spore by meiosis. Many of the genome features observed in are consistent with genomic changes due to female meiotic drive, a mechanism possible only in heterosporous plants that produce distinct microspores and megaspores. These results redefine the genetic identity of and provide insights into its invasive success. The marked variation in genome composition and structure within challenges the prevailing model of fern genome evolution while aligning with expectations for angiosperms, another heterosporous lineage.

Observation-constrained sensitivities of Arctic methane emissions to warming.

Liu G, Peng S, Shen L … +4 more , Ciais P, Nisbet EG, Lan X, Michel SE

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372146 · Publisher ↗

The sensitivity of pan-Arctic (60 to 90°N) natural methane emissions to climate warming lacks direct observational constraints. Long-term atmospheric measurements of methane, which reflect integrated Arctic fluxes and at... The sensitivity of pan-Arctic (60 to 90°N) natural methane emissions to climate warming lacks direct observational constraints. Long-term atmospheric measurements of methane, which reflect integrated Arctic fluxes and atmospheric transport, show that in the pan-Arctic the autumn-to-winter CH build-up (as indicated by the "autumn zero crossing date") is becoming earlier. This advancing trend in autumn zero crossing date is explained by growing natural Arctic CH emissions in response to climate warming in July, August and September, with a rate of increase of 0.14 ± 0.04 Tg CH y during the period 1998-2020. Atmospheric C observational records allowed us to attribute this increase to 0.08 ± 0.02 Tg CH y from natural biogenic emissions (wetlands, lakes, permafrost soils) and 0.06 ± 0.02 Tg CH y from wildfire emissions. Our results point to a larger warming sensitivity of natural emissions (3.1 ± 0.9 Tg CH y per °C) than previous estimates, and potentially a larger positive feedback on climate warming.

1D domino-like phase transformation enables material programming in 2D MoTe.

Liu X, Chen M, Liu P … +3 more , Niu H, Sun Y, Chen XQ

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372145 · Publisher ↗

Phase transformation is a fundamental phenomenon in nature, vital for both the scientific understanding and industrial applications of materials. The emergence of two-dimensional (2D) materials introduces new physical at... Phase transformation is a fundamental phenomenon in nature, vital for both the scientific understanding and industrial applications of materials. The emergence of two-dimensional (2D) materials introduces new physical attributes that challenge traditional phase transformation theories due to their reduced dimensionality. In monolayer transition metal dichalcogenides (TMDCs), phase transformation is typically described as a martensitic process characterized by concerted atomic displacements. Nevertheless, the large energy barrier in 2D TMDCs makes such transformations difficult to realize, posing a substantial challenge to the experimental research on the microscopic mechanism, and hindering the precise regulation of material properties. To address this, we investigate the phase transformation in monolayer MoTe through advanced molecular dynamics simulations accelerated by deep learning potential. Our results uncover that the phase transformation proceeds in a one-dimensional (1D), domino-like manner, exhibiting features of both martensitic and reconstructive transformations. This unique mechanism provides tunability over the process, enabling remarkably enhanced nonlinear optical responses and rapid electrical switching. This work advances current phase transformation understanding and provides perspectives for the phase engineering in other 2D materials.

Antimicrobial peptoids pass rapidly through bacterial membranes and flocculate ribosomes and DNA: A single-cell fluorescence study.

Zhu Y, Nielsen JE, Molchanova N … +11 more , Mustafi M, Herlan C, Fleck B, Bräse S, Schepers U, Sørensen K, Zielke C, Lin JS, Weisshaar JC, Jenssen H, Barron AE

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372144 · Publisher ↗

Certain peptoids designed as mimics of host defense peptides such as LL-37 exhibit potent, broad-spectrum antibacterial, antifungal, antiparasitic, and antiviral activity with minimal cytotoxicity. Previous fixed-cell st... Certain peptoids designed as mimics of host defense peptides such as LL-37 exhibit potent, broad-spectrum antibacterial, antifungal, antiparasitic, and antiviral activity with minimal cytotoxicity. Previous fixed-cell studies have suggested that the peptoids can pass through bacterial membranes and rapidly kill bacteria by aggregating intracellular macroanions, including ribosomes and DNA. However, the dynamic mechanisms of action of these biomimetic peptoids have remained elusive. We employed single-bacterial-cell, time-resolved fluorescence microscopy, and single-particle tracking methods to investigate the effects of the 12mer peptoid TM1, along with shorter alkylated and brominated analogues, on cytoplasmic membrane permeabilization and DNA and ribosome rigidification of . Our results demonstrate that TM1 and several of its analogues permeabilize the cytoplasmic membrane within five minutes of flowing the peptoid solution over the cells-faster than seen for the important human antimicrobial peptide LL-37-and rigidify DNA and ribosomes as effectively as LL-37. Detailed biophysical structural and dynamical studies show that TM1 binds to both DNA (double-stranded and single-stranded) and single-stranded RNA in a similar manner to LL-37, which is well known to display strong nucleic acid binding. These results support our hypothesis that TM1 and its analogues exert their antimicrobial effects through intracellular aggregation of biomacromolecules such as ribosomes, RNA, and DNA. TM1 displays a higher affinity for RNA compared to DNA, suggesting it will preferentially bind in vivo to bacterial ribosomes. Our study yields insight into the dynamic effects of antimicrobial peptoids, facilitating their future development as biomimetic anti-infectives, with the additional advantage of protease invulnerability.

The mechanism for ligand activation of the Smoothened G protein-coupled receptor.

Yu RD, Vo AP, Kim SK … +1 more , Goddard WA

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372143 · Publisher ↗

The Smoothened (SMO) G protein-coupled receptor is a key part of the Hedgehog (Hh) signaling pathway, and it is an oncoprotein that is an important target for understanding cancers such as basal cell carcinoma. However,... The Smoothened (SMO) G protein-coupled receptor is a key part of the Hedgehog (Hh) signaling pathway, and it is an oncoprotein that is an important target for understanding cancers such as basal cell carcinoma. However, its mechanism of activation remains unknown. To this end, we investigate here the sequence of G protein and cholesterol (CHL) ligand binding to SMO on the pathway toward activation. Our results are consistent with the G protein-first activation pathway of SMO in the Hh signaling pathway. In this model, CHL first binds to the cysteine rich domain (CRD) of the inactive SMO, which remains inactive at this stage. The G protein can then spontaneously bind to this SMO, forming a precoupled complex that remains inactive while Patched (PTCH) is attached to the membrane. Upon binding of the Hh ligand to PTCH, the CHL levels in the membrane increase, enabling CHL to also bind to the transmembrane domain (TMD) of SMO. With CHL occupying both the CRD and the TMD sites, opening of the G protein becomes energetically favorable, promoting GDP release and initiating downstream G-protein signaling.

Reply to Wang: Policy failure can be assessed from observed outcomes.

He Y, Bu Y

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372142 · Publisher ↗

Abstract loading — click title to view on PubMed.

A general framework for predicting the ecological effects of range expansions in marine systems.

Beshai RA, Sorte CJB

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372141 · Publisher ↗

Warming global temperatures are driving species to shift beyond their historical geographic ranges into novel, expanded ranges, where they may have both positive and negative effects on recipient populations. Although no... Warming global temperatures are driving species to shift beyond their historical geographic ranges into novel, expanded ranges, where they may have both positive and negative effects on recipient populations. Although no framework currently exists to anticipate these effects, invasion biology theory suggests expanders' effects may be predictable from expanders' historical roles and trophic positions. We conducted a global synthesis of over 1,200 population-level effects of marine range-expanding species reported across 1,075 studies. We hypothesized that, similar to invasive species, expanding species' impacts could be predicted by (H1) their ecological roles in their historical ranges and (H2) their trophic levels. We found that effects in these species' historical ranges reliably predict their impacts in expanded ranges, but that, overall, marine range expanders tend to be more detrimental-or less beneficial-in novel communities. Higher trophic level expanders tend to have stronger effects (both positive and negative) on resident species than lower trophic level expanders. Effect magnitudes were further modulated by the type of interaction (e.g., predation, competition, physical disturbance, etc.), with the strongest effects arising from indirect interactions. Finally, we found that native producers experienced some of the strongest effects when compared to humans, vertebrates, or invertebrates. Together, our results indicate that existing knowledge of species' roles are key to anticipating which climate-driven range expansions are likely to have the largest effects on recipient communities.

A reset clock cannot keep time: Thermal overprinting obscures Great Unconformity origins in North China.

McDannell KT, Gallagher K, Guenthner WR … +2 more , Keller CB, Shuster DL

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372140 · Publisher ↗

Abstract loading — click title to view on PubMed.

Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism.

Chen B, Wang J, Qian Q … +21 more , Zhang G, Wang Y, Li M, Tan R, Yang Z, Zhao W, Ciampa G, Yang Bennett DS, Liu Y, Zhu Q, Zhu Z, Masenga SK, Vue Z, Le H, Shi Q, Zingman LV, Hinton AO, Hall DD, Abel ED, Yang L, Song LS

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372139 · Publisher ↗

Dysfunctional adipocyte calcium handling is implicated in obesity and thermogenesis. Junctophilins (JPs) stabilize calcium microdomain junctions between the plasma membrane and endoplasmic reticulum, but whether JPs are... Dysfunctional adipocyte calcium handling is implicated in obesity and thermogenesis. Junctophilins (JPs) stabilize calcium microdomain junctions between the plasma membrane and endoplasmic reticulum, but whether JPs are required for adipocyte function is not known. We show that JP2 is enriched in thermogenic brown adipose tissue (BAT) relative to other fat depots and is downregulated under conditions of nutrient overload. Conditional knockdown of JP2 in adipocytes, and more selectively in BAT, exacerbates cold intolerance and susceptibility to diet induced obesity. Mechanistically, JP2-depleted brown adipocytes exhibit calcium handling dysfunction with elevated cytosolic calcium levels at baseline but diminished norepinephrine-induced calcium transients, reduced store-operated calcium entry. Basal cytosolic calcium overload accounts for an increase in calpain activation and ensuing downregulation of STIM1 and hormone-sensitive lipase in JP2-depleted cells. Furthermore, JP2 silencing in brown adipocytes reduced oxygen consumption rates and compromised mitochondrial structure and quality. Together, these findings demonstrate that JP2 is essential for normal calcium homeostasis in brown adipocytes and reveal a critical role for JP2 in thermogenesis and resistance to diet-induced metabolic dysregulation.

Multiscale characterization of the human claustrum from histology to MRI.

Calarco N, Progri S, Kashyap S … +6 more , Xie S, Lepage C, Gift Cabalo D, Bernhardt BC, Evans AC, Uludağ K

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372138 · Publisher ↗

The claustrum is a thin, bilateral structure embedded deep within the human brain. Its widespread cortical connectivity has motivated perhaps the broadest range of functional hypotheses of any subcortical structure. Yet... The claustrum is a thin, bilateral structure embedded deep within the human brain. Its widespread cortical connectivity has motivated perhaps the broadest range of functional hypotheses of any subcortical structure. Yet its complex, sheet-like morphology has hindered investigation in living humans, leaving a small in vivo MRI literature marked by large and often implausible discrepancies. Here, we construct a three-dimensional histological "gold standard" model of the human claustrum and systematically evaluate three ultra-high field 7-Tesla MRI datasets against this reference and its downsampled derivatives. We show that apparent discrepancies in MRI-based claustrum morphology arise primarily from resolution-dependent effects rather than contrast limitations, which transform the claustrum's intricate sheet into an artifactually thickened ribbon. Despite this, submillimeter MRI reliably captures a dorsal "core" containing most claustral volume and cell density and encompassing major corticoclaustral connectivity, and at the highest acquired resolution (0.5 mm isotropic), the ventral claustrum's extension into the temporal lobe is partially recovered, with uncertainty reflecting boundary imprecision rather than anatomical absence. Together, these findings overturn the view that the human claustrum is inaccessible to MRI and establish a foundation for future functional and clinical investigation in the living human brain.

Local partisan context and mental health.

Baxter-King R, Brown JR, Enos RD … +2 more , Naeim A, Vavreck L

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372137 · Publisher ↗

We find that, relative to Republicans residing in more Republican neighborhoods, Republicans in neighborhoods with a higher concentration of Democratic residents report higher levels of anxiety, depression, and lonelines... We find that, relative to Republicans residing in more Republican neighborhoods, Republicans in neighborhoods with a higher concentration of Democratic residents report higher levels of anxiety, depression, and loneliness. While Democrats in general report worse mental health than Republicans, Democrats show no sensitivity to partisan context. Using a large-scale national survey and fine-grained data on residential political context, we establish that these patterns persist even when examining partisans who live in the same Zip Codes, and while controlling for other individual and geographic features. The correlation is strongest for the most strongly partisan individuals, suggesting that politics is a significant factor in the relationship. For Republicans, the size of the relationship between partisan context and mental health is comparable to or larger than the correlation between mental health reports and other contextual features of residential areas, such as neighborhood poverty or the way racial minorities respond to changes in the racial or ethnic composition of local geography.

ILK binding to β1 integrin is indirect and mediated by kindlin-2.

Reinhardt SCM, Böttcher RT, Brod F … +3 more , Speidel JD, Jungmann R, Fässler R

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372136 · Publisher ↗

Integrin-linked kinase (ILK) and kindlin-2 (K2) are key components of focal adhesions (FAs) that regulate cell-matrix adhesion and integrin signaling. Both proteins directly bind each other, but how they influence each o... Integrin-linked kinase (ILK) and kindlin-2 (K2) are key components of focal adhesions (FAs) that regulate cell-matrix adhesion and integrin signaling. Both proteins directly bind each other, but how they influence each other's localization to FAs and binding to integrins remains a subject of ongoing debate. Here, we establish a sensitive workflow to study protein-protein interactions in cells by combining methods from biochemistry, cell biology, and superresolution microscopy. Together with an analytical framework, this approach allowed us to distinguish direct from indirect molecular interactions and construct detailed interaction networks. Disrupting the ILK-K2 interaction reduced ILK localization to FAs and compromised integrin function, whereas K2 recruitment was unaffected. Our interdisciplinary approach also revealed that ILK does not directly bind β1-integrin cytosolic domains in vitro and in cells. Instead, ILK was recruited to integrins exclusively through a K2-dependent mechanism, primarily via K2 bridging ILK and β1 integrins. These findings define the hierarchical relationship between ILK and K2 in FAs and highlight the essential role of K2-mediated ILK recruitment for integrin adhesion and signaling.

Dynamic positioning of Rpc34 winged helix in RNA polymerase III elongation complex for its stability with implications for reinitiation.

Wu JS, Lin YC, Wei YY … +6 more , Lin HH, Liu YC, Chang JW, Tu IP, Chen HT, Chang WH

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372135 · Publisher ↗

RNA polymerase III (Pol III) is specialized for the high-throughput synthesis of short RNAs, a capability linked to its unique TFIIE- and TFIIF-like subcomplexes that are stably associated through different stages of tra... RNA polymerase III (Pol III) is specialized for the high-throughput synthesis of short RNAs, a capability linked to its unique TFIIE- and TFIIF-like subcomplexes that are stably associated through different stages of transcription. To date, the role of a winged helix domain (WH2) of Rpc34 subunit in the TFIIE-like subcomplex during elongation has remained a conundrum because its density is consistently absent in cryo-EM structures of Pol III elongation complexes (ECs), suggesting its high conformational mobility. In this study, we employed single-molecule Förster resonance energy transfer (smFRET) and nano-positioning triangulation to characterize the dynamics and determine the position of the Rpc34-WH2 domain within transcription-competent but nontranslocating Pol III ECs. To achieve the required site-specific labeling, we developed a chemical biology framework that utilizes azido-carrying unnatural amino acid incorporation and a thiol-capping strategy to eliminate off-target alkyne-thiol cross-reactivity. With the acceptor at Rpc34-WH2 and the donor at a defined position on the DNA template as the reference point, our smFRET results reveal that Rpc34-WH2 dynamically transitions among three discrete states, corresponding to preferred positional sites in downstream, middle, and upstream regions across the DNA-binding cleft. One of these sites coincides with Rpc34-WH2's position in the preinitiation complex, indicating positional similarity across transcriptional states. Together with prior Pol I and Pol II studies, these findings establish Rpc34-WH2 as a mobile regulatory element that engages the Pol III EC through transient, weak interactions. Additionally, the bio-orthogonal labeling strategy presented here provides a robust, generalizable route for smFRET studies of large, multisubunit protein assemblies.

European beech reproduction is not reduced by drought, including the 2003, 2018, and 2022 extremes.

Szymkowiak J, Bogdziewicz M, Kelly D … +23 more , Foest J, Braun S, Beudert B, Chianucci F, Cutini A, Gaulton R, Gratzer G, Kölbl A, Kunstler G, Lageard JGA, Meesenburg H, Mezzavilla F, Mund M, Nussbaumer A, Pesendorfer MB, Schmidt W, Thimonier A, Thomas PA, Vacek S, Vacek Z, Verstraeten A, Wagner M, Hacket-Pain A

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372134 · Publisher ↗

Climate change is intensifying drought stress in temperate forests, but its effects on tree reproduction, central to forest regeneration and migration capability, remain poorly understood. Here, we analyze 221 time serie... Climate change is intensifying drought stress in temperate forests, but its effects on tree reproduction, central to forest regeneration and migration capability, remain poorly understood. Here, we analyze 221 time series of beech () seed production across Europe to test whether drought reduces seed output. We isolate drought exposure during the flowering, pollination, and seed maturation phases of reproduction, and test for legacy effects on future reproduction. Seed production was not impaired by summer drought, and dry spring conditions were associated with increased output, likely via enhanced pollen dispersal. Thus, once initiated, beech reproduction is not reduced by drought, with no suppression of reproduction the following year. Reproduction was not reduced at the driest sites during exceptional European summer droughts in 2003, 2018, and 2022. Considered alongside prior evidence that drought suppresses forest growth and elevates mortality, these findings indicate that vital rates can respond in opposite directions to the same stressor. Such contrasts may sustain forest reproduction during heat-drought events yet shift demographic balance toward higher mortality and turnover as climatic extremes intensify.

Constructing a lower-bound estimate of the global number of insect species on a hyperdiverse empirical foundation.

Colwell RK, Guzman LM, Steinke D … +13 more , Chao A, Janzen DH, Hallwachs W, Baker A, Fernández-Triana JL, Hebert PDN, Joyce F, Puschendorf R, Quicke DLJ, Rougerie R, Smith MA, Zamora N, Sharkey MJ

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372133 · Publisher ↗

Estimating the number of insect species on Earth is a daunting challenge. The current consensus estimate-about six million species-is likely far too low, as we will show. Our estimate of the global number of insect speci... Estimating the number of insect species on Earth is a daunting challenge. The current consensus estimate-about six million species-is likely far too low, as we will show. Our estimate of the global number of insect species rests on a sample of more than 1,600,000 DNA-barcoded insect specimens representing 53,945 species from 15 "core" Malaise traps deployed in dry forest, cloud forest, and rainforest ecosystems of the Área de Conservación Guanacaste (ACG) in Costa Rica. Even this massive sample fails to reveal the full extent of ACG insect species richness. To estimate total ACG insect richness, we adjust the observed count of insect species by an "undersampling ratio," computed for a hyperdiverse subfamily of parasitoid wasps (Braconidae: Microgastrinae). The ratio compares microgastrine richness from the core Malaise traps to a lower-bound estimate of true microgastrine richness-including undetected species-based on 21,669 specimens from three sources: the 15 core Malaise traps, 15 "peripheral" Malaise traps spanning all three ecosystems, and 11,373 DNA-barcoded specimens reared from some 1,500 species of microgastrine-parasitized caterpillars (Lepidoptera). To estimate global insect richness, we apply Earth/ACG ratios for tree species and several animal taxa to upscale our estimate of ACG insect richness (nearly 333,000 species). Adopting conservative assumptions, we reach an estimate of 14 to 20 million insect species on Earth, depending on the upscaling group-two to three times the current consensus estimates. Upscaling instead from a point estimate of ACG richness with a wide CI, global estimates reach nearly 30 million species.

Optimal interventions to curb urban conflagration.

Chulahwat A, Mahmoud H

Proc Natl Acad Sci U S A · 2026 Jul · PMID 42372132 · Publisher ↗

Understanding the efficacy of wildfire mitigation policies is a clear first step toward curbing wildfire losses during an urban conflagration. In this study, we used a validated model to quantify the impact of the spatia... Understanding the efficacy of wildfire mitigation policies is a clear first step toward curbing wildfire losses during an urban conflagration. In this study, we used a validated model to quantify the impact of the spatial distribution of the combined management of open-space vegetation and mitigation of the home ignition zone (HIZ) on the resulting fire boundary and damage to the built environment in the Palisades area of Los Angeles, California. Fuel management in open-space involves reducing vegetation density by a specific percentage to emulate vegetation thinning and prescribed burning. HIZ mitigation involves hardening building features and removing defensible space fuel. For each type of intervension, we employed both random and targeted strategies to quantify their effectiveness in reducing the fire boundary and mean relative vulnerability of buildings. When combined vegetation management and HIZ mitigation are applied randomly, we observed a maximum reduction in mean relative vulnerability of 57%, while targeted strategies result in a maximum reduction of 78%. The study demonstrates the effectiveness of combining mitigation strategies in reducing damage caused by urban conflagrations.
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