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Airborne β-caryophyllene disrupts virus–vector mutualism by priming tomato defenses
Whiteflies pose a major threat to crops worldwide, primarily because they transmit begomoviruses with which they have evolved intricate mutualistic relationships. The mutualisms are known to exacerbate whitefly invasions and drive widespread plant virus pandemics. Yet, certain plant genotypes are able to resist both the whiteflies and the viruses and a good understanding of the underlying mechanisms could help to develop more resistant varieties. Here, we show that the viruliferous whitefly Bemisia tabaci induces an early and strong release of the sesquiterpene β-caryophyllene in cultivated tomato plants. This volatile functions as an airborne signal that primes neighboring conspecifics for enhanced resistance to begomoviruses, including Tomato yellow leaf curl virus and Papaya leaf curl China virus. These results challenge the view that whitefly-induced volatile emissions primarily benefit the insect vector, suggesting instead that the plant prioritizes antiviral defense over antiherbivore resistance. β-Caryophyllene exposure was also found to enhance the emission of β-Caryophyllene, methyl salicylate and β-myrcene upon whitefly attack, increasing plant attractiveness to the parasitoid Encarsia formosa . Using a β-caryophyllene overproducing transgenic tomato line and synthetic β-caryophyllene dispensers, we confirmed that β-caryophyllene exposure primes antipathogen defenses in tomato plants and confers improved plant fitness under sustained infestation by viruliferous whiteflies. Importantly, this defense priming is genotype-specific and limited to certain tomato cultivars, suggesting that β-caryophyllene-mediated resistance can be harnessed through selective breeding. Our findings reveal a volatile-based mechanism by which tomato plants may counteract the virus–vector mutualism, offering promising avenues for integrated pest and disease management.
Anthropogenically-driven escalating impact of soil-based compound dry-hot extremes on vegetation productivity
A temporal and spatial atlas of adaptive immune responses in the lymph node following viral infection
The spatial organization of adaptive immune cells within lymph nodes is critical for understanding immune responses during infection and disease. Here, we introduce AIR-SPACE, an integrative approach that combines high-resolution spatial transcriptomics with paired, high-fidelity long-read sequencing of T and B cell receptors. This method enables the simultaneous analysis of cellular transcriptomes and adaptive immune receptor (AIR) repertoires within their native spatial context. We applied AIR-SPACE to mouse popliteal lymph nodes at five distinct time points after Vaccinia virus footpad infection and constructed a comprehensive map of the developing adaptive immune response. Our analysis revealed heterogeneous activation niches, characterized by Interferon-gamma (IFN-γ) production, during the early stages of infection. At later stages, we delineated subanatomical structures within the germinal center (GC) and observed evidence that antibody-producing plasma cells differentiate and exit the GC through the dark zone. Furthermore, by combining clonotype data with spatial lineage tracing, we demonstrate that B cell clones are shared among multiple GCs within the same lymph node, reinforcing the concept of a dynamic, interconnected network of GCs. Overall, our study demonstrates how AIR-SPACE can be used to gain insight into the spatial dynamics of infection responses within lymphoid organs.
Expanding the DNA damaging potential of artificial metallo-nucleases with click chemistry
Abstract Recently, copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) click chemistry has emerged as a promising approach for designing new artificial metallo-nucleases (AMNs) with DNA-damaging properties. By functionalising a central organic azide with three alkyne donors, Tri-Click (TC) ligands capable of chelating three copper ions through the donor group and triazole linker can be generated. However, the versatility of this approach along with the influence of specific donors on metal binding, DNA recognition, and cellular DNA damage in an anticancer context remains poorly understood. Here, we prepare a series of Tri-Click ligands incorporating systematic cyclic and acyclic N-, O-, and S-donors and evaluate their AMN activities. Screening experiments pinpoint planar N-donor ligands as high value agents. Among these, the copper complex of Tri-Click-Pyridine (Cu 3 -TC-Py) displays significant potential. We characterise its activity using single-molecule imaging, microscale thermophoresis, FRET-based binding assays, molecular dynamics, and intracellular DNA interaction studies in human and functional bacterial cells. We report the emergence of Cu 3 -TC-Py as a lead AMN with high reactivity for DNA damage applications central to anticancer therapy.
Baculoviruses hijack host midgut-derived tachykinin to regulate phototactic climbing behavior and promote viral transmission
Baculoviruses are large DNA viruses that mainly infect insects. During infection, viral egress from midgut cells and subsequent behavior changes lead to terminally infected insects migrating to higher elevations on plant branches or tree limbs. However, the neural mechanisms driving this hyperactivity remain poorly understood. In this study, we demonstrate that the climbing behavior of Helicoverpa armigera larvae enhances the dispersal of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV). Our findings reveal that HearNPV triggers a calcium response in enteroendocrine cells, leading to the release of midgut-derived tachykinin (TK). Released TK activates its receptor (TKR) in the brain, thereby promoting phototaxis and climbing behavior. Additionally, HaTTD14 functions as a downstream regulator of the TK–TKR signaling pathway. These results provide insights into the neural and molecular mechanisms driving baculovirus-induced hyperactivity, which aids in viral transmission.
Use of 3D and multidimensional X-ray imaging to see beneath the surface
Human gut microbiota and brain evolution
Maximising environmental savings from silicon photovoltaics manufacturing to 2035
Abstract The silicon photovoltaics market is transitioning from the incumbent passivated emitter rear cell to the higher efficiency tunnel oxide passivated contact technology and it is crucial to understand the environmental impact of this change. Here, we conduct life cycle assessment to compare both technologies quantitatively and identify environmental savings in 15 of 16 environmental impact categories for tunnel oxide passivated contact. This includes a 6.5% reduction in carbon dioxide equivalent emissions, per watt peak at the expense of 15.2% increase in metal resource use, for photovoltaic modules manufactured in China and transported to central Europe. A critical factor in photovoltaics manufacturing is the carbon intensity of the electricity mix. We model the impact of photovoltaics production across different global regions, incorporating future electricity mix scenarios and a projection for photovoltaics deployment. Our model provides a forecast of the environmental impact of global photovoltaics manufacturing and identifies a potential reduction of 8.2 gigatonnes of carbon dioxide equivalent emissions by 2035, depending on manufacturing location.
Behavioral tuning of spider silk thread stiffness circumvents biomaterial trade-offs
Biological polymers often face a trade-off between stiffness, strength, and extensibility: Materials that are strong and stiff tend to be brittle, while those that are elastic and extensible usually lack strength. Here, we show that netcasting spiders (Deinopidae) overcome this trade-off by forming mixed-silk metastructures, which enable both high elastic deformation and load resistance. These spiders have evolved a unique predatory strategy, casting a sticky silk web over prey, which subjects the web radii to extreme strains far exceeding those sustained by typical spider silk fibers. The radii consist of a compound filament with an elastomeric core surrounded by looped bundles of thin fibers. This architecture results in an unusual mechanical profile: The threads are initially compliant and highly extensible, but they stiffen as the fiber loops straighten, enhancing load-bearing capacity. Notably, spiders control this compound architecture through a reel-spinning technique, controlling loop formation and fiber mixture to establish an elasticity gradient across the web—stiff and strong in the main frame lines, yet soft and hyperelastic in the lower radii that undergo the greatest deformation during prey capture. These findings represent a unique case of behavioral modulation of silk processing to circumvent biomaterial trade-offs, enabling extraordinary dynamics and specialization of web architecture. The herein described principle of looped fiber-reinforced elastomers may also be transferred to the design of artificial materials for applications that require both high elasticity and strength.
Author Correction: Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities
Large declines in organofluorine contamination indicated by subarctic marine mammal tissues
The ocean is thought to be the terminal sink for per- and polyfluoroalkyl substances (PFAS), persistent organofluorine chemicals used widely in modern commerce for decades. Industry and stewardship programs phased out the most abundantly produced legacy PFAS in the early 2000s due to toxicity concerns. However, they have since been replaced by shorter carbon chain and “novel” chemistries, and past work hypothesized likely increases in these replacement PFAS that were not previously quantifiable. To address this gap, we measured bulk extractable organofluorine (EOF) in archived liver and muscle tissues from pelagic Subarctic pilot whales over the last several decades. Results show EOF concentrations peaked in 2011 and declined by over 60% by 2023. Among a broad suite of targeted and suspect PFAS measured using high-resolution mass spectrometry, only one was consistently increasing through 2023. Tissue concentrations of four main legacy PFAS that accounted for over 75% of EOF were all decreasing by 2023. The timing of peak concentrations depended primarily on whether they were transported to the subarctic by ocean circulation or atmospheric deposition, with the latter declining much faster. Oceanic transport and bioaccumulation modeling suggests that decadal-scale lags between production and food web bioaccumulation are primarily driven by marine transport processes. Large declines in tissue concentrations in this study reinforce the effectiveness of phase-outs in chemical production. However, other work showing stable or increasing EOF in human serum suggests many emerging PFAS with more neutral physicochemical properties may be preferentially accumulating in terrestrial and nearshore environments compared to legacy PFAS.
MerTK-triggered TGFβ1 autocrine signal regulates microglial response to neurodegeneration
An in vivo and in vitro spatiotemporal profile of human midbrain development
Abstract The dopaminergic system has key roles in human physiology and is implicated in a broad range of neurological and neuropsychiatric conditions that are increasingly investigated using induced pluripotent stem cell-derived midbrain models. To determine similarities of such models to human systems, here we undertake single-cell and spatial profiling of first and second trimester fetal midbrain and compare it to in vitro midbrain models. Histological examination reveals that, by the second trimester, fetal midbrain tissue exhibits structural complexity comparable to that of adults. At the molecular level, single-cell profiling uncovers differences in cellular composition across models, with brain organoids most closely resembling late first trimester tissue — an observation supported by meta-integration of existing midbrain datasets. By reconstructing developmental trajectories of neuronal and astrocytic lineages, we map gene expression dynamics associated with maturation. Importantly, integration of spatial transcriptomics provides critical context for aligning organoid models, revealing that their spatial organization and intercellular signaling resemble the architecture and microenvironment of the second trimester midbrain. Ultimately, we leverage our findings to study Dopamine Transporter Deficiency Syndrome progression in patient-derived midbrain organoids, validating their relevance. Understanding the extent of human tissue recapitulation in midbrain laboratory models is essential to justify their use as biological proxies.
Oligomeric assembly of the gatekeeper InvE orchestrates hierarchical type III protein secretion in <i>Salmonella</i> Typhimurium
Type III secretion systems (T3SS) are critical virulence machines in many Gram-negative bacteria, enabling hierarchical secretion of translocases followed by effectors. In the Salmonella enterica serovar Typhimurium SPI-1 T3SS, the regulatory protein InvE (SctW) enforces this order. Here, we show that InvE assembles into tetramers and higher-order oligomers and that oligomerization is essential for function. A 2.4 Å cryo-electron microscopy (cryo-EM) structure reveals a tetramer built as a dimer of antiparallel dimers. Photocrosslinking maps one set of residues to the interdimer seams in this tetramer, while crosslinks from additional sites suggest lateral docking between dimers in alternative registries in vivo. Blue-native electrophoresis and SEC–MALS detect native high-molecular-weight species consistent with such assemblies. DNA-PAINT superresolution microscopy confirms the presence of higher-order InvE oligomers in vivo. Charge-reversal mutations that disrupt oligomerization collapse InvE to monomers and abolish secretion, effector translocation, invasion, and virulence. Together, these data define an oligomerization-based switch in which InvE reuses the dimeric face to form higher-order contacts that govern the transition from translocase to effector secretion.
Overcoming the trade-off in reverse osmosis membranes through homologous matching
Mammals that can develop type 2 diabetes have a similarly structured β-sheet amyloid oligomer
Some mammals develop amyloid plaques and type 2 diabetes, much like humans, depending on the sequence of their islet amyloid polypeptide (IAPP). In humans, IAPP forms a toxic oligomer with a parallel β-sheet across residues 23 FGAIL 28 S. Using two-dimensional infrared spectroscopy, we monitor the structure of IAPP from seven different mammals, five of which are from species that can develop type 2 diabetes (ferret, raccoon, cat, baboon, and human) and three from those that do not (hamster, rat, and pig). G24 is isotope labeled to monitor for the presence of the oligomeric β-sheet previously found in human IAPP. For the species that develop type 2 diabetes, their IAPP is cytotoxic, and a β-sheet at G24 is observed during the lag phase prior to fibril formation. In contrast, the species that do not develop type 2 diabetes have nontoxic IAPP, and their IAPP does not form this β-sheet structure. Pig IAPP forms oligomers, but with a different structure that is nontoxic. Thus, an oligomer with a parallel β-sheet at G24 that resembles that of the known human IAPP oligomer correlates with cytotoxicity and propensity for type 2 diabetes. These results indicate that the sequence within the 20 to 29 region of human islet amyloid polypeptide (hIAPP), long known to correlate with type 2 diabetes in mammals, determines the structure and toxicity of an oligomer, supporting the oligomer hypothesis for type 2 diabetes and providing an explanation other than plaque formation for why some mammals develop insulin deficiency in late-stage type 2 diabetes, and others do not.
Organic di-selenide hydrogel microspheres for multimodal treatment of osteoarthritis
Abstract Osteoarthritis (OA) involves multiple pathological processes and presents significant clinical challenges in treatment. Traditional therapies focus on individual factors in cartilage, synovium, or subchondral bone, limiting their ability to comprehensively address OA pathogenesis. In this study, a ROS/MMP13 dual-responsive organic selenium hydrogel microsphere (HSPHR) is developed to trigger a localized microenvironmental response specific to early OA by exploiting the disease’s pathological features. Simultaneously, the organic selenium component effectively enhances selenoprotein levels in cartilage, synovium, and subchondral bone, enabling multimodal treatment for osteoarthritis. HSPHR injections into joints reduce cartilage damage, synovial hyperplasia, and bone sclerosis in post-traumatic OA, while promoting new cartilage in defect models. It enhances selenoprotein synthesis and activates the PI3K-AKT-mTOR pathway in key cells, improving mitochondrial function and antioxidant capacity, thus reversing OA-related changes. Here, we present a multimodal therapeutic strategy for OA lesions and reveal shared regulatory pathways among different cell types. This approach offers distinct insights for the multimodal treatment of degenerative joint diseases.