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Biology subjects

Guo, Q.

Publications and source records attributed to Guo, Q..

At least 19 recordsLinked to original sources

Assessing fish biodiversity and community structure in the Ganjiang River using eDNA metabarcoding

Hydropower development has emerged as a major driver of global environmental change, causing significant ecological damage to freshwater ecosystems and threatening aquatic biodiversity. However, the impact of cascade dams on fish communities in large river systems remains poorly understood, particularly in biodiversity hotspots such as China. Here, we used environmental DNA (eDNA) metabarcoding to assess the spatiotemporal patterns of fish diversity and community structure in the Ganjiang River, the largest tributary of the Yangtze River, in relation to cascade hydropower development. We collected water samples from 19 sites along the main stem and major tributaries in both wet and dry seasons, and analyzed the eDNA data using high-throughput sequencing and advanced bioinformatics pipelines. Our results revealed significant seasonal and spatial variations in fish diversity and community composition, with lower species richness and distinct assemblages in the impounded sections upstream of the dams compared to the downstream reaches. The fish communities were strongly influenced by environmental factors such as water temperature, pH, dissolved oxygen, and nutrients, which exhibited complex interactions with dam operation and land use practices. Spatial scale analyses further indicated that the impact of dams on fish diversity was most pronounced at the local scale, but also detectable at the regional scale. Our findings provide novel insights into the ecological consequences of cascade hydro-power development on fish communities and highlight the importance of considering spatial scales and environmental heterogeneity in assessing the impacts of human activities on freshwater biodiversity. Our study demonstrates the power of eDNA metabarcoding as a cost-effective and non-invasive tool for biodiversity assessment and conservation planning in large river systems facing multiple stressors and knowledge gaps.

ecology↗

Molecular anatomy of the glomerular filtration barrier reveals topology-encoded albumin sieving

The kidney filters plasma rapidly while retaining albumin, yet where and how this selectivity is encoded within the glomerular filtration barrier remain unresolved. Here we combine cryo-electron tomography (cryo-ET) of vitrified mouse glomeruli with structure-resolved transport modelling to predict albumin passage from the native three-dimensional architecture of the barrier. Among the three barrier layers, endothelial fenestrae and the flexible Nephrin-Neph1 slit-diaphragm lattice are substantially permeable to albumin. The glomerular basement membrane (GBM) instead provides the dominant restriction through steric exclusion governed by void-network topology. In local GBM reconstructions, water traverses broadly connected void space, whereas narrow throats exclude albumin, leaving few accessible paths. To scale this mechanism to the tissue level, we combine structural statistics from local cryo-ET volumes with mesoscale measurements of GBM heterogeneity to generate representative ensembles. Integrating these ensembles with other layers predicts whole-barrier albumin sieving in close agreement with an independent measurement. The topology-driven mechanism also explains early filtration failure in Alport syndrome mice, in which collagen-IV disruption remodels the GBM network and opens albumin-accessible paths while cellular interfaces remain preserved. These findings identify the structural origin of glomerular albumin selectivity and establish a quantitative route from locally resolved architecture to tissue-scale physiology.

physiology↗

Structural streamlining of axonemal doublet microtubules in Plasmodium male gametes

Male gametogenesis in malaria parasites produces up to eight flagellated gametes within approximately 15 min, requiring de novo construction of motile axonemes on an unusually short timescale. Here we combine cellular cryo-electron tomography, high-resolution cryo-EM, proteomics, and parasite genetics to define the molecular architecture and assembly states of the Plasmodium male gamete axoneme. The doublet microtubules retain the principal surface-associated motility modules but contain a markedly reduced luminal microtubule inner protein network. Their inner junction lacks PACRG and is instead organized by CFAP20 and CFAP52, whose combined loss disrupts doublet integrity and exflagellation. We further identify a calmodulin protein at the outer dynein arm docking region and show that outer dynein arms accumulate progressively during gametogenesis. These findings establish distinct form of axonemal remodeling in Plasmodium and reveal the ordered assembly of structural and motor modules during rapid male gamete formation.

cell biology↗

Decoding natural scenes from patterned optogenetic responses in mouse visual cortex

A central challenge in developing visual cortical prostheses is to determine how visual stimuli should be transformed into effective patterns of cortical stimulation. Although advances in stimulation technologies, including optogenetics, provide increasingly precise control over cortical activity, it remains unclear whether artificially evoked activity can reproduce the information content of naturally evoked visual representations. Here we establish a quantitative framework for evaluating visual encoding strategies by decoding cortical responses evoked by natural vision and patterned optogenetic stimulation. We developed a novel dual-modal paradigm in awake mice to bridge the gap between endogenous photostimulation and artificial network driving. By co-expressing the high-performance calcium indicator GCaMP6s and the red-shifted, ultra-sensitive opsin rsChRmine-oScarlet in the primary visual cortex (V1), we successfully translated dynamic natural movie frames into patterned, spatiotemporal optogenetic stimulation. Quantitative comparisons of macro-scale dynamics demonstrated that this patterned optogenetic injection evokes cortical states highly comparable and representationally aligned with those driven by actual visual photostimulation. To systematically evaluate the fidelity of these responses, we developed STAR, a deep learning model featuring spatial and temporal attention mechanisms, and successfully reconstructed the frames of natural movies from V1 signals under both experimental modalities. Collectively, our results demonstrate that complex sensory information can be both naturally encoded and synthetically injected into V1 circuits with high decoding fidelity. This work provides an empirical and computational proof-of-concept for intelligent, closed-loop biomimetic encoders, establishing a robust framework for next-generation cortical visual neuroprostheses and bidirectional brain-machine interfaces.

neuroscience↗

nubbin, ventral veinless, and pdm3 play diverse roles in butterfly wing pattern development

Butterfly wings present a tremendous gallery of colorful patterns, offering a unique opportunity to study how developmental pattern formation processes evolve. We still do not understand the genetic basis of several key aspects of wing pattern development, however. Three paralogous POU domain transcription factors nubbin, ventral veinless (vvl), and pdm3 are all known wing development genes in Drosophila melanogaster. Here we combine gene expression and knockout approaches to show that each of these genes plays multiple novel wing patterning roles in the common buckeye butterfly, Junonia coenia. We found that nubbin controls eyespot pattern determination via a non-cell autonomous repressor-like effect originating at the wing veins, such that nubbin knockouts have larger eyespots. nubbin also regulates pigment identity and scale morphology across the wings. We also found that vvl regulates pigment identity of the discal bands and ventral hindwing. Last, we found that pdm3 is required for determining the outer rings of eyespot patterns, where it is co-expressed with spalt and the lncRNA ivory. pdm3 is also necessary for determining wing margin stripes, where it is again co-expressed with spalt, leading us to propose that the eyespot and wing margin gene regulatory networks could be homologous. Finally, pdm3 affects pigmentation of the ventral hindwing, phenocopying the seasonally-plastic color switch in J. coenia. Together, our work shows that POU domain transcription factors play diverse roles in butterfly wing pattern development and highlights nubbin as one of the first genes implicated in the repressive function of wing veins in color pattern determination. Highlights- Gene expression and knockouts reveal three POU factors regulate butterfly wing color pattern - nubbin regulates eyespot development, likely via a repressor from the wing veins - nubbin controls scale color and morphology across the wing - pdm3 coordinates eyespot development and is co-expressed with spalt and ivory - Expression of genes in the eyespot and wing margin suggests network homology

developmental biology↗

A structured-illumination miniscope for optically sectioned imaging and real-time neural decoding

Single-photon miniscopes enable large-scale calcium imaging in freely behaving animals but are limited by out-of-focus background fluorescence that degrades image contrast and single-cell signal fidelity. Multiphoton approaches address this limitation but remain costly and complex. Here we introduce a lightweight (<3 g), low-cost structured illumination miniscope that achieves optical sectioning in freely behaving mice. Using HiLo imaging implemented with a simple Ronchi grating and time-multiplexed excitation, the system strongly suppresses background fluorescence while preserving the speed, field of view, and accessibility of widefield miniscopes, and supports optical-sectioned multi-plane imaging to increase neuronal yield. Using hippocampal recordings, we show enhanced region-of-interest (ROI)-based signal quality and spatial information readout, allowing simple ROI-averaged signals to approach the performance of offline algorithm-extracted signals. We further demonstrate a proof-of-principle closed-loop brain-machine interface enabled by rapid online signal extraction and real-time neural decoding. Together, these results establish structured illumination as a practical and accessible strategy for achieving high-contrast calcium imaging with miniaturized microscopes.

neuroscience↗

Spatiotemporal Cascade of AP1/CCA1-TOC1 Module Gates Stem Development

Stem development is crucial in plant vertical architecture and overall crop improvement. The molecular mechanisms underlying the initiation and circadian growth of stem remain still enigmatic. Here, we demonstrate that APETALA1 (AP1) spatially initiates circadian stem growth through a noncell-autonomous role of TIMING OF CAB EXPRESSION1 (TOC1) emanating from the floral meristem to inflorescence meristem in Arabidopsis thaliana. Mechanistically, AP1 interacts with and recruits CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) to associate TOC1. Dynamic formation of the AP1-CCA1 complex is crucial for maintaining the circadian rhythmicity and expression of TOC1. Tissue-specific expression of TOC1 in floral meristems rescues the developmental defects of toc1 mutants at both functional and transcriptional levels. Furthermore, TOC1 directly activates the circadian expression of pectin methylesterase gene family, which is critical for its role in stem development. AP1 homologs regulate circadian stem elongation and plant height in wheat and rice, underscoring the conserved mechanism across flowering plants. Our findings uncovered a spatiotemporal regulatory cascade gating stem development and identified candidate genes for crop improvement.

plant biology↗

Deciphering interaction syntax via decoupling intrinsic lineages and niche pressure

Spatial transcriptomics enables the mapping of gene expression within intact tissues, yet a fundamental gap remains between knowing where cells are and understanding how they interact. A cells measured transcriptome reflects both its intrinsic lineage identity and niche pressure. Here we introduce TRINUS, a self-supervised model that deciphers interaction syntax by generative decoupling of a cells intrinsic lineage identity from the extrinsic niche pressure. TRINUS maintains a library of context-free cell prototypes to isolate lineage identity while modeling cooperative interaction dependencies among neighbors. We validated TRINUS on synthetic datasets with known interaction logic and benchmarked it against existing methods with superior performance in cell clustering and spatial domain detection. Applied across diverse platforms and biological systems, TRINUS resolves multi-level interaction syntax and maps tissue-wide interaction patterns in colorectal cancer, and identifies stage-specific signaling dependencies and time-dependent receptor windows during mouse organogenesis. We also show TRINUSs bidirectional in silico engineering capability in the ovarian tumor microenvironment, where forward perturbation revealed subtype-specific macrophage immunosuppressive programs via virtual transplantation and inverse design identified molecular modifications in macrophages predicted to rescue adjacent T-cell function. Collectively, TRINUS provides a practical tool for interaction syntax discovery and predictive tissue engineering on spatial transcriptomics data.

bioinformatics↗

Tripeptidyl peptidase II is essential for maintaining cerebrovascular homeostasis of female mice and represents a novel therapeutic target for vascular dementia

Although cerebrovascular impairment is a known common driver of both Vascular dementia (VaD) and Alzheimers disease (AD), the underlying mechanisms remain poorly defined. Substantial evidence has demonstrated that brain-derived estrogen is essential for cerebrovascular health and neuroprotection. Consequently, therapeutic strategies that can replicate the beneficial effects of estrogen replacement therapy (ERT) in the brain while avoiding its peripheral risks are being actively pursued. Here, we demonstrate that tripeptidyl peptidase II (TPP2) is essential for cerebrovascular homeostasis in adult female mice by orchestrating intracellular Ca{superscript 2} distribution and local estrogen biosynthesis. Specifically, TPP2 deficiency triggers a vicious cycle of Ca{superscript 2} imbalance and estrogen deficiency, thereby disrupting the anticipatory unfolded protein response (UPR). This disruption consequently drives aberrant pexophagic flux and ultimately depletes ether-linked phosphatidylcholine (PC-O)--the essential building block of endothelial cell (EC) membranes. In addition, we identified PC-O as a key facilitator of choline uptake through FLVCR2 and therefore its deficiency causes subsequent choline depletion as well as significantly decreased acetylcholine (ACh). Consistent with the fact that choline is a building block of PC and that ACh is a primary driver of vascular dilation, TPP2 depletion leads to significant cerebrovascular degeneration characterized by narrowed lumens, decreased EC number, and abnormal aggregation of ECs within the blood vessel. Additionally, AAV-mediated specific expression of Far1 in ECs to promote ether-PC biosynthesis significantly increases cerebrovascular volume and diameter in hippocampi of adult female TPP2 knockout (T2KO) mice. Importantly, ectopic expression of Far1 in ECs not only significantly ameliorates memory impairment in global and conditional TPP2-depleted female mice, but also significantly improves memory performance of naturally aged female mice. In total, our findings establish TPP2 as a key determinant of cerebrovascular homeostasis in adult female mice, positioning it as a novel therapeutic candidate for the treatment of VaD and AD.

neuroscience↗

The Par complex regulates apical-basal cell polarity through modulation of FAK signaling homeostasis

Cell polarity complexes are essential for embryogenesis, but their regulatory mechanisms during early developmental transitions remain incompletely understood. Here, we individually deleted the Crumbs, Par, and Scrib polarity complexes in mouse embryonic stem cells (mESCs). While loss of any single complex did not affect pluripotency or proliferation, deletion of Par complex disrupted the naive-to-primed transition and impaired subsequent differentiation, particularly lumen formation in neural tube organoids. Mechanistically, Par complex deficiency led to hyperphosphorylation of focal adhesion kinase (FAK) at the primed stage, driving a morphological shift from flat monolayer clusters to dome-shaped colonies. FAK inhibition rescued the aberrant morphology. Upstream, Par complex loss increased AKT phosphorylation, which remodeled extracellular matrix (ECM) and regulated integrin signaling via FURIN-LEFTY, ultimately modulating FAK activity. In addition, conditioned medium from wild-type cells partially rescued differentiation defects in Par knockout cells in a LEFTY-dependent manner. These phenotypes were consistently observed in naive-to-primed transition, neural stem cell differentiation, embryoid body formation, teratoma assays, and neural tube organoid differentiation. Together, these findings establish a Par complex-AKT-FURIN-LEFTY-ECM-integrin-FAK signaling cascade that links apical-basal polarity to early lineage specification and morphogenesis, providing a mechanistic framework for how polarity cues are translated into developmental outcomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/722465v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@179e0adorg.highwire.dtl.DTLVardef@8d83bdorg.highwire.dtl.DTLVardef@c425fforg.highwire.dtl.DTLVardef@19a8ee5_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementThis study elucidates the molecular mechanism by which the Par complex regulates the establishment of cell polarity. The authors demonstrate that the Par complex promotes the expression of the protein convertase FURIN via AKT signaling, thereby enhancing the maturation and secretion of LEFTY protein. This process remodels the ECM and modulates integrin signaling, ultimately regulating FAK activity and controlling the establishment of cell polarity. These findings reveal how polarity cues govern early lineage specification and morphogenesis, with implications across multiple developmental contexts.

developmental biology↗

Distinct functions of PBRM1 and BAP1 reconcile the course of kidney cancer evolution and disease progression

Clear cell renal cell carcinoma (ccRCC) progresses along two predominant evolutionary trajectories, defined by PBRM1 ([~]40%) or BAP1 ([~]15%) mutations on a VHL-inactivated background. They have distinct patterns of evolutionary tempo and mode, and vastly different clinical outcomes, yet the underlying genotype-specific molecular phenotypic programmes are unknown. We established a patient-derived preclinical model biobank that captures the genetic diversity of ccRCC. Through integrative analyses of preclinical models and tumour bulk and single cell profiling, we identified transcriptional and epigenetic changes specific to PBRM1- and BAP1-driven ccRCC. Modelling PBRM1 loss in vitro demonstrates that it reinforces renal lineage identity and maintains progenitor-like cell state. In contrast, BAP1 loss drives inflammatory signalling and chromosomal instability. These insights reconcile the distinct evolutionary modes (branched versus punctuated), tempo (slow versus fast) and clinical outcomes associated with PBRM1 and BAP1 mutations, respectively, establishing a framework for patient stratification and genotype-directed therapeutic development.

cancer biology↗

eBiota: Designing microbial communities from large seed pools with desired function using rapid optimization and deep learning

Designing microbial communities to generate target products is crucial for biotechnology, agriculture, and disease treatment. However, rationally designing such communities from large seed pools has become a major challenge, as the rapidly expanding number of complete microbial genomes greatly expands the search space and sharply increases the required screening time and computational cost. Here, we introduce eBiota, a platform for ab initio design of microbial communities from a pool of 21,514 strains to generate target products. eBiota not only identifies optimal strain combinations but also simulates community behaviors, including microbial interactions and relative abundances. eBiota integrates three modules: CoreBFS, a graph-based search algorithm that rapidly screens for bacteria with complete metabolic pathways related to the target product; ProdFBA, an extended flux balance analysis that identifies microbial consortia with maximal production efficiency; and DeepCooc, a deep learning model trained on 23,323 microbiome samples across various environments to infer co-occurrence patterns. We validated eBiotas capabilities in microbial community design and production efficiency calculation using public microbiome datasets, ranging from single strains to six-member consortia. Further in vitro experiments involving 94 strains confirmed eBiotas ability to identify species that inhibit pathogen growth and to accurately model the relative abundances within complex microbial communities. As an initial digital twin, eBiota provides a powerful platform for the rational design of functional microbial communities, offering new opportunities for metabolic engineering and synthetic biology.

bioengineering↗

KuafuPrimer: Machine learning empowers the design of 16S amplicon sequencing primers toward minimal bias for bacterial communities

Amplicon sequencing protocol targeting the 16S rRNA gene is a widely used and cost-effective method for exploring bacterial communities. However, its performance is often limited by primer bias arising from the arbitrary use of universal primers across diverse microbial communities and habitats. We propose KuafuPrimer to design the optimal 16S rRNA gene primers toward minimal bias for targeted bacterial communities, using few-shot machine learning to guide the primer design procedure based on a small number of samples. Simulations on 809 samples across 26 representative environments and habitats showed that KuafuPrimer-designed primers outperformed the universal primers in taxonomic accuracy, achieving an averaged 16.31% relative reduction in primer bias, with reductions up to 46.08% in plant samples. Notably, KuafuPrimer detected 29 rare and key taxa undetectable by the universal primers. Validation with 317 longitudinal gut microbiota samples demonstrated that KuafuPrimer-designed primers consistently outperformed the universal primers across temporal, individual, and cohort levels, with relative bias reductions of 5.03%, 3.53%, and 3.10%, respectively. Finally, in real PCR experiments on human gut samples from Clostridioides difficile-infected and healthy groups showed that polymerase chain reaction products using KuafuPrimer-designed primers correlated better with metagenomic data compared to the universal primers. More importantly, KuafuPrimer successfully detected Clostridioides difficile, the key pathogen missed by the universal primers, highlighting its potential for improving clinical diagnostics. In summary, KuafuPrimer provides a machine learning-based primer design strategy for targeted bacterial communities, with demonstrated utility in large-scale microbiome initiatives, longitudinal surveys and clinical diagnostics.

bioinformatics↗

rRNA Expansion Segments Mediate Ribosome Dimerization as a Conserved Stress Response

Inhibition of mRNA translation is a common feature in proteostatic stress cellular responses. Puromycin, a widely used compound for studying translation, disrupts protein synthesis by mimicking the 3 end of aminoacyl-tRNAs. Despite its extensive use as a research tool to probe the connection between translation activity and various physiological and pathological states, the cellular response associated with puromycin-induced translation stress remains incompletely understood. Utilizing in situ cellular electron tomography and topology analysis, we visualized the translation machinery at high resolution. Our analysis revealed that puromycin-treated neuronal cells exhibit an accumulation of "idle ribosomes" characterized by the binding of eIF5A, indicating a close association of this factor with translationally inactive ribosome states under stress. Additionally, the idle ribosomes formed dimeric complexes mediated by ribosomal RNA expansion segments, suggesting an evolved mechanism involving these regions in translation hibernating and protecting idle ribosomes. We show that the hibernating disome formation is not unique to puromycin administration but represents a conserved mechanism as a response to different cellular stressors including those associated with endoplasmic reticulum (ER) stress and amino acid depletion. Altogether, our findings shed light on previously unexplored aspects regarding unique states of mammalian ribosome hibernation, and collectively offers new avenues for understanding the correlation of cellular stress response and the regulation of protein synthesis.

molecular biology↗

Promoter editing of starch branching enzyme IIb and granule-bound starch synthase I balances resistant starch content and amylose content in rice

Increasing attention is being focused on the glycemic index (GI) of daily food for humans, and the resistant starch content (RSC) is an important indicator of GI for starch-rich staple foods. In recent years, some studies revealed that the loss function of single or multiple key enzymes in the primary pathway of starch synthesis substantially increases RSC in rice, such as starch branching enzyme IIb (BEIIb) and soluble starch synthase IIIa (OsSSIIIa). However, a noteworthy negative characteristic of these high RSC mutants is the substantially increased amylose content (AC). AC as a major determinator of rice eating quality, must not be higher than an acceptable limit for most consumers. To solve this problem, in this study, we adopted two promoter editing (PE) editing strategies to develop rice germplasms with a better balance of RSC and AC: one is to edit the promoter of BEIIb in a low AC rice variety, another is to edit the promoter of Waxy (Wx) gene in a BEIIb loss of function mutant. Using AC[&le;]20%, which is the range of premium quality rice in China as a criteria, we finally obtained 2 homozygous lines with significantly increased RSC ([&ge;]5%) in the NG46 background by promoter editing of BEIIb and 1 homozygous line in the YouTang2 (YT2, a BEIIb mutant) background by promoter editing of Wx gene. Further analysis revealed that AC and the amount of long-chain branches of amylopectin are positively correlated with RSC in the population of BEIIb PE lines. However, unexpectedly, the Wx PE-line with substantially decreased AC (17.7%) also showed significantly increased RSC (16.9%). Our study not only produces useful germplasms for the high RSC rice breeding in the future but also provides an insight into understanding the relationship between AC and RSC in defective BEIIb rice.

plant biology↗

The GTPase activating protein Gyp6 binds Retromer and inactivates Rab7/Ypt7 to coordinate the formation of endosomal carriers

The Retromer coat is conserved in all eukaryotes and is crucial for the correct intracellular sorting of many transmembrane receptors and lysosomal hydrolases. Retromer is an effector of the late endosomal small GTPase RAB7 and is also implicated in its inactivation required for proper endosomal maturation. Here, we explore the role of controlled GTP hydrolysis by the RAB7 ortholog Ypt7 in the formation of Retromer-coated membrane carriers in yeast. Proximity labelling and genetic ablation identify the GTPase Activating Protein (GAP) Gyp6 as a critical regulator of Ypt7 activity in the context or Retromer. Structural studies show that Retromer recruits Gyp6 through its Vps29 subunit, which recognises a specific PL motif and a secondary binding site in the C-terminal domain of Gyp6. This interaction does not occur with other yeast GAPs. Ablation of the Gyp6-Retromer interface or the catalytic activity of Gyp6 leads to the accumulation of tubular structures on endo-lysosomal compartments and to increased association of Ypt7 with Retromer and its cargo Vps10. These results support a model in which Gyp6 controls the switch from Ypt7-dependent Retromer coat assembly and cargo collection to the departure of the carrier through membrane fission and uncoating.

cell biology↗

Spent Mushroom Substrate Adsorbs Fusaric Acid to Protect the Cucumber Rhizosphere Microbiome and Alleviates Fusarium Wilt

Caused by Fusarium oxysporum f. sp. cucumerinum, cucumber Fusarium wilt threatens cucumber production worldwide. In addition to pesticides, using spent mushroom substrate (SMS) has a protective effect against Fusarium infection in cucumber, partly through effects on the microbiome. Fusaric acid (FA), a phytotoxic virulence factor secreted by Fusarium, disrupts both plant physiology and the rhizosphere microbial community. Herein, we investigated the relationship between SMS and this virulence factor. Bioassays demonstrated that SMS adsorbed FA both in culture supernatants and in soil. Adsorption behaviour conformed to the Langmuir-Freundlich isotherm model, with a maximum adsorption capacity of 52.72 g/g. Kinetics followed a pseudo-second-order model, indicating physical and chemical adsorption. Scanning electron microscopy showed that SMS had a porous surface, facilitating FA capture. Fourier transform infrared spectroscopy and chemical blocking assays were used to identify secondary amide groups as the key binding sites. In a dual-compartment pot system designed to isolate adsorption from other direct effects, SMS treatment significantly reduced the FA concentration in the cucumber rhizosphere and mitigated FA-induced disease aggravation. This lowered the disease index by up to 25%. Bacterial 16S metabarcoding showed that FA disrupted the rhizosphere bacterial diversity and community structure. However, when FA was adsorbed by SMS, the microbial diversity and community stability were restored. FA reduced the abundance of sensitive taxa such as Bacillus. Meanwhile, SMS-adsorbed FA preserved its relative abundance, suggesting a selective protective effect for FA-sensitive rhizobacteria. These findings indicate that SMS protects cucumber against Fusarium by alleviating FA toxicity toward beneficial microbes. Through FA adsorption, SMS amendment stabilised the rhizosphere microbial community and reduced disease incidence. This highlights the potential of SMS as a sustainable and microbiome-friendly strategy for managing soil-borne diseases.

microbiology↗

Identifying membrane-bound transcriptional regulatory proteins from rare but evolutionarily conserved domain combinations

Transcriptional regulatory proteins, including transcription factors (TFs) and chromatin modifiers, must act inside cell nuclei, but membrane-bound transcription factors (MBTFs) are first anchored in membranes before nuclear translocation. Known MBTFs are vital for processes from myelin expression (MYRF) to cholesterol homeostasis (SREBP), yet their overall diversity remains uncharted. We hypothesized that additional membrane-bound transcriptional regulators (MBTRs) might exist, so we developed a bioinformatics screen to prioritize membrane proteins that are likely to regulate transcription. Our approach leverages domain composition by positing that surprising domain combinations suggest novel biological functions. We searched for rare but evolutionarily conserved pairings of transmembrane domains with domains likely involved in transcriptional regulation. Our method rediscovered known MBTFs and membrane-bound histone kinases, and identified novel MBTR candidates, including transmembrane histone N-acetyltransferases, a putative new subclass of MBTFs that share MYRFs DNA-binding domain, and the prolactin regulatory element-binding protein PREB (SEC12). Assays using recombinant PREB demonstrated that the transmembrane domain is the determinant of PREB subcellular localization, governing its distribution between the membrane and the nucleus in mouse embryonic stem cells. These findings underscore the utility of our method and provide a framework for investigating MBTRs that likely facilitate the integration of extracellular signals with transcriptional responses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/695554v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@15c71e9org.highwire.dtl.DTLVardef@3aa8e8org.highwire.dtl.DTLVardef@1272f0eorg.highwire.dtl.DTLVardef@18246e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗