Acinetobacter baumannii is a multidrug-resistant pathogen that colonizes the gut, increasing the risk of subsequent infection and transmission. Recent work showed that A. baumannii catabolizes ornithine, a non-preferred carbon source, to colonize the gut. However, the mechanisms of carbon preference were unknown in A. baumannii . Here, experimental evolution identified the conserved RNA-binding protein CsrA as a regulator of carbon preference in A. baumannii , a previously unreported CsrA function. RNA immunoprecipitation sequencing (RIP-Seq) revealed hundreds of CsrA-associated transcripts. A. baumannii CsrA directly bound and repressed expression of the ast arginine/ornithine catabolic operons. The Pseudomonas aeruginosa CsrA homolog RsmA repressed arginine/ornithine catabolic operon expression, suggesting this CsrA function extends to other bacterial taxa. Finally, CsrA was required for competitive fitness during A. baumannii gut colonization. These findings uncover a previously unrecognized role for a global regulator in A. baumannii carbon preference and persistence in the gut, a critical reservoir for multidrug-resistant pathogens. ### Competing Interest Statement The authors have declared no competing interest. American Heart Association, https://ror.org/013kjyp64, 25PRE1374972 National Institutes of Health, https://ror.org/01cwqze88, R35GM156848, R01AI189516, R01AI192538 Burroughs Wellcome Fund, https://ror.org/01d35cw23, 1548433
Alzheimer's disease (AD) features widespread extracellular amyloid-β plaques but selective intraneuronal tau accumulation in cortical layers II/III and V, while layer IV remains relatively resistant. Here, we combined subcellular spatial transcriptomics with co-registered Aβ and pTau immunohistochemistry to determine why neurons exposed to comparable plaque-associated pathology differ in somatic pTau accumulation. Plaque-associated neuritic stress occurred similarly across layers, but layer IV neurons showed attenuated pTau accumulation and reduced somatic expression of a shared neurite-soma stress program involving DCTN1, CALM3, NORAD, and PIN1. Trajectory analysis within layers identified tau-vulnerable and resistant neuronal states implicating calcium signaling, retrograde transport, and lysosomal function. Notably, astrocytic APOE-neuronal LRP1 co-expression increased significantly along the pTau-vulnerable trajectory, and APOE ϵ4 was associated with stronger coupling of local plaque pathology to pTau-associated molecular programs. These findings reveal neuronal programs and neuron-glia interactions underlying selective tau vulnerability and resistance in AD, highlighting potential tau-targeting therapeutics. ### Competing Interest Statement MEW, LG, and AD are employees of Abbvie. SD received research funding from Abbvie Inc. Abbvie participated in the single-nuclei RNA sequencing (snRNA-seq) data generation and analysis, review, and approval of the publication. BTH owns stock in Novartis; he serves on the SAB of Dewpoint and has an option for stock. He serves on a scientific advisory board or is a consultant for AbbVie, Arbor Bio, Argo, Arvinas, BioClec, Biogen, BMS, Cell Signaling, Cure Alz Fund, CurieBio, Dewpoint, Eisai, Etiome, Pfizer, Sanofi, Takeda, TD Cowen, Third Rock, UCB, Vigil, Violet, Voyager, WaveBreak. His laboratory is supported by research grants from the National Institutes of Health, Cure Alzheimer's Fund, Tau Consortium, and the JPB Foundation - and sponsored research agreement from Abbvie and Sanofi. He has a collaborative project with Biogen and Neurimmune. These interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. AS-P has a material transfer agreement with Ionis Pharmaceuticals, Inc. and has received research funds from AbbVie, Inc. The remaining authors declare no competing interests. Alzheimer's Association, https://ror.org/0375f4d26, ABA-25-1372179 Massachusetts Life Sciences Center, https://ror.org/033km2469 Karen Toffler Charitable Trust Cure Alzheimers Fund, https://ror.org/05ewr7t48 National Institute on Aging, https://ror.org/049v75w11, R01AG071567 National Institute on Aging, https://ror.org/049v75w11, P30AG062421
Genomic variation shapes phenotypic diversity, yet how genetic variation contributes to transcript isoform diversity remains poorly understood at the population scale. Here, we integrated transcriptomic data from 240 lettuce accessions with a lettuce pangenome to construct a comprehensive pan isoform atlas comprising 531,657 isoforms from 49,729 transcribed loci. Isoform presence absence variation (iPAV) captured extensive transcript diversification during domestication and horticultural differentiation, providing additional resolution beyond locus-level analyses, particularly within loci shared across the population. To facilitate the systematic analysis of isoform trait associations, we developed ISONET-GWAS, a computational framework that integrates isoform-based association mapping, functional annotation, and network-based candidate prioritization. ISONET-GWAS recovered the known chlorophyll regulator LsGLK, identified 455 metabolite isoform associations across 77 metabolites, and prioritized candidate regulators of chlorophyll metabolism supported by functional validation. Genome-wide splicing quantitative trait locus (sQTL) mapping identified 10,498 sQTL associations, revealing widespread distal genetic associations with alternative splicing and candidate trans-sQTL hotspots. Notably, we identified a trans-sQTL hotspot overlapping LsPPR, which encodes a pentatricopeptide repeat RNA-binding protein. Perturbation of LsPPR resulted in widespread changes in alternative splicing of floweing-related genes, accompanied by delayed bolting and flowering and altered splicing of flowering-related genes. Together, our study establishes a population-scale pan-isoform resource and a broadly applicable analytical strategy for isoform-level trait association, candidate prioritization, and complementary analysis of the genetic regulation of alternative splicing in crops. ### Competing Interest Statement The authors have declared no competing interest. the National Key Research and Development Program of China, 2023YFF1000100 the National Natural Science Foundation of China award, 32573026 the scientific research start-up funding from Hubei Hongshan Laboratory, 11020102 the Fundamental Research Funds for the Central Universities, 2662024SZ005 the Young Scientist Fostering Funds for the National Key Laboratory for Germplasm Innovation & Utilization of Horticultural Crops, Horti-PY-2023-004
The rising threat of drug–resistant tuberculosis has renewed interest in bacteriophage therapy as an urgently needed alternative. Rational engineering of these viruses, however, requires an atomic-level understanding of virion architecture. Mycobacteriophage SWU1 belongs to subcluster A2, one of the few mycobacteriophage lineages known to infect Mycobacterium tuberculosis ( M. tuberculosis ). Using single-particle cryogenic electron microscopy (cryo-EM), we resolved essentially the entire SWU1 virion architecture by localized reconstruction of four modules, the capsid, portal vertex, tail and baseplate, at resolutions of 3.62 Å, 3.51 Å, 3.70 Å and 3.22 Å, respectively. The T=7 capsid comprises 415 copies of an HK97-fold major capsid protein and lacks any decoration protein in density. The 12–fold portal reconciles its C5–C12 mismatch with the capsid vertex through defined, non-equivalent subunit contacts. The baseplate carries a 13-fold tail-fiber ring on a 6-fold hub, a geometry without precedent among characterized phages, established here by symmetry-free reconstruction. These findings provide the critical insights into the assembly and infection of SWU1, laying a structural foundation for the future optimization of phage-based anti-TB therapeutics. ### Competing Interest Statement The authors have declared no competing interest. Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project, 2025ZD01999800 Major Project of Guangzhou National Laboratory, GZNL2024A01024, GZNL2026C01005 National Natural Science Foundation of China, 82472325, 32394010, 32273005 National Key Research and Development Program of China, 2022YFA1305900, 2021YFD1800403
Soybean (Glycine max) seeds contain approximately 20% oil and 40% protein and are important for food, feed, and biofuel. Improving soybean productivity and seed quality requires optimizing carbon partitioning during seed development. Previously, seed-specific suppression of the lipase-encoding gene Sugar-Dependent 1 (SDP1) increased seed oil content by approximately 5% while slightly reducing raffinose family oligosaccharides without compromising protein content. Seed-specific SDP1 suppression also increased seed size by 18-25% without affecting seed number, resulting in greater seed biomass per plant. To determine the developmental basis of the increased seed size, we investigated the cellular and molecular mechanisms underlying this phenotype. Microscopy and biochemical analyses showed that larger seeds were associated with increased seed cell size and enhanced lignocellulosic cell wall accumulation. Temporal biochemical and transcriptomic analyses further revealed coordinated changes in hormone homeostasis, including altered levels of abscisic acid, 12-oxo-phytodienoic acid, and jasmonoyl-isoleucine, together with differential expression of F-box and RING/U-box family genes. The results indicate that the enhanced seed size resulting from SDP1 suppression is associated with coordinated changes in cellular development, cell wall accumulation, hormone homeostasis, and regulation of gene expression during seed development. Developmental and metabolic changes associated with the increased seed size phenotype support SDP1 manipulation as a potential strategy for improving soybean seed yield and quality. ### Competing Interest Statement The authors have declared no competing interest. United Soybean Board, https://ror.org/03az66838, 24-203-S-B-1-A, 26-203-S-B-1-A, 27-203-A-1-B U.S. National Science Foundation, DBI-2242822 United States Department of Agriculture National Institute of Food and Agriculture, 2023-67017-39419 Office of Biological and Environmental Research, https://ror.org/0114b2m14, DE SC0023142
