http://www.rssboard.org/rss-specification 720 https://escholarship.org/uc/lbnl_bs/rss Recent eScholarship items from BioSciences Thu, 30 Jul 2026 12:57:22 +0000 https://escholarship.org/uc/item/71k8c9hg Dissolved organic matter (DOM) is a central component of Earth's carbon cycle and one of the planet's most chemically diverse pools, yet the molecular structures of its constituents remain largely unresolved. This limitation has hindered our ability to link DOM composition to microbial processes and ecosystem function. Here we present ENVnet, a global molecular repository built from tandem mass spectrometry data collected across 13 terrestrial and aquatic environment types, including 419 newly generated samples that expand publicly available DOM metabolomics data and cover previously underrepresented environments. By computationally deconvolving chimeric mass spectra, a longstanding challenge in environmental metabolomics, we recover high-quality fragmentation data for &gt;22,000 distinct molecular features (defined by a specific precursor mass and fragmentation pattern). Using ENVnet, we uncover conserved and environment-specific molecular patterns in DOM composition and underlying... https://escholarship.org/uc/item/71k8c9hg Wed, 29 Jul 2026 00:00:00 +0000 Bowen, Benjamin P https://orcid.org/0000-0003-1368-3958 Harwood, Thomas V de Raad, Markus https://orcid.org/0000-0001-8263-9198 Louie, Katherine B https://orcid.org/0000-0002-6787-7558 Kosina, Suzanne M https://orcid.org/0000-0003-2885-1248 McMahon, Katherine D https://orcid.org/0000-0002-7038-026X Taş, Neslihan Bouskill, Nicholas J Hazen, Terry C https://orcid.org/0000-0002-2536-9993 Bench, Shellie R Mackelprang, Rachel Petras, Daniel https://orcid.org/0000-0002-6561-3022 Wang, Mingxun https://orcid.org/0000-0001-7647-6097 Maestre, Fernando T https://orcid.org/0000-0002-7434-4856 Giovannoni, Stephen J https://orcid.org/0000-0002-2431-4296 Northen, Trent R https://orcid.org/0000-0001-8404-3259 https://escholarship.org/uc/item/28g0x24g In Arabidopsis (Arabidopsis thaliana) roots, growth initiation and cessation are organized into distinct zones. How regulatory mechanisms are integrated to coordinate these processes and maintain proper growth progression over time remains poorly understood. Here, we demonstrate that the peptide hormone PLANT PEPTIDE CONTAINING SULFATED TYROSINE 1 (PSY1) promotes root growth by controlling cell elongation. Higher levels of PSY1 lead to longer differentiated cells with a shootward displacement of characteristics common to mature cells. PSY1 activates genes involved in the biosynthesis of flavonols, a group of plant-specific specialized metabolites. Consistent with these transcriptional changes, metabolomic analysis reveals an enrichment of diverse flavonol glycosides upon PSY1 treatment. Using genetic and chemical approaches, we show that PSY1-mediated flavonol accumulation is localized to the differentiation zone and is required for PSY1 function. PSY1 signaling in this zone is... https://escholarship.org/uc/item/28g0x24g Wed, 29 Jul 2026 00:00:00 +0000 Ercoli, Maria Florencia https://orcid.org/0000-0001-5587-6227 Shigenaga, Alexandra M Teixeira de Araujo, Artur Louie, Katherine B Bowen, Benjamin P https://orcid.org/0000-0003-1368-3958 Weitz, Tracy S Ramesh, Sangeetha https://orcid.org/0000-0002-9229-2009 Jain, Rashmi Northen, Trent R https://orcid.org/0000-0001-8404-3259 Ronald, Pamela C https://orcid.org/0000-0002-4107-1345 https://escholarship.org/uc/item/9s09z94h Synchrotron radiation (SR) sources provide unparalleled brilliance, collimation, coherence, and tunability, enabling specialized techniques that are crucial for advancing medical research across diverse fields from radiation oncology to rational drug design. Certain SR methods, such as macromolecular crystallography, are highly developed and automated, and have been used for decades for both fundamental understanding of biomolecules as well as pharmaceutical design, while other methods, such as microbeam radiation therapy, represent relatively recent developments. Scattering and diffraction methods using SR can provide atomic-level structural mapping of proteins, nucleic acids, and complexes. Imaging applications using SR continue to be developed and advanced for mapping of biological structures and potential use as diagnostics in disease detection. Spectroscopic methods are used to study elemental distributions relevant for detection of contamination in biological systems. Collectively,... https://escholarship.org/uc/item/9s09z94h Tue, 28 Jul 2026 00:00:00 +0000 Osborn, Lydia Inman, Jamie L Ralston, Corie Y https://orcid.org/0000-0002-7899-0951 https://escholarship.org/uc/item/7cr6h1q3 BackgroundDiatoms are a class of algae that play an essential role in global ecology and produce valuable chemicals. They are known for forming intricate nanostructured silica cell walls (frustules). The introduction of non-siliceous elements like aluminum into diatoms induces properties such as a lower dissolution rate of the frustule, increasing the specific surface area of the frustule and enhancing metabolism. Previous studies have focused primarily on characterizing physiological impacts, leaving the genetic response(s) to non-siliceous elements largely unexplored.ResultsThis study investigates the transcriptional response of the pennate diatom, Entomoneis vertebralis to dissolved aluminum. Our findings reveal that in the presence of added 10&nbsp;µM aluminum, biogenic silica content of the cell wall increases approximately twofold along with significant changes to core metabolism. An increase in transcription of genes encoding nitrate transporters has been observed despite... https://escholarship.org/uc/item/7cr6h1q3 Tue, 28 Jul 2026 00:00:00 +0000 Ragunathan, Ramya Purdy, Hugh M Seppala, Susanna Gwak, Hosu Calhoun, Sara https://orcid.org/0000-0003-2942-1338 Twining, Benjamin S Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Chmelka, Bradley F Brzezinski, Mark A O’Malley, Michelle A https://escholarship.org/uc/item/71f4g784 BACKGROUND: The integration of many disparate forms of data is essential for understanding the microbial world and its interaction with the environment and human health. Doing so is particularly challenging in the context of microbe-host and microbe-microbe interactions that contribute to health or environmental outcomes. There are thousands of relevant microbial species, and millions of interactions among those microbes and with their environment or host. Integrated information (e.g., about host and microbial physiology, genetics, and metabolism) facilitates deeper understanding of complex mechanisms and helps interpret correlative results. RESULTS: The KG-Microbe construction framework is a novel approach to harmonizing bacterial and archaeal data in the form of a Findable, Accessible, Interoperable, Reusable (FAIR) and AI-ready knowledge graph (KG). Starting from a core KG with organismal traits, environments and growth preferences and the integration of established ontologies,... https://escholarship.org/uc/item/71f4g784 Tue, 28 Jul 2026 00:00:00 +0000 Santangelo, Brook E Hegde, Harshad Caufield, J Harry Reese, Justin Kliegr, Tomas Hunter, Lawrence E Lozupone, Catherine A Mungall, Christopher J Joachimiak, Marcin P https://escholarship.org/uc/item/6pt4h8sk All biological systems, from low complexity (single molecules) to high complexity (whole cells), must find a way to maintain stability and function under a wide array of environmental conditions. Archaea have been found to be particularly effective at inhabiting the most extreme environments found on Earth. Proto-cells at the origin of life are hypothesised to have originated under even harsher conditions. Therefore, in this review, we summarise our recent works which have provided insights into the molecular bases for adaptation in various archaeal and proto-cell systems, to temperature and high hydrostatic pressure. First, we discuss adaptation in archaeal membranes, which differ significantly from membranes of Bacteria and eukaryotes, having been adapted by evolution to extreme environments. Next, we consider how functionality could have arisen and been maintained in simple proto-membranes. Finally, we discuss proteome and cell-wide adaptation strategies seen in adapted vs... https://escholarship.org/uc/item/6pt4h8sk Tue, 28 Jul 2026 00:00:00 +0000 Peters, J LoRicco, JG Saracco, M Caliò, A Oger, P https://escholarship.org/uc/item/69r1d201 The biological small-angle X-ray scattering (bioSAXS) beamline BM29 at the ESRF, operated by the ESRF-EMBL Joint Structural Biology and bioImaging Group (JSBIG), resumed user operation in September 2020 following the ESRF extremely brilliant source (EBS) upgrade. To exploit the high quality of X-ray beam delivered by this new fourth-generation synchrotron source, BM29 underwent significant refurbishment, including source optimization, instrument upgrades, and a complete redesign of the whole experimental control system. Here, we introduce the BioSAXS Customized Beamline Environment (BSxCuBE-Web), a new open-source, web-based platform designed to streamline, automate and enhance bioSAXS data collection. BSxCuBE-Web offers an intuitive and user-friendly interface for expert and non-expert users alike, to easily define and run bioSAXS experiments, as well as to monitor both raw and processed data. Its adaptable architecture facilitates its deployment on beamlines beyond the ESRF.... https://escholarship.org/uc/item/69r1d201 Tue, 28 Jul 2026 00:00:00 +0000 Florial, Jean Baptiste Oscarsson, Marcus Beteva, Antonia Fisher, Stuart Kieffer, Jérôme Calio, Antonino https://orcid.org/0000-0003-2324-2902 Fisher, Hayden Brennich, Martha Moussaoui, Dihia Popov, Anton Soler-Lopez, Montserrat Pernot, Petra Tully, Mark D McCarthy, Andrew A https://escholarship.org/uc/item/5w41x9kr The microalga <i>Nannochloropsis</i> is an important organism for algae-based biocommodity production of food, feed, and fuel, among other products. Using PacBio Revio, we sequenced, assembled, and annotated a 26.41 Mbp <i>Nannochloropsis oceanica</i> C018 genome. https://escholarship.org/uc/item/5w41x9kr Tue, 28 Jul 2026 00:00:00 +0000 Estrada-Graf, Adrian Koneru, Hari Arnold, Jason Calhoun, Sara https://orcid.org/0000-0003-2942-1338 Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Johnson, Zackary I https://escholarship.org/uc/item/5fr4v6gf Coniferous forest soils represent a globally important carbon sink, where the microbiome is essential for carbon flux between tree roots, rhizosphere, litter and soil. Soil habitats, such as roots, rhizosphere, bulk soil and litter differ in physicochemical properties and composition of highly specialized microbial communities, whose activity reflects the seasonality of temperature and tree activity of these mid- to high-latitude biomes. Here we present a multi-omic dataset encompassing 160 samples collected from four coniferous forest soil habitats in the Czech Republic and Norway, sampled in early summer, late summer, early winter and late winter that characterize the composition, genomic potential and activity of tree roots and microbiome. For each sample, we provide metabarcoding-based composition of bacterial, fungal and eukaryotic communities, results of shotgun DNA sequencing (metagenomes) and shotgun RNA sequencing (metatranscriptomes) illustrating the functional potential... https://escholarship.org/uc/item/5fr4v6gf Tue, 28 Jul 2026 00:00:00 +0000 Human, Zander Rainier Štursová, Martina Odriozola, Iñaki Větrovský, Tomáš Howe, Adina Navrátilová, Diana López-Mondéjar, Rubén Žifčáková, Lucia Brabcová, Vendula Mundra, Sunil Thoen, Ella Morgado, Luis Fiore-Donno, Anna Maria Bonkowski, Michael Adamczyk, Bartosz Kohout, Petr Lipton, Mary S Calhoun, Sara https://orcid.org/0000-0003-2942-1338 LaButti, Kurt https://orcid.org/0000-0002-5838-1972 Lipzen, Anna https://orcid.org/0000-0003-2293-9329 Keymanesh, Keykhosrow Tejomurthula, Sravanthi https://orcid.org/0000-0002-2186-3388 Pennacchio, Christa Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Martin, Francis Kauserud, Håvard Baldrian, Petr https://escholarship.org/uc/item/2pf9x7kb The interrogation of data across biological and environmental systems has become increasingly complex. Fortunately, communities are adopting the FAIR (Findable, Accessible, Interoperable, Reusable) data principles for individual datasets, and continue to develop domain-specific, machine-actionable standards. However, integrating FAIR data for meta-analysis across data resources is still challenging. Understanding how disparate datasets are organized remains a manual, time-consuming process. Updating FAIR databases to reflect changes in knowledge is slow, allowing stale annotations and incorrect relationships to propagate, amplified by Artificial Intelligence (AI) systems that harvest data. Building on FAIR, we argue that data should be iteratively updated and improved. FAIR + COPE (Comparable, Organized, Predictive, Engaged) takes FAIR data and makes it Comparable, rapidly Organized (applying / updating standards) for Predictive models, which can be validated and improved by an... https://escholarship.org/uc/item/2pf9x7kb Tue, 28 Jul 2026 00:00:00 +0000 Wood-Charlson, Elisha M https://orcid.org/0000-0001-9557-7715 Akerstrom, Wolmar N Anderson, Lindsey Borton, Mikayla A Burley, Stephen K Byers, Neil Chandramouliswaran, Ishwar Costes, Sylvain V Dehal, Paramvir S https://orcid.org/0000-0001-5810-2497 Doktycz, Mitchel Eloe-Fadrosh, Emiley https://orcid.org/0000-0002-8162-1276 Henry, Christopher Fagnan, Kjiersten Fiehn, Oliver https://orcid.org/0000-0002-6261-8928 Halappanavar, Mahantesh Hurwitz, Bonnie Joachimiak, Marcin P Jungbluth, Sean Koblitz, Julia Mahmud, Gazi McCue, Lee Ann Metz, Thomas O Mouncey, Nigel https://orcid.org/0000-0001-5380-1256 Mungall, Christopher J Nelson, Tiffanie M Skye, Valerie Saravia-Butler, Amanda M Saripalli, V Ratna Tringe, Susannah G https://orcid.org/0000-0001-6479-8427 Van Den Bossche, Tim Arkin, Adam P https://orcid.org/0000-0002-4999-2931 https://escholarship.org/uc/item/1kw299fc Capsular polysaccharide (CPS) is essential for <i>Streptococcus pneumoniae</i> virulence. Yet, the mechanism linking CPS to peptidoglycan (PG) remains unclear. Here, we identified a strong negative genetic interaction between the genes encoding the putative capsule ligase CpsA and the WalK histidine kinase, a component of the WalRK two-component system regulating cell wall homeostasis. In the absence of <i>cpsA</i>, capsule polymers compete with wall teichoic acids for ligase activity to PG. This induces cell wall stress and is sensed by the WalRK system. Overexpression of the PG hydrolase <i>pcsB</i> or disruption of the PG-modifying enzymes <i>pgdA</i> and <i>oatA</i>(<i>adr</i>) restored growth of strains lacking <i>cpsA</i> and <i>walK</i>. Furthermore, CpsA overproduction compensates for the loss of other LytR-Cps2A-Psr (LCP) ligases, suggesting it can support capsule and wall teichoic acid syntheses. These findings support the model that LCP ligases are semi-redundant, although... https://escholarship.org/uc/item/1kw299fc Tue, 28 Jul 2026 00:00:00 +0000 Zik, Justin J https://orcid.org/0000-0003-0260-2446 Fu, Zeyu Price, Morgan N https://orcid.org/0000-0002-4251-0362 Li, Yujie Yuan, Qiao Arkin, Adam P Deutschbauer, Adam M Flores-Kim, Josue Sham, Lok-To https://orcid.org/0000-0001-9047-0310 https://escholarship.org/uc/item/17b9x1nn Protein oxidative footprinting, using hydroxyl radical labeling detected by bottom-up proteomics, has progressed from an emerging method to a widely used approach in structural biology. Hydroxyl radicals generated from hydrogen peroxide (via photolysis, Fenton chemistry or electrochemistry) or directly from water (via X-rays, plasma or gamma rays) irreversibly encode structural information within protein side chains, which is read out using standard liquid chromatography–mass spectrometry workflows. Quantitative changes in labeling report on solvent accessibility and reveal effects of protein–protein interactions, ligand binding, protein folding, conformational changes or applied stress. Comparing labeling patterns between states provides detailed maps of structural changes and interaction sites. Over the past decade, oxidative footprinting has proven valuable as a solution-phase and in-cell method for protein structure analysis. This Perspective summarizes best practices for... https://escholarship.org/uc/item/17b9x1nn Tue, 28 Jul 2026 00:00:00 +0000 Wecksler, Aaron T Wang, Lingfei Bernstein, Lisa J Huang, Richard Y-C Gupta, Sayan Kristensen, Line G https://orcid.org/0000-0002-7819-2861 Ralston, Corie Y https://orcid.org/0000-0002-7899-0951 Sobott, Frank Sun, Yan Brenowitz, Michael Farquhar, Erik R Chance, Mark R Kuang, Xinyi Cynthia Gross, Michael L Jones, Lisa M Novak, Petr Misra, Sandeep K Sharp, Joshua S https://escholarship.org/uc/item/34b6462x Pancreatic beta cells contain insulin secretory granules (ISGs), organelles where proinsulin is converted into insulin. As ISGs mature, they undergo extensive biophysical remodeling, producing a spectrum of subpopulations with heterogeneous molecular and spatial characteristics. However, systematic methods to define ISG subpopulations remain underdeveloped. To address this gap in knowledge, we employed soft X-ray tomography (SXT), which can quantitatively measure the biochemical density of ISGs within whole beta cells. Using unsupervised clustering, we classified subpopulations based on molecular density, size, and spatial positioning. Across different insulin secretory stimuli, we observed shifts toward mature and releasable subtypes, demonstrating that exogenous signals can dynamically remodel ISG subpopulation distributions. We extended this methodology to primary beta cells characterized using volume electron microscopy (vEM). Integrating subpopulations from SXT and vEM uncovered... https://escholarship.org/uc/item/34b6462x Mon, 27 Jul 2026 00:00:00 +0000 Chang, Kevin Deshmukh, Aneesh Verma, Riva Loconte, Valentina White, Kate L https://escholarship.org/uc/item/7zh7x6wn Crassulacean Acid Metabolism (CAM) is an adaptation that temporally separates carbon uptake at night from photosynthesis during the day. CAM has evolved repeatedly across vascular plants, as its emergence may depend on simple regulatory changes to deeply conserved metabolic pathways. Modern CAM research relies heavily on interpretation of transcriptomic data, though regulation occurs at multiple levels following transcription. Additionally, while most research to date has focused on a handful of genes and metabolites in the core CAM pathway, the co-option of conserved regulatory and functional genes is bound to have wide ranging effects on other aspects of primary metabolism. In this study, we integrate transcriptomic, proteomic, and metabolomic data to compare primary metabolism between the CAM species Yucca aloifolia and closely related C3 species, Y. filamentosa. We observe minimal correlation between protein abundance and mRNA expression, suggesting significant post-transcriptional... https://escholarship.org/uc/item/7zh7x6wn Wed, 22 Jul 2026 00:00:00 +0000 Wickell, David Field, Richard Weitz, Karl Chu, Rosalie Trejo, Jesse Tolic, Nikola Munoz, Nathalie Munoz Hundley, Hope Savage, Emily https://orcid.org/0000-0002-7129-8989 Lipzen, Anna https://orcid.org/0000-0003-2293-9329 Leebens-Mack, Jim Heyduk, Karolina https://escholarship.org/uc/item/5mq165n6 Engineering the genetic code—by reassigning multiple of the 64 natural codons—enables making organisms resistant to all viruses, preventing genetic information exchange, and allowing the biosynthesis of genetically encoded unnatural polymers. However, synonymous codon replacement—recoding—is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using genome synthesis, directed evolution, and genome-transcriptome-translatome-proteome co-profiling on multiple synthetic Escherichia coli genomes. We construct six partially recoded E. coli strains bearing up to 45.8% of a synthetic genome with a deleterious 57-codon genetic code. As our analyses revealed widespread defects—including unassigned codons in Syn61 and Syn57—we apply multi-omics to revise our genome design and mitigate defects. Using multi-omics, we show that recoding induces transcriptional and translational changes leading to fitness defects under hundreds of conditions.... https://escholarship.org/uc/item/5mq165n6 Wed, 22 Jul 2026 00:00:00 +0000 Nyerges, Akos Chiappino-Pepe, Anush Budnik, Bogdan Baas-Thomas, Maximilien Rhuby, Elissa Flynn, Regan Yan, Shirui Ostrov, Nili Liu, Min Wang, Meizhou Zheng, Qingmei Hu, Fangxiang Chen, Kangming Rudolph, Alexandra Chen, Dawn Ahn, Jenny Spencer, Owen Ayalavarapu, Venkat Tarver, Angela Harmon-Smith, Miranda Hamilton, Matthew https://orcid.org/0000-0003-0062-2048 Blaby, Ian https://orcid.org/0000-0002-1631-3154 Yoshikuni, Yasuo Hajian, Behnoush Jin, Adeline Kintses, Balint Szamel, Monika Seregi, Viktoria Shen, Yue Li, Zilong Church, George M https://escholarship.org/uc/item/4w48v836 Serial femtosecond crystallography (SFX) and continuous serial electron diffraction (c-SerialED) both enable high-resolution structure determination from protein microcrystals with minimal radiation damage, making it ideal for studying redox-active metalloenzymes. Here, c-SerialED and SFX were used to solve structures of the class Ia ribonucleotide reductase R2 subunit in oxidized (Fe^III-Fe^III), reduced (Fe^II-Fe^II), and re-oxidized states at ∼1.8 Å resolution, capturing three points in a redox reaction. These results demonstrate that c-SerialED can track reversible changes at the redox-site, enabling future time-resolved studies. Comparison between c-SerialED structures and SFX diffraction and emission data confirmed minimal radiation damage. Furthermore, previously reported structures use mercury in the crystallization condition and show mercury-induced conformational changes. Here, we use mercury-free crystallization conditions and... https://escholarship.org/uc/item/4w48v836 Wed, 22 Jul 2026 00:00:00 +0000 Pacoste, Laura Kumar, Rohit Srinivas, Vivek Makita, Hiroki Simon, Philipp S Bannerjee, Rahul Minnetian, Natalie M Bhowmick, Asmit Paley, Daniel W Mittan-Moreau, David W Chatterjee, Kuntal Rosenberg, Daniel J Batyuk, Alexander Gee, Leland B Alonso-Mori, Roberto Sauter, Nicholas K https://orcid.org/0000-0003-2786-6552 Yano, Junko https://orcid.org/0000-0001-6308-9071 Yachandra, Vittal K https://orcid.org/0000-0002-3983-7858 John, Juliane Aurelius, Oskar Brewster, Aaron S https://orcid.org/0000-0002-0908-7822 Kern, Jan F Blomberg, Buster Lebrette, Hugo Xu, Hongyi Hofer, Gerhard Högbom, Martin Zou, Xiaodong https://escholarship.org/uc/item/4hh5110j Soil organic matter (SOM) decomposition by microorganisms is a major uncertainty in predicting terrestrial carbon–atmosphere feedbacks, partly because we lack understanding of the microbial diversity involved in depolymerizing different carbon pools across environmental gradients. We address this gap using a continental-scale dataset pairing shotgun metagenomes with high-resolution SOM chemistry, assembling 0.76 Tbp of prokaryotic MAGs (828 genomes) and identifying 66,727 SOM molecules from 47 standardized U.S. soil cores selected using respiration rates from 106 soils. Integrating these datasets reveals widespread microbial potential for depolymerizing chemically-recalcitrant SOM previously considered stable. We uncover complementary metabolic specialization between genera affiliated with two abundant bacterial orders, Rhizobiales and Chthoniobacterales, and an archaeal order, Nitrososphaerales. This metabolic partitioning is consistent across soil depths and activity levels,... https://escholarship.org/uc/item/4hh5110j Wed, 22 Jul 2026 00:00:00 +0000 Song, Young C Shi, Cheng Stratton, Kelly G Ayala-Ortiz, Christian Stohel, Izabel Freire-Zapata, Viviana Tfaily, Malak M Eloe-Fadrosh, Emiley https://orcid.org/0000-0002-8162-1276 Graham, Emily B https://escholarship.org/uc/item/2n16j1n4 Microbial methanogenesis is a major contributor to global warming, and methane fluxes represent a loss of energy and electrons from industrial ecosystems. The chemical space of methane control strategies is still underexplored. Most known methanogenesis inhibitors target methanogenic archaeal enzymes. However, interference with the exchange of syntrophic electron carriers (H₂ or formate) in methanogenic systems presents an additional target for methane control. Here, we show that hypophosphite (H₂PO₂^-), an inorganic formate analogue, is a potent and selective inhibitor of syntrophic methanogenesis versus primary fermentation in rice field sediments and cattle rumens. Hypophosphite is also generally recognized as safe and relatively nontoxic to plants and animals. Genetic screens and physiological assays in the model methanogen <i>Methanococcus maripaludis</i> S2 implicate formate metabolism as the target of hypophosphite inhibition.... https://escholarship.org/uc/item/2n16j1n4 Wed, 22 Jul 2026 00:00:00 +0000 Hu, Ruiwen https://orcid.org/0009-0007-1039-6490 Weaver, Matt E Day, Leslie A Marquez, John Mark Aronson, Heidi S Meier, David AO Romero, Pedro Halim, Mohd Farid Abdul Maxwell, Alesha D Costa, Kyle C Deutschbauer, Adam M Price, Morgan N https://orcid.org/0000-0002-4251-0362 Hess, Matthias https://orcid.org/0000-0003-0321-0380 Roy, Koushik Singha Radanielson, Ando Mariot Coates, John D Tsesmetzis, Nicolas Carlson, Hans K https://orcid.org/0000-0002-1583-5313 https://escholarship.org/uc/item/9qj5q67m Viruses are abundant and ecologically important in soils, yet the persistence and production dynamics of extracellular virions remain poorly understood. We applied genome-resolved stable isotope probing viromics (SIP-viromics), combining H₂¹⁸O labeling with viral metagenomics, to track virion turnover in seasonally dry grassland soils following rewetting. We identified 354 viral populations (vOTUs) using individual-sample and combined virome assemblies. Only 22% of vOTUs exhibited significant ¹⁸O enrichment, indicating active replication and new virion production during the 1-week incubation; the majority (78%) persisted without detectable replication, consistent with a viral seed bank. Active vOTUs accounted for 4.76-5.15% of total virions per gram of soil, with viral loads ranging from 3.15 × 10¹⁰ to 6.59 × 10¹⁰ virions per gram. Probabilistic and deterministic sensitivity analyses spanning viral DNA fraction and genome... https://escholarship.org/uc/item/9qj5q67m Thu, 16 Jul 2026 00:00:00 +0000 Trubl, Gareth Roux, Simon https://orcid.org/0000-0002-5831-5895 Kellom, Matthew https://orcid.org/0000-0002-8310-7078 Vyshenska, Dariia Tomatsu, Andy Singh, Kanwar Kimbrel, Jeffrey A Eloe-Fadrosh, Emiley https://orcid.org/0000-0002-8162-1276 Malmstrom, Rex R Pett-Ridge, Jennifer Blazewicz, Steven J https://escholarship.org/uc/item/9nk8x5jm CNS vascular endothelial cells (ECs) exhibit a distinctive gene expression program that is foundational for the blood-brain barrier (BBB). Previous research identified candidate cis-regulatory elements (CREs) that were hypothesized to control this program. In this work, transgenic mice and recombinant adeno-associated virus (rAAV) vectors have been used to interrogate these candidate CREs in vivo. These experiments show that an 850 bp genomic DNA segment ∼60 kb 5' of Slc2a1 possesses enhancer activity that is (1) specific for BBB+ CNS ECs and (2) both necessary and sufficient for BBB+ EC gene expression. A screen of &gt;8,000 genomic DNA segments from CNS EC-specific CRE candidates reveals several hundred with enhancer activity. Transcription factors ERG and LEF1 are shown to occupy sites in brain ECs that are highly enriched in candidate and experimentally validated CREs, lending strong support to a model in which canonical Wnt signaling activates the BBB program via LEF1. https://escholarship.org/uc/item/9nk8x5jm Thu, 16 Jul 2026 00:00:00 +0000 Li, Zhongming Rattner, Amir Wang, Yanshu Smallwood, Philip M Sabbagh, Mark Mannion, Brandon J Pennacchio, Len A https://orcid.org/0000-0002-8748-3732 Nathans, Jeremy https://escholarship.org/uc/item/8460m7wb Thirdhand smoke (THS), lingering tobacco residues on surfaces and in dust after smoking, has emerged as a growing public health concern. While the carcinogenic risks of first- and secondhand smoke are well established, the tumorigenic potential of THS remains inadequately understood. In this perspective, we systematically review the known THS-related compounds together with the existing biological findings to provide evidence on the carcinogenic potential of THS. We assess the role of THS in the context of the classic multistage model of tumorigenesis to address whether THS acts primarily as a tumor initiator, or as a promoter, or both. We also discuss methodological challenges in isolating the effects of THS on human health and the importance of animal models and outline emerging strategies for risk assessment, biomarker discovery, and precision prevention. This Perspective is the first to integrate chemical, toxicological, and mechanistic evidence to evaluate the carcinogenic... https://escholarship.org/uc/item/8460m7wb Thu, 16 Jul 2026 00:00:00 +0000 Wang, Pin Liu, Xinyin Xia, Yankai Chang, Hang Hang, Bo Mao, Jian-Hua https://orcid.org/0000-0001-9320-6021 https://escholarship.org/uc/item/3693d74b We report the successful resolution of the multiplet structure of Kα1 x-ray emission in manganese (Mn) complexes through seeded stimulated x-ray emission spectroscopy (seeded S-XES). Using a femtosecond pump pulse above the Mn K edge to generate simultaneous 1s core holes, and a second-color tunable seed pulse to initiate the stimulated emission process, we were able to enhance individual lines within the Kα1 emission. This approach allows to resolve the fine multiplet features that are obscured by lifetime broadening in conventional (spontaneous) Mn Kα XES. The work builds on our previous observation that S-XES from Mn(II) and Mn(VII) complexes pumped at high intensities can exhibit stimulated emission without sacrificing the chemical sensitivity to oxidation states. This technique opens the door to controlled high-resolution electronic structure spectroscopy in transition-metal complexes beyond the core-hole lifetime, with potential applications in catalysis, inorganic chemistry,... https://escholarship.org/uc/item/3693d74b Thu, 16 Jul 2026 00:00:00 +0000 Kroll, Thomas Doyle, Margaret Halavanau, Aliaksei Linker, Thomas M Everts, Joshua Michine, Yurina Fuller, Franklin D Weninger, Clemens Alonso-Mori, Roberto Pellegrini, Claudio Benediktovitch, Andrei Yabashi, Makina Inoue, Ichiro Inubushi, Yuichi Osaka, Taito Hara, Toru Yamada, Jumpei Kern, Jan https://orcid.org/0000-0002-7272-1603 Yano, Junko https://orcid.org/0000-0001-6308-9071 Yachandra, Vittal K https://orcid.org/0000-0002-3983-7858 Rohringer, Nina Yoneda, Hitoki Bergmann, Uwe https://escholarship.org/uc/item/29c9b0kp Artificial metalloenzymes (ArMs) expand the suite of synthetically valuable, new-to-nature biocatalytic reactions. Integrating these enzymes into biosynthetic pathways enables reactions not found in nature to occur in living cells with the intermediates or products of the metabolic pathways. However, the integration of reactions catalyzed by ArMs into complex metabolic pathways is constrained by the lack of methods to assemble these ArMs in organisms that are commonly used for metabolic engineering. We report the assembly of an iridium-containing artificial metalloenzyme (Ir-ArM) in <i>Streptomyces albus</i>, a Gram-positive bacterial chassis widely used for the heterologous expression of natural products. In this engineered organism, the Ir-ArM assembles in the cytoplasm and catalyzes abiological carbene transfer to the unactivated, disubstituted double bond of an exogenously added terpene with turnover numbers (TONs) that are two times higher than those for the same reaction... https://escholarship.org/uc/item/29c9b0kp Thu, 16 Jul 2026 00:00:00 +0000 Chakraborty, Sukriyo Hwang, Soonkyu Huang, Jing Chen, Dongping Chen, Yan Petzold, Christopher J https://orcid.org/0000-0002-8270-5228 Clark, Douglas S Mukhopadhyay, Aindrila https://orcid.org/0000-0002-6513-7425 Keasling, Jay D https://orcid.org/0000-0003-4170-6088 Hartwig, John F https://escholarship.org/uc/item/8b69v71x In many bioprocesses, maximum achievable titers are limited below economically viable levels by toxic accumulation of the primary end-product. To combat end-product inhibition, a variety of in situ product removal technologies have been developed to selectively remove or partition toxic bioproducts, thereby prolonging fermentation and improving overall process efficiency. Use of an in situ organic overlay to partition toxic hydrophobic products is a commonly employed approach, but this technique occupies valuable space in the fermentor, imposes replacement costs for unrecovered solvent, and increases downstream separation due to formation of stable emulsions. In addition, for many volatile hydrophobic products produced under aerobic conditions—including medium-chain alcohols, esters, monoterpenes, and other aviation fuel precursors—a significant fraction of the product is volatilized to the fermentor off-gas and must be recovered separately to maximize product yield. To address... https://escholarship.org/uc/item/8b69v71x Wed, 15 Jul 2026 00:00:00 +0000 Araujo Barcelos, Carolina https://orcid.org/0000-0001-8252-3937 Mendez-Perez, Daniel Lee, Taek Soon Sundstrom, Eric https://orcid.org/0000-0003-4983-5415 https://escholarship.org/uc/item/8z12199k BackgroundPopulation-scale radiation exposure assessment during radiological emergencies is hindered by the slow and costly nature of current methods, creating a need for rapid, affordable screening tools. Radiation biodosimetry using peripheral blood counts is a promising approach, but estimating low-dose exposures and exposure at extended time points remains challenging, especially when accounting for inter-individual differences in radiation sensitivity.MethodsWe analyze complete blood count (CBC) profiles from a retrospective cohort of 1151 male and female BALB/cJ and C57BL/6 J mice exposed to total-body X-ray radiation at doses ranging from 0.05 to 4 Gy. CBCs are collected 1 to 150 days post exposure. We develop a predictive model of radiation exposure using a sparse representation learning strategy to identify the most informative CBC parameters. Model performance is evaluated through exhaustive cross-validation and validated in a double-blind prospective cohort of 431 animals.... https://escholarship.org/uc/item/8z12199k Tue, 14 Jul 2026 00:00:00 +0000 Chang, Hang Yao, Yiyan DeChant, Jared Obst-Huebl, Lieselotte https://orcid.org/0000-0001-9236-8037 Wan, Kenneth H https://orcid.org/0000-0002-9203-1909 Park, Soo Fisher, William Nakamura, Kei https://orcid.org/0000-0001-9842-7114 Celniker, Susan E Snijders, Antoine M Mao, Jian-Hua https://orcid.org/0000-0001-9320-6021 Inman, Jamie L https://escholarship.org/uc/item/8b51028t Diamond nanoparticles hosting nitrogen vacancy (NV) center defects are powerful tools for studying chemical and biological systems. These quantum sensors convert spin-state information into readily detectable fluorescence signals, sensitive to magnetic fields, temperature, and paramagnetic species. These tools can be useful for a range of biological applications including the monitoring of oxidative stress and cell metabolism. We demonstrate extracellular measurements of oxidative stress indicators in fermentation cultures using NV-diamond-based quantum sensing. Optically detected magnetic resonance signals show dose-dependent responses to stress-induced ROS in filtered fermentation media. This work indicates the potential of NV diamond as a biosensing tool with biotechnology applications. https://escholarship.org/uc/item/8b51028t Thu, 2 Jul 2026 00:00:00 +0000 Jones, Zachary R Torelli, Marco D Tanjore, Deepti https://orcid.org/0000-0001-6507-4359 Shenderova, Olga Ajoy, Ashok https://escholarship.org/uc/item/6hm0w9g1 Enabling simultaneous time-resolved spectroscopy and X-ray footprinting mass spectrometry to study conformational dynamics in protein https://escholarship.org/uc/item/6hm0w9g1 Thu, 2 Jul 2026 00:00:00 +0000 Gupta, Sayan Paul, Sathi Rad, Behzad Kristensen, Line G Russell, Brandon https://orcid.org/0000-0001-8949-2432 Kahan, Darren N https://orcid.org/0000-0002-8245-3489 Ralston, Corie https://orcid.org/0000-0002-7899-0951 https://escholarship.org/uc/item/3094v8ct Triticum turgidum cv Kronos is a tetraploid wheat cultivar that underpins one of the most widely used community platforms for functional genomics. Over the past decade, researchers have generated c. 3000 exome-capture (EC) and promoter-capture (PC) datasets linked to mutagenized seed stocks, along with extensive transcriptomic and phenotypic resources. However, the absence of a reference genome has constrained their full utility. We assembled a chromosome-scale reference genome for Kronos, with high-confidence annotations, including manual curation of over 1000 disease resistance (nucleotide-binding leucine-rich repeat (NLR)) genes and genome-wide identification of microRNAs and phasiRNAs. We additionally reanalyzed EC and PC data to capture mutational landscapes across ethyl methane sulphonate-mutagenized Kronos populations. We revealed previously hidden NLR diversity and resolved their genomic organization at chromosomal ends. Re-analysis of capture datasets enabled high-resolution... https://escholarship.org/uc/item/3094v8ct Tue, 30 Jun 2026 00:00:00 +0000 Seong, Kyungyong Kumar, Rakesh Prigozhin, Daniil M https://orcid.org/0000-0003-2075-0231 Lunde, China Ribeiro, Thales Henrique Cherubino Bélanger, Sébastien Hsieh, Jo‐Wei Allison Tang, McCree Meyers, Blake C https://orcid.org/0000-0003-3436-6097 Krasileva, Ksenia V https://orcid.org/0000-0002-1679-0700 https://escholarship.org/uc/item/9c06s8g2 PARP1 detection of DNA strand breaks allosterically leads to PARP1 synthesis of poly(ADP-ribose) modifications that signal DNA damage. HPF1 engages activated PARP1 to control modification site selection. Understanding of the mechanism of DNA break detection and catalytic activation is incomplete, due largely to limited structural information for full-length PARP1. Here, single-particle cryo-EM provides views of the full complement of PARP1 domains engaging a DNA single-strand break in the presence of HPF1 and a fragment of binding partner Timeless. Cryo-EM, single-molecule DNA dynamics, and small-angle X-ray scattering analysis indicate that PARP1 remains dynamic even when the multi-domain structure is organized on a DNA break, with the minimal catalytic region displaying high mobility relative to domains engaging damage. We propose that the organization of PARP1 domains on a DNA break releases a tethered, constitutively active catalytic region to modify molecules in a radius... https://escholarship.org/uc/item/9c06s8g2 Mon, 29 Jun 2026 00:00:00 +0000 Sverzhinsky, Aleksandr Xue, Huijun Langelier, Marie-France Muniz Corrêa, Marcelo V Del Mundo, Joshua Classen, Scott https://orcid.org/0000-0002-5500-9104 Hammel, Michal https://orcid.org/0000-0002-5610-9289 Rothenberg, Eli Pascal, John M https://escholarship.org/uc/item/6hc3n8p8 Protein-hydroxylation catalysed by Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases is an important regulatory mechanism in human biology. Such oxygenases typically coordinate their Fe(II) cofactor via a conserved triad of an aspartate- or glutamate- and two histidine-residues. By contrast, aspartate/asparagine β-hydroxylase (AspH), which catalyses asparagine/aspartate-residue oxidation in epidermal growth factor-like domains (EGFDs), has only two histidine-residues (H679, H725), with a water occupying the site normally occupied by an aspartate- or glutamate-residue. We describe mechanistic studies with catalytically active AspH crystals. Turnover studies with single crystals under cryogenic conditions give (3 R)-hydroxylated EGFDs with the product alcohol coordinating Fe(II) trans to H725. Time-resolved serial crystallography of microcrystals using an acoustic droplet ejection system, coupled to X-ray emission analyses, demonstrate turnover within 1.5 s, giving a product... https://escholarship.org/uc/item/6hc3n8p8 Mon, 29 Jun 2026 00:00:00 +0000 de Munnik, Mariska Brasnett, Amelia Zhou, Tiankun Myers, William Wang, Yicheng Chatterjee, Kuntal Tumber, Anthony Marshall, Stephen A Simon, Philipp S https://orcid.org/0000-0002-2859-4475 Aller, Pierre Shilova, Anastasiia Axford, Danny Makita, Hiroki Paley, Daniel W Tiwari, Vandana Stead, Alexander T Dehe, Sebastian Sanchez, Humberto Rosenberg, Daniel J Alonso-Mori, Roberto Bhowmick, Asmit Yano, Junko https://orcid.org/0000-0001-6308-9071 Yachandra, Vittal K https://orcid.org/0000-0002-3983-7858 Park, Jaehyun Park, Sehan Orville, Allen M Brewitz, Lennart Kern, Jan F https://orcid.org/0000-0002-7272-1603 Schofield, Christopher J Rabe, Patrick https://escholarship.org/uc/item/3s14x7d0 Plant roots release a wide array of metabolites into the rhizosphere, shaping microbial communities and their functions. While metagenomics has expanded our understanding of these communities, little is known about the physiology of their members in host environments. Transcriptome analysis via RNA sequencing is a common approach to learning more, but its use has been challenging because of low bacterial biomass and interference from plant RNA. To overcome this, we developed a randomly-barcoded promoter-library insertion sequencing (RB-PI-seq) combined with chassis-independent recombinase-assisted genome engineering (CRAGE). Using Pseudomonas simiae WCS417 as a model rhizobacterium, this method enabled targeted amplification of barcoded transcripts, bypassing plant RNA interference and allowing measurement of thousands of promoter activities during Arabidopsis root colonization. Our analysis revealed temporally resolved transcriptional regulation, including those associated with... https://escholarship.org/uc/item/3s14x7d0 Mon, 29 Jun 2026 00:00:00 +0000 Honda, Tomoya Yu, Sora Mai, Dung https://orcid.org/0000-0001-5916-3486 Baumgart, Leo https://orcid.org/0000-0002-2773-5897 Chan, Emory M https://orcid.org/0000-0002-5655-0146 Babnigg, Gyorgy Yoshikuni, Yasuo https://escholarship.org/uc/item/3bv0g1pt Unveiling interfaces at sub-nanometer scales is essential for advancing the understanding of complex chemical transformations. However, characterizing solid-liquid interfaces with high dimensional sensitivity and temporal resolution remains challenging, due to their dynamic nature and inaccessibility by conventional probes. Here we present an approach, Pattern-enhanced Resonant Soft X-ray Scattering, to overcome the challenges. Rooted in a “sample-as-optics” philosophy, this technique utilizes precisely engineered line-grating nanopatterns to modulate near-field X-ray illumination, coherently enhancing scattering signals from the line-gratings. We implement the method using Ni line-grating nanopatterns in electrochemical water oxidation. The periodic nanostructures serve as diffractive optical elements to reveal the Ni oxidation gradients and structural dynamics at the electrode-electrolyte interfaces. Finite-element simulations corroborate the observed trends by modeling variations... https://escholarship.org/uc/item/3bv0g1pt Mon, 29 Jun 2026 00:00:00 +0000 Li, Haoyi https://orcid.org/0000-0002-0723-8068 Andrle, Kas Zhang, Qi https://orcid.org/0000-0002-2915-7605 Cordova, Isvar A Yang, Yao Peng, Zhengxing Yang, Feipeng Freychet, Guillaume Dhuey, Scott Hexemer, Alexander https://orcid.org/0000-0002-5269-0125 Helms, Brett A https://orcid.org/0000-0003-3925-4174 Chao, Weilun La Fontaine, Bruno Ruiz, Ricardo https://orcid.org/0000-0002-1698-4281 Guo, Jinghua https://orcid.org/0000-0002-8576-2172 Yang, Wanli https://orcid.org/0000-0003-0666-8063 Yano, Junko https://orcid.org/0000-0001-6308-9071 Wang, Cheng https://orcid.org/0000-0001-7192-5471 https://escholarship.org/uc/item/4r71m7fs BackgroundComparative genomics and plastome phylogenomics have advanced significantly in recent years, highlighting the diversity, possible admixture, and non-neutral evolution of the predominantly considered non-recombinant chloroplast genomes in angiosperms. The grass genus Brachypodium serves as a powerful model for studying evolutionary processes in monocots.ResultsWe analyzed 287 plastomes across the native circum-Mediterranean range of the three annual Brachypodium species (B. distachyon, B. stacei, B. hybridum), focusing on their structural variation, selection patterns and phylogenomic relationships. Our analyses confirmed the differentiation of the S and D plastomes, inherited respectively from the diploid progenitor species B. stacei and B. distachyon. We identified novel structural rearrangements and indels, and unique repeat motifs, along with widespread heteroplasmy, particularly in ancestral B. hybridum-D plastotypes. SNP diversity varied among plastotypes, reflecting... https://escholarship.org/uc/item/4r71m7fs Fri, 26 Jun 2026 00:00:00 +0000 Campos, Miguel Vogel, John P https://orcid.org/0000-0003-1786-2689 Pérez-Collazos, Ernesto Catalán, Pilar https://escholarship.org/uc/item/3w89w6n6 BackgroundTo strengthen the national energy supply, there is an increasing demand for domestically generated aviation fuels. Bio-derived advanced aviation fuels offer the opportunity to meet this domestic need while presenting a unique opportunity to investigate the production of novel aviation fuels. Isoprenol, a chemical precursor to such novel fuels, has been shown to be a biologically producible compound in model organisms, but its bio-producibility needs to be further explored in organisms more compatible with industrial bioproduction.ResultsIn this work, we evaluate isoprenol production using the promising bioproduction yeast, Rhodosporidium toruloides. First, we show successful isoprenol production using the IPP-bypass pathways most successful in laboratory strains of E. coli and S. cerevisiae. Next, we demonstrate that increased flux through the mevalonate pathway only modestly increases isoprenol titers. Using proteomics, we identified a potential bottleneck in production... https://escholarship.org/uc/item/3w89w6n6 Fri, 26 Jun 2026 00:00:00 +0000 Garcia, Valentina E Geiselman, Gina M Hwang, Hee Jin Chen, Yan Gin, Jennifer W https://orcid.org/0000-0001-5636-7563 McFadden-Mitchell, Jack Montgomery, Veronica Kakumanu, Ramu Goswami, Shubhasish McCauley, Joshua Adamczyk, Paul A Baidoo, Edward EK https://orcid.org/0000-0001-5787-1219 Petzold, Christopher J https://orcid.org/0000-0002-8270-5228 Simmons, Blake A https://orcid.org/0000-0002-1918-3463 Lee, Taek Soon https://orcid.org/0000-0002-0764-2626 Gladden, John M https://orcid.org/0000-0002-6985-2485 https://escholarship.org/uc/item/4nr7w0h2 Natural deep eutectic solvents (NDESs) are promising biomass pretreatment media, but their industrial application is often hindered by high viscosity. To address this limitation, diol-enhanced ternary DESs (TDESs) were prepared by incorporating 1,4-butanediol (1,4-BDO) or ethylene glycol (EG) into a choline chloride (ChCl) and 3,4-dihydroxybenzoic acid (DHBA) system. The applied TDESs maintained a liquid state at room temperature and had significantly reduced viscosity compared to the binary DES (BDES). In addition, the applied diols increased lignin solubility and suppressed lignin condensation by intercepting reactive carbocation intermediates. As a result, the recovered lignins from diol-induced TDES pretreatments showed better preservation of β-O-4 linkages and reduced condensation, improving their potential for downstream valorization. The diol-assisted DES systems showed a synergistic effect from the reduced viscosity, enhanced lignin solubility, and suppression of unwanted... https://escholarship.org/uc/item/4nr7w0h2 Tue, 23 Jun 2026 00:00:00 +0000 Yoon, Chaehwi Ryu, Jiae Jeong, Soyeon Eudes, Aymerick https://orcid.org/0000-0002-1387-6111 Kim, Kwang Ho Yoo, Chang Geun https://escholarship.org/uc/item/5261m716 Birds and mammals exhibit extraordinary facial diversity, reflecting adaptations to distinct ecological niches and feeding strategies. While core face-building developmental programs are conserved and orchestrated by interactions between ectodermal organizers and the underlying mesenchyme, mechanisms driving facial shape variation remain poorly understood. Here, we integrate single-cell transcriptomic and chromatin accessibility profiling of mouse and chicken developing face to construct a comparative regulatory map. Although both ectodermal and mesenchymal populations display distinct regulatory features in each species, the mesenchyme exhibits markedly greater divergence, pointing to its central role in shaping facial morphology. We further reveal unexpected molecular complexity in the main face-shaping organizer, including a mouse-specific <i>Shh/Wnt5a</i> expression domain. At key morphogen loci (<i>Bmp4</i>, <i>Fgf8</i>, and <i>Wnt5a</i>), conserved and lineage-specific enhancers... https://escholarship.org/uc/item/5261m716 Thu, 18 Jun 2026 00:00:00 +0000 Kyomen, Stella Seton, Louk WG Cook, Laura E https://orcid.org/0000-0002-4459-2592 Escamilla-Vega, Elio Murillo-Rincón, Andrea P Jacobsen, Alexander Damatac, Amor Fortmann-Grote, Carsten Fuss, Janina Visel, Axel https://orcid.org/0000-0002-4130-7784 Kaucká, Markéta https://escholarship.org/uc/item/2sp79776 Groundwater acidification co-occurring with nitrate pollution is a common, global environmental health hazard. Denitrifying bacteria have been leveraged for the <i>in situ</i> removal of nitrate in groundwater. However, co-existing stressors-such as low pH-reduce the efficacy of biological removal processes. <i>Castellaniella</i> sp. str. MT123 is a complete denitrifier that was isolated from acidic, nitrate-contaminated groundwater. The strain grows robustly by nitrate respiration at pH &lt; 6.0, completely reducing nitrate to dinitrogen gas. Genomic analyses of MT123 revealed few previously characterized acid tolerance genes. Thus, we utilized a combination of proteomics, metabolomics, and competitive mutant fitness to characterize the genetic mechanisms of MT123 acclimation to growth under mildly acidic conditions. We found that glutamate accumulation is critical in the acid acclimation of MT123, possibly through consumption of intracellular protons via glutamate decarboxylation... https://escholarship.org/uc/item/2sp79776 Wed, 17 Jun 2026 00:00:00 +0000 Goff, Jennifer L Durrence, Konnor L Thorgersen, Michael P Trotter, Valentine V https://orcid.org/0000-0002-1784-9487 Chen, Yan Kosina, Suzanne M https://orcid.org/0000-0003-2885-1248 Wang, Audrey LW Poole, Farris L Northen, Trent R Petzold, Christopher J https://orcid.org/0000-0002-8270-5228 Deutschbauer, Adam M Adams, Michael WW https://escholarship.org/uc/item/8kd38654 Polyethylene (PE) is ubiquitous in modern environments yet remains highly recalcitrant, accumulating due to inefficient and poorly understood microbial degradation. Here, we used a comparative genomics framework to identify genetic features associated with the PE-degrading phenotype by analyzing 97 bacterial genomes with experimental evidence of PE degradation alongside 87 phylogenetically balanced control genomes lacking documented activity. Genome-wide functional annotation and orthology inference revealed a coherent set of gene families, significantly enriched in PE-degraders, including extracellular proteins, oxidoreductases, membrane transport systems, regulatory and stress-response functions consistent with growth at hydrophobic, high-molecular-weight carbon source. To assess whether a minimal genomic signature could discriminate degraders from controls, we applied an integer linear programming (ILP) approach to presence/absence and copy-number-thresholded orthogroup matrices.... https://escholarship.org/uc/item/8kd38654 Tue, 16 Jun 2026 00:00:00 +0000 Peixoto, Julianna Rocha, Rodrigo Steindorff, Andrei Krüger, Ricardo https://escholarship.org/uc/item/68k308v4 Giant viruses play crucial ecological roles in aquatic ecosystems, yet their evolutionary dynamics in response to environmental changes, particularly in freshwater environments, are not well understood. We analyzed a 20-year time series (2000-2019) of 471 co-assembled metagenomes from Lake Mendota (USA) to reconstruct 1512 giant virus metagenome-assembled genomes, providing insights into viral genome evolution. Viruses in the order Imitervirales dominate the virome, remaining consistent across seasons and years. Our findings reveal gene duplication (23% of genes) and horizontal gene transfer (29% of genes) as key drivers of genomic innovation. A co-occurrence network analysis indicates increased virus-host interactions following the introduction of an invasive predatory zooplankton in 2009, highlighting potential hosts in Bigyra, Perkinsea, and Euglenozoa. While single nucleotide polymorphism analysis shows predominantly purifying selection in viral genes, there is a significant... https://escholarship.org/uc/item/68k308v4 Tue, 16 Jun 2026 00:00:00 +0000 Vasquez, Yumary M Romero, Miguel F https://orcid.org/0000-0002-3799-717X Bowers, Robert M https://orcid.org/0000-0002-0028-0407 Rohwer, Robin R https://orcid.org/0000-0002-2664-6489 McMahon, Katherine D https://orcid.org/0000-0002-7038-026X Woyke, Tanja https://orcid.org/0000-0002-9485-5637 Schulz, Frederik https://orcid.org/0000-0002-4932-4677 https://escholarship.org/uc/item/3k23z7th Lipid nanoparticles (LNPs) are versatile carriers for nucleic acid (NA) therapeutics, including ASOs, siRNA, mRNA, and poly-IC. While lipid composition is known to influence LNP properties, the impact of NA length on morphology and internal structure is less understood, particularly during the stages of carrier-cargo assembly. Here, we examine NA length and lipid composition immediately after mixing using high-throughput SAXS, dynamic light scattering, and cryogenic electron microscopy. All LNPs form ordered NA/lipid compartments, with longer NAs promoting inverse hexagonal (H_II) phases and larger intercompartment distances. In contrast, short NAs, especially in formulations with SM102 ionizable lipid, favor lamellar phases. SAXS peak deconvolution quantifies ordered versus disordered phases via a Robustness of Ordered Phase factor, which correlates with particle size and encapsulation efficiency. Formulations with MC3 ionizable and DOPE helper lipids exhibit the most... https://escholarship.org/uc/item/3k23z7th Wed, 10 Jun 2026 00:00:00 +0000 Hammel, Michal https://orcid.org/0000-0002-5610-9289 Fan, Yuchen Kim, Lee Joon Zang, Nanzhi Xiao, Baixue Calio, Antonino https://orcid.org/0000-0003-2324-2902 Yen, Chun-Wan Hura, Greg L https://escholarship.org/uc/item/2tp8r25f Pretreatment of poplar biomass with butylamine released &gt;100 g L −1 of fermentable sugars and supported the biosynthesis of three different bioproducts. Low-boiling alkylamines such as butylamine offer promise as effective biomass pretreatment solvents that can be readily recovered and recycled; however, their capability to support microbial conversion of nutrients present in hydrolysates represents an important area for investigation. Here we employed butylamine to pretreat poplar biomass and characterize its effects on the release of fermentable sugars after solvent removal and enzymatic hydrolysis, as well as the biocompatibility of the produced hydrolysates with three organisms commonly used as bioconversion hosts. We observed that residual butylamine and the derivative butylacetamide were present in high enough concentrations to exert toxicity to strains of Aspergillus niger , Pseudomonas putida , and Rhodosporidium toruloides that produce malic acid, isoprenol and bisabolene,... https://escholarship.org/uc/item/2tp8r25f Wed, 10 Jun 2026 00:00:00 +0000 Jia, Jiayuan Dietrich, Demian Pidatala, Venkataramana R Turumtay, Emine Akyuz Baidoo, Edward EK Barcelos, Carolina A Palasz, Joseph Rahman, Md Maksudur Kang, Chae Won Garcia, Valentina E Koleski, Edward Panich, Justin Sundstrom, Eric R https://orcid.org/0000-0003-4983-5415 Eudes, Aymerick https://orcid.org/0000-0002-1387-6111 Choudhary, Hemant Lee, Taek Soon Gladden, John M https://orcid.org/0000-0002-6985-2485 Simmons, Blake A https://orcid.org/0000-0002-1918-3463 Kim, Joonhoon Rodriguez, Alberto https://escholarship.org/uc/item/9fn6w55v Correction to: Nature Microbiologyhttps://doi.org/10.1038/s41564-025-02116-2, published online 26 September 2025. In the version of this article initially published, in the first paragraph of the “Survey on data reuse” section, a note on participant consent, confidentiality and institutional review was missing and has now been inserted in the HTML and PDF versions of the article. https://escholarship.org/uc/item/9fn6w55v Fri, 5 Jun 2026 00:00:00 +0000 Hug, Laura A Hatzenpichler, Roland Moraru, Cristina Soares, André R Meyer, Folker Heyder, Anke Probst, Alexander J https://escholarship.org/uc/item/4cn2981q Nuclear mechanics is remodeled not only by extracellular forces but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the nuclear structures undergo drastic reorganization, but little is known about how nuclear mechanobiology changes as a result. We show that the nucleus softens dramatically during the infection. To understand the phenomenon, we used advanced microscopy and computational modeling. We discovered that the enlarged viral replication compartment had a low biomolecular density, partially explaining the observed nuclear softening. The mobility of the nuclear lamina decreased, which suggests increased rigidity and an inability to induce softening. However, computational modeling supported by experimental data showed that reduced outward forces, such as cytoskeletal pull and intranuclear osmotic pressure acting both on and within the nucleus, can explain the decreased nuclear stiffness. Our findings... https://escholarship.org/uc/item/4cn2981q Fri, 5 Jun 2026 00:00:00 +0000 Tervonen, Aapo Ruokolainen, Visa Leclerc, Simon Tieu, Katie Lyonnais, Sébastien Niskanen, Henri Chen, Jian-Hua Gupta, Alka Kaikkonen, Minna Larabell, Carolyn Muriaux, Delphine Mattola, Salla Conway, Daniel Ihalainen, Teemu Aho, Vesa Vihinen-Ranta, Maija https://escholarship.org/uc/item/4dt9033k Enhanced biological phosphorus removal (EBPR) systems often rely on exogenous carbon sources, such as volatile fatty acids (VFAs), to achieve higher P removal. Here, we employed DNA quantitative stable isotope probing (qSIP) using two VFAs, acetate and propionate, in cyclic anaerobic/aerobic incubations to assess their effects on P cycling and microbial activity with biomass from two full-scale EBPR water resource-recovery facilities that utilize VFA addition. We found that anaerobic VFA uptake preferences differed within known groups of PAOs, such as <i>Candidatus</i> Accumulibacter and <i>Tetrasphaera</i>-affiliated members (e.g., <i>Ca</i>. Phosphoribacter), between the two biomasses. The combination of qSIP with metagenomics identified isotopically labeled phages that were linked to active PAOs, highlighting their potential roles in modulating EBPR community composition and activity. The highest levels of anaerobic labeling from acetate were in genomes belonging to <i>Saccharimonadales</i>... https://escholarship.org/uc/item/4dt9033k Thu, 4 Jun 2026 00:00:00 +0000 Sampara, Pranav Tomatsu, Andy Malmstrom, Rex R https://orcid.org/0000-0002-4758-7369 Ziels, Ryan M https://escholarship.org/uc/item/41p6v8d6 Soft X-ray tomography (SXT) is an invaluable tool for quantitatively analyzing cellular structures at suboptical isotropic resolution. However, it has traditionally depended on manual segmentation, limiting its scalability for large datasets. Here, we leverage a deep learning-based autosegmentation pipeline to segment and label cellular structures in hundreds of cells across three <i>Saccharomyces cerevisiae</i> strains. This task-based pipeline uses manual iterative refinement to improve segmentation accuracy for key structures, including the cell body, nucleus, vacuole, and lipid droplets, enabling high-throughput and precise phenotypic analysis. Using this approach, we quantitatively compared the three-dimensional (3D) whole-cell morphometric characteristics of wild-type, VPH1-GFP, and <i>vac14</i> strains, uncovering detailed strain-specific cell and organelle size and shape variations. We show the utility of SXT data for precise 3D curvature analysis of entire organelles... https://escholarship.org/uc/item/41p6v8d6 Thu, 4 Jun 2026 00:00:00 +0000 Chen, Jianhua https://orcid.org/0000-0002-7998-0878 Mirvis, Mary Ekman, Axel Vanslembrouck, Bieke Le Gros, Mark Larabell, Carolyn Marshall, Wallace F https://escholarship.org/uc/item/36v2q29h This Genome Watch article highlights the importance of predictive models for identifying and characterizing the roles of phage tail-like particles as a tool for bioengineering and biocontrol. https://escholarship.org/uc/item/36v2q29h Wed, 3 Jun 2026 00:00:00 +0000 Cho, Heejung Dao, Thai Q https://escholarship.org/uc/item/8sn705jr Scaling biomanufacturing from laboratory to industrial scale poses significant challenges, especially for continuous fermentation. This study investigates these challenges using a β-carotene-producing Yarrowia lipolytica strain. Through fermentation experiments and proteomics, we have assessed how fermentation modes, carbon sources, dissolved O₂, and media composition influence long-term bioproduction. In shaking flask subcultures, the strain maintained β-carotene production for over ~30 generations. However, in continuous fermentations, subpopulation shifted toward faster-growing low-producers, leading to significant production losses within just ~18 growth generations. This process was accelerated by O₂ limitation and high bioreactor dilution rates. Using canola oil as a carbon source increases population heterogeneity but enhances β-carotene biosynthesis and prolongs production compared with glucose-based media. Kinetic modeling suggests that strains optimized... https://escholarship.org/uc/item/8sn705jr Mon, 25 May 2026 00:00:00 +0000 Worland, Alyssa M Xu, Vincent A Duran, Maria F Gitman, Philip Hunter-Cevera, Kristen Klemm, Cinzia Sun, Yufei Sanchis, Diego Ruiz Ledesma-Amaro, Rodrigo Pomraning, Kyle R Tanjore, Deepti https://orcid.org/0000-0001-6507-4359 Blenner, Mark Tang, Yinjie J https://escholarship.org/uc/item/5sz3g043 <p> Correction for ‘Sustainable bioproduction of the blue pigment indigoidine: Expanding the range of heterologous products in R. toruloides to include non-ribosomal peptides’ by Maren Wehrs et al. , Green Chem. , 2019, 21 , 3394–3406. </p> https://escholarship.org/uc/item/5sz3g043 Mon, 25 May 2026 00:00:00 +0000 Wehrs, Maren Gladden, John M https://orcid.org/0000-0002-6985-2485 Liu, Yuzhong Platz, Lukas Prahl, Jan-Philip Moon, Jadie Papa, Gabriella https://orcid.org/0000-0001-5011-5752 Sundstrom, Eric https://orcid.org/0000-0003-4983-5415 Geiselman, Gina M Tanjore, Deepti https://orcid.org/0000-0001-6507-4359 Keasling, Jay D https://orcid.org/0000-0003-4170-6088 Pray, Todd R Simmons, Blake A https://orcid.org/0000-0002-1918-3463 Mukhopadhyay, Aindrila https://orcid.org/0000-0002-6513-7425 https://escholarship.org/uc/item/32m5d7j1 Feedstock variability is a significant barrier to the scale-up and commercialization of lignocellulosic biofuel technologies. Variability in feedstock characteristics and behavior creates numerous challenges to the biorefining industry by affecting continuous operation and biofuels yields. Currently, feedstock variability is understood and explained largely on the basis of chemical composition. Physical and mechanical properties and behavior of lignocellulosic feedstock in various unit operations, studied through advanced analytical methods, can further explain variability. Such studies will enable us in developing processes and designing equipment to improve operation and conversion performance. In this perspective, we review several advanced analytical methods that measure density, moisture content, thermal properties, flowability, grindability, rheology properties, and micromorphological characteristics. We also discuss the correlations and interactions among these properties... https://escholarship.org/uc/item/32m5d7j1 Mon, 25 May 2026 00:00:00 +0000 Yan, Jipeng Oyedeji, Oluwafemi Leal, Juan H Donohoe, Bryon S Semelsberger, Troy A Li, Chenlin Hoover, Amber N Webb, Erin Bose, Elizabeth A Zeng, Yining Williams, C Luke Schaller, Kastli D Sun, Ning https://orcid.org/0000-0002-9689-9430 Ray, Allison E Tanjore, Deepti https://orcid.org/0000-0001-6507-4359 https://escholarship.org/uc/item/5f61q0gf The structural biology method of X-ray footprinting mass spectrometry (XFMS) is available at two national synchrotron beamlines in the USA: one at the Advanced Light Source (ALS) on the West Coast and the other at the National Synchrotron Light Source II on the East Coast. XFMS is a solution-state technique that utilizes oxidative modifications of proteins at micromolar concentrations in aqueous buffer to extract structural information. X-rays are employed to generate hydroxyl radicals in situ, which covalently modify specific protein side chains. These modifications are subsequently quantified using liquid chromatography and mass spectrometry. Ratiometric changes in modification levels between two protein states (e.g. with and without ligand) generate a relative solvent accessibility map of the protein pairs, which serves to reveal structural features. Up until recently, the XFMS capability was available as part of a shared program at the ALS without a dedicated beamline. In... https://escholarship.org/uc/item/5f61q0gf Thu, 21 May 2026 00:00:00 +0000 Gupta, Sayan Russell, Brandon https://orcid.org/0000-0001-8949-2432 Kristensen, Line G https://orcid.org/0000-0002-7819-2861 de Chant, Jared Lu, Anthony https://orcid.org/0000-0001-9098-9913 Obst-Huebl, Lieselotte https://orcid.org/0000-0001-9236-8037 Rad, Behzad Tyler, James Subramanian, Simruthi Kidd, Savannah https://orcid.org/0000-0002-7162-3358 Paul, Sathi Chen, Yan Petzold, Christopher J https://orcid.org/0000-0002-8270-5228 Kahan, Darren N https://orcid.org/0000-0002-8245-3489 Costello, Shawn M Nakamura, Kei Inman, Jamie L MacDowell, Alastair A Spucces, Adrian Ralston, Corie Y https://orcid.org/0000-0002-7899-0951 https://escholarship.org/uc/item/26r2v553 This perspective outlines emerging trends, key challenges, and future opportunities in evolutionary and comparative genomics. Our starting point are the topics presented at the 2024 EMBO Early Career Lecture Course "Evolutionary and Comparative Genomics", which highlighted recent conceptual and methodological advances in areas ranging from microbial pangenomes, protein evolution, hybrid speciation, novel gene origination and transposon dynamics. Here, we emphasize the role of computational and molecular approaches, providing a forward-looking view on where the field is headed and how it is being reshaped by new technologies and approaches. https://escholarship.org/uc/item/26r2v553 Mon, 18 May 2026 00:00:00 +0000 Gavriilidou, Athina Stamatakis, Alexandros Kupczok, Anne Bista, Iliana Jiggins, Chris D Fernández, Rosa Skourtanioti, Eirini Amoutzias, Grigoris Delneri, Daniela Kyrpides, Nikos https://orcid.org/0000-0002-6131-0462 Nikolaou, Christoforos Pittis, Alexandros A Manousaki, Tereza Vakirlis, Nikolaos https://escholarship.org/uc/item/8gb9j1gf Eukaryotic genomes harbor many forms of variation, including nucleotide diversity and structural polymorphisms, which experience natural selection and contribute to genome evolution and biodiversity. Harnessing this variation for agriculture hinges on our ability to detect, quantify, catalog, and deploy genetic diversity. Here, we explore seven complete genomes of the emerging biofuel crop pennycress (Thlaspi arvense) drawn from across the species' current genetic diversity to catalog variation in genome structure and content. Across this new pangenome resource, we find contrasting evolutionary modes in different genomic zones. Gene-poor, repeat-rich pericentromeric regions experience frequent rearrangements, including repeated centromere repositioning. By contrast, conserved gene-dense chromosome arms maintain large-scale synteny across accessions even in fast-evolving NOD-like receptor immune genes, where microsynteny breaks down across species, but gene cluster positioning... https://escholarship.org/uc/item/8gb9j1gf Fri, 15 May 2026 00:00:00 +0000 Bird, Kevin A Rifkin, Joanna L McLaughlin, Chloee M Harder, Avril M Basnet, Pawan Katz, Ella Brůna, Tomáš Barry, Kerrie https://orcid.org/0000-0002-8999-6785 Boston, LoriBeth Daum, Christopher https://orcid.org/0000-0003-3895-5892 Guo, Jie Lipzen, Anna https://orcid.org/0000-0003-2293-9329 Plott, Christopher Jenkins, Jerry W Walstead, Rachel Rajasekar, Shanmugam Talag, Jayson Frels, Katherine Greenham, Kathleen Ellison, Shelby Grimwood, Jane Schmutz, Jeremy Edger, Patrick P Pires, J Chris Lovell, John T Kliebenstein, Daniel J https://orcid.org/0000-0001-5759-3175 https://escholarship.org/uc/item/7427z4wp YAP1 is a cotranscription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested whether YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. In this study, we find that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression, and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility, such as genes associated with stem cell states,... https://escholarship.org/uc/item/7427z4wp Fri, 15 May 2026 00:00:00 +0000 Fresques, Tara Lopez, Jennifer C Hussey, Deborah Miyano, Masaru Garbe, James C https://orcid.org/0000-0002-4041-3868 Hinz, Stefan Sayaman, Rosalyn W Li, Aimin Schmolze, Daniel Van Bedford, Serenity Stampfer, Martha R https://orcid.org/0000-0002-3801-5086 LaBarge, Mark A https://escholarship.org/uc/item/39c6s8tn Multipolar scattering models, such as the transferable aspherical atom model, account for atomic chemical interactions and provide a more accurate representation of experimental data. However, the simpler independent atom model (IAM), which assumes non-interacting atoms, is the only model available in the most widely used macromolecular refinement programs. This is primarily because IAM offers a hard-to-beat combination of computational efficiency and modelling power at typical macromolecular resolutions. By contrast, more accurate multipolar modelling has historically been limited due to its computational cost and the absence of an interface between software capable of calculating structure factors and gradients based on multipolar models and software designed for macromolecular refinement. This work introduces <i>pyDiSCaMB</i>, a Python software package designed to integrate between the computational crystallography toolbox (<i>cctbx</i>) and the quantum crystallography library... https://escholarship.org/uc/item/39c6s8tn Fri, 15 May 2026 00:00:00 +0000 Femoen, Viljar J Pacoste, Laura Chodkiewicz, Michał Leszek Afonine, Pavel V Poon, Billy K Kulik, Marta Golon, Łukasz Moriarty, Nigel W https://orcid.org/0000-0001-8857-9464 Adams, Paul D https://orcid.org/0000-0001-9333-8219 Hofer, Gerhard Dominiak, Paulina Maria Liebschner, Dorothee https://orcid.org/0000-0003-3921-3209 Zou, Xiaodong https://escholarship.org/uc/item/151482pd Ectomycorrhizal fungi (EMF) produce mycelia with variable extension and complexity, which can be classified according to soil 'exploration types' (ETs). ETs have received attention as one of the few mycorrhizal trait frameworks, but without an empirical classification of ET functional diversity and environmental preferences, understanding and interpreting EMF biogeographic patterns has been difficult. We conducted a synthesis combining: comparative EMF genomics to describe functional divergence in decomposition and nutrient cycling genes across ETs; and EMF trait distribution modeling across continental Europe, pairing soil and root EMF surveys to establish biogeographic ET niche profiles. We demonstrate a signature of ETs encoded in EMF genomes, which is independent from phylogeny and linked to biomass production strategies. EMF ET relative abundances were separated by soil, root, and dominant tree leaf type habitats and exhibited unique correlations with forest biotic (e.g.... https://escholarship.org/uc/item/151482pd Fri, 15 May 2026 00:00:00 +0000 Mansfield, Thomas M Zarsav, Artin Cox, Filipa Suz, Laura M Bidartondo, Martin I van der Linde, Sietse Barsoum, Nadia Averill, Colin Kuo, Alan https://orcid.org/0000-0003-3514-3530 Tedersoo, Leho Rautio, Pasi Gessler, Arthur De Vos, Bruno Croisé, Luc Meesenburg, Henning Wagner, Markus Jacob, Frank Lech, Paweł Kowalska, Anna Greve, Martin Popova, Genoveva Frey, Beat Schaub, Marcus Ferretti, Marco Waldner, Peter Calatayud, Vicent Canullo, Roberto Papitto, Giancarlo Marinšek, Aleksander Vesterdal, Lars Ingerslev, Morten Meissner, Helge Timmermann, Volkmar Eickenscheidt, Nadine Schmitz, Andreas Martin, Francis M Spatafora, Joseph Kennedy, Peter G Kohler, Annegret Plett, Jonathan M Anderson, Ian C Branco, Sara Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Pires, Chris J Unruh, Sarah A Zettler, Lawrence W Miettinen, Otto Viner, Ilya May, Tom W Lebel, Teresa Catcheside, David EA Catcheside, Pamela S Vonow, Helen P Burgoyne, Leigh A Haska, Julia Anthony, Mark A https://escholarship.org/uc/item/2zr0520r The current status of advanced water splitting pathways (using photoelectrochemical, biological and thermochemical platforms) toward viable technologies to produce renewable and sustainable hydrogen is assessed in a virtual international meeting. Hydrogen is an essential fuel and feedstock that can be produced in multiple ways to meet requirements for technological sectors that include energy storage, transportation, petroleum refining, and ammonia synthesis. To consider the future state of hydrogen manufacturing, a team of experts has assembled and examined three emerging hydrogen production technologies – photoelectrochemical, biological, and thermochemical. Each of these emerging technologies holds significant long-term potential for cost reduction while lowering industrial emissions associated with conventional methods of hydrogen manufacture ( e.g. , steam methane reforming) by using sunlight and renewable resources as primary sources of energy and feedstock, respectively.... https://escholarship.org/uc/item/2zr0520r Thu, 14 May 2026 00:00:00 +0000 Chou, Katherine J Acevedo, Yaset Agbo, Peter https://orcid.org/0000-0003-3066-4791 Bayon, Alicia Beliaev, Alexander S Beyenal, Haluk Croft, Trevor Elgowainy, Amgad Esposito, Daniel V Falter, Christoph Ginley, David S Haussener, Sophia Hu, Shu Koepf, Erik Kumar, Dhananjay Lidor, Alon Logan, Bruce E Loutzenhiser, Peter Mandalika, Anurag S Maness, PinChing Meyer, Gerald J Nathan, Graham J Rossi, Ruggero Stechel, Ellen B Sundstrom, Eric R https://orcid.org/0000-0003-4983-5415 Warren, Emily Wendt, Lynn M Xiang, CX McDaniel, Anthony H Houle, Frances A https://orcid.org/0000-0001-5571-2548 https://escholarship.org/uc/item/27d5n301 Transcription factors establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility and regulating gene expression1. Mapping accessible chromatin offers critical insights into transcriptional control, but available datasets for human development are restricted to bulk tissue, single organs or single modalities2. Here we present the Human Development Multiomic Atlas, a single-cell atlas of chromatin accessibility and gene expression from 817,740 fetal cells across 12 organs, spanning 203 cell types and more than 1 million candidate cis-regulatory elements, many of which exhibit organ-specific in vivo enhancer activity. Deep learning models trained to predict accessibility from local DNA sequence unravel a comprehensive lexicon of motifs that influence accessibility, including composite motifs exhibiting distinct syntactic constraints that are predicted to mediate transcription factor cooperativity.... https://escholarship.org/uc/item/27d5n301 Thu, 14 May 2026 00:00:00 +0000 Liu, Betty B Jessa, Selin Kim, Samuel H Ng, Yan Ting Higashino, Soon Il Marinov, Georgi K Chen, Derek C Parks, Benjamin E Li, Li Nguyen, Tri C Wang, Austin T Wang, Sean K Tan, Meng How Tan, Serena Y Kosicki, Michael Pennacchio, Len A https://orcid.org/0000-0002-8748-3732 Ben-David, Eyal Pasca, Anca M Kundaje, Anshul Farh, Kyle KH Greenleaf, William J https://escholarship.org/uc/item/4fd96726 A large number of biological entities assemble into icosahedral structures, and these are ubiquitous throughout nature. Examples include eukaryotic and prokaryotic viral capsids and more recently discovered bacterial microcompartments. Viral capsids and bacterial microcompartments are both composed of pentameric and hexameric subunits; however, they differ in the type of cargo they encapsulate: nucleic acid or protein. Also, both depart from strict icosahedral symmetry: while this is less common in viruses, among bacterial microcompartments, diverse and heterogeneous polyhedra are common. We review shared principles and key distinctions between the self-directed assembly of various icosahedral architectures and their polyhedral variants in nature and explore the concept that there are multiple paths, influenced by their cargo, to arriving at similar protein cage morphologies. https://escholarship.org/uc/item/4fd96726 Wed, 13 May 2026 00:00:00 +0000 Parent, Kristin N Kerfeld, Cheryl A https://orcid.org/0000-0002-9977-8482 https://escholarship.org/uc/item/16g2s3xh Endophytic fungi from Deschampsia antarctica, the southernmost flowering plant, provide insights into the cold adaptation mechanisms of plant-associated fungi in extreme environments. This study presents the genome sequences and comparative analysis of eight fungal isolates from D. antarctica leaves. These Antarctic fungal isolates were analyzed alongside 121 plant-associated fungal genomes to uncover signatures of adaptation and endophytic specialization. Antarctic endophytes show striking patterns, including reduced genome size (∼26.3&nbsp;Mb on average), streamlined gene content (∼8844 genes), and notably small secretomes (∼288 proteins). Despite this reduced gene repertoire, they maintain a robust set of genes encoding carbohydrate-active enzymes (CAZymes) but lack those for lignin and bacterial cell wall degradation, indicating a symbiotic lifestyle that avoids host damage and predation. One isolate, Alternaria sp. UNIPAMPA017 stood out, with 26% of its genome occupied by... https://escholarship.org/uc/item/16g2s3xh Wed, 13 May 2026 00:00:00 +0000 Lucini, Fabíola Lebreton, Annie Seifollahi, Elaheh Barry, Kerrie W https://orcid.org/0000-0002-8999-6785 Haridas, Sajeet Ahrendt, Steven https://orcid.org/0000-0001-8492-4830 Hayes, Richard D https://orcid.org/0000-0002-5236-7918 LaButti, Kurt https://orcid.org/0000-0002-5838-1972 Pangilinan, Jasmyn Riley, Robert https://orcid.org/0000-0003-0224-0975 Wang, Jie Lipzen, Anna https://orcid.org/0000-0003-2293-9329 He, Guifen Eichenberger, Joanne Kuo, Alan https://orcid.org/0000-0003-3514-3530 Mondo, Stephen J https://orcid.org/0000-0001-5797-0647 Andreopoulos, Willian Drula, Elodie Bonito, Gregori Vilgalys, Rytas Albuquerque, Margeli P Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Batista, Thiago Mafra Miyauchi, Shingo Martin, Francis M Victoria, Filipe C https://escholarship.org/uc/item/5kf76306 Microbial nitrification of fertilizers represents is a significant global source of greenhouse gas emissions. This process increases emissions, fosters toxic algal blooms, and raises crop production costs. Some plants naturally release biological nitrification inhibitors to suppress ammonium-oxidizing microbes and reduce nitrification. Engineering nitrification inhibitor production into food and bioenergy crops via synthetic biology offers a promising mitigation strategy, but its success depends on addressing gaps in our understanding of inhibitor degradation in soil. This study begins to fill this gap by identifying a previously unknown microbial pathway for degrading phenylpropanoid methyl esters, a key class of aromatic nitrification inhibitors. Using transcriptomics and high-throughput functional genomics, we discovered genes essential for phenylpropanoid methyl ester degradation. Genetic and biochemical analyses revealed two novel enzymes, including a newly identified phenylpropanoid... https://escholarship.org/uc/item/5kf76306 Thu, 7 May 2026 00:00:00 +0000 Wilson, Andrew Van Fossen, Elise Shrestha, Ritu Frank, Andrew Trotter, Valentine https://orcid.org/0000-0002-1784-9487 Baldino, Henri Poirier, Brenton Kim, Young-Mo Nelson, William Simmons, Tuesday Coleman-Derr, Devin Deutschbauer, Adam Egbert, Robert Elmore, Joshua https://escholarship.org/uc/item/0nt0t4k2 The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate... https://escholarship.org/uc/item/0nt0t4k2 Wed, 6 May 2026 00:00:00 +0000 Kelliher, Julia M Mirzayi, Chloe Bordenstein, Sarah R Oliver, Aaron https://orcid.org/0000-0002-0410-8284 Kellogg, Christina A Hatcher, Eneida L Berg, Maureen Baldrian, Petr Aljumaah, Mashael Miller, Cassandra Maria Luz Mungall, Christopher Novak, Vlastimil https://orcid.org/0000-0001-7890-4593 Palucki, Alexis Smith, Ethan Tabassum, Nazifa Bonito, Gregory Brister, J Rodney Chain, Patrick SG Chen, Mingfei Degregori, Samuel Dundore-Arias, Jose Pablo Emerson, Joanne B https://orcid.org/0000-0001-9983-5566 Moreira C. Fernandes, Vanessa Flores, Roberto Gonzalez, Antonio Hansen, Zoe A Jackson, Scott A Moustafa, Ahmed M Northen, Trent R https://orcid.org/0000-0001-8404-3259 Pariente, Nonia Pett-Ridge, Jennifer Record, Sydne Reji, Linta Reysenbach, Anna-Louise Rich, Virginia I Richardson, Lorna Roux, Simon https://orcid.org/0000-0002-5831-5895 Schriml, Lynn M Shabman, Reed S Sierra, Maria A Sullivan, Matthew B Sundaramurthy, Punithavathi Thibault, Katherine M Thompson, Luke R Tighe, Scott Vereen, Ethell Eloe-Fadrosh, Emiley A https://orcid.org/0000-0002-8162-1276 https://escholarship.org/uc/item/8s85j1vr Background: Advances in medicine depend on analyzing large and complex data sources, but discovery is partly constrained by the limited time and domain expertise of human researchers. Agentic artificial intelligence (agentic AI) can accelerate discovery by automating components of the scientific workflow, including information retrieval, data analysis, and knowledge synthesis. Aim: OpenScientist, an open-source agentic AI co-scientist, aims to accelerate biomedical discovery by semi-autonomously investigating scientist-defined queries and generating clinically relevant, verifiable scientific insights. Methods: Domain experts evaluated OpenScientist for novel discoveries in four clinical case studies: (1) a prespecified analysis in a community-based Alzheimer's disease biomarker cohort, (2) unsupervised modeling for plasma proteomic survival prediction, (3) hypothesis investigation in single-cell transcriptomic data from neurons with neurofibrillary tangles, and (4) hypothesis... https://escholarship.org/uc/item/8s85j1vr Tue, 5 May 2026 00:00:00 +0000 Roberts, Kaleigh F Abrams, Zachary B Cappelletti, Luca Moqri, Mahdi Heugel, Nicholas Caufield, J Harry Bourdenx, Mathieu Li, Yan Banerjee, Jineta Foschini, Luca Galeano, Diego Harris, Nomi L Li, Melody Ying, Kejun Melendez, Justin A Barthélemy, Nicolas R Bollinger, James G He, Yingxin Ovod, Vitaliy Benzinger, Tammie LS Flores, Shaney Gordon, Brian A Ojewole, Adegoke A Phatak, Mukta Elbert, Donald L Biber, Sarah Landsness, Eric C Mungall, Christopher J Bateman, Randall J Reese, Justin T https://escholarship.org/uc/item/1wh3c8n2 Science benefits from rapid open data sharing, but current guidelines for data reuse were established two decades ago, when databases were several million times smaller than they are today. These guidelines are largely unfamiliar to the scientific community, and, owing to the rapid increase in biological data generated in the past decade, they are also outdated. As a result, there is a lack of community standards suited to the current landscape and inconsistent implementation of data sharing policies across institutions. Here we discuss current sequence data sharing policies and their benefits and drawbacks, and present a roadmap to establish guidelines for equitable sequence data reuse, developed in consultation with a data consortium of 167 microbiome scientists. We propose the use of a Data Reuse Information (DRI) tag for public sequence data, which will be associated with at least one Open Researcher and Contributor ID (ORCID) account. The machine-readable DRI tag indicates... https://escholarship.org/uc/item/1wh3c8n2 Mon, 27 Apr 2026 00:00:00 +0000 Hug, Laura A Hatzenpichler, Roland Moraru, Cristina Soares, André R Meyer, Folker Heyder, Anke Probst, Alexander J https://escholarship.org/uc/item/82f783zt Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an unprecedented tryptophan handshake dimer, conserved interface di-Trp-Pro pocket, and adjustable "wrist" enabling an open-closed conformational switch. EEPD1 dimer cooperatively binds complex dsDNA replication... https://escholarship.org/uc/item/82f783zt Fri, 24 Apr 2026 00:00:00 +0000 Shen, Runze Sarker, Altaf H https://orcid.org/0000-0001-6868-8460 Chen, Yue Liu, Min Roy, Sunetra Arvai, Andrew S Bacolla, Albino Ahmed, Zamal Katsonis, Panagiotis Hammel, Michal Kuraoka, Isao Tsai, Miaw-Sheue Irie, Corydon Webb, Lukas Lichtarge, Olivier Tsai, Chi-Lin Tsutakawa, Susan E https://orcid.org/0000-0002-4918-4571 Schlacher, Katharina Tainer, John A https://escholarship.org/uc/item/7931m174 <i>Agrobacterium</i> is not only a costly plant pathogen but is also an essential tool for plant transformation. Though <i>Agrobacterium</i>-mediated transformation (AMT) has been heavily studied, its polygenic nature and complex transcriptional regulation make identification of the genetic basis of transformational efficiency difficult through traditional genetic and bioinformatic approaches. Here, we use a bottom-up synthetic approach to systematically engineer the tumor-inducing plasmid (pTi), wherein the majority of virulence machinery is encoded. Using a validated toolkit to control <i>Agrobacterium</i> gene expression <i>in planta</i>, we perform a quantitative dissection of AMT to investigate the contributions of critical <i>vir</i>-genes at different expression levels. We construct a synthetic pTi capable of transient plant and stable fungal transformation and characterize bottlenecks and solutions for complex polygenic synthetic pTi designs. Our reductionist approach... https://escholarship.org/uc/item/7931m174 Fri, 24 Apr 2026 00:00:00 +0000 Thompson, Mitchell G Kirkpatrick, Liam D Szarzanowicz, Matthew J Geiselman, Gina M Waldburger, Lucas M Pearson, Allison N Vuu, Khanh M Markel, Kasey Hummel, Niklas FC Incha, Matthew R Suazo, Dennis D https://orcid.org/0000-0001-5088-9328 Tahmin, Claudine Cui, Ruoming Liu, Shuying Cevallos, Jasmine Pannu, Hamreet Lapp, Nathan Liu, Di Gin, Jennifer W https://orcid.org/0000-0001-5636-7563 Chen, Yan Petzold, Christopher J https://orcid.org/0000-0002-8270-5228 Gladden, John M https://orcid.org/0000-0002-6985-2485 Keasling, Jay D https://orcid.org/0000-0003-4170-6088 Chang, Jeff H Weisberg, Alexandra J Shih, Patrick M https://escholarship.org/uc/item/70s4j2b6 Time-resolved step-scan Fourier transform infrared (FTIR) difference spectroscopy was used to obtain (A₁ ^- - A₁) FTIR difference spectra from photosystem I (PSI) samples isolated from eight phylogenetically diverse cyanobacterial strains and one green alga, totaling 13 PSI preparations. These included samples from cells grown under far-red light and PSI in monomeric, dimeric, trimeric, and tetrameric states. Spectral profiles were shown to be independent of oligomeric state. Remarkably, all (A₁ ^- - A₁) FTIR difference spectra exhibited high similarity, underscoring the robustness of the technique and indicating minimal experimental variability. This congruence reveals a highly conserved environment for the phylloquinone cofactor at the A₁ binding site across diverse taxa. Conserved bands associated with the A₀ pigment further suggest structural continuity from A₀ to A₁.... https://escholarship.org/uc/item/70s4j2b6 Fri, 24 Apr 2026 00:00:00 +0000 Hastings, Gary Makita, Hiroki Agarwala, Neva Nelson, Michael R Kirpich, Julia S Singh, Komalpreet Parameswaran, Sreeja Ali, Fedaa Bruce, Barry D Liu, Haijun Luo, Lujun Xu, Wu Redding, Kevin Schade, Claudia Mäusle, Sarah M Nürnberg, Dennis J https://escholarship.org/uc/item/5k04t6m1 Ubiquilins are molecular chaperones that play multifaceted roles in proteostasis, with point mutations in UBQLN2 leading to altered phase-separation properties and amyotrophic lateral sclerosis (ALS). Our mechanistic understanding of this essential process has been hindered by a lack of structural information on the STI1 domain, which is essential for ubiquilin chaperone activity and phase separation. Here, we present the first crystal structure of a ubiquilin-family STI1 domain bound to a transmembrane domain (TMD), and show that ALS mutations disrupt the STI1-TMD interaction. We further demonstrate that ubiquilins contain multiple conserved internal sequences that bind to the STI1 domain, including the PXX-repeat region that is a hotspot for ALS mutations. We propose that these placeholder sequences prevent solvent exposure of the STI1 hydrophobic groove and contribute to the multivalency that drives ubiquilin phase-separation. Together, this work provides a new paradigm for... https://escholarship.org/uc/item/5k04t6m1 Fri, 24 Apr 2026 00:00:00 +0000 Onwunma, Joan Binsabaan, Saeed Allen, Shawn P Thanthirige, Sachini R Gaur, Deepika Sankaran, Banumathi Wohlever, Matthew L https://escholarship.org/uc/item/4bb4x35r Hybridization is a major force driving diversification, migration, and adaptation in Quercus species. While population genetics and phylogenetics have traditionally been used for studying these processes, advances in sequencing technology now enable us to incorporate comparative and pan-genomic approaches as well. Here, we present a highly contiguous, chromosome-scale and haplotype-resolved genome assembly for the southern live oak, Quercus virginiana, the first reference genome for section Virentes, as part of the American Campus Tree Genomes program. Originating from a clone of Auburn University's historic "Toomer's Oak," this assembly contributes to the pool of genomic resources for investigating recombination, haplotype variation, and structural genomic changes influencing hybridization potential in this clade and across Quercus. It also provides insights into the architecture of the putative centromeric regions within the genus. Alongside other oak references, the Q. virginiana... https://escholarship.org/uc/item/4bb4x35r Fri, 24 Apr 2026 00:00:00 +0000 Aközbek, Laramie Meharg, Zachary Abendroth-McGhee, Jillian Akinsipe, Tosin Dhakal, Rijan Gladstone, Nicholas Pervaiz, Zahida Patel, Sejal Rossi, Giovani Rutland, Claudia Ann Bendickson, Caroline Kranz, Adam Martinson, Ellen O Egan, Scott P Feltus, F Alex Clarke, David J Lovell, John T Webber, Jenell Boston, Lori Beth Hale, Haley McCoy, Hannah Grimwood, Jane Carey, Sarah B Goertzen, Leslie Harkess, Alex https://escholarship.org/uc/item/80k0m3f3 Benzylisoquinoline alkaloids (BIAs) represent a vast group of specialized plant metabolites with diverse pharmaceutical applications, synthesized by a variety of gene families. Among the multiple plant lineages that produce BIAs, the most notable is the poppy family (Papaveraceae), with California poppy (Eschscholzia californica) emerging as a model organism. Here, we report a haplotype-resolved genome assembly, in combination with a high-density expression atlas, for California poppy. Genome analyses reveal recent diversification of BIA biosynthesis genes in poppy through localized duplications. Furthermore, we demonstrate that the degree of phylogenetic relatedness among paralogs within BIA biosynthesis-associated gene families correlates with similarities in gene expression. In contrast, gene families involved in carotenoid biosynthesis, which contributes to the intense orange petal pigmentation, are not phylogenetically clustered, and floral developmental regulators exhibit... https://escholarship.org/uc/item/80k0m3f3 Wed, 22 Apr 2026 00:00:00 +0000 Rössner, Le-Han Rössner, Clemens Kong, Doudou Lotz, Dominik Weisert, Andrea Yamada, Yasuyuki Sato, Fumihiko Davies, Kevin Rupp, Oliver Fuchs, Jörg Baldwin, Ethan A Lovell, John McKain, Michael R Barry, Kerrie https://orcid.org/0000-0002-8999-6785 Bruna, Tomas Talag, Jayson Jenkins, Jerry Walstead, Rachel Grimwood, Jane Schmutz, Jeremy Leebens-Mack, James H Becker, Annette https://escholarship.org/uc/item/5v08699h Cryo-electron tomography (cryo-ET) has emerged as the preferred technique for visualizing the organization of macromolecular complexes in situ and resolving their structures at subnanometre resolution [Tegunov et al. (2021), Nat. Methods, 18, 186-193]. Despite improvements in data quality as a result of advances in detector technology, microscope stability and stage precision, the analysis and interpretation of tomograms remains challenging due to a low signal-to-noise ratio and reconstruction artifacts stemming from experimental constraints in specimen tilt during data collection resulting in a missing wedge in the Fourier space. Recently, self-supervised deep-learning methods have been proposed for contrast enhancement and reduction of resolution anisotropy in reconstructed tomograms. Here, we evaluate several state-of-the-art deep-learning methods which aim to improve the interpretability of cryo-ET reconstructions, with a focus on their performance on downstream tasks of template... https://escholarship.org/uc/item/5v08699h Wed, 22 Apr 2026 00:00:00 +0000 Jones, Henry N Deshmukh, Aneesh Pande, Kanupriya https://orcid.org/0000-0003-4272-9273 https://escholarship.org/uc/item/21q909f3 In macromolecular structure refinement, the low observation-to-parameter ratio and the lack of high-resolution data are countered by using a priori information in the form of restraints. Having accurate geometries of the chemical entities in the sample is paramount for generating accurate chemical restraints and, therefore, accurate macromolecular structures. In particular, it is desirable to have accurate restraints for known and novel ligand entities. Quantum mechanics (QM) can minimize the energy of a ligand by adjusting its geometry, and these geometries can be used to generate restraints for macromolecular refinement. This article describes a library of approximately 37 000 small molecules extracted from the Chemical Component Dictionary in the Protein Data Bank and minimized by density-functional QM. The library includes restraint files for use in crystallography or cryo-EM refinement, along with files suitable for molecular-dynamics simulation. Because the geometries are... https://escholarship.org/uc/item/21q909f3 Wed, 22 Apr 2026 00:00:00 +0000 Moriarty, Nigel W https://orcid.org/0000-0001-8857-9464 Case, David A Liebschner, Dorothee https://orcid.org/0000-0003-3921-3209 Adams, Paul D https://orcid.org/0000-0001-9333-8219 https://escholarship.org/uc/item/1df8g58q Natural products (NPs) are a rich source of therapeutic and agricultural compounds. Unfortunately, many promising metabolites are not expressed under standard laboratory conditions. Deepening our understanding of the regulatory networks governing NP biosynthetic genes is essential for unlocking this hidden chemical diversity. Cluster-situated regulators (CSRs) are transcription factors involved in the regulation of NPs, but their full regulatory range has remained elusive due to limited genome-wide data. Using DNA Affinity Purification Sequencing (DAP-seq), we defined the predicted regulons for 84 CSR homologs across 78 <i>Streptomyces</i> strains. CSRs in this cohort exerted influence across multiple cellular processes, with particularly strong impacts on other transcription factors throughout the genome. Approximately 30% of predicted NP biosynthetic gene clusters (BGCs) contained CSR-regulated genes. In strains encoding multiple CSR homologs, we observed substantial overlap... https://escholarship.org/uc/item/1df8g58q Wed, 22 Apr 2026 00:00:00 +0000 Wilbanks, Lauren E Brajkovich, Elliot N Baumgart, Leo Zhang, Yu Grosjean, Nicolas Blaby, Ian https://orcid.org/0000-0002-1631-3154 Parkinson, Elizabeth I https://escholarship.org/uc/item/98c1h62r The spatial organization and interactions of constituent components influence cell growth and determine physical and chemical properties of the cell wall, including its rigidity, flexibility, and degradability. Elucidating the interactions between cell wall polysaccharides is crucial for advancing our knowledge of how cell walls are assembled and for designing approaches to efficiently break down cell walls to produce renewable energy and biomaterials. Here, we investigated the effect of defects in the biosynthesis of cell wall components on the nanoscale organization of cellulose in primary cell walls through grazing incidence wide angle X-ray scattering (GIWAXS) measurements of hypocotyls of wild type Arabidopsis thaliana and of cellulose, pectin, and xyloglucan (hemicellulose) deficient mutants. GIWAXS reveals changes in lattice spacings, coherence lengths, and relative crystalline content for cellulose between wild type and mutant plants. In addition, X-ray pole figures constructed... https://escholarship.org/uc/item/98c1h62r Tue, 21 Apr 2026 00:00:00 +0000 Rongpipi, Sintu Barnes, William J Siemianowski, Oskar Ye, Dan Del Mundo, Joshua T Duncombe, Sydney Xin, Xiaoran Zhu, Chenhui https://orcid.org/0000-0003-1263-5065 Toney, Michael F Gu, Ying Anderson, Charles T Gomez, Enrique D Gomez, Esther W https://escholarship.org/uc/item/7007x17t Capsular polysaccharide (CPS) is essential for <i>Streptococcus pneumoniae</i> virulence. Yet, the mechanism linking CPS to peptidoglycan (PG) remains unclear. Here, we identified a strong negative genetic interaction between the genes encoding the putative capsule ligase CpsA and the WalK histidine kinase, a component of the WalRK two-component system regulating cell wall homeostasis. In the absence of <i>cpsA</i> , capsule polymers compete with wall teichoic acids for ligase activity to PG. This induces cell wall stress and is sensed by the WalRK system. Overexpression of the PG hydrolase <i>pcsB</i> or disruption of the PG-modifying enzymes <i>pgdA</i> and <i>oatA</i> restored growth of strains lacking <i>cpsA</i> and <i>walK</i> . Furthermore, CpsA overproduction compensates for the loss of other LytR-Cps2A-Psr (LCP) ligases, suggesting it can support capsule and wall teichoic acid syntheses. These findings support the model that LCP ligases are semi-redundant, although they... https://escholarship.org/uc/item/7007x17t Tue, 21 Apr 2026 00:00:00 +0000 Zik, Justin J Fu, Zeyu Price, Morgan N Li, Yujie Qiao, Yuan Arkin, Adam P https://orcid.org/0000-0002-4999-2931 Deutschbauer, Adam M Flores-Kim, Josue Sham, Lok-To https://escholarship.org/uc/item/3w41t16x Workflow management systems (WMS) are essential for creating and automating multi-step data analyses and ensuring the reproducibility of biological insights. Although numerous WMS solutions exist, few provide deep integration of command-line software with the R and Bioconductor ecosystems, where a substantial portion of statistical modeling and downstream scientific analysis is performed by a large user base. systemPipeR addresses this gap by offering a unified environment that links R-based analytical steps with command-line tools through a standardized workflow specification. It enables the design and execution of reproducible workflows on both local and high-performance computing systems, while allowing users to select the most appropriate R or command-line tool for each analysis step. The latest version introduces a fully redesigned architecture that streamlines workflow construction, execution, monitoring, and reporting. Key enhancements include a flexible workflow management... https://escholarship.org/uc/item/3w41t16x Tue, 21 Apr 2026 00:00:00 +0000 Zhang, Le Cassol, Daniela https://orcid.org/0000-0003-2417-6337 Gongol, Brendan Girke, Thomas https://orcid.org/0000-0003-0710-3777 https://escholarship.org/uc/item/3ht0p7jb [This corrects the article DOI: 10.7717/peerj.4029.]. https://escholarship.org/uc/item/3ht0p7jb Tue, 21 Apr 2026 00:00:00 +0000 Lang, Jenna M Coil, David A https://orcid.org/0000-0001-6049-8240 Neches, Russell Y https://orcid.org/0000-0002-2055-8381 Brown, Wendy E Cavalier, Darlene Severance, Mark Hampton-Marcell, Jarrad T Gilbert, Jack A https://orcid.org/0000-0001-7920-7001 Eisen, Jonathan A https://orcid.org/0000-0002-0159-2197 https://escholarship.org/uc/item/2jq23803 Introduction: While most studies focus on the effectors involved in plant infection, another important aspect is the degradation of the plant cell wall, as this is the main physical barrier protecting the plant from pathogens. The plant cell wall mainly consists of polysaccharides, proteins and the aromatic polymer lignin, but the type of polysaccharide differs significantly between plant types, species and tissues. It can therefore be expected that pathogens of specific plants have evolved to produce those plant polysaccharide degrading enzymes that match the polysaccharides in the cell wall of their host plant. Methods: In this study, we compared the plant polysaccharide degradation potential of 56 <i>Dothideomycetes</i> and 42 <i>Sordariomycetes</i> species to identify evolutionary patterns related to either host plant or phylogenomic classification of the fungal species. Results and discussion: Our results show that the CAZy content of these fungi does not correlate with their... https://escholarship.org/uc/item/2jq23803 Tue, 21 Apr 2026 00:00:00 +0000 Kandemir, Hazal Peng, Mao Koster, Max Groenewald, Johannes Z Crous, Pedro W Steindorff, Andrei S de Vries, Ronald P https://escholarship.org/uc/item/1wr5z22w Abstract Carbonic anhydrase (CA) enzymes catalyze the interconversion of carbon dioxide and bicarbonate with an efficiency exceeded only by superoxide dismutase. CA enzymes have convergently evolved multiple times from phylogenetically distant organisms into eight classes that are structurally unrelated, but share physiological functions involved in photosynthesis, respiration, pH homeostasis, CO2 transport, and carbonyl sulfide hydrolysis that play central roles in medicine and the environment. Here, we leverage the recent surge in publicly available genomes and metagenomes to re-examine our understanding of the abundance, diversity, and phylogenetic relationships of the three major CA classes in Bacteria/Archaea and microbial Eukaryotes (Fungi, algae). We recovered a total of 57,218 α-, β-, and γ-CA sequences from 24,184 metagenomes and genomes, including the first detection of α-CA from an archaeal species. CA sequences formed 3,859 protein clusters (1,188 with ≥ 3 sequences)... https://escholarship.org/uc/item/1wr5z22w Tue, 21 Apr 2026 00:00:00 +0000 Franco, Mario EE Singer, Esther https://orcid.org/0000-0002-3126-2199 Roux, Simon https://orcid.org/0000-0002-5831-5895 Meredith, Laura K U’Ren, Jana M https://escholarship.org/uc/item/11b1683w Trichoderma fungi support sustainable agriculture by suppressing plant diseases and improving crop performance. However, emerging pathogenicity of Trichoderma warrants further ecological and genetic characterization. Here we used machine learning to correlate genomic data from 37 Trichoderma strains with over 140 phenotypic traits, spanning metabolic versatility, biotic interactions, stress tolerance and reproductive strategies. We determined Trichoderma to be an ancient, genetically cohesive and physiologically diverse genus with spores capable of germination in water and dispersal via air and water droplets. Metabolic preferences indicate universal adaptation to mycoparasitism and to niches like arboreal microbial mats, alongside broader saprotrophic versatility. Our analyses are consistent with character displacement among close relatives and convergent evolution in distant lineages, with both processes shaping ecological plasticity and traits including dispersal modes, terrestrialization... https://escholarship.org/uc/item/11b1683w Mon, 20 Apr 2026 00:00:00 +0000 Steindorff, Andrei S Cai, Feng M Ding, Mingyue Jiang, Siqi Atanasova, Lea Baker, Scott E Barbosa-Filho, Jomal Rodrigues Bayram Akcapinar, Gunseli Brown, Daren W Chaverri, Priscila Chen, Peijie Chenthamara, Komal Daum, Chris Drula, Elodie Dubey, Mukesh Brandström Durling, Mikael Flatschacher, Daniel Ebner, Thomas Emri, Tamás Gao, Renwei Georg, Raphaela Castro Henrissat, Bernard Hermosa, Rosa Herrera-Estrella, Alfredo Hinterdobler, Wolfgang Kainz, Philipp Karlsson, Magnus Kredics, László Kubicek, Christian P Kuo, Alan https://orcid.org/0000-0003-3514-3530 LaButti, Kurt https://orcid.org/0000-0002-5838-1972 Lipzen, Anna https://orcid.org/0000-0003-2293-9329 Lorito, Matteo Mach, Robert L Manganiello, Gelsomina Marik, Tamás Martinez-Reyes, Natalia Mayrhofer-Reinhartshuber, Michael Miskei, Márton Moisan, Marie-Claude Mondo, Stephen https://orcid.org/0000-0001-5797-0647 Monte, Enrique Ng, Vivian https://orcid.org/0000-0001-8941-6931 Pang, Guan Pangilinan, Jasmyn Peng, Mao Piombo, Edoardo Pócsi, István Rahimi, Mohammad Javad Reddy, Sumitha K Riley, Robert https://orcid.org/0000-0003-0224-0975 Sarrocco, Sabrina Schmal, Matthias Schmoll, Monika Szűcs, Attila Woo, Sheridan L Yarden, Oded Zeilinger, Susanne Zimmermann, Christian Shelest, Ekaterina Tsang, Adrian Berka, Randy de Vries, Ronald P Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Druzhinina, Irina S https://escholarship.org/uc/item/7rr0p6zq Rice paddies significantly contribute to atmospheric methane (CH4). Here, we show that two independent rice genotypes overexpressing genes for PLANT PEPTIDES CONTAINING SULFATED TYROSINE (PSY) reduce cumulative CH4 emissions by 38% (PSY1) and 58% (PSY2) over 70 days of growth compared with controls. Genome-resolved metatranscriptomic data from PSY rhizosphere soils reveal lower ratios of gene activities for (mostly hydrogenotrophic) CH4 production versus consumption, decreased activity of H2-producing genes, and increased activity of bacterial H2 oxidation pathways. Metabolic modeling using metagenomic and metabolomic data predicts elevated H2 oxidation and suppressed H2 production in the PSY rhizosphere. Assembled genomes of rhizosphere H2-oxidizing bacteria are enriched in genes utilizing gluconeogenic acids compared with H2-producing counterparts, and their activities are likely stimulated by elevated levels of gluconeogenic acids, primarily amino acids, in PSY root exudates.... https://escholarship.org/uc/item/7rr0p6zq Fri, 17 Apr 2026 00:00:00 +0000 Shi, Ling-Dong Ercoli, Maria Florencia https://orcid.org/0000-0001-5587-6227 Kim, Junhyeong de Araujo Junior, Artur Teixeira Estera-Molina, Katerina Soni, Subah Weitz, Tracy Satomi Shigenaga, Alexandra M Dukovski, Ilija Sachdeva, Rohan Turumtay, Halbay https://orcid.org/0000-0003-4224-8103 Louie, Katherine B Bowen, Benjamin P https://orcid.org/0000-0003-1368-3958 Kosina, Suzanne M https://orcid.org/0000-0003-2885-1248 Scheller, Henrik V https://orcid.org/0000-0002-6702-3560 Pett-Ridge, Jennifer Segrè, Daniel Northen, Trent R Ronald, Pamela C https://orcid.org/0000-0002-4107-1345 Banfield, Jillian F https://escholarship.org/uc/item/5nj3j1s6 Photosynthetic organelles in eukaryotes originated through primary endosymbiosis with a cyanobacterium, an event that profoundly shaped the evolutionary landscape of the eukaryotic tree of life. Primary plastids in Archaeplastida, especially in cultivable plants and algae, contribute most to known plastid diversity. Secondary and higher-order endosymbiosis, involving eukaryotic hosts and algal endosymbionts, further spread photosynthesis among protists within the CASH lineages (Cryptophyta, Alveolata, Stramenopila, and Haptophyta). Despite various hypotheses explaining secondary plastid evolution and distribution, empirical support remains limited. Here, we employ cultivation-independent global metagenomics to expand plastid diversity and investigate plastid origins. We capture 1,027 plastid sequences, including 300 novel sequences belonging to previously unsequenced plastids and representing yet-to-be described microeukaryotes. This includes a new lineage that offers insights... https://escholarship.org/uc/item/5nj3j1s6 Fri, 17 Apr 2026 00:00:00 +0000 Shrestha, Bikash https://orcid.org/0000-0001-6349-3007 Romero, Miguel F Villada, Juan C https://orcid.org/0000-0003-2216-4279 Blaby-Haas, Crysten E https://orcid.org/0000-0002-1583-1291 Schulz, Frederik https://escholarship.org/uc/item/2cj4p0m0 Microbial metabolic gene clusters encode the biosynthesis or catabolism of metabolites that facilitate ecological specialization, mediate microbiome interactions and constitute a major source of medicines and crop protection agents. Here, we present BiG-SCAPE and BiG-SLiCE 2.0, next-generation methods that facilitate scalable, accurate and interactive gene cluster analyses. BiG-SCAPE 2.0 updates its classification, alignment methods, and visualizations, enabling more accurate analysis, up to 8x faster runtimes and halved memory requirements. BiG-SLiCE 2.0 updates its distance metric, pHMM database, and classification logic, resulting in increased sensitivity nearing that of BiG-SCAPE. Analysis of 260,630 biosynthetic gene clusters from publicly available genomes reveals that both tools generate concurring estimates of gene cluster diversity, thus providing significantly extended methodological support for recent evidence indicating that the vast majority of natural product diversity... https://escholarship.org/uc/item/2cj4p0m0 Fri, 17 Apr 2026 00:00:00 +0000 Draisma, Arjan Loureiro, Catarina Louwen, Nico LL Kautsar, Satria A Navarro-Muñoz, Jorge C Doering, Drew T Mouncey, Nigel J https://orcid.org/0000-0001-5380-1256 Medema, Marnix H https://escholarship.org/uc/item/4q21f37c Small polarons remain a bottleneck in realizing efficient transition metal oxide devices. Routes to engineer small polaron coupling to electronic states and lattice modes to control carrier localization remain unclear. Here, we measure small polaron formation in CuFeO₂ using transient extreme ultraviolet reflection spectroscopy and compare to theoretical predictions in realistically parametrized Holstein models, demonstrating that polaron localization depends on coupling to high-frequency versus low-frequency phonon bath components. We measure small polaron formation on a comparable ∼100 fs timescale to other Fe(III) compounds. Dynamic delocalization of the polaron follows formation through a coherent lattice expansion between Fe-O layers and charge-sharing with surrounding Fe(IV) states. Simulations reveal two major factors dictate polaron formation timescales: phonon density and reorganization energy distributions between acoustic and optical modes, matching experimental... https://escholarship.org/uc/item/4q21f37c Thu, 16 Apr 2026 00:00:00 +0000 Mendes, JocelynL Bhattacharyya, Srijan Huang, Chengye Michelsen, Jonathan M Klein, Isabel M Babbe, Finn Sayer, Thomas Li, Tianchu Cooper, Jason K Liu, Hanzhe Ginsberg, Naomi S https://orcid.org/0000-0002-5660-3586 Montoya-Castillo, Andrés Cushing, Scott K https://escholarship.org/uc/item/4691h8zs The use of X-ray structures to determine and interpret the ferryl iron-oxygen bond order in molecular oxygen-activating heme enzymes has, in the past, been controversial. This has mainly stemmed from the susceptibility of ferryl species to X-ray-induced electronic state changes. In this work we establishe using time-resolved serial femtosecond X-ray crystallography (tr-SFX) on a dye-decolourising peroxidase that the ferryl intermediate species (Compounds I and II) captured following in situ mixing of microcrystals with H2O2 have single, rather than the double bond character expected. X-ray emission validated tr-SFX data with quantum refinement, time-dependent-DFT calculations and QM/MM geometry optimizations together support the concept that the single iron-oxygen bond character is not an indication of ferryl reduction or a protonated form (FeIV-OH) but is instead attributed to the existence of accessible excited states possessing ferric-oxyl (FeIII–O•–) character. Such states... https://escholarship.org/uc/item/4691h8zs Wed, 15 Apr 2026 00:00:00 +0000 Williams, Lewis J Kamps, Jos JAG Brânzanic, Adrian MV Lehene, Maria Lundgren, Kristoffer JM Ryde, Ulf Chatterjee, Kuntal Doyle, Margaret D Simon, Philipp S https://orcid.org/0000-0002-2859-4475 Makita, Hiroki Thompson, Amy J Brewster, Aaron S https://orcid.org/0000-0002-0908-7822 Zhou, Tiankun Lučić, Marina Wilson, Michael T Aller, Pierre Sanchez-Weatherby, Juan Gee, Leland Dehe, Sebastian Mous, Sandra Yano, Junko https://orcid.org/0000-0001-6308-9071 Yachandra, Vittal K https://orcid.org/0000-0002-3983-7858 Hough, Michael A Orville, Allen M Kern, Jan F https://orcid.org/0000-0002-7272-1603 Silaghi-Dumitrescu, Radu L Worrall, Jonathan AR https://escholarship.org/uc/item/8zn495ch Infiltration of Agrobacterium tumefaciens into Nicotiana benthamiana has become a foundational technique in plant biology, enabling efficient delivery of transgenes in planta with technical ease, robust signal, and relatively high throughput. Despite transient expression’s prevalence in disciplines such as synthetic biology, little work has been done to describe and address the variability inherent in this system, a concern for experiments that rely on highly quantitative readouts. In a comprehensive analysis of N. benthamiana agroinfiltration experiments, we model sources of variability that affect transient expression. Our findings emphasize the need to validate normalization methods under the specific conditions of each study, as distinct normalization schemes do not always reduce variation either within or between experiments. Using a dataset of 1915 plants collected over three years, we develop a model of variation in N. benthamiana transient expression, using power analysis... https://escholarship.org/uc/item/8zn495ch Tue, 14 Apr 2026 00:00:00 +0000 Tang, Sophia N Szarzanowicz, Matthew J Lanctot, Amy Sirirungruang, Sasilada Kirkpatrick, Liam D Drako, Krista Alamos, Simon Cheng, Lyurui Waldburger, Lucas M Liu, Shuying Huang, Lena Kazaz, Sami Akyuz Turumtay, Emine Baidoo, Edward https://orcid.org/0000-0001-5787-1219 Eudes, Aymerick https://orcid.org/0000-0002-1387-6111 Thompson, Mitchell G Shih, Patrick M https://escholarship.org/uc/item/64v8j4b5 Large language models (LLMs) show promise in supporting differential diagnosis, but their performance is challenging to evaluate due to the unstructured nature of their responses, and their accuracy compared to existing diagnostic tools is not well characterized. To assess the current capabilities of LLMs to diagnose genetic diseases, we benchmarked these models on 5213 previously published case reports using the Phenopacket Schema, the Human Phenotype Ontology and Mondo disease ontology. Prompts generated from each phenopacket were sent to seven LLMs, including four generalist models and three LLMs specialized for medical applications. The same phenopackets were used as input to a widely used diagnostic tool, Exomiser, in phenotype-only mode. The best LLM ranked the correct diagnosis first in 23.6% of cases, whereas Exomiser did so in 35.5% of cases. While the performance of LLMs for supporting differential diagnosis has been improving, it has not reached the level of commonly... https://escholarship.org/uc/item/64v8j4b5 Tue, 14 Apr 2026 00:00:00 +0000 Reese, Justin T Chimirri, Leonardo Bridges, Yasemin Danis, Daniel Caufield, J Harry Gargano, Michael A Kroll, Carlo Schmeder, Andrew Liu, Fengchen https://orcid.org/0009-0006-4632-9604 Wissink, Kyran McMurry, Julie A Graefe, Adam SL Niyonkuru, Enock Korn, Daniel R Casiraghi, Elena Valentini, Giorgio Jacobsen, Julius OB Haendel, Melissa Smedley, Damian Mungall, Christopher J Robinson, Peter N https://escholarship.org/uc/item/1jp6k8pn The recent demonstration that members of at least three classes of archaea affiliated with the Thermoproteota superphylum are involved in the production of the climate-active gas methane has sparked discussions about how well we understand the diversity of methanogens. Here, we show that members of all three of these lineages, as well as several other, yet uncultured and physiologically uncharacterized groups within the Thermoproteota that encode the key enzyme of anaerobic methane cycling, methyl-coenzyme M reductase (MCR), are widely distributed in anoxic ecosystems. We postulate that the taxonomic, metabolic, and ecological diversity of methanogenic and MCR-encoding Thermoproteota are poorly understood, and that the contribution of methylotrophic and thermoproteotal methanogenesis to methane production is largely unknown. We hypothesize that thermoproteotal methanogens could contribute, potentially substantially, to methane emissions in many anoxic environments that harbor... https://escholarship.org/uc/item/1jp6k8pn Mon, 13 Apr 2026 00:00:00 +0000 Jay, Zackary J Kellom, Matthew https://orcid.org/0000-0002-8310-7078 Eloe-Fadrosh, Emiley https://orcid.org/0000-0002-8162-1276 Hatzenpichler, Roland https://escholarship.org/uc/item/6p54d42r <p>Production and purification of vanillin from lignin using ion exchange, and subsequent conversion to aminophenol ionic liquid precursors.</p> <p> Lignin is a complex polyphenolic substance that collectively represents the largest renewable source of aromatic carbon on Earth. Despite low yield and purity from depolymerized lignin, bio-derived vanillin (4-hydroxy-3-methoxybenzaldehyde) is a desirable molecule in the food/beverage and fragrance industries. To maximize vanillin yield from commercially-available softwood lignin, a series of oxidation reactions were conducted using a Box-Behnken statistical design. By varying time, temperature and O ₂ pressure, optimal conditions were selected using the Response Surface Method, and a maximum vanillin yield of 5.3 wt% was achieved. Flash chromatography of depolymerized lignin was investigated by comparing anion exchange and reversed-phase resins and fractions were characterized by GC-MS, GPC-HPLC, FT-IR and NMR. Anion exchange... https://escholarship.org/uc/item/6p54d42r Thu, 9 Apr 2026 00:00:00 +0000 Liu, Shihong Das, Lalitendu Blauch, David N Veronee, Charlie Dou, Chang https://orcid.org/0000-0002-9871-2641 Gladden, John https://orcid.org/0000-0002-6985-2485 Sun, Ning https://orcid.org/0000-0002-9689-9430 Socha, Aaron M https://escholarship.org/uc/item/3v48v571 <i>Karenia brevis</i> regularly forms harmful blooms along the West Florida Shelf that negatively affect marine and terrestrial organisms through toxin production. These blooms impose economic and environmental hardship, driving the need for research to understand the factors influencing their dynamics and to mitigate their impacts. A mostly unresolved issue is the potential role of viruses in bloom termination. We conducted an experiment incubating <i>K. brevis</i> cultures with size-fractionated bloom water samples. Flow cytometry revealed giant virus-like populations (VLPs) in replicate cultures with &lt;1&nbsp;μm-filtered and &lt;0.2&nbsp;μm-filtered bloom water. The VLPs abundance was paralleled by declines in photoefficiency and culture lysis. Metagenomic analyses of the lysates revealed 11 giant virus genomes (35%-100% complete) representing 7 viral operational taxonomic units (vOTUs) within the order <i>Imitervirales</i> (<i>Nucleocytoviricota</i>). Ten of these vOTUs... https://escholarship.org/uc/item/3v48v571 Thu, 9 Apr 2026 00:00:00 +0000 Booker, Anne Fei, Cong Amin, Shady Custer, James Watkins, Kai Yaeger, William Ahn, So Vidyarathna, Nayani Burns, Alexandra Klass, Sarah Glibert, Patricia Heil, Cynthia Schulz, Frederik Martínez Martínez, Joaquín https://escholarship.org/uc/item/1dg2k0bw Benzylamines are key intermediates in pharmaceuticals, agrochemicals, and polymers, but their conventional production relies on benzyl chloride - a petroleum-derived compound with high toxicity and energy demands. Lignin, accounting for up to 30% of plant biomass, is the largest renewable source of aromatic carbon on Earth. However, its highly complex and recalcitrant structure poses a major barrier to efficient conversion into high-value chemicals. Here, we developed a catalytic approach to convert commercial kraft lignin into phenolic benzylamines through selective depolymerization and subsequent functionalization. We systematically evaluated the effects of three alcohol solvents, formic acid (FA), and a ruthenium-on‑carbon (Ru/C) catalyst on monophenol yield and selectivity. Up to 6.5&nbsp;wt% monophenol yield was achieved using methanol (MeOH), FA, and Ru/C at 300&nbsp;°C for 2&nbsp;h. Quantum thermodynamic simulations based on the COSMO-RS model confirmed the superior solvation... https://escholarship.org/uc/item/1dg2k0bw Thu, 9 Apr 2026 00:00:00 +0000 Dou, Chang https://orcid.org/0000-0002-9871-2641 Yang, Minliang Kumar, Nikhil Aguilar, Rolin A Hitt, Addison J Gonzalez, Griffen Scown, Corinne D https://orcid.org/0000-0003-2078-1126 Sale, Kenneth L Choudhary, Hemant Socha, Aaron M Sun, Ning https://orcid.org/0000-0002-9689-9430 https://escholarship.org/uc/item/8tm1v6zj The growth of metagenomics-derived amino acid sequence data has transformed our understanding of protein function, microbial diversity, and evolutionary relationships. However, the vast majority of these proteins remain functionally uncharacterized. Grouping the millions of such uncharacterized sequences with the few experimentally characterized ones allows the transfer of annotations, while the inspection of conserved residues with multiple sequence alignments can provide clues to function, even in the absence of existing functional information. To address the challenges associated with this data surge and the need to group sequences, we present a scalable, open-source, parametrizable Nextflow pipeline (nf-core/proteinfamilies) that generates nascent protein families or assigns new proteins to existing families. The computational benchmarks demonstrated that resource usage scales approximately linearly with input size, and the biological benchmarks showed that the generated protein... https://escholarship.org/uc/item/8tm1v6zj Mon, 6 Apr 2026 00:00:00 +0000 Karatzas, Evangelos Beracochea, Martin Baltoumas, Fotis A Aplakidou, Eleni Richardson, Lorna Yates, James A Fellows Lundin, Daniel community, nf-core Buluç, Aydin Kyrpides, Nikos C https://orcid.org/0000-0002-6131-0462 Georgakopoulos-Soares, Ilias Pavlopoulos, Georgios A https://orcid.org/0000-0002-4577-8276 Finn, Robert D https://escholarship.org/uc/item/895730mq BACKGROUND: Scientific research relies on well-structured, standardized data; however, much of it is stored in formats such as free-text lab notebooks, nonstandardized spreadsheets, or data repositories. This lack of structure challenges interoperability, making data integration, validation, and reuse difficult. FINDINGS: LinkML (Linked Data Modeling Language) is an open framework that simplifies the process of authoring, validating, and sharing data. LinkML can describe a range of data structures, from flat, list-based models to complex, interrelated, and normalized models that utilize polymorphism and compound inheritance. It offers an approachable syntax that is not tied to any one technical architecture and can be integrated seamlessly with many existing frameworks. The LinkML syntax provides a standard way to describe schemas, classes, and relationships, allowing modelers to build well-defined, stable, and optionally ontology-aligned data structures. Once defined, LinkML... https://escholarship.org/uc/item/895730mq Mon, 6 Apr 2026 00:00:00 +0000 Moxon, Sierra AT Solbrig, Harold Harris, Nomi L https://orcid.org/0000-0001-6315-3707 Kalita, Patrick Miller, Mark A Patil, Sujay Schaper, Kevin Bizon, Chris Caufield, J Harry Cuesta, Silvano Cirujano Cox, Corey Dekervel, Frank Dooley, Damion M Duncan, William D Fliss, Tim Gehrke, Sarah Graefe, Adam SL Hegde, Harshad Ireland, AJ Jacobsen, Julius OB Krishnamurthy, Madan Kroll, Carlo Linke, David Ly, Ryan https://orcid.org/0000-0001-9238-0642 Matentzoglu, Nicolas Overton, James A Saunders, Jonny L Unni, Deepak R Vaidya, Gaurav Vierdag, Wouter-Michiel AM Bruskiewich, Richard M Carbon, Seth Cavanna, Eric Chandonia, John-Marc Cholia, Shreyas https://orcid.org/0000-0002-4775-8201 Dichter, Ben Eloe-Fadrosh, Emiley A Emonet, Vincent Essaid, Shahim Yates, James A Fellows Flack, Joseph Ghosh, Satrajit S Goutte-Gattat, Damien Jarecka, Dorota Jiao, Dazhi Joachimiak, Marcin P Korolev, Vlad Lapkin, Volodymyr McLoughlin, Noel Miller, Sierra D Milton, Michael Moore, Josh Munoz-Torres, Moni Nichols, B Nolan Reese, Justin T Savage, Victoria Stroemert, Philip Teoh, Jeremy Thessen, Anne To, Isaac Trivedi, Puja Vialard, Vincent Whetzel, Trish Ruebel, Oliver Chute, Christopher G Brush, Matthew H Haendel, Melissa A Mungall, Christopher J https://escholarship.org/uc/item/6gk6f7js Thirdhand smoke (THS) is linked to adverse health effects, but the effect of genetic variations on behavioral outcomes is poorly understood. To investigate this, we assessed anxiety- and memory-related behaviors in 820 mice from 21 strains of the genetically diverse Collaborative Cross (CC) mouse that were exposed to THS from 4 through 10&nbsp;weeks of age. Anxiety was evaluated with a light/dark box assay with a previously established risk score system. Females were generally more sensitive: THS reduced anxiety risk in strains CC013, CC019, and CC051, but increased risk in CC036 and CC061, while males showed no significant effects. Memory was tested using passive avoidance: impairments were observed in both sexes in CC016 and CC019, with sex-dependent effects in CC002 and CC051. A genome-wide association study identified 2,347 SNPs associated with anxiety and 1,568 SNPs with memory, with 32 and 85 SNPs, respectively, interacting with THS exposure. Enrichment analyses revealed... https://escholarship.org/uc/item/6gk6f7js Mon, 6 Apr 2026 00:00:00 +0000 Yao, Yiyan Wang, Dawei Wang, Pin Ton, Ethan Schick, Suzaynn F https://orcid.org/0000-0001-7101-3077 Jacob, Peyton Tang, Xiaochen https://orcid.org/0000-0003-4168-9871 Destaillats, Hugo Hang, Bo Snijders, Antoine M Mao, Jian-Hua https://orcid.org/0000-0001-9320-6021 Inman, Jamie L Chang, Hang https://escholarship.org/uc/item/5wk090j4 Originating from aquatic unicellular ancestors, over the course of ~1 billion years, the fungi have evolved to occupy nearly all aerobic environments on the planet, diversified into millions of different ‘species’ and have developed complex multicellular structures. Their relatively small, simple genomes have facilitated massive-scale sequencing and allowed us to explore genome evolution across an ancient eukaryotic kingdom. With thousands of genomes from diverse lineages now available, this Review will discuss insights into fungal biology and evolution gleaned with genomics and other multi-omics approaches. Using published genomes available through GenBank and the Joint Genome Institute’s MycoCosm platform, we generated kingdom-wide phylogenies and used them to highlight how fungal genomes have changed over time. With this phylogeny as a guide, we also discuss major evolutionary transitions that occurred across the fungal kingdom. Although progress has been made, these efforts... https://escholarship.org/uc/item/5wk090j4 Thu, 2 Apr 2026 00:00:00 +0000 Mondo, Stephen J https://orcid.org/0000-0001-5797-0647 Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 https://escholarship.org/uc/item/52n3x1s0 The continued emergence of pathogens, whether novel, re-emerging, or engineered, poses a persistent global biosecurity and public health challenge. Recent outbreaks, including COVID-19, Lassa fever, Marburg virus, mpox, and avian influenza, underscore the urgent need for robust systems that enable rapid surveillance, early diagnosis, and timely countermeasures before widespread human transmission occurs. In this article, we focus on early detection technologies and systematically evaluate current diagnostic and sensing modalities. We highlight sequencing and spectroscopy as two complementary approaches capable of providing broad, agnostic detection and rich biological insight. Our analysis emphasizes that scientific innovation alone is insufficient: effective preparedness also requires improved data curation, integration, and sharing to build AI-ready resources that accelerate future responses. We argue for coordinated advances in both technological capabilities and supporting... https://escholarship.org/uc/item/52n3x1s0 Thu, 2 Apr 2026 00:00:00 +0000 Sakkos, Anastasiya Saint-John, Brandon Tyml, Tomas Myskova, Eva https://orcid.org/0000-0003-3015-1953 Aureli, Lorenzo Inman, Jamie L Snijders, Antoine M Mouncey, Nigel J https://orcid.org/0000-0001-5380-1256 Mukundan, Harshini Schulz, Frederik https://escholarship.org/uc/item/75v9n6hx The genomes of white-rot fungi hold extended repertoires of enzymes active on virtually all the chemical bonds that intertwine lignocellulose polymers, and several Trametes species have been identified as powerful tools for biorefinery or bioremediation. However, only few studies have addressed the intra-species polymorphism one would expect from fungal strains collected in contrasted environments. We compared the genome sequence of pairs of strains collected in different geographic areas, for each of three fungal species. Using an updated list of the predicted functions for fungal ligno- and cellulolytic enzymes (CAZymes), we observed a high conservation of the gene repertoires among the six strains. We compared the adaptative response of the fungi grown on crystalline cellulose, wheat straw, aspen or pine sawdust by transcriptomics and secretomics. The gene regulation profiles were determined by the species and the substrates, rather than the strain. The secretomes did not show... https://escholarship.org/uc/item/75v9n6hx Wed, 1 Apr 2026 00:00:00 +0000 Drula, E Navarro, D Lambert, J Chaduli, D Lomascolo, A Heilmann, C Grisel, S Barry, K https://orcid.org/0000-0002-8999-6785 Labutti, K https://orcid.org/0000-0002-5838-1972 Andreopoulos, B Siyoun, L Tejomurthula, S https://orcid.org/0000-0002-2186-3388 Lipzen, A https://orcid.org/0000-0003-2293-9329 Riley, R https://orcid.org/0000-0003-0224-0975 Grigoriev, Igor V https://orcid.org/0000-0002-3136-8903 Miyauchi, S Rosso, MN https://escholarship.org/uc/item/7df5f8f9 Human norovirus (HuNoV) is a significant cause of gastroenteritis worldwide, affecting people of all age groups. There are currently no vaccines or drugs available, leaving susceptible populations vulnerable to severe or protracted illness. A HuNoV cultivation system is pivotal for screening norovirus antivirals. While the human intestinal enteroid cultivation system allows robust replication of multiple HuNoV strains, it presents technical and cost barriers. Tulane virus (TV), a surrogate for HuNoV, replicates well in monkey kidney cell lines and is closely related to norovirus in cellular biology. Here, we determined the structures of TV protease (TV-Pro) alone and in complex with rupintrivir, a picornavirus inhibitor that also inhibits HuNoV proteases (HuNoV-Pro). Our data validate TV as an efficient surrogate system for rapid screening of HuNoV protease inhibitors. The TV protease structure exhibits significant backbone similarity to the GI.1 HuNoV protease in the substrate-binding... https://escholarship.org/uc/item/7df5f8f9 Tue, 31 Mar 2026 00:00:00 +0000 Pham, Son Sharma, Nikhil Sankaran, Banumathi Nguyen, Jalen Estes, Mary K Hyser, Joseph M Prasad, BV Venkataram https://escholarship.org/uc/item/7d51t1mb Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠-including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology-a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including... https://escholarship.org/uc/item/7d51t1mb Tue, 31 Mar 2026 00:00:00 +0000 Vasilevsky, Nicole A Toro, Sabrina Matentzoglu, Nicolas Flack, Joseph E Mullen, Kathleen R Hegde, Harshad Gehrke, Sarah Whetzel, Patricia L Shwetar, Yousif Harris, Nomi L https://orcid.org/0000-0001-6315-3707 Ngu, Mee S Alyea, Gioconda L Kane, Megan S Roncaglia, Paola Sid, Eric Thaxton, Courtney L Wood, Valerie Abraham, Roshini S Achatz, Maria Isabel Ajuyah, Pamela Amberger, Joanna S Babb, Lawrence Baker, Jasmine Balhoff, James P Berg, Jonathan S Bhalla, Amol Ros, Xavier Bofill-De Braun, Ian R Broeren, Eleanor C Byer, Blake K Byrne, Alicia B Callahan, Tiffany J Carmody, Leigh C Chan, Lauren E Clause, Amanda R Cohen, Julie S DeLuca, Marcello Deuitch, Natalie T Flowers, May Fraser, Jamie Fujiwara, Toyofumi Gitau, Vanessa Goldstein, Jennifer L Gration, Dylan Groza, Tudor Gyori, Benjamin M Hankey, William Hilton, Jason A Himmelstein, Daniel S Hong, Stephanie S Hoyt, Charles T Huether, Robert Hurwitz, Eric Jacobsen, Julius OB Kikuchi, Atsuo Köhler, Sebastian Korn, Daniel R Lagorce, David Laraway, Bryan J Li, Jane Y Malheiro, Adriana J McLaughlin, James Meldal, Birgit HM Mohan, Shruthi Moxon, Sierra AT Munoz-Torres, Monica C https://orcid.org/0000-0001-8430-6039 Nelson, Tristan H Nicholas, Frank W Ochoa, David Olson, Daniel Oprea, Tudor I Oskotsky, Tomiko T https://orcid.org/0000-0001-7393-5120 Osumi-Sutherland, David Paris, Kelley Parkinson, Helen E Pendlington, Zoë M Peng, Xiao P Pizzino, Amy Plon, Sharon E Powell, Bradford C Ratliff, Julie C Rehm, Heidi L Remennik, Lyubov Riggs, Erin R Roberts, Sean Robinson, Peter N Ross, Justyne E Schaper, Kevin Schilder, Brian M Schmidt, Johanna L Sharp, Elliott W Similuk, Morgan N Smedley, Damian Sneddon, Tam P Sparks, Rachel Stefancsik, Ray Stupp, Gregory S Sundar, Shilpa Takatsuki, Terue Tammen, Imke https://escholarship.org/uc/item/6h8935hh Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (jumbo gut) phages with genomes of 360 to 402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect <i>Bacteroides</i> and/or <i>Phocaeicola</i>. Although three of the four major groups of Jug phages shared &gt;90% genome-wide sequence identity, their large terminase subunits exhibited only 38 to 57% identity, suggesting horizontal acquisition from other phages. Over 1500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug... https://escholarship.org/uc/item/6h8935hh Tue, 31 Mar 2026 00:00:00 +0000 Chen, LinXing Camargo, Antonio Pedro https://orcid.org/0000-0003-3913-2484 Qin, Yiting Koonin, Eugene V Wang, Haoyu Zou, Yuanqiang Duan, Yi Li, Hao https://escholarship.org/uc/item/43x746xm Persistent drought affects global crop production and is becoming more severe in many parts of the world in recent decades. Deciphering how plants respond to drought will facilitate the development of flexible mitigation strategies. Sorghum bicolor L. Moench (sorghum), a major cereal crop and an emerging bioenergy crop, exhibits remarkable resilience to drought. To better understand the molecular traits that underlie sorghum's remarkable drought tolerance, we undertook a large-scale sorghum gene expression profiling effort, totaling nearly 1500 transcriptome profiles, across a 3-year field study with replicated plots in California's Central Valley. This study included time-resolved gene expression data from roots and leaves of two sorghum genotypes, BTx642 and RTx430, with different pre-flowering and post-flowering drought-tolerance adaptations under control and drought conditions. Quantification of genotype-specific drought tolerance effects was enabled by de novo sequencing,... https://escholarship.org/uc/item/43x746xm Tue, 31 Mar 2026 00:00:00 +0000 Cole, Benjamin Zhang, Wenxin Shi, Junming Wang, Hao Baker, Christopher Varoquaux, Nelle Hollingsworth, Joy Hutmacher, Robert Dahlberg, Jeffery Pierroz, Grady Barry, Kerrie W https://orcid.org/0000-0002-8999-6785 Singan, Vasanth Yoshinaga, Yuko https://orcid.org/0000-0002-4978-9394 Daum, Christopher https://orcid.org/0000-0003-3895-5892 Zane, Matthew Blow, Matthew https://orcid.org/0000-0002-8844-9149 O’Malley, Ronan Shu, Shengqiang Jenkins, Jerry W Lovell, John T Schmutz, Jeremy Taylor, John W Coleman‐Derr, Devin Visel, Axel Lemaux, Peggy G Purdom, Elizabeth https://orcid.org/0000-0001-9455-7990 Vogel, John P https://orcid.org/0000-0003-1786-2689