Author: slquinlan

NAR Genom Bioinform. 2026 Sep 15;8(3):lqag107. doi: 10.1093/nargab/lqag107. eCollection 2026 Sep.

ABSTRACT

Genomic DNA encodes regulatory information that determines where, when, and to what extent genes are expressed. Theoretically, we should be able to identify these transcriptional “instructions” by examining genomic DNA sequence alone, yet this has remained challenging. Here we present the Vertebrate Regulatory MOdule Detector (VRMOD), a method that accurately predicts gene regulatory sequences using only the query genomic sequences. We applied VRMOD to 309 Ensembl genomes, generating a compendium of high-resolution, genome-position-fixed cis-regulatory modules without parameter tuning. We performed extensive computational evaluation and experimental validation of VRMOD predictions. Notably, VRMOD predicted three sub-enhancers within the human hs52 enhancer at the FTO locus from the VISTA database, including one missed by existing methods. Using a chicken embryo system and 3D tissue imaging, we showed that each sub-enhancer exhibits restricted spatiotemporal activity within specific subsets of tissues where the full enhancer is active. We further demonstrated VRMOD’s utility for identifying evolutionarily non-conserved enhancers, annotating regulatory sequences in non-model organisms, and identifying candidate disease-causal variants. Collectively, VRMOD provides a universal coordinate reference system for regulatory sequences across 309 vertebrate genomes and enables genome-wide annotation of non-coding regulatory elements in any vertebrate species using genomic sequence alone.

PMID:42745980 | PMC:PMC13575426 | DOI:10.1093/nargab/lqag107

Mol Plant Pathol. 2026 Sep;27(9):e70345. doi: 10.1111/mpp.70345.

ABSTRACT

TAXONOMY: Cucurbit leaf crumple virus (CuLCrV); Begomovirus cucurbitae; Geminiviridae; Geplafuvirales.

GEOGRAPHICAL DISTRIBUTION: The presence of CuLCrV is exclusively limited to North America, mainly Mexico and the United States.

PHYSICAL PROPERTIES: CuLCrV is a bipartite begomovirus comprising two circular single-stranded DNA molecules (DNA-A and DNA-B), encapsidated within geminate icosahedral particles.

GENOME AND ORGANIZATION: CuLCrV possesses a bipartite genome of DNA-A (2632 nucleotides) and DNA-B (2600 nucleotides). DNA-A contains five open reading frames (ORFs): AV1 (coat protein), AC1 (replication-associated protein), AC2 (transcriptional activator protein), AC3 (replication enhancer protein) and AC4. DNA-B contains two ORFs: BV1 (nuclear shuttle protein) and BC1 (movement protein).

TRANSMISSION: CuLCrV is transmitted by the sweetpotato whitefly, Bemisia tabaci, in a persistent, circulative and non-propagative manner.

HOSTS: CuLCrV primarily infects crop members of the Cucurbitaceae and snap bean (Phaseolus vulgaris, Fabaceae). Multiple weed species belonging to Brassicaceae, Convolvulaceae, Cucurbitaceae and Verbenaceae act as persistent virus reservoir hosts.

SYMPTOMS: Symptom expression varies with host and infection timing. In cucurbits, infection induces leaf crumpling, thickening and downward curling of leaves, with green streaks and distortion of fruits. In snap bean, symptoms include leaf distortion, chlorosis and malformed pods.

CONTROL: No commercial cultivars with resistance to CuLCrV are available for cucurbit crops, although some resistance has been reported in snap bean cultivars. Therefore, management relies primarily on integrated disease management.

PMID:42740504 | DOI:10.1111/mpp.70345

J Cell Sci. 2026 Sep 14:jcs.264648. doi: 10.1242/jcs.264648. Online ahead of print.

ABSTRACT

SPEF1 is a conserved calponin-homology domain protein that decorates the seam of central pair microtubules in the distal segment of motile cilia. Here, we show that in the ciliate Tetrahymena, loss of SPEF1 disrupts the central pair throughout the middle segment, which comprises most of the cilium, producing gaps in the microtubule lattice, truncations of proximal microtubule regions, and loss of lateral projections. Although visible structural defects were restricted to the central microtubules, SPEF1 also localized to the ciliary outer doublets and to all classes of non-ciliary cortical microtubules. Within cilia, SPEF1 was strongly enriched near the distal tip but was also present throughout the middle segment, where it was more abundant on the central than on the outer doublet microtubules. In live cilia, most SPEF1 particles were stationary and turned over slowly; some underwent diffusion, but none moved by intraflagellar transport. Central pair defects arose early during ciliary assembly. We propose that SPEF1 functions as a general microtubule stabilizer whose activity is particularly important for the assembly of central pair microtubules within the middle ciliary segment.

PMID:42733355 | DOI:10.1242/jcs.264648

Ecol Evol. 2026 Sep 11;16(9):e74347. doi: 10.1002/ece3.74347. eCollection 2026 Sep.

ABSTRACT

Information about biological traits essential for pest management, such as species identity, diet and movement often require laborious and time-intensive studies on pest natural history, in both laboratory and field settings. However, new agricultural pest threats are continually emerging, often requiring prompt responses with limited information. Using a combination of molecular gut content analysis and RAD-seq, we examined the species identities, plant diet composition, and population genetic structure of an emerging and important agricultural pest in the US, the peanut burrower bug, Pangaeus bilineatus Say (Hemiptera, Cydnidae). We found that two, morphologically similar, burrowing bug species (including P. bilineatus) were commonly caught in light traps near peanut fields, one of which (Dallasiellus lugubris) was not previously considered a pest of peanut. Molecular gut content analysis revealed a wide, but somewhat distinct, variety of plants among the diets of both bug species. Surprisingly, peanut was a rare part of the diet of either species. RAD-seq analysis revealed evidence consistent with weak isolation-by-distance and modest spatial genetic differentiation for both species. Together, these results suggest a potential pest complex where previously only one species was in focus. Moreover, their broad diets and spatially restricted population dispersal patterns may also explain the sporadic nature of damage that has been recorded for this potential pest complex. Responses to emerging pest challenges can benefit from insights generated by population genomics techniques, opening up new avenues for research and supporting efforts to quickly tailor management strategies for novel pests.

PMID:42730235 | PMC:PMC13564106 | DOI:10.1002/ece3.74347

Front Plant Sci. 2026 Aug 31;17:1942553. doi: 10.3389/fpls.2026.1942553. eCollection 2026.

ABSTRACT

Serine hydroxymethyltransferase (SHMT) is an enzyme essential for one-carbon metabolism. In higher plants, multiple SHMT genes code for isoforms that function in the cytosol, nucleus, mitochondria, and chloroplasts. The soybean genome contains two cytosolic SHMTs, GmSHMT05 and GmSHMT08, sharing high sequence identity and similar expression throughout soybean development. In certain soybean genotypes, two amino acid substitutions negatively impact GmSHMT08’s ability to bind to tetrahydrofolate (THF), leading to a gain-of-function in resistance to the soybean cyst nematode (SCN). Whether this perturbation to the enzyme has other functional consequences for soybean growth and development remains unknown. Here, we investigated the roles of cytosolic GmSHMTs in soybean growth and development. We determined that the 3D structure and folate-binding affinity of GmSHMT05 are highly similar to the version of GmSHMT08 found in susceptible soybeans. We further measured phenotypic traits of two ethyl methanesulfonate-derived Gmshmt08 mutant plants in an SCN-resistant soybean background. Aboveground soybean growth and development were similar, except the Gmshmt08 mutant plants showed a significant increase in pods/plant in field phenotyping trials. Belowground analyses revealed a significant increase in lateral root and total root length in mutant plants, and CRISPR-Cas9 editing demonstrated an essential role of cytosolic SHMTs in root growth. Taken together, our results indicate that GmSHMT05 sustains overall soybean growth and development in the absence of GmSHMT08; however, GmSHMT08’s gain-of-function in SCN resistance negatively influences pod and root growth, highlighting a potential trade-off between soybean defense and development that may impact yield when breeding with GmSHMT08 to develop SCN-resistant varieties.

PMID:42729520 | PMC:PMC13563002 | DOI:10.3389/fpls.2026.1942553

Cell Mol Bioeng. 2026 Aug 27;19(4):535-548. doi: 10.1007/s12195-026-00933-x. eCollection 2026 Aug.

ABSTRACT

Interest in human mesenchymal stromal cells (MSCs) as an immune therapeutic has been on the increase over the past two decades with preclinical research yielding promising results, but so far only a singular MSC-based immunotherapy has been approved by the U.S. Food and Drug Administration (FDA). A major barrier for MSC clinical translation is the lack of reliable potency metrics and sufficient understanding of the mechanisms of action, as reported by the National Cell Manufacturing Consortium (NCMC). We integrated high-content morphological profiling and targeted sphingolipid analysis across MSC donors exhibiting a range of IFN-γ induced indoleamine-2,3-deoxygenase (IDO) activities to investigate the role of cell membrane components in MSC immunomodulatory function. High- and low IDO potency cells have distinct morphological signatures that are also reflected in the sphingolipid (SL) activity, with low IDO potency cell lines having low sphingomyelinase activity and high IDO potency cell lines having high sphingomyelinase activity. Perturbation of SL metabolism through the addition of exogenous neutral sphingomyelinase not only shifted morphological signatures to mimic those of high potency, but also significantly increased IDO activity within both high and low IDO potency donors. Additionally, these perturbations resulted in increased extracellular vesicle production with rich SL content and a stark reduction of TNF-α following EV treatment of activated macrophages. Together, these findings link morphology features from potent MSCs to sphingolipid remodeling and suggest a tractable strategy to tune MSC immunomodulatory potency.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12195-026-00933-x.

PMID:42729496 | PMC:PMC13562489 | DOI:10.1007/s12195-026-00933-x

Phys Rev Lett. 2026 Aug 28;137(9):091804. doi: 10.1103/jngg-1nf3.

ABSTRACT

This Letter presents the first evidence of the simultaneous production of two Z bosons and one photon with the ATLAS detector at the Large Hadron Collider. The measurement is performed using the full Run-2 dataset, recorded from 2015 to 2018, of proton-proton collisions at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 140 fb^{-1}. The fully leptonic final state with four leptons and one photon is analyzed, pp→ZZγ→ℓ^{+}ℓ^{-}ℓ^{‘+}ℓ^{‘-}γ with ℓ,ℓ^{‘}=e or μ. This final state is measured in a fiducial region where photon final-state radiation is minimized, and the photon has a transverse momentum of p_{T}^{γ}>20 GeV. Eight events are selected, with a background estimate of 0.92±0.15. This results in an observed (expected) significance of the ZZγ final state of 4.4σ (4.0σ). The measured cross section for pp→ZZγ→ℓ^{+}ℓ^{-}ℓ^{‘+}ℓ^{‘-}γ in the fiducial region is σ_{ZZγ}=0.144_{-0.051}^{+0.065}(stat)_{-0.004}^{+0.008}(syst) fb, in agreement with the standard model prediction of σ_{fid}^{SM}=0.130±0.006 fb.

PMID:42726943 | DOI:10.1103/jngg-1nf3

Am J Health Syst Pharm. 2026 Sep 10:zxag282. doi: 10.1093/ajhp/zxag282. Online ahead of print.

ABSTRACT

PURPOSE: Large language models (LLMs) have proven performance for certain diagnostic tasks; however, limited studies have evaluated their consistency in recommending appropriate medication regimens for a given diagnosis. Medication management is a complex task that requires synthesis of drug formulation and complete order instructions for safe use. Here, the performance of GPT-4o, an LLM available with OpenAI’s ChatGPT, was tested on 3 medication management tasks.

METHODS: GPT-4o performance was tested on 3 medication tasks: identifying available formulations for a given generic drug name, identifying drug-drug interactions (DDIs) for a given medication regimen, and preparing a medication order for a given generic drug name. For each experiment, the model’s raw text response was captured exactly as returned and evaluated using clinician evaluation in addition to standard LLM metrics, including Term Frequency-Inverse Document Frequency (TF-IDF) vectors, normalized Levenshtein similarity, and Recall-Oriented Understudy for Gisting Evaluation (ROUGE-1/ROUGE-L) F1 score between each response and its reference string.

RESULTS: For the first task of drug-formulation matching, GPT-4o had 49% accuracy for generic medications being matched to all available formulations, with an average of 1.23 omissions per medication and 1.14 hallucinations per medication. For the second task of drug-drug interaction identification, the accuracy was 54.7% for identifying the DDI pair. For the third task, GPT-4o generated order sentences containing no medication or abbreviation errors in 65.8% of the cases.

CONCLUSION: Model performance for basic medication tasks was consistently poor. This evaluation highlights the need for domain-specific training through clinician-annotated datasets and a comprehensive evaluation framework for benchmarking performance.

PMID:42717660 | DOI:10.1093/ajhp/zxag282

EXCLI J. 2026 Jul 27;25:1215-1218. doi: 10.17179/excli2026-9686. eCollection 2026.

ABSTRACT

[This corrects the article on p. 1107 in vol. 25, PMID: 42517087.].

PMID:42712687 | PMC:PMC13550661 | DOI:10.17179/excli2026-9686

Front Plant Sci. 2026 Aug 26;17:1893113. doi: 10.3389/fpls.2026.1893113. eCollection 2026.

ABSTRACT

Winter wheat plays a viable role in agriculture, not only as a primary grain crop but also as a valuable forage source that bridges fall-spring forage gaps in many regions, including the southeastern (SE) U.S. Despite its nutritive potential, genetic basis of forage-quality traits remains insufficiently understood, limiting breeding efforts for dual-purpose cultivars. This study aimed to dissect the genetic architecture of forage quality in 182 soft red winter wheat (SRWW) genotypes adapted to the SE U.S. using genome-wide association study (GWAS). Field experiments were carried out in randomized complete block design across three Georgia locations over two growing seasons (2023-2025), with forage sampled at the end of tillering and evaluated using near-infrared reflectance spectroscopy. Significant phenotypic variation was observed for dry matter (DM), crude protein (CP), acid and neutral detergent fiber (ADF, NDF), acid detergent lignin (ADL), total digestible nutrients (TDN), sugars (SUG), and relative forage quality (RFQ). Heritability estimates ranged from low-to-moderate in combined environments and from low-to-high within individual locations. Correlation analysis revealed strong positive associations among fiber-related traits and negative associations with TDN, RFQ, and SUG, while CP declined with increasing fiber. Genome-wide association analysis identified 282 significant marker-trait associations (P < 1×10^-4) across 19 chromosomes, which were consolidated into 121 QTLs, including 27 major-effect QTLs. Three QTLs QRfq.uga-3B.1, QRfq.uga-3B.2 (RFQ) and QDm/Sug.uga-7A (DM, SUG) were stable across locations while QAdf/Adl.uga-2A (ADF, ADL) and QDm/Sug.uga-7A (DM, SUG) indicated multi-trait control. Notably, 25 of the 27 major QTLs were putatively novel, highlighting substantial untapped allelic diversity for forage-quality improvement in SE SRWW. Favorable allele accumulation resulted in an overall improvement in forage quality, increasing desirable nutritive traits (DM, RFQ, SUG, CP) while reducing undesirable traits (ADF, ADL). Candidate gene analysis linked six major QTLs with genes implicated in abiotic stress response, plant development, and metabolic regulation, supporting their functional relevance in forage-quality determination. Incorporating these loci into breeding programs provides a robust genetic framework for marker-assisted selection, enabling the development of dual-purpose wheat cultivars with enhanced forage quality, thereby strengthening wheat’s utility as a reliable forage resource during periods of seasonal feed scarcity in SE production systems.

PMID:42718753 | PMC:PMC13553917 | DOI:10.3389/fpls.2026.1893113