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Recent Submissions
Genomic approaches to accelerate American chestnut restoration
Westbrook, Jared W.; Malukiewicz, Joanna; Zhang, Qian; Sreedasyam, Avinash; Jenkins, Jerry W.; Lakoba, Vasiliy; Fitzsimmons, Sara; Van Clief, Jamie; Collins, Kendra; Hoy, Stephen; Stark, Cassie; Graboski, Lake; Jenkins, Eric; Saielli, Thomas M.; Jarrett, Benjamin T.; Wigfield, Lucinda J.; Kerwien, Lauren M.; Wilbur, Ciera; Sandercock, Alexander M.; Craddock, J. Hill; Keriö, Susanna; Zhebentyayeva, Tetyana; Fan, Shenghua; Thomas, Austin M.; Abbott, Albert G.; Nelson, C. Dana; Xia, Xiaoxia; McKenna, James R.; Kell, Caleb; Williams, Melissa; Boston, LoriBeth; Plott, Christopher; Carle, Florian; Swatt, Jack; Ostroff, Jack; Jeffers, Steven N.; McKeever, Kathleen; Smith, Erica; Ellis, Thomas J.; James, Joseph B.; Sisco, Paul; Newhouse, Andrew; Carlson, Erik; Powell, William A.; Hebard, Frederick V.; Scrivani, John; Heverly, Caragh; Cipollini, Martin; Clark, Brian; Evans, Eric; Levine, Bruce; Carlson, John E.; Goodstein, David; Orebaugh, Jack; Yang, Zamin K.; Martin, Madhavi Z.; Tannous, Joanna; Rush, Tomás A.; Engle, Nancy L.; Tschaplinski, Timothy J.; Grimwood, Jane; Schmutz, Jeremy; Holliday, Jason A.; Lovell, John T. (American Association for the Advancement of Science, 2026-02)
More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. However, progress has been slow because of the complex genetic architecture of resistance. To better understand blight resistance, we compared reference genomes, gene expression responses, and stem metabolite profiles of the resistant Chinese and susceptible American chestnut species. To accelerate resistance breeding, we conducted large-scale phenotyping and genotyping in hybrids of these species. Simulation and inoculation experiments suggest that significant resistance gains are possible through selectively breeding trees with an average of 70 to 85% American chestnut ancestry. The resources developed in this work are foundational for breeding to create diverse restoration populations with sufficient disease resistance and competitive growth.
Concurrent increase in fatty acid oxidation and fatty acid synthesis: a unique metabolic state in a pig model of pediatric steatotic liver disease
Yadav, Ravi; Lima, Marta R. M.; McMillan, Ryan P.; Sunny, Nishanth E.; El-Kadi, Samer W. (American Physiological Society, 2025-11-18)
Steatotic liver disease (SLD) is a spectrum of chronic and progressive disorders. Although often associated with obesity, it can afflict individuals without obesity, including infants. We previously reported that neonatal pigs fed formulas enriched with medium-chain fatty acids (MCFAs), rather than long-chain fatty acids (LCFAs), developed steatosis by day 7 and steatohepatitis by day 14. Here, we examined hepatic regulation of lipolytic and lipogenic pathways and associated metabolic outcomes. Neonatal pigs (n = 18) were fed isocaloric formulas containing MCFAs or LCFAs for 7, 14, or 21 days. Transcript abundance of most lipolytic and lipogenic genes was greater in MCFA- than in LCFA-fed pigs, independent of feeding duration. Upregulation of lipolytic genes of MCFA-fed pigs corresponded with greater lauric (P = 0.04) and palmitic (P = 0.03) acid oxidation, and greater plasma β-hydroxybutyrate concentrations than LCFA counterparts (P = 0.06). Upregulation of lipogenic genes in the MCFA group coincided with greater hepatic medium- (C12:0, C14:0) and long- (C16:0, C16:1) chain fatty acid concentrations (P < 0.05), and greater de novo lipogenic index at all time points (P < 0.001) compared with the LCFA group. Principal component and partial least squares analyses indicated that MCFA-fed pigs clustered with upregulated lipogenic, lipolytic, and transport genes, and were associated with greater medium-chain fatty acids and hepatic fat. However, LCFA-fed pigs clustered with greater polyunsaturated fatty acids and reduced transcript abundance of these genes. These findings demonstrate that pediatric SLD pathophysiology involves metabolic adaptations where fatty acid uptake and synthesis overwhelm the liver's oxidative or export capacity, causing net lipid accumulation.NEW & NOTEWORTHY We identify a distinct metabolic state in neonatal pigs with SLD. Contrary to the prevailing paradigm, disease development and progression to the more severe steatohepatitis occur despite enhanced hepatic fatty acid oxidation and the concurrent upregulation of both lipolytic and lipogenic gene expression. This paradoxical metabolic state, where increased fatty acid oxidation fails to prevent progressive steatosis, provides new insights into early-life SLD pathophysiology.
Assessing the Effects of Exoskeletons on Physical Demands, Trip and Slip Risks, and User Perceptions in Manual Mining Tasks
Akinwande, Feyisayo Alexander (Virginia Tech, 2026-02-25)
Work-related musculoskeletal disorders (WMSDs) are a major health concern worldwide in the mining sector and are associated with frequent exposure to risk factors prevalent in manual mining tasks. Occupational exoskeletons (EXOs) are a promising ergonomic intervention to mitigate WMSD risk, by reducing physical demands and improving work performance. The purpose of this dissertation was to assess the potential benefits of using EXOs for addressing health and safety challenges encountered by miners, while also examining the limitations associated with EXO use, as a means of providing new evidence to guide the effective selection and application of passive arm-support exoskeletons (ASEs) and back-support exoskeletons (BSEs), help avoid unintended/preventable side effects resulting from this technology, and aid in maximizing the benefits of EXO use in mining.
The first study identified and assessed the opportunities for and feasibility of implementing EXOs in mining, through an online survey with industry stakeholders. Miners reported potential benefits of EXOs for lifting and overhead work and shared concerns about EXO use. They also emphasize the need to ensure task compatibility, comfort, and affordability to ensure safe and effective adoption in mining.
The second study quantified the potential benefits and risks of using ASEs and BSEs for diverse manual mining tasks using controlled lab-based simulations. Both ASE and BSE effects were device- and task-specific. BSEs significantly reduced peak trunk extensor activity during lifting and overhead installation tasks, although perceptions of exertion and discomfort differed by device: soft BSE reduced perceived upper-back exertion, whereas rigid BSE increased waist/hip discomfort. ASEs also differed in their effects on total shoulder muscle activity across tasks, but their use reduced perceived exertion across most body regions with minimal reported discomfort.
The third study assessed the effects of BSEs on trip and slip risks during load carriage on different surface slopes. Using both BSEs differentially altered minimum foot clearance (MFC) and required coefficient of friction (RCoF). Rigid BSEs increased right foot MFC and RCoF, whereas the soft BSE largely preserved baseline gait mechanics, with no significant effects on objective slip or trip risk metrics.
Overall, we found that the efficacy of ASEs and BSEs are highly device- and task-dependent. These results provide critical insights to inform evidence-based guidelines for the safe implementation of occupational EXOs in mining and other physically demanding industries.
Confinement in fibrous environments positions and orients mitotic spindles
Sarkar, Apurba; Jana, Aniket; Agashe, Atharva; Wang, Ji; Kapania, Rakesh; Gov, Nir S.; DeLuca, Jennifer G.; Paul, Raja; Nain, Amrinder S. (Oxford University Press, 2025-07)
Accurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and tilting of the metaphase plate (MP). To understand the effect of confinement on mitosis by fibers (ECM confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels. Rounded mitotic bodies are anchored in place by actin retraction fibers (RFs) originating from adhesions on fibers. We discover that the extent of confinement influences RF organization in 3D, forming triangular and band-like patterns on the cell cortex under low and high confinement, respectively. Our mechanistic analysis reveals that the patterning of RFs on the cell cortex is the primary driver of the MP rotation. A stochastic Monte Carlo simulation of the centrosome, chromosome, membrane interactions, and 3D arrangement of RFs recovers MP tilting trends observed experimentally. Under high ECM confinement, the fibers can mechanically pinch the cortex, causing the MP to have localized deformations at contact sites with fibers. Interestingly, high ECM confinement leads to low and high MP tilts, which we mechanistically show to depend upon the extent of cortical deformation, RF patterning, and MP position. We identify that cortical deformation and RFs work in tandem to limit MP tilt, while asymmetric positioning of MP leads to high tilts. Overall, we provide fundamental insights into how mitosis may proceed in ECM-confining microenvironments in vivo.
Volumetric imaging of the 3D orientation of cellular structures with a polarized fluorescence light-sheet microscope
Chandler, Talon; Guo, Min; Su, Yijun; Chen, Jiji; Wu, Yicong; Liu, Junyu; Agashe, Atharva; Fischer, Robert S.; Mehta, Shalin B.; Kumar, Abhishek; Baskin, Tobias I.; Jaumouille, Valentin; Liu, Huafeng; Swaminathan, Vinay; Nain, Amrinder S.; Oldenbourg, Rudolf; La Riviere, Patrick J.; Shroff, Hari (National Academy of Sciences, 2025-02-21)
Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations in biological samples, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the diffraction-limited three-dimensional distribution of the orientations and positions of ensembles of fluorescent dipoles that label biological structures. We share a set of visualization, histogram, and profiling tools for interpreting these positions and orientations. We model the distributions based on the polarization-dependent efficiency of excitation and detection of emitted fluorescence, using coarse-grained representations we call orientation distribution functions (ODFs). We apply ODFs to create physics-informed models of image formation with spatio-angular point-spread and transfer functions. We use theory and experiment to conclude that light-sheet tilting is a necessary part of our design for recovering all three-dimensional orientations. We use our system to extend known two-dimensional results to three dimensions in FM1-43-labeled giant unilamellar vesicles, fast-scarlet-labeled cellulose in xylem cells, and phalloidin-labeled actin in U2OS cells. Additionally, we observe phalloidin-labeled actin in mouse fibroblasts grown on grids of labeled nanowires and identify correlations between local actin alignment and global cell-scale orientation, indicating cellular coordination across length scales.