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The continuous release of glucosinolates into the soil by Brassicaceae root exudation is a prerequisite to maintaining toxic levels of breakdown products such as isothiocyanates (ITCs). ITCs influence plant and microbial diversity in ecosystems, while fungi and Rhizobiaceae are particularly injured. Studies explaining the molecular mechanisms of the negative effects are presently limited. Therefore, we investigated the early effects of cyclic ITC goitrin on proteomes of the host and symbiotic Mesorhizobium loti in the nodules of Lotus japonicus and of free-living bacteria. In the nodules, many host proteins had a higher abundance, among them, peroxidases and pathogenesis-related PR-10 proteins functioning in the abscisic-acid-activated signaling pathway. In the microsymbiont, transporter proteins as a prominent group are enhanced; some proteins involved in N-fixation decreased. The proteomes give a report about the loss of immunity suppression resulting in the termination of symbiosis, which initiates nodule senescence. Free-living M. loti are severely damaged, indicated, i.a., by a decrease in transporter proteins, the assumed candidates for goitrin protein complex formation, and high proteolysis. The production of chicoric acid by the accompanying bacteria is inhibitory for M. loti but connected to goitrin elimination, as confirmed by mass spectrometric (MS) analysis. In summary, the nodulation process is severely affected by goitrin, causing nodule dysfunction and failed nodule development. N deficiency conditions leads to yellowish leaves and leaf abscission.

Background: Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships., Methods: Cross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features. Principal component analysis (PCA) was used to reduce data dimensionality to six principal components. An elastic principal tree was fitted to the reduced space. 4,585 participants from COPDGene Phase 2 were used to test longitudinal trajectories. 2,652 participants from SPIROMICS tested external reproducibility., Results: Our analysis used cross-sectional data to create an elastic principal tree, where the concept of time is represented by distance on the tree. Six clinically distinct tree segments were identified that differed by lung function, symptoms, and CT features: 1) Subclinical (SC); 2) Parenchymal Abnormality (PA); 3) Chronic Bronchitis (CB); 4) Emphysema Male (EM); 5) Emphysema Female (EF); and 6) Severe Airways (SA) disease. Cross-sectional SPIROMICS data confirmed similar groupings. 5-year data from COPDGene mapped longitudinal changes onto the tree. 29% of patients changed segment during follow-up; longitudinal trajectories confirmed a net flow of patients along the tree, from SC towards Emphysema, although alternative trajectories were noted, through airway disease predominant phenotypes, CB and SA., Conclusion: This novel analytic methodology provides an approach to defining longitudinal phenotypic trajectories using cross sectional data. These insights are clinically relevant and could facilitate precision therapy and future trials to modify disease progression.

Vegetative desiccation tolerance has evolved within the genera Craterostigma and Lindernia . A centre of endemism and diversification for these plants appears to occur in ancient tropical montane rainforests of east Africa in Kenya and Tanzania. Lindernia subracemosa , a desiccation-sensitive relative of Craterostigma plantagineum , occurs in these rainforests and experiences adequate rainfall and thus does not require desiccation tolerance. However, sharing this inselberg habitat, another species, Lindernia brevidens , does retain vegetative desiccation tolerance and is also related to the resurrection plant C. plantagineum found in South Africa. Leaf material was collected from all three species at different stages of hydration: fully hydrated (ca. 90% relative water content), half-dry (ca. 45% relative water content) and fully desiccated (ca. 5% relative water content). Cell wall monosaccharide datasets were collected from all three species. Comprehensive microarray polymer profiling (CoMPP) was performed using ca. 27 plant cell-wall-specific antibodies and carbohydrate-binding module probes. Some differences in pectin, xyloglucan and extension epitopes were observed between the selected species. Overall, cell wall compositions were similar, suggesting that wall modifications in response to vegetative desiccation involve subtle cell wall remodelling that is not reflected by the compositional analysis and that the plants and their walls are constitutively protected against desiccation.

To survive extreme desiccation, seeds enter a period of quiescence that can last millennia. Seed quiescence involves the accumulation of protective storage proteins and lipids through unknown adjustments in protein homeostasis (proteostasis). Here, we show that mutation of all six type-II metacaspase (MCA-II) proteases in Arabidopsis thaliana disturbs proteostasis in seeds. MCA-II mutant seeds fail to restrict the AAA ATPase CELL DIVISION CYCLE 48 (CDC48) at the endoplasmic reticulum to discard misfolded proteins, compromising seed storability. Endoplasmic reticulum (ER) localization of CDC48 relies on the MCA-IIs-dependent cleavage of PUX10 (ubiquitination regulatory X domain-containing 10), the adaptor protein responsible for titrating CDC48 to lipid droplets. PUX10 cleavage enables the shuttling of CDC48 between lipid droplets and the ER, providing an important regulatory mechanism sustaining spatiotemporal proteolysis, lipid droplet dynamics, and protein homeostasis. In turn, the removal of the PUX10 adaptor in MCA-II mutant seeds partially restores proteostasis, CDC48 localization, and lipid droplet dynamics prolonging seed lifespan. Taken together, we uncover a proteolytic module conferring seed longevity., (© 2024. The Author(s).)

Introduction: The African oil palm ( Elaeis guineensis Jacq.) is the predominant oil crop in the world. In addition to triacylglycerols, crude palm oil (CPO) extracted from the mesocarp of the fruits, contains high amounts of provitamin A (carotenes) and vitamin E (tocochromanols). Because of their unsaturated nature, the carotenes are prone to oxidation and therefore are in part limiting for the shelf life of CPO., Methods: A tree with unusual toochromanol composition was identified by HPLC screening of the mesocarp of wild trees. Polymorphisms in a candidate gene were identified by DNA sequencing. The candidate protein was heterologously expressed in Escherichia coli coli and Arabidopsis thaliana to test for enzyme activity. Oxidative stability of the CPO was studied by following carotene degradation over time., Results: In the present study, a wild Oil Palm tree (C59) from Cameroon was identified that lacks α-tocopherol and α-tocotrienol and instead accumulates the respective γ forms, suggesting that the activity of γ-tocopherol methyltransferase (VTE4) was affected. Sequencing of the VTE4 locus in the genome of plant C59 identified a G/C polymorphism that causes the exchange of a highly conserved tryptophan at position 290 with serine. The W290S exchange renders the VTE4 enzyme inactive, as shown after expression in Escherichia coli and Arabidopsis thaliana . The oxidative stability of carotenes in the mesocarp of the wild palm C59 was enhanced compared with control accessions. Furthermore, supplementation of commercial palm oil with different tocochromanols showed that γ-tocotrienol exerts a stronger effect during the protection of carotenes against oxidation than α-tocotrienol., Discussion: Therefore, the introduction of the high γ-tocotrienol trait into elite breeding lines represents a potent strategy to protect carotenes against oxidation and extend the shelf life of CPO, hence allowing the development of a value added high-carotene CPO to be used to fight against vitamin A deficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gutbrod, Pottier, Shirvani, Gutbrod, Djien-Nyami, Emade Ngoudjede, Ngando-Ebongue and Dörmann.)

Plants must cope with a variety of stressors during their life cycle, and the adaptive responses to these environmental cues involve all cellular organelles. Among them, comparatively little is known about the contribution of cytosolic lipid droplets (LDs) and their core set of neutral lipids and associated surface proteins to the rewiring of cellular processes in response to stress. Here, we analyzed the changes that occur in the lipidome and proteome of Arabidopsis (Arabidopsis thaliana) leaves after pathogen infection with Botrytis cinerea or Pseudomonas syringae, or after heat stress. Analyses were carried out in wild-type plants and the oil-rich double mutant trigalactosyldiacylglycerol1-1 sugar dependent 1-4 (tgd1-1 sdp1-4) that allowed for an allied study of the LD proteome in stressed leaves. Using liquid chromatography-tandem mass spectrometry-based methods, we showed that a hyperaccumulation of the primary LD core lipid triacylglycerol is a general response to stress and that acyl chain and sterol composition are remodeled during cellular adaptation. Likewise, comparative analysis of the LD protein composition in stress-treated leaves highlighted the plasticity of the LD proteome as part of the general stress response. We further identified at least two additional LD-associated proteins, whose localization to LDs in leaves was confirmed by confocal microscopy of fluorescent protein fusions. Taken together, these results highlight LDs as dynamic contributors to the cellular adaptation processes that underlie how plants respond to environmental stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Plants need to acclimate to different stresses to optimize growth under unfavorable conditions. In Arabidopsis (Arabidopsis thaliana), the abundance of the chloroplast envelope protein FATTY ACID EXPORT PROTEIN1 (FAX1) decreases after the onset of low temperatures. However, how FAX1 degradation occurs and whether altered FAX1 abundance contributes to cold tolerance in plants remains unclear. The rapid cold-induced increase in RHOMBOID-LIKE PROTEASE11 (RBL11) transcript levels, the physical interaction of RBL11 with FAX1, the specific FAX1 degradation after RBL11 expression, and the absence of cold-induced FAX1 degradation in rbl11 loss-of-function mutants suggest that this enzyme is responsible for FAX1 degradation. Proteomic analyses showed that rbl11 mutants have higher levels of FAX1 and other proteins involved in membrane lipid homeostasis, suggesting that RBL11 is a key element in the remodeling of membrane properties during cold conditions. Consequently, in the cold, rbl11 mutants show a shift in lipid biosynthesis toward the eukaryotic pathway, which coincides with impaired cold tolerance. To test whether cold sensitivity is due to increased FAX1 levels, we analyzed FAX1 overexpressors. The rbl11 mutants and FAX1 overexpressor lines show superimposable phenotypic defects upon exposure to cold temperatures. Our re-sults show that the cold-induced degradation of FAX1 by RBL11 is critical for Arabidop-sis to survive cold and freezing periods., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chlorophyll degradation causes the release of phytol, which is converted into phytyl diphosphate (phytyl-PP) by phytol kinase (VITAMIN E PATHWAY GENE5 [VTE5]) and phytyl phosphate (phytyl-P) kinase (VTE6). The kinase pathway is important for tocopherol synthesis, as the Arabidopsis (Arabidopsis thaliana) vte5 mutant contains reduced levels of tocopherol. Arabidopsis harbors one paralog of VTE5, farnesol kinase (FOLK) involved in farnesol phosphorylation. Here, we demonstrate that VTE5 and FOLK harbor kinase activities for phytol, geranylgeraniol, and farnesol with different specificities. While the tocopherol content of the folk mutant is unchanged, vte5-2 folk plants completely lack tocopherol. Tocopherol deficiency in vte5-2 plants can be complemented by overexpression of FOLK, indicating that FOLK is an authentic gene of tocopherol synthesis. The vte5-2 folk plants contain only ∼40% of wild-type amounts of phylloquinone, demonstrating that VTE5 and FOLK both contribute in part to phylloquinone synthesis. Tocotrienol and menaquinone-4 were produced in vte5-2 folk plants after supplementation with homogentisate or 1,4-dihydroxy-2-naphthoic acid, respectively, indicating that their synthesis is independent of the VTE5/FOLK pathway. These results show that phytyl moieties for tocopherol synthesis are completely but, for phylloquinone production, only partially derived from geranylgeranyl-chlorophyll and phytol phosphorylation by VTE5 and FOLK., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale and Objectives: Small airways disease (SAD) and emphysema are significant components of chronic obstructive pulmonary disease (COPD), a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema. Specifically, topologic PRM can define local patterns of both diseases to characterize how and in whom COPD progresses. We aimed to determine if distribution of CT-based PRM of functional SAD (fSAD) is associated with emphysema progression., Materials and Methods: We analyzed paired inspiratory-expiratory chest CT scans at baseline and 5-year follow up in 1495 COPDGene subjects using topological analyses of PRM classifications. By spatially aligning temporal scans, we mapped local emphysema at year five to baseline lobar PRM-derived topological readouts. K-means clustering was applied to all observations. Subjects were subtyped based on predominant PRM cluster assignments and assessed using non-parametric statistical tests to determine differences in PRM values, pulmonary function metrics, and clinical measures., Results: We identified distinct lobar imaging patterns and classified subjects into three radiologic subtypes: emphysema-dominant (ED), fSAD-dominant (FD), and fSAD-transition (FT: transition from healthy lung to fSAD). Relative to year five emphysema, FT showed rapid local emphysema progression (-57.5% ± 1.1) compared to FD (-49.9% ± 0.5) and ED (-33.1% ± 0.4). FT consisted primarily of at-risk subjects (roughly 60%) with normal spirometry., Conclusion: The FT subtype of COPD may allow earlier identification of individuals without spirometrically-defined COPD at-risk for developing emphysema., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Craig J. Galban reports financial support for article publishing charges; equipment, drugs, or supplies; and statistical analysis were provided by the National Heart, Lung, and Blood Institute of the National Institutes of Health. MeiLan K. Han, Craig J. Galban, and Charles R. Hatt report financial support was provided by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Charles R. Hatt reports a relationship with Imbio, LLC that includes employment. Craig J. Galban has patent licensed to Imbio, LLC. Craig J. Galban and Benjamin A. Hoff have patent licensed to Imbio, LLC. Personal fees from Konica Minolta and Continuing Education Alliance (W.W.L.); financial interest in Imbio, LLC (B.A.H. and C.J.G.); stock options in Imbio, Inc. (C.R.H.); personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Amgen, UpToDate, Altesa Biopharma, Medscape, NACE, MDBriefcase and Integrity (M.K.H.); either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association (M.K.H.); participation in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution (M.K.H.); stock options from Meissa Vaccines and Altesa Biopharma (M.K.H.) are reported. For the remaining authors no interests were declared., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline., Methods: PRM metrics of normal lung (PRM Norm ) and functional SAD (PRM fSAD ) were generated from CT scans collected as part of the COPDGene study (n = 8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRM Norm and PRM fSAD . Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV 1 decline using a machine learning model., Results: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRM fSAD and PRM Norm were independently associated with the amount of emphysema. Readouts χ fSAD (β of 0.106, p < 0.001) and V fSAD (β of 0.065, p = 0.004) were also independently associated with FEV 1 % predicted. The machine learning model using PRM topologies as inputs predicted FEV 1 decline over five years with an AUC of 0.69., Conclusions: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRM fSAD and PRM Norm may show promise as an early indicator of emphysema onset and COPD progression., (© 2024. The Author(s).)

Homogentisate Phytyltransferase ( HPT ) catalyzes condensation of homogentisate (HGA) and phytyl diphosphate (PDP) to produce tocopherols, but can also synthesize tocotrienols using geranylgeranyl diphosphate (GGDP) in plants engineered for deregulated HGA synthesis. In contrast to prior tocotrienol biofortification efforts, engineering enhanced tocopherol concentrations in green oilseeds has proven more challenging due to the integral role of chlorophyll metabolism in supplying the PDP substrate. This study show that RNAi suppression of CHLSYN coupled with HPT overexpression increases tocopherol concentrations by >two-fold in Arabidopsis seeds. We obtained additional increases in seed tocopherol concentrations by engineering increased HGA production via overexpression of bacterial TyrA that encodes chorismate mutase/prephenate dehydrogenase activities. In overexpression lines, seed tocopherol concentrations increased nearly three-fold, and resulted in modest tocotrienol accumulation. We further increased total tocochromanol concentrations by enhancing production of HGA and GGDP by overexpression of the gene for hydroxyphenylpyruvate dioxygenase (HPPD). This shifted metabolism towards increased amounts of tocotrienols relative to tocopherols, which was reflected in corresponding increases in ratios of GGDP/PDP in these seeds. Overall, our results provide a theoretical basis for genetic improvement of total tocopherol concentrations in green oilseeds (e.g., rapeseed, soybean) through strategies that include seed-suppression of CHLSYN coupled with increased HGA production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Qin, Chen, Zhou, Zhang, Zhang, Xu, Gan, Liu, Romer, Dörmann, Cahoon and Zhang.)

Background: Because chest CT scan has largely supplanted surgical lung biopsy for diagnosing most cases of interstitial lung disease (ILD), tools to standardize CT scan interpretation are urgently needed., Research Question: Does a deep learning (DL)-based classifier for usual interstitial pneumonia (UIP) derived using CT scan features accurately discriminate radiologist-determined visual UIP?, Study Design and Methods: A retrospective cohort study was performed. Chest CT scans acquired in individuals with and without ILD were drawn from a variety of public and private data sources. Using radiologist-determined visual UIP as ground truth, a convolutional neural network was used to learn discrete CT scan features of UIP, with outputs used to predict the likelihood of UIP using a linear support vector machine. Test performance characteristics were assessed in an independent performance cohort and multicenter ILD clinical cohort. Transplant-free survival was compared between UIP classification approaches using the Kaplan-Meier estimator and Cox proportional hazards regression., Results: A total of 2,907 chest CT scans were included in the training (n = 1,934), validation (n = 408), and performance (n = 565) data sets. The prevalence of radiologist-determined visual UIP was 12.4% and 37.1% in the performance and ILD clinical cohorts, respectively. The DL-based UIP classifier predicted visual UIP in the performance cohort with sensitivity and specificity of 93% and 86%, respectively, and in the multicenter ILD clinical cohort with 81% and 77%, respectively. DL-based and visual UIP classification similarly discriminated survival, and outcomes were consistent among cases with positive DL-based UIP classification irrespective of visual classification., Interpretation: A DL-based classifier for UIP demonstrated good test performance across a wide range of UIP prevalence and similarly discriminated survival when compared with radiologist-determined UIP. This automated tool could efficiently screen for UIP in patients undergoing chest CT scan and identify a high-risk phenotype among those with known ILD., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. K., K. L., S. Z., and C. H. are employees of Imbio, Inc. H. G., E. S., S. L., and C. S. are paid consultants for Imbio, Inc. J. H. C., A. A., and J. M. O. report consulting fees from Genentech unrelated to this investigation. None declared (L. C., J. V. P., J. M. W., A. W. M., S. G., A. G.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The plant homeodomain (PHD) finger with a conserved Cys4-His-Cys3 motif is a common zinc-binding domain, which is widely present in all eukaryotic genomes. The PHD finger is the "reader" domain of methylation marks in histone H3 and plays a role in the regulation of gene expression patterns. Numerous proteins containing the PHD finger have been found in plants. In this review, we summarize the functional studies on PHD finger proteins in plant growth and development and responses to abiotic stresses in recent years. Some PHD finger proteins, such as VIN3, VILs, and Ehd3, are involved in the regulation of flowering time, while some PHD finger proteins participate in the pollen development, for example, MS, TIP3, and MMD1. Furthermore, other PHD finger proteins regulate the plant tolerance to abiotic stresses, including Alfin1, ALs, and AtSIZ1. Research suggests that PHD finger proteins, as an essential transcription regulator family, play critical roles in various plant biological processes, which is helpful in understanding the molecular mechanisms of novel PHD finger proteins to perform specific function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quan, Chan, Wei, Mao, Bartels and Liu.)

The cyclic depsipeptide FR900359 (FR) is derived from the soil bacterium Chromobacterium vaccinii and known to bind G q proteins of mammals and insects, thereby abolishing the signal transduction of their G q protein-coupled receptors, a process that leads to severe physiological consequences. Due to their highly conserved structure, G q family of proteins are a superior ecological target for FR producing organisms, resulting in a defense towards a broad range of harmful organisms. Here, we focus on the question whether bacteria like C. vaccinii are important factors in soil in that their secondary metabolites impair, e.g., plant harming organisms like nematodes. We prove that the G q inhibitor FR is produced under soil-like conditions. Furthermore, FR inhibits heterologously expressed Gα q proteins of the nematodes Caenorhabditis elegans and Heterodera schachtii in the micromolar range. Additionally, in vivo experiments with C. elegans and the plant parasitic cyst nematode H. schachtii demonstrated that FR reduces locomotion of C. elegans and H. schachtii. Finally, egg-laying of C. elegans and hatching of juvenile stage 2 of H. schachtii from its cysts is inhibited by FR, suggesting that FR might reduce nematode dispersion and proliferation. This study supports the idea that C. vaccinii and its excreted metabolome in the soil might contribute to an ecological equilibrium, maintaining and establishing the successful growth of plants., (© 2023. The Author(s).)

Purpose: Diagnosis and surveillance of thoracic aortic aneurysm (TAA) involves measuring the aortic diameter at various locations along the length of the aorta, often using computed tomography angiography (CTA). Currently, measurements are performed by human raters using specialized software for three-dimensional analysis, a time-consuming process, requiring 15 to 45 min of focused effort. Thus, we aimed to develop a convolutional neural network (CNN)-based algorithm for fully automated and accurate aortic measurements., Approach: Using 212 CTA scans, we trained a CNN to perform segmentation and localization of key landmarks jointly. Segmentation mask and landmarks are subsequently used to obtain the centerline and cross-sectional diameters of the aorta. Subsequently, a cubic spline is fit to the aortic boundary at the sinuses of Valsalva to avoid errors related inclusions of coronary artery origins. Performance was evaluated on a test set of 60 scans with automated measurements compared against expert manual raters., Result: Compared to training separate networks for each task, joint training yielded higher accuracy for segmentation, especially at the boundary ( p < 0.001 ), but a marginally worse (0.2 to 0.5 mm) accuracy for landmark localization ( p < 0.001 ). Mean absolute error between human and automated was ≤ 1    mm at six of nine standard clinical measurement locations. However, higher errors were noted in the aortic root and arch regions, ranging between 1.4 and 2.2 mm, although agreement of manual raters was also lower in these regions., Conclusion: Fully automated aortic diameter measurements in TAA are feasible using a CNN-based algorithm. Automated measurements demonstrated low errors that are comparable in magnitude to those with manual raters; however, measurement error was highest in the aortic root and arch., (© 2023 The Authors.)

Purpose: The purpose of this study was to anatomically correlate ventilation defects with regions of air trapping by whole lung, lung lobe, and airway segment in the context of airway mucus plugging in asthma. Methods: A total of 34 asthmatics [13M:21F, 13 mild/moderate, median age (range) of 49.5 (36.8-53.3) years and 21 severe, 56.1 (47.1-62.6) years] and 4 healthy subjects [1M:3F, 38.5 (26.6-52.2) years] underwent HP 3 He MRI and CT imaging. HP 3 He MRI was assessed for ventilation defects using a semi-automated k-means clustering algorithm. Inspiratory and expiratory CTs were analyzed using parametric response mapping (PRM) to quantify markers of emphysema and functional small airways disease (fSAD). Segmental and lobar lung masks were obtained from CT and registered to HP 3 He MRI in order to localize ventilation defect percent (VDP), at the lobar and segmental level, to regions of fSAD and mucus plugging. Spearman's correlation was utilized to compare biomarkers on a global and lobar level, and a multivariate analysis was conducted to predict segmental fSAD given segmental VDP (sVDP) and mucus score as variables in order to further understand the functional relationships between regional measures of obstruction. Results: On a global level, fSAD was correlated with whole lung VDP ( r = 0.65, p < 0.001), mucus score ( r = 0.55, p < 0.01), and moderately correlated (-0.60 ≤ r ≤ -0.56, p < 0.001) to percent predicted (%p) FEV1, FEF25-75 and FEV1/FVC, and more weakly correlated to FVC%p (-0.38 ≤ r ≤ -0.35, p < 0.001) as expected from previous work. On a regional level, lobar VDP, mucus scores, and fSAD were also moderately correlated (r from 0.45-0.66, p < 0.01). For segmental colocalization, the model of best fit was a piecewise quadratic model, which suggests that sVDP may be increasing due to local airway obstruction that does not manifest as fSAD until more extensive disease is present. sVDP was more sensitive to the presence of a mucus plugs overall, but the prediction of fSAD using multivariate regression showed an interaction in the presence of a mucus plugs when sVDP was between 4% and 10% ( p < 0.001). Conclusion: This multi-modality study in asthma confirmed that areas of ventilation defects are spatially correlated with air trapping at the level of the airway segment and suggests VDP and fSAD are sensitive to specific sources of airway obstruction in asthma, including mucus plugs., Competing Interests: SF receives research support from GE Healthcare and serves on the scientific advisory board of Polarean PLC. KC and CH are currently employees of Imbio LLC. LD and NJ are Principal Investigators in the NHLBI PrecISE Trial network that has relationships with the following companies for drug support and equipment contracts: Glaxo Smith Kline, Laurel, Sun Pharma, Vifor/OM Pharm, Vitaeris/CSL Behring, Vitaflo, Vyaire, Caire Diagnostics, MIR, Propeller Health, ZEPHYRx. NJ reports grants and personal fees from AstraZeneca, and personal fees from GSK and Boehringer Ingelheim for consultations outside the submitted work. LD has consulted with Glaxo Smith Kline, AstraZeneca, Sanofi and OM Pharma during the course of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Carey, Hotvedt, Mummy, Lee, Denlinger, Schiebler, Sorkness, Jarjour, Hatt, Galban and Fain.)

Early detection of lung cancer is critical for improvement of patient survival. To address the clinical need for efficacious treatments, genetically engineered mouse models (GEMM) have become integral in identifying and evaluating the molecular underpinnings of this complex disease that may be exploited as therapeutic targets. Assessment of GEMM tumor burden on histopathological sections performed by manual inspection is both time consuming and prone to subjective bias. Therefore, an interplay of needs and challenges exists for computer-aided diagnostic tools, for accurate and efficient analysis of these histopathology images. In this paper, we propose a simple machine learning approach called the graph-based sparse principal component analysis (GS-PCA) network, for automated detection of cancerous lesions on histological lung slides stained by hematoxylin and eosin (H&E). Our method comprises four steps: 1) cascaded graph-based sparse PCA, 2) PCA binary hashing, 3) block-wise histograms, and 4) support vector machine (SVM) classification. In our proposed architecture, graph-based sparse PCA is employed to learn the filter banks of the multiple stages of a convolutional network. This is followed by PCA hashing and block histograms for indexing and pooling. The meaningful features extracted from this GS-PCA are then fed to an SVM classifier. We evaluate the performance of the proposed algorithm on H&E slides obtained from an inducible K-ras G12D lung cancer mouse model using precision/recall rates, F β -score, Tanimoto coefficient, and area under the curve (AUC) of the receiver operator characteristic (ROC) and show that our algorithm is efficient and provides improved detection accuracy compared to existing algorithms., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Charles Hatt is employed by and has stock options in Imbio, Inc. Dr. Craig Galban is co-inventor of Parametric Response Mapping, which the University of Michigan has licensed to Imbio, Inc., and has a financial interest in Imbio, Inc., (Copyright © 2023. Published by Elsevier Inc.)

Toxic breakdown products of young Camelina sativa (L.) Crantz, glucosinolates can eliminate microorganisms in the soil. Since microorganisms are essential for phosphate cycling, only insensitive microorganisms with phosphate-solubilizing activity can improve C. sativa's phosphate supply. In this study, 33 P-labeled phosphate, inductively coupled plasma mass spectrometry and pot experiments unveiled that not only Trichoderma viride and Pseudomonas laurentiana used as phosphate-solubilizing inoculants, but also intrinsic soil microorganisms, including Penicillium aurantiogriseum , and the assemblies of root-colonizing microorganisms solubilized as well phosphate from apatite, trigger off competitive behavior between the organisms. Driving factors in the competitiveness are plant and microbial secondary metabolites, while glucosinolates of Camelina and their breakdown products are regarded as key compounds that inhibit the pathogen P. aurantiogriseum , but also seem to impede root colonization of T. viride . On the other hand, fungal diketopiperazine combined with glucosinolates is fatal to Camelina . The results may contribute to explain the contradictory effects of phosphate-solubilizing microorganisms when used as biofertilizers. Further studies will elucidate impacts of released secondary metabolites on coexisting microorganisms and plants under different environmental conditions.

Purpose: The purpose of this study was to train and validate machine learning models for predicting rapid decline of forced expiratory volume in 1 s (FEV 1 ) in individuals with a smoking history at-risk-for chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD 0), or with mild-to-moderate (GOLD 1-2) COPD. We trained multiple models to predict rapid FEV 1 decline using demographic, clinical and radiologic biomarker data. Training and internal validation data were obtained from the COPDGene study and prediction models were validated against the SPIROMICS cohort. Methods: We used GOLD 0-2 participants ( n = 3,821) from COPDGene (60.0 ± 8.8 years, 49.9% male) for variable selection and model training. Accelerated lung function decline was defined as a mean drop in FEV 1 % predicted of > 1.5%/year at 5-year follow-up. We built logistic regression models predicting accelerated decline based on 22 chest CT imaging biomarker, pulmonary function, symptom, and demographic features. Models were validated using n = 885 SPIROMICS subjects (63.6 ± 8.6 years, 47.8% male). Results: The most important variables for predicting FEV 1 decline in GOLD 0 participants were bronchodilator responsiveness (BDR), post bronchodilator FEV 1 % predicted (FEV 1 .pp.post), and CT-derived expiratory lung volume; among GOLD 1 and 2 subjects, they were BDR, age, and PRM lower lobes fSAD . In the validation cohort, GOLD 0 and GOLD 1-2 full variable models had significant predictive performance with AUCs of 0.620 ± 0.081 ( p = 0.041) and 0.640 ± 0.059 ( p < 0.001). Subjects with higher model-derived risk scores had significantly greater odds of FEV 1 decline than those with lower scores. Conclusion: Predicting FEV 1 decline in at-risk patients remains challenging but a combination of clinical, physiologic and imaging variables provided the best performance across two COPD cohorts., Competing Interests: WL reports personal fees from Konica Minolta and Continuing Education Alliance. JC reports grants from NHLBI and the COPD Foundation, during performance of this study; grants from NHLBI, NIAID, the Department of Veterans Affairs, and the Department of Defense, outside this study; consulting fees (paid to his institution) from AstraZeneca PLC and CLS Behring, LLC, outside this study; and personal fees from AstraZeneca Global, outside this study. CG is co-inventor of Parametric Response Mapping, which the University of Michigan has licensed to Imbio, LLC., and has a financial interest in Imbio, LLC. MH reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Amgen, UpToDate, Altesa Biopharma, Medscape, NACE, MDBriefcase and Integrity. She has received either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. She has received stock options from Meissa Vaccines and Altesa Biopharma. CH is employed by and has stock options in Imbio, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Labaki, Murray, Martinez, Curtis, Hoffman, Ram, Bell, Galban, Han and Hatt.)

Resurrection plants can survive prolonged life without water (anhydrobiosis) in regions with seasonal drying. This desiccation tolerance requires the coordination of numerous cellular processes across space and time, and individual plant tissues face unique constraints related to their function. Here, we analyzed the complex, octoploid genome of the model resurrection plant Craterostigma (C. plantagineum), and surveyed spatial and temporal expression dynamics to identify genetic elements underlying desiccation tolerance. Homeologous genes within the Craterostigma genome have divergent expression profiles, suggesting the subgenomes contribute differently to desiccation tolerance traits. The Craterostigma genome contains almost 200 tandemly duplicated early light-induced proteins, a hallmark trait of desiccation tolerance, with massive upregulation under water deficit. We identified a core network of desiccation-responsive genes across all tissues, but observed almost entirely unique expression dynamics in each tissue during recovery. Roots and leaves have differential responses related to light and photoprotection, autophagy and nutrient transport, reflecting their divergent functions. Our findings highlight a universal set of likely ancestral desiccation tolerance mechanisms to protect cellular macromolecules under anhydrobiosis, with secondary adaptations related to tissue function., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Abutilon theophrasti Medik. (velvetleaf) is a problematic annual weed in field crops which has invaded many temperate parts of the world. Since the loss of crop yields can be extensive, approaches to manage the weed include not only conventional methods, but also biological methods, for instance by microorganisms releasing phytotoxins and plant-derived allelochemicals. Additionally, benzoxazinoid-rich rye mulches effective in managing common weeds like Amaranthus retroflexus L. have been tested for this purpose. However, recent methods for biological control are still unreliable in terms of intensity and duration. Rye mulches were also ineffective in managing velvetleaf. In this review, we present the attempts to reduce velvetleaf infestation by biological methods and discuss possible reasons for the failure. The resilience of velvetleaf may be due to the extraordinary capacity of the plant to collect, for its own survival, the most suitable microorganisms from a given farming site, genetic and epigenetic adaptations, and a high stress memory. Such properties may have developed together with other advantageous abilities during selection by humans when the plant was used as a crop. Rewilding could be responsible for improving the microbiomes of A. theophrasti .

Genetic variants in TMEM106B are a common risk factor for frontotemporal lobar degeneration and the most important modifier of disease risk in patients with progranulin (GRN) mutations (FTLD-GRN). TMEM106B is encoding a lysosomal transmembrane protein of unknown molecular function. How it mediates its disease-modifying function remains enigmatic. Several TMEM106B single nucleotide polymorphisms (SNPs) are significantly associated with disease risk in FTLD-GRN carriers, of which all except one are within intronic sequences of TMEM106B. Of note, the non-coding SNPs are in high linkage disequilibrium with the coding SNP rs3173615 located in exon six of TMEM106B, resulting in a threonine to serine change at amino acid 185 in the minor allele, which is protective in FTLD-GRN carriers. To investigate the functional consequences of this variant in vivo, we generated and characterized a knockin mouse model harboring the Tmem106b T186S variant. We analyzed the effect of this protective variant on FTLD pathology by crossing Tmem106b T186S mice with Grn -/- knockout mice, a model for GRN-mediated FTLD. We did not observe the amelioration of any of the investigated Grn -/- knockout phenotypes, including transcriptomic changes, lipid alterations, or microgliosis in Tmem106b T186S/T186S × Grn -/- mice, indicating that the Tmem106b T186S variant is not protective in the Grn -/- knockout mouse model. These data suggest that effects of the associated SNPs not directly linked to the amino acid exchange in TMEM106B are critical for the modifying effect., (© 2023. The Author(s).)

Isoprenoids in plants are synthesized following the plastidial methylerythritol-4-phosphate (MEP) pathway or the mevalonate pathway localized to the cytosol and peroxisomes. Isoprenyl-diphosphates (isoprenyl-PP) are important intermediates for the synthesis of chlorophyll, carotenoids, sterols, and other isoprenoids in plants. The quantification of isoprenyl-PP is challenging due to the amphipathic structure, the low abundance, and the susceptibility to hydrolysis during extraction and storage. Different methods for the measurement of isoprenyl-phosphates have been developed. Isoprenyl-phosphates can be measured after radioactive labeling or after derivatization. Liquid chromatography-mass spectrometry (LC-MS) methods provide enhanced sensitivity, but still require the extraction from large amounts of sample material. In the protocol presented here, the monophosphates and diphosphates of farnesol, geranylgeraniol and phytol are isolated from plant material with an isopropanol-containing buffer and quantified by LC-MS using citronellyl-P and citronellyl-PP as internal standards. With a low limit of detection for phytyl-P, geranylgeranyl-P, phytyl-PP, and geranylgeranyl-PP, isoprenyl-phosphates can be accurately measured in Arabidopsis leaves or seeds starting with only 20mg of fresh weight., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Peppermint (Mentha x piperita) is a species with inhibitory allelopathic properties due to its high amounts of terpenes. Recent studies have disclosed dosage dependent growth promotion or defense reactions in plants when facing appropriate amounts of Mentha bouquet terpenes. These positive effects could be of interest for agricultural applications. To obtain more insights into leaf growth modulations, the expression of Arabidopsis and Brassica rapa TCP transcription factors were studied after fumigation with M. x piperita bouquets (Arabidopsis), with M. x piperita essential oil or with limonene (Arabidopsis and Chinese cabbage). According to qPCR studies, expression of TCP3, TCP24, and TCP20 were downregulated by all treatments in Arabidopsis, leading to altered leaf growth. Expressions of B. rapa TCPs after fumigation with the essential oil or limonene were less affected. Extensive greenhouse and polytunnel trials with white cabbage and Mentha plants showed that the developmental stage of the leaves, the dosage, and the fumigation time are of crucial importance for changed fresh and dry weights. Although further research is needed, the study may contribute to a more intensive utilization of ecologically friendly and species diversity conservation and positive allelopathic interactions in future agricultural systems.

Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de novo synthase (FAS), they depend on host-derived fatty acids. AMF colonization is accompanied by expression of specific lipid genes and synthesis of sn -2 monoacylglycerols (MAGs). It is unknown how host-derived fatty acids are taken up by AMF. We describe the characterization of two AMP-binding domain protein genes from Rhizophagus irregularis , RiFAT1 and RiFAT2 , with sequence similarity to Saccharomyces cerevisiae fatty acid transporter 1 ( FAT1 ). Uptake of 13 C-myristic acid (14:0) and, to a lesser extent, 13 C-palmitic acid (16:0) was enhanced after expression of RiFAT1 or RiFAT2 in S. cerevisiae Δ fat1 cells. The uptake of 2 H-labeled fatty acids from 2 H-myristoylglycerol or 2 H-palmitoylglycerol was also increased after RiFAT1 and RiFAT2 expression in Δ fat , but intact 2 H-MAGs were not detected. RiFAT1 and RiFAT2 expression was induced in colonized roots compared with extraradical mycelium. 13 C-label in the AMF-specific palmitvaccenic acid (16:1Δ11) and eicosatrienoic acid (20:3) were detected in colonized roots only when 13 C 2 -acetate was supplemented but not 13 C-fatty acids, demonstrating that de novo synthesized, host-derived fatty acids are rapidly taken up by R. irregularis from the roots. The results show that RiFAT1 and RiFAT2 are involved in the uptake of myristic acid (14:0) and palmitic acid (16:0), while fatty acids from MAGs are only taken up after hydrolysis. Therefore, the two proteins might be involved in fatty acid import into the fungal arbuscules in colonized roots.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Cells steadily adapt their membrane glycerophospholipid (GPL) composition to changing environmental and developmental conditions. While the regulation of membrane homeostasis via GPL synthesis in bacteria has been studied in detail, the mechanisms underlying the controlled degradation of endogenous GPLs remain unknown. Thus far, the function of intracellular phospholipases A (PLAs) in GPL remodeling (Lands cycle) in bacteria is not clearly established. Here, we identified the first cytoplasmic membrane-bound phospholipase A 1 (PlaF) from Pseudomonas aeruginosa , which might be involved in the Lands cycle. PlaF is an important virulence factor, as the P. aeruginosa Δ plaF mutant showed strongly attenuated virulence in Galleria mellonella and macrophages. We present a 2.0-Å-resolution crystal structure of PlaF, the first structure that reveals homodimerization of a single-pass transmembrane (TM) full-length protein. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. The dimerization site and the catalytic sites are linked by an intricate ligand-mediated interaction network, which might explain the product (fatty acid) feedback inhibition observed with the purified PlaF protein. We used molecular dynamics simulations and configurational free energy computations to suggest a model of PlaF activation through a coupled monomerization and tilting of the monomer in the membrane, which constrains the active site cavity into contact with the GPL substrates. Thus, these data show the importance of the PlaF-mediated GPL remodeling pathway for virulence and could pave the way for the development of novel therapeutics targeting PlaF., Competing Interests: FB, JG, MC, SS, MS, BT, LR, SF, PD, HG, RB, KJ, FK No competing interests declared, (© 2022, Bleffert et al.)

Modified atmosphere (MA) packaging plays an important role in improving food quality and safety. By using different gas mixtures and packaging materials the shelf life of fresh produce can significantly be increased. A Gram-negative-staining, rod-shaped, orange-pigmented strain DH-B6 T , has been isolated from MA packed raw pork sausage (20% CO 2 , 80% O 2 ). The strain produced biofilms and showed growth at high CO 2 levels of up to 40%. Complete 16S rRNA gene and whole-genome sequences revealed that strain DH-B6 T belongs to the genus Chryseobacterium , being closely related to strain Chryseobacterium indologenes DSM 16777 T (98.4%), followed by Chryseobacterium gleum NCTC11432 T (98.3%) and Chryseobacterium lactis KC1864 T (98.2%). Average nucleotide identity value between DH-B6 T and C. indologenes DSM 16777 T was 81.1% and digital DNA-DNA hybridisation was 24.9%, respectively. The DNA G+C content was 35.51 mol%. Chemotaxonomical analysis revealed the presence of the rare glycine lipid cytolipin, the serine-glycine lipid flavolipin and the sulfonolipid sulfobacin A, as well as phosphatidylethanolamine, monohexosyldiacylglycerol and ornithine lipid, including the hydroxylated forms. Major fatty acids were iC 15 : 0 (50.7%) and iC 17 : 1 cis 9 (28.7%), followed by iC 15 : 0 2-OH (7.0%) and iC 17 : 0 3-OH (6.2%). The isolated strain contained MK-6 as the only respiratory quinone and flexirubin-like pigments were detected as the major pigments. Based on the phenotypic, chemotaxonomic and phylogenetic characteristics, the strain DH-B6 T (=DSM 110542 T =LMG 31915 T ) represents a novel species of the genus Chryseobacterium , for which the name Chryseobacterium capnotolerans sp. nov. is proposed. Emended descriptions of the genus Chryseobacterium and eight species of this genus based on polar lipid characterisation are also proposed.