Background: Abdominal and thoracic CT provide a valuable opportunity for osteoporosis screening regardless of the clinical indication for imaging. Purpose: To establish reference normative ranges for first lumbar vertebra (L1) trabecular attenuation values across all adult ages to measure bone mineral density (BMD) at routine CT. Materials and Methods: Reference data were constructed from 20 374 abdominal and/or thoracic CT examinations performed at 120 kV. Data were derived from adults (mean age, 60 years 6 12 [standard deviation]; 56.1% [11 428 of 20 374] women). CT examinations were performed with (n = 4263) or without (n = 16 111) intravenous contrast agent administration for a variety of unrelated clinical indications between 2000 and 2018. L1 Hounsfield unit measurement was obtained either with a customized automated tool (n = 11 270) or manually by individual readers (n = 9104). The effects of patient age, sex, contrast agent, and manual regionof-interest versus fully automated L1 Hounsfield unit measurement were assessed using multivariable logistic regression analysis. Results: Mean L1 attenuation decreased linearly with age at a rate of 2.5 HU per year, averaging 226 HU 6 44 for patients younger than 30 years and 89 HU 6 38 for patients 90 years or older. Women had a higher mean L1 attenuation compared with men (P , .008) until menopause, after which both groups had similar values. Administration of intravenous contrast agent resulted in negligible differences in mean L1 attenuation values except in patients younger than 40 years. The fully automated method resulted in measurements that were average 21 HU higher compared with manual measurement (P , .004); at intrapatient subanalysis, this difference was related to the level of transverse measurement used (midvertebra vs off-midline level). Conclusion: Normative ranges of L1 vertebra trabecular attenuation were established across all adult ages, and these can serve as a quick reference at routine CT to identify adults with low bone mineral density who are at risk for osteoporosis.

Our understanding of polyploid genome evolution is constrained because we cannot know the exact founders of a particular polyploid. To differentiate between founder effects and post polyploidization evolution, we use a pan-genomic approach to study the allotetraploid Brachypodium hybridum and its diploid progenitors. Comparative analysis suggests that most B. hybridum whole gene presence/absence variation is part of the standing variation in its diploid progenitors. Analysis of nuclear single nucleotide variants, plastomes and k-mers associated with retrotransposons reveals two independent origins for B. hybridum,~1.4 and~0.14 million years ago. Examination of gene expression in the younger B. hybridum lineage reveals no bias in overall subgenome expression. Our results are consistent with a gradual accumulation of genomic changes after polyploidization and a lack of subgenome expression dominance. Significantly, if we did not use a pan-genomic approach, we would grossly overestimate the number of genomic changes attributable to post polyploidization evolution.

Background Body CT scans are frequently done for a wide range of clinical indications, but potentially valuable biometric information typically goes unused. We aimed to compare the prognostic ability of automated CT-based body composition biomarkers derived from previously developed deep-learning and feature-based algorithms with that of clinical parameters (Framingham risk score [FRS] and body-mass index [BMI]) for predicting major cardiovascular events and overall survival in an adult screening cohort.Methods In this retrospective cohort study, mature and fully automated CT-based algorithms with predefined metrics for quantifying aortic calcification, muscle density, ratio of visceral to subcutaneous fat, liver fat, and bone mineral density were applied to a generally healthy asymptomatic outpatient cohort of adults aged 18 years or older undergoing abdominal CT for routine colorectal cancer screening. To assess the association between the predictive measures (CT-based vs FRS and BMI) and downstream adverse events (death or myocardial infarction, cerebrovascular accident, or congestive heart failure subsequent to CT scanning), we used both an event-free survival analysis and logistic regression to compute receiver operating characteristic curves (ROCs) . Findings 9223 people (mean age 57•1 years [SD 7•8]; 5152 [56%] women and 4071 [44%] men) who underwent CT scans between April, 2004, and December, 2016, were included in this analysis. In the longitudinal clinical follow-up (median 8•8 years [IQR 5•1-11•6]), subsequent major cardiovascular events or death occurred in 1831 (20%) patients. Significant differences were observed for all five automated CT-based body composition measures according to adverse events (p<0•001). Univariate 5-year area under the ROC (AUROC) values for predicting death were 0•743 (95% CI 0•705-0•780) for aortic calcification, 0•721 (0•683-0•759) for muscle density, 0•661 (0•625-0•697) for ratio of visceral to subcutaneous fat, 0•619 (0•582-0•656) for liver density, and 0•646 (0•603-0•688) for vertebral density, compared with 0•499 (0•454-0•544) for BMI and 0•688 (0•650-0•727) for FRS.Univariate hazard ratios for highestrisk quartile versus others for these same CT measures were 4•53 (95% CI 3•82-5•37) for aortic calcification, 3•58 (3•02-4•23) for muscle density, 2•28 (1•92-2•71) for the ratio of visceral to subcutaneous fat, 1•82 (1•52-2•17) for liver density, and 2•73 (2•31-3•23) for vertebral density, compared with 1•36 (1•13-1•64) for BMI and 2•82 (2•36-3•37) for FRS. Multivariate combinations of CT biomarkers further improved prediction over clinical parameters (p<0•05 for AUROCs). For example, the 2-year AUROC from combining aortic calcification, muscle density, and liver density for predicting death was 0•811 (95% CI 0•761-0•860).Interpretation Fully automated quantitative tissue biomarkers derived from CT scans can outperform established clinical parameters for presymptomatic risk stratification for future serious adverse events and add opportunistic value to CT scans performed fo...

Background and AimsSpecies and hybrids of the genus Miscanthus contain attributes that make them front-runners among current selections of dedicated bioenergy crops. A key trait for plant biomass conversion to biofuels and biomaterials is cell-wall quality; however, knowledge of cell-wall composition and biology in Miscanthus species is limited. This study presents data on cell-wall compositional changes as a function of development and tissue type across selected genotypes, and considers implications for the development of miscanthus as a sustainable and renewable bioenergy feedstock.MethodsCell-wall biomass was analysed for 25 genotypes, considering different developmental stages and stem vs. leaf compositional variability, by Fourier transform mid-infrared spectroscopy and lignin determination. In addition, a Clostridium phytofermentans bioassay was used to assess cell-wall digestibility and conversion to ethanol.Key ResultsImportant cell-wall compositional differences between miscanthus stem and leaf samples were found to be predominantly associated with structural carbohydrates. Lignin content increased as plants matured and was higher in stem tissues. Although stem lignin concentration correlated inversely with ethanol production, no such correlation was observed for leaves. Leaf tissue contributed significantly to total above-ground biomass at all stages, although the extent of this contribution was genotype-dependent.ConclusionsIt is hypothesized that divergent carbohydrate compositions and modifications in stem and leaf tissues are major determinants for observed differences in cell-wall quality. The findings indicate that improvement of lignocellulosic feedstocks should encompass tissue-dependent variation as it affects amenability to biological conversion. For gene–trait associations relating to cell-wall quality, the data support the separate examination of leaf and stem composition, as tissue-specific traits may be masked by considering only total above-ground biomass samples, and sample variability could be mostly due to varying tissue contributions to total biomass.

Summary Miscanthus spp. are promising lignocellulosic energy crops, but cell wall recalcitrance to deconstruction still hinders their widespread use as bioenergy and biomaterial feedstocks. Identification of cell wall characteristics desirable for biorefining applications is crucial for lignocellulosic biomass improvement. However, the task of scoring biomass quality is often complicated by the lack of a reference for a given feedstock.A multidimensional cell wall analysis was performed to generate a reference profile for leaf and stem biomass from several miscanthus genotypes harvested at three developmentally distinct time points. A comprehensive suite of 155 monoclonal antibodies was used to monitor changes in distribution, structure and extractability of noncellulosic cell wall matrix glycans.Glycan microarrays complemented with immunohistochemistry elucidated the nature of compositional variation, and in situ distribution of carbohydrate epitopes. Key observations demonstrated that there are crucial differences in miscanthus cell wall glycomes, which may impact biomass amenability to deconstruction.For the first time, variations in miscanthus cell wall glycan components were comprehensively characterized across different harvests, organs and genotypes, to generate a representative reference profile for miscanthus cell wall biomass. Ultimately, this portrait of the miscanthus cell wall will help to steer breeding and genetic engineering strategies for the development of superior energy crops.

We sought to determine if vertebral trabecular attenuation values measured on routine body computed tomography (CT) scans obtained for a variety of unrelated indications can predict future osteoporotic fractures at multiple skeletal sites. For this Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved retrospective cohort study, trabecular attenuation of the first lumbar vertebra was measured in 1966 consecutive older adults who underwent chest and/or abdominal CT at a single institution over the course of 1 year. New pathologic fragility fractures that occurred after a patient's CT study date were identified through an electronic health record database query using International Classification of Diseases (ICD)-9 codes for vertebral, hip, and extremity fractures. Univariate and multivariate Cox proportional hazards regression were performed to determine the effect of L trabecular attenuation on fracture-free survival. Age at CT, sex, and presence of a prior fragility fracture were included as confounders in multivariate survival analysis. Model discriminative capability was assessed through calculation of an optimism-corrected concordance index. A total of 507 patients (mean age 73.4 ± 6.3 years; 277 women, 230 men) were included in the final analysis. The median post-CT follow-up interval was 5.8 years (interquartile range 2.1-11.0 years). Univariate analysis showed that L attenuation values ≤90 Hounsfield units (HU) are significantly associated with decreased fracture-free survival (p < 0.001 by log-rank test). After adjusting for age, sex, prior fracture, glucocorticoid use, bisphosphonate use, chronic kidney disease, tobacco use, ethanol abuse, cancer history, and rheumatoid arthritis history, multivariate analysis demonstrated a persistent modest effect of L attenuation on fracture-free survival (hazard ratio [HR] = 0.63 per 10-unit increase; 95% confidence interval [CI] 0.47-0.85). The model concordance index was 0.700. Ten-year probabilities for major osteoporosis-related fractures straddled the treatment threshold for most subcohorts over the observed L HU range. In conclusion, for patients undergoing body CT scanning for any indication, L vertebral trabecular attenuation is a simple measure that, when ≤90 HU, identifies patients with a significant decrease in fracture-free survival. © 2018 American Society for Bone and Mineral Research.

BackgroundLignin is a significant barrier in the conversion of plant biomass to bioethanol. Cinnamyl alcohol dehydrogenase (CAD) and caffeic acid O-methyltransferase (COMT) catalyze key steps in the pathway of lignin monomer biosynthesis. Brown midrib mutants in Zea mays and Sorghum bicolor with impaired CAD or COMT activity have attracted considerable agronomic interest for their altered lignin composition and improved digestibility. Here, we identified and functionally characterized candidate genes encoding CAD and COMT enzymes in the grass model species Brachypodium distachyon with the aim of improving crops for efficient biofuel production.ResultsWe developed transgenic plants overexpressing artificial microRNA designed to silence BdCAD1 or BdCOMT4. Both transgenes caused altered flowering time and increased stem count and weight. Downregulation of BdCAD1 caused a leaf brown midrib phenotype, the first time this phenotype has been observed in a C3 plant. While acetyl bromide soluble lignin measurements were equivalent in BdCAD1 downregulated and control plants, histochemical staining and thioacidolysis indicated a decrease in lignin syringyl units and reduced syringyl/guaiacyl ratio in the transgenic plants. BdCOMT4 downregulated plants exhibited a reduction in total lignin content and decreased Maule staining of syringyl units in stem. Ethanol yield by microbial fermentation was enhanced in amiR-cad1-8 plants.ConclusionThese results have elucidated two key genes in the lignin biosynthetic pathway in B. distachyon that, when perturbed, may result in greater stem biomass yield and bioconversion efficiency.

The small, annual grass Brachypodium distachyon (L.) Beauv., a close relative of wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.), is a powerful model system for cereals and bioenergy grasses. Genome-wide association studies (GWAS) of natural variation can elucidate the genetic basis of complex traits but have been so far limited in B. distachyon by the lack of large numbers of well-characterized and sufficiently diverse accessions. Here, we report on genotyping-by-sequencing (GBS) of 84 B. distachyon, seven B. hybridum, and three B. stacei accessions with diverse geographic origins including Albania, Armenia, Georgia, Italy, Spain, and Turkey. Over 90,000 high-quality single-nucleotide polymorphisms (SNPs) distributed across the Bd21 reference genome were identified. Our results confirm the hybrid nature of the B. hybridum genome, which appears as a mosaic of B. distachyon-like and B. stacei-like sequences. Analysis of more than 50,000 SNPs for the B. distachyon accessions revealed three distinct, genetically defined populations. Surprisingly, these genomic profiles are associated with differences in flowering time rather than with broad geographic origin. High levels of differentiation in loci associated with floral development support the differences in flowering phenology between B. distachyon populations. Genome-wide association studies combining genotypic and phenotypic data also suggest the presence of one or more photoperiodism, circadian clock, and vernalization genes in loci associated with flowering time variation within B. distachyon populations. Our characterization elucidates genes underlying population differences, expands the germplasm resources available for Brachypodium, and illustrates the feasibility and limitations of GWAS in this model grass. Core Ideas• Genotyping diverse Brachypodium accessions expands research tools for grasses.• The B. hybridum genome is a mosaic of B. distachyonand B. stacei-like sequences.• Three distinct, genetically defined populations of B. distachyon were identified.• Flowering time, more than geography, distinguishes B. distachyon populations.• Results support the feasibility of genome-wide association studies in a model grass.