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BACKGROUND AND OBJECTIVES: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder with a well-characterized disease phenotype but considerable interindividual heterogeneity that is not well understood. The aim of this study was to evaluate the effects of dystrophin variations and genetic modifiers of DMD on rate and age of muscle replacement by fat. METHODS: One hundred seventy-five corticosteroid treated participants from the ImagingDMD natural history study underwent repeated magnetic resonance spectroscopy (MRS) of the vastus lateralis (VL) and soleus (SOL) to determine muscle fat fraction (FF). MRS was performed annually in most instances; however, some individuals had additional visits at 3 or 6 monthss intervals. FF changes over time were modeled using nonlinear mixed effects to estimate disease trajectories based on the age that the VL or SOL reached half-maximum change in FF (mu) and the time required for FF change (sigma). Computed mu and sigma values were evaluated for dystrophin variations that have demonstrated the ability to lead to a mild phenotype as well as compared between different genetic polymorphism groups. RESULTS: Participants with dystrophin gene deletions amenable to exon 8 skipping (n = 4) had minimal increases in SOL FF and had an increase in VL mu value by 4.4 years compared with a reference cohort (p = 0.039). Participants with nonsense variations within exons that may produce milder phenotypes (n = 11) also had minimal increases in SOL and VL FFs. No differences in estimated FF trajectories were seen for individuals amenable to exon 44 skipping (n = 10). Modeling of the SPP1, LTBP4, and thrombospondin-1 (THBS1) genetic modifiers did not result in significant differences in muscle FF trajectories between genotype groups (p > 0.05); however, trends were noted for the polymorphisms associated with long-range regulation of LTBP4 and THBS1 that deserve further follow-up. DISCUSSION: The results of this study link the historically mild phenotypes seen in individuals amenable to exon 8 skipping and with certain nonsense variations with alterations in trajectories of lower extremity muscle replacement by fat.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearsons correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P

Target leaf spot (TLS) of sorghum, a foliar disease caused by the necrotrophic fungus Bipolaris cookei (also known as Bipolaris sorghicola), can affect grain yield in sorghum by causing premature drying of leaves and defoliation. Two sorghum recombinant inbred line (RIL) populations, BTx623/BTx642 and BTx623/SC155-14E, were assessed for TLS resistance in replicated trials. Using least square mean trait data, four TLS resistance QTL were identified, two in each population. Of these, three were previously unidentified while a major QTL on chromosome 5 in the BTx623/BTx642 RIL population corresponded to the previously identified TLS resistance gene ds1. A set of sorghum lines were assessed for production of reactive oxygen species induced by treatment with the microbe-associated molecular pattern (MAMP) flg22 (a derivative of flagellin). Flg22-induced ROS production varied between lines in a consistent fashion. One QTL associated with variation in the flg22 response was detected in the RIL populations. No evidence was found to link variation in the MAMP response to variation in TLS resistance.

BackgroundMRI is the imaging modality of choice for diagnosis and intervention assessment in neurological disease. Its full potential has not been realized due in part to challenges in harmonizing advanced techniques across multiple sites.PurposeTo develop a method for the assessment of reliability and repeatability of advanced multisite-multisession neuroimaging studies and specifically to assess the reliability of an advanced MRI protocol, including multiband fMRI and diffusion tensor MRI, in a multisite setting.Study typeProspective.PopulationTwice repeated measurement of a single subject with stable relapsing-remitting multiple sclerosis (MS) at seven institutions.Field strength/sequenceA 3 T MRI protocol included higher spatial resolution anatomical scans, a variable flip-angle longitudinal relaxation rate constant (R1 ≡ 1/T1 ) measurement, quantitative magnetization transfer imaging, diffusion tensor imaging, and a resting-state fMRI (rsFMRI) series.AssessmentMultiple methods of assessing intrasite repeatability and intersite reliability were evaluated for imaging metrics derived from each sequence.Statistical testsStudent's t-test, Pearson's r, and intraclass correlation coefficient (ICC) (2,1) were employed to assess repeatability and reliability. Two new statistical metrics are introduced that frame reliability and repeatability in the respective units of the measurements themselves.ResultsIntrasite repeatability was excellent for quantitative R1 , magnetization transfer ratio (MTR), and diffusion-weighted imaging (DWI) based metrics (r > 0.95). rsFMRI metrics were less repeatable (r = 0.8). Intersite reliability was excellent for R1 , MTR, and DWI (ICC >0.9), and moderate for rsFMRI metrics (ICC∼0.4).Data conclusionFrom most reliable to least, using a new reliability metric introduced here, MTR > R1 > DWI > rsFMRI; for repeatability, MTR > DWI > R1 > rsFMRI. A graphical method for at-a-glance assessment of reliability and repeatability, effect sizes, and outlier identification in multisite-multisession neuroimaging studies is introduced.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:878-888.

ObjectiveTo summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.MethodsClinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.ResultsA wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.ConclusionsImaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

Black pericarp sorghum has notable value due to the biosynthesis of 3-deoxyanthocyanidins (3-DOAs), a rare class of bioactive polyphenols valued as antioxidant food additives and as bioactive compounds with cytotoxicity to human cancer cells. A metabolic and transcriptomic study was conducted to ascertain the cellular events leading to the activation of 3-DOA biosynthesis in black sorghum pericarp. Prolonged exposure of pericarp during grain maturation to high-fluence ultraviolet (UV) light resulted in elevated levels of reactive oxygen species (ROS) and the activation of 3-DOA biosynthesis in pericarp tissues. In conjunction with 3-DOA biosynthesis was the transcriptional activation of specific family members of early and late flavonoid biosynthesis pathway genes as well as the downstream activation of defense-related pathways. Promoter analysis of genes highly correlated with 3-DOA biosynthesis in black pericarp were enriched in MYB and HHO5/ARR-B motifs. Light microscopy studies of black pericarp tissues suggest that 3-DOAs are predominantly localized in the epicarp and are associated with the cell wall. A working model of UV-induced 3-DOA biosynthesis in black pericarp is proposed that shares features of plant immunity associated with pathogen attack or mechanical wounding. The present model depicts ROS accumulation, the transcriptional activation of receptor kinases and transcription factors (TFs) including NAC, WRKY, bHLH, AP2, and C2H2 Zinc finger domain. This study identified key biosynthetic and regulatory genes of 3-DOA accumulation in black pericarp and provided a deeper understanding of the gene networks and cellular events controlling this tissueand genotype-specific trait. [ABSTRACT FROM AUTHOR]

Grain sorghum [Sorghum bicolor (L.) Moench] is an important crop native to Africa and grown in many subtropical and temperate regions worldwide. The variability in production environments underscores the plasticity of sorghum genotypes and provides an opportunity to predict sorghum hybrid performance in novel environments. Reaction norms informed by envirotype data can aid in modeling the differential responses of genotypes across multi‐environment trials and ultimately increase the prediction accuracies of hybrid performance. In this study, a combination of genomic and enviromic information was applied to predict grain sorghum hybrid performance across United States sorghum production environments. Seven models based on additive, dominance, environment, and envirotype effects in two forms, and their interactions were tested under three cross‐validation schemes that simulate genomic prediction scenarios encountered by breeding programs. Relationship matrices for hybrids and environments were created from molecular and envirotypic data, respectively, to predict hybrid performance under a hierarchal Bayesian framework. When predicting unobserved environments, the envirotypic reaction norm model based on typologies produced the highest prediction accuracies for every temperate environment, but results vary in the subtropical environments, which has not been demonstrated in prior enviromic research. This study also demonstrated for the first time that envirotype data can effectively define established United States sorghum production regions and may assist breeders in resource allocation. Results support using sparse hybrid trials when breeding programs apply genomic predictions. Therefore, envirotype‐assisted genomic prediction models can expand the information available to a sorghum breeding program and aid breeders in efficiently designing hybrid trials. Core Ideas: Envirotyping can increase the information available to a plant breeding program.Enviromic‐assisted genomic prediction can increase the prediction accuracy of unobserved environments.Genomic prediction can greatly support a breeding program when combined with sparse hybrid trials. [ABSTRACT FROM AUTHOR]

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a consensus statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this consensus statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge. [ABSTRACT FROM AUTHOR]

The North American Imaging in Multiple Sclerosis (NAIMS) Cooperative represents a network of 27 academic centers focused on accelerating the pace of magnetic resonance imaging (MRI) research in multiple sclerosis (MS) through idea exchange and collaboration. Recently, NAIMS completed its first project evaluating the feasibility of implementation and reproducibility of quantitative MRI measures derived from scanning a single MS patient using a high-resolution 3T protocol at seven sites. The results showed the feasibility of utilizing advanced quantitative MRI measures in multicenter studies and demonstrated the importance of careful standardization of scanning protocols, central image processing, and strategies to account for inter-site variability.

[This corrects the article DOI: 10.1371/journal.pone.0195511.].

Sorghum (Sorghum bicolor) is an important grain and forage crop grown across the US. In some areas, sorghum can become feral along roadsides and other ruderal areas, as a result of seed spill during harvest or transport. In some of these situations, feral sorghum grows in or near established johnsongrass (S. halepense) populations. Johnsongrass, a wild relative of sorghum and an incredibly noxious weed, is capable of hybridizing with cultivated sorghum. Because commercial hybrid sorghum cultivars are produced with cytoplasmic male sterility, progeny of the hybrid crop which compose the founder feral populations also segregate for male sterility. Consequently, male sterility in feral sorghum may increase the risk of outcrossing with johnsongrass. Using field surveys and spatial modelling, the present study aimed at documenting the occurrence of feral sorghum and understanding the anthropogenic and environmental factors that influence its distribution. Further, this research documented the sympatry of feral sorghum and johnsongrass in the roadside habitat. A total of 2077 sites were visited during a systematic field survey conducted in fall 2014 in South Texas. Feral sorghum and johnsongrass were found in 360 and 939 sites, while the species co-existed at 48 sites (2.3% of all surveyed sites). The binary logistic analysis showed a significant association between the presence of feral sorghum and road type, road body-type, micro-topography of the sampling site, nearby land use, and the presence of johnsongrass, but no association with the distance to the nearest grain sorting facility. The probability of finding feral sorghum away from johnsongrass patches was generally higher than finding them co-occur in the same location. A probability map for spatial distribution of feral sorghum was developed using the nearby land use type and the regional habitat suitability for johnsongrass as two key predictors. Overall, results show that feral sorghum and johnsongrass co-occur at low frequencies in the roadside habitats of South Texas, but these low levels still present a significant opportunity for hybridization between the two species outside of cultivated fields.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.