Corrigendum: Seed coat pattern QTL and development in cowpea (Vigna unguiculata [L.] Walp.).

[This corrects the article DOI: 10.3389/fpls.2019.01346.].

Comparison of image quality of subtracted and nonsubtracted breath hold VIBE and free breathing GRASP in the evaluation of renal masses.

OBJECTIVE: To compare the image quality of subtracted and nonsubtracted images obtained using volumetric interpolated breath-hold exam (VIBE) and free breathing T1 weighted Golden-angle Radial Sparse Parallel (GRASP). METHODS: We retrospectively evaluated 27 consecutive patients who underwent MRI for the evaluation of renal masses. Contrast enhanced VIBE and free breathing GRASP imaging were performed, and subtraction images generated. Two radiologists performed quantitative and qualitative evaluations of image quality of nonsubtracted and subtracted data sets. Statistical analysis was performed using the Wilcoxon signed-rank test, paired t-test and kappa statistics. RESULTS: VIBE images scored statistically higher for the following parameters in the coronal and axial plane: sharpness, streak artifact, image noise, and overall image quality for standard and subtracted images (all P values P < 0.001). GRASP images had significantly less subtraction artifact in the coronal (P = 0.042) plane with a similar trend in the axial plane (P = 0.079). Interreader Kappa values for qualitative images scores were fair to good (0.23-0.71). Quantitative subtracted GRASP images had significant less subtraction artifact compared to VIBE in the anterior-posterior (3.9 mm SD 2.6 mm versus 5.8 mm SD 3.6 mm, P = 0.010), and craniocaudal direction (4.4 mm SD 2.9 mm versus 7.0 mm SD 5.3 mm, P = 0.010); a trend was seen in the left-right direction (2.6 mm SD 1.4 mm versus 4.0 mm SD 3.9 mm, P = 0.084). CONCLUSION: VIBE images have significantly better image quality than free breathing GRASP images, however free breathing GRASP images have significantly less subtraction artifact.

Seed Coat Pattern QTL and Development in Cowpea (Vigna unguiculata [L.] Walp.).

The appearance of the seed is an important aspect of consumer preference for cowpea (Vigna unguiculata [L.] Walp.). Seed coat pattern in cowpea has been a subject of study for over a century. This study makes use of newly available resources, including mapping populations, a reference genome and additional genome assemblies, and a high-density single nucleotide polymorphism genotyping platform, to map various seed coat pattern traits to three loci, concurrent with the Color Factor (C), Watson (W), and Holstein (H) factors identified previously. Several gene models encoding proteins involved in regulating the later stages of the flavonoid biosynthesis pathway have been identified as candidate genes, including a basic helix-loop-helix gene (Vigun07g110700) for the C locus, a WD-repeat gene (Vigun09g139900) for the W locus and an E3 ubiquitin ligase gene (Vigun10g163900) for the H locus. A model of seed coat development, consisting of six distinct stages, is described to explain some of the observed pattern phenotypes.

Can MR enterography screen for perianal disease in pediatric inflammatory bowel disease?

BACKGROUND: Pediatric Crohn's disease is associated with perianal disease (PAD). Magnetic resonance enterography (MRE) assesses small bowel involvement in pediatric inflammatory bowel disease (PIBD). Pelvic MRI (P-MRI) is the gold standard for assessing PAD. PURPOSE: To determine if MRE can accurately detect PAD in PIBD, distinguishing perianal fistulae (PAF) from perianal abscesses (PAA), referenced against P-MRI. STUDY TYPE: Retrospective. POPULATION: Seventy-seven PIBD patients, 27 females (mean age 14.1 years), with P-MRI and MRE within 6 months. FIELD STRENGTH/SEQUENCE: 1.5T and 3T; P-MRI: sagittal fat suppressed (FS) T2 fast spin-echo (FSE), coronal short tau inversion recovery, axial T1 FSE, coronal and axial postcontrast FS T1 FSE; MRE: coronal balanced steady-state free-precession (SSFP), coronal cine SSFP, coronal and axial single-shot T2 FS, axial SSFP, coronal ultrafast 3D T1 -weighted gradient echo FS (3D T1 GE), axial diffusion-weighted imaging, coronal and axial postcontrast 3D T1 GE FS. ASSESSMENT: Two radiologists independently, then by consensus, assessed randomized MRI exams, recording PAF number, location, and length; and PAA number, location, length, and volume. Sensitivity analysis used clinical disease as the gold standard, calculated separately for P-MRI and MRE. STATISTICAL TESTS: Comparing MRE and P-MRI consensus data, sensitivity, specificity, positive, and negative predictive values (P/NPV) were calculated. Inter- and intrareader reliability were assessed using kappa statistics. RESULTS: P-MRI and MRE were paired, detecting PAD in 73 patients, PAF in 63, and PAA in 31 P-MRI. MRE sensitivities, specificities, PPV, and NPV were: PAD 82%, 100%, 100%, 23%; PAF 74%, 71%, 92%, 38%; PAA 51%, 85%, 69%, 72%; clinical 82%, 22%, 37%, 69%; clinical P-MRI 96%, 8%, 37%, 80%. MRE interreader agreement for PAD was moderate (kappa = 0.51 [0.29-0.73]), fair for PAF and PAA. DATA CONCLUSION: Using a standard technique, MRE can detect PAD with high specificity and moderate sensitivity in PIBD, missing some PAF and small PAA. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1638-1645.

Unmet eye care needs among a homeless youth population.

OBJECTIVE: To assess the rate of visual impairment and quantify the unmet eye care needs within Toronto's homeless youth community. DESIGN: Prospective and cross sectional. PARTICIPANTS: Ninety randomly selected homeless youth aged 16-24 years. METHODS: From each of 9 participating homeless youth shelters and drop-in centres in Toronto, 10 English-speaking youths between ages 16 and 24 were randomly recruited. Information regarding sociodemographics, medical history, subjective visual acuity, and access to eye care was collected. Comprehensive visual screening and undilated direct fundoscopy were also performed. RESULTS: The median age of participants was 21 years (interquartile range = 19-23 years), and 62.2% were male. Most participants were homeless for less than 5 years (90%) and earning less than $500 monthly (57.8%). Despite 51.1% of participants having previously owned corrective lenses, only 20% of participants currently owned them when assessed/at study time. When analyzing the better-seeing eye, presenting visual acuity was 20/50 or worse in 18.9% (95% CI 10.8%-27.0%) of participants. Pinhole occlusion decreased the number to 2.2% (95% CI 0%-5.3%). The most common cause of visual impairment was uncorrected refractive error. Ocular pathology was observed in 8 participants. Compared to adults, youth have similar functional visual impairment (adults 24.0%, youth 18.9%) but less impairment uncorrectable by pinhole occlusion (adults 11.0%, youth 2.2%) and are less dissatisfied with their vision (adults 70.0%, youths 36.7%). Although a higher proportion of homeless youths have visited an eye specialist in the past year (adults 14.0%; youths 17.8%), neither group is visiting as frequently as the Canadian average (41%) (p < 0.01). CONCLUSIONS: Homeless youth have a high prevalence of visual impairment, even when living within a system of universal health insurance. Ongoing vision-screening programs, readily accessible free eye clinics, and particularly low-cost glasses may help address this need.

Infarct-Associated Bone Sarcomas: Multimodality Imaging Findings.

OBJECTIVE: The objective of our study was to characterize infarct-associated bone sarcoma and its imaging features. MATERIALS AND METHODS: Our databases were searched for instances of sarcoma arising in association with osteonecrosis. Demographic and imaging data were recorded. The imaging studies of 258 patients with sarcomas were reviewed to determine whether underlying osteonecrosis was present. Radiographic and MRI studies of patients with bone infarction were reviewed to categorize the various appearances of infarction and to determine if sarcomas tended to arise in a particular pattern. A literature review was performed. RESULTS: Nine infarct-associated bone sarcomas were found in eight patients: seven malignant fibrous histiocytomas (MFHs) and two osteosarcomas. All occurred in the femur or tibia; multifocal infarction was documented in all patients except one. Sarcomas were commonly associated with a so-called "mature"-type pattern of osteonecrosis-that is, with well-defined calcified margins. Osteolysis of infarct-associated MFHs was often overlooked at initial presentation and was often detected only after pathologic fracture. CT and MRI revealed cortical penetration in all cases; infarct margin disruption was evident, but preservation of fat within the infarct was typical. Increased radiotracer activity with relative central photopenia was characteristic of large infarct-associated bone sarcomas on scintigraphy. All lesions, including those treated at our institution and those found in the literature, were metaphyseal or diaphyseal, and although epiphyseal extension of sarcoma from a metadiaphyseal infarct was common, no purely epiphyseal lesions were encountered. CONCLUSION: Radiologists must remain vigilant for this rare occurrence, especially in patients with new pain in an area of known bone infarction.

Development of a cost-efficient novel method for rapid, concurrent genotyping of five common single nucleotide polymorphisms of the brain derived neurotrophic factor (BDNF) gene by tetra-primer amplification refractory mutation system.

Brain derived neurotrophic factor (BDNF) is a molecular trophic factor that plays a key role in neuronal survival and plasticity. Single nucleotide polymorphisms (SNPs) of the BDNF gene have been associated with specific phenotypic traits in a large number of neuropsychiatric disorders and the response to psychotherapeutic medications in patient populations. Nevertheless, due to study differences and occasionally contrasting findings, substantial further research is required to understand in better detail the association between specific BDNF SNPs and these psychiatric disorders. While considerable progress has been made recently in developing advanced genotyping platforms of SNPs, many high-throughput probe- or array-based detection methods currently available are limited by high costs, slow processing times or access to advanced instrumentation. The polymerase chain reaction (PCR)-based, tetra-primer amplification refractory mutation system (T-ARMS) method is a potential alternative technique for detecting SNP genotypes efficiently, quickly, easily, and cheaply. As a tool in psychopathology research, T-ARMS was shown to be capable of detecting five common SNPs in the BDNF gene (rs6265, rs988748, rs11030104, 11757G/C and rs7103411), which are all SNPs with previously demonstrated clinical relevance to schizophrenia and depression. The present technique therefore represents a suitable protocol for many research laboratories to study the genetic correlates of BDNF in psychiatric disorders. Copyright Copyright © 2015 John Wiley & Sons, Ltd.

Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report.

Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities.

Incidence, prevalence, and temporal trends of microscopic colitis: a systematic review and meta-analysis.

OBJECTIVES: A systematic review and meta-analysis was conducted to provide an accurate estimate of the incidence rate of microscopic colitis (MC) and to assess the association between medication use and the risk of MC. METHODS: We searched Medline, Embase, and Institute for Scientific Information (ISI) Web of Science up to 26 September 2014 to identify published epidemiological studies of MC. The pooled incidence rate, female-to-male incidence rate ratio, age at diagnosis, prevalence, as well as odds ratios (ORs) of MC in association with medication use were calculated using a fixed-effects model or a random-effects model. RESULTS: Of the 1,972 citations retrieved, 25 studies were included. Pooled incidence rate of collagenous colitis (CC) was 4.14 (95% confidence interval (CI) 2.89-5.40) per 100,000 person-years and 4.85 (95% CI, 3.45-6.25) for lymphocytic colitis (LC). The female-to-male incidence rate ratios were 3.05 (95% CI 2.92-3.19) for CC and 1.92 (95% CI 1.53-2.31) for LC. The median age at diagnosis for CC was 64.9 (range, 57.03-72.78) years, similar to LC (median 62.18, range 53.99-70.38). Furthermore, the incidence rate of MC increased with rising age. A steadily increasing trend of incidence rate for both CC and LC was observed before 2000; however, the incidence rate since then has become stable in the United States, Sweden, and Spain. An increased risk of MC was associated with the use of proton pump inhibitors (PPIs) and selective serotonin reuptake inhibitors (SSRIs) (OR 2.68, 95% CI 1.73-4.17 and OR 2.41, 95% CI 1.64-3.53, respectively). CONCLUSIONS: MC is a common disease process. Female gender, increased age, and the use of PPIs and SSRIs are associated with a significantly increased risk of developing MC. Further work is needed to evaluate reported data from developing countries and to elucidate the biologic mechanisms behind the risk factors for MC.

Mapping membrane protein backbone dynamics: a comparison of site-directed spin labeling with NMR 15N-relaxation measurements.

The ability to detect nanosecond backbone dynamics with site-directed spin labeling (SDSL) in soluble proteins has been well established. However, for membrane proteins, the nitroxide appears to have more interactions with the protein surface, potentially hindering the sensitivity to backbone motions. To determine whether membrane protein backbone dynamics could be mapped with SDSL, a nitroxide was introduced at 55 independent sites in a model polytopic membrane protein, TM0026. Electron paramagnetic resonance spectral parameters were compared with NMR (15)N-relaxation data. Sequential scans revealed backbone dynamics with the same trends observed for the R1 relaxation rate, suggesting that nitroxide dynamics remain coupled to the backbone on membrane proteins.

Tuning micelle dimensions and properties with binary surfactant mixtures.

Detergent micelles are used in many areas of research and technology, in particular, as mimics of the cellular membranes in the purification and biochemical and structural characterization of membrane proteins. Applications of detergent micelles are often hindered by the limited set of properties of commercially available detergents. Mixtures of micelle-forming detergents provide a means to systematically obtain additional micellar properties and expand the repertoire of micelle features available; however, our understanding of the properties of detergent mixtures is still limited. In this study, the shape and size of binary mixtures of seven different detergents commonly used in molecular host-guest systems and membrane protein research were investigated. The data suggests that the detergents form ideally mixed micelles with sizes and shapes different from those of pure individual micelles. For most measurements of size, the mixtures varied linearly with detergent mole fraction and therefore can be calculated from the values of the pure detergents. We propose that properties such as the geometry, size, and surface charge can be systematically and predictably tuned for specific applications.

Structure of the Neisserial outer membrane protein Opa60: loop flexibility essential to receptor recognition and bacterial engulfment.

The structure and dynamics of Opa proteins, which we report herein, are responsible for the receptor-mediated engulfment of Neisseria gonorrheae or Neisseria meningitidis by human cells and can offer deep understanding into the molecular recognition of pathogen-host receptor interactions. Such interactions are vital to understanding bacterial pathogenesis as well as the mechanism of foreign body entry to a human cell, which may provide insights for the development of targeted pharmaceutical delivery systems. The size and dynamics of the extracellular loops of Opa60 required a hybrid refinement approach wherein membrane and distance restraints were used to generate an initial NMR structural ensemble, which was then further refined using molecular dynamics in a DMPC bilayer. The resulting ensemble revealed that the extracellular loops, which bind host receptors, occupy compact conformations, interact with each other weakly, and are dynamic on the nanosecond time scale. We predict that this conformational sampling is critical for enabling diverse Opa loop sequences to engage a common set of receptors.

Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane.

Dysregulation of oxidative phosphorylation is associated with increased mitochondrial reactive oxygen species production and some of the most prevalent human diseases including obesity, cancer, diabetes, neurodegeneration, and heart disease. Chemical 'mitochondrial uncouplers' are lipophilic weak acids that transport protons into the mitochondrial matrix via a pathway that is independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. Mitochondrial uncouplers also lessen the proton motive force across the mitochondrial inner membrane and thereby increase the rate of mitochondrial respiration while decreasing production of reactive oxygen species. Thus, mitochondrial uncouplers are valuable chemical tools that enable the measurement of maximal mitochondrial respiration and they have been used therapeutically to decrease mitochondrial reactive oxygen species production. However, the most widely used protonophore uncouplers such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and 2,4-dinitrophenol have off-target activity at other membranes that lead to a range of undesired effects including plasma membrane depolarization, mitochondrial inhibition, and cytotoxicity. These unwanted properties interfere with the measurement of mitochondrial function and result in a narrow therapeutic index that limits their usefulness in the clinic. To identify new mitochondrial uncouplers that lack off-target activity at the plasma membrane we screened a small molecule chemical library. Herein we report the identification and validation of a novel mitochondrial protonophore uncoupler (2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine, named BAM15, that does not depolarize the plasma membrane. Compared to FCCP, an uncoupler of equal potency, BAM15 treatment of cultured cells stimulates a higher maximum rate of mitochondrial respiration and is less cytotoxic. Furthermore, BAM15 is bioactive in vivo and dose-dependently protects mice from acute renal ischemic-reperfusion injury. From a technical standpoint, BAM15 represents an effective new tool that allows the study of mitochondrial function in the absence of off-target effects that can confound data interpretation. From a therapeutic perspective, BAM15-mediated protection from ischemia-reperfusion injury and its reduced toxicity will hopefully reignite interest in pharmacological uncoupling for the treatment of the myriad of diseases that are associated with altered mitochondrial function.

Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.

Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted.

Sparing of coarse stereopsis in stereodeficient children with a history of amblyopia.

Stereoscopic depth perception may be obtained from small retinal disparities that can be fused for single vision (fine stereopsis), but reliable depth information is also obtained from larger disparities that produce double vision (coarse stereopsis). Here we assess the possibility that the early development of coarse stereopsis makes it resilient to the factors that cause amblyopia by comparing performance in children with a history of strabismic, anisometropic, or aniso-strabismic amblyopia and age-matched controls (5-12 years). The task was to indicate whether a cartoon character was nearer or farther away than a zero-disparity reference frame. Test disparities were grouped into fine and coarse ranges based on preliminary assessment of diplopia thresholds. In the fine range, accuracy increased with disparity for both groups, but children in the amblyopia group performed significantly worse than children in the control group, particularly when their amblyopia was associated with strabismus. In the coarse range, accuracy was constant across all disparities for both groups although performance appeared to be poorer in the aniso-strabismic group. These results suggest that, under some conditions, stereopsis for large disparities may be spared when stereopsis for small disparities is disrupted by early visual deprivation. This undetected residual binocular function has important clinical implications given recent efforts to improve amblyopia treatment outcomes by employing binocular treatment protocols.

Dependence of micelle size and shape on detergent alkyl chain length and head group.

Micelle-forming detergents provide an amphipathic environment that can mimic lipid bilayers and are important tools for solubilizing membrane proteins for functional and structural investigations in vitro. However, the formation of a soluble protein-detergent complex (PDC) currently relies on empirical screening of detergents, and a stable and functional PDC is often not obtained. To provide a foundation for systematic comparisons between the properties of the detergent micelle and the resulting PDC, a comprehensive set of detergents commonly used for membrane protein studies are systematically investigated. Using small-angle X-ray scattering (SAXS), micelle shapes and sizes are determined for phosphocholines with 10, 12, and 14 alkyl carbons, glucosides with 8, 9, and 10 alkyl carbons, maltosides with 8, 10, and 12 alkyl carbons, and lysophosphatidyl glycerols with 14 and 16 alkyl carbons. The SAXS profiles are well described by two-component ellipsoid models, with an electron rich outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core composed of the alkyl chains. The minor axis of the elliptical micelle core from these models is constrained by the length of the alkyl chain, and increases by 1.2-1.5 Šper carbon addition to the alkyl chain. The major elliptical axis also increases with chain length; however, the ellipticity remains approximately constant for each detergent series. In addition, the aggregation number of these detergents increases by ∼16 monomers per micelle for each alkyl carbon added. The data provide a comprehensive view of the determinants of micelle shape and size and provide a baseline for correlating micelle properties with protein-detergent interactions.

Vessel tortuosity causing false positives in detecting renal artery stenosis on Doppler ultrasound.

INTRODUCTION: Color Doppler ultrasound (CDUS) is currently preferred to screen for renal artery stenosis (RAS); however, a wide range of sensitivities and specificities have been reported. We wanted to identify potential factors contributing to this wide range and to improve CDUS screening for RAS. We noted RAS was overcalled when the peak systolic velocity (PSV) was found in the mid-main renal artery, and we sought to determine whether this was a consistent source of error. METHODS: We reviewed the medical records of patients at Northshore University Healthsystems with a positive RAS examination by CDUS from 2009 to 2012, defined as a PSV greater than 200 cm/s and/or a renal artery-to-aorta ratio greater than 3.5. Patients were included who had an elevated PSV in the mid-main renal artery and had a confirmatory imaging study (angiography, magnetic resonance angiography, or computed tomography angiography). RESULTS: Of the 16 arteries demonstrating a PSV in the mid-renal artery, 15 did not have significant stenosis on the subsequent study. The 1 true positive was a patient with fibromuscular dysplasia. DISCUSSION: This study demonstrates a high false-positive rate (94%) when the PSV is in the mid-main renal artery. We suspect this pattern is due to the tortuous mid-main renal artery causing falsely elevated velocities that meet criteria for RAS. Fibromuscular dysplasia may also produce the same pattern and should be distinguished from vessel tortuosity. If the false-positive rate of Doppler ultrasound can be decreased, fewer patients will be subjected to an unnecessary follow-up study and possibly invasive procedures.