CT image-based biomarkers for opportunistic screening of osteoporotic fractures: a systematic review and meta-analysis.

The use of opportunistic computed tomography (CT) image-based biomarkers may be a low-cost strategy for screening older individuals at high risk for osteoporotic fractures and populations that are not sufficiently targeted. This review aimed to assess the discriminative ability of image-based biomarkers derived from existing clinical routine CT scans for hip, vertebral, and major osteoporotic fracture prediction. A systematic search in PubMed MEDLINE, Embase, Cochrane, and Web of Science was conducted from the earliest indexing date until July 2023. The evaluation of study quality was carried out using a modified Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. The primary outcome of interest was the area under the curve (AUC) and its corresponding 95% confidence intervals (CIs) obtained for four main categories of biomarkers: areal bone mineral density (BMD), image attenuation, volumetric BMD, and finite element (FE)-derived biomarkers. The meta-analyses were performed using random effects models. Sixty-one studies were included in this review, among which 35 were synthesized in a meta-analysis and the remaining articles were qualitatively synthesized. In comparison to the pooled AUC of areal BMD (0.73 [95% CI 0.71-0.75]), the pooled AUC values for predicting osteoporotic fractures for FE-derived parameters (0.77 [95% CI 0.72-0.81]; p < 0.01) and volumetric BMD (0.76 [95% CI 0.71-0.81]; p < 0.01) were significantly higher, but there was no significant difference with the pooled AUC for image attenuation (0.73 [95% CI 0.66-0.79]; p = 0.93). Compared to areal BMD, volumetric BMD and FE-derived parameters may provide a significant improvement in the discrimination of osteoporotic fractures using opportunistic CT assessments.

Longitudinal MR-based proton-density fat fraction (PDFF) and T2* for the assessment of associations between bone marrow changes and myelotoxic chemotherapy.

OBJECTIVES: MR imaging-based proton density fat fraction (PDFF) and T2* imaging has shown to be useful for the evaluation of degenerative changes in the spine. Therefore, the aim of this study was to investigate the influence of myelotoxic chemotherapy on the PDFF and T2* of the thoracolumbar spine in comparison to changes in bone mineral density (BMD). METHODS: In this study, 19 patients were included who had received myelotoxic chemotherapy (MC) and had received a MR imaging scan of the thoracolumbar vertebrates before and after the MC. Every patient was matched for age, sex, and time between the MRI scans to two controls without MC. All patients underwent 3-T MR imaging including the thoracolumbar spine comprising chemical shift encoding-based water-fat imaging to extract PDFF and T2* maps. Moreover, trabecular BMD values were determined before and after chemotherapy. Longitudinal changes in PDFF and T2* were evaluated and compared to changes in BMD. RESULTS: Absolute mean differences of PDFF values between scans before and after MC were at 8.7% (p = 0.01) and at -0.5% (p = 0.57) in the control group, resulting in significantly higher changes in PDFF in patients with MC (p = 0.008). BMD and T2* values neither showed significant changes in patients with nor in those without myelotoxic chemotherapy (p = 0.15 and p = 0.47). There was an inverse, yet non-significant correlation between changes in PDFF and BMD found in patients with myelotoxic chemotherapy (r = -0.41, p = 0.12). CONCLUSION: Therefore, PDFF could be a useful non-invasive biomarker in order to detect changes in the bone marrow in patients receiving myelotoxic therapy. CLINICAL RELEVANCE STATEMENT: Using PDFF as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment may help enable more targeted countermeasures at commencing states of bone marrow degradation and reduce risks of possible fragility fractures. KEY POINTS: Quantifying changes in bone marrow fat fraction, as well as T2* caused by myelotoxic pharmaceuticals using proton density fat fraction, is feasible. Proton density fat fraction could potentially be established as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

Large tandem duplications affect gene expression, 3D organization, and plant-pathogen response.

Rapid plant genome evolution is crucial to adapt to environmental changes. Chromosomal rearrangements and gene copy number variation (CNV) are two important tools for genome evolution and sources for the creation of new genes. However, their emergence takes many generations. In this study, we show that in Arabidopsis thaliana, a significant loss of ribosomal RNA (rRNA) genes with a past history of a mutation for the chromatin assembly factor 1 (CAF1) complex causes rapid changes in the genome structure. Using long-read sequencing and microscopic approaches, we have identified up to 15 independent large tandem duplications in direct orientation (TDDOs) ranging from 60 kb to 1.44 Mb. Our data suggest that these TDDOs appeared within a few generations, leading to the duplication of hundreds of genes. By subsequently focusing on a line only containing 20% of rRNA gene copies (20rDNA line), we investigated the impact of TDDOs on 3D genome organization, gene expression, and cytosine methylation. We found that duplicated genes often accumulate more transcripts. Among them, several are involved in plant-pathogen response, which could explain why the 20rDNA line is hyper-resistant to both bacterial and nematode infections. Finally, we show that the TDDOs create gene fusions and/or truncations and discuss their potential implications for the evolution of plant genomes.

Targeted transcriptomics reveals signatures of large-scale independent origins and concerted regulation of effector genes in Radopholus similis.

The burrowing nematode, Radopholus similis, is an economically important plant-parasitic nematode that inflicts damage and yield loss to a wide range of crops. This migratory endoparasite is widely distributed in warmer regions and causes extensive destruction to the root systems of important food crops (e.g., citrus, banana). Despite the economic importance of this nematode, little is known about the repertoire of effectors owned by this species. Here we combined spatially and temporally resolved next-generation sequencing datasets of R. similis to select a list of candidates for the identification of effector genes for this species. We confirmed spatial expression of transcripts of 30 new candidate effectors within the esophageal glands of R. similis by in situ hybridization, revealing a large number of pioneer genes specific to this nematode. We identify a gland promoter motif specifically associated with the subventral glands (named Rs-SUG box), a putative hallmark of spatial and concerted regulation of these effectors. Nematode transcriptome analyses confirmed the expression of these effectors during the interaction with the host, with a large number of pioneer genes being especially abundant. Our data revealed that R. similis holds a diverse and emergent repertoire of effectors, which has been shaped by various evolutionary events, including neofunctionalization, horizontal gene transfer, and possibly by de novo gene birth. In addition, we also report the first GH62 gene so far discovered for any metazoan and putatively acquired by lateral gene transfer from a bacterial donor. Considering the economic damage caused by R. similis, this information provides valuable data to elucidate the mode of parasitism of this nematode.

miR778 mediates gene expression, histone modification, and DNA methylation during cyst nematode parasitism.

Despite the known critical regulatory functions of microRNAs, histone modifications, and DNA methylation in reprograming plant epigenomes in response to pathogen infection, the molecular mechanisms underlying the tight coordination of these components remain poorly understood. Here, we show how Arabidopsis (Arabidopsis thaliana) miR778 coordinately modulates the root transcriptome, histone methylation, and DNA methylation via post-transcriptional regulation of the H3K9 methyltransferases SU(var)3-9 homolog 5 (SUVH5) and SUVH6 upon infection by the beet cyst nematode Heterodera schachtii. miR778 post-transcriptionally silences SUVH5 and SUVH6 upon nematode infection. Manipulation of the expression of miR778 and its two target genes significantly altered plant susceptibility to H. schachtii. RNA-seq analysis revealed a key role of SUVH5 and SUVH6 in reprograming the transcriptome of Arabidopsis roots upon H. schachtii infection. In addition, chromatin immunoprecipitation (ChIP)-seq analysis established SUVH5 and SUVH6 as the main enzymes mediating H3K9me2 deposition in Arabidopsis roots in response to nematode infection. ChIP-seq analysis also showed that these methyltransferases possess distinct DNA binding preferences in that they are targeting transposable elements under noninfected conditions and protein-coding genes in infected plants. Further analyses indicated that H3K9me2 deposition directed by SUVH5 and SUVH6 contributes to gene expression changes both in roots and in nematode feeding sites and preferentially associates with CG DNA methylation. Together, our results uncovered multi-layered epigenetic regulatory mechanisms coordinated by miR778 during Arabidopsis-H. schachtii interactions.

Functional magnetic resonance imaging in migraine: A systematic review.

BACKGROUND: Migraine is a highly prevalent primary headache disorder. Despite a high burden of disease, key disease mechanisms are not entirely understood. Functional magnetic resonance imaging is an imaging method using the blood-oxygen-level-dependent signal, which has been increasingly used in migraine research over recent years. This systematic review summarizes recent findings employing functional magnetic resonance imaging for the investigation of migraine. METHODS: We conducted a systematic search and selection of functional magnetic resonance imaging applications in migraine from April 2014 to December 2021 (PubMed and references of identified articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). Methodological details and main findings were extracted and synthesized. RESULTS: Out of 224 articles identified, 114 were included after selection. Repeatedly emerging structures of interest included the insula, brainstem, limbic system, hypothalamus, thalamus, and functional networks. Assessment of functional brain changes in response to treatment is emerging, and machine learning has been used to investigate potential functional magnetic resonance imaging-based markers of migraine. CONCLUSIONS: A wide variety of functional magnetic resonance imaging-based metrics were found altered across the brain for heterogeneous migraine cohorts, partially correlating with clinical parameters and supporting the concept to conceive migraine as a brain state. However, a majority of findings from previous studies have not been replicated, and studies varied considerably regarding image acquisition and analyses techniques. Thus, while functional magnetic resonance imaging appears to have the potential to advance our understanding of migraine pathophysiology, replication of findings in large representative datasets and precise, standardized reporting of clinical data would likely benefit the field and further increase the value of observations.

Magnetic Fingerprints in an All-Organic Radical Molecular Break Junction.

Polycyclic aromatic hydrocarbons radicals are organic molecules with a nonzero total magnetic moment. Here, we report on charge-transport experiments with bianthracene-based radicals using a mechanically controlled break junction technique at low temperatures (6 K). The conductance spectra demonstrate that the magnetism of the diradical is preserved in solid-state devices and that it manifests itself either in the form of a Kondo resonance or inelastic electron tunneling spectroscopy signature caused by spin-flip processes. The magnetic fingerprints depend on the exact configuration of the molecule in the junction; this picture is supported by reference measurements on a radical molecule with the same backbone but with one free spin, in which only Kondo anomalies are observed. The results show that the open-shell structures based on the bianthracene core are interesting systems to study spin-spin interactions in solid-state devices, and this may open the way to control them either electrically or by mechanical strain.

Headache frequency and neck pain are associated with trapezius muscle T2 in tension-type headache among young adults.

BACKGROUND: Tension-type headache (TTH) is the most prevalent primary headache disorder. Neck pain is commonly associated with primary headaches and the trigemino-cervical complex (TCC) refers to the convergence of trigeminal and cervical afferents onto neurons of the brainstem, thus conceptualizes the emergence of headache in relation to neck pain. However, no objective biomarkers exist for the myofascial involvement in primary headaches. This study aimed to investigate the involvement of the trapezius muscles in primary headache disorders by quantitative magnetic resonance imaging (MRI), and to explore associations between muscle T2 values and headache frequency and neck pain. METHODS: This cohort study prospectively enrolled fifty participants (41 females, age range 20-31 years): 16 subjects with TTH only (TTH-), 12 with mixed-type TTH plus migraine (TTH+), and 22 healthy controls (HC). The participants completed fat-suppressed T2-prepared three-dimensional turbo spin-echo MRI, a headache diary (over 30 days prior to MRI), manual palpation (two weeks before MRI), and evaluation of neck pain (on the day of MRI). The bilateral trapezius muscles were manually segmented, followed by muscle T2 extraction. Associations between muscle T2 and the presence of neck pain as well as the number of days with headache (considering the 30 days prior to imaging using the headache calendar) were analyzed using regression models (adjusting for age, sex, and body mass index). RESULTS: The TTH+ group demonstrated the highest muscle T2 values (right side: 31.4 ± 1.2 ms, left side: 31.4 ± 0.8 ms) as compared to the TTH- group or HC group (p < 0.001). Muscle T2 was significantly associated with the number of headache days (ß-coefficient: 2.04, p = 0.04) and the presence of neck pain (odds ratio: 2.26, p = 0.04). With muscle T2 as the predictor, the area under the curve for differentiating between HC and the TTH+ group was 0.82. CONCLUSIONS: Increased T2 of trapezius muscles may represent an objective imaging biomarker for myofascial involvement in primary headache disorders, which could help to improve patient phenotyping and therapy evaluation. Pathophysiologically, the increased muscle T2 values could be interpreted as a surrogate of neurogenic inflammation and peripheral sensitization within myofascial tissues.

On quantification errors of R2*$$ {R}_2

PURPOSE: To study the effect of field inhomogeneity distributions in trabecularized bone regions on the gradient echo (GRE) signal with short TEs and to characterize quantification errors on R2*$$ {R}_2^{\ast } $$ and proton density fat fraction (PDFF) maps when using a water-fat model with an exponential R2*$$ {R}_2^{\ast } $$ decay model at short TEs. METHODS: Field distortions were simulated based on a trabecular bone micro CT dataset. Simulations were performed for different bone volume fractions (BV/TV) and for different bone-fat composition values. A multi-TE UTE acquisition was developed to acquire multiple UTEs with random order to minimize eddy currents. The acquisition was validated in phantoms and applied in vivo in a volunteer's ankle and knee. Chemical shift encoded MRI (CSE-MRI) based on a Cartesian multi-TE GRE scan was acquired in the spine of patients with metastatic bone disease. RESULTS: Simulations showed that signal deviations from the exponential signal decay at short TEs were more prominent for a higher BV/TV. UTE multi-TE measurements reproduced in vivo the simulation-based predicted behavior. In regions with high BV/TV, the presence of field inhomogeneities induced an R2*$$ {R}_2^{\ast } $$ underestimation in trabecularized bone marrow when using CSE-MRI at 3T with a short TE. CONCLUSION: R2*$$ {R}_2^{\ast } $$ can be underestimated when using short TEs (<2 ms at 3 T) and a water-fat model with an exponential R2*$$ {R}_2^{\ast } $$ decay model in multi-echo GRE acquisitions of trabecularized bone marrow.

Preconditioned water-fat total field inversion: Application to spine quantitative susceptibility mapping.

PURPOSE: To (a) develop a preconditioned water-fat total field inversion (wfTFI) algorithm that directly estimates the susceptibility map from complex multi-echo gradient echo data for water-fat regions and to (b) evaluate the performance of the proposed wfTFI quantitative susceptibility mapping (QSM) method in comparison with a local field inversion (LFI) method and a linear total field inversion (TFI) method in the spine. METHODS: Numerical simulations and in vivo spine multi-echo gradient echo measurements were performed to compare wfTFI to an algorithm based on disjoint background field removal (BFR) and LFI and to a formerly proposed TFI algorithm. The data from 1 healthy volunteer and 10 patients with metastatic bone disease were included in the analysis. Clinical routine computed tomography (CT) images were used as a reference standard to distinguish osteoblastic from osteolytic changes. The ability of the QSM methods to distinguish osteoblastic from osteolytic changes was evaluated. RESULTS: The proposed wfTFI method was able to decrease the normalized root mean square error compared to the LFI and TFI methods in the simulation. The in vivo wfTFI susceptibility maps showed reduced BFR artifacts, noise amplification, and streaking artifacts compared to the LFI and TFI maps. wfTFI provided a significantly higher diagnostic confidence in differentiating osteolytic and osteoblastic lesions in the spine compared to the LFI method (p = .012). CONCLUSION: The proposed wfTFI method can minimize BFR artifacts, noise amplification, and streaking artifacts in water-fat regions and can thus better differentiate between osteoblastic and osteolytic changes in patients with metastatic disease compared to LFI and the original TFI method.

Beyond mean value analysis - a voxel-based analysis of the quantitative MR biomarker water T2 in the presence of fatty infiltration in skeletal muscle tissue of patients with neuromuscular diseases.

The main pathologies in the muscles of patients with neuromuscular diseases (NMD) are fatty infiltration and edema. Recently, quantitative magnetic resonance (MR) imaging for determination of the MR biomarkers proton density fat fraction (PDFF) and water T2 (T2w ) has been advanced. Biophysical effects or pathology can have different effects on MR biomarkers. Thus, for heterogeneously affected muscles, the routinely performed mean or median value analyses of MR biomarkers are questionable. Our work presents a voxel-based histogram analysis of PDFF and T2w images to point out potential quantification errors. In 12 patients with NMD, chemical-shift encoding-based water-fat imaging for PDFF and T2 mapping with spectral adiabatic inversion recovery (SPAIR) for T2w determination was performed. Segmentation of nine thigh muscles was performed bilaterally (n = 216). PDFF and T2 maps were coregistered. A voxel-based comparison of PDFF and T2w showed a decreased T2w with increasing PDFF. Mean T2w and mean T2w without fatty voxels (PDFF < 10%) show good agreement, whereas standard deviation (σ) T2w and σ T2w without fatty voxels show increasing difference with increasing values of σ. Thereby two subgroups can be observed, referring to muscles in which the exclusion of fatty voxels has a negligible influence versus muscles in which a strong dependency of the T2w value distribution on the exclusion of fatty voxels is present. Because of the two opposite effects that influence T2w in a voxel, namely, (i) a pathophysiologically increased water mobility leading to T2w elevation, and (ii) a dependency of T2w on the PDFF leading to decreased T2w , the T2w distribution within a muscle might be heterogenous and the routine mean or median analysis can lead to a misinterpretation of the muscle health. It was concluded that muscle T2w mean values can wrongly suggest healthy muscle tissue. A deeper analysis of the underlying value distribution is necessary. Therefore, a quantitative analysis of T2w histograms is a potential alternative.

Automated detection of the contrast phase in MDCT by an artificial neural network improves the accuracy of opportunistic bone mineral density measurements.

OBJECTIVES: To determine the accuracy of an artificial neural network (ANN) for fully automated detection of the presence and phase of iodinated contrast agent in routine abdominal multidetector computed tomography (MDCT) scans and evaluate the effect of contrast correction for osteoporosis screening. METHODS: This HIPPA-compliant study retrospectively included 579 MDCT scans in 193 patients (62.4 ± 14.6 years, 48 women). Three different ANN models (2D DenseNet with random slice selection, 2D DenseNet with anatomy-guided slice selection, 3D DenseNet) were trained in 462 MDCT scans of 154 patients (threefold cross-validation), who underwent triphasic CT. All ANN models were tested in 117 unseen triphasic scans of 39 patients, as well as in a public MDCT dataset containing 311 patients. In the triphasic test scans, trabecular volumetric bone mineral density (BMD) was calculated using a fully automated pipeline. Root-mean-square errors (RMSE) of BMD measurements with and without correction for contrast application were calculated in comparison to nonenhanced (NE) scans. RESULTS: The 2D DenseNet with anatomy-guided slice selection outperformed the competing models and achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set (public dataset: F1 score 0.93; accuracy 94.2%). Application of contrast agent resulted in significant BMD biases (all p < .001; portal-venous (PV): RMSE 18.7 mg/ml, mean difference 17.5 mg/ml; arterial (AR): RMSE 6.92 mg/ml, mean difference 5.68 mg/ml). After the fully automated correction, this bias was no longer significant (p > .05; PV: RMSE 9.45 mg/ml, mean difference 1.28 mg/ml; AR: RMSE 3.98 mg/ml, mean difference 0.94 mg/ml). CONCLUSION: Automatic detection of the contrast phase in multicenter CT data was achieved with high accuracy, minimizing the contrast-induced error in BMD measurements. KEY POINTS: • A 2D DenseNet with anatomy-guided slice selection achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set. In a public dataset, an F1 score of 0.93 and an accuracy of 94.2% were obtained. • Automated adjustment for contrast injection improved the accuracy of lumbar bone mineral density measurements (RMSE 18.7 mg/ml vs. 9.45 mg/ml respectively, in the portal-venous phase). • An artificial neural network can reliably reveal the presence and phase of iodinated contrast agent in multidetector CT scans ( https://github.com/ferchonavarro/anatomy_guided_contrast_c ). This allows minimizing the contrast-induced error in opportunistic bone mineral density measurements.

Imaging of Metabolic Bone Diseases: The Spine View, Part I.

Metabolic bone diseases comprise a wide spectrum. Of them, osteoporosis is the most frequent and the most commonly found in the spine, with a high impact on health care systems and on morbidity due to vertebral fractures (VFs).This article discusses state-of-the-art techniques on the imaging of metabolic bone diseases in the spine, from the well-established methods to the latest improvements, recent developments, and future perspectives.We review the classical features of involvement of metabolic conditions involving the spine. Then we analyze the different imaging techniques for the diagnosis, characterization, and monitoring of metabolic bone disease: dual-energy X-ray absorptiometry (DXA) and DXA-based fracture risk assessment applications or indexes, such as the geometric parameters, Bone Strain Index, and Trabecular Bone Score; quantitative computed tomography; and magnetic resonance and ultrasonography-based techniques, such as radiofrequency echographic multi spectrometry. We also describe the current possibilities of imaging to guide the treatment of VFs secondary to metabolic bone disease.

Imaging of Metabolic Bone Diseases: The Spine View, Part II.

Metabolic bone diseases comprise a wide spectrum. Osteoporosis, the most frequent, characteristically involves the spine, with a high impact on health care systems and on the morbidity of patients due to the occurrence of vertebral fractures (VFs).Part II of this review completes an overview of state-of-the-art techniques on the imaging of metabolic bone diseases of the spine, focusing on specific populations and future perspectives. We address the relevance of diagnosis and current status on VF assessment and quantification. We also analyze the diagnostic techniques in the pediatric population and then review the assessment of body composition around the spine and its potential application. We conclude with a discussion of the future of osteoporosis screening, through opportunistic diagnosis and the application of artificial intelligence.

Esophageal Gland RNA-Seq Resource of a Virulent and Avirulent Population of the Soybean Cyst Nematode Heterodera glycines.

The soybean cyst nematode Heterodera glycines is the most economically devastating pathogen of soybean in the United States and threatens to become even more damaging through the selection of virulent nematode populations in the field that can overcome natural resistance mechanisms in soybean cultivars. This pathogen, therefore, demands intense transcriptomic/genomic research inquiries into the biology of its parasitic mechanisms. H. glycines delivers effector proteins that are produced in specialized gland cells into the soybean root to enable infection. The study of effector proteins, thus, is particularly promising when exploring novel management options against this pathogen. Here, we announce the availability of a gland cell-specific RNA-seq resource. These data represent an expression snapshot of gland cell activity during early soybean infection of a virulent and an avirulent H. glycines population, providing a unique and highly valuable resource for scientists examining effector biology and nematode virulence.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Estimating vertebral bone marrow fat unsaturation based on short-TE STEAM MRS.

PURPOSE: To define a metric for the separability between water and olefinic fat peaks that defines a threshold beyond which the extraction of the olefinic fat peak from vertebral bone marrow short-echo time-stimulated echo acquisition mode MRS at 3T is feasible when using a constrained peak fitting based on the triglyceride fat model. METHODS: The water and olefinic peak height difference was defined as a metric for quantifying the separability of water and olefinic fat peaks. Fat unsaturation was determined using an unconstrained olefinic peak fitting and a constrained fitting of all fat peaks to the triglyceride model. The agreement between the two peak-fitting methods was used to define a threshold on water and olefinic peak height difference separating two groups (A and B), based on L5 short-echo time-stimulated echo acquisition mode (TE = 11 ms) spectra from 252 subjects measured at 3T. RESULTS: A threshold on water and olefinic peak height difference was defined. Group A with a good agreement of the olefinic fat peak between the two peak-fitting methods showed a mean number of double bounds = 2.95 ± 0.21, a mean number of methylene-interrupted double bounds = 0.94 ± 0.16 and also a significantly lower coefficient of variation for all fatty acid composition parameters compared to group B (p < .001). The water and olefinic peak height difference value showed an inverse association with fat fraction. CONCLUSION: A threshold of a metric quantifying the separability of the water peak and the olefinic fat peaks was defined for the estimation of the vertebral bone marrow fat unsaturation from short-echo time-stimulated echo acquisition mode MRS. The proposed methodology shows that the assessment of vertebral bone marrow unsaturation is feasible with a short-echo time-stimulated echo acquisition mode MRS in subjects with a higher fat fraction.

Phytonematode peptide effectors exploit a host post-translational trafficking mechanism to the ER using a novel translocation signal.

Cyst nematodes induce a multicellular feeding site within roots called a syncytium. It remains unknown how root cells are primed for incorporation into the developing syncytium. Furthermore, it is unclear how CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide effectors secreted into the cytoplasm of the initial feeding cell could have an effect on plant cells so distant from where the nematode is feeding as the syncytium expands. Here we describe a novel translocation signal within nematode CLE effectors that is recognized by plant cell secretory machinery to redirect these peptides from the cytoplasm to the apoplast of plant cells. We show that the translocation signal is functionally conserved across CLE effectors identified in nematode species spanning three genera and multiple plant species, operative across plant cell types, and can traffic other unrelated small peptides from the cytoplasm to the apoplast of host cells via a previously unknown post-translational mechanism of endoplasmic reticulum (ER) translocation. Our results uncover a mechanism of effector trafficking that is unprecedented in any plant pathogen to date, andthey illustrate how phytonematodes can deliver effector proteins into host cells and then hijack plant cellular processes for their export back out of the cell to function as external signaling molecules to distant cells.

Physiological variation of the vertebral bone marrow water T2 relaxation time.

The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = -0.429/-0.210 female/male) and for water T2 versus PDFF (r = -0.580/-0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.

An Effector from the Cyst Nematode Heterodera schachtii Derepresses Host rRNA Genes by Altering Histone Acetylation.

Cyst nematodes are plant-pathogenic animals that secrete effector proteins into plant root cells to alter host gene expression and reprogram these cells to form specialized feeding sites, known as syncytia. The molecular mechanisms of these effectors are mostly unknown. We determined that the sugar beet cyst nematode (Heterodera schachtii) 32E03 effector protein strongly inhibits the activities of Arabidopsis thaliana histone deacetylases including the HDT1 enzyme, which has a known function in the regulation of rRNA gene expression through chromatin modifications. We determined that plants expressing the 32E03 coding sequence exhibited increased acetylation of histone H3 along the rDNA chromatin. At low 32E03 expression levels, these chromatin changes triggered the derepression of a subset of rRNA genes, which were conducive to H. schachtii parasitism. By contrast, high levels of 32E03 caused profound bidirectional transcription along the rDNA, which triggered rDNA-specific small RNA production leading to RNA-directed DNA methylation and silencing of rDNA, which inhibited nematode development. Our data show that the 32E03 effector alters plant rRNA gene expression by modulating rDNA chromatin in a dose-dependent manner. Thus, the 32E03 effector epigenetically regulates plant gene expression to promote cyst nematode parasitism.