A comprehensive approach for correcting voxel‐wise b‐value errors in diffusion MRI

Purpose In diffusion MRI, the actual b‐value played out on the scanner may deviate from the nominal value due to magnetic field imperfections. A simple image‐based correction method for this problem is presented. Methods The apparent diffusion constant (ADC) of a water phantom was measured voxel‐wise along 64 diffusion directions at b = 1000 s/mm2. The true diffusion constant of water was estimated, considering the phantom temperature. A voxel‐wise correction factor, providing an effective b‐value including any magnetic field deviations, was determined for each diffusion direction by relating the measured ADC to the true diffusion constant. To test the method, the measured b‐value map was used to calculate the corrected voxel‐wise ADC for additionally acquired diffusion data sets on the same water phantom and data sets acquired on a small water phantom at three different positions. Diffusion tensor was estimated by applying the measured b‐value map to phantom and in vivo data sets. Results The b‐value‐corrected ADC maps of the phantom showed the expected spatial uniformity as well as a marked improvement in consistency across diffusion directions. The b‐value correction for the brain data resulted in a 5.8% and 5.5% decrease in mean diffusivity and angular differences of the primary diffusion direction of 2.71° and 0.73° inside gray and white matter, respectively. Conclusion The actual b‐value deviates significantly from its nominal setting, leading to a spatially variable error in the common diffusion outcome measures. The suggested method measures and corrects these artifacts

A common core RNP structure shared between the small nuclear box C/D RNPs and the spliceosomal U 4 snRNP.

AbstractThe box C/D snoRNAs function in directing 2′-O-methylation and/or as chaperones in the processing of ribosomal RNA. We show here that Snu13p (15.5kD in human), a component of the U4/U6.U5 tri-snRNP, is also associated with the box C/D snoRNAs. Indeed, genetic depletion of Snu13p in yeast leads to a major defect in RNA metabolism. The box C/D motif can be folded into a stem-internal loop-stem structure, almost identical to the 15.5kD binding site in the U4 snRNA. Consistent with this, the box C/D motif binds Snu13p/15.5kD in vitro. The similarities in structure and function observed between the U4 snRNP (chaperone for U6) and the box C/D snoRNPs raises the interesting possibility that these particles may have evolved from a common ancestral RNP

Recruiting Hard-to-Reach Subjects for Exercise Interventions: A Multi-Centre and Multi-Stage Approach Targeting General Practitioners and Their Community-Dwelling and Mobility-Limited Patients

The general practitioner (GP)’s practice appears to be an ideal venue for recruiting community-dwelling older adults with limited mobility. This study (Current Controlled Trials ISRCTN17727272) aimed at evaluating the recruiting process used for a multi-centre exercise intervention (HOMEfit). Each of six steps resulted in an absolute number of patients (N1–N6). Sex and age (for N4–N6) and reasons for dropping out were assessed. Patient database screening (N1–N3) at 15 GP practices yielded N1 = 5,990 patients aged 70 and above who had visited their GP within the past 6 months, N2 = 5,467 after exclusion of institutionalised patients, N3 = 1,545 patients eligible. Using a pre-defined limitation algorithm in order to conserve the practices’ resources resulted in N4 = 1,214 patients (80.3 ± 5.6 years, 68% female), who were then officially invited to the final assessment of eligibility at the GP’s practice. N5 = 434 patients (79.5 ± 5.4 years, 69% female) attended the practice screening (n = 13 of whom had not received an official invitation). Finally, N6 = 209 (79.8 ± 5.2 years, 74% female) were randomised after they were judged eligible and had given their written informed consent to participate in the randomised controlled trial (overall recruitment rate: 4.4%). The general strategy of utilising a GP’s practice to recruit the target group proved beneficial. The data and experiences presented here can help planners of future exercise-intervention studies

The Conserved Nup107-160 Complex Is Critical for Nuclear Pore Complex Assembly

AbstractNuclear pore complexes (NPCs) are large multiprotein assemblies that allow traffic between the cytoplasm and the nucleus. During mitosis in higher eukaryotes, the Nuclear Envelope (NE) breaks down and NPCs disassemble. How NPCs reassemble and incorporate into the NE upon mitotic exit is poorly understood. We demonstrate a function for the conserved Nup107-160 complex in this process. Partial in vivo depletion of Nup133 or Nup107 via RNAi in HeLa cells resulted in reduced levels of multiple nucleoporins and decreased NPC density in the NE. Immunodepletion of the entire Nup107-160 complex from in vitro nuclear assembly reactions produced nuclei with a continuous NE but no NPCs. This phenotype was reversible only if Nup107-160 complex was readded before closed NE formation. Depletion also prevented association of FG-repeat nucleoporins with chromatin. We propose a stepwise model in which postmitotic NPC assembly initiates on chromatin via early recruitment of the Nup107-160 complex

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

A Noninvasive Imaging Toolbox Indicates Limited Therapeutic Potential of Conditionally Activated Macrophages in a Mouse Model of Multiple Organ Dysfunction

Cell-based regenerative medicine therapies require robust preclinical safety, efficacy, biodistribution, and engraftment data prior to clinical testing. To address these challenges, we have developed an imaging toolbox comprising multispectral optoacoustic tomography and ultrasonography, which allows the degree of kidney, liver, and cardiac injury and the extent of functional recovery to be assessed noninvasively in a mouse model of multiorgan dysfunction. This toolbox allowed us to determine the therapeutic effects of adoptively transferred macrophages. Using bioluminescence imaging, we could then investigate the association between amelioration and biodistribution. Macrophage therapy provided limited improvement of kidney and liver function, although not significantly so, without amelioration of histological damage. No improvement in cardiac function was observed. Biodistribution analysis showed that macrophages homed and persisted in the injured kidneys and liver but did not populate the heart. Our data suggest that the limited improvement observed in kidney and liver function could be mediated by M2 macrophages. More importantly, we demonstrate here the utility of the imaging toolbox for assessing the efficacy of potential regenerative medicine therapies in multiple organs

Target‐oriented habitat and wildlife management: estimating forage quantity and quality of semi‐natural grasslands with Sentinel‐1 and Sentinel‐2 data

Semi‐natural grasslands represent ecosystems with high biodiversity. Their conservation depends on the removal of biomass, for example, through grazing by livestock or wildlife. For this, spatially explicit information about grassland forage quantity and quality is a prerequisite for efficient management. The recent advancements of the Sentinel satellite mission offer new possibilities to support the conservation of semi‐natural grasslands. In this study, the combined use of radar (Sentinel‐1) and multispectral (Sentinel‐2) data to predict forage quantity and quality indicators of semi‐natural grassland in Germany was investigated. Field data for organic acid detergent fibre concentration (oADF), crude protein concentration (CP), compressed sward height (CSH) and standing biomass dry weight (DM) collected between 2015 and 2017 were related to remote sensing data using the random forest regression algorithm. In total, 102 optical‐ and radar‐based predictor variables were used to derive an optimized dataset, maximizing the predictive power of the respective model. High R2 values were obtained for the grassland quality indicators oADF (R2 = 0.79, RMSE = 2.29%) and CP (R2 = 0.72, RMSE = 1.70%) using 15 and 8 predictor variables respectively. Lower R2 values were achieved for the quantity indicators CSH (R2 = 0.60, RMSE = 2.77 cm) and DM (R2 = 0.45, RMSE = 90.84 g/m²). A permutation‐based variable importance measure indicated a strong contribution of simple ratio‐based optical indices to the model performance. In particular, the ratios between the narrow near‐infrared and red‐edge region were among the most important variables. The model performance for oADF, CP and CSH was only marginally increased by adding Sentinel‐1 data. For DM, no positive effect on the model performance was observed by combining Sentinel‐1 and Sentinel‐2 data. Thus, optical Sentinel‐2 data might be sufficient to accurately predict forage quality, and to some extent also quantity indicators of semi‐natural grassland

Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy

Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers