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Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours., (© 2024. The Author(s).)

Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organs. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposes transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue-remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs., Competing Interests: Declaration of interests C.B. is a cofounder and scientific advisor of Myllia Biotechnology and Neurolentech., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body. Here we employ human embryonic stem cell differentiation to define how neuromesodermal progenitor (NMP)-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control., Competing Interests: AG, CS, IG, FW, IM, MW, TF, MG, AB, CB, FH, MT, MG, AT No competing interests declared, (© 2022, Gogolou et al.)

Dolichol, a long-chain polyisoprenoid broadly distributed in all tissues and cellular membranes with unknown function(s), might have a role in free radical metabolism [it accumulates in older tissues and decreases after CCl4 (in liver) or phenylhydrazine (in spleen and liver) administration]. The effects of the NADPH-ADP-Fe system on Dolichol levels in isolated hepatocytes were explored and the time-course of changes was compared with the release of MDA in the incubation medium and the decrease in CoQ 9 and 10 and Vitamin E levels. Results showed that the system increased lipid peroxidation and decreased Dolichol and CoQ levels in-parallel fashions and lowered Vitamin E levels with shorter latency. Meanwhile, no increase in dead cells and no Dolichol release in the medium were detected. In conclusion, an increase in oxidative stress possibly caused a rapid degradation of dolichol by the same (unknown) mechanism responsible for the breakdown of Ubiquinone isoprenoid chains.

Dynamic MRI is restricted due to the time required to obtain enough data to reconstruct the image sequence. Several undersampled reconstruction techniques have been proposed to reduce the acquisition time. In most of these techniques the nonacquired data are recovered by modeling the temporal information as varying pixel intensities represented in time or in temporal frequencies. Here we propose a new approach that recovers the missing data through a motion estimation of the object elements ("obels," or pieces of tissue) of the image. This method assumes that an obel displacement through the sequence has lower bandwidth than fluctuations in pixel intensities caused by the motion, and thus it can be modeled with fewer parameters. Preliminary results show that this technique can effectively reconstruct (with root mean square (RMS) errors below 4%) cardiac images and joints with undersampling factors of 8 and 4, respectively. Moreover, in the reconstruction process an approximation of the motion vectors is obtained for each obel, which can be used to quantify dynamic information. In this method the motion need not be confined to a part of the field of view (FOV) or to a portion of the temporal frequency. It is appropriate for dynamic studies in which the obels' motion model has fewer parameters than the number of acquired samples., ((c) 2007 Wiley-Liss, Inc.)

Magnetic resonance spectroscopic imaging (MRSI) is a noninvasive technique for producing spatially localized spectra. MRSI presents the important challenge of reducing the scan time while maintaining the spatial resolution. The preferred approach for this is to use time-varying readout gradients to collect the spatial and chemical-shift information. Fast, three-dimensional (3D) spatial encoded methods also reduce the scan time. Despite the existence of several new and faster 3D encoded methods, or k-space trajectories, for magnetic resonance imaging (MRI), only stack of spirals and echo planar have been studied in 3D MRSI. A novel formulation for designing fast, 3D k-space trajectory applicable to 3D MRSI is presented. This approach is simple and consists of rays expanding from the origin of k-space into a revolving sphere, collecting spectral data of all 3D spatial k-space at different times in the same scan. This article describes this new method and presents some results of its application to 3D MRSI. This technique allows some degree of undersampling; hence, it is possible to reconstruct high-quality undersampled spectroscopic imaging in order to recognize different compounds in short scan times. Additionally, the method is tested in regular 3D MRI. This proposed method can also be used for dynamic undersampled imaging.

In 3D MRI, sampling k-space with traditional trajectories can be excessively time-consuming. Fast imaging trajectories are used in an attempt to efficiently cover the k-space and reduce the scan time without significantly affecting the image quality. In many applications, further reductions in scan time can be achieved via undersampling of the k-space; however, no clearly optimal method exists. In most 3D trajectories the k-space is divided into regions that are sampled with shots that share a common geometry (e.g., spirals). A different approach is to design trajectories that gradually but uniformly cover the k-space. In the current work, successive shots progressively add sampled regions to the 3D frequency space. By cutting the sequence short, a natural undersampled method is obtained. This can be particularly efficient because in these types of trajectories the contribution of new information by later shots is less significant. In this work the performance of progressive trajectories for different degrees of undersampling is assessed with trajectories based on missile guidance (MG) ideas. The results show that the approach can be efficient in terms of reducing the scan time, and performs better than the stack of spirals (SOS) technique, particularly under nonideal conditions., (Copyright 2005 Wiley-Liss, Inc.)

Three-dimensional (3D) k-space trajectories are needed to acquire volumetric images in MRI. While scan time is determined by the trajectory efficiency, image quality and distortions depend on the shape of the trajectories. There are several 3D trajectory strategies for sampling the k-space using rectilinear or curve schemes. Since there is no evidence about their optimality in terms of image quality and acquisition time, a new design method based on missile guidance ideas is explored. Since air-to-air missile guidance shares similar goals and constraints with the problem of k-space trajectory design, a control approach for missiles is used to design a 3D trajectory. The k-space is divided into small cubes, and each one is treated as a target to be sampled. The main goal is to cover the entire space as quickly and efficiently as possible, with good performance under different conditions. This novel design method is compared to other trajectories using simulated and real data. As an example, a trajectory that requires 0.11 times the number of shots needed by the cylindrical 3DFT acquisition was designed. This trajectory requires more shots (1.66 times) than the stack of spirals, but behaves better under nonideal conditions, such as off-resonance and motion.

This work explores the use of magnetic resonance imaging (MRI) for nondestructive determination of wood characteristics and for 3D wood modeling. In this context, one of the applications under development is the automatic recognition and reconstruction of rings from transversal images obtained from MRI scanners. The algorithm analyzes a set of transversal MRI images, detecting and reconstructing growth ring edges. The information generated is then interpolated in order to obtain an accurate 3D picture of the log and its fundamental constituents (individual rings, knots, defects, etc). Results also show that the technique has potential for defect recognition, providing a powerful tool for future developments in wood analysis. The results are encouraging and further research is needed to develop automatic detection not only of rings, but also of different types of defects that are of paramount importance in the sawmill and plywood industries.

Image quality and total scan time in MRI are determined in large part by the trajectory employed to sample the Fourier space. Each trajectory has different properties like coverage of k-space, scan time, sensitivity to off-resonance conditions, etc. These properties are often contradictory, therefore a universal optimal trajectory does not exist and ultimately, it will depend on the image characteristics sought. Most trajectories used today are designed based on intuition and k-space analysis more than with optimization methods. This work presents a 3D k-space trajectory design method based on Genetic Algorithm optimization. Genetic Algorithms have been chosen because they are particularly good for searching large solution spaces. They emulate the natural evolutionary process allowing better offsprings to survive. The objective function searches the maximum of the trajectory's k-space coverage subject to hardware constraints for a fixed scanning time using the trajectory's torsion as its optimization variable. The method proved to be effective for generating k-space trajectories. They are compared with well-established trajectories. The results of simulated experiments show that they can be appropriate for image acquisition under certain special conditions, like off-resonance and undersampling. This design method can be extended to include other objective functions for different behaviors.

Magnetic Resonance Imaging opens an alternative way to analyze wood structures using a non-destructive technology. It provides high resolution, compound-based contrast manipulation and increased data acquisition flexibility. The technique is particularly useful for tree logs, since they present several characteristics that can be used to reduce the long scan time. This study proposes a method that takes advantage of the log cylindrical symmetry, acquiring transverse 1-D projections with a helical and undersampled pattern. Linear interpolation is used to estimate the skipped data and slice images are reconstructed by filtered backprojection. The sequence is improved using selective multi-pass scanning, without major variations of the scan time. Computer simulations and experimental results show that the proposed technique can increase the scan speed by a factor of 6, while maintaining the ability to identify typical tree log characteristics.

A post-processing technique is presented for correcting images undersampled in k-space. The method works by taking advantage of the image's background zeros (dynamically segmented through the application of a threshold) to extrapolate the missing k-space samples. The algorithm can produce good quality images from a small set of k-space frequencies with only a few iterations of simple matrix operations, using the image entropy as the focus criterion. It does not require any special patient preparation, extra pulse sequences, complex gradient programming or specialized hardware. This makes it a good candidate for any application that requires short scan times or where only few frequencies can be sampled.

A simplified model for the arterial pressure control system was implemented on a personal computer using Matlab Simulink. Model responses to variations of systemic vascular resistance were comparable to those predicted by physiology. Computer simulation suggested that including this model of the internal pressure control system within the design of an external controller would achieve better arterial pressure control and faster response than previous systems.