Genomic analysis of adult thrombotic microangiopathies in less than 3 days: from rapid to fast genomics to treatment.

Using nanopore sequencing, we showed the feasibility and impact of rapid genomic screening for managing thrombotic microangiopathies in 18 prospective cases, achieving diagnoses in <3 days. We compared the results with standard exome sequencing, cost efficiency, and complement blockade initiation.

Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis.

Objectives: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment. Their mechanism of action raises the question of possible exacerbation of preexisting multiple sclerosis (MS). The aim of our study was to assess the risk of increased MS activity, defined by the occurrence of a relapse and/or a new MRI lesion, after ICI initiation.

Starch deficiency in tomato causes transcriptional reprogramming that modulates fruit development, metabolism, and stress responses.

Tomato (Solanum lycopersicum) fruit store carbon as starch during early development and mobilize it at the onset of ripening. Starch accumulation has been suggested to buffer fluctuations in carbon supply to the fruit under abiotic stress, and contribute to sugar levels in ripe fruit. However, the role of starch accumulation and metabolism during fruit development is still unclear.

Numerical simulations of high viscosity DNAPL recovery in highly permeable porous media under isothermal and non-isothermal conditions.

We developed a decimetric size model based on coupling generalized Darcy's law and heat-transfer equations to model viscous dense non-aqueous phase liquid (DNAPL) pumping through highly permeable porous media under non-isothermal conditions. The presence of fingering and non-wetting phase ganglia was modeled through an unsteady capillary diffusion coefficient and an arbitrary heterogeneous permeability field. The model was validated using existing experimental data of a simple case, an oil injection in a 2D tank packed with glass beads.

Spatiotemporal dynamics of the tomato fruit transcriptome under prolonged water stress.

Water availability influences all aspects of plant growth and development; however, most studies of plant responses to drought have focused on vegetative organs, notably roots and leaves. Far less is known about the molecular bases of drought acclimation responses in fruits, which are complex organs with distinct tissue types. To obtain a more comprehensive picture of the molecular mechanisms governing fruit development under drought, we profiled the transcriptomes of a spectrum of fruit tissues from tomato (Solanum lycopersicum), spanning early growth through ripening and collected from plants grown under varying intensities of water stress.

Experimental study of thermally enhanced recovery of high-viscosity DNAPL in saturated porous media under non-isothermal conditions.

Thermal enhancement is known to be an efficient way to decrease the residual saturation of some common dense non-aqueous phase liquids (DNAPLs) after pumping. However, the effect of transient heat transfer during the recovery of a high-viscosity contaminant, such as coal tar, in highly permeable porous media is still unknown. A 2D tank experimental setup allowing monitoring of temperature and saturation fields during DNAPL pumping has been developed.

The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe auto-immune disease of the central nervous system driven by pathogenic antibodies mainly directed against aquaporin-4 (AQP4-Ab). Treatment of NMOSD currently relies on immunosuppressants (mycophenolate mofetil, azathioprine) or B-cell-depleting therapy (rituximab). B-cell differentiation into antibody-producing cells requires T follicular helper cells (Tfh).

Two new convenient syntheses of 14C-squalene from turbinaric acid.

Carbon-14 labeled (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, also known as squalene, was synthesized as a tool for pharmacokinetic studies. Two simple and efficient labeling approaches were developed to give [2- C]-squalene and [3- C]-squalene from a halogenated precursor derived from turbinaric acid. They were obtained in 13.

Cabazitaxel is more active than first-generation taxanes in ABCB1(+) cell lines due to its reduced affinity for P-glycoprotein.

Purpose: The primary aim of this study was to determine cabazitaxel's affinity for the ABCB1/P-glycoprotein (P-gp) transporter compared to first-generation taxanes.

Methods: We determined the kinetics of drug accumulation and retention using [C]-labeled taxanes in multidrug-resistant (MDR) cells. In addition, membrane-enriched fractions isolated from doxorubicin-selected MES-SA/Dx5 cells were used to determine sodium orthovanadate-sensitive ATPase stimulation after exposure to taxanes.

New chimeric RNAs in acute myeloid leukemia.

High-throughput next generation sequencing (NGS) technologies enable the detection of biomarkers used for tumor classification, disease monitoring and cancer therapy. Whole-transcriptome analysis using RNA-seq is important, not only as a means of understanding the mechanisms responsible for complex diseases but also to efficiently identify novel genes/exons, splice isoforms, RNA editing, allele-specific mutations, differential gene expression and fusion-transcripts or chimeric RNA (chRNA). We used Crac, a tool that uses genomic locations and local coverage to classify biological events and directly infer splice and chimeric junctions within a single read.

High-resolution spatiotemporal transcriptome mapping of tomato fruit development and ripening.

Tomato (Solanum lycopersicum) is an established model for studying fruit biology; however, most studies of tomato fruit growth and ripening are based on homogenized pericarp, and do not consider the internal tissues, or the expression signatures of individual cell and tissue types. We present a spatiotemporally resolved transcriptome analysis of tomato fruit ontogeny, using laser microdissection (LM) or hand dissection coupled with RNA-Seq analysis. Regulatory and structural gene networks, including families of transcription factors and hormone synthesis and signaling pathways, are defined across tissue and developmental spectra.

DE-kupl: exhaustive capture of biological variation in RNA-seq data through k-mer decomposition.

We introduce a k-mer-based computational protocol, DE-kupl, for capturing local RNA variation in a set of RNA-seq libraries, independently of a reference genome or transcriptome. DE-kupl extracts all k-mers with differential abundance directly from the raw data files. This enables the retrieval of virtually all variation present in an RNA-seq data set.

SimBA: A methodology and tools for evaluating the performance of RNA-Seq bioinformatic pipelines.

Background: The evolution of next-generation sequencing (NGS) technologies has led to increased focus on RNA-Seq. Many bioinformatic tools have been developed for RNA-Seq analysis, each with unique performance characteristics and configuration parameters. Users face an increasingly complex task in understanding which bioinformatic tools are best for their specific needs and how they should be configured.

MOG antibody-related disorders: common features and uncommon presentations.

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included.

The Tomato Expression Atlas.

Summary: With the development of new high-throughput DNA sequencing technologies and decreasing costs, large gene expression datasets are being generated at an accelerating rate, but can be complex to visualize. New, more interactive and intuitive tools are needed to visualize the spatiotemporal context of expression data and help elucidate gene function. Using tomato fruit as a model, we have developed the Tomato Expression Atlas to facilitate effective data analysis, allowing the simultaneous visualization of groups of genes at a cell/tissue level of resolution within an organ, enhancing hypothesis development and testing in addition to candidate gene identification.

On the evaluation of the fidelity of supervised classifiers in the prediction of chimeric RNAs.

Background: High-throughput sequencing technology and bioinformatics have identified chimeric RNAs (chRNAs), raising the possibility of chRNAs expressing particularly in diseases can be used as potential biomarkers in both diagnosis and prognosis.

Results: The task of discriminating true chRNAs from the false ones poses an interesting Machine Learning (ML) challenge. First of all, the sequencing data may contain false reads due to technical artifacts and during the analysis process, bioinformatics tools may generate false positives due to methodological biases.

Laser microdissection of tomato fruit cell and tissue types for transcriptome profiling.

This protocol enables transcriptome profiling of specific cell or tissue types that are isolated from tomato using laser microdissection (LM). To prepare tissue for LM, fruit samples are first fixed in optimal cutting temperature (OCT) medium and frozen in molds. The tissue is then sectioned using a cryostat before being dissected using an LM instrument.

FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling.

Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the ) locus, with mutants displaying reduced maintenance of heat-induced gene expression.