Search bioRxiv⌕ Search

Biology subjects

Ferreiro, A.

Publications and source records attributed to Ferreiro, A..

4 recordsLinked to original sources

Resomapper: A Versatile Pipeline for Multiparametric MRI Processing. A Demonstrative Application in Mouse Brain Imaging

ObjectivesMagnetic resonance imaging (MRI) is essential in both research and clinical settings, with quantitative MRI (qMRI) enhancing reproducibility and sensitivity. However, qMRI processing can be complex, especially for users with limited coding experience. We introduce Resomapper, an open-source, cross-platform tool that integrates established processing libraries into a unified, user-friendly workflow, simplifying qMRI analysis while promoting accessibility, reproducibility, and data sharing. Materials and MethodsResomapper is a Python-based pipeline designed for intuitive multiparametric MRI processing. It supports T1, T2, and T2* relaxometry, magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) model fitting. The software includes advanced preprocessing options such as denoising, Gibbs artifact removal, and bias field correction. Users can process data interactively through a sequential pipeline or via an automated JSON-configured workflow, both executable through simple command-line instructions. Resomapper ensures compatibility by converting raw MRI data from different formats into the standardized NIfTI format within a BIDS-like structure, enhancing reproducibility, scalability, and data management efficiency. To demonstrate its application, we present a brain MRI study carried out on healthy, adult C57BL/6J mice, both sexes. MRI acquisitions were conducted on a Bruker Biospec 7T system using a multiparametric MRI protocol that included anatomical T2W images, T2 and T2* maps, MTI and DTI. The data were processed with Resomapper and co-registered using ANTsPy. Finally, a region of interest (ROI)-based analysis was performed to examine differences between sexes and brain areas, focusing on the cortex (Cx), hippocampus, (HPC), thalamus (Thal), and hypothalamus (HTH). ResultsDifferences in all MRI parameters were found across brain regions, as expected. Additionally, a small significant sex difference in T2* was observed, with higher values in the thalamus and hypothalamus of female mice compared to males. This may reflect sex-specific responses to anesthesia. Moreover, this study also serves as a reference for standardized multiparametric qMRI studies in mice using Resomapper. ConclusionsBy integrating multiple processing tools into a single, accessible framework, Resomapper streamlines qMRI workflows and enables reproducible, high-quality image analysis. Thanks to its ability to handle diverse preprocessing techniques, multiple imaging modalities, and standardized data formats, the software proves to be a valuable resource for researchers with varying levels of programming expertise.

neuroscience↗

Integrated data from R405W desmin knock-in mice highlight alterations of mitochondrial function, protein quality control, and myofibrillar structure in the initial stages of myofibrillar myopathy

BackgroundMutations in the desmin gene cause skeletal myopathies and cardiomyopathies. The objective of this study was to elucidate the molecular pathology induced by the expression of R405W mutant desmin in murine skeletal muscle tissue. MethodsA comprehensive characterization of the skeletal muscle pathology in hetero- and homozygous R405W desmin knock-in mice was performed, employing grip strength, blood acylcarnitine and amino acid, histological, ultrastructural, immunofluorescence, immunoblot, ribosomal stalling, RNA sequencing and proteomic analyses. ResultsBoth hetero- and homozygous R405W desmin knock-in mice showed classical myopathological features of a myofibrillar myopathy with desmin-positive protein aggregation, degenerative changes of the myofibrillar apparatus, increased autophagic build-up, and mitochondrial alterations. Muscle weakness and increased blood concentrations of acylcarnitines and amino acids were only present in homozygous animals. During its translation, mutant desmin does not induce terminal ribosomal stalling. Analyses of RNA sequencing and proteomic data from soleus muscle of 3-month-old mice depicted 59 up- and 2 down-regulated mRNAs and 101 up- and 18 down-regulated proteins that were shared between the heterozygous and homozygous genotypes in the respective omics datasets compared to the wild-type genotype. Combined analysis of the omics data demonstrated 187 significantly dysregulated candidates distributed across four groups of regulation. A down-regulation on the mRNA and protein levels was observed for a multitude of mitochondrial proteins including essential proton gradient-dependent carriers. Up-regulation on both omics levels was present for the transcription factor Mlf1, which is a binding partner of protein quality control related Dnajb6. Down-regulated on mRNA but up-regulated on the protein level was the sarcomeric lesion marker Xirp2 (xin actin-binding repeat-containing protein 2), whereas Ces2c (acylcarnitine hydrolase) was regulated in the opposite way. ConclusionsThe present study demonstrates that the expression of mutant desmin results in a myofibrillar myopathy in hetero- and homozygous R405W desmin knock-in mice. Combined morphological, transcriptomic and proteomic analyses helped to decipher the complex pattern of early pathological changes induced by the expression of mutant desmin. Our findings highlight the importance of major mitochondrial alterations, including essential proton gradient-dependent carriers as well as Dnajb6-related protein quality control and Xin-related myofibrillar damage, in the molecular pathogenesis of desminopathies.

neuroscience↗

Exploring the vomeronasal organ in an endangered antelope species

The dama gazelle is a threatened and scarcely studied species of northern Africa. Human pressure has depleted the population of dama gazelles from tens of thousands to a few hundred individuals. Since 1970, after deriving from a founder population of the last 17 surviving individuals in the Western Sahara, it has been reproduced naturally in captivity. Although certain aspects of the reproductive biology of the dama gazelle have been established in preparation for the future implementation of assisted reproductive technology there is a lack of information regarding the role of semiochemical-mediated communication in the sexual behavior of the dama gazelle. This is partially due to the lack of a neuroanatomical and morphofunctional characterization of the dama gazelle vomeronasal organ (VNO); the sensory organ responsible for the processing of pheromones. This study aims to determine the presence in the dama gazelle of a VNO fully equipped to carry out its neurosensory function and to contribute to the understanding of the interspecific variability of the VNO of ruminants. Employing histological, lectin-histochemical and immunohistochemical techniques we have performed a detailed morphofunctional evaluation of the dama gazelle VNO along its entire longitudinal axis. The findings suggest that studies of the VNO should take a similar approach, as there are significant structural and neurochemical transformations that the organ exhibits as a whole. This study contributes to the understanding of the VNO in dama gazelles and provides a basis for future studies on semiochemical-mediated communication and reproductive management of this species.

neuroscience↗

Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut

Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. By exposing the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, we uncovered the consequences of gut transit, inter-species competition, antibiotic pressure, and engineered genetic function on the processes under selective pressure during both within-genome and horizontal evolutionary modes. We then show the utility of EcN as a chassis for engineered function by achieving the highest reported reduction in serum phenylalanine levels in a mouse model of phenylketonuria using an engineered probiotic. Collectively, we demonstrate a generalizable pipeline which can be applied to other probiotic strains to better understand their safety and engineering potential.

evolutionary biology↗