Biology subjects

Huguet, A.

Publications and source records attributed to Huguet, A..

4 recordsLinked to original sources

bioRxiv2024

Upregulation of FasII underlies synergistic neuropathological and behavioral defects in a Drosophila model of myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder that has been extensively studied for decades, yet our understanding of its neuropathological aspect remains rudimentary. In this study, we characterized a novel model of DM1 neuropathology by expressing untranslated expanded CUG repeats at the Drosophila larval neuromuscular junction. In this model, both pre- and postsynaptic expression of CUG repeats participate to induce reduction of synaptic boutons, increase of arbor disassembly and impairment of larval locomotor activity. We found that the expression of CUG repeats caused an upregulation of the cell adhesion molecule, FasII (NCAM1 in mammals), in both the motor neurons and the body wall muscles. Knockdown of fasII was sufficient to rescue bouton numbers and locomotor impairment in this model. Further analyses identified the upregulation of the FasII-C isoform as a major contributor of these phenotypes. Remarkably, overexpressing the FasII-A-PEST+ isoform rescued the synaptic and behavioral defects, likely by outcompeting the upregulated FasII-C. Our study provided the foundation for a basic mechanism of synapse dysregulation in DM1.

neuroscience↗

bioRxiv2022

Membrane lipid adaptation of soil Gram-negative bacteria isolates to temperature and pH

3-hydroxy fatty acids (3-OH FAs) are characteristic components of the Gram-negative bacterial membrane, recently proposed as promising temperature and pH (paleo) proxies in soil. Nevertheless, to date, the relationships between the 3-OH FA distribution and temperature/pH are only based on empirical studies, with no work at the microbial level. This work investigated the influence of growth temperature and pH on the lipid profile in three strains of soil Gram-negative bacteria belonging to the Bacteroidetes phylum. Even though the non-hydroxy FAs were more abundant than the 3-OH FAs in the investigated strains, we showed the important role of the 3-OH FAs in the membrane adaptation of Gram-negative bacteria to temperature. The strains shared a common adaptation mechanism to temperature, with a significant increase in the ratio of anteiso vs. iso or normal 3-OH FAs at lower temperature. In contrast with temperature, no common adaptation mechanism to pH was noticed, the variations in the FA lipid profiles differing from one strain to another. The models envisioning the reconstruction of environmental changes in soils should include the whole suite of 3-OH FAs present in the membrane of Gram-negative bacteria, as all of them can be influenced by temperature or pH at the microbial level.

microbiology↗

bioRxiv2022

Molecular Acclimation of Halobacterium salinarum to Halite Brine Inclusions

1Halophilic microorganisms have long been known to survive within the brine inclusions of salt crystals, as evidenced by the change in color for salt crystals containing pigmented halophiles. However, the molecular mechanisms allowing this survival has remained an open question for decades. While protocols for the surface sterilization of halite (NaCl) have enabled isolation of cells and DNA from within halite brine inclusions, "-omics" based approaches have faced two main technical challenges: (1) removal of all contaminating organic biomolecules (including proteins) from halite surfaces, and (2) performing selective biomolecule extractions directly from cells contained within halite brine inclusions with sufficient speed to avoid modifications in gene expression during extraction. In this study, we present methods to resolve these two technical challenges. In addition, we apply these methods to perform the first examination of the early acclimation of a model haloarchaeon (Halobacterium salinarum NRC-1) to halite brine inclusions. Examinations of the proteome of Halobacterium cells two months post-evaporation revealed a high degree of similarity with stationary phase liquid cultures, but with a sharp down-regulation of ribosomal proteins. Low quantities of RNA from halite brine inclusions corroborate the hypothesis of low transcriptional and translational activities. While proteins for central metabolism were part of the shared proteome between liquid cultures and halite brine inclusions, proteins involved in cell mobility (archaellum, gas vesicles) were either absent or less abundant in halite samples. Proteins unique to cells within brine inclusions included transporters, suggesting modified interactions between cells and the surrounding brine inclusion microenvironment. The methods and hypotheses presented here enable future studies of the survival of halophiles in both culture model and natural halite systems.

microbiology↗

bioRxiv2018

Straightjacket/α 2δ 3 deregulation is associated with cardiac conduction defects in Myotonic Dystrophy type 1

Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a complex toxic CTG repeat disorder involving misbalance between two RNA- binding factors, MBNL1 and CELF1. How this pathogenic DM1 condition translates into cardiac conduction disorders remains poorly understood. Here, we simulated MBNL1 and CELF1 misbalance in the Drosophila heart and identified associated gene deregulations using TU-tagging based transcriptional profiling of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels and among them increased expression of straightjacket/2{delta}3 that encodes a regulatory subunit of a voltage-gated calcium channel. Straightjacket overexpression in the fly heart leads to asynchronous heart beating, a hallmark of affected conduction, whereas cardiac straightjacket knockdown improves these symptoms in DM1 fly models. We also show that ventricular 2{delta}3 expression is low in healthy mice and humans but significantly elevated in ventricular muscles from DM1 patients with conduction defects. Taken together, this suggests that reducing the straightjacket/2{delta}3 transcript levels in ventricular cardiomyocytes could represent a strategy to prevent conduction defects and in particular intraventricular conduction delay associated with DM1 pathology.

genomics↗