Biology subjects

Rey, M.

Publications and source records attributed to Rey, M..

7 recordsLinked to original sources

bioRxiv2026

Core-sheath coupling controls flagellar curvature and motility in Leptospira

Spirochete pathogens are among the most invasive bacteria known, causing syphilis, Lyme disease, and leptospirosis. Their tissue penetration depends on periplasmic flagellar filaments that, unlike other bacterial flagella, are encased in a spirochete-specific multi-protein sheath and deform the cell body into motile waves. How these filaments achieve the mechanical properties needed for invasive motility has remained unclear. Here we determine complete atomic structures of the Leptospira endoflagellar filament, revealing an elaborate sheath of 9 to 12 distinct asymmetrically arranged proteins. We show that the flagellin variant forming the filament core determines sheath composition, producing curvatures ranging from [~]3.5 {micro}m-1 to [~]5 {micro}m-1. The lower-curvature architecture, employed by pathogenic Leptospira interrogans, proves essential for motility in viscous environments and during infection. Thus, Leptospira achieves environment-specific motility through modular core-sheath coupling, linking atomic-scale structural plasticity to large-scale changes in swimming behaviour. Conservation of key sheath components suggests this mechanism may extend across spirochetes.

microbiology↗

bioRxiv2024

Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors.

Early immune reconstitution after autologous hematopoietic stem cell transplantation (autoHSCT) is associated with a better outcome in a variety of cancers. NK cells constitute the first lymphocyte subset to recover in the blood after autoHSCT. We have in-depth characterized them in pediatric patients with different tumors and found that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, were more immature and activated, and exhibited an increased expression of inhibitory receptors, while activating receptors levels were diminished. This activated and decidual-like phenotype was characterized by increased CD56, CD9, CD49a, CD151, CD38, HLA-DR and CD55 expression. We also determined plasma levels of several cytokines and found that their concentrations were associated with the observed changes in NK cells phenotype. In vitro experiments, including flow cytometry and single-cell RNA sequencing (scRNA-seq), recapitulated the changes observed in NK cells early after autoHSCT. Specifically, results revealed that the combination of IL-15 and TGF-{beta} induced, at least partially, this distinctive phenotype on NK cells after autoHSCT. Finally, we have observed a positive correlation between relapse and the percentage of CD56dim NK cells shortly after autoHSCT in our cohort of pediatric patients. Altogether, our work is of relevance to understand the physiopathology of NK cells during the immune system reconstitution after autoHSCT in children and potentially help in the management of these patients.

immunology↗

bioRxiv2023

DiscoGen: Learning to Discover Gene Regulatory Networks

Accurately inferring Gene Regulatory Networks (GRNs) is a critical and challenging task in biology. GRNs model the activatory and inhibitory interactions between genes and are inherently causal in nature. To accurately identify GRNs, perturbational data is required. However, most GRN discovery methods only operate on observational data. Recent advances in neural network-based causal discovery methods have significantly improved causal discovery, including handling interventional data, improvements in performance and scalability. However, applying state-of-the-art (SOTA) causal discovery methods in biology poses challenges, such as noisy data and a large number of samples. Thus, adapting the causal discovery methods is necessary to handle these challenges. In this paper, we introduce DiscoGen, a neural network-based GRN discovery method that can denoise gene expression measurements and handle interventional data. We demonstrate that our model outperforms SOTA neural network-based causal discovery methods.

genomics↗

bioRxiv2023

Inhibition of broomrape germination by 2,4-diacetylphloroglucinol produced by environmental Pseudomonas.

Phloroglucinol compounds (PGCs) produced by environmental Pseudomonas are well known for their capacity to limit plant-pathogen infection. Although PGCs and more specifically 2,4-diacetylphloroglucinol (DAPG) are well studied for their antimicrobial properties, they are to some extent toxic for crop plants. Parasitic weeds such as broomrapes (Phelipanche ramosa and Orobanche cumana) cause severe damage to crops and their development must be controlled. Here, we assessed the potential herbicidal effect of the bacterial model Pseudomonas ogarae F113, a PGCs-producing bacterium, on parasitic weed germination. We show using a mutagenesis approach that PGCs produced in bacterial supernatants are the main determinant inhibiting the germination of broomrapes. The use of individual or cocktails of pure PGCs revealed that the inhibition of the germination depends on the PGCs molecular structure and their concentrations as well as the broomrape species and pathovars. Furthermore, the inhibition caused by the PGCs is irreversible, causing a brown coloration of the broomrape seeds. Then, we evaluated in non-sterile soils the ability of bacterial inoculants or chemical DAPG to limit the infection of broomrapes on oil seed rape. Only the inoculation of PGCs-producing bacteria limited the infection of P. ramosa. Moreover, elemental profiling analysis of oil seed rape revealed that neither the inoculant nor applied DAPG affected the nutrition capacity of the oil seed rape. Our study expands the knowledge on the role that these multi-talented plant-beneficial Pseudomonas play in the environment and open new avenues for the development of natural bioherbicides to ward off parasitic plant infection.

microbiology↗

bioRxiv2021

Universal amyloidogenicity of patient-derivedimmunoglobulin light chains

The deposition of immunoglobulin light chains (IgLCs) in the form of amorphous aggregates or amyloid fibrils in different tissues of patients can lead to severe and potentially fatal organ damage, requiring transplantation in some cases. There has been great interest in recent years to elucidate the origin of the very different in vivo solubilities of IgLCs, as well as the molecular determinants that drive either the formation of ordered amyloid fibrils or disordered amorphous aggregates. It is commonly thought that the reason of this differential aggregation behaviour is to be found in the amino acid sequences of the respective IgLCs, i.e. that some sequences display higher intrinsic tendencies to form amyloid fibrils. Here we perform in depth Thermodynamic and Aggregation Fingerprinting (ThAgg-Fip) of 9 multiple myeloma patient-derived IgLCs, the amino acid sequences of all of which we have solved by de novo protein sequencing with mass spectrometry. The latter technique was also used for one IgLc from a patient with AL amyloidosis. We find that all samples also contain proteases that fragment the proteins under physiologically relevant mildly acidic pH conditions, leading to amyloid fibril formation in all cases. Our results suggest that while every pathogenic IgLC has a unique ThAgg fingerprint, all sequences have comparable amyloidogenic potential. Therefore, extrinsic factors, in particular presence of, and susceptibility to, proteolytic cleavage is likely to be a strong determinant of in vivo aggregation behaviour. The important conclusion, which is corroborated by systematic analysis of our sequences, as well as many sequences of IgLCs from amyloidosis patients reported in the literature, challenges the current paradigm of the link between sequence and amyloid fibril formation of pathogenic light chains.

biophysics↗

bioRxiv2018

Theta bursts precede, and spindles follow, cortical and thalamic downstates in human NREM sleep

AbstractSince their discovery, slow oscillations have been observed to group spindles during non-REM sleep. Previous studies assert that the slow oscillation downstate (DS) is preceded by slow spindles (10-12Hz), and followed by fast spindles (12-16Hz). Here, using both direct transcortical recordings in patients with intractable epilepsy (n=10, 8 female), as well as scalp EEG recordings from a healthy cohort (n=3, 1 female), we find in multiple cortical areas that both slow and fast spindles follow the DS. Although discrete oscillations do precede DSs, they are theta bursts (TB) centered at 5-8Hz. TBs were more pronounced for DSs in NREM stage N2 compared with N3. TB with similar properties occur in the thalamus, but unlike spindles they have no clear temporal relationship with cortical TB. These differences in corticothalamic dynamics, as well as differences between spindles and theta in coupling high frequency content, are consistent with NREM theta having separate generative mechanisms from spindles. The final inhibitory cycle of the TB coincides with the DS peak, suggesting that in N2, TB may help trigger the DS. Since the transition to N1 is marked by the appearance of theta, and the transition to N2 by the appearance of DS and thus spindles, a role of TB in triggering DS could help explain the sequence of electrophysiological events characterizing sleep. Finally, the coordinated appearance of spindles and DSs are implicated in memory consolidation processes, and the current findings redefine their temporal coupling with theta during NREM sleep.\n\nSignificance StatementSleep is characterized by large slow waves which modulate brain activity. Prominent among these are downstates, periods of a few tenths of a second when most cells stop firing, and spindles, oscillations at about twelve times a second lasting for about a second. In this study, we provide the first detailed description of another kind of sleep wave: theta bursts, a brief oscillation at about six cycles per second. We show, recording during natural sleep directly from the human cortex and thalamus, as well as on the human scalp, that theta bursts precede, and spindles follow downstates. Theta bursts may help trigger downstates in some circumstances, and organize cortical and thalamic activity so that memories can be consolidated during sleep.

neuroscience↗

bioRxiv2017

The Generation and Propagation of the Human Alpha Rhythm

IntroductionThe alpha rhythm (7-13 Hz) is the longest studied brain oscillation and has been theorized to play a key role in cognition. Still, substantial uncertainty remains over its physiology. In this study, we used micro and macro electrodes in patients undergoing surgery for epilepsy to measure the intracortical and thalamic generators of the human alpha rhythm. We first found that alpha propagates from higher-order anterosuperior cortex towards the lower-order occipital poles, consistent with alpha effecting top-down processing. This cortical alpha drives thalamic alpha, reversing prevailing theories of a thalamic alpha pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortex, contravening the popular conception of alpha as an infragranular rhythm. Together, these results demonstrate that the alpha rhythm reflects short-range supragranular feedback which propagates from higher-order to lower order cortex and cortex to thalamus. These physiological insights explain how alpha could mediate feedback throughout the thalamocortical system.

neuroscience↗