Biology subjects

Lucas, P.

Publications and source records attributed to Lucas, P..

10 recordsLinked to original sources

bioRxiv2026

Ancient and current association of the Trichinella complex with negative-sense and double-stranded RNA viruses

The earliest records of Trichinellosis might be found in bibles that recommend against pork consumption due to the spread of a disease that resembles what is now identified as Trichinellosis. Parasitic nematodes (round worms) of the genus Trichinella form a complex of at least 13 species with a broad geographic range. Herein, through data mining of transcriptomic data, and re-sequencing of the transcriptome of representative isolates, we demonstrate the presence of viruses within 10 recognized Trichinella species. We provide genome sequences of 4 viral species of negative sense RNA viruses that belong the Family Lispiviridae, Order Mononegavirales and of 8 novel viruses of double-stranded RNA viruses that belong to a novel sub-order within the order Ghabrivirales. The integration of viral genome fragments within encapsulated Trichinella genomes demonstrate that these parasite-virus associations are ancient. Overall, viruses show co-diversification with their parasitic hosts. Yet the phylogenetic position of viruses revealed past host jump from an ancestral encapsulated Trichinella species to the ancestral T. pseudospiralis, and challenges previous dogma on the phylogeny and biogeography of Trichinella species in North America. ImportanceWe are witnessing the emergence of a novel field of research focusing on viruses of parasites, and their role in parasite pathogenicity. Herein we describe the characterization of viruses within 10 recognized species of Trichinella. The viruses were distantly related to known viruses which led us to propose the creation of a novel genera, and a novel sub-order. We demonstrated the integration of viral genome fragments within the genome of Trichinella species and an on-going process of birth and death of viral integration. Finally, we showed that virus phylogenetic analyses can provide fine-tuned information of their parasitic host evolutionary history. This study demonstrates the ancient and close association between Trichinella and viruses, and strong species specificity. Further studies are now needed to determine whether the newly discovered viruses could be targeted for the development of novel diagnostic approaches.

microbiology↗

bioRxiv2026

Diversity of pheromone temporal coding disruptions by plant volatiles

Moth pheromone-sensitive olfactory receptor neurons (Phe-ORNs) encode the intermittent structure of pheromone plumes through precisely timed spikes, a mechanism that is essential for odor plume tracking behavior in flying insects. However, natural olfactory scenes are composed of diverse volatile plant compounds (VPCs) with complex temporal dynamics whose effects on pheromone signal intermittency encoding remain unclear. Two lines of research, encoding of pheromone intermittency and background interference, remain largely disconnected. Here, we performed electrophysiological recordings from moth Phe-ORNs to quantify their responses to turbulent plume-like flickering pheromone stimuli in constant or fluctuating backgrounds of a diversity of VPCs. We found that some VPCs reversibly disrupted the temporal coding of various subregions of the pheromone stimulus and the trial-to-trial variability. While Phe-ORN activation by VPCs partially accounted for the decrease in coding performance, Phe-ORN gain reduction was insufficient to explain the full extent of the disruption. Some VPCs disrupt temporal coding without activating Phe-ORNs, and others activate Phe-ORNs without altering temporal coding. A continuous background noise can induce strong adaptation and limit dynamic range, whereas a fluctuating background can interfere with pheromone pulse encoding by disrupting spike timing. Altogether, these results indicate that the pheromone detection system must contend with multiple forms of background noise rather than a uniform disturbance. Timing is key for olfactory navigation, and our results raise questions regarding how downstream circuits would process noisy sensory inputs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/713794v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1c44fb6org.highwire.dtl.DTLVardef@14d5982org.highwire.dtl.DTLVardef@12f94a2org.highwire.dtl.DTLVardef@c731ee_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

MRTF promotes breast cancer cell motility through SRF-dependent upregulation of DIAPH3 expression

Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type vs functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRFs interaction is critical for MRTF-A-induced promotion of both 2D and 3D cell migration, while the SAP-domain function is important selectively for 3D cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRFs interaction of MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases vs primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human breast cancer, justifying future development of a specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer. SIGNIFICANCEO_LIActin cytoskeletal dysregulation gives rise to metastatic dissemination of cancer cells. This study mechanistically investigates the impact of specific functional disruption of MRTF (a transcriptional co-factor of SRF) on breast cancer cell migration. C_LIO_LIThis study establishes a novel mechanism linking mDia2 to MRTF-dependent regulation of cell migration and provides clinical evidence for the association between MRTF activity and increased malignancy in human breast cancer. C_LIO_LIFindings from these studies justify future exploration of specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer. C_LI

cell biology↗

bioRxiv2023

Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in both homeostatic and pathological states. It also participates in organogenesis, HIV-1 infection and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. Activation of CXCR4 by CXCL12 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation to chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues in TMV and TMVI. Using this structural motif as a template, we performed in silico molecular modeling followed by in vitro screening of a small compound library to identify negative allosteric modulators of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small molecule that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both in vitro and in vivo while preserving ligand binding and receptor internalization. Significance StatementThe chemokine receptor CXCR4 and its ligand CXCL12 are key for development, hematopoiesis, neutrophil homeostasis and lymphocyte trafficking. The only commercially available CXCR4 antagonist currently approved for clinical use is plerixafor (AMD3100), a small compound that blocks the ligand-binding site. Unfortunately, its clinical use is limited by poor pharmacokinetics and adverse effects associated with long-term administration. Here, we performed in silico analyses of a small aromatic compound library and in vitro screening to identify allosteric CXCR4 modulators. These compounds abolish the ability of cells to sense chemoattractant gradients without affecting other ligand-mediated functions such as cAMP production or receptor internalization. The selected compounds were also effective in vivo, as demonstrated by reduced tumorigenesis and metastasis in a zebrafish tumor model. Our study describes a new approach to selectively alter some GPCR functions while maintaining other functions.

cell biology↗

bioRxiv2022

Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming

Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming. Here, using biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy, we demonstrate that growth hormone (GH) functions as a metabolic modulator to reprogram inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MO). We found that exogenous treatment of GM-MO with recombinant human GH suppressed glycolysis, lactate production and non-mitochondrial respiration, and enhanced mitochondrial oxidative phosphorylation. Likewise, GH treatment augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered a new target to intervene in multiple inflammatory diseases.

immunology↗

bioRxiv2022

Stimulus duration encoding occurs early in the moth olfactory pathway

Pheromones convey rich ethological information and guide insects search behavior. Insects navigating in turbulent environments are tasked with the challenge of coding the temporal structure of an odor plume, obliging recognition of the onset and offset of whiffs of odor. The coding mechanisms that shape odor offset recognition remain elusive. We designed a device to deliver sharp pheromone pulses and simultaneously measured the response dynamics from pheromone-tuned olfactory receptor neurons (ORNs) in male moths and Drosophila. We show that concentration-invariant stimulus duration encoding is implemented in moth ORNs by spike frequency adaptation at two time scales. A linear-nonlinear model fully captures the underlying neural computations and offers an insight into their biophysical mechanisms. Drosophila use pheromone cis-vaccenyl acetate (cVA) only for very short distance communication and are not faced with the need to encode the statistics of the cVA plume. Their cVA-sensitive ORNs are indeed unable to encode odor-off events. Expression of moth pheromone receptors in Drosophila cVA-sensitive ORNs indicates that stimulus-offset coding is receptor independent. In moth ORNs, stimulus-offset coding breaks down for short (<200 ms) whiffs. This physiological constraint matches the behavioral latency of switching from the upwind surge to crosswind cast flight upon losing contact with the pheromone.

neuroscience↗

bioRxiv2021

A world of viruses nested within parasites: Unraveling viral diversity within parasitic flatworms (Platyhelminthes)

Because parasites have an inextricable relationship with their host, they have the potential to serve as viral reservoirs or facilitate virus host-shifts. Yet, little is known about viruses infecting parasitic hosts except for blood-feeding arthropods that are well-known vectors of zoonotic viruses. Herein we uncover viruses of flatworms (Phylum Platyhelminthes, group Neodermata) that specialize in parasitizing vertebrates and their ancestral free-living relatives. We discovered 115 novel viral sequences, including 1 in Macrostomorpha, 5 in Polycladida, 44 in Tricladida, 1 in Monogenea, 15 in Cestoda and 49 in Trematoda, through data mining. The majority of newly identified viruses constitute novel families or genera. Phylogenetic analyses show that the virome of flatworms changed dramatically during the transition of Neodermatans to a parasitic lifestyle. Most Neodermatan viruses seem to co-diversify with their host, with the exception of rhabdoviruses which may switch host more often, based on phylogenetic relationships. Neodermatan rhabodviruses also have an ancestral position to vertebrate-associated viruses, including Lyssaviruses, suggesting that vertebrate rhabdoviruses emerged from a flatworm rhabdovirus in a parasitized host. This study reveals an extensive diversity of viruses in Platyhelminthes and highlights the need to evaluate the role of viral infection in flatworm-associated diseases.

microbiology↗

bioRxiv2020

Effects of an odor background on moth pheromone communication: constituent identity matters more than blend complexity

Olfaction allows insects to communicate with pheromones even in complex olfactory landscapes. It is generally admitted that, due to the binding selectivity of the receptors, general odorants should weakly interfere with pheromone detection. However, laboratory studies show that volatile plant compounds (VPCs) modulate responses to the pheromone in male moths. We used extracellular electrophysiology and calcium imaging to measure the responses to the pheromone of receptor and central neurons in males Agrotis ipsilon while exposed to simple or composite backgrounds of VPCs. Maps of activities were built using calcium-imaging to visualize which areas in antennal lobes (ALs) were affected by VPCs. To mimic a natural olfactory landscape short pheromone puffs were delivered over VPC backgrounds. We chose a panel of VPCs with different chemical structures and physicochemical properties representative of the odorant variety encountered by a moth. We evaluated the intrinsic activity of each VPC and compared the impact of VPC backgrounds at antenna and antennal lobe levels. Then, we prepared binary, ternary and quaternary combinations to determine whether blend activity could be deduced from that of its components. Our data confirm that a VPC background interfere with the moth pheromone system in a dose-dependent manner. Interference with the neuronal coding of pheromone signal starts at the periphery. VPCs showed differences in their capacity to elicit Phe-ORN firing response that cannot be explained by differences in stimulus intensities because we adjusted the source concentrations to vapor pressures. Thus, these differences must be attributed to the selectivity of ORs or any other olfactory proteins. The neuronal network in the ALs, which reformats the ORN-input, did not improve pheromone salience. We postulate that the AL network might have evolved to increase sensitivity and encode for fast changes over a wide range of concentrations, possibly at some cost for selectivity. Comparing three- or four-component blends to binary blends or single compound indicated that a blend showed the activity of its most active compound. Thus, although the diversity of a background might increase the probability of including a VPC interacting with the pheromone system, chemical diversity does not seem to be a prominent factor per se. Global warming is significantly affecting plant metabolism so that the emissions of VPCs and resulting odorscapes are modified. Increase in atmospheric mixing rates of VPCs will change olfactory landscapes which, as confirmed in our study, might impact pheromone communication.

neuroscience↗

bioRxiv2019

Characterization of vertically and cross-species transmitted viruses in the cestode parasite Schistocephalus solidus

Parasitic flatworms (Neodermata) represent a public health and economic burden due to associated debilitating diseases and limited therapeutic treatments available. Despite their importance, there is scarce information regarding flatworm-associated microbes. We report the discovery of six RNA viruses in the cestode Schistocephalus solidus. None were closely related to classified viruses and they represent new taxa. Mining transcriptomic data revealed the broad distribution of these viruses in Alaskan and European S. solidus populations. We demonstrate through in vitro culture of S. solidus that five of these viruses are vertically transmitted. With experimental infections and field-sampling, we show that one of the viruses is transmitted to parasitized hosts. The impact of these viruses in parasite fitness and pathogenicity, and in host-parasite co-evolutionary dynamics remains to be determined. The detection of six novel viruses in this first characterization of viruses in Neodermatans likely represents a fraction of virus diversity in parasitic flatworms.

microbiology↗

bioRxiv2017

Olfactory coding in the turbulent realm

Long-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs) and antennal lobe projection neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m) from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear-nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.\n\nAuthor SummaryLong-distance olfactory search is a difficult task because atmospheric turbulence erases global gradients and makes the plume discontinuous. The dynamics of odor detections is the sole information about the position of the source. Male moths successfully track female pheromone plumes at large distances. Here we show that the moth olfactory system encodes olfactory scenes simulating variable distances from the odor source by characterizing puff onsets and offsets. A single projection neuron is sufficient to provide an accurate representation of the dynamic pheromone time course at any distance to the source while this information seems to be encoded at the population level in olfactory receptor neurons.

neuroscience↗