Biology subjects

Hebert, C.

Publications and source records attributed to Hebert, C..

10 recordsLinked to original sources

bioRxiv2026

Robust V(D)J Recombination in the Absence of SA1/2-mediated Chromatin Loops

The cohesin ring complex organizes and mediates functional activity of the genome through chromatin loop extrusion1,2. Cohesin comprises a core SMC1-SMC3-RAD21 ring associated with multiple regulatory proteins, including SA1 and SA2 paralogs that bind mutually-exclusively to a RAD21 site3,4. Functional studies of cohesin complexes in vivo often employ inactivation of particular components2,3. However, inactivation of SA1 or SA2 in mice is limited by mouse embryonic lethality5-7 and, for dual SA1/2-inactivation by cycling cell lethality8-10. For these reasons, it remains unknown whether the requirement for SA1/2 in loop extrusion in vitro11,12 applies in vivo1,2, and whether these factors have overlapping or distinct functions in regulating this process3. Here, we employ G0/G1-arrested v-Abl pro-B lines, which are viable in the absence of cohesin-complex factors13,14, to dissect SA1 and SA2 functions in V(D)J recombination, a strictly G0/G1-specific process that harnesses loop extrusion to effect distinct Igh and Ig{kappa} locus recombination mechanisms15,16. Robust long-range Igh or Ig{kappa} V(D)J recombination continued unabated in the absence of SA1 or SA2. However, inactivation of both abrogated most positioned chromatin loops genome-wide and also abolished long-range Igh V(D)J recombination with a phenotype similar to RAD21 (cohesin) inactivation13. Yet, robust Ig{kappa} V(D)J recombination continued upon dual SA1/2-inactivation, which along with Hi-C findings, demonstrates ongoing loop-extrusion in the absence of SA1/2. Correspondingly, replacement of weak Igh V(D)J recombination signal sequences (RSSs) that target V(D)J recombination activity, with strong Ig{kappa} counterparts15 restored long-range Igh V(D)J recombination in SA1/2 inactivated cells. We conclude that SA1/2 together maintain loop extrusion impediments and genome-wide architecture in G0/G1-arrested cells; and, in their absence, loop extrusion proceeds unimpeded. Remarkably, strong RSSs allow Ig{kappa} to function normally in the absence of internal positioned loop structure across the 3.1-mega-base Ig{kappa} locus. We discuss implications of our findings for long-range gene regulation in G0/G1-arrested cells more broadly.

immunology↗

bioRxiv2026

Attenuated estrogen signaling disrupts placentation and drives trophoblast defects in Down syndrome

Proper establishment of the primitive placenta and subsequent tissue homeostasis in the mature placenta are critical for successful pregnancy in humans. Placental insufficiency is associated with adverse pregnancy outcomes, including fetal growth restriction, preeclampsia, and pregnancy loss. Moreover, emerging evidence suggests that placental defects are associated with long-term health challenges that manifest well into adulthood; yet the etiologies of such diseases are largely unknown. Defining the mechanistic basis for placental deficiencies, therefore, has important implications for improving both reproductive health and the lifelong well-being of affected children. Down syndrome is characterized by placental defects of unknown mechanistic origin, and notably, individuals with Down syndrome are at increased risk of developing diseases commonly associated with placental insufficiency later in life. Using induced pluripotent stem cells from Down syndrome patients, we found that stem cell-based embryo models (i.e., blastoids) and directed differentiation systems recapitulate trophoblast cell fate defects observed in placentas affected by Down syndrome. Furthermore, we demonstrate that attenuated estrogen signaling contributes to placental syncytialization defects and identify NRIP1, a transcriptional corepressor of estrogen receptor that is located on chromosome 21, as a key driver of trophoblast cell fate defects. Increased gene dosage of NRIP1 in an otherwise diploid cell line phenocopies cell fate defects observed in trophoblasts affected by Down syndrome. Our study suggests that estrogen signaling is a crucial regulator of trophoblast development and may serve as a potential target for therapeutic intervention. Highlights and eTOC blurbO_LIEstrogen signaling mediates syncytiotrophoblast fusion C_LIO_LIHuman iPS cells provide a tractable model for trophoblast defects in Down syndrome C_LIO_LITrophoblast differentiation and estrogen signaling are disrupted in Down syndrome C_LIO_LIIncreased NRIP1 expression is sufficient to induce trophoblast defects C_LI Logsdon and colleagues apply patient-derived induced pluripotent stem cells to recapitulate placentation defects observed in Down syndrome. The authors demonstrate that attenuated estrogen signaling disrupts trophoblast differentiation and identify NRIP1, a gene found on chromosome 21 that dampens estrogen signaling, as a regulator of trophoblast maturation. NRIP1 and estrogen signaling may represent important therapeutic targets for infertility and Down syndrome.

developmental biology↗

bioRxiv2026

Inferring biodiversity from indicator species using co-occurrence network structure

Biodiversity loss is accelerating worldwide, yet comprehensive assessment of species assemblages across environmental gradients remains impractical for ecological forecasting and conservation. Indicator species are therefore widely used as proxies for community composition, but existing approaches struggle to reconstruct full assemblages, particularly for rare or poorly sampled species. Here we present an integrated framework combining indicator species analysis, ecological network theory, and machine learning to infer the occurrence of non-indicator species from assemblage data. By leveraging structural properties of species co-occurrence networks, the approach captures latent community structure without explicit environmental modeling, enabling inference under sparse sampling. Across species abundance gradients, we identify three distinct regimes of predictability: high predictability for abundant species, reduced performance for species of intermediate prevalence, and unexpectedly strong predictability for rare species driven by strong co-occurrence structure with indicator species. By exploiting complementary information captured by multiple network metrics, the framework recovers species with diverse connectivity profiles and consistently outperforms richness-based or random indicator selection in both accuracy and coverage. Overall, this data-efficient approach provides a transferable pathway for biodiversity monitoring and forecasting, while offering new insights into the network organization of ecological communities.

ecology↗

bioRxiv2025

Large-scale integrative taxonomy of the smallest insects reveals astonishing temperate diversity

Fairyflies (Hymenoptera: Chalcidoidea: Mymaridae) are a diverse but taxonomically neglected group of parasitoid wasps that attack eggs of other insects. Being among the very smallest of all insects, they are often overlooked in biodiversity surveys despite being one of the most abundant microhymenoptera in many habitats. The traditional approach of morphological sorting for species delimitation can be challenging due to their minute size and meticulous slide-mounting technique. Ways to accelerate their discovery are needed. We conducted the first large-scale study of Mymaridae in temperate forests, combining DNA megabarcoding and the Large-scale Integrative Taxonomy (LIT) workflow to describe their diversity. We obtained COI barcodes from 2,098 specimens and used ASAP and RESL for species delimitation. Between 42 and 114 molecular clusters were delimited. Reducing morphological validation to only 9% of the sample enabled accurate determination while limiting time and effort. We confirmed the presence of 55 species, including many potentially new to science. The LIT workflow was effective for Mymaridae, although cryptic diversity remains unresolved in some large clusters, especially in the genera Alaptus and Anagrus, where high haplotype diversity and morphological ambiguity suggest additional hidden species. DNA reference databases proved unreliable, with less than 1% correct species matches, highlighting the taxonomic gap for this group. Nonetheless, we contributed 16 new identified reference barcodes to public databases and added new provincial and national species records for Canada. Our results demonstrate the value of combining molecular and morphological data in a standardized workflow and underscore the importance of improving reference databases for effective biodiversity assessments of dark taxa like microhymenoptera.

zoology↗

bioRxiv2022

Graphene-based thin film microelectrode technology for in vivo high resolution neural recording and stimulation

Neuroprosthetic technology aims to restore nervous system functionality in cases of severe damage or degeneration by recording and stimulating the electrical activity of the neural tissue. One of the key factors determining the quality of the neuroprostheses is the electrode material used to establish electrical communication with the neural tissue, which is subject to strict electrical, electrochemical, and mechanical specifications as well as biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin film technology and its engineering to form flexible neural implants. Bench measurements show that the developed microelectrodes offer low impedance and high charge injection capacity throughout millions of pulses. In vivo electrode performance was assessed in rodents both from brain surface and intracortically showing high-fidelity recording performance, while stimulation performance was assessed with an intrafascicular implant that demonstrated low current thresholds and high selectivity for activating subsets of axons within the sciatic nerve. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical and intraneural implantation. Overall, this works describes a novel graphene-based thin film microelectrode technology and demonstrates its potential for high-precision neural interfacing in both recording and stimulation applications.

bioengineering↗

bioRxiv2022

Long-term effect of forest harvesting on boreal species assemblages under climate change

Logging is the main human disturbance impacting biodiversity in forest ecosystems. However, the impact of forest harvesting on biodiversity is modulated by abiotic conditions through complex relationships that remain poorly documented. Therefore, the interplay between forest management and climate change can no longer be ignored. Our aim was to study the expected long-term variations in the assemblage of bird and beetle communities following modifications in forest management under different climate change scenarios. We developed species distribution models to predict the occurrence of 87 species of birds and beetles in eastern Canadian boreal forests over the next century. We simulated three climate scenarios (baseline, RCP4.5 and RCP8.5) under which we varied the level of harvesting. We also analyzed the regional assemblage dissimilarity by decomposing it into balanced variations in species occupancy and occupancy gradient. We predict that forest harvesting will alter the diversity by increasing assemblage dissimilarity under all the studied climate scenarios, mainly due to species turnover. Species turnover intensity was greater for ground-dwelling beetles, probably because they have lower dispersal capacity than flying beetles or birds. A good dispersal capacity allows species to travel more easily between ecosystems across the landscape when they search for suitable habitats after a disturbance. Regionally, an overall increase in the probability of occupancy is projected for bird species, whereas a decrease is predicted for beetles, a variation that could reflect differences in ecological traits between taxa. Our results further predict a decrease in the number of species that increase their occupancy after harvest under the most severe climatic scenario for both taxa. We anticipate that under severe climate change, increasing forest disturbance will be detrimental to beetles associated with old forests but also with young forests after disturbances.

ecology↗

bioRxiv2022

Effects of global change on animal biodiversity in boreal forest landscape: an assemblage dissimilarity analysis

Despite an increasing number of studies highlighting the impacts of climate change on boreal species, the main factors that will drive changes in species assemblages remain ambiguous. We quantify two climate-induced pathways based on direct and indirect effects on species occupancy and assemblage dis-similarity under different harvest management scenarios. The direct climate effects illustrate the impact of climate variables while the indirect effects are reflected through the changes in land cover composition. To understand the main causes in assemblage dissimilarity, we analyze the regional and the latitudinal species assemblage dissimilarity by decomposing it into balanced variation in species occupancy and occurrence and occupancy and occurrence gradient. We develop empirical models to predict the distribution of more than 100 bird and beetle species in the Cote-Nord region of Quebec over the next century. Our results show that the two pathways are complementary and alter biodiversity, mainly caused by balanced variation in species occupancy and occurrence. At the regional scale, both effects have an impact on decreasing the number of winning species. Yet, responses are much larger in magnitude under mixed climate effects (a mixture of direct and indirect effects). Regional assemblage dissimilarity reached 0.77 and 0.69 under mixed effects versus 0.09 and 0.10 under indirect effects for beetles and birds, respectively, between RCP8.5 and baseline climate scenarios when considering harvesting. Therefore, inclusion of climatic variables considers aspects other than just those related to forest landscapes, such as life cycles of animal species. Latitudinally, assemblage dissimilarity increased following the climate conditions pattern. Our analysis contributes to the understanding of how climate change alters biodiversity by reshaping community composition and highlights the importance of climate variables in biodiversity prediction.

ecology↗

bioRxiv2021

Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes

Mapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.

neuroscience↗

bioRxiv2018

The River Runs Through It: the Athabasca River Delivers Mercury to Aquatic Birds Breeding Far Downstream

This study examined factors contributing to temporal variability (2009-2017) in total mercury (THg) concentrations in aquatic bird eggs collected in the Peace-Athabasca Delta and Lake Athabasca in northern Alberta. Factors examined included annual changes in oil sands production, bird diets, forest fires, and flow of the Athabasca River. Surface mining activities associated with Albertas Athabasca oil sands are centered north of Fort McMurray, Alberta, adjacent to the northward-flowing Athabasca River. Previous studies have found that oil sands industrial operations release mercury into the local (within ~50 km) environment. However, temporal trends in egg THg levels did not track trends in synthetic oil production from the oil sands. Intraspecific fluctuations in bird diet also could not explain annual variability in egg THg levels. Annual extent of forest fires in Alberta was only related to egg THg concentrations in California Gulls from Lake Athabasca; annual levels in other species showed no relationship with fire extent. The inclusion of more terrestrial foods in gull diets may have contributed to this difference. For the majority of species, annual fluctuations in maximal flow of the Athabasca River were important in influencing annual egg THg levels. Eggs collected following years of high flow had higher THg concentrations with distinct stable Hg isotope compositions. Riverine processes associated with suspended sediment were likely critical in regulating Hg availability to nesting birds. This study highlights the importance of the Athabasca River as a conduit for Hg transport to ecologically-sensitive downstream ecosystems such as the Peace-Athabasca Delta and Wood Buffalo National Park (a UNESCO World Heritage Site). Human activities that increase atmospheric Hg deposition to the Athabasca River watershed, or that enhance Hg releases to the river through erosion of Hg-bearing soils, will likely increase the availability of Hg to organisms inhabiting downstream areas.

pharmacology and toxicology↗

bioRxiv2018

Pixel: a digital lab assistant to integrate biological data in multi-omics projects

BackgroundIn biology, high-throughput experimental technologies, also referred as "omics" technologies, are increasingly used in research laboratories. Several thousands of gene expression measurements can be obtained in a single experiment. Researchers are routinely facing the challenge to annotate, store, explore and mine all the biological information they have at their disposal. We present here the Pixel web application (Pixel Web App), an original content management platform to help people involved in a multi-omics biological project. MethodsThe Pixel Web App is built with open source technologies and hosted on the collaborative development platform GitHub (https://github.com/Candihub/pixel). It is written in Python using the Django framework and stores all the data in a PostgreSQL database. It is developed in the open and licensed under the BSD 3-clause license. The Pixel Web App is also heavily tested with both unit and functional tests, a strong code coverage and continuous integration provided by CircleCI. To ease the development and the deployment of the Pixel Web App, Docker and Docker Compose are used to bundle the application as well as its dependencies. ResultsThe Pixel Web App offers researchers an intuitive way to annotate, store, explore and mine their multi-omics results. It can be installed on a personal computer or on a server to fit the needs of many users. In addition, anyone can enhance the application to better suit their needs, either by contributing directly on GitHub (encouraged) or by extending Pixel on their own. The Pixel Web App does not provide any computational programs to analyze the data. Still, it helps to rapidly explore and mine existing results and holds a strategic position in the management of research data.

bioinformatics↗