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Beaulieu, M.

Publications and source records attributed to Beaulieu, M..

13 recordsLinked to original sources

Sedimentary ancient DNA analysis from the Iron Age courtyard and cooking pit site of Rodskjaer in Troms, Northern Norway

Courtyard sites, which are Iron Age structures unique to Norway, are often associated with cooking pit fields suggesting feasting practices, but little is known about the main purpose of these sites. To address this, a framework for sedimentary ancient DNA (sedaDNA) metabarcoding sampling was undertaken at the site of Rodskjaer, northern Norway. Of the 63 sediment samples from cooking pits, fire pits, a hearth, a fireplace, the natural shell-sand and topsoil, 52 successfully detected plant and animal sedaDNA. The plant diversity was high with 41-100 taxa. SedaDNA identified archaeologically significant taxa that were not detected by other methods, including Avena (oats), Quercus (oak), Equus (horse), and Salmo salar (salmon). Additionally, from inter-sample comparison, and with reference to worm sedaDNA we identified the archaeological contexts that were affected by partial bioturbation and root penetration that restricted interpretation of spatial or temporal differences in use of these features. This pioneering study shows the importance of taking many samples from modern and natural sediments as well as using multi-proxy analysis when conducting sedaDNA metabarcoding studies at open-air archaeological sites. If these factors are taken into consideration, sedaDNA from cooking pits can be a valuable resource for investigating uses of courtyard and cooking pit field sites.

genetics↗

The Muskox Way: Humans, plants and animals in northeast Greenland through the Holocene

The Muskox Way hypothesis suggests that the first humans entering northeast Greenland from Arctic Canada followed and hunted muskox. Yet whether muskox arrived before people remains debated, as only two bones predate the Independence culture (4500-3900 cal BP). More broadly, the arrival of plants and animals, and how the three periods of human settlement related to ecosystem changes, remain poorly understood. We analysed sedimentary ancient DNA from lakes in Wandel Dal (Late Sommersoe and Midsommersoe) and Zackenberg, identifying 121 native plants and nine animal taxa. In Wandel Dal, the plant assemblage indicates a warmer climate than today about 8200-3900 years ago, followed by an abrupt change in flora and sedimentation rate at 3900 cal BP, especially at Midsommersoe. Muskox DNA is present continuously at Midsommersoe from 7400 cal BP, about three millennia before humans arrived. The Zackenberg record dates to 12,200 cal BP, with arctic forbs, grasses, ferns and crowberry in the earliest layers, willow from 8200 cal BP and birch from 7200 cal BP, but muskox only in the last 2500 years, the latter period coinciding with Greenlandic Dorset culture. The arrival of the Thule culture in 1400 CE coincides with a slight increase in plant richness at Wandel Dal and an increase in mammal detections. Reindeer occurred only in samples older than 6000 years, consistent with their absence from archaeological bone records. Overall, humans arrived long after the first megafauna and appear to have had limited impact on their populations, although cultural periods coincided with environmental changes.

ecology↗

Dynamic sedimentary ancient DNA models of Fennoscandic Holocene plant communities reveal the role of temperature and competition

Ecosystems are constantly responding to shifting environmental conditions, and the observed structure of ecological communities at any given discrete observation timepoint is part of a larger dynamic response. However, we lack long-term time series of ecosystem responses allowing understanding of the processes driving community dynamics. Sedimentary ancient DNA (sed aDNA) offers novel opportunities to link empirical data with ecological processes, providing near continuous records of plant and animal community changes over millennia. Here, we analyzed metabarcoding data from 10 lakes from Northern Fennoscandia characterizing plant and mammal communities at temporal resolution of 100 years over several millenia. We used sed aDNA data to test how biotic processes, including temperature-dependent plant growth, competition, shading, and herbivory, may have driven the dynamics of Fennoscandic Holocene plant communities since the Last Glacial Maximum. We compared the explanatory power of ordinary differential equation-based models simulating community changes and including these processes. The fit of the models improved with the consideration of temperature dependent densification and biotic interactions, most notably shading. When considering individual taxa, the importance of shading and herbivory was greatest for the dwarf shrubs, while tree and shrub taxa were more often best predicted by models without competition. Our study demonstrates how using sed aDNA time series together with process-based inverse modelling can uncover the mechanisms of species response to climate change, offering potential for more realistic predictions.

ecology↗

The analysis of a large dataset of PCR-test results in the community reveals the impact of age, variants and vaccination status on SARS-CoV-2 viral dynamics

The COVID-19 pandemic has shown the value of large-scale community PCR tests for epidemic surveillance, but the viral load measurements they provide have seldom been exploited to reconstruct within-host trajectories. Because these data are collected for diagnostic rather than research purposes, they are characterized by sparse longitudinal follow-up, heterogeneous sampling, and missing metadata, raising uncertainty about their usefulness to reconstruct with-host viral dynamics. We first conducted a simulation study to assess the feasibility of estimating the viral dynamics patterns from such datasets. Across multiple scenarios replicating realistic sampling patterns, we found that peak viral load and clearance time could be estimated with good accuracy, although uncertainty tended to be underestimated. Parameters driving early viral kinetics, e.g. incubation and proliferation time, were mostly estimated with poor precision, as most community tests are conducted after symptom onset, later in infection. We then applied this framework to a large dataset of 322,218 PCR tests associated with symptomatic SARS-CoV-2 infections in France between July 2021 and March 2022, encompassing both Delta-variant circulation and the emergence of first Omicron variants. We quantified the effects of age, vaccination, and variants on viral load trajectories. Age [≥]65 years was consistently associated with longer clearance time, extending the duration of detectable viral load by 2 to 6 days. Vaccination shortened the clearance time by 2 to 4 days but had minimal impact on peak viral load. Infections by Omicron-variants were associated with a lower peak viral load and shorter clearance times compared with pre-Omicron (Delta) infections. Thus, community PCR tests can be leveraged to identify key parameters of viral dynamics. As multiplex PCR testing becomes increasingly widespread, establishing robust frameworks for data collection, sharing, and privacy protection will be essential to support the use of these data. Author SummaryIn this study, we explored whether viral load data collected routinely in community laboratories can help us understand how factors like age, vaccination, and viral variant influence the course of infection. These data, collected for diagnostic purposes rather than research, are large but often incomplete, with most individuals tested only after the time of symptoms onset. We first used simulations to assess whether, despite these limitations, key aspects of viral dynamics can be reliably estimated. We then applied our approach to millions of test results collected in France during periods dominated by Delta and Omicron variants. We found that older age was consistently associated with longer infection duration, while vaccination reduced the time the virus remained detectable without affecting peak viral levels. Omicron infections were generally associated with lower peak viral load and somewhat faster clearance than pre-Omicron infections. Overall, our work demonstrates that community testing data, can provide valuable insights into viral dynamics and help monitor the effects of new variants or interventions. As multiplex tests become more common, facilitating and improving data collection, sharing, and privacy protection will be essential to make the most of these resources in future outbreaks.

systems biology↗

Flexible foraging effort shapes Adelie penguin reproductive success across Antarctica and sea ice conditions

Understanding how species deal with diverse environmental conditions is crucial for predicting their future responses to climate change. In Antarctica, changing sea ice dynamics threaten ice-dependent species. Whilebehavioural adjustmentscould help mitigate these threats, their effectiveness under future environmental conditions and potential thresholds remain unclear. Long-term studies and circumpolar approaches could address this challenge. Our 15-year study (2010-2024) of over 23,000 foraging trips from Adelie penguins (Pygoscelis adeliae) in East Antarctica, identified a non-linear relationship between sea ice concentration (SIC) and foraging effort when landfast ice was absent, a situation anticipated to define the species future habitat during chick-rearing. Minimal effort occurred at 10-20% SIC, but more than doubled with the presence of landfast ice or heavy pack-ice, with females showing greater sensitivity to these ice changes. Acircumpolar analysis of similar data demonstrated that foraging effort during chick-guarding predicted reproductive success across ten Adelie penguin populations. Reproductive success remained high until foraging trips exceeded approximately 29 hours, after which performance declined sharply. This indicates that while behavioural flexibility can buffer against moderate environmental changes, it has clear limits. Our findings establish foraging trip duration as a valuable early warning indicator for population responses to environmental change.

ecology↗

Declining juvenile survival of Adelie penguins in Antarctica

As summer sea ice around Antarctica reaches modern lows, quantifying the demographic response of polar species to such environmental changes becomes critical. To achieve this, synthesizing results across species ranges and elucidating the environmental factors driving population dynamics are key. Adelie penguins are considered reliable indicators of changes in Antarctica but the processes through which sea ice and other environmental factors shape their population dynamics are still unclear, especially for critical age groups such as juveniles. Using a 17-year dataset of Adelie penguins electronically tagged in Adelie Land (Antarctica), we found that juvenile survival probability was most impacted by sea ice concentration near their natal colony right after fledging, with lower ice concentrations detrimental to survival. Importantly, we found that juvenile survival declined by 32% from 2007 to 2020, mirroring trends at other distant colonies. The emergence of similar patterns at opposite ends of the continent may be an early signal for shifts in population trends expected from climate change.

ecology↗

A miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing

Genome-Wide-Association studies have involved miR-137 in schizophrenia. However, the biology underlying this statistical evidence is unclear. Statistical polygenic risk for schizophrenia is associated with working memory, while other biological evidence involves miR-137 in emotion processing. We investigated the function of miR-137 target schizophrenia risk genes in humans. We identified a prefrontal co-expression pathway of schizophrenia-associated miR-137 targets and validated the association with miR-137 expression in neuroblastoma cells. Alleles predicting greater co-expression of this pathway were associated with greater prefrontal activation during emotion processing in two independent cohorts of healthy volunteers (N1=222; N2=136). Statistical polygenic risk for schizophrenia was instead associated with prefrontal activation during working memory. A co-expression pathway links miR-137 and its target genes to emotion processing and risk for schizophrenia. Low prefrontal miR-137 expression may be related with SCZ risk via increased expression of target risk genes, itself associated with increased prefrontal activation during emotion processing.

neuroscience↗

Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells

Mitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.

neuroscience↗

A non-linear relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin

We investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule {beta}2-arrestin is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and on survival of adult-born granule cells are absent in the {beta}2-arrestin knockout ({beta}2-Arr KO) mice. To our surprise fluoxetine induced a dramatic upregulation of doublecortin (DCX) in the {beta}2-Arr KO mice, indicating that DCX expression can be increased even though AHN is not. We discovered two other conditions where DCX expression is regulated non linearly compared to levels of AHN: a chronic stress model where DCX is upregulated and an inflammation model where DCX is down regulated. We conclude that assessing DCX expression alone to quantify levels of AHN can be misleading and that caution should be applied when label retention techniques are not available. HIGHLIGHTSO_LI{beta}2-arrestin ({beta}-Arr2) is required for the antidepressant-like effects of fluoxetine. C_LIO_LIA dramatic upregulation of doublecortin (DCX) is observed in the {beta}2-Arr KO mice after antidepressant treatment whereas its effects on proliferation of neural progenitors and on survival of adult-born granule cells are absent. C_LIO_LIDCX is more upregulated than the number of young neurons in a mouse model of depression. C_LIO_LIDCX is more down regulated than the number of young neurons in a model of inflammation. C_LIO_LImicroRNAs (miRs) may contribute to the regulation of DCX mRNA expression. C_LI

neuroscience↗

Groucho/TLE opposes axial to hypaxial motor neuron development

Spinal cord motor neuron diversity and the ensuing variety of motor circuits allow for the processing of elaborate muscular behaviours such as body posture and breathing. Little is known, however, about the molecular mechanisms behind the specification of axial and hypaxial motor neurons controlling postural and respiratory functions respectively. Here we show that the Groucho/TLE (TLE) transcriptional corepressor is a multi-step regulator of axial and hypaxial motor neuron diversification in the developing spinal cord. TLE first promotes axial motor neuron specification at the expense of hypaxial identity by cooperating with non-canonical WNT5A signalling within the motor neuron progenitor domain. TLE further acts during post-mitotic motor neuron diversification to promote axial motor neuron topology and axonal connectivity whilst suppressing hypaxial traits. These findings provide evidence for essential and sequential roles of TLE in the spatial and temporal coordination of events regulating the development of motor neurons influencing posture and controlling respiration. HIGHLIGHTSO_LIGroucho/TLE mediates non-canonical WNT signalling in developing motor neurons C_LIO_LINon canonical WNT:TLE pathway regulates thoracic motor neuron diversification C_LIO_LITLE promotes axial while inhibiting hypaxial motor neuron development C_LIO_LITLE influences developing motor neuron topology and muscle innervation C_LI IN BRIEFSalin-Cantegrel et al use in ovo engineered approaches to show that a non-canonical WNT:TLE pathway coordinates temporally and spatially separated elements of motor neuron diversification, repressing hypaxial motor neuron development to promote the axial fate. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/986323v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@e2d96dorg.highwire.dtl.DTLVardef@130baf4org.highwire.dtl.DTLVardef@41fa32org.highwire.dtl.DTLVardef@190ebd3_HPS_FORMAT_FIGEXP M_FIG TLE contribution to the development of thoracic somatic motor columns Progenitor cells in the ventral pMN domain are exposed to higher concentrations of non-canonical WNTs and express more TLE. Cooperation of non-canonical WNTs and TLE renders ventral pMN progenitors refractory to a respiratory MN fate, thereby contributing to the separation of MMC and RMC MN lineages. Differentiating MNs that maintain high TLE expression also maintain LHX3 expression, adopt axial motor neuron topology and connect to axial muscles. TLE activity in differentiating MMC MNs prevents the acquisition of respiratory MN topology and innervation traits. C_FIG

neuroscience↗

Robust Production of Uniform Human Cerebral Organoids from Pluripotent Stem Cells

Human cerebral organoid (hCO) models offer the opportunity to understand fundamental processes underlying human specific cortical development and pathophysiology in an experimentally tractable system. While diverse methods to generate brain organoids have been developed, a major challenge has been the production of organoids with reproducible cell type heterogeneity and macroscopic morphology. Here, we directly addressed this problem by establishing a robust production pipeline to generate morphologically consistent (ie uniform) hCOs and achieve a success rate of >80%. These hCOs include both a radial glial stem cell compartment and electrophysiologically competent mature neurons. Moreover, we show using immunofluorescence microscopy and single cell profiling, that individual organoids display reproducible cell type compositions that are conserved upon extended culture. We expect that application of this method will provide new insights into brain development and disease processes.

neuroscience↗

Differential oxidative costs of locomotory and genital damage in an orb-weaving spider

In animals that regularly experience tissue loss, physiological responses may have evolved to overcome the related costs. Changes in oxidative status may reflect such self-maintenance mechanisms. Here, we investigated how markers of oxidative status varied in female orb-weaving spiders (Larinia jeskovi) by mimicking two distinct types of tissue loss they may naturally encounter: damage to their locomotory system and damage to their external genital structure, as inflicted by males to females during copulation (external female genital mutilation). Damage to the locomotory system resulted in a significant shift in the oxidative status reflecting investment into self-maintenance. In contrast, the loss of the genital structure did not result in quantitative changes of oxidative markers. The lack of response to genital mutilation suggests that genital mutilation is physiologically not costly for female spiders. The cost incurred to females rather arises from genital mutilation preventing the females from remating with another male.

evolutionary biology↗

CRISPR/Cas9 mediated intersectional knockout of GSK3β in D2 receptor expressing mPFC neurons reveals contributions to emotional regulation

BackgroundGlycogen synthase kinase 3{beta} (GSK3{beta}) regulates neurodevelopment, synaptic plasticity as well as mood, cognition, social interaction, and depressive-like behaviors. Inhibition of GSK3{beta} is a shared consequence of treatment by lithium, SSRIs, ketamine and antipsychotics. GSK3{beta} activity is regulated by dopamine D2 receptor signaling and can be inhibited by psychoactive drugs in a D2 receptor dependent manner. Functions of GSK3{beta} in striatal D2 neurons has been studied extensively. However, GSK3{beta} is ubiquitously expressed in the brain and D2 receptor expressing cells are distributed as a mosaic in multiple cortical regions. This complicates the interrogation of GSK3{beta} functions in cortical D2 cells in a circuit defined manner using conventional animal models.\n\nMethodsWe have used a CRISPR/Cas9 mediated intersectional approach to achieve targeted deletion of GSK3{beta} in D2 expressing neurons of the adult medial prefrontal cortex (mPFC).\n\nResultsIsolation and analysis of ribosome associated RNA specifically from mPFC D2 neurons lacking GSK3{beta} demonstrated large scale translatome alterations. Deletion of GSK3{beta} in mPFC D2 neurons revealed its contribution to anxiety-related, cognitive, and social behaviors.\n\nConclusionsOur results underscore the viability of intersectional knockout approach to study functions of a ubiquitous gene in a network defined fashion while uncovering a contribution of GSK3{beta} expressed in mPFC D2 neurons in the regulation of behavioral dimensions related to mood and emotions. This advances our understanding of GSK3{beta} action at a brain circuit level and can potentially lead to the development of circuit selective therapeutics.

neuroscience↗