Biology subjects

Jacob, S.

Publications and source records attributed to Jacob, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Enhancing Germination and Assessing the Longevity of Native Plants' Seeds with Dormancy through Different Priming Techniques

Vachellia pachyceras and Convolvulus oxyphyllus are native species of arid and semi-arid desert regions, including Kuwait. They are inherently adapted to extreme conditions characterized by high temperature, prolonged drought and limited rainfall. They contribute significantly, to restore the ecosystem by providing food and shelter for wildlife. Despite their ecological importance, seed germination in both species is constrained by dormancy, and natural recruitment of seedlings is limited by narrow and unpredictable rainfall windows, severely restricting opportunities for establishment. In this context, seed priming is an effective pre-sowing technique that enables uniform and rapid germination within the short window of favorable conditions. This study aims to identify the optimal seed-priming techniques for these two keystone native species and to assess the effect of priming on seed longevity. The seeds were scarified to remove the physical dormancy prior to priming treatments. Relative seed longevity was measured for primed seeds through artificial ageing and analyzed using probit analysis and analysis of variance. Results showed that hormonal priming [(mechanical scarification + 100 ppm gibberellic acid (GA3)] for six hours and hydropriming (mechanical scarification + soaking in water) for 8 hours (h) were effective treatments among the tested priming treatments for V. pachyceras. The estimated p50 value (i.e., number of days to lose seed viability to 50%) was 22 days for hormonal priming and 21 days for hydropriming. Mechanical scarification followed by one and half hour of hydropriming was the most effective in C. oxyphyllus (p50 = 74 days). Based on these results, the longevity of V. pachyceras and C. oxyphyllus could be considered medium. Further studies are needed to determine the effectiveness of seed priming on additional ecologically and economically important native species to achieve success in revegetation programs.

ecology↗

bioRxiv2025

Environmental complexity constrains evolutionary adaptation across taxa

Complex environments combining multiple stressors are the new norm worldwide. Adaptive evolution will be critical to population persistence under these combined challenges, but how environmental complexity affects the pace of evolution remains poorly understood. Using a meta-experimental evolution approach, we exposed 14 species, from bacteria to unicellular eukaryotes and plants, to single stressors and their pairwise combinations for multiple generations, while keeping the overall stress level comparable. Populations evolving under combined stressors tended to have lower fitness increase in the selective environments, higher fitness reductions in the control environment, and shallower relation between initial maladaptation and fitness gain, than under single stressors. However, these responses varied with species and stressor type. Accounting for such constraints on evolutionary dynamics should prove crucial for the management of biodiversity. Significance StatementA pressing challenges for modern science and society in the face of ongoing global change is understanding what limits the capacity of living organisms to adapt to complex environments combining multiple stressors. To answer to this question, we conducted a large-scale meta-experimental evolution design across a diversity of organisms, exposing them for multiple generations to either single or combined-stress treatments. Combined stressors led to less adaptive fitness gain than single stressors, and imposed additional costs through reduced fitness in non-stressful conditions. This unique combination of meta-experimental approach with a careful distinction between environmental complexity and overall stress allowed us to gain robust quantitative evidence on how environmental complexity can impact the pace of evolution.

evolutionary biology↗

bioRxiv2025

Inoculation of indigenous nitrogen-fixers isolated from the Kuwait desert enhances seedling growth and nutrient uptake in a greenhouse bioassay

Desert soil degradation, primarily caused by anthropogenic disturbance and desertification, poses significant challenges for ecosystem restoration in degraded ecosystems. Soil microbial communities, particularly diazotrophs, play a crucial role in different soil system processes, including nutrient cycling, and can improve nitrogen-limited characteristics of nutrient-poor soil systems. Free-living and root-associated nitrogen-fixing bacteria have great potential to enhance nitrogen availability in the nitrogen-limited soil and support host plant growth and nutrient acquisition. Free-living nitrogen-fixing bacteria and root-associated rhizobacteria contribute a substantial amount of nitrogen to ecosystems, including arid lands. This study evaluated the growth performance and nutrient uptake ability of four native plant species of Kuwait inoculated with a consortium of selected indigenous putative diazotrophs isolated from the Kuwait desert. The seedlings of Vachellia pachyceras were inoculated with both indigenous root-nodule bacteria isolated from Kuwait desert and a commercial inoculum to evaluate their symbiotic efficiency. The seedlings were cultivated under greenhouse conditions in both native desert soils and in potting mix to assess the extent to which growth medium influenced inoculation response. The primary objective was to determine whether the inoculated indigenous N2 fixing bacteria could contribute early seedling development and nutrient acquisition, thereby supporting their potential use them as biofertilizer in future large-scale restoration efforts. Bacterial inoculation significantly enhanced plant dry mass and nutrient uptake across all tested plant species compared to the non-inoculated controls. The magnitude of improvement varied with bacterial density, plant species, and growth medium used. These findings are consistent with evidence that isolated indigenous N2-fixers have the potential to enhance plant growth and nutrient uptake in selected native plant species, supporting their use as biofertilizers for restoration and revegetation efforts in arid environments. This study represents the first evaluation of Kuwaits native seedlings inoculated with indigenous diazotrophs, highlighting their potential for sustainable ecosystem restoration.

ecology↗

bioRxiv2025

Oncogenic Ppm1d mutations deregulate the p53 pathway in primary mouse gliomas

Importance of StudyProtein phosphatase magnesium-dependent 1D (PPM1D) is frequently mutated in diffuse midline gliomas (DMGs). DMGs are rare pediatric brain tumors with limited treatment options. Due to the cancers rapid progression, patients usually survive 12-24 months after diagnosis. This underscores the critical need to better understand the molecular mechanisms driving DMGs. This study describes a novel mouse model that provides a powerful platform to investigate PPM1D-driven tumor biology and offers mechanistic insights into disease development and progression. Furthermore, it serves as a valuable preclinical system for evaluating therapeutic strategies and identifying translational opportunities to target Ppm1d-mutant tumors. BackgroundDiffuse midline gliomas (DMGs) are incurable brain tumors with limited treatment options. Approximately 20% of DMGs harbor truncating mutations in exon 6 of phosphatase PPM1D, which stabilize the protein and deregulate p53 signaling. However, the consequences of these mutations for tumor initiation, progression, and therapy remain unclear. MethodsWe developed a conditional Ppm1d-loxP-exon6-loxP-exon6-E518X-tag mouse allele (Ppm1d-flex-6) that enables lineage-, spatial-, and temporal-specific expression of a DMG-derived truncated Ppm1d protein from its endogenous locus in the presence of Cre-recombinase. Ubiquitous activation of mutant Ppm1d was modeled using the Meox2-Cre driver, and primary gliomas were modeled using the RCAS/tv-a system to introduce Cre and PDGFB co-drivers into Nestin-positive neural stem cells. Complementary studies were performed in mouse embryonic fibroblasts (MEFs) expressing truncated Ppm1d following Cre recombination. ResultsWhile Meox2-Cre-driven ubiquitous recombination of Ppm1d-flex-6 produced muted phenotypes, Ppm1d-flex-6 recombination in Nestin+ neural stem cells accelerated gliomagenesis. Its oncogenic effect was weaker than complete p53 loss, and it did not accelerate tumorigenesis further in p53-null tumors. Single-cell RNA-sequencing revealed that Ppm1d-flex-6 gliomas adopt more progenitor-like transcriptional states and upregulate p53- and cell cycle associated pathways. In MEFs, Ppm1d-flex-6 enhanced proliferation and shifted transcriptomic programs toward MAPK and PI3K-Akt signaling, while impairing DNA damage responses, including reduced {gamma}-H2AX induction after irradiation. These defects sensitized cells to radiation and decreased clonogenic survival after ionizing radiation and PARP inhibition. ConclusionsPpm1d mutations confer intermediate suppression of the p53 pathway, consistent with the clinical features of PPM1D-mutant DMGs and are associated with radiosensitivity and PARP inhibitor vulnerability.

genetics↗

bioRxiv2025

Central carbon metabolism switching in lytic versus temperate coral reef viral communities

Coral reefs are declining globally due in part to bacterial overgrowth, a process known as microbialization. However, the role of bacteriophages that may inhibit microbialization by infecting and killing these bacteria remains poorly understood, especially their metabolic impacts on bacterial proliferation. To address this, we analyzed central carbon metabolism gene frequencies in viral communities from healthy (lytic-dominated) and degraded (temperate-dominated) Central Pacific coral reefs. We found that viral metabolism shifted broadly from being dominated by metabolism that builds up pools of central intermediates on degraded reefs dominated by temperate viral infection ("anaplerotic" reactions) to metabolism that consumes these pools to prioritize production of metabolic precursors for virion construction on healthy reefs dominated by lytic infection ("cataplerotic" reactions). This switch was shown by the over-representation of Entner-Doudoroff (ED) glycolysis genes on degraded, temperate-dominated reefs and of pentose phosphate pathway (PPP) and reductive tricarboxylic acid cycle (TCA) genes on healthy, lytic-dominated reefs. As a result of this metabolic dichotomy, our qualitative compartment modeling revealed two distinct ecosystem states: (i) healthy reefs, where lytic viral metabolism enhances viral production and suppresses bacterial overgrowth, and (ii) degraded reefs, where temperate viral metabolism accelerates bacterial proliferation. Because viral switching between lytic and temperate lifestyles is a known function of host physiological state, these findings position viral metabolism as both a driver of reef decline and a conservation lever, with metabolically mediated "re-viralization" offering a novel strategy to restore reef resilience.

ecology↗

bioRxiv2025

Circadian rhythms and the light-dark cycle interact to regulate amyloid plaque accumulation and tau phosphorylation in 5xFAD mice

BackgroundCircadian disruption has long been appreciated as a downstream consequence of Alzheimers Disease in humans. However, an upstream role for behavioral circadian disruption in regulating AD pathology remains an open question. MethodsTo determine the role of the central circadian clock in the suprachiasmatic nucleus (SCN) in regulating amyloid pathology, we generated mice harboring deletion of the critical clock gene Bmal1 in GABAergic neurons using VGAT-iCre, which is expressed in >95% of SCN cells, and crossed this line to the 5xFAD amyloid mouse model. To examine the role of the light-dark cycle in this process, we aged these mice in either regular 12:12 light-dark (LD) or constant darkness (DD) conditions. Transcriptional, behavioral, and physiological rhythms were examined in VGAT-iCre; Bmal1fl/fl; 5xFAD (VGAT-BMAL1KO;5xFAD) mice under varying light conditions. Amyloid plaque deposition, peri-plaque tau phosphorylation, glial activation, and transcriptomic changes were examined. ResultsVGAT-BMAL1KO;5xFAD mice showed loss of SCN BMAL1 expression and severe disruption of behavioral rhythms in both LD and DD, with loss of day-night rhythms in consolidated sleep and blunting of rhythmic clock gene expression in the brain. Surprisingly, VGAT-BMAL1KO;5xFAD mice kept under LD showed reduced total plaque accumulation and peri-plaque tau phosphorylation, compared to Cre-negative controls. These changes were gated by the light-dark cycle, as they were absent in VGAT-BMAL1KO;5xFAD mice kept in DD conditions. Total plaque accumulation was also reduced in control 5xFAD mice kept in DD as compared to LD, suggesting a general effect of light-dark cycle on amyloid aggregation. Expression of murine presenilin 1 (Psen1), as well as amyloidogenic cleavage of amyloid precursor protein, were suppressed in VGAT-BMAL1KO;5xFAD specifically under LD conditions. ConclusionsIn 5xFAD mice, the central circadian clock and the light-dark cycle interact to regulate amyloid pathology. Disruption of the central clock in the presence of a light-dark cycle may reduce APP cleavage and plaque formation. These results call into question the proposed simple positive feedback loop between circadian rhythm disruption and Alzheimers Disease pathology.

neuroscience↗

bioRxiv2024

One Health in Eastern Africa: No barriers for ESBL producing E. coli transmission or independent antimicrobial resistance gene flow across ecological compartments

The One Health paradigm considers the interdependence of human, animal and environmental health. In high-income countries, limited evidence has been found from recent studies to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, and we are all interconnected it would be important to know if closer interaction of humans with animals and the environment in low-income present a contrasting picture. We used whole genome sequencing to investigate the genomic diversity and to infer transmission of extended spectrum beta-lactamase producing Escherichia coli (ESBL-Ec) between different ecological niches (humans, animals and the environment). We found high diversity of ESBL-Ec with 172 genomic clusters and 167 sequence types identified from 2,344 genomes. Common ESBL genes, blaCTX-M-15 (67.6%) and blaCTX-M-27 (14.2%) were carried on a complex network of different plasmids, presenting multiple pathways for dissemination and revealing the high force of selection. Using fine-scale genomic clustering across multiple thresholds ranging from 0 to 20 single nucleotide polymorphisms, we found that genomes isolated from humans, animals and the environment formed overlapping clusters, indicating recent ESBL-Ec transmission and co-circulation both within and between ecological compartments. These findings demonstrate that the One Health approach is highly relevant to tackling AMR in low-income settings, and therefore critical to consider if we are to address the rise of AMR globally.

genomics↗

bioRxiv2023

The macronuclear genomic landscape within Tetrahymena thermophila

The extent of intraspecific genomic variation is key to understanding species evolutionary history, including recent adaptive shifts. Intraspecific genomic variation remains poorly explored in eukaryotic microorganisms, especially in the nuclear dimorphic ciliates, despite their fundamental role as laboratory model systems and their ecological importance in many ecosystems. We sequenced the macronuclear genome of 22 laboratory strains of the oligohymenophoran Tetrahymena thermophila, a model species in both cellular biology and evolutionary ecology. We explored polymorphisms at the junctions of programmed eliminated sequences, and reveal their utility to barcode very closely related cells. As for other species of the genus Tetrahymena, we confirm micronuclear centromeres as gene diversification centres in T. thermophila, but also reveal a two-speed evolution in these regions. In the rest of the genome, we highlight recent diversification of genes encoding for extracellular proteins and cell adhesion. We discuss all these findings in relation with ciliates ecology and cellular characteristics. Impact StatementThis is the first study of population genomics in the ciliate Tetrahymena thermophila. This bacterivore species plays an important role in aquatic trophic chains and is widely used as a model in cell and molecular biology, ecology, evolution or toxicology. As all ciliates, it contains a germline micronucleus and a somatic macronucleus. Sequencing of the macronucleus reveals that the centromeric region of the micronucleus are simultaneously a region of new gene diversification, as observed in other Tetrahymena species, and a region containing highly conserved genes. The results also confirm that the formation of the macronucleus from the micronucleus is highly imprecise. Interestingly, this process generates a genomic barcode that can discriminate cells derived from a given sexual reproduction event, allowing to study more finely population dynamics/history in nature. Data summaryAll data are fully provided in Supplementary Materials. The raw data of the 22 Tetrahymena genomes have been deposited in the Sequence Read Archive (https://www-ncbi-nlm-nih-gov.inee.bib.cnrs.fr/bioproject/PRJNA1012331). Accession numbers are listed in Table S1 (available in the online version of this article).

genomics↗

bioRxiv2023

An array of signal-specific MoYpd1 isoforms determines full virulence in the pathogenic fungus Magnaporthe oryzae

Magnaporthe oryzae is placed first on a list of the worlds top ten plant pathogens with the highest scientific and economic importance. The pathogen is highly evolved to sense environmental changes quickly to invade different tissues of its host plant successfully. Here, we found alternative splicing (AS) as a previously unknown mechanism of how the pathogen may handle rapidly changing situations during in planta growth. The AS facilitates the production of multiple mRNAs and, consequently, protein isoforms with distinct biological functions from a single gene. The locus MGG_07173 occurs only once in the genome of M. oryzae and encodes the phosphotransfer protein MoYpd1p, which plays an important role in the high osmolarity glycerol (HOG) signaling pathway for osmoregulation. Originating from this locus, at least three MoYPD1 isoforms are produced in a signal-specific manner. The transcript levels of these MoYPD1-isoforms were individually affected by external stress, which is equally present in host plant tissues. Potassium salt (KCI) stress raised MoYPD1_T0 and MoYPD1_T2 abundance, whereas osmotic stress by sorbitol elevates MoYPD1_T1 levels. In line with this, signal-specific nuclear translocation of green fluorescent protein-fused MoYpd1p isoforms in response to stress was observed. The protein isoforms MoYpd1p_T0 and MoYpd1p_T2 were detected in the nucleus following KCl treatment, whereas MoYpd1p_T1 did likewise upon sorbitol stress. Mutant strains that produce only one of the MoYpd1p isoforms are less virulent, suggesting a combination thereof is required to invade the host successfully. Using in silico protein-protein interaction studies, we were able to assign different roles to respective isoforms in the HOG signaling pathway and predicted interactions with other signaling pathways. In summary, we demonstrate the signal-specific production of MoYpd1p isoforms that individually increase signal diversity and orchestrate virulence in the rice blast fungus M. oryzae. Authors summaryThe worlds population rises rapidly and a major problem is the global food security. Magnaporthe oryzae is placed first on a list of the worlds top ten plant pathogens with the highest scientific and economic importance since it causes blast, the most devastating disease of cultivated rice, which is the major food source for more than half of the world population. In this study, we demonstrate signal-specific production of a signaling protein, MoYpd1p, and show for the first time that the isoforms individually increase signal diversity and orchestrate virulence in the rice blast fungus M. oryzae. These results will help to better understand the molecular basis of pathogenicity of the rice blast fungus and consequently open the door to develop new strategies for plant protection and food security. In addition, our study is a valuable contribution to the basic research area of signaling mechanisms in in filamentous pathogenic fungi, and will thus be of high interest for a broad readership of the scientific community.

microbiology↗

bioRxiv2023

Bacteriophage-mediated decolonization of Enterobacteriaceae in a novel Galleria mellonella gut colonization model

PurposeGalleria mellonella larvae have emerged as an invertebrate model for studying bacterial pathogenesis and novel therapeutic options due to ethical concerns associated with the use of mammalian models such as mice. The benefits of using G. mellonella larvae include a less complex microbiome in the gut, making it suitable for gut colonization studies. The intestinal colonization of Klebsiella pneumoniae (Kp) and Escherichia coli (Ec), two of the most antibiotic-resistant bacteria on the World Health Organizations (WHO) priority list, plays a key role in the spread of antibiotic resistance. Bacteriophage therapy is emerging as a promising alternative for antibiotic-resistant bacteria due to its ability to specifically target and infect bacterial hosts, making it suitable for gut decontamination. This study aimed to establish a novel Enterobacteriaceae G. mellonella larvae gut colonization model and compare the efficacy of conventional antibiotic treatment with a one-time phage cocktail in decolonizing the gut. ApproachLarvae were force-fed with different concentrations of bacterial doses of K. pneumoniae and E. coli at 0 h, 24 h, and 48 h, followed by survival monitoring at 24 h intervals. After 48 h and 120 h of the last force feed, the colony forming unit (CFU) count in the gut was evaluated. After successful colonization, larvae were one-time force-fed with either a 107 PFU/larvae bacteriophage cocktail or with ciprofloxacin 4 mg/L or meropenem 2 mg/L. After 24 h post phage feeding, CFU counts were determined. Main findingsThree bacterial doses of 106 CFU/larvae led to a stable gut colonization in the larvae gut regardless of the K. pneumoniae and E. coli strains. Bacteriophage force-feeding reduced bacterial colonization by 4 log10 CFU/larvae whereas antibiotic treatment led to a 2 log10 CFU/larvae reduction compared to the control. The novel alternative G. mellonella model for gut colonization studies can be used for proof-of-concept studies, reducing or even obviating the number of follow-up experiments in vertebrate models.

microbiology↗

bioRxiv2022

A key regulator with a MIF-like domain orchestrates cellular differentiation and virulence in the fungal pathogen Magnaporthe oryzae

MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) is a pleiotropic protein with chemotactic, pro-inflammatory, and growth-promoting activities first discovered in mammals. In parasites, MIF homologs are involved in immune evasion and pathogenesis. Here, we present the first comprehensive analysis of a MIF protein from the devastating plant pathogen Magnaporthe oryzae (Mo). The fungal genome encodes a single MIF protein (MoMIF1) that, unlike the human homolog, harbors multiple low-complexity regions (LCRs) and is unique to Ascomycota. Following infection, MoMIF1 is expressed in the biotrophic phase of the fungus, and is strongly down-regulated during subsequent necrotrophic growth in leaves and roots. We show that MoMIF1 is secreted during plant infection, affects the production of the mycotoxin tenuazonic acid and inhibits plant cell death. Our results show that MoMIF1 is a novel key regulator of fungal virulence that maintains the balance between biotrophy and necrotrophy during the different phases of fungal infection.

plant biology↗

bioRxiv2022

Genomic screening reveals UBA1 as a potent and druggable target in c-MYC-high TNBC models

Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer-related deaths, despite accounting for only 10%-15% of total breast cancer cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1). Targeting UBA1 with the first in-class UBA1 inhibitor TAK-243 induced unresolvable ER-stress and activating transcription factor 4 (ATF4)-mediated upregulation of pro-apoptotic NOXA, leading to cell death. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. In an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. Lastly, c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. We posit UBA1 is an important new target in TNBC expressing high levels of c-MYC. SignificanceGenomic screening of TNBC cell lines revealed broad sensitivity to depletion of the E1 ubiquitin enzyme, UBA1. Disrupting UBA1 with the first in-class inhibitor TAK-243 in TNBC models induces ER-stress through an ATF4-NOXA axis that is dependent on c-MYC, leading to apoptosis, in vitro and in vivo, primary tumor growth inhibition and metastatic inhibition.

cancer biology↗

bioRxiv2021

Social information use for spatial decision in Zootoca vivipara

Movements of individuals are conditioned by information acquisition coming from either personal or social sources. Yet, little is known about the processes used by individuals to make movement decisions when facing multiple sources of social information simultaneously. This study aimed to test experimentally how social information from multiple sources is used to make movement decisions, and whether a contrast in this information allows individuals to orientate in space. We used common lizards (Zootoca vivipara) in a replicated experimental setting: one focal individual received information from two other individuals coming from peripheral environments, before being given the opportunity to relocate in one or another of the peripheral environments. Our analyses revealed that the behavior of informants, their mothers morphology, as well as the quality of informants environment, affected movement decisions: the probability to relocate from the focal area increased when informants displayed traits associated with low resources (no food intake, poor maternal condition) or high competition (high activity). The physical condition of individuals also mediated the use of social information about food intake, with a match between resource availability in informants and personal condition. Conversely, spatial orientation was not affected by the contrast of phenotype between informants nor by spatial variability in resource availability. This study highlights that multiple social information sources can be used for movement decisions, likely because these information sources reflect the quality of the surrounding environment (e.g., competition level or resources availability). It also emphasizes that social information use for movement is conditioned by individual phenotype.

ecology↗

bioRxiv2021

Plastic cell morphology changes during dispersal

Dispersal is the movement of organisms from one habitat to another that potentially results in gene flow. It is often found to be plastic, allowing organisms to adjust dispersal movements depending on environmental conditions. A fundamental aim in ecology is to understand the determinants underlying dispersal and its plasticity. We utilized 22 strains of the ciliate Tetrahymena thermophila to determine if different phenotypic dispersal strategies co-exist within a species and which mechanisms underlie this variability. We quantified the cell morphologies impacting cell motility and dispersal. Distinct differences in innate cellular morphology and dispersal rates were detected, but no universally utilized combinations of morphological parameters correlate with dispersal. Rather, multiple distinct and plastic morphological changes impact cilia-dependent motility during dispersal, especially in proficient dispersing strains facing challenging environmental conditions. Combining ecology and cell biology experiments, we show that dispersal can be promoted through a panel of plastic motility-associated changes to cell morphology and motile cilia. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/448130v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1aad069org.highwire.dtl.DTLVardef@158adbdorg.highwire.dtl.DTLVardef@f6570forg.highwire.dtl.DTLVardef@cdc249_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LITetrahymena thermophila exhibits intra-specific diversity in morphology and dispersal. C_LIO_LICell motility behavior during dispersal changes with cilia length and cell shape. C_LIO_LICells from proficient dispersing strains transiently change basal body and cilia position. C_LIO_LIStarvation-induced dispersal triggers increased basal body and cilia density and caudal cilium formation in rapid-swimming cells. C_LI

cell biology↗

bioRxiv2021

Dispersal syndromes affect ecosystem functioning in ciliate microcosms

Dispersal is a key process mediating ecological and evolutionary dynamics. Its effects on metapopulations dynamics, population genetics or species range distribution can depend on phenotypic differences between dispersing and non-dispersing individuals (i.e., dispersal syndromes). However, scaling up to the importance of dispersal syndromes for meta-ecosystems have rarely been considered, despite intraspecific phenotypic variability is now recognised as an important factor mediating ecosystem functioning. In this study, we characterised the intraspecific variability of dispersal syndromes in twenty isolated genotypes of the ciliate Tetrahymena thermophila to test their consequences for biomass productivity in communities composed of five Tetrahymena species. To do so, dispersers and residents of each genotype were introduced, each separately, in ciliate communities composed of four other competing species of the genus Tetrahymena to investigate the effects of dispersal syndromes. We found that introducing dispersers led to a lower biomass compared to introducing residents. This effect was highly consistent across the twenty T. thermophila genotypes despite their marked differences of dispersal syndromes. Finally, we found a strong genotypic effect on biomass production, confirming that intraspecific variability in general affected ecosystem functions in our system. Our study shows that intraspecific variability and the existence of dispersal syndromes can impact the functioning of spatially structured ecosystems in a consistent and therefore predictable way.

ecology↗

bioRxiv2021

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs) and we show that these cultures are permissive to retroviral (e.g. HIV-1, HTLV-1) replication. In addition, we also examine the potential effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection.

cell biology↗

bioRxiv2020

Deep learning and automated Cell Painting reveal Parkinson's disease-specific signatures in primary patient fibroblasts

Drug discovery for diseases such as Parkinsons disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinsons disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platforms robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separate LRRK2 and sporadic Parkinsons disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.

cell biology↗

bioRxiv2019

Transgenerational dispersal plasticity and its fitness consequences are under genetic control

Phenotypic plasticity, the ability of one genotype to produce different phenotypes in different environments, plays a central role in species response to environmental changes. Transgenerational plasticity (TGP) allows the transmission of this environmentally-induced phenotypic variation across generations, and can influence adaptation. To date, the genetic control of TGP, its long-term stability, and its potential costs remain largely unknown, mostly because empirical demonstrations of TGP across many generations in several genetic backgrounds are scarce. Here, we examined how genotype determines the TGP of dispersal, a fundamental process in ecology and evolution. We used an experimental approach involving ~200 clonal generations in a model-species of ciliate to determine if and how TGP influences the expression of dispersal-related traits in several genotypes. Our results show that morphological and movement traits associated with dispersal are plastic, and that these modifications are inherited over at least 35 generations. We also highlight that genotype modulates the fitness costs and benefits associated with plastic dispersal strategies. Our study suggests that genotype-dependent TGP could play a critical role in eco-evolutionary dynamics as dispersal determines gene flow and the long-term persistence of natural populations. More generally, it outlines the tremendous importance that genotype-dependent TGP could have in the ability of organisms to cope with current and future environmental changes.\n\nSignificanceThe genetic control of the transgenerational plasticity is still poorly understood despite its critical role in species responses to environmental changes. We examined how genotype determines transgenerational plasticity of a complex trait (i.e., dispersal) in a model-species of ciliate across ~200 clonal generations. Our results provide evidence that plastic phenotypic variation linked to dispersal is stably inherited over tens of generations and that cell genotype modulates the expression and fitness cost of transgenerational plasticity.

evolutionary biology↗