Biology subjects

Janssens, S.

Publications and source records attributed to Janssens, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Genotoxic and metabolic stress drive divergent senescence programs in human microglia

Microglial dysfunction is a hallmark of brain ageing linked to the accumulation of senescent microglial phenotypes that promote chronic neuroinflammation. Both genotoxic and metabolic stress have been implicated in microglial senescence; yet, whether distinct stressors shape senescence programs remain unclear. Here, we investigated the impact of chronic genotoxic and metabolic stress on senescence-associated phenotypes in the human microglia cell line HMC3. Cells were exposed to doxorubicin to induce sustained DNA damage or to chronic high-glucose conditions to model metabolic stress. Both stress paradigms induced characteristic senescence features including cellular and nuclear hypertrophy, increased senescence-associated {beta} galactosidase activity and reduced metabolic viability without significant cell loss. Both conditions activated the p53-p21 pathway and sustained DNA damage signalling, whereas metabolic stress additionally induced p16 expression and peripheral nuclear localisation of p21, suggesting divergence in senescence regulatory pathways. Mitochondrial alterations were evident under both conditions, Dox-induced stress was associated with downregulation of NRF2-TFAM signalling, whereas HG-induced stress induced NRF2-TFAM activation alongside increased KEAP1 expression, suggesting a constrained antioxidant response. This was accompanied by activation of mitochondrial and antioxidant stress responses that did not restore mitochondrial content. Furthermore, both stressors induced robust inflammatory activation, with genotoxic stress promoting a chemokine-rich senescence-associated secretory phenotype, while metabolic stress induced an interferon-associated inflammatory signature. Collectively, these findings demonstrated that chronic genotoxic and metabolic stress drive distinct yet overlapping senescence programs characterised by morphological changes, mitochondrial remodelling and persistent inflammatory activation. These stress-specific responses may differentially contribute to neurodegenerative processes and disease susceptibility.

neuroscience↗

bioRxiv2026

DNA damage-induced senescence reshapes transcriptomic and functional landscape of human neural progenitor cells

Ageing-related decline in hippocampal neurogenesis has been associated with cognitive impairment and neurodegenerative disease, yet experimentally tractable human models to study the underlying cellular and molecular mechanisms remain limited. Cellular senescence has emerged as a candidate driver of age-related tissue dysfunction, but its induction and consequences in human NPCs have not been well characterized. Here, we established a human in vitro model of NPC senescence using induced pluripotent stem cell-derived NPCs exposed to transient low-dose doxorubicin to activate the DNA damage response (DDR) while minimizing acute cytotoxicity. Doxorubicin-treated NPCs developed a stable senescent phenotype characterized by increased senescence-associated {beta}-galactosidase activity, reduced proliferation, persistent DNA damage, and sustained induction of p21 and p16. Transcriptomic profiling revealed widespread senescence-associated remodeling, including activation of p53 and inflammatory programs and repression of cell cycle and DNA repair pathways. Senescent NPCs exhibited apoptosis resistance despite transcriptional priming of apoptotic pathways and underwent mitochondrial remodeling with a shift towards oxidative metabolism. In parallel, they acquired a senescence-associated secretory phenotype enriched in inflammatory, TGF{beta}-related and pro-angiogenic factors, and conditioned media from these cells promoted angiogenesis in vascular organoids. Importantly, key senescence-associated features were recapitulated in human hippocampal organoids, confirming the robustness of this paradigm in a three-dimensional neural context. Together, these findings establish a tractable human model of DDR-driven NPC senescence and identify senescence as a mechanism linking genotoxic stress to impaired progenitor function, metabolic rewiring, and paracrine niche remodeling relevant to hippocampal ageing and neurodegeneration.

neuroscience↗

bioRxiv2026

Periweaning diet-induced activation of an IFNγ-mediated regulatory circuit promotes the homeostasis of cytotoxic CD8+ T Cells

Balancing pathogen defence with maintaining tolerance to environmental antigens, such as food or commensals, in neonates is essential for survival and the establishment of life-long immune homeostasis. Instructed by environmental signals type 1 conventional dendritic cells (cDC1) drive either T cell tolerance or immunity. Here, we uncover an interferon (IFN)-{gamma}-driven regulatory circuit in early life that relays dietary cues to spleen cDC1. Loss-of-function demonstrates that IFN{gamma}-mediated STAT1-signaling induces an immunogenic maturation program in spleen cDC1 that instructs cDC1 to expand effector memory CD8 T cells. This program emerges during weaning, when IFN{gamma} production from lymphocytes rises, it occurs in germ-free mice and remains responsive to dietary intervention in adult mice. During the transition from breastfeeding to solid food at weaning, this circuit relays dietary information to spleen cDC1 to shape the effector phenotype of food-antigen specific CD8+ T cells in a feed-forward manner, allowing cDC1 to recalibrate the T cell pool at the moment of nutritional independence.

immunology↗

bioRxiv2025

Integrated multi-modal data analysis for computational modeling of healthy and location-dependent myocardial infarction conditions in porcine hearts

Porcine hearts are widely used for preclinical cardiac evaluation. Computational models, by effectively integrating comprehensive experimental data, often reinforce this preclinical assessment. Using extensive multi-modal data, we developed swine ventricular digital twins for healthy and chronic myocardial infarction (MI) conditions to investigate the roles of the cardiac conduction system (CS), spatial repolarization heterogeneities, cardiomyocyte orientation, cell-to-cell coupling, and MI characteristics on ventricular function. We analyzed cardiac magnetic resonance (CMR) images, electrocardiograms (ECGs), and optical (OM) and electroanatomical mapping from 5 healthy and 10 MI pigs. CS architectures were built from OM and ECG recordings. Myocardial fiber orientation, action potential characteristics, and cell-to-cell conductivity in MI tissue were defined from OM and CMR data. Simulated ECGs for healthy and MI models of left anterior descending and left circumflex occlusions were compared to experimental ECGs and used to assess MI-induced changes. Personalized fiber orientation minimally affected electrophysiology, with conduction velocity (CV) and action potential duration (APD) changing less than 3.6% with respect to standard orientation. Accurate CS and repolarization heterogeneities reproduced depolarization (0.76 QRS similarity) and repolarization (0.74 T-wave similarity) patterns. Incorporating experimentally guided MI-induced alterations enabled replication of MI depolarization and repolarization features (relative errors: 0.5% CV, 2.9% APD), yielded realistic T-wave morphologies (0.63 similarity), and revealed ECG patterns specific to vessel-dependent occlusions. Thus, by integrating extensive multi-modal data, we advance porcine cardiac digital twins and demonstrate the influence of key structural and electrophysiological parameters on healthy and MI heart function, providing a robust computational framework for mechanistic and translational applications. Author summaryPigs are commonly used as preclinical models for cardiac evaluation due to their close resemblance to the human heart. Computational cardiac electrophysiology often supports and extends this preclinical assessment. However, the reliability of these in silico representations depends on the effective integration of comprehensive experimental data. Using extensive multi-modal data, we developed swine ventricular digital twins under healthy and chronic myocardial infarction conditions. These models allowed us to investigate the influence of the cardiac conduction system, spatial repolarization heterogeneities, cardiomyocyte orientation, cell-to-cell coupling, and vessel-specific infarction characteristics on ventricular function. Our results show that cardiomyocyte orientation exerts only a minor effect on electrophysiology, with average conduction velocity showing a slight decrease and action potential duration remaining unchanged when comparing standard versus personalized orientations. Accurate representation of conduction system architecture and repolarization heterogeneities enabled closed reproduction of experimental depolarization and repolarization patterns. Furthermore, by integrating experimentally guided reductions in cell-to-cell coupling and inward rectifier potassium current, along with personalized post-infarction activation alterations and a novel porcine cellular model, we were able to faithfully replicate infarction-specific depolarization-repolarization features. These refinements produced realistic T-wave morphologies and revealed electrocardiographic signatures associated with vessel-dependent infarctions, underscoring the translational potential of our approach.

bioengineering↗

bioRxiv2025

Over-expression and increased copy numbers of a cytochrome P450 and two UDP-glucuronosyltransferase genes in macrocyclic lactone resistant Psoroptes ovis of cattle

Psoroptes ovis is a mite species that feeds on sheep, cattle, other ungulates, rabbits, and horses, which can develop into a severe exudative dermatitis known as psoroptic mange. The macrocyclic lactone (ML) family of acaricides are commonly used to control psoroptic mange. However, certain strains of cattle and sheep mites have developed resistance against MLs, which has led to reduced treatment efficacy and even treatment failure. Here we investigated the genetic basis of ML resistance in mites collected from cattle across Belgium. We compared gene expression between susceptible and resistant mites before and after exposure to ivermectin and genetic diversity between a single susceptible and resistant populations. We generated chromosomal genome assemblies of Psoroptes ovis derived from sheep and cattle respectively and correlated genomic diversity of susceptible and resistant mite populations sampled across Belgium. Gene expression data revealed constitutive over-expression of a cytochrome P450 monooxygenase (CYP) gene and two tandemly located UDP-glucuronosyltransferase (UGT) genes among others. On investigation of the genomic data, we observed copy number variation at both loci in population genomic data. The CYP gene is not amplified in the susceptible population but occurs in multiple copies in all resistant populations and is associated with a peak in Fst between resistant and susceptible populations indicative of selection. By contrast, the two UGT genes are massively and tandemly amplified in all populations including the susceptible dataset with a weaker associated signal of selection than the amplified CYP. Hence, distinct mechanisms of amplification and gene regulation are occurring at these putative resistance loci in P. ovis. Author SummaryFor the first time, we investigated the genetic basis of resistance in scab mites to a key family of drugs (Macrocyclic Lactones) used to control this parasite. Scab mite infestations can cause serious welfare issues in affected cattle and sheep with associated economic impact on production. To identify genes associated with resistance, we applied a combination of approaches including targeted sequencing of candidate genes, genome sequencing and gene expression comparisons of resistant mites with mites that are still susceptible to treatment. We were able to rule-out one family of candidate genes but identified very high expression of genes from two gene families that metabolise, and thereby detoxify, the treatment drug in resistant mites. On examination of the genomic context of these genes we found that the genes had undergone an increase in copy number in the resistant mites compared to the susceptible mites. With our now much increased understanding of resistance in scab mites we can track the spread of resistance using markers in these genes present in resistant mites. We can also now test the suitability of alternative treatments that restore the lethality of Macrocyclic Lactones in scab mites, mitigating the damaging effects of resistance in this species.

genomics↗

bioRxiv2024

Unravelling the molecular activation of the reparative cardiac fibroblasts after myocardial infarction

Activated cardiac fibroblasts (Postn+ CFs) are responsible for the healing of the heart tissue after a myocardial infarction (MI). However, so far little is known about the moment that CFs are activated, and the genes involved in this process. This is especially relevant in the context of CF heterogeneity and their role in the response to the damage. In this context, we have described a subpopulation of activated CFs responsible for the healing scar and for preventing the rupture of the ventricle after the damage: the Reparative Cardiac Fibroblasts (RCFs). Our new data indicate that RCFs directly derived from activated CFs, and this transcriptional shift happens in a close window after damage. Interestingly, our results exhibited two different molecular dynamics that would give rise to this activation and, consequently, the appearance of definitive RCFs. Using bulk RNA-Seq, RNAScope and Spatial Transcriptomics, we anatomically localized some of the genes related to both dynamics in the infarcted heart and highlight the potential role of Aspn as a new marker of this transcriptional transition in mice, pigs and patients.

bioinformatics↗

bioRxiv2024

High-throughput phenotyping reveals multiple drought responses of wild and cultivated Phaseolinae beans

Crop production worldwide is increasingly affected by drought stress. Although drought tolerance of a plant may be achieved through morphological, structural, physiological, cellular, and molecular adaptations, most studies remain limited to quantifying the effect of drought on biomass yield. Using a high-throughput phenotypic imaging system, we evaluated the drought tolerance of 151 bean accessions (Phaseolinae; Fabaceae) by quantifying five different traits simultaneously: biomass, water use efficiency, relative water content, chlorophyll content, and root/shoot ratio. Since crop wild relatives are important resources for breeding programmes, both wild and cultivated accessions were analyzed, the majority never evaluated for drought tolerance before. We demonstrate that the five traits are affected very differently by drought in the studied accessions, although a cluster analysis grouped the accessions into five distinct clusters with similar responses. We correlated the results for each accession to local climate variables at their original collection sites. Except for the root/shoot ratio, the results of all indicators were related to precipitation data, confirming that drought tolerant accessions grow in arid environments. This broader knowledge on the complex responses of plants to drought stress may prove an invaluable resource for future crop production. HighlightThis study presents an innovative approach for the fast evaluation of different drought tolerance traits of legumes. Multiple responses to drought were observed in the economically important Phaseolinae beans.

plant biology↗

bioRxiv2023

Activation of goblet cell stress sensor IRE1β is controlled by the mucin chaperone AGR2

As secretory cells specialized in the production of mucins, intestinal goblet cells are challenged by the need for efficient protein folding. Goblet cells express Inositol-Requiring Enzyme 1{beta} (IRE1{beta}), a unique unfolded protein response (UPR) sensor that is part of an adaptive mechanism that regulates the demands of mucin production and secretion. However, how IRE1{beta} activity is tuned to mucus folding load remains unknown. We identified the disulfide isomerase and mucin chaperone AGR2 as a goblet cell specific protein that crucially regulates IRE1{beta}-, but not IRE1-mediated signaling. AGR2 binding to IRE1{beta} disrupts IRE1{beta} dimerization, thereby blocking its downstream endonuclease activity. Depletion of endogenous AGR2 from goblet cells induces spontaneous IRE1{beta} activation, suggesting that alterations in AGR2 availability in the endoplasmic reticulum sets the threshold for IRE1{beta} activation. We found that AGR2 mutants lacking their catalytic cysteine or displaying the disease-associated mutation H117Y were no longer able to dampen IRE1{beta} activity. Collectively, these results demonstrate that AGR2 is a central chaperone regulating the goblet cell UPR by acting as a rheostat of IRE1{beta} endonuclease activity.

cell biology↗

bioRxiv2023

Type 1 immunity enables neonatal thymic ILC1 production

Thymic atrophy occurs following type 1 inflammatory conditions like viral infection and sepsis, resulting in cell death and disruption of T-cell development. However, it remains undetermined whether the thymus actively contributes to the immune response. Thus, we cultured neonatal thymus ex vivo with the type 1 cytokines IL-12 plus IL-18, resulting in a rapid shift from steady-state T-cell development to the production, expansion, and thymic exit of CXCR6+CD62L- type 1 innate lymphoid cells (ILC1s). Single-cell RNA-sequencing and functional assays identified these cells as embryonic-wave-derived KLRG1+ ILC1s that mainly differentiated from immature neonatal thymic ILC1s. Confocal 3D imaging confirmed neonatal thymic ILC1 expansion during MCMV infection. Furthermore, thymic grafts revealed in vivo thymic ILC1 egress and type 1 inflammation-induced homing of thymus-derived KLRG1+ ILC1s to the liver and peritoneal cavity. Altogether, our data reveal a novel thymic function where type 1 immunity enables the production and peripheral homing of thymic-derived ILC1s. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/530451v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@d768corg.highwire.dtl.DTLVardef@1e20d77org.highwire.dtl.DTLVardef@1e206bforg.highwire.dtl.DTLVardef@292108_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Global Phylogeny of the Brassicaceae Provides Important Insights into Gene Discordance

The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most published family phylogenies are incompletely sampled, generally contain massive polytomies, and/or show incongruent topologies between datasets. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Brassicaceae Tree of Life, or BrassiToL) based on nuclear (>1,000 genes, almost all 349 genera and 53 tribes) and plastome (60 genes, 79% of the genera, all tribes) data. We found cytonuclear discordance between nuclear and plastome-derived phylogenies, which is likely a result of rampant hybridisation among closely and more distantly related species, and highlight rogue taxa. To evaluate the impact of this rampant hybridisation on the nuclear phylogeny reconstruction, we performed four different sampling routines that increasingly removed variable data and likely paralogs. Our resulting cleaned subset of 297 nuclear genes revealed high support for the tribes, while support for the main lineages remained relatively low. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene icehouse origin of the family. Finally, we propose five new or re-established tribes, including the recognition of Arabidopsideae, a monotypic tribe to accommodate Arabidopsis. With a worldwide community of thousands of researchers working on this family, our new, densely sampled family phylogeny will be an indispensable tool to further highlight Brassicaceae as an excellent model family for studies on biodiversity and plant biology.

evolutionary biology↗

bioRxiv2022

Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity.

The IRE1/XBPls axis of the unfolded protein response (UPR) plays divergent roles in dendritic cell (DC) biology in steady state versus tumor contexts. Whereas tumor associated DCs show dysfunctional IRE1/XBP1s activation that curtails their function, the homeostasis of conventional type 1 DCs (cDC1) in tissues requires intact IRE1 RNase activity. Considering that cDC1s are key orchestrators of antitumor immunity, it is relevant to understand the functional versus dysfunctional roles of IRE1/XBP1s in tumor DC subtypes. Here, we show that cDC1s constitutively activate IRE1 RNase within subcutaneous B16 melanoma and MC38 adenocarcinoma tumor models. Mice lacking XBP1s in DCs display increased melanoma tumor growth, reduced T cell effector responses and accumulation of terminal exhausted CD8+ T cells. Transcriptomic studies revealed that XBP1 deficiency in tumor cDCls decreased expression of mRNAs encoding XBPls and regulated IRE1 dependent decay (RIDD) targets. Finally, we find that the dysregulated melanoma growth and impaired T cell immunity noticed in XBP1 deficient mice are attributed to RIDD induction in DCs. This work indicates that IREl RNase activity in melanoma/MC38-associated DCs fine tunes aspects of antitumor immunity independently of XBP1s, revealing a differential role for the UPR axis that depends on the DC subtype and cancer model.

immunology↗

bioRxiv2021

Distinct cDC subsets co-operate in CD40 agonist response while suppressive microenvironments and lack of antigens subvert efficacy

Agonistic CD40 therapy has shown to inhibit cancer progression, but only in a fraction of patients. Hence, understanding the cancer cell-intrinsic and microenvironmental determinants of CD40 therapy response is crucial to identify responsive patient populations and design efficient combination treatments. Here, we showed that the therapeutic efficacy of CD40 in responder melanoma tumours, relied on pre-existing cDC1-primed CD8+ T cells, however cDC1s were dispensable after CD40 administration. Surprisingly, in response to CD40 the abundance of activated cDCs, potentially derived from cDC2s increased, thereby further activating antitumour CD8+ T cells. Hence, distinct cDC subsets are required to induce CD40 responses. By contrast, lung tumours, characterised by a high abundance of macrophages, were resistant to CD40 therapy. Combining CD40 therapy with macrophage depletion led to tumour growth inhibition only in the presence of strong neoantigens. Accordingly, treatment with immunogenic cell-death inducing chemotherapy sensitised non-immunogenic tumours to CD40 therapy.

cancer biology↗

bioRxiv2021

Effects of forest disturbance and regeneration on tree species composition and traits in DR Congo

Despite their key role in biodiversity conservation, forests of the Congo Basin are increasingly threatened by human activities. Whereas deforestation is very conspicuous, it remains challenging to monitor the impact of forest degradation under a more or less intact canopy. Likewise, the outcomes of forest regeneration following agricultural abandonment remain poorly studied in the Congo Basin. Here, we surveyed 125 vegetation quadrats across 25 forest inventory plots in the Yangambi region, and based on historical land-use maps. We aimed to assess both the impact of anthropogenic disturbance and forest recovery on tree species diversity, tree functional traits, community composition, canopy cover, and forest structure, as compared to undisturbed old-growth forest. We found that undisturbed old-growth forest harboured more tree individuals, particularly individuals with a smaller diameter, as well as species with a higher wood density when compared to both disturbed old-growth and regrowth forest. Moreover, species diversity was highest in disturbed old-growth forest. Tree species composition was significantly different between undisturbed old-growth forest and the other two forest categories. Our findings indicate that anthropogenic disturbance results in a degraded forest structure and may reduce the forests ability to store carbon. Whereas species diversity recovered 60 years after agricultural abandonment, species composition remained different from undisturbed old-growth forest. Our study illustrates the need for more extensive vegetation surveys in the Congo Basin in order to quantify the effects of human disturbance under a closed canopy.

ecology↗

bioRxiv2021

High heritabilities for antibiotic usage show potential to breed for disease resistance in finishing pigs

The use of antimicrobials in animal production is under public debate, mainly due to the risk of transfer of resistance to pathogenic bacteria in humans. Therefore, measures have been taken during the last decades to reduce antibiotic usage in animals, for instance by national monitoring programmes and by improving animal health management. Although some initiatives exist in molecular genetic selection, quantitative genetic selection of animals towards decreased antibiotic usage is an underexplored area to reduce antibiotic usage. However, this strategy could yield cumulative effects. In this study we derived new phenotypes from on-farm parenteral antibiotic records from commercially grown crossbred finishing pigs used in the progeny test of Pietrain terminal sires to investigate the heritability of antibiotics usage. Parenteral antibiotic records, production parameters and pedigree records of 2238 fullsib pens from two experimental farms in Belgium between 2014 and 2020 were analysed. Heritability estimates were moderate (18-44%) for phenotypes derived from all antibiotic treatments, and low (1-15%) for phenotypes derived from treatments against respiratory diseases only. Moreover, genetic correlations between these new phenotypes and mortality were low to moderate (0.08-0.60) and no strong adverse genetic correlations with production traits were found. The high heritabilities and favourable genetic correlations suggest these new phenotypes derived from on-farm antibiotics records to be promising for inclusion in future pig breeding programs to breed for a decrease in antibiotics usage.

genetics↗

bioRxiv2021

Genetic diversity of the pathogenic banana Fusarium wilt in northern Viet Nam

Fusarium is one of the most important fungal genera of plant pathogens that affect the cultivation of a wide range of crops. Agricultural losses caused by Fusarium oxysporum f. sp. cubense (Foc) have a direct effect on the income, subsistence and nourishment of thousands of smallholder farmers worldwide. In addition, also commercial growers are strongly affected. For Viet Nam, predictions on the impact of Foc for the future are dramatic with an estimated loss in banana production area of 8% within the next 5 years and up to 71% within the next 25 years. In the current study we applied a combined morphological - molecular approach to assess the taxonomic identity and phylogenetic position of the different Foc isolates that were collected in northern Viet Nam. In addition, we aim to estimate the proportion of the different Fusarium races that are infecting bananas in northern Viet Nam. The morphology of the isolates was investigated by growing the collected Fusarium isolates on four distinct nutritious media (PDA, SNA, CLA, and OMA). Molecular phylogenetic relationships were inferred by sequencing partial rpb1, rpb2 and tef1a genes and adding the obtained sequences into a large phylogenetic framework. The present study showed that Foc Race 1 is the most common strain in northern Viet Nam, causing 74% of all the infections. A more in-depth molecular characterization shows that of the Foc Race 1 infections, 92% are caused by Fusarium tardichlamydosporum and 8% by F. duoseptatum. Compared to Foc Race 1, Foc TR4 (represented by F. odoratissimum) account for only 10.5% of the Fusarium wilting in northern Viet Nam demonstrating that Foc TR4 is not yet a dominant strain in the region. Foc Race 2 infections of Vietnamese bananas also account for 10.5% of the Fusarium wilting in northern Viet Nam. One of the isolates cultured from diseased bananas collected in northern Viet Nam was phylogenetically not positioned within the F. oxysporum species complex (FOSC), but in contrast fell within the Fusarium fujikuroi species complex (FFSC). As a result, it is possible that a new pathogen for bananas has been found. Besides being present on several ABB Tay banana, Foc Race 1 was also found as pathogen on wild Musa lutea, showing the importance of wild bananas as possible sink for Foc.

evolutionary biology↗

bioRxiv2021

Maximizing genetic representation in seed collections from populations of self and cross-pollinated banana wild relatives

BackgroundConservation of plant genetic resources, including the wild relatives of crops, plays an important and well recognised role in addressing some of the key challenges faced by humanity and the planet including ending hunger and biodiversity loss. However, the genetic diversity and representativeness of ex situ collections, especially that contained in seed collections, is often unknown. This limits meaningful assessments against conservation targets, impairs targeting of future collecting and limits their use. We assessed genetic representation of seed collections compared to source populations for three wild relatives of bananas and plantains. Focal species and sampling regions were Musa acuminata subsp. banksii (Papua New Guinea), M. balbisiana (Viet Nam) and M. maclayi s.l. (Bougainville, Papua New Guinea). We sequenced 445 samples using suites of 16-20 existing and newly developed taxon-specific polymorphic microsatellite markers. Samples of each species were from five populations in a region; 15 leaf samples and 16 seed samples from one infructescence ( bunch) for each population. ResultsAllelic richness of seeds compared to populations was 51%, 81% and 93% (M. acuminata, M. balbisiana and M. maclayi respectively). Seed samples represented all common alleles in populations but omitted some rarer alleles. The number of collections required to achieve the 70% target of the Global Strategy for Plant Conservation was species dependent, relating to mating systems. Musa acuminata populations had low heterozygosity and diversity, indicating self-fertilization; many bunches were needed (>15) to represent regional alleles to 70%; over 90% of the alleles from a bunch are included in only two seeds. Musa maclayi was characteristically cross-fertilizing; only three bunches were needed to represent regional alleles; within a bunch, 16 seeds represent alleles. Musa balbisiana, considered cross-fertilized, had low genetic diversity; seeds of four bunches are needed to represent regional alleles; only two seeds represent alleles in a bunch. ConclusionsWe demonstrate empirical measurement of representation of genetic material in seeds collections in ex situ conservation towards conservation targets. Species mating systems profoundly affected genetic representation in seed collections and therefore should be a primary consideration to maximize genetic representation. Results are applicable to sampling strategies for other wild species.

genetics↗

bioRxiv2020

The IRE1 Inhibitor KIRA6 Curtails The Inflammatory Trait Of Immunogenic Anticancer Treatments By Targeting HSP60 Independent Of IRE1

Cellular stress evoked by immunogenic anticancer treatments engaging the unfolded protein response (UPR) can elicit inflammation with conflicting therapeutic outcomes. To define cell-autonomous mechanisms coupling the UPR to molecular mediators of inflammation, we profiled the transcriptome of cancer cells responding to immunogenic or weakly immunogenic-treatments. Bioinformatics-driven pathway analysis indicated that immunogenic treatments instigated NF-{kappa}B/AP-1-inflammatory pathways, which were abolished by the IRE1-kinase inhibitor KIRA6. Cell-free fractions of chemotherapy and KIRA6 co-treated cancer cells were deprived of pro-inflammatory/chemoattractant factors and failed to mobilize innate immune cells. Strikingly, these potent KIRA6 anti-inflammatory effects were found to be independent of IRE1. Generation of a KIRA6-clickable photoaffinity probe, mass spectrometry and co-immunoprecipitation analysis identified cytosolic HSP60 as a KIRA6 off-target in the NF-{kappa}B pathway. In sum, our study unravels that inflammation evoked by immunogenic treatments is curtailed by KIRA6 independently of IRE1 and further suggests great caution in interpreting the anti-inflammatory action of IRE1 chemical inhibitors.

cancer biology↗

bioRxiv2020

Multiple origins of insular woodiness on the Canary Islands are consistent with palaeoclimatic aridification

AimInsular woodiness, referring to the evolutionary transition from herbaceousness towards woodiness on islands, has arisen at least 38 times on the Canary Islands. Distribution patterns and physiological experiments have suggested a link between insular woodiness and increased drought stress resistance in current-day species, but we do not know in which palaeoclimatic conditions these insular woody lineages originated. Therefore, we estimated the timing of colonisation events and origin of woodiness of multiple Canary Island lineages and reviewed the palaeoclimate based on literature. LocationCanary Islands (Spain). Taxon37 lineages, including 24 insular woody and 13 non-insular woody (i.e. herbaceous, ancestrally woody, and derived woody). MethodsTo enable a simultaneous dating analysis for all 37 lineages, two chloroplast markers (matK and rbcL) for 135 Canary Island species and 103 closely related continental relatives were sequenced and aligned to an existing matK-rbcL dataset including ca 24,000 species that was calibrated with 42 fossils from outside the Canaries. After constraining the species to the family level, 200 RAxML runs were performed and dated with TreePL. ResultsWoodiness in 80-90% of the insular woody lineages originated within the last 7 Myr, coinciding with the onset of major aridification events nearby the Canaries (start of north African desertification, followed by Messinian salinity crisis); in ca 55-65% of the insular woody lineages studied, woodiness developed within the last 3.2 Myr during which Mediterranean seasonality (yearly summer droughts) became established on the Canaries, followed by dry Pleistocene glacial fluctuations. Main conclusionsAlthough details of the initial colonisation and settlement of many island plant lineages remain elusive, our results are consistent with palaeodrought as a potential driver for woodiness in most of the insular woody Canary Island lineages studied.

evolutionary biology↗