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Michel, A.

Publications and source records attributed to Michel, A..

At least 19 recordsLinked to original sources

Plasticity of genetic regulation during cellular learning

Even under physiological conditions, cells are exposed to multiple, spatially and temporally complex signals and need to regularly adjust their response to survive and function. At least in some cases, identifying the appropriate response relies on the ability cells to learn from experience. For example, budding yeast cells learn to ignore futile mating signals. Using this paradigm, we investigated the genetic requirements supporting learning in single cells. We show that it arises from the dynamics of a large, highly redundant and plastic genetic network, where the contribution of most genes to learning varies across experimental replicates. Furthermore, this network is highly resistant to genetic perturbations and involves a broad panel of cellular functions and sensing pathways, suggesting that it can integrate a large diversity of inputs. Together, our data support the notion that cellular learning is an emerging feature of the information storage capability inherent to large sets of interacting genes, indicating that it should be widely conserved across cell types.

cell biology↗

The effects of elevated seawater pH and total alkalinity following dosing of sodium hydroxide in Calanus finmarchicus

Ocean Alkalinity Enhancement (OAE) is a marine carbon dioxide removal (mCDR) strategy that involves adding alkaline substances to surface waters to enhance CO2 uptake and storage. The dispersal of alkaline materials such as sodium hydroxide (NaOH) into seawater can cause rapid increases in pH and total alkalinity (TA) that substantially exceeds natural variability in marine environments. Such fluctuations may negatively affect marine life, especially small animals like copepods who cannot avoid OAE plumes and whose physiological processes could be disrupted by large and rapid shifts in seawater pH. To address knowledge gaps regarding potential biological impacts of OAE, we studied these effects in Calanus finmarchicus, a keystone copepod species in the Northwest Atlantic Ocean. We exposed C. finmarchicus from the late juvenile copepodite stages and adult females to NaOH-dosed seawater at pH 10.5 ([~]5,000 {micro}mol kg-1 TA) and pH 9.0 ([~]3,150 {micro}mol kg-1 TA) for durations that reflect expected short-term exposure times during field OAE deployments (pH 10.5: 1, 5, 10 minutes; pH 9.0: 1, 15, 30 minutes). None of the treatment combinations resulted in mortality immediately after the initial exposure. Individuals were monitored for survival for 72 hours post-exposure (hpe), and only one treatment group (juveniles exposed to pH 10.5 for 10 minutes) showed a significant reduction in final survival; no other pH-duration combination showed increased mortality. Effects on the ability to initiate an escape response were more substantial. Adult females treated with pH 10.5 for 5 or 10 minutes showed a significant reduction in escape response immediately after exposure. In contrast, juveniles showed no immediate change in escape response following exposure to pH 10.5 or pH 9.0, although juveniles exposed to pH 10.5 for 10 minutes exhibited reduced escape response at 24 hpe. Using microrespirometry, we measured oxygen consumption following a 10-minute exposure to pH 10.5 and detected no effect on routine metabolic rate immediately post-exposure or at 12 hpe. Overall, our results suggest that C. finmarchicus is relatively tolerant to short-term exposures to very high pH and alkalinity. Future work should prioritize longer-term exposure under more moderate ocean OAE conditions.

ecology↗

Key determinants of T cell epitope recognition revealed by TCR specificity profiles

Interactions between T-Cell Receptors (TCRs) and antigenic peptides presented on Major Histocompatibility Complex (MHC) molecules are central to the immune recognition of infected and malignant cells. The complexity of the TCR sequence space, the flexibility of the TCR-epitope interface and the lack of a standardized framework to visualize TCR specificity have hindered a comprehensive understanding of the principles governing TCR-epitope recognition across a broad range of epitopes. Here, we introduce a fully interpretable probabilistic framework, termed TCR specificity profiles (TSPs), which captures fundamental properties distinguishing epitope-specific from baseline TCR repertoires. We demonstrate that TSPs unravel key determinants of TCR-epitope recognition specificity. By identifying and analyzing TCRs recognizing dozens of epitope variants, we show that TSPs accurately predict cross-reactivity and reveal how TCR specificity evolves with epitope sequence, binding mode and MHC restriction. TSPs further enable interpretation of machine learning tools and reveal how AlphaFold3 can be used to decipher key determinants of TCR-epitope recognition specificity.

immunology↗

The environmental stress response controls the biophysical properties of the cytoplasm and is critical for survival in quiescence

All organisms have evolved survival strategies to cope with changes in environmental conditions. Nutrient deprivation, one of the most frequently encountered stresses in nature, causes haploid budding yeast to enter a reversible state of non-proliferation known as quiescence, which entails extensive remodeling of gene expression, metabolism and the cellular biophysical properties. Yeast cells can adapt to and survive long periods of time in glucose starvation-induced quiescence, provided they are able to respire in the early stages of glucose withdrawal. When respiration is blocked during glucose withdrawal, cells prematurely age and exhibit markedly reduced survival and cytoplasmic diffusion. We find here that respiration is required to induce a quiescence-related gene expression program. Induction of this program prior to withdrawing glucose in respiration-inhibited cells bypasses the need for respiration and rescues survival and biophysical properties to levels seen in glucose-starved but respiration-competent cells. This rescue effect relies on proteomic adaptation, which partially occurs through inactivation of Ras/PKA signaling and activation of the environmental stress response via the transcription factors Msn2/4. This signaling cascade triggers the expression of stress response genes and modulates the cytoplasmic diffusion state of cells, ensuring long-term survival in quiescence even in the absence of respiration. Our results highlight the importance of stress adaptation in quiescence and aging, integrating gene expression control and modulation of cytoplasmic properties to maintain cell fitness.

cell biology↗

Terrain ruggedness and human activities influence the distribution of Grauer's gorillas and eastern chimpanzees in the Tayna Nature Reserve, Democratic Republic of Congo

The Albertine Rift Hotspot in east-central Africa is one of the most biodiverse regions in the world. It hosts a number of conservation-priority species, including Critically Endangered Grauers gorillas and Endangered eastern chimpanzees. Yet, prolonged insecurity in the region has made wildlife monitoring and conservation challenging. This is particularly true of the northeastern limits of the range of Grauers gorillas, where wide stretches of unprotected forest could harbor behaviorally and genetically unique peripheral populations of great apes and other species. Here, we developed a rapid wildlife survey method to map population distributions and monitor the impact of various human activities in the Tayna Nature Reserve in eastern Democratic Republic of Congo. Despite a lack of surveys since the early 2000s, we find that Grauers gorillas and eastern chimpanzees, as well as a number of smaller-bodied species, have persisted in Tayna. Observations of gorilla and chimpanzee signs were highly heterogeneous. They were less dense near human settlements and artisanal mines and peaked in areas with rugged terrain. The association with rugged terrain may be a result of historical anthropogenic pressure, behavioral avoidance of human activities, and/or ecological preference. Maintaining connectivity between patches of suitable great ape habitat will be critical for long-term great ape conservation in the Albertine Rift region. Our findings also demonstrate the utility of priority species monitoring driven by local communities for conservation initiatives.

ecology↗

Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies

Alpha-synuclein (aSyn) post-translational modifications (PTMs), particularly phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LBs), Lewy neurites, and other types of aSyn pathological aggregates in the brain of patients with Parkinsons disease (PD) and other synucleinopathies. However, our knowledge about the precise role of PTMs in regulating the different stages of pathology formation, neurodegeneration, and aSyn pathology spreading remains incomplete. In this work, we applied a systematic approach to address this knowledge gap with an emphasis on mapping and elucidating the role of post-fibrillization C-terminal aSyn truncations in regulating the uptake, processing, seeding activity, and formation of LB-like inclusions and maturations in a well-established neuronal seeding model that recapitulates all the stages leading to LB formation and neurodegeneration. Our work shows that C-terminal cleavage of aSyn fibrils at multiple sites is a conserved process that occurs rapidly after and during the formation of intracellular LB-like aSyn inclusions in all neuronal seeding models. Interestingly, blocking the cleavage of internalized fibrils does not influence their seeding activity, whereas inhibiting the enzymes that regulate the cleavage of newly formed fibrils (e.g., calpains 1 and 2) significantly alters the formation of LB-like inclusions. We also show that C-terminal truncations, in combination with other PTMs, play a crucial role in regulating the interactome and remodeling of newly formed aSyn fibrils, including their shortening, lateral association, and packing during LB formation and maturation. Altogether, our results demonstrate that post-fibrillization C-terminal truncations have a differential role at different stages of aSyn aggregation and pathology formation. These insights, combined with the abundance of truncated aSyn species in LBs, have significant implications in understanding aSyn pathological diversity and developing therapeutic strategies targeting the C-terminus of aSyn or its proteolytic processing.

neuroscience↗

Spatio-temporal T cell tracking for personalized TCR-T designs in childhood cancer

Immune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers. Here, we present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood. Specifically, we tracked T cell dynamics longitudinally from the tumor to cells in circulating over a time course of 12 months, revealing a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity. These findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.

genomics↗

Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in the ABCD1 gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord of ABCD1-/y mice. We used single nuclei RNA seq to identify the pathways altered in the ABCD1-/y mouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss of ABCD1. These data suggest that Elovl1 inhibition may have broader consequences in ABCD1-/y mice than correction of lipid homeostasis.

pharmacology and toxicology↗

Exploring the PET in vivo generator 134Ce as a theranostic match for 225Ac

PurposeThe radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of 134Ce offer perspectives for developing innovative in vivo investigations not possible with 225Ac. In this work, 225Ac- and 134Ce-labeled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, 134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging. MethodsThe precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with 225Ac or 134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The 225Ac and 134Ce-labeled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody. ResultsIn vitro and in vivo studies with both 225Ac and 134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the 134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of 134Ces PET-compatible daughter 134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing 225Ac-labelled tracers are not quantitatively represented by 134Ce PET imaging. ConclusionWhen employing slow-internalizing vectors, 134Ce might not be an ideal match for 225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of 134La. However, this same characteristic makes it possible to estimate the redistribution of 225Acs progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/591165v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@ca3cb6org.highwire.dtl.DTLVardef@157eac6org.highwire.dtl.DTLVardef@f6ac6dorg.highwire.dtl.DTLVardef@b24d87_HPS_FORMAT_FIGEXP M_FIG C_FIG Redistribution of progeny. Investigating the 225Ac and 134Ce decay chain. This figure was created with BioRender.

pharmacology and toxicology↗

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor

Cellular senescence is now acknowledged as a key contributor to organismal ageing and late-life disease. Although popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and its paracrine effects. To address these issues, we repurposed the small molecule inhibitor inflachromene (ICM) to induce senescence to human primary cells. Within six days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered significant similarity of the two states. Notably though, ICM suppresses the proinflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM induces a senescence-like phenotype rapidly and synchronously thereby allowing the study of its core regulatory program without any confounding heterogeneity.

genomics↗

Tumor-reactive clonotype dynamics underlying clinical response to TIL therapy in melanoma

The profiles, specificity and dynamics of tumor-specific clonotypes that are associated with clinical response to adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) remain unclear. Using single-cell RNA/TCR-sequencing, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients treated with TIL-ACT. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, which were more effectively mobilized upon in vitro expansion, yielding products with higher numbers of tumor-specific CD8+ cells, which also preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes, and with cell products mostly composed of blood-borne clonotypes mainly persisting in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost the specific signatures of states originally exhibited in tumors, including exhaustion, and in responders acquired an intermediate exhausted effector state after tumor engraftment, revealing important functional cell reinvigoration.

cancer biology↗

Role of pollen flavonoids in the heather-bumble bee-parasite interactions

There is evidence that specialised metabolites of flowering plants occur in both vegetative parts and floral resources (i.e., pollen and nectar), exposing pollinators to their biological activities. While such metabolites may be toxic to bees, it may also help them to deal with environmental stressors. One example is heather nectar which has been shown to limit bumble bee infection by a trypanosomatid parasite, Crithidia sp., because of callunene activity. Besides in nectar, heather harbours high content of specialised metabolites in pollen such as flavonoids but they have been poorly investigated. In this study, we aimed to assess the impact of Crithidia sp., heather pollen and its flavonoids on bumble bees using non-parasitised and parasitised microcolonies fed either control pollen diet (i.e., willow pollen), heather pollen diet, or flavonoid-supplemented pollen diet. We found that heather pollen and its flavonoids significantly affected microcolonies by decreasing pollen collection as well as offspring production, and by increasing male fat body content while parasite exposure had no significant effect except for an increase in male fat body. We did not highlight any medicinal effect of heather pollen or its flavonoids on parasitised bumble bees. Our results provide insight into the impact of pollen specialised metabolites in heather-bumble bee-parasite interactions. They underline the contrasting roles for bumble bees of the two floral resources and highlight the importance of considering both nectar and pollen when addressing medicinal effects of a plant towards pollinators.

ecology↗

Nanopore adaptive sampling of a metagenomic sample derived from a human monkeypox case

In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore Whole Genome Sequencing of a local monkeypox sample on a PromethION 24. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. Nanopore sequencing is a highly versatile method to characterize a virus in real-time without pre-sequencing target enrichment.

microbiology↗

Unsupervised encoding selection through ensemble pruning for biomedical classification

BackgroundOwing to the rising levels of multi-resistant pathogens, antimicrobial peptides, an alternative strategy to classic antibiotics, got more attention. A crucial part is thereby the costly identification and validation. With the ever-growing amount of annotated peptides, researchers leverage artificial intelligence to circumvent the cumbersome, wet-lab-based identification and automate the detection of promising candidates. However, the prediction of a peptides function is not limited to antimicrobial efficiency. To date, multiple studies successfully classified additional properties, e.g., antiviral or cell-penetrating effects. In this light, ensemble classifiers are employed aiming to further improve the prediction. Although we recently presented a workflow to significantly diminish the initial encoding choice, an entire unsupervised encoding selection, considering various machine learning models, is still lacking. ResultsWe developed a workflow, automatically selecting encodings and generating classifier ensembles by employing sophisticated pruning methods. We observed that the Pareto frontier pruning is a good method to create encoding ensembles for the datasets at hand. In addition, encodings combined with the Decision Tree classifier as the base model are often superior. However, our results also demonstrate that none of the ensemble building techniques is outstanding for all datasets. ConclusionThe workflow conducts multiple pruning methods to evaluate ensemble classifiers composed from a wide range of peptide encodings and base models. Consequently, researchers can use the workflow for unsupervised encoding selection and ensemble creation. Ultimately, the extensible workflow can be used as a plugin for the PEPTIDE REACToR, further establishing it as a versatile tool in the domain.

bioinformatics↗

Isolated Grauer's gorilla populations differ in diet and gut microbiome

The animal gut microbiome has been implicated in a number of key biological processes, ranging from digestion to behavior, and has also been suggested to facilitate local adaptation. However, studies in wild animals rarely compare multiple populations that differ ecologically, which is the level at which local adaptation may occur. Further, few studies simultaneously characterize diet and the gut microbiome from the same sample, despite the likely presence of co-dependencies. Here, we investigate the interplay between diet and gut microbiome in three geographically isolated populations of the critically endangered Grauers gorilla, which we show to be genetically differentiated. We find population- and social group-specific dietary and gut microbial profiles and co-variation between diet and gut microbiome, despite the presence of core microbial taxa. There was no detectable effect of age, sex, or genetic relatedness on the microbiome. Diet differed considerably across populations, with the high-altitude population consuming a lower diversity of plants compared to low-altitude populations, consistent with food plant availability constraining diet. The observed pattern of covariation between diet and gut microbiome is likely a result of long-term social and ecological factors. Our study suggests that the gut microbiome is sufficiently plastic to support flexible food selection and hence contribute to local adaptation.

ecology↗

Prevalence of bovine tuberculosis and characterization of the members of the Mycobacterium tuberculosis complex from slaughtered cattle in Rwanda

BackgroundBovine tuberculosis (bTB) is an endemic disease in Rwanda, but little is known about its prevalence and causative mycobacterial species. The disease causes tremendous losses in livestock and wildlife and remains a significant threat to public health. Materials and methodsA cross-sectional study employing a systematic random sampling of cattle (n=300) with the collection of retropharyngeal lymph nodes and tonsils (n=300) irrespective of granulomatous lesions was carried out in six abattoirs to investigate the prevalence and identify mycobacterial species using culture, acid-fast bacteria staining, polymerase chain reaction, and GeneXpert assay. Individual risk factors and the origin of samples were analysed for association with the prevalence. FindingsOf the 300 samples, six were collected with visible TB-like lesions. Our findings demonstrated the presence of Mycobacterium tuberculosis complex (MTBC) in 1.7% (5/300) of sampled slaughtered cattle. M. bovis was isolated from 1.3% (4/300) animals while one case was caused by a rifampicin-resistance (RR) M. tuberculosis. Non-tuberculous mycobacteria were identified in 12.0% (36/300) of the sampled cattle. There were no significant associations between the prevalence and abattoir category, age, sex, and breeds of slaughtered cattle. ConclusionsThis study is the first in Rwanda to isolate both M. bovis and RR M. tuberculosis in slaughtered cattle indicating that bTB is prevalent in Rwanda with a low prevalence. The isolation of RR M. tuberculosis from cattle indicates possible zooanthroponotic transmission of M. tuberculosis and close human-cattle contact. To protect humans against occupational zoonotic diseases, it is essential to control bTB in cattle and raise the awareness among all occupational groups as well as reinforce biosafety at the farm level and in the abattoirs. Authors summaryTuberculosis in cattle (bTB) causes financial losses to livestock owners and is a disease transmissible to humans especially those with an occupational risk through exposure to infected animals and animal products. This study aimed to identify the prevalence of bTB and characterize the mycobacterial species from cattle slaughtered in the six abattoirs in Rwanda. Four M. bovis, as well as one rifampicin-resistant (RR) M. tuberculosis, were identified from slaughtered cattle and, thus, the apparent bTB prevalence was 1.7% (5/300). Likely, the RR M. tuberculosis isolate was mostly likely of human origin and transmitted to cattle during close human-cattle contact. It is therefore essential to control bTB in cattle and reinforce the protection of farmworkers and abattoir workers who are always exposed to infected animals.

microbiology↗

The origin and drivers of Neotropical plant and tetrapod diversification

The origins and evolution of the outstanding Neotropical biodiversity are still debated. A comprehensive understanding is hindered by the lack of deep-time comparative data across wide phylogenetic and ecological contexts. Here, we evaluate four evolutionary scenarios assuming different diversification trajectories and drivers of Neotropical diversification, and assess their variation across Neotropical regions and taxa. Our analysis of 150 phylogenies (12,512 species) of seed plants and tetrapods reveals that Neotropical diversity has mostly expanded through time (70% of the clades), while scenarios of saturated and declining diversity also account for 21% and 9% of Neotropical diversity, respectively. We identify five biogeographic areas that represent distinctive units of long-term Neotropical evolution (Pan-Amazonia, Dry Diagonal, Bahama-Antilles, Galapagos, and an elsewhere region) and find that diversity dynamics do not differ across these areas, suggesting no geographic structure in long-term Neotropical diversification. In contrast, diversification dynamics differ substantially across taxa: plant diversity mostly expanded through time (88%), while a substantial fraction (43%) of tetrapod diversity accumulated at a slower pace or declined toward the present. These opposite evolutionary patterns may reflect different capacities for plants and tetrapods to cope with climate change, with potential implications for future adaptation and ecosystem resilience.

evolutionary biology↗

There is more than chitin synthase in insect resistance to benzoylureas: Molecular markers associated with teflubenzuron resistance in Spodoptera frugiperda

Chitin synthesis inhibitors are successfully used in pest control and are an excellent option for use in integrated pest management programs due to their low non-target effects. Reports on field-evolved resistance of lepidopteran pests to chitin synthesis inhibitors and the selection of laboratory resistant strains to these products require a detailed investigation on the resistance mechanisms and on the identification of molecular markers to support the implementation of efficient monitoring and resistance management programs. Teflubenzuron is a chitin synthesis inhibitor highly effective in controlling lepidopteran pests, including nowadays the world widely distributed fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera: Noctuidae). We report the selection of a laboratory strain of S. frugiperda resistant to teflubenzuron, and its use for the characterization of the inheritance of resistance, evaluation of cross-resistance to other chitin-synthesis inhibitors and the identification of a set of single nucleotide polymorphisms (SNPs) for use as candidate molecular markers for monitoring the evolution of resistance of S. frugiperda to teflubenzuron. The resistance of the selected strain of S. frugiperda to teflubenzuron was characterized as polygenic, autosomal, and incompletely recessive. The resistance ratio observed was nearly 1,365-fold. Teflubenzuron-resistant strain showed some cross-resistance to lufenuron and novaluron but not to chlorfluazuron. We also detected a set of 72 SNPs that could support monitoring of the resistance frequency to teflubenzuron in field populations. Our data contribute to the understanding of the resistance mechanisms and the inheritance of polygenic resistance of S. frugiperda to benzoylureas. We also contribute with candidate markers as tools for monitoring the emergence and spread of teflubenzuron resistance in S. frugiperda.

evolutionary biology↗