Biology subjects

Moretti, M.

Publications and source records attributed to Moretti, M..

12 recordsLinked to original sources

bioRxiv2026

Joint effects of climate change and urbanization accelerate plant biodiversity loss across urban green spaces

Urbanization and climate change are rapidly reshaping biodiversity worldwide, yet their combined impacts on ecosystems remain poorly understood. Urban green spaces (UGS) underpin urban biodiversity, but differ widely in their structure, management, and exposure to global change. Here, we examine how these two drivers jointly influence plant communities across five major UGS types (allotments, private gardens, residential green spaces, parks, and ruderal areas) in three socio-culturally distinct Swiss cities. By combining vegetation surveys from 180 sites (60 sites per city) with species-specific thermal niches, high-resolution projections of historical and future urban microclimates, and land-use change scenarios, we trace how climate-driven species loss interacts with the shifting availability of urban habitats to shape biodiversity outcomes by mid-century. We found that UGS types differed markedly in their contributions to biodiversity, with allotments and ruderal areas supporting disproportionately high compositional uniqueness. However, climate change alone was projected to drive substantial plant diversity declines across all UGS types, with 40-80% of species exceeding their thermal niches by mid-century based on climate change scenario and UGS type. Although allotments exhibited relatively greater tolerance due to broader community-level thermal preferences, this advantage was undermined by their rapid decline under urbanization. When considered jointly, climate change and urbanization generated widespread biodiversity losses through complementary mechanisms: climate change drove species declines, while urbanization amplified these losses by disproportionately reducing high-value habitats. These results reveal a consistent trajectory of biodiversity decline across urban landscapes and highlight the need to conserve high-diversity yet shrinking UGS, particularly allotments, while enhancing the ecological value and climate resilience of expanding UGS, such as parks and residential areas, to safeguard future urban biodiversity under global change.

ecology↗

bioRxiv2026

Investigating the mechanism of resistance to indaziflam in Poa annua

Indaziflam is an effective herbicide for controlling Poa annua, a weed, in turfgrass, orchards, and rangelands. An RNA-seq analysis was performed to identify differentially expressed genes associated with indaziflam-resistance in P. annua populations, with heterologous transformation performed for validation of candidate gene. Additionally, whole transcriptome variant calling was used to determine potential target site mutations. Transcriptome data were analyzed using weighted gene co-expression network analysis, Multiple modules were identified with high correlation to ED50 values of the resistant and susceptible populations. A cytochrome P450, CYP81A91_A, was identified that was homologous to CYP81A10 that confers resistance to five different herbicidal modes of action in Lolium rigidum. A single nucleotide polymorphism (SNP) causing an amino acid change (Thr432Arg) in coatomer subunit {gamma} was identified P. annua populations and several others originating from orchards. The up-regulated and positively correlated CYP81A91_A identified, when transformed to Arabidopsis thaliana, did not provide resistance to indaziflam; however, it did provide multifold resistance to simazine, another triazine class herbicide from a different MOA. A SNP in coatomer subunit {gamma} (Thr432Arg) was identified that may provide target site resistance given that coatomer proteins are involved in vesicle trafficking and in recycling of the cellulose synthase. HIGHLIGHTThis paper is a in-depth characterization of indaziflam resistance in Poa annua that identifies a novel mutation in coatomer subunit {gamma} as the potential root cause.

plant biology↗

bioRxiv2026

Small habitat patches can be the largest contributors to urban biodiversity across taxonomic groups

AimAs cities densify and expand, the careful planning and design of green spaces are essential for supporting urban biodiversity. Here, we evaluate the relative contribution of habitat patches of varying size, quality, and connectivity to urban biodiversity and assess environmental factors driving differences in species richness and community composition. LocationZurich, Switzerland. Time period: 2008-2018.Major taxa studied: Invertebrates, vertebrates, and trees. MethodsWe analyzed species occupancy data from 452 habitat patches. We quantified alpha, beta, and gamma diversity, assessed species-area relationships, and applied generalized dissimilarity modelling to test the role of patch area, connectivity, and habitat quality--proxied through environmental variables, including vegetation complexity, water presence, and forest isolation--in shaping community composition. ResultsAlpha diversity increased significantly with area, although small patches (usually < 5 ha) disproportionately contributed to beta diversity. Per unit area, groups of small patches yielded higher gamma diversity than equivalent areas of large patches, particularly for trees and invertebrates. Community composition was strongly influenced by patch area, with effects mediated by vegetation complexity, water, and isolation, with responses differing among taxa. Main conclusionsSmall habitat patches play a critical role in enhancing overall urban biodiversity. They increase species richness through cumulative area effects and promote community turnover (mediated by environmental heterogeneity). Maintaining networks of small patches alongside large green spaces is therefore key to conserving biodiversity in urban landscapes.

ecology↗

bioRxiv2025

Targeting Aberrant FGFR Signaling with Infigratinib Enhances the Efficacy of BTK/PI3K Inhibitors and Bendamustine in Lymphoma Cells

BackgroundAberrant fibroblast growth factor receptor (FGFR) signaling sustains survival and drug tolerance in various cancers, including B-cell lymphomas. We profiled FGFR/FGF expression and evaluated the FGFR1-3 inhibitor infigratinib, both alone and in combination with standard agents, in models of mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and diffuse large B-cell lymphoma (DLBCL). MethodsTwenty-eight cell lines (MCL n=10; MZL n=7, including BTK/PI3K inhibitor-resistant derivatives; ABC-DLBCL n=3; GCB-DLBCL n=8) were tested by 72-h MTT assays for single-agent and fixed-ratio combination activity. Transcriptome profiling (4, 8, 12 h) was performed in MZL Karpas1718 cells treated with infigratinib (500 nM), ibrutinib (10 nM), or the combination. ResultsMCL preferentially expressed FGFR3/FGF9, whereas ABC-DLBCL and MZL expressed FGFR1/FGF2; FGFR1 was further enriched in resistant MZL models, consistent with autocrine activation. Infigratinib showed dose-dependent but modest single-agent activity across the panel (median IC50 3.58 M, indicating limited efficacy at clinically achievable exposures ([≤]500 nM). However, combinations were broadly synergistic: in MCL, infigratinib with ibrutinib (4/4 lines) and bendamustine (5/5) outperformed either agent alone, with weaker effects with rituximab (2/4). In MZL (parental and resistant), infigratinib synergized with ibrutinib (6/6), copanlisib (6/6), and idelalisib (4/6), restoring sensitivity in resistant derivatives; synergy occurred at infigratinib concentrations [≤]500 nM. Mechanistically, RNA-seq revealed largely distinct single-agent programs: ibrutinib suppressed BCR/NF-{kappa}B/inflammatory signaling, while infigratinib preferentially repressed E2F/MYC cell-cycle modules. In contrast, the combination concomitantly downregulated NF-{kappa}B pathways and abrogated MYC target signatures, with coordinated modulation of apoptosis and DNA-repair transcripts. ConclusionsFGFR1/3-driven autocrine signaling contributes to adaptive survival in MCL and MZL. Although infigratinib has limited single-agent activity, it potentiates BTK/PI3K inhibitors and bendamustine at clinically relevant concentrations and reverses acquired resistance, supporting biomarker-guided clinical evaluation of FGFR blockade in relapsed/refractory MCL and MZL.

cancer biology↗

bioRxiv2025

High-Throughput Screening Identifies PLK1 Inhibition as a Strategy to Potentiate BTK Blockade in Marginal Zone Lymphoma

B-cell receptor (BCR) signaling is a key therapeutic target in B-cell lymphomas, and Bruton tyrosine kinase inhibitors (BTKi) have demonstrated clinical efficacy in marginal zone lymphoma (MZL). However, the rate of complete remissions is relatively low, and resistance remains a significant clinical challenge, underscoring the need for novel combination strategies. To identify compounds that enhance the activity of BTKi and overcome resistance, we conducted a high-throughput screen of 1,695 compounds using a previously developed MZL model of acquired resistance to BTK and PI3K inhibitors derived from the Karpas1718 cell line. Thirty-three compounds showed single-agent anti-proliferative activity in the nanomolar range, both in the Karpas1718-resistant and parental cells. Based on their clinical potential in combination with BTKi, seven compounds were selected for further validation. The polo-like kinase 1 (PLK1) inhibitor rigosertib emerged as a top candidate, showing strong activity in both parental and BTKi-resistant cell lines. Combination treatment of rigosertib and BTKi zanubrutinib resulted in broad transcriptomic changes, characterized by the downregulation of pathways involved in B-cell activation, proliferation, and BCR signaling. Mechanistically, the combination reduced phosphorylation of key BCR pathway components and inhibited NF-{kappa}B nuclear translocation. These findings suggest that PLK1 inhibition can overcome BTKi resistance by further inhibiting BCR signaling through the canonical NF-{kappa}B pathway. Therefore, the dual pharmacological inhibition of BTK and PLK1 is a promising therapeutic approach for patients with MZL and warrants further preclinical and clinical investigations.

cancer biology↗

bioRxiv2025

A High-Throughput Bone Marrow 3D Co-Culture System to Develop Resistance to B Cell Receptor Signaling Targeted Agents in B Cell Non-Hodgkin Lymphoma

B cell receptor (BCR) signaling plays a central role in the pathogenesis of B cell lymphomas, making it a crucial therapeutic target. The advent of BCR-targeted inhibitors, particularly those directed at PI3K and BTK, has revolutionized treatment for B cell non-Hodgkin lymphoma (B-NHL). However, therapeutic resistance remains a significant clinical challenge. Increasing evidence suggests that the tumor microenvironment (TME), particularly the bone marrow (BM) microenvironment, is crucial in driving cancer progression and therapeutic resistance. The BM microenvironment provides a specialized niche where lymphoma cells can evade therapy through interactions with stromal cells and extracellular matrix (ECM) components. Bone marrow stromal cells (BMSCs) contribute significantly to this resistance. In this study, we developed an in vitro 3D model to better understand B cell lymphoma biology and drug resistance mechanisms. We co-cultured lymphoma cell lines with primary BMSCs in a 3D fibrin gel matrix using a high-throughput and automated system. Our results revealed that BMSCs modulate lymphoma cell growth and reduce their sensitivity to the PI3K inhibitor copanlisib and the BTK inhibitor ibrutinib. Furthermore, this model allowed us to identify IGFBP-3, Serpin E1, and PTX-3 as potential mediators of therapeutic resistance. These findings underscore the value of using 3D co-culture models in preclinical settings to more accurately study drug resistance, as they more closely simulate the BM microenvironments complexity than traditional 2D models, thus improving the predictive value of drug testing in B cell lymphomas. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/632958v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@72bc6aorg.highwire.dtl.DTLVardef@afdda2org.highwire.dtl.DTLVardef@1fff494org.highwire.dtl.DTLVardef@11252cf_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVisual AbstractC_FLOATNO C_FIG

cancer biology↗

bioRxiv2024

A global synthesis on land-cover changes in watersheds shaping freshwater detrital food webs

Anthropogenic land-cover changes are among the most pressing global threats to both aquatic and terrestrial ecosystems, jeopardising biodiversity and the critical connections between these systems. Resource flows and trophic interactions intricately link aquatic and terrestrial ecosystems, with terrestrial-derived detritus playing a foundational role in supporting aquatic food webs. These detrital inputs form essential cross-ecosystem linkages, underpinning key ecological processes and providing vital resources for aquatic communities. Yet, little research has focused on how land-cover changes cascade across this linkage. To better understand how land-cover changes in the watershed influence freshwater detrital food webs, we conducted a meta-analysis of field studies reporting the effects of vegetation changes on freshwater detrital consumers and organic matter decomposition. The results from 144 studies, reporting 1235 comparisons, showed that, overall, land-cover changes in the watershed vegetation, especially through harvest and land-use conversion, have negative effects on aquatic biodiversity and ecosystem processes. These vegetation changes reduced diversity, abundance, and biomass across multiple trophic levels in freshwater detrital food webs. Studies examining multiple organism groups most often observed negative responses across multiple trophic levels, suggesting that the land-cover changes negatively affected multiple detrital food web components simultaneously. Our results also show that outcomes of restoration of watershed vegetation were context-dependent, and no clear trend of improvement was visible. Therefore, conservation of natural riparian and catchment vegetation are key to maintain freshwater ecosystem processes and aquatic biodiversity worldwide, and more efficient and evidence-based restoration measures are urgently needed. As our global synthesis shows that direct human-induced alterations of vegetation type in watersheds have significant negative effects on freshwater detrital food webs, there is a pressing need to consider cross-ecosystem consequences of land-cover changes in conservation and ecosystem management.

ecology↗

bioRxiv2024

Biodiversity and riparian forests are mutual biological drivers of ecosystem functions in temperate and tropical streams

Fluxes of energy, matter, and organisms sustain linkages and functions within and between ecosystems. Yet, how biological drivers influence interactions and functions at the interface between aquatic and terrestrial environments (i.e., aquatic-terrestrial ecosystem functions) locally and across regions has received little attention. To test the relative importance of biological drivers on multiple aquatic-terrestrial ecosystem functions, we subsidised local terrestrial detritus in forested and non-forested stream sites in a temperate and tropical region. We also manipulated leaf litter diversity (horizontal biodiversity of resources) and macroinvertebrate access (vertical biodiversity of consumers). We measured secondary production of aquatic fungi, in-stream leaf litter nitrogen loss, and decomposition rates. The simultaneous provision of all three ecosystem functions (i.e., multifunctionality) was positively driven by vertical biodiversity and riparian forests in both regions. In both tropical and temperate streams, nitrogen loss was associated with vertical biodiversity. Decomposition rates were also enhanced by vertical biodiversity and linked to other ecosystem functions. These results reveal strong and consistent effects of biodiversity and riparian forests on aquatic-terrestrial ecosystem functions in freshwater detrital food webs in both temperate and tropical headwater streams. Thus, disentangling the drivers of ecosystem functions in these systems requires an understanding of underlying mechanisms beyond ecosystem borders.

ecology↗

bioRxiv2023

Rational positioning of 3D printed micro-bricks to realize high-fidelity, multi-functional soft-hard interfaces

AO_SCPLOWBSTRACTC_SCPLOWLiving organisms have developed design principles, such as functional gradients (FGs), to interface hard materials with soft ones (e.g., bone and tendon). Mimicking such design principles can address the challenges faced when developing engineered constructs with soft-hard interfaces. To date, implementing these FG design principles has been primarily performed by varying the ratio of the hard phase to that of the soft phase. Such design approaches, however, lead to inaccurate mechanical properties within the transition zone. That is due to the highly nonlinear relationship between the material distribution at the microscale and the macroscale mechanical properties. Here, we 3D print micro-bricks from either a soft or a hard phase and study the nonlinear relationship between their arrangements within the transition zone and the resulting macroscale properties. We carry out experiments at the micro- and macroscales as well as finite element simulations at both scales. Based on the obtained results, we develop a co-continuous power-law model relating the arrangement of the micro-bricks to the local mechanical properties of the micro-brick composites. We then use this model to rationally design FGs at the individual micro-brick level and create two types of biomimetic soft-hard constructs, including a specimen modeling bone-ligament junctions in the knee and another modeling the nucleus pulposus-annulus fibrosus interface in intervertebral discs. We show that the implemented FGs drastically enhance the stiffness, strength, and toughness of both types of specimens as compared to non-graded designs. Furthermore, we hypothesize that our soft-hard FGs regulate the behavior of murine preosteoblasts and primary human bone marrow-derived mesenchymal stromal cells (hBMSCc). We culture those cells to confirm the effects of soft-hard interfaces on cell morphology as well as on regulating the expression of focal adhesion kinase, subcellular localization, and YAP nuclear translocation of hBMSCs. Taken together, our results pave the way for the rational design of soft-hard interfaces at the micro-brick level and (biomedical) applications of such designs.

bioengineering↗

bioRxiv2023

Habitat amount, temperature and biotic interactions drive community structure, life-history traits, and performance traits of cavity-nesting bees and wasps and their natural enemies in cities

O_LIUrban ecosystems are associated with socio-ecological conditions that can filter and promote taxa. However, the strength of the effect of ecological filtering on biodiversity could vary among biotic and abiotic factors. Here, we investigate the effects of habitat amount, temperature, and host-enemy biotic interactions in shaping communities of cavity-nesting bees and wasps (CNBW) and their natural enemies. C_LIO_LIWe installed trap-nests in 80 sites distributed along urban intensity gradients in 5 European cities (Antwerp, Paris, Poznan, Tartu and Zurich). We quantified the species richness and abundance of CNBW hosts and their natural enemies, as well as two performance traits (survival and parasitism) and two life-history traits (sex ratio and number of offspring per nest for the hosts). We analysed the importance of the abiotic and biotic variables using generalized linear models and multi-model inference. C_LIO_LIWe found that habitat amount and temperature were the main drivers of CNBW host responses, with larger habitat amounts resulting in higher species richness and abundance, and a larger total number of brood cells per nest for both bees and wasps, as well as a larger probability of survival for bees. Conversely, higher local temperatures decreased species richness, abundance, survival rate, number of brood cells per nest, and proportion of females in CNBW hosts. C_LIO_LIBiotic interactions with natural enemies shaped wasp species richness, with higher levels of parasitism resulting in more wasp species. Similarly, our results showed direct density-dependence between CNBW hosts and their natural enemies. C_LIO_LIOverall, our study highlights the importance of habitat amount and temperature in shaping urban food webs, through direct effects on hosts responses and the subsequent consequences for their natural enemies. As cities prepare to tackle the future consequences of global change, strategies that make it possible to maintain available habitat and mitigate urban overheating emerge as a key urban adaptation for biodiversity conservation. C_LI

ecology↗

bioRxiv2021

Systems biology analysis identifies TCF7L1 as a key regulator of metastasis in Ewing sarcoma

Identification of cancer stemness genes is crucial to understanding the underlying biology of therapy resistance, relapse, and metastasis. Ewing sarcoma (EwS) is the second most common bone tumor in children and adolescents. It is a highly aggressive cancer associated with a dismal survival rate (<30%) for patients with metastatic disease at diagnosis ([~]25% of cases). Hence, deciphering the underlying mechanisms of metastasis is imperative. EwS tumors are characterized by a remarkably silent genome with a single driver mutation generating an oncogenic fusion transcription factor (EWSR1-ETS). Thus, EwS constitutes an ideal model to study how perturbation of a transcriptional network by a dominant oncogene can mediate metastasis, even though canonical metastasis-associated genes are not mutated. Here, through the implementation of an integrative systems biology approach, we identified transcription factor 7 like 1 (TCF7L1, alias TCF3) as a prognostically-relevant and EWSR1-ETS suppressed determinant of metastasis in EwS. We demonstrated that conditional TCF7L1 re-expression significantly reduces EwS single-cell migration, invasion and anchorage-independent growth in 3D assays in vitro, and tumorigenesis in vivo mediated by its DNA binding domain. In primary EwS tumors as well as in functional orthotopic in vivo models, low TCF7L1 expression was associated with pro-metastatic gene signatures and a much higher migratory and metastatic capacity of EwS cells, which correlated with poor outcome of EwS patients. Collectively, our findings establish TCF7L1 as a major regulator of metastasis in EwS, which may be utilized as a prognostic biomarker and open inroads to future therapeutic intervention.

cancer biology↗

bioRxiv2019

Oncogenic hijacking of a developmental transcription factor evokes therapeutic vulnerability for ROS-induction in Ewing sarcoma

Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of transcription factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers.\n\nHere, we show that EWSR1-FLI1 hijacks the developmental transcription factor SOX6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that SOX6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol.\n\nCollectively, our results exemplify how aberrant activation of a developmental transcription factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

cancer biology↗