Biology subjects

Moro, L.

Publications and source records attributed to Moro, L..

9 recordsLinked to original sources

bioRxiv2026

Inhibition of the Adenosine pathway activates the immune response against Mesothelioma.

BackgroundMesothelioma (Me) is an aggressive cancer with limited response to conventional therapies. The tumors harsh microenvironment contributes to immune escape and therapy resistance and the effects of ICIs on Me are still unclear. Adenosine, an immunosuppressive molecule produced from AMP by the enzyme CD73, accumulates in hypoxic tumor areas. Elevated CD73 and adenosine receptor A2B (A2Br) levels on Me cells are linked to worse patient outcomes, indicating their important role in disease progression and potential as targets for treatment. AimThis study characterizes the Me-ME (micro environment) and evaluates the efficacy of TT-4 (A2B inibitor) and AB680 (CD73 inibitor), alone or with aPD-1, using 3D models in vitro and in vivo. MethodsCD73 and A2B receptor levels were quantified in tumor and normal samples using qRT-PCR and IHC. Cells lines were treated with CoCl2 to mimic hypoxia, then CD73, A2Br and related markers were analyzed. MSTO-211H and REN cells were silenced for CD73, grown as spheroids and adenosine release was measured. Co-culture spheroids of MSTO-211H and Jurkat cells were treated with AMP and CD73 inhibitor, then analyzed for viability and immune markers. An orthotopic Me model was established by injecting AB1-B/c-LUC cells and monitored by in vivo imaging. Proteomic analysis of spheroids was conducted to identify proteins and pathways involved. ResultsHypoxia boosts CD73 and A2Br expression in Me cells, leading to adenosine production via CD73. In 3D co-cultures, AB680 lowered Me cell viability and enhanced activation of Jurkat T cells. In mice, combining aPD-1 therapy with A2Br or CD73 inhibitors strongly reduced tumor growth. Proteomics identified 93 proteins influenced by adenosine signaling through A2B. ConclusionTargeting the adenosine pathway alongside PD-1 blockade offers a promising new immunotherapy strategy for Me.

cancer biology↗

bioRxiv2026

HOW FIVE DECADES OF LAND-COVER CHANGE RESHAPED SUITABLE HABITAT FOR PUERTO RICAN TREE SPECIES

AimHuman land-use has dramatically altered the amount, quality, and connectivity of habitat for species worldwide. Understanding how these changes affect individual species is essential for predicting the overall consequences of land-use change for biodiversity. LocationThe Caribbean island of Puerto Rico. Forest cover on the island increased from about 18 to 45% from the late 1940s to the early 2000s. MethodsUsing data on geographic distributions and functional traits for 454 tree species, we evaluated how gain of potential habitat was related to species-specific climatic associations and life-history strategies. We estimated species-specific potential habitat (climatically suitable and forested) with species distribution models and data on forest cover. We characterized each species niche breadth (the range of environmental conditions it occupies) and niche position (the environmental conditions it prefers) to compare with the conditions in reforested areas. ResultsSpecies with relatively more potential habitat in 1951 (climatically suitable and forested) also had relatively larger gains in potential habitat from 1951 to 2000. Species that tend to occupy conditions different from those common in reforested areas (i.e., more marginal habitats) gained relatively less potential habitat and species with broad environmental niches gained more potential habitat. Additionally, species with relatively acquisitive functional traits gained more suitable habitat than those with relatively conservative traits. Main conclusionsOur results show that Puerto Ricos reforestation preferentially increased habitat for species that (1) already had suitable habitat in the landscape, (2) tolerate a wide range of climatic conditions, and (3) exhibit fast, acquisitive functional strategies. These findings illustrate how land-use change in heterogeneous tropical landscapes can generate non-uniform habitat gains across species, potentially favoring generalist over specialist species and reshaping community composition.

ecology↗

bioRxiv2026

A comparative dataset on population genetics, traits, and distributions for nineteen Caribbean tree species

Although genetic diversity is a fundamental component of biodiversity, we lack data for a majority of species, particularly in biodiversity hotspots such as tropical forests. We present a comparative genetic dataset of 19 tropical tree species (including one palm) from the Caribbean island of Puerto Rico and neighboring islands (Hispanola and the US Virgin Islands). Using a reduced-representation sequencing technique (SLAF-seq), we identified species-specific single-nucleotide polymorphism (SNP) datasets with 24,413 to 433,637 high-quality SNPs per species. The focal species represent a range of life-history and climate associations, which may be relevant to their genetic structure. Therefore, we also include complementary information on species functional traits (wood density, leaf thickness, specific leaf area, maximum height, and seed dry mass), as well as geographic distributions and climatic associations from species distribution models.

genetics↗

bioRxiv2025

Metabolic Maturation Unveils Left Ventricular Identity in WNT ON/OFF Human Pluripotent Stem Cell-Derived Cardiomyocytes

Deriving high-purity mature left ventricular (LV) cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) is a priority for cardiovascular research and for future therapeutic applications. Small-molecule WNT modulation (WNT ON/OFF) is currently the predominant differentiation method; however, a critical discordance exists regarding its cardiac subtype outcome. While lineage tracing suggests a First Heart Field (FHF) bias, phenotypic characterizations report significant heterogeneity regarding definitive ventricular markers, leading to controversy about the cardiac subtypes generated by this method. Here, we demonstrate that this apparent heterogeneity is a result of CM immaturity. Using single-cell protein analysis, we first show that WNT ON/OFF generates an NKX2.5+ progenitor pool that robustly co-expresses HAND1, confirming uniform FHF specification regardless of differentiation efficiency. We then demonstrate that the CM population negative for the ventricular marker MYL2 observed at early differentiation timepoints mostly represents immature LV cardiomyocytes that have not yet acquired their definitive phenotype. By implementing a targeted metabolic maturation regime, we unlocked this identity, achieving 95% MYL2+/HAND1+/TBX5+ LV CMs by day 38, substantially earlier and with higher chamber-specific purity than previously reported. This phenotypic resolution was accompanied by advanced structural maturation, including sarcomeric protein isoform switching, multinucleation, and notably, the assembly of polarized XIRP2+ intercalated discs, a hallmark of postnatal CM maturation not previously described in 2D differentiations. Validated across three independent hPSC lines, these findings provide the field with a rapid, high-fidelity platform for generating pure mature LV cardiomyocytes for disease modeling and therapeutic research.

developmental biology↗

bioRxiv2025

Multilayered human activities shape the microbial communities of groundwater-dependent ecosystems in an arid oceanic island

Island coastal aquifers, though physically small compared to continental groundwater systems, are of huge ecological and societal importance, sustaining functions that connect to locally crucial provision, maintenance and culture ecosystem services. Those functions are largely dependent on the presence of highly adapted biological communities, for which, their microbial communities remain understudied. Our goal is to describe the bacterial communities across the groundwater-dependent ecosystems on Lanzarote, spanning a gradient of anthropogenic pollution using 16SrRNA amplicon sequencing. We sampled coastal caves and pools, wells and water galleries, springs, saltworks and marine bays affected by submarine groundwater discharge. Ecological analyses highlight that richness and composition of bacterial communities strongly depend on the type of habitats. Pathogens and human-derived species were ubiquitous in our samples, but, strikingly, caves and wells were strongly enriched with them compared to other habitats. We propose that our results highlight the susceptibility of groundwater environments to pollution and indicate that aquifers act as reservoirs of biological contamination in addition to natural diversity--regardless of their salinity. Since this enrichment might compromise some of the functions and services that groundwater-dependent ecosystems provide in oceanic islands, we call for integrative conservation strategies that include hydrological and biological perspectives into the decision making.

microbiology↗

bioRxiv2024

SHEN-LONG, a novel cardiac regulatory locus, regulates cardiac master transcription factor NKX2-5 in pluripotent stem cell derived cardiomyocytes

Cardiac development is a finely regulated process, transforming undifferentiated cells into the specialized cell components of the heart. Super-Enhancers (SE), clusters of enhancers densely populated with transcription factors, play a central role in cell fate decisions, including cardiogenesis. In this work, we studied a cardiac SE in chr3q25.31. This locus also contains a cardiac specific long non-coding RNA: LINC00881 (LINC881). We termed this region of interest SHEN-LONG (Super Heart ENhancer and LONG non-coding LINC881), and selected it for further functional characterization. Our analysis revealed SHEN-LONG is a hotspot of cardiac kernel transcription factor binding sites. Cardiac differentiation of human iPSC with partial Knock Out of SHEN-LONG resulted in cardiomyocytes with reduced NKX2-5 expression, a master cardiac transcription factor, suggesting a significant role of SHEN-LONG in this process. Whole transcriptome sequencing of SHEN-LONG KO cardiomyocytes produced 134 differentially expressed genes located at great distances (>4Mb) emphasizing its long-range functional impact. A regulation mediated essentially by the SE and not by LINC881 was confirmed when LINC881 overexpression did not recover NKX2-5 expression. These findings provide insights into a novel NKX2-5 regulatory mechanism. The knowledge gained in this work may pave the way for advances in therapeutic interventions for cardiovascular disorders.

molecular biology↗

bioRxiv2023

The transcription factor OCT6 promotes the dissolution of the naive pluripotent state by repressing Nanog and activating a formative state gene regulatory network.

Animal development relies on complex gene regulatory networks (GRNs) that govern the nearly irreversible changes that occur during cell differentiation. In this work we aimed to determine key transcription factors (TFs) associated with the dissolution of the naive pluripotent state and the acquisition of a formative identity. We identified OCT6 as one of the earliest TFs induced during the onset of mouse embryonic stem cell (mESCs) differentiation. To investigate its role, we generated an Oct6 knockout mESC line, which failed to acquire the characteristic cell morphology associated with the formative state. Transcriptome analysis of differentiating cells revealed nearly 300 differentially expressed genes compared to wild-type cells, including pluripotency TFs Nanog, Klf2, Nr5a2, Prdm14, and Esrrb, that failed to correctly downregulate. Notably, premature expression of OCT6 in naive cells triggered a rapid morphological transformation mirroring differentiation, accompanied by self-induction of Oct6 and expression of TFs such as Sox3, Zic2/3, Foxp1, as well as the formative genes Dnmt3A and FGF5. Strikingly, the majority of OCT6 expressing cells did not express NANOG. Gene expression and single molecule RNA-FISH analysis confirmed that this regulation was at the transcriptional level. Collectively, our results establish OCT6 as a key TF in the dissolution of the naive pluripotent state and support a model where Oct6 and Nanog form a double negative feedback loop which could act as a toggle switch important for the transition to the formative state. HighlightsO_LIOct6 is rapidly induced as mESCs exit ground state pluripotency. C_LIO_LILoss of OCT6 negatively affects the transition to formative pluripotency. C_LIO_LIPremature expression of OCT6 in mESCs is sufficient to induce a formative-like phenotype. C_LIO_LIOCT6 and NANOG repress each other forming a double negative feedback loop. C_LI

developmental biology↗

bioRxiv2019

The Dream Catcher experiment: Blinded analyses disconfirm markers of dreaming consciousness in EEG spectral power

The Dream Catcher test defines the criteria for a genuine discovery of the neural constituents of phenomenal consciousness. Passing the test implies that some patterns of purely brain-based data directly correspond to the subjective features of phenomenal experience, which would help to bridge the explanatory gap between consciousness and brain. Here, we conducted the Dream Catcher test for the first time in a graded and simplified form, capturing its core idea. The experiment involved a Data Team, who measured participants brain activity during sleep and collected dream reports, and a blinded Analysis Team, who was challenged to predict better than chance, based solely on brain measurements, whether or not a participant had a dream experience. Using a serial-awakening paradigm, the Data Team prepared 54 one-minute polysomnograms of NREM sleep--27 of dreamful sleep (3 from each of the 9 participants) and 27 of dreamless sleep--redacting from them all associated participant and dream information. The Analysis Team attempted to classify each recording as either dreamless or dreamful using an unsupervised machine learning classifier, based on hypothesis-driven, extracted features of EEG spectral power and electrode location. The procedure was repeated over five iterations with a gradual removal of blindness. At no level of blindness did the Analysis Team perform significantly better than chance, suggesting that EEG spectral power does not carry any signatures of phenomenal consciousness. Furthermore, we demonstrate an outright failure to replicate key findings of recently reported correlates of dreaming consciousness.\n\nHighlightsThe first reported attempt of the Dream Catcher test.\nThe correlates of conscious experience may not lie in EEG spectral power.\nReported markers of NREM dreaming consciousness misperformed in a blinded setting.\nThose markers also could not be confirmed in an unblinded setting.

neuroscience↗

bioRxiv2018

IFN-γ induces epithelial-to-mesenchymal transition of cancer cells via an unique microRNA processing

Interferon-{gamma} (IFN{gamma}) is a potent cytokine in modulating tumor immunity and tumoricidal effects. We demonstrate a new function of IFN{gamma} in inducing epithelial-to-mesenchymal transition (EMT) in normal and cancer cells from different cell types. IFN{gamma} activates JAK-STAT signaling pathway leading to the transcription of IFN-stimulated genes (ISGs), such as interferon-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster, as well as pre-miR-101 and pre-miR-128 with a similar 5-end structure with pre-miR-363. Noticeably, these suppressive miRNAs have similar functions by targeting EMT transcription factors in prostate cancer (PCa) cells. We further demonstrated that IFIT5 plays a critical role in IFN{gamma}-induced cell invasiveness in vitro and lung metastasis in vivo. Clinically, IFIT5 is highly elevated in high-grade PCa and its expression inversely correlates with these suppressive miRNAs. Altogether, this study unveils pro-tumorigenic role of the IFN pathway via a new mechanism of action, which certainly raises concern about its clinical application.

cancer biology↗