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Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neovascularização Patológica , Colangiocarcinoma/patologia , Colangiocarcinoma/irrigação sanguínea , Humanos , Neoplasias dos Ductos Biliares/patologia , Masculino , Feminino , Neovascularização Patológica/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Densidade MicrovascularRESUMO
Background: Gastric cancer brain metastasis (GCBM) represents a rare but highly aggressive malignancy. Metastatic cancer cells are highly heterogeneous and differentially remodels brain vasculature and immune microenvironments, which affects the treatment effectiveness and patient outcome. This study aimed to investigate the spatial interactions among different cell components, especially the vasculature system and the brain microenvironment of GCBM patients. Methods: We used digital spatial profiling to examine 140 regions composing tumor, immune, and brain tissues from three GCBM patients. Transcriptomic data with spatial information were analyzed for tissue areas related to different blood recruitment strategies. For validation, independent analysis of patient bulk transcriptomic data and in vivo single-cell transcriptomic data were performed. Results: Angiogenesis and blood vessel co-option co-existed within the same GCBM lesion. Tumors with high epithelial-mesenchymal transition and an enhanced transcriptomic gene signature composed of CTNNB1, SPARC, VIM, SMAD3, SMAD4, TGFB1, TGFB2, and TGFB3 were more prone to adopt blood vessel co-option than angiogenesis. Enriched macrophage infiltration, angiogenic chemokines, and NAMPT were found in angiogenic areas, while increased T cells, T cell activating cytokines, and reduced NAMPT were found in vessel co-option regions. Spatially, angiogenesis was enriched at the tumor edge, which showed higher DMBT1 expression than the tumor center. Conclusions: This study mapped the orchestrated spatial characteristics of tumor and immunological compositions that support the conventional and atypical vascularization strategies in GCBM. Our data provided molecular insights for more effective combinations of anti-vascular and immune therapies.
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Rapid body colouration changes in some animals, such as chameleons and octopuses, serve dual functions: camouflage and intraspecific communication. It has been hypothesized that these colouration changes originally evolved to provide camouflage and subsequently were co-opted as social signals; however, experimental model systems that are suitable for studying such evolutionary processes are limited. Here, we investigated the relationship between rapid colouration changes of the blackened markings and aggressive behaviours in male Oryzias celebensis, an Indonesian medaka fish, under triadic relationships (two males and one female) or three males conditions with two different environmental backgrounds. In an algae-covered tank, mimicking the common laboratory rearing conditions, males with blackened markings exhibited more frequent attacks towards different conspecific individuals compared with non-blackened males and females. The blackened males were seldom attacked by non-blackened males and females. By contrast, neither aggressive behaviours nor black colouration changes were observed in the transparent background condition with a brighter environment. These indicated that the blackened markings in O. celebensis serve as a social signal depending on the environmental backgrounds. Considering that such colouration changes for camouflage are widely conserved among teleost fishes, the traits are likely to be co-opted for displaying social signals in O. celebensis.
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Agressão , Oryzias , Pigmentação , Animais , Masculino , Feminino , Oryzias/fisiologia , Comportamento Social , Meio AmbienteRESUMO
Vascular co-option is a consequence of the direct interaction between perivascular cells, known as pericytes (PCs), and glioblastoma multiforme (GBM) cells (GBMcs). This process is essential for inducing changes in the pericytes' anti-tumoral and immunoreactive phenotypes. Starting from the initial stages of carcinogenesis in GBM, PCs conditioned by GBMcs undergo proliferation, acquire a pro-tumoral and immunosuppressive phenotype by expressing and secreting immunosuppressive molecules, and significantly hinder the activation of T cells, thereby facilitating tumor growth. Inhibiting the pericyte (PC) conditioning mechanisms in the GBM tumor microenvironment (TME) results in immunological activation and tumor disappearance. This underscores the pivotal role of PCs as a key cell in the TME, responsible for tumor-induced immunosuppression and enabling GBM cells to evade the immune system. Other cells within the TME, such as tumor-associated macrophages (TAMs) and microglia, have also been identified as contributors to this immunomodulation. In this paper, we will review the role of these three cell types in the immunosuppressive properties of the TME. Our conclusion is that the cellular heterogeneity of immunocompetent cells within the TME may lead to the misinterpretation of cellular lineage identification due to different reactive stages and the identification of PCs as TAMs. Consequently, novel therapies could be developed to disrupt GBM-PC interactions and/or PC conditioning through vascular co-option, thereby exposing GBMcs to the immune system.
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Neoplasias Encefálicas , Pericitos , Microambiente Tumoral , Pericitos/imunologia , Pericitos/patologia , Pericitos/metabolismo , Humanos , Microambiente Tumoral/imunologia , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Glioma/imunologia , Glioma/patologia , Glioma/metabolismo , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/metabolismo , Progressão da Doença , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologiaRESUMO
Tumor vasculature is pivotal in regulating tumor perfusion, immune cell infiltration, metastasis, and invasion. The vascular status of the tumor is intricately linked to its immune landscape and response to immunotherapy. Vessel co-option means that tumor tissue adeptly exploits pre-existing blood vessels in the para-carcinoma region to foster its growth rather than inducing angiogenesis. It emerges as a significant mechanism contributing to anti-angiogenic therapy resistance. Different from angiogenic tumors, vessel co-option presents a distinctive vascular-immune niche characterized by varying states and distribution of immune cells, including T-cells, tumor-associated macrophages, neutrophils, and hepatic stellate cells. This unique composition contributes to an immunosuppressive tumor microenvironment that is crucial in modulating the response to cancer immunotherapy. In this review, we systematically reviewed the evidence and molecular mechanisms of vessel co-option in liver cancer, while also exploring its implications for anti-angiogenic drug resistance and the immune microenvironment, to provide new ideas and clues for screening patients with liver cancer who are effective in immunotherapy.
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[This corrects the article DOI: 10.3389/fpsyg.2023.1176067.].
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Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology treatments. Clinical drugs frequently target the VEGF signalling pathway during sprouting angiogenesis. Accumulating evidence suggests that tumours can evade antiangiogenic therapy through other angiogenesis mechanisms in addition to the vascular sprouting mechanism involving endothelial cells. These mechanisms include (1) sprouting angiogenesis, (2) vasculogenic mimicry, (3) vessel intussusception, (4) vascular co-option, (5) cancer stem cell-derived angiogenesis, and (6) bone marrow-derived angiogenesis. Other non-sprouting angiogenic mechanisms are not entirely dependent on the VEGF signalling pathway. In clinical practice, the conversion of vascular mechanisms is closely related to the enhancement of tumour drug resistance, which often leads to clinical treatment failure. This article summarizes recent studies on six processes of tumour angiogenesis and provides suggestions for developing more effective techniques to improve the efficacy of antiangiogenic treatment.
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Sexual selection involving female choice or female preference ('inter-sexual' selection) and/or male-male competition ('intra-sexual' selection) is one of the key mechanisms for evolutionary diversification and speciation. In particular, sexual selection is recently suggested to be an important mode to drive the evolution of the "novel" phenotype (i.e., "evolutionary novelty"). Despite extensive studies performed on sexually selected traits or male-specific ornaments (or weapon-like structures) with respect to their evolutionary origin, history and fitness benefits, relatively little is known about the molecular genetic mechanisms underlying their developmental process. However, with advances in genomic technologies (including whole transcriptome analysis using Next Generation Sequencing [NGS] techniques; RNA-Seq), progress has been made to unveil the genetic background underpinning diverse sexually selected traits in different animal taxa. In the present review, empirical data on the genes, genetic mechanisms, or regulatory pathways underlying various sexually selected traits were compiled to explore whether "common" genetic architectures shape the development and evolution of these traits across evolutionarily distant animal lineages. It is shown that the recruitment of the pre-existing genetic network for a new purpose (i.e., gene network "co-option") is rather widespread in the development and evolution of sexually selected traits, indicating that particular genes or gene sets are repeatedly involved in different sexually selected traits. Information on genes or genetic mechanisms regulating the development of sexually selected traits is an essential piece to complete a whole picture of the origin and evolution of sexually selected traits.
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The development of complex phenotypes requires the coordinated action of many genes across space and time, yet many species have evolved the ability to develop multiple discrete, alternate phenotypes1-3. Such polymorphisms are often controlled by supergenes, sets of tightly-linked mutations in one or more loci that function together to produce a complex phenotype4. Although theories of supergene evolution are well-established, the mutations that cause functional differences between supergene alleles remain essentially unknown. doublesex is the master regulator of insect sexual differentiation but functions as a supergene in multiple Papilio swallowtail butterflies, where divergent dsx alleles control development of discrete non-mimetic or mimetic female wing color patterns5-7. Here we demonstrate that the functional elements of the mimetic allele in Papilio alphenor are six new cis-regulatory elements (CREs) spread across 150 kb that are bound by DSX itself. Our findings provide experimental support to classic supergene theory and suggest that the evolution of auto-regulation may provide a simple route to supergene origination and to the co-option of pleiotropic genes into new developmental roles.
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Vessel co-option (VCO) is a non-angiogenic mechanism of vascularization that has been associated to anti-angiogenic therapy. In VCO, cancer cells hijack the pre-existing blood vessels and use them to obtain oxygen and nutrients and invade adjacent tissue. Multiple primary tumors and metastases undergo VCO in highly vascularized tissues such as the lungs, liver or brain. VCO has been associated with a worse prognosis. The cellular and molecular mechanisms that undergo VCO are poorly understood. Recent studies have demonstrated that co-opted vessels show a quiescent phenotype in contrast to angiogenic tumor blood vessels. On the other hand, it is believed that during VCO, cancer cells are adhered to basement membrane from pre-existing blood vessels by using integrins, show enhanced motility and a mesenchymal phenotype. Other components of the tumor microenvironment (TME) such as extracellular matrix, immune cells or extracellular vesicles play important roles in vessel co-option maintenance. There are no strategies to inhibit VCO, and thus, to eliminate resistance to anti-angiogenic therapy. This review summarizes all the molecular mechanisms involved in vessel co-option analyzing the possible therapeutic strategies to inhibit this process.
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Imunoterapia , Neoplasias , Humanos , Neovascularização Patológica/tratamento farmacológico , Membrana Basal , Encéfalo , Divisão Celular , Neoplasias/tratamento farmacológicoRESUMO
Three different mechanisms of neovascularization have been described in tumor growth, including sprouting angiogenesis, intussusceptive microvascular growth and glomeruloid vascular proliferation. Tumors can also grow by means of alternative mechanisms including vascular co-option, vasculogenic mimicry, angiotropism, and recruitment of endothelial precursor cells. Vascular co-option occurs in tumors independently of sprouting angiogenesis and the non-angiogenic cancer cells are described as exploiting pre-existing vessels. Vascular co-option is more frequently observed in tumors of densely vascularized organs, including the brain, lung and liver, and vascular co-option represents one of the main mechanisms involved in metastasis, as occurs in liver and lung, and resistance to anti-angiogenic therapy. The aim of this review article is to analyze the role of vascular co-option as mechanism through which tumors develop resistance to anti-angiogenic conventional therapeutic approaches and how blocking co-option can suppress tumor growth.
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Animals consume a wide variety of food sources to adapt to different environments. However, the genetic mechanisms underlying the acquisition of evolutionarily novel feeding morphology remain largely unknown. While the nematode Caenorhabditis elegans feeds on bacteria, the satellite species Pristionchus pacificus exhibits predatory feeding behavior toward other nematodes, which is an evolutionarily novel feeding habit. Here, we found that the astacin metalloprotease Ppa-NAS-6 is required for the predatory killing by P. pacificus. Ppa-nas-6 mutants were defective in predation-associated characteristics, specifically the tooth morphogenesis and tooth movement during predation. Comparison of expression patterns and rescue experiments of nas-6 in P. pacificus and C. elegans suggested that alteration of the spatial expression patterns of NAS-6 may be vital for acquiring predation-related traits. Reporter analysis of the Ppa-nas-6 promoter in C. elegans revealed that the alteration in expression patterns was caused by evolutionary changes in cis- and trans-regulatory elements. This study suggests that the co-option of a metalloprotease is involved in an evolutionarily novel feeding morphology.
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Nematoides , Rabditídios , Animais , Caenorhabditis elegans/genética , Comportamento Predatório , Nematoides/genética , Metaloproteases/genética , Rabditídios/genéticaRESUMO
For 25 years, the predominant evolutionary theory of romantic love has been Fisher's theory of independent emotion systems. That theory suggests that sex drive, romantic attraction (romantic love), and attachment are associated with distinct neurobiological and endocrinological systems which evolved independently of each other. Psychological and neurobiological evidence, however, suggest that a competing theory requires attention. A theory of co-opting mother-infant bonding sometime in the recent evolutionary history of humans may partially account for the evolution of romantic love. I present a case for this theory and a new approach to the science of romantic love drawing on human psychological, neurobiological, and (neuro)endocrinological studies as well as animal studies. The hope is that this theoretical review, along with other publications, will generate debate in the literature about the merits of the theory of co-opting mother-infant bonding and a new evolutionary approach to the science of romantic love.
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This article tackles the theoretical thinking behind PPI and inclusion, input from people with neurodiverse conditions. By providing a perspective on how the prefix "Neuro" is positioned in a neutral and authoritative way (exemplified through our brief review of articles within Cortex), we explore how "epistemic injustice" (a concept used frequently in law, politics, philosophy and social science) can potentially arise. Epistemic injustice typically refers to a pernicious power dynamic whereby oppressed groups are silenced (Fricker 2007), either because certain voices are not given weight ("testimonial injustice"), or the ways in which they are allowed to speak (e.g., interpret their own experiences) are limited ("hermeneutical injustice") (Kidd and Carel 2016). We show how, for "neurodiversity", the mainstream "neuro" narratives are often positively felt by those deemed to be neurodiverse, and the lines between oppressor and oppressed break down, as both neuroscientists and people with neurodiverse conditions co-opt and influence each other's positions.
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The emergence of sporophytes, that is, diploid multicellular bodies in plants, facilitated plant diversification and the evolution of complexity. Although sporophytes may have evolved in an ancestral alga exhibiting a haplontic life cycle with a unicellular diploid and multicellular haploid (gametophyte) phase, the mechanism by which this novelty originated remains largely unknown. Ulotrichalean marine green algae (Ulvophyceae) are one of the few extant groups with haplontic-like life cycles. In this study, we show that zygotes of the ulotrichalean alga Monostroma angicava, which usually develop into unicellular cysts, exhibit a developmental variation producing multicellular reproductive sporophytes. Multicellular development likely occurred stochastically in individual zygotes, but its ratio responded plastically to growth conditions. Sporophytes showed identical morphological development to gametophytes, which should reflect the expression of the same genetic programme directing multicellular development. Considering that sporophytes were evolutionarily derived in Ulotrichales, this implies that sporophytes emerged by co-opting the gametophyte developmental programme to the diploid phase. This study suggests a possible mechanism of sporophyte formation in haplontic life cycles, contributing to the understanding of the evolutionary transition from unicellular to multicellular diploid body plans in green plants.
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Clorófitas , Zigoto , Animais , Plantas/genética , Clorófitas/genética , Reprodução , Estágios do Ciclo de VidaRESUMO
Zhao et al. recently reported results which, they claim, suggest that sexual selection produces the multimodal displays seen in little torrent frogs (Amolops torrentis) by co-opting limb movements that originally evolved to support parasite defense (Zhao et al., 2022). Here, we explain why we believe this conclusion to be premature.
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Parasitos , Animais , Masculino , Anuros , Ranidae , AcústicaRESUMO
Organisms across the tree of life colonize novel environments by partnering with bacterial symbionts. These symbioses are characterized by intimate integration of host/endosymbiont biology at multiple levels, including metabolically. Metabolic integration is particularly important for sap-feeding insects and their symbionts, which supplement nutritionally unbalanced host diets. Many studies reveal parallel evolution of host/endosymbiont metabolic complementarity in amino acid biosynthesis, raising questions about how amino acid metabolism is regulated, how regulatory mechanisms evolve, and the extent to which similar mechanisms evolve in different systems. In the aphid/Buchnera symbiosis, the transporter ApGLNT1 (Acyrthosiphon pisum glutamine transporter 1) supplies glutamine, an amino donor in transamination reactions, to bacteriocytes (where Buchnera reside) and is competitively inhibited by Buchnera-supplied arginine-consistent with a role regulating amino acid metabolism given host demand for Buchnera-produced amino acids. We examined how ApGLNT1 evolved a regulatory role by functionally characterizing orthologs in insects with and without endosymbionts. ApGLNT1 orthologs are functionally similar, and orthology searches coupled with homology modeling revealed that GLNT1 is ancient and structurally conserved across insects. Our results indicate that the ApGLNT1 symbiotic regulatory role is derived from its ancestral role and, in aphids, is likely facilitated by loss of arginine biosynthesis through the urea cycle. Given consistent loss of host arginine biosynthesis and retention of endosymbiont arginine supply, we hypothesize that GLNT1 is a general mechanism regulating amino acid metabolism in sap-feeding insects. This work fills a gap, highlighting the broad importance of co-option of ancestral proteins to novel contexts in the evolution of host/symbiont systems.
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Afídeos , Buchnera , Animais , Glutamina/metabolismo , Afídeos/microbiologia , Buchnera/genética , Buchnera/metabolismo , Aminoácidos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Arginina/metabolismo , Simbiose/fisiologiaRESUMO
Copper is a critical element for eukaryotic life involved in numerous cellular functions, including redox balance, but is toxic in excess. Therefore, tight regulation of copper acquisition and homeostasis is essential for cell physiology and survival. Here, we identify a different regulatory mechanism for cellular copper homeostasis that requires the presence of an endogenous retroviral envelope glycoprotein called Refrex1. We show that cells respond to elevated extracellular copper by increasing the expression of Refrex1, which regulates copper acquisition through interaction with the main copper transporter CTR1. Downmodulation of Refrex1 results in intracellular copper accumulation leading to reactive oxygen species (ROS) production and subsequent apoptosis, which is prevented by copper chelator treatment. Our results show that Refrex1 has been co-opted for its ability to regulate copper entry through CTR1 in order to limit copper excess, redox imbalance, and ensuing cell death, strongly suggesting that other endogenous retroviruses may have similar metabolic functions among vertebrates.
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Proteínas de Transporte de Cátions , Retrovirus Endógenos , Animais , Cobre/farmacologia , Cobre/metabolismo , Transportador de Cobre 1/metabolismo , Sobrevivência Celular , Retrovirus Endógenos/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Homeostase/fisiologiaRESUMO
Novel phenotypes are increasingly recognized to have evolved by co-option of conserved genes into new developmental contexts, yet the process by which co-opted genes modify existing developmental programs remains obscure. Here, we provide insight into this process by characterizing the role of co-opted doublesex in butterfly wing color pattern development. dsx is the master regulator of insect sex differentiation but has been co-opted to control the switch between discrete nonmimetic and mimetic patterns in Papilio alphenor and its relatives through the evolution of novel mimetic alleles. We found dynamic spatial and temporal expression pattern differences between mimetic and nonmimetic butterflies throughout wing development. A mimetic color pattern program is switched on by a pulse of dsx expression in early pupal development that causes acute and long-term differential gene expression, particularly in Wnt and Hedgehog signaling pathways. RNAi suggested opposing, novel roles for these pathways in mimetic pattern development. Importantly, Dsx co-option caused Engrailed, a primary target of Hedgehog signaling, to gain a novel expression domain early in pupal wing development that is propagated through mid-pupal development to specify novel mimetic patterns despite becoming decoupled from Dsx expression itself. Altogether, our findings provide multiple views into how co-opted genes can both cause and elicit changes to conserved networks and pathways to result in development of novel, adaptive phenotypes.
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Borboletas , Proteínas Hedgehog , Animais , Borboletas/genética , Alelos , Frequência Cardíaca , FenótipoRESUMO
A key component of parental care is avoiding killing and eating one's own offspring. Many organisms commit infanticide but switch to parental care when their own offspring are expected, known as temporal kin recognition. It is unclear why such types of indirect kin recognition are so common across taxa. One possibility is that temporal kin recognition may evolve through alteration of simple mechanisms, such as co-opting mechanisms that influence the regulation of timing and feeding in other contexts. Here, we determine whether takeout, a gene implicated in coordinating feeding, influences temporal kin recognition in Nicrophorus orbicollis. We found that takeout expression was not associated with non-parental feeding changes resulting from hunger, or a general transition to the full parental care repertoire. However, beetles that accepted and provided care to their offspring had a higher takeout expression than beetles that committed infanticide. Together, these data support the idea that the evolution of temporal kin recognition may be enabled by co-option of mechanisms that integrate feeding behaviour in other contexts.