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The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes.
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Recent experimental research has observed two kinds of priming effects on quantity implicatures. One is the Strong-Weak contrast, where more quantity implicatures are observed after prime trials forcing interpretations with quantity implicatures ('Strong primes') than after prime trials forcing interpretations without quantity implicatures ('Weak primes'). The other effect is the Alternative-Weak contrast, where prime trials mentioning alternative expressions ('Alternative primes') similarly lead to more quantity implicatures. It has been claimed that both of these effects should be understood in terms of increased salience of alternative expressions used to compute quantity implicatures. We present experimental evidence that speaks against this hypothesis. With the help of novel baseline conditions, which were absent in previous studies on implicature priming, we observe that the results in the priming paradigm commonly used in the literature are inverse preference effects in the sense that robust priming effects are observed towards interpretations that are normally unexpected, and depending on the baseline expectation, each of the three prime types mentioned above may have priming effects. We furthermore investigated different types of alternative priming for so-called ad hoc implicatures and found that for these implicatures, presenting an alternative expression in a simple sentence does not have a priming effect on the implicature of a similarly simple sentence, but presenting it in a more complex conjunctive construction does. Our results also show that conjunctions of similar but irrelevant expressions have a similarly robust priming effect and that conjunctive sentences with two conjuncts do not give rise to priming effects on the interpretation of sentences of the same syntactic complexity, but those with three conjuncts do. To make sense of these observations, we propose that what crucially matters for priming implicatures is incremental change in one's probabilistic expectations about the current conversational context brought about by a process we call context adaptation.
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Comunicação , Idioma , HumanosRESUMO
Mesenchymal stromal cells (MSCs) are known for their immunomodulatory activity. Here, we report that MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) impact CD8 T cell fate through a multifaceted mechanism. We observed that hAMSCs are able to impact the metabolism of naive CD8 lymphocytes by downregulating the phosphorylation of mTOR and AKT, thus blocking cell differentiation. This effect is due to the ability of hAMSCs to reduce the expression of two receptors, IL-12Rß1 and IL-2RA, resulting in reduced phosphorylation of STAT4 and STAT5. In addition, hAMSCs reduce the expression of two transcriptional factors, Tbet and Eomes, directly involved in early effector cell commitment. Our results unravel an unknown feature of MSCs, offering alternative mechanistic insights into the effects of MSCs for the treatment of diseases characterized by an altered activation of memory subsets, such as autoimmune diseases and graft versus host disease.
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The tumor microenvironment (TME) is comprised of different cellular components, such as immune and stromal cells, which co-operate in unison to promote tumor progression and metastasis. In the last decade, there has been an increasing focus on one specific component of the TME, the stromal component, often referred to as Cancer-Associated Fibroblasts (CAF). CAF modulate the immune response and alter the composition of the extracellular matrix with a decisive impact on the response to immunotherapies and conventional chemotherapy. The most recent publications based on single-cell analysis have underlined CAF heterogeneity and the unique plasticity that strongly impact the TME. In this review, we focus not only on the characterization of CAF based on the most recent findings, but also on their impact on the immune system. We also discuss clinical trials and preclinical studies where targeting CAF revealed controversial results. Therefore, future efforts should focus on understanding the functional properties of individual subtypes of CAF, taking into consideration the peculiarities of each pathological context.
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Plural morphology in English is associated with a multiplicity inference. For example, "Emily fed giraffes" is typically interpreted to mean that Emily fed multiple giraffes. It has long been observed that this inference disappears in downward-entailing linguistic environments, such as in the scope of negation. For example, "Emily didn't feed giraffes" does not merely suggest that she didn't feed multiple giraffes, but rather that she didn't feed any. There are three main approaches to explaining this puzzle: the first proposes that the plural is ambiguous, and invokes a preference for stronger meanings; the second derives multiplicity inferences as implicatures; and the third provides a homogeneity-based account. These different approaches can all account for the interpretation of the plural across upward- and downward-entailing environments. They differ, however, in what they predict for three further aspects of the plural: the status of positive and negative plural sentences in singular contexts, children's acquisition of plural meanings, and the relationship between plural meanings and scalar implicatures. In this paper, we report on three experiments investigating adults' and preschool-aged children's interpretation of plural morphology in English. The experiments reveal that participants distinguish positive and negative plural sentences presented in singular contexts, and that adults assign a different status to these positive and negative sentences. It is also observed that children, unlike adults, tend to accept underinformative positive plural sentences in singular contexts - in parallel with their behavior on standard scalar implicatures - while they are relatively more adult-like when it comes to negative plural sentences in the same contexts, showing a tendency to reject the negative sentences. We discuss how the findings of the three experiments are expected on a scalar implicature approach to multiplicity inferences, and the open challenges they pose for the ambiguity and homogeneity approaches.
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Idioma , Semântica , Adulto , Pré-Escolar , Humanos , Desenvolvimento da Linguagem , LinguísticaRESUMO
Presuppositions convey information that comprehenders assume to be true, even when it is tangential to the communicator's main message. For example, a class of verbs called 'factives' (e.g. realize, know) trigger the presupposition that the events or states conveyed by their sentential complements are true. In contrast, non-factive verbs (e.g. think, believe) do not trigger this presupposition. We asked whether, during language comprehension, presuppositions triggered by factive verbs are encoded within the comprehender's discourse model, with neural consequences if violated by later bottom-up inputs. Using event-related potentials (ERPs), we examined neural activity to words that were either consistent or inconsistent with events/states conveyed by the complements of factive versus non-factive verbs while comprehenders read and actively monitored the coherence of short discourse scenarios. We focused on the modulation of a posteriorly-distributed late positivity or P600. This ERP component is produced when comprehenders constrain their discourse model such that it restricts predictions only to event structures that are compatible with this model, and new input violates these event structure predictions. Between 500 and 700â¯ms, we observed a larger amplitude late posterior positivity/P600 on words that were inconsistent (versus consistent) with the events/states conveyed by the complements of factive verbs. No such effect was observed following non-factive verbs. These findings suggest that, during active discourse comprehension, the presuppositions triggered by factive verbs are encoded and maintained within the comprehender's discourse model. Downstream input that is inconsistent with these presuppositions violates event structure predictions and conflicts with this prior model, producing the late posterior positivity/P600.
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Encéfalo/fisiologia , Compreensão/fisiologia , Potenciais Evocados/fisiologia , Conhecimento , Idioma , Adolescente , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Previous developmental studies have revealed variation in children's ability to compute scalar inferences. While children have been shown to struggle with standard scalar inferences (e.g., with scalar quantifiers like "some") (Chierchia, Crain, Guasti, Gualmini, & Meroni, 2001; Guasti et al., 2005; Noveck, 2001; Papafragou & Musolino, 2003), there is also a growing handful of inferences that children have been reported to derive quite readily (Barner & Bachrach, 2010; Hochstein, Bale, Fox, & Barner, 2016; Papafragou & Musolino, 2003; Singh, Wexler, Astle-Rahim, Kamawar, & Fox, 2016; Stiller, Goodman, & Frank, 2015; Tieu, Romoli, Zhou, & Crain, 2016; Tieu et al., 2017). One recent approach, which we refer to as the Alternatives-based approach, attributes the variability in children's performance to limitations in how children engage with the alternative sentences that are required to compute the relevant inferences. Specifically, if the alternative sentences can be generated by simplifying the assertion, rather than by lexically replacing one scalar term with another, children should be better able to compute the inference. In this paper, we investigated this prediction by assessing how children and adults interpret sentences that embed disjunction under a universal quantifier, such as "Every elephant caught a big butterfly or a small butterfly". For adults, such sentences typically give rise to the distributive inference that some elephant caught a big butterfly and some elephant caught a small butterfly (Crnic, Chemla, & Fox, 2015; Fox, 2007; Gazdar, 1979). Another possible interpretation, though not one typically accessed by adults, is the conjunctive inference that every elephant caught a big butterfly and a small butterfly (Singh, Wexler, Astle-Rahim, Kamawar, & Fox, 2016). Crucially, for our purposes, it has been argued that both of these inferences can be derived using alternatives that are generated by deleting parts of the asserted sentence, rather than through lexical replacement, making these sentences an ideal test case for evaluating the predictions of the Alternatives-based approach. The findings of our experimental study reveal that children are indeed able to successfully compute this class of inferences, providing support for the Alternatives-based approach as a viable explanation of children's variable success in computing scalar inferences.
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Semântica , Pensamento , Criança , Compreensão , Feminino , Humanos , Desenvolvimento da Linguagem , Lógica , Masculino , LeituraRESUMO
Previous developmental studies of conjunction have focused on the syntax of phrasal and sentential coordination (Lust, 1977; de Villiers, Tager-Flusberg & Hakuta, 1977; Bloom, Lahey, Hood, Lifter & Fiess, 1980, among others). The present study examined the flexibility of children's interpretation of conjunction. Specifically, when two predicates that can apply simultaneously to a single individual are conjoined in the scope of a plural definite (The bears are big and white), conjunction receives a Boolean, intersective interpretation. However, when the conjoined predicates cannot apply simultaneously to an individual (The bears are big and small), conjunction receives a weaker 'split' interpretation (Krifka, 1990; Lasersohn, 1995; Winter, 1996). Our experiments reveal that preschool-aged children are sensitive to both intersective and split interpretations, and can use their lexical and world knowledge of the relevant predicates in order to select an appropriate reading.