Grounding Figurative Language Use in Incompatible Ontological Categorizations

We propose a formal criterion for delineating literal from figurative speech (metonymies, metaphors, etc.). It is centered around the notion of categorization conflicts that follow from the context of the utterance. In addition, we consider the problem of granularity, which is posed by the dependence of our approach on the underlying ontology, and compare our distinction with alternative reference-based explanations

Overview of Drug Transporters in Human Placenta

The transport of drugs across the placenta is a point of great importance in pharmacotherapy during pregnancy. However, the knowledge of drug transport in pregnancy is mostly based on experimental clinical data, and the underlying biological mechanisms are not fully understood. In this review, we summarize the current knowledge of drug transporters in the human placenta. We only refer to human data since the placenta demonstrates great diversity among species. In addition, we describe the experimental models that have been used in human placental transport studies and discuss their availability. A better understanding of placental drug transporters will be beneficial for the health of pregnant women who need drug treatment and their fetuses

A Conceptual Reasoning Approach to Textual Ellipsis

We present a hybrid text understanding methodology for the resolution of textual ellipsis. It integrates conceptual criteria (based on the well-formedness and conceptual strength of role chains in a terminological knowledge base) and functional constraints reflecting the utterances' information structure (based on the distinction between context-bound and unbound discourse elements). The methodological framework for text ellipsis resolution is the centering model that has been adapted to these constraints.Comment: 5 pages, uuencoded gzipped PS file (see also Technical Report at: http://www.coling.uni-freiburg.de/public/papers/ecai96.ps.gz

The Role of Non-Coding RNAs in the Human Placenta

Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools

Splenic B1 B Cells Acquire a Proliferative and Anti-Inflamatory Profile During Pregnancy in Mice

B cells are a heterogeneous cell population with differential ontogeny, anatomical location, and functions. B1 B cells are a distinct subpopulation characterized by their unique capacity of self-renewal, the production of large quantities of IL-10, and the ability to secrete protective, anti-inflammatory natural antibodies (NAbs), presumably upon down-regulation of CD1d expression. Although natural antibodies are thought to be protective, due to their polyreactivity, their participation in certain autoimmune diseases has been suggested. In the context of pregnancy, the role of B1 B cells has been discussed controversially. While in human pregnancies B1 B cells and natural/polyreactive antibodies they produce are involved in the development of preeclampsia, in mice they promote healthy gestation and fetal protection. In this work, we aimed to functionally characterize the splenic B1 B cell population during pregnancy in mice. Functional enrichment analysis using only up-regulated transcripts from a transcriptomic profile performed on total splenic B cells from pregnant compared to non-pregnant mice showed augmented cell cycle and DNA replication pathways. Proliferation studies by flow cytometry showed augmented Ki-67 proliferation marker expression and percentages of B1 B cells. Furthermore, B1 B cells produced higher levels of IL-10 and lower levels of TNF-α leading to an increased IL-10/TNF-α ratio and showing an immunoregulatory phenotype. Finally, we observed lower expression of CD1d on B1 B cells, suggesting a higher capacity to produce NAbs in the context of pregnancy. In summary, our results showed not only an expanded and proliferative splenic B1 B cell population during pregnancy but also the acquisition of immunomodulatory capacities suggesting its critical role in the intricate process of pregnancy tolerance

Emerging Concepts in Innate Lymphoid Cells, Memory, and Reproduction

Members of the innate immune system, innate lymphoid cells (ILCs), encompass five major populations (Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells) whose functions include defense against pathogens, surveillance of tumorigenesis, and regulation of tissue homeostasis and remodeling. ILCs are present in the uterine environment of humans and mice and are dynamically regulated during the reproductive cycle and pregnancy. These cells have been repurposed to support pregnancy promoting maternal immune tolerance and placental development. To accomplish their tasks, immune cells employ several cellular and molecular mechanisms. They have the capacity to remember a previously encountered antigen and mount a more effective response to succeeding events. Memory responses are not an exclusive feature of the adaptive immune system, but also occur in innate immune cells. Innate immune memory has already been demonstrated in monocytes/macrophages, neutrophils, dendritic cells, and ILCs. A population of decidual NK cells characterized by elevated expression of NKG2C and LILRB1 as well as a distinctive transcriptional and epigenetic profile was found to expand during subsequent pregnancies in humans. These cells secrete high amounts of interferon-γ and vascular endothelial growth factor likely favoring placentation. Similarly, uterine ILC1s in mice upregulate CXCR6 and expand in second pregnancies. These data provide evidence on the development of immunological memory of pregnancy. In this article, the characteristics, functions, and localization of ILCs are reviewed, emphasizing available data on the uterine environment. Following, the concept of innate immune memory and its mechanisms, which include epigenetic changes and metabolic rewiring, are presented. Finally, the emerging role of innate immune memory on reproduction is discussed. Advances in the comprehension of ILC functions and innate immune memory may contribute to uncovering the immunological mechanisms underlying female fertility/infertility, placental development, and distinct outcomes in second pregnancies related to higher birth weight and lower incidence of complications

Editorial: Immunological challenges around pregnancy complications associated with failures of maternal tolerance to the fetus

Obstetric

Synergies of Extracellular Vesicles and Microchimerism in Promoting Immunotolerance During Pregnancy

The concept of biological identity has been traditionally a central issue in immunology. The assumption that entities foreign to a specific organism should be rejected by its immune system, while self-entities do not trigger an immune response is challenged by the expanded immunotolerance observed in pregnancy. To explain this “immunological paradox”, as it was first called by Sir Peter Medawar, several mechanisms have been described in the last decades. Among them, the intentional transfer and retention of small amounts of cells between a mother and her child have gained back attention. These microchimeric cells contribute to expanding allotolerance in both organisms and enhancing genetic fitness, but they could also provoke aberrant alloimmune activation. Understanding the mechanisms used by microchimeric cells to exert their function in pregnancy has proven to be challenging as per definition they are extremely rare. Profiting from studies in the field of transplantation and cancer research, a synergistic effect of microchimerism and cellular communication based on the secretion of extracellular vesicles (EVs) has begun to be unveiled. EVs are already known to play a pivotal role in feto-maternal tolerance by transferring cargo from fetal to maternal immune cells to reshape their function. A further aspect of EVs is their function in antigen presentation either directly or on the surface of recipient cells. Here, we review the current understanding of microchimerism in the feto-maternal tolerance during human pregnancy and the potential role of EVs in mediating the allorecognition and tropism of microchimeric cells

Understanding metonymies in discourse

We propose a new computational model for the resolution of metonymies, a particular type of figurative language. Typically, metonymies are considered as a violation of semantic constraints (e.g., those expressed by selectional restrictions) that require some repair mechanism (e.g., type coercion) for proper interpretation. We reject this view, arguing that it misses out on the interpretation of a considerable number of utterances. Instead, we treat literal and figurative language on a par, by computing both kinds of interpretation independently from each other as long as their semantic representation structures are consistent with the underlying knowledge representation structures of the domain of discourse. The following general heuristic principles apply for making reasonable selections from the emerging readings. We argue that the embedding of utterances in a coherent discourse context is as important for recognizing and interpreting metonymic utterances as intrasentential semantic constraints. Therefore, in our approach, (metonymic or literal) interpretations that establish referential cohesion are preferred over ones that do not. In addition, metonymic interpretations that conform to a metonymy schema are preferred over metonymic ones that do not, and metonymic interpretations that are in conformance with knowledge-based aptness conditions are preferred over metonymic ones that are not. We lend further credit to our model by discussing empirical data from an evaluation study which highlights the importance of the discourse embedding of metonymy interpretation for both anaphora and metonymy resolution

Human-BasedNewApproachMethodologiesin DevelopmentalToxicityTesting:AStepAheadfromtheState oftheArtwithaFeto–PlacentalOrgan-on-ChipPlatform

Download PDFsettingsOrder Article Reprints Open AccessReview Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform by Michaela Luconi 1,2,†ORCID,Miguel A. Sogorb 3,†ORCID,Udo R. Markert 4ORCID,Emilio Benfenati 5,Tobias May 6,Susanne Wolbank 7ORCID,Alessandra Roncaglioni 5,Astrid Schmidt 4,Marco Straccia 8ORCID andSabrina Tait 9,*ORCID 1 Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy 2 I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Viale Medaglie d’Oro 305, 00136 Rome, Italy 3 Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Avenida de la Universidad s/n, 03202 Elche, Spain 4 Placenta Lab, Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany 5 Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy 6 InSCREENeX GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany 7 Ludwig Boltzmann Institut for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse 13, 1200 Vienna, Austria 8 FRESCI by Science&Strategy SL, C/Roure Monjo 33, Vacarisses, 08233 Barcelona, Spain 9 Centre for Gender-Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Environ. Res. Public Health 2022, 19(23), 15828; https://doi.org/10.3390/ijerph192315828 Submission received: 24 October 2022 / Revised: 20 November 2022 / Accepted: 25 November 2022 / Published: 28 November 2022 (This article belongs to the Section Toxicology and Public Health) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Developmental toxicity testing urgently requires the implementation of human-relevant new approach methodologies (NAMs) that better recapitulate the peculiar nature of human physiology during pregnancy, especially the placenta and the maternal/fetal interface, which represent a key stage for human lifelong health. Fit-for-purpose NAMs for the placental–fetal interface are desirable to improve the biological knowledge of environmental exposure at the molecular level and to reduce the high cost, time and ethical impact of animal studies. This article reviews the state of the art on the available in vitro (placental, fetal and amniotic cell-based systems) and in silico NAMs of human relevance for developmental toxicity testing purposes; in addition, we considered available Adverse Outcome Pathways related to developmental toxicity. The OECD TG 414 for the identification and assessment of deleterious effects of prenatal exposure to chemicals on developing organisms will be discussed to delineate the regulatory context and to better debate what is missing and needed in the context of the Developmental Origins of Health and Disease hypothesis to significantly improve this sector. Starting from this analysis, the development of a novel human feto–placental organ-on-chip platform will be introduced as an innovative future alternative tool for developmental toxicity testing, considering possible implementation and validation strategies to overcome the limitation of the current animal studies and NAMs available in regulatory toxicology and in the biomedical field