Great expectations: Specific lexical anticipation influences the processing of spoken language

<p>Abstract</p> <p>Background</p> <p>Recently several studies have shown that people use contextual information to make predictions about the rest of the sentence or story as the text unfolds. Using event related potentials (ERPs) we tested whether these on-line predictions are based on a message-level representation of the discourse or on simple automatic activation by individual words. Subjects heard short stories that were highly constraining for one specific noun, or stories that were not specifically predictive but contained the same prime words as the predictive stories. To test whether listeners make specific predictions critical nouns were preceded by an adjective that was inflected according to, or in contrast with, the gender of the expected noun.</p> <p>Results</p> <p>When the message of the preceding discourse was predictive, adjectives with an unexpected gender inflection evoked a negative deflection over right-frontal electrodes between 300 and 600 ms. This effect was not present in the prime control context, indicating that the prediction mismatch does not hinge on word-based priming but is based on the actual message of the discourse.</p> <p>Conclusion</p> <p>When listening to a constraining discourse people rapidly make very specific predictions about the remainder of the story, as the story unfolds. These predictions are not simply based on word-based automatic activation, but take into account the actual message of the discourse.</p

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Right hemisphere has the last laugh: neural dynamics of joke appreciation

Understanding a joke relies on semantic, mnemonic, inferential, and emotional contributions from multiple brain areas. Anatomically constrained magnetoencephalography (aMEG) combining high-density whole-head MEG with anatomical magnetic resonance imaging allowed us to estimate where the humor-specific brain activations occur and to understand their temporal sequence. Punch lines provided either funny, not funny (semantically congruent), or nonsensical (incongruent) replies to joke questions. Healthy subjects rated them as being funny or not funny. As expected, incongruous endings evoke the largest N400m in left-dominant temporo-prefrontal areas, due to integration difficulty. In contrast, funny punch lines evoke the smallest N400m during this initial lexical–semantic stage, consistent with their primed “surface congruity” with the setup question. In line with its sensitivity to ambiguity, the anteromedial prefrontal cortex may contribute to the subsequent “second take” processing, which, for jokes, presumably reflects detection of a clever “twist” contained in the funny punch lines. Joke-selective activity simultaneously emerges in the right prefrontal cortex, which may lead an extended bilateral temporo-frontal network in establishing the distant unexpected creative coherence between the punch line and the setup. This progression from an initially promising but misleading integration from left frontotemporal associations, to medial prefrontal ambiguity evaluation and right prefrontal reprocessing, may reflect the essential tension and resolution underlying humor

First RNA-seq approach to study fruit set and parthenocarpy in zucchini (Cucurbita pepo L.)

[EN] Background: Zucchini fruit set can be limited due to unfavourable environmental conditions in off-seasons crops that caused ineffective pollination/fertilization. Parthenocarpy, the natural or artificial fruit development without fertilization, has been recognized as an important trait to avoid this problem, and is related to auxin signalling. Nevertheless, differences found in transcriptome analysis during early fruit development of zucchini suggest that other complementary pathways could regulate fruit formation in parthenocarpic cultivars of this species. The development of next-generation sequencing technologies (NGS) as RNA-sequencing (RNA-seq) opens a new horizon for mapping and quantifying transcriptome to understand the molecular basis of pathways that could regulate parthenocarpy in this species. The aim of the current study was to analyze fruit transcriptome of two cultivars of zucchini, a non-parthenocarpic cultivar and a parthenocarpic cultivar, in an attempt to identify key genes involved in parthenocarpy. Results: RNA-seq analysis of six libraries (unpollinated, pollinated and auxin treated fruit in a non-parthenocarpic and parthenocarpic cultivar) was performed mapping to a new version of C. pepo transcriptome, with a mean of 92% success rate of mapping. In the non-parthenocarpic cultivar, 6479 and 2186 genes were differentially expressed (DEGs) in pollinated fruit and auxin treated fruit, respectively. In the parthenocarpic cultivar, 10,497 in pollinated fruit and 5718 in auxin treated fruit. A comparison between transcriptome of the unpollinated fruit for each cultivar has been performed determining that 6120 genes were differentially expressed. Annotation analysis of these DEGs revealed that cell cycle, regulation of transcription, carbohydrate metabolism and coordination between auxin, ethylene and gibberellin were enriched biological processes during pollinated and parthenocarpic fruit set. Conclusion: This analysis revealed the important role of hormones during fruit set, establishing the activating role of auxins and gibberellins against the inhibitory role of ethylene and different candidate genes that could be useful as markers for parthenocarpic selection in the current breeding programs of zucchini.Research worked is supported by the project RTA2014-00078 from the Spanish Institute of Agronomy Research INIA (Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria) and also PP.AVA.AVA201601.7, FEDER y FSE (Programa Operativo FSE de Andalucia 2007-2013 "Andalucia se mueve con Europa"). TPV is supported by a FPI scholarship from RTA2011-00044-C02-01/02 project of INIA. 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Quick identification of acute chest pain patients study (QICS)

<p>Abstract</p> <p>Background</p> <p>Patients with acute chest pain are often referred to the emergency ward and extensively investigated. Investigations are costly and could induce unnecessary complications, especially with invasive diagnostics. Nevertheless, chest pain patients have high mortalities. Fast identification of high-risk patients is crucial. Therefore several strategies have been developed including specific symptoms, signs, laboratory measurements, and imaging.</p> <p>Methods/Design</p> <p>The Quick Identification of acute Chest pain Study (QICS) will investigate whether a combined use of specific symptoms and signs, electrocardiography, routine and new laboratory measures, adjunctive imaging including electron beam (EBT) computed tomography (CT) and contrast multislice CT (MSCT) will have a high diagnostic yield for patients with acute chest pain. All patients will be investigated according a standardized protocol in the Emergency Department. Serum and plasma will be frozen for future analysis for a wide range of biomarkers at a later time point. The primary endpoint is the safe recognition of low-risk chest pain patients directly at presentation. Secondary endpoint is the identification of a wide range of sensitive predictive clinical markers, chemical biomarkers and radiological markers in acute chest pain patients. Chemical biomarkers will be compared to quantitative CT measurements of coronary atherosclerosis as a surrogate endpoint. Chemical biomarkers will also be compared in head to head comparison and for their additional value.</p> <p>Discussion</p> <p>This will be a very extensive investigation of a wide range of risk predictors in acute chest pain patients. New reliable fast and cheap diagnostic algorithm resulting from the test results might improve chest pain patients' prognosis, and reduce unnecessary costs and diagnostic complications.</p

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Task-dependent evaluative processing of moral and emotional content during comprehension: an ERP study

Recently, we showed that when participants passively read about moral transgressions (e.g., adultery) they implicitly engage in the evaluative (good–bad) categorization of incoming information, as indicated by a larger event-related brain potential (ERP) positivity to immoral than moral scenarios (Leuthold, Kunkel, Mackenzie, & Filik, 2015). Behavioral and neuroimaging studies indicated that explicit moral tasks prioritize the semantic-cognitive analysis of incoming information but that implicit tasks, as used in Leuthold et al. (2015), favor their affective processing. Therefore, it is unclear whether an affective categorization process is also involved when participants perform explicit moral judgments. Thus, in two experiments, we used similarly constructed morality and emotion materials for which their moral and emotional content had to be inferred from the context. Target sentences from negative vs. neutral emotional scenarios and from moral vs. immoral scenarios were presented using rapid serial visual presentation. In Experiment 1, participants made moral judgments for moral materials and emotional judgments for emotion materials. Negative compared to neutral emotional scenarios elicited a larger posterior ERP positivity (LPP) about 200 ms after critical word onset, whereas immoral compared to moral scenarios elicited a larger anterior negativity (500-700 ms). In Experiment 2, where the same emotional judgment to both types of materials was required, a larger LPP was triggered for both types of materials. These results accord with the view that morality scenarios trigger a semantic-cognitive analysis when participants explicitly judge the moral content of incoming linguistic information but an affective evaluation when judging their emotional content