The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis

Fondazione Cariplo (grant no. 2015–0564 to A.M.)Cluster Alisei (grant no. MEDINTECH CTN01_00177_962865 to A.M.)European Research Council (grant no. 669415-PHII to A.M.)Italian Association for Cancer Research (AIRC IG-2016 grant no. 19014 to A.M.; AIRC 5 × 1000 grant no. 21147 to A.M.; AIRC IG-2016 grant no. 19213 to M.L.)Medical Research Council (Pathobiology of Early Arthritis Cohort grant no. 36661 to C.P.)Arthritis Research UK Experimental Treatment Centre (grant no. 20022 to C.P.

Discourse Phenomena in Typological Perspective: An overview

This book aims at investigating discourse phenomena (i.e., linguistic elements and constructions that help to manage the organization, flow, and outcome of communication) from a typological and cross-linguistic perspective. Although it is a well-established idea in functional-typological approaches that grammar is shaped by discourse use, systematic typological cross-linguistic investigations on discourse phenomena are relatively rare. This volume aims at bridging this gap, by integrating different linguistic subfields, such as discourse analysis, pragmatics, and typology. The contributions, both theoretically and empirically oriented, focus on a broad variety of discourse phenomena (ranging from discourse markers to discourse function of grammatical markers, to strategies that manage the discourse and information flow) while adopting a typological perspective and considering typologically distant languages

Counterfactual conditionals: Linguistic variation in italian and beyond

The aim of this paper is to integrate the analysis of the intra-linguistic variation attested in the coding of counterfactual conditionals in spoken Italian with a larger cross-linguistic perspective. We start by providing a sociolinguistically-informed discussion of the counterfactual conditional strategies attested in spoken Italian, through a corpus-based analysis. After describing the corpus and the parameters of analysis, we provide a typology of the attested constructions, based on the verbal forms employed for protasis and apodosis, showing that the observed variation goes beyond the representations available in the literature. In particular, we describe the spread of counterfactual imperfective past indicative forms, which are especially frequent in symmetrical constructions and are argued to be associated to lower educational achievements and, to a lesser extent, to informal contexts. We then consider the picture of Italian counterfactual conditionals within a wider perspective, to verify whether the patterns described for Italian follow more general tendencies. After addressing some crucial methodological issues, concerning the problems raised by the integration of a sociolinguistic and a cross-linguistic approach, we argue that Italian data are probably to be analyzed as manifestations of a widespread trend towards the use of symmetrical countefactual constructions on the one hand and the use of past habituals for functions connected to the irrealis domain on the other hand

Feasibility of Early Intervention Through Home-Based and Parent-Delivered Infant Massage in Infants at High Risk for Cerebral Palsy

Infant massage (IM) can be considered an early intervention program that leads to the environmental enrichment framework. The effectiveness of IM to promote neurodevelopment in preterm infants has been proved, but studies on infants with early brain damage are still lacking. The main aim of this study was to assess the feasibility, acceptability and usability of IM, carried out by parents at home, on infants at high risk for Cerebral Palsy. An IM daily diary and an ad hoc questionnaire, called Infant Massage Questionnaire Parent-Infant Experiences (IMQPE), were developed. IMQPE consisted of a total of 30 questions, divided into 5 areas. The parents were trained to carry out the IM with a home-based course, conducted by an expert therapist. The intensive IM program was set according to a defined daily length of at least 20 min, with a frequency of at least 5 days per week for a total of 8 weeks. Data collection consisted in the selection of the variables around the characteristics, both of the infants and the mothers, IM dosage and frequency, different body parts of the infants involved and IMQPE scores. Variable selection was carried out by minimizing the Bayesian Information Criteria (BIC) over all possible variable subsets. Nineteen high-risk infants, aged 4.83 ± 1.22 months, received IM at home for 8 weeks. The massage was given by the infants' mothers with a mean daily session dose of 27.79 ± 7.88 min and a total of 21.04 ± 8.49 h. 89.74% and 100% of mothers performed the IM for the minimum daily dosage and the frequency recommended, respectively. All the families filled in the IMQPE, with a Total mean score of 79.59% and of 82.22% in General Information on IM, 76.30% in Infant's intervention-related changes, 76.85% in IM Suitability, 79.07% in Infant's acceptance and 83.52% in Time required for the training. Different best predictors in mothers and in infants have been found. These data provide evidence of the feasibility of performing IM at home on infants at high risk for CP. Study registration: www.clinicaltrial.com (NCT03211533 and NCT03234959)

Efficiency of a mathematical model in generating CAD/CAM-partial crowns with natural tooth morphology

The "biogeneric tooth model" can be used for computer-aided design (CAD) of the occlusal surface of dental restorations. From digital 3D-data, it automatically retrieves a morphology matching the natural surface left after preparation. This study evaluates the potential of this method for generating well-matched and well-adjusted CAD/computer-aided manufacturing (CAM) fabricated partial crowns. Twelve models with partial crown preparations were mounted into an articulator. Partial crowns were designed with the Cerec 3D CAD software based on the biogeneric tooth model (Biog.CAD) and, for control, with a conventional data-based Cerec 3D CAD software (Conv.CAD). The design time was measured, and the naturalness of the morphology was visually assessed. The restorations were milled, cemented on the models, and the vertical discrepancy and the time for final occlusal adjustment were measured. The Biog.CAD software offered a significantly higher naturalness (up to 225 to 11 scores) and was significantly faster by 251 (+/-78) s in designing partial crowns (p < 0.01) compared to Conv.CAD software. Vertical discrepancy, 0.52 (+/-0.28) mm for Conv.CAD and 0.46 (+/-0.19) mm for Biog.CAD, and occlusal adjustment time, 118 (+/-132) s for Conv.CAD and 102 (+/-77) s for Biog.CAD, did not differ significantly. In conclusion, the biogeneric tooth model is able to generate occlusal morphology of partial crowns in a fully automated process with higher naturalness compared to conventional interactive CAD software

The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell–mediated resistance to metastasis

The plasma membrane tetraspan molecule MS4A4A is selectively expressed by macrophage-lineage cells, but its function is unknown. Here we report that MS4A4A was restricted to murine and human mononuclear phagocytes and was induced during monocyte-to-macrophage differentiation in the presence of interleukin 4 or dexamethasone. Human MS4A4A was co-expressed with M2/M2-like molecules in subsets of normal tissue-resident macrophages, infiltrating macrophages from inflamed synovium and tumor-associated macrophages. MS4A4A interacted and colocalized with the β-glucan receptor dectin-1 in lipid rafts. In response to dectin-1 ligands, Ms4a4a-deficient macrophages showed defective signaling and defective production of effector molecules. In experimental models of tumor progression and metastasis, Ms4a4a deficiency in macrophages had no impact on primary tumor growth, but was essential for dectin-1-mediated activation of macrophages and natural killer (NK) cell–mediated metastasis control. Thus, MS4A4A is a tetraspan molecule selectively expressed in macrophages during differentiation and polarization, essential for dectin-1-dependent activation of NK cell–mediated resistance to metastasis

Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver

Type 1 innate lymphoid cells (ILC1) are tissue-resident lymphocytes that provide early protection against bacterial and viral infections. Discrete transcriptional states of ILC1 have been identified in homeostatic and pathological contexts. However, whether these states delineate ILC1 with different functional properties is not completely understood. Here, we show that liver ILC1 are heterogeneous for the expression of distinct effector molecules and surface receptors, including granzyme A (GzmA) and CD160, in mice. ILC1 expressing high levels of GzmA are enriched in the liver of adult mice, and represent the main hepatic ILC1 population at birth. However, the heterogeneity of GzmA and CD160 expression in hepatic ILC1 begins perinatally and increases with age. GzmA+ ILC1 differ from NK cells for the limited homeostatic requirements of JAK/STAT signals and the transcription factor Nfil3. Moreover, by employing Rorc(γt)-fate map (fm) reporter mice, we established that ILC3-ILC1 plasticity contributes to delineate the heterogeneity of liver ILC1, with RORγt-fm+ cells skewed toward a GzmA–CD160+ phenotype. Finally, we showed that ILC1 defined by the expression of GzmA and CD160 are characterized by graded cytotoxic potential and ability to produce IFN-γ. In conclusion, our findings help deconvoluting ILC1 heterogeneity and provide evidence for functional diversification of liver ILC1