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MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that represent important posttranscriptional regulators of protein-encoding genes. In particular, miRNAs play key roles in regulating cellular processes such as proliferation, migration, and cell differentiation. Recently, miRNAs emerged as critical regulators of osteoclasts (OCs) biology and have been involved in OCs pathogenic role in several disorders. OCs are multinucleated cells generated from myeloid precursors in the bone marrow, specialized in bone resorption. While there is a growing number of information on the cytokines and signaling pathways that are critical to control the differentiation of osteoclast precursors (OCPs) into mature OCs, the connection between OC differentiation steps and miRNAs is less well-understood. The present review will first summarize our current understanding of the miRNA-regulated pathways in the sequential steps required for OC formation, from the motility and migration of OCPs to the cell-cell fusion and the final formation of the actin ring and ruffled border in the functionally resorbing multinucleated OCs. Then, considering the difficulty of working on primary OCs and on the generation of robust data we will give an update on the most recent advances in the detection technologies for miRNAs quantification and how these are of particular interest for the understanding of OC biology and their use as potential biomarkers.

This study analyzes the experiences of undergraduate peer- tutors in a heritage language writing center (HLWC) located at a large public university in the United States. As former heritage language (HL) students themselves, tutors have to navigate the complexities of being bilingual advocates for their tutees while promoting the linguistic ideals of the academic community, where literacy expectations can be more rigid. In order to delve into their experiences at the center, this qualitative investigation examines the end- of- term reflections of 19 Spanish HL tutors working at a Spanish HLWC, addressing the following questions: (1) How do tutors perceive their role as language advocates and arbiters? (2) How can these beliefs be supported or addressed by the HL program? Ideal tutors occupy a middle ground between being a peer- student and an expert- student, whose role is to scaffold the mentee's process. However, we find that HL tutors struggle with competing linguistic expectations between the heritage and the academic community. Finally, we discuss three areas of tension that are important to address in HL tutor training and program design: ambivalent notions about students' proficiency and preparedness, their role in the instructional team, and their relationship to expertise. Keywords peer tutoring, heritage language education, writing program administration

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady-state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardii CNCM I-745 ( Sb ) in vivo reduced bone loss in ovariectomized but not sham mice by reducing inflammatory osteoclastogenesis. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of Tlr2, Dectin-1, and Mincle specifically inhibited directly the differentiation of inflammatory but not steady-state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.

This study analyzes the experiences of undergraduate peer-tutors in a Heritage Spanish Writing Center (HSWC). Tutors, uniquely positioned as the bridge between heritage language students and the linguistic ideals of the academic community, struggle to balance being a bilingual advocate while promoting language practices that operate within a monolingual framework. This is particularly evident in the context of students’ writing development, where literacy expectations can be more rigid. The tutors are former students who completedthe Spanish as a Heritage Language (SHL) program and, by the end of the series, had displayed increased tolerance towards their own language practices and become more conscious of their linguistic choices. However, we wanted to know if this milestone was transferred to the tutoring room once these SHL students became tutors in the program. We collected written reflections from 19 tutors over the course of two academic quarters. Our goal was to analyze how tutors navigate the transition from student to tutor and how the relationship to their new role evolves throughout the first year, specifically: 1) what they value in terms of language and literacy, 2) what strategies they use, and 3) what challenges they encounter. We find that as tutors gain more experience and utilize the support system of the other tutors, they learn to engage with the students’ writing, develop confidence in tutoring academic Spanish, and take on a mentoring role. Even with these gains, tutors still struggle with providing “adequate” feedback and negotiating the role between peer and tutor.

Over 500 primary immunodeficiency diseases (PID) have been described, but immunological assessment after a severe infection is not routine. We aimed to evaluate the feasibility of a PID screening protocol and calculate PID prevalence in children admitted for severe infection in a pediatric intensive care unit (PICU). This monocentric retrospective study evaluated the feasibility of a PID monitoring protocol after severe infection in children aged 1 month to 16 years-old hospitalized in the Montpellier University Hospital from January 2018 to December 2020. Follow-up consultations at 3 and 12 months included the three main PID screening scores, comprehensive immunological and genetic screenings. Among 1125 children admitted to the PICU, 46 had severe infections and caused by bacterial (48%), viral (39%) or fungal (2%) pathogens. Before infection, none had completed any screening score recommended by dedicated societies (Jeffrey Modell Foundation, German Patients’ Organization for Primary Immunodeficiencies, French Reference Center for Hereditary Immunodeficiencies). At 3 months, three patients had a PID diagnosis (6.5% prevalence, 95% CI 1.4–17.9). These were associated with a deletion of chromosomal region 22q11.21 (DiGeorge syndrome), ELANE mutation (Elastase deficiency or Severe Congenital Neutropenia 1), and C5 deficiency Forty children (87%) presented immunological anomalies without a formal PID diagnosis. These persisted in only 4/17 children tested at 12 months. The most frequent abnormalities were low NK lymphocytes (41.18%), and abnormal B lymphocyte population distribution (25%). The observed PID prevalence post-severe infection matches previous reports, even with a high rate of viral infections, often overlooked. Systematic PID investigation after severe infection, regardless of the pathogen, should be implemented to improve early detection and treatment.

As about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID. To this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex , quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later. None of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016). Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.

T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.

A highly productive derivational process, diminutive suffixation in Spanish (e.g., gatito ~ gatiko/gatico ‘little/well-known/beloved/awful cat’ < gato ‘cat’) has received much attention in the morphology–phonology interface literature. The present study contributes a novel comparative analysis of a dissimilatory alternation between diminutive suffix allomorphs -ito/a and -ico/a (-iko/a) across three Hispano-Romance varieties. In Judeo-Spanish, the voiceless dorsal stop [k] of default -iko/a dissimilates to coronal [t] after any dorsal segment [k, ɡ, ɡʷ, x, w] in the base-final syllable. In Colombian Spanish, the voiceless coronal stop [t] of default -ito/a dissimilates to dorsal [k] after only an identical [t] in the base-final syllable. By contrast, Castilian Spanish -ito/a does not dissimilate, thereby providing a baseline for comparison. All three varieties allow for optional iteration of the suffix, which conveys greater smallness or endearment than the simple diminutive, e.g., Castilian Spanish gatitito ‘little/beloved kitty’, without dissimilation. Iterated diminutives in Colombian Spanish show two patterns of dissimilation, which have not been fully acknowledged in the previous literature. For example, either (i) [it] and [ik] alternate to avoid adjacent identical syllable onsets, e.g., gat[ikitíko], or (ii) [it] is iterated until alternating with word-final [ik], e.g., gat[ititíko]. In all three Hispano-Romance varieties, base-final unstressed vowels are deleted before a vowel-initial diminutive suffix, followed by unstressed -o/a, and stress (indicated by an acute accent) is shifted rightward onto the penultimate syllable of the diminutive word. Vowel deletion and stress shift apply recursively in iterated diminutives. We propose an Optimality Theory analysis of these alternations in terms of suffix allomorphy that is phonologically conditioned by consonantal place dissimilation. The analysis is formalized as an interaction among constraints that enforce prosodic unmarkedness, output–output correspondence, allomorph preference, and similarity avoidance. We consider theoretical alternatives and compare our analysis to other recent proposals.

This article analyzes the writing development of heritage speakers (hs) of Spanish in an intermediate level composition course at the University of California, Davis. The data comprised 480 essays written by 80 students from two groups: one who received face-to-face peer tutoring before the covid-19 pandemic (Fall 2019), and one who received online tutoring during the pandemic (Fall 2020). These data were analyzed in terms of lexical richness as measured by (a) lexical density, (b) lexical sophistication, and (c) lexical variation in both in-person and online settings. Findings revealed that lexical density and lexical sophistication were similar in both groups. However, the online group had higher levels of lexical variation throughout their essays. We conclude that online tutoring is an effective alternative to face-to-face tutoring, showing no disadvantages in terms of students’ lexical richness and offering a significant advantage with respect to lexical variation. Finally, we offer suggestions for hs tutor training in an online setting.

This article traces the development of voiced prepalatal obstruents /dʒ⌢/ and /ʒ/ in Judeo-Spanish, the language spoken by the Sephardic Jews since before their expulsion from late-15th century Spain. Using Medieval Spanish as a comparative starting point, we examine diachronic innovations in the phonological status and distribution of affricate /dʒ⌢/ and fricative /ʒ/ in Judeo-Spanish during the diaspora, focusing in particular on the effects of lexical borrowing from Turkish and French in territories of the former Ottoman Empire. In contemporary Sephardic communities that are in contact with non-Sephardic varieties of Mainstream Spanish, some speakers occasionally replace syllable-initial /∫/, /dʒ⌢/, and /ʒ/ in certain Judeo-Spanish words by a voiceless velar /x/ in efforts to accommodate the pronunciation of the corresponding Mainstream Spanish cognate form. We provide a novel analysis of Judeo-Spanish voiced prepalatal obstruents, including their diachronic and synchronic variation under language contact. The analysis combines a constraint-based approach to phonological alternations, as formalized in Optimality Theory, with a usage-based representation of the mental lexicon, as proposed in Exemplar Theory, to account for speaker- and word-specific variability. A hybrid theoretical model provides a more nuanced understanding of the relationship between lexicon and grammar in Judeo-Spanish phonology than is available in previous structuralist descriptions.