miR-181a/b downregulation exerts a protective action on mitochondrial disease models.

Mitochondrial diseases (MDs) are a heterogeneous group of devastating and often fatal disorders due to defective oxidative phosphorylation. Despite the recent advances in mitochondrial medicine, effective therapies are still not available for these conditions. Here, we demonstrate that the microRNAs miR-181a and miR-181b (miR-181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these miRNAs enhances mitochondrial turnover in the retina through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested the effect of miR-181a/b inactivation in different animal models of MDs, such as microphthalmia with linear skin lesions and Leber\u27s hereditary optic neuropathy. We found that miR-181a/b downregulation strongly protects retinal neurons from cell death and significantly ameliorates the disease phenotype in all tested models. Altogether, our results demonstrate that miR-181a/b regulate mitochondrial homeostasis and that these miRNAs may be effective gene-independent therapeutic targets for MDs characterized by neuronal degeneration

miR-181a/b downregulation exerts a protective action on mitochondrial disease models.

Mitochondrial diseases (MDs) are a heterogeneous group of devastating and often fatal disorders due to defective oxidative phosphorylation. Despite the recent advances in mitochondrial medicine, effective therapies are still not available for these conditions. Here, we demonstrate that the microRNAs miR-181a and miR-181b (miR-181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these miRNAs enhances mitochondrial turnover in the retina through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested the effect of miR-181a/b inactivation in different animal models of MDs, such as microphthalmia with linear skin lesions and Leber's hereditary optic neuropathy. We found that miR-181a/b downregulation strongly protects retinal neurons from cell death and significantly ameliorates the disease phenotype in all tested models. Altogether, our results demonstrate that miR-181a/b regulate mitochondrial homeostasis and that these miRNAs may be effective gene-independent therapeutic targets for MDs characterized by neuronal degeneration.Italian Fondazione Telethon (grant no. TGM16YGM02 to S. Ban, the Fondazione Roma (grant no. RP‐201300000009 to S. Ban)) and the AFM‐Telethon (grant no. 20685 to B.F.). A.I. received an Umberto Veronesi Fellowship. This research was carried out in the frame of Programme STAR, financially supported by UniNA and Compagnia di San Paolo (Bando STAR, 16‐CSP‐UNINA‐048, to A.I)

Lezione frontale e lezione online: le principali differenze

Il più grave errore che possiamo commettere nell’avvicinarci alla didattica a distanza è quello di pensare che sia identica a quella in aula, solo con una webcam e uno schermo di mezzo (Bruschi & Perissinotto, 2020). Fornire apprendimento online richiede approcci e abilità diversi rispetto a tenere lezioni in una classe fisica. In particolare, durante lo scoppio della pandemia, gli insegnanti che tradizionalmente lavoravano in classi fisiche, hanno dovuto adattarsi e imparare da soli per insegnare agli studenti tramite piattaforme online. La didattica digitale non può essere la riproposizione della lezione frontale, in quanto essa favorisce la riconcettualizzazione della tecnologia come risorsa culturale “normale” per la didattica (è quanto avviene quando il cellulare, o il tablet, vengono utilizzati in classe per svolgere attività di apprendimento). Sebbene sia stato il modo tradizionale di apprendere per decenni, lo stile di apprendimento di alcuni studenti non si adatta a quello di una classe piena. In classe, il valore di un insegnante va oltre il corso tenuto. La tecnologia può anche essere introdotta in classe come un efficace supplemento alle lezioni in presenza (Rivoltella, 2013). In particolare, questo contributo affronta l’uso delle tecnologie in aula e come queste possono essere un valido supporto alla didattica.The most serious mistake we can make when approaching distance learning is to think that it is identical to classroom learning, only with addition of a webcam and a screen (Bruschi & Perissinotto, 2020). To plan online learning requires different approaches and skills compared to lessons that take place in a traditional classroom. During the pandemic period, teachers had to learn quickly teaching methods through online platforms. Digital teaching cannot be the re-proposal of the frontal lesson as it favors the reconceptualisation of technology as a “normal” cultural resource for teaching (as happens when the mobile phone or tablet are used in class to promote learning activities). Although it has been the traditional way of learning for decades, some students’ learning style does not match that of a traditional classroom, here the value that is recognized in a teacher does not depend only on his teaching. Technology can also be introduced into the classroom as an effective supplement to face-to-face lessons (Rivoltella, 2013). This contribution intends to offer a reflection about the introduction of technologies in a traditional classroom and how these can be a valid support for teaching

TEACHING ENGLISH WITH A CHILLY FORMAT: THE GRAPHIC NOVEL!

Recently, the term graphic novel is commonly used in the educational area, and it’s often associated with another term, which is ‘comic book ‘. In a typical perception, the graphic novel provides an interesting way to communicate language concepts with a number of characteristics that may help students learning in a more effective manner rather than traditional textbooks. Given that it has been introduced in school lessons, it has certainly represented an opportunity for teachers. However...what exactly is a graphic novel? It is a didactic tool. A graphic novel, as its name suggests, is a novel that tells a complete story via illustrations. A graphic novel will offer the type of resolution that one expects from a novel, even if it is part of a series. Effectively, this makes a graphic novel longer and more substantive than a comic book, which is a serialized excerpt from a larger narrative story. Humankind has long told stories via images, beginning, perhaps, with the cave paintings of ancient civilizations. It was in the twentieth century, that we witnessed the rise in the use of comic books, which experienced a golden age during the Great Depression and World War II with the ascendance of Marvel and DC Comics. The Cold War era saw comic books and novels emerge into what is now known as a graphic novel. The term “graphic novel” traces back to an essay written by Richard Kyle in the comic book fanzine Capa-Alpha (although to this day there is not one fixed definition of “graphic novel”). The term is thought to have become mainstream with the publication of Will Eisner's A Contract with God in 1978. The authors provide an overview of the graphic novel format and its use in school lessons. The work is aimed at describing the most important steps of this format, with its implications for teachers and students and the theoretical base that highlights how and why it can be a useful tool to present content relevant for the current generation of students. The authors provide examples of how the graphic novel medium could be applied to English concepts and conclude with the future prospects of this studying/teaching tool

La professionalità dell’insegnante nella scuola dell’emergenza

L’emergenza causata dalla pandemia di Covid-19 ha avuto un impatto significativo sul sistema di istruzione e formazione. In un momento così complesso e problematico, la rilettura della proposta di Ferrière offre importanti spunti di riflessione: fra questi limitare l’insegnamento a pochi contenuti, rifiutando un’educazione enciclopedica. La scuola, in particolare al tempo dell’emergenza sanitaria che ha visto limitato e ri-pensato il tempo e il luogo didattico, deve orientarsi alla promozione di apprendimenti significativi e allo sviluppo di competenze trasversali. A partire dalle premesse esposte, questo contributo si propone di comprendere come le scuole italiane abbiano affrontato il periodo emergenziale con lo scopo di indagare in che misura la didattica a distanza ha impattato sulla professionalità docente e, in particolare, sull’azione didattica. Il lavoro brevemente presenta gli esiti di una sintesi narrativa dei principali studi di settore che hanno indagato la professionalità docente nella scuola della Pandemia, allo scopo di delineare le caratteristiche dell’insegnamento efficace “d’emergenza” e/o evidenziare i limiti della proposta di insegnamento.The emergency caused by the Covid-19 Pandemic had a significant impact on the education and training system. At this complex and problematic time, the reinterpretation of Ferrière’s proposal offers some food for thought: among them to limit the teaching to a few contents, refusing an encyclopedic education. The school should be geared towards the promotion of meaningful learning and the development of the soft skills, especially at the time of the health emergency which provided for a change in the time and place of teaching. According to the premises, this work aims to understand how the Italian schools have addressed the emergency, with the intention of investigating the extent to which distance learning has impacted on the teaching professionalism and on the teaching action. The work briefly discusses the results of a narrative synthesis of the main studies that investigated the teaching professionalism in the school of Pandemic, to outline the characteristics of effective teaching and/or highlight the limitations of the training proposal

The laboratory as a pedagogical space: an experience with the students of the University of Salerno

In contemporary society, the role and functions of university education have undergone a profound change. The university is no longer a place of élite education reserved for the training of some professions traditionally considered prestigious, nor does it deal exclusively with theoretical and applicative research, but, following the overall evolution of the training systems, it has taken on the typical characteristics a mandatory segment of the training system, that is, necessary for access to most of the contemporary professions. In this context, the individual is increasingly in need of an environment that provides him with the cognitive, emotional, relational and managerial skills necessary for an autonomous and responsible choice in his career path. Therefore, university teaching has the task of generating a profound change in its organization, in relation to the needs of the socio-culturalworking context and the development of different professions. In this context, great attention is paid to the activity of the university laboratory, in terms of reorganization of teaching and as a pedagogical space in which alternative solutions are tested that pave the way for an integration between theory and practice. A place of conjugation between teachers, students and researchers, which requires reflection on the purposes of education and knowledge of the disciplines of study. The laboratories, within the university course, were conceived as a hinge capable of welding the times of formal preparation and practical preparation through analysis, planning and meta-reflection [1] [2] [3] or as a place / operationalization structure of the theory-practice-theory nexus [4]. The laboratory can become an effective tool to strengthen the relationship between training and the world of work, it can become a place capable of nourishing and legitimizing the development of professionalization [2]. If we consider the dimension of the spiral articulation of theory and practice, the learning does not only concern decontextualized knowledge or declinations of knowledge in knowing how to do or knowing how to be, but converge on the construction of skills: disciplinary contents, interdisciplinary plots and skills here they are not an object of learning in themselves but become a means at the service of the treatment of certain situations. The purpose of this work is to theoretically investigate the importance of laboratory activity in the university environment, not only in terms of the application of theory, but as a research space and pedagogical area, in which possible strategies for solving problems are tested that professionalism will face in the world of work. Specifically, it presents a university laboratory experience of Experimental Pedagogy, lived with the students of the Master's Degree Course in Pedagogical Sciences (LM 85) of the University of Salerno. This contribution lays the foundations for a subsequent empirical investigation to be conducted on the laboratory activities present in the degree courses of the educational professions (L19, LM85 and LM57) of the aforementioned University, to understand the logical levels of the learning that takes place in this phase, in relationship to the transfer of disciplines, and its impacts in response to the world of work

Sex-Specific Effects of Short-Term Oral Administration of Food-Grade Titanium Dioxide Nanoparticles in the Liver and Kidneys of Adult Rats

Titanium dioxide (TiO2) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO2 is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO2 nanoparticles (NPs) (primary size 2 NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO2 NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO2 NPs in other items that can lead to human exposure

Study of the role of the Ofd1 protein in the hippocampus

The Oral-facial-digital type 1 syndrome (OFD1, MIM 311200) is a developmental disorder that belongs to a heterogeneous group of cilipathies. OFD1 is transmitted as an X-linked dominant condition with male embryonic lethality. The females, however, have abnormalities affecting the face, the oral cavity and the skeletal structures. The OFD1 gene, responsible for the disease, codifies for the OFD1 protein, localized in the basal body of the primary cilium and in centrosome. During embryonic development OFD1 is essential in the process of ciliogenesis and left-right axis specification. The primary cilium is crucial in Hedgehog signal transduction pathway, essential in the organization of the nervous system. Few OFD1 cases display mental retardation that is not associated with structural abnormalities of the CNS and this suggests that the primary cilium might have role in maintaining brain function. We know that Ofd1 is expressed in Mus musculus hippocampus, cerebellum and olfactory bulbs. In order to evaluate the role of Ofd1 in cerebral functions we used as a model organism transgenic mice in which the Ofd1 gene was conditionally inactivated in the hippocampus from day P21. A month after birth, hippocampi showed no morphological alterations in their organization. The images obtained at CLSM showed the presence of the primary cilium that has, in particular at the level of the cells of the dentate gyrus, reduced size in KO compared to wt. It was observed by TEM in KO samples the presence of prociglia both in the cells of the dentate gyrus and of the CA1 region with the presence of alterations in the microtubular basal body organization. These preliminary data confirm that the presence of Ofd1 is essential for maintaining the primary cilium that is altered due to the onset of neurological defects present in OFD1

Risk Assessment of Transgender People: Development of Rodent Models Mimicking Gender-Affirming Hormone Therapies and Identification of Sex-Dimorphic Liver Genes as Novel Biomarkers of Sex Transition

Transgender (TG) describes individuals whose gender identity differs from the social norms. TG people undergoing gender-affirming hormone therapy (HT) may be considered a sub-group of the population susceptible to environmental contaminants for their targets and modes of action. The aim of this study is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex were subcutaneously exposed to three doses of HT (plus control) selected starting from available data. The demasculinizing-feminizing models (dMF) were β-estradiol plus cyproterone acetate, at 0.09 + 0.33, 0.09 + 0.93 and 0.18 + 0.33 mg, respectively, five times/week. The defeminizing-masculinizing models (dFM) were testosterone (T) at 0.45, 0.95 and 2.05 mg, two times/week. Clitoral gain and sperm count, histopathological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 were evaluated. In the dMF model, the selected doses—leading to T serum levels at the range of the corresponding cisgender—induced strong general toxicity and cannot be used in long-term studies. In the dFM model, 0.45 mg of T represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suitable biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models