80 research outputs found
Lo sguardo degli studenti sulle ingiustizie a scuola
Studentsâ perceptions regarding injustice at school are widespread in every educational stages and refer especially to classroom management and learning assessment strategies used by teachers. In this contribution we present the results of an investigation about injustice at school, realized asking to 175 university students of three different courses (Primary education sciences and Human Resource Development at University of Milan â Bicocca and Engineering Management of Politecnico di Milano) to describe one incident of injusticeregarding their past school experiences. The research was conducted using mixed method approach. The results highlight the importance of studentâs perception of injustice about the relationship between students and teachers and among students, the importance of assessment criteria and the importance of teaching strategies adopted.I vissuti di ingiustizia sono molto diffusi tra gli studenti di qualsiasi ordine di scuola ed essi si riferiscono soprattutto alla gestione della classe da parte degli insegnanti e alla valutazione degli apprendimenti. In questo articolo vengono riportati i primi risultati di unâindagine condotta chiedendo a 175 studenti universitari di Scienze della Formazione Primaria, Formazione e Sviluppo delle Risorse Umane (UniversitĂ di Milano Bicocca) e di Ingegneria Gestionale (Politecnico di Milano) di descrivere un episodio di ingiustizia di cui erano stati soggetti o testimoni a scuola. Lâanalisi, condotta con metodi qualitativi e quantitativi, secondo lâapproccio mixed-method, ha fornito interessanti riflessioni sul peso che i vissuti di ingiustizia degli studenti hanno nella relazione in classe con gli insegnanti e con i compagni, nella valutazione e piĂč in generale nel processo di insegnamento e apprendimento
Giustizia e ingiustizia a scuola nelle parole dei futuri maestri
The words justice and injustice often feature in studentsâ reflections on their experience of school, most frequently in relation to assessment, teacher-student relations and modes of class management.In this paper, we present the preliminary results of a study in which 82 trainee primary school teachers described both an episode of justice and an episode of injustice that they had either directly experienced or witnessed during their own school years. The data analysis was carried out using mixed-mode methodology and provided interesting insights into issues such as assessment and relationships in the classroom, as well as highlighting the need for teachers to receive training in interpersonal skills to complement their subject knowledge.Le parole giustizia e ingiustizia ricorrono spesso nelle riflessioni che gli studenti fanno sulla loro esperienza scolastica e coinvolgono la valutazione scolastica, la relazione insegnante-allievi e in generale le modalitĂ con cui Ăš gestita la classe. In questo articolo vengono riportati i primi risultati di unâindagine condotta chiedendo a 82 studenti universitari di Scienze della Formazione Primaria di descrivere un episodio di giustizia e uno di ingiustizia di cui erano stati soggetti o testimoni a scuola. Lâanalisi, condotta con metodi qualitativi e quantitativi secondo il paradigma del mixed-method, ha fornito interessanti riflessioni sul tema della valutazione e della relazione in classe oltre a suggerire indicazioni per una formazione degli insegnanti che ai contenuti disciplinari affianchi buone capacitĂ relazionali
Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis.
Abstract Nicotinamide mononucleotide adenylyltransferase (NMNAT), a member of the nucleotidyltransferase α/ÎČ-phosphodiesterases superfamily, catalyzes a universal step (NMN + ATP = NAD + PPi) in NAD biosynthesis. Localized within the nucleus, the activity of the human enzyme is greatly altered in tumor cells, rendering it a promising target for cancer chemotherapy. By using a combination of single isomorphous replacement and density modification techniques, the human NMNAT structure was solved by x-ray crystallography to a 2.5-A resolution, revealing a hexamer that is composed of α/ÎČ-topology subunits. The active site topology of the enzyme, analyzed through homology modeling and structural comparison with other NMNATs, yielded convincing evidence for a substrate-induced conformational change. We also observed remarkable structural conservation in the ATP-recognition motifs GXXXPX(T/H)XXH and SXTXXR, which we take to be the universal signature for NMNATs. Structural comparison of human and prokaryotic NMNATs may also lead to the rational design of highly selective antimicrobial drugs
2,6-Diphenyl-imidazopyridine derivatives as novel prototypes of anticancer agents targeting aldehyde dehydrogenase
Aldehyde dehydrogenase (ALDH) superfamily comprises 19 different enzyme types located in specific subcellular districts, including cytosol and mitocondria. Their main function is to oxidize endogenous and exogenous aldehydes produced in human cells. In particular, isoforms 1A1, 1A2 and 1A3 catalyze the transformation of retinal into retinoic acid, which is a potent differentiation tissue factor for cellular development. Overexpression of these three isoforms in cancer stem cells (CSC), underlined in recent studies, is to date extremely important in cancer field, as it offers the chance to use these proteins both as prognostic marker and as novel targets in the fight against cancer. Here we present a novel series of 2,6-diphenyl-imidazol[1,2-a]pyridines, designed as aldehyde dehydrogenase inhibitors by means of a structured-based optimizations of a previously developed lead, GA11. The novel compounds were evaluated in vitro for their activity and selectivity against the three isoforms of the ALDH1A family, and investigated through crystallization and modeling studies for their ability to interact with the catalytic site of the 1A3 isoform. Tested in vitro on different populations of CSCs, obtained from glioma, colorectal and prostate tissue specimens, they exhibited a relevant anti-proliferative efficacy, thus paving the way for treating cancer by means of the still untapped aldehyde dehydrogenases
S-CMC-Lys protective effects on human respiratory cells during oxidative stress.
The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys) stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of the most important redox regulatory mechanisms, the aim of this study was to evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration during an oxidative stress induced by the hydroxyl radical (xOH). Experiments were performed on cultured human respiratory WI-26VA4 cells by means of patch-clamp experiments in whole-cell configuration and of fluorimetric analyses at confocal microscope. xOH exposure induced an irreversible inhibition of the GSH and chloride currents that was prevented if the cells were incubated with S-CMC-Lys. In this instance, the currents were inhibited by the specific blocker CFTR(inh)-172. CFT1-C2 cells, which lack a functional CFTR channel, were not responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric measurements performed on the S-CMC-Lys-incubated cells revealed a significant increase of the GSH concentration that was completely hindered after oxidative stress and abolished by CFTR(inh)-172. The cellular content of reactive oxygen species was significantly lower in the S-CMC-Lys-treated cells either before or after xOH exposure. As a conclusion, S-CMC-Lys could exert a protective function during oxidative stress, therefore preventing or reducing the ROS-mediated inflammatory response
Primary brain calcification: an international study reporting novel variants and associated phenotypes.
Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (nâ=â34, 19.2%) or VUS (nâ=â11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetÂź convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetÂź model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Historiografia econĂŽmica do dĂzimo agrĂĄrio na Ibero-AmĂ©rica: os casos do Brasil e Nova Espanha, sĂ©culo XVIII
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Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase (NMNAT) has long been known as the master enzyme in NAD biosynthesis in living organisms. A burst of investigations on NMNAT, going beyond enzymology, have paralleled increasing discoveries of key roles played by NAD homeostasis in a number or patho-physiological conditions. The availability of in-depth kinetics and structural enzymology analyses carried out on NMNATs from different organisms offer a powerful tool for uncovering fascinating evolutionary relationships. On the other hand, additional functions featuring NMNAT have emerged from investigations aimed at unraveling the molecular mechanisms responsible for complex biological phenomena such as neurodegeneration. NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at a crossroads of multiple cellular processes. The resultant wealth of biochemical data has built a robust framework upon which design of NMNAT activators, inhibitors or enzyme variants of potential medical interest can be based
Ribelli, attivisti, militanti e viaggiatori (Politiche e miti nella relazione fra culture antagoniste italiane e movimento zapatista in Chiapas)
L'analyse des relations existantes entre les différentes composantes des mouvements antagonistes italiens et la révolte zapatiste au Chiapas conduit à mettre en relief certains aspects caractéristiques des cultures politiques altermondialistes, apparues à partir de la seconde moitié des années quatre-vingt-dix sur la scÚne européenne et mondiale. L'étude de telles relations contribue, en effet, à délimiter certaines nouvelles conceptions de la politique dont les mouvements altermondialistes se sont fait porteurs et promoteurs, dans un contexte historique de mutations substantielles des équilibres politiques mondiaux. J'ai observé les antagonistes dans leurs contextes nationaux respectifs et dans leurs voyages vers le Chiapas.The analysis of existing relationships between the various components of antagonistic movements in Italy and the Zapatista uprising in Chiapas led to emphasize certain characteristic aspects of antiglobalization political cultures, emerged from the second half of the ninety on the scene European and global. The study of such relationships helps in fact to define some new concepts of political anti globalization movements have been porters and promoters, in a historical context of substantial changes of global political balance. l observed the antagonists in their respective national contexts and their trips to Chiapas.PARIS3-BU (751052102) / SudocSudocFranceF
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