102,028 research outputs found
Neural stem cells differentiated from human induced pluripotent stem cells (iPSCs) as a novel in vitro model to study developmental pathways in Huntington Disease
Huntington Disease (HD) is an autosomal dominant disorder characterized by motor, cognitive and behavioral features caused by a CAG expansion in the HTT (huntingtin) gene beyond 35 repeats. Since the discovery of the HTT mutation 24 years ago, more than 15,000 papers have been published on HD. However, both the role of the huntingtin (wtHTT) in healthy individuals and the molecular mechanisms by which the mutated huntingtin causes the disease remain unclear. The discovery of induced pluripotent stem cell (iPSC) technology offer the possibility to generate patient-specific iPS cells and to enable the development of in vitro HD models that more accurately reflect the human disease. The disease-specific iPSCs can be differentiated into relevant cell-types affected in HD, holding a great potential for disease modeling and drug screening. In the present study, we have obtained dermal fibroblasts from 16 HD patients and 6 healthy controls. Fibroblasts from a young adult healthy control, a young subject with 43 CAG repeats, in an early stage of the disease and two JHD (Juvenile Huntington disease) patients were reprogrammed into induced pluripotent stem cells. All iPS clones that show an uniform flat morphology are characterized for their stemness and pluripotency, both in vitro through embryoid bodies formation and in vivo through teratoma formation assay. iPS cells from a JHD (85CAG) and healthy control, were differentiated into neurospheres of neural precursors (NPCs) by a new protocol optimized for differentiation of iPSCs derived embryoid bodies expressing all the three germ layers (ectoderm, mesoderm and endoderm) in neurospheres of Neural Stem Cells (NSCs). Differentiation assay confirmed that they possessed the potentiality, to differentiate into subtypes of neuronal and glial cells. Gene expression profiling was performed on iPSC HD-derived neurospheres using GeneChip Human Transcriptome Array 2.0. iPSC HD-derived neurospheres exhibit an impaired brain development processes when compared with iPSC-derived neurospheres from healthy individuals. This study aimed to produce a valid model of the Huntington disease. This novel in vitro model will permit us to have a closer view to neuronal development networks by morphologically and physiological studies on the cell types obtained from the neuropheres of NPC
Recent development of monoamine oxidase inhibitors
The monoamine oxidases (MAO-A and MAO-B) are flavoenzymes located in the outer mitochondrial membrane responsible for the oxidative deamination of many endogenous and exogenous monoamines. Recognition of the importance of monoamine oxidases as targets for drug intervention for the treatment of a variety of conditions, such as schizophrenia, Alzheimer's disease, Parkinson's disease and other psychiatric and neurological disorders, has produced an enormous interest in the development of molecules that act as inhibitors on these enzymes. This review mainly focuses on the numerous monoamine oxidase inhibitor (MAO-I)-related patents published from August 2002 to June 2005. In this paper recent developments of monoamine oxidase inhibitors are reported, ordering all patents by molecular structure. A structure-activity relationship (SAR) study that reports on known MAO inhibitors is also outlined before a discussion on new associations with other drugs of classical MAO inhibitors and their new target
Taltac, una piattaforma per l’analisi automatica dei testi
TaLTaC2 (T2) is a ‘metric’ software for the automatic analysis of texts of various types (collections of documents and fragments, short texts from surveys, websites etc.). T2 allows for both a lexical and a textual treatment, and for the full integration of (unstructured) textual data with (structured) codified data - the latter associated with the units of context. The lexical unit of the analysis is mixed, both words and multiwords. The search and extraction of information exploits statistico-linguistic resources – both standard and tailor-made – as well as weighing criteria of a statistical and quantitative nature. Linguistic and semantic annotations are also employed. This allows the user to individuate keywords and elements of terminology at the level of the whole corpus, of parts of it and of single units of context. The results can be exported via matrices, and this makes multi-dimensional analyses possible that express associations between words and latent sense models
Focusing on new monoamine oxidase inhibitors
Importance of the field: Monoamine oxidase (MAO) plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. Furthermore, modulators of neurotransmitters exert pleiotropic effects on mental and cognitive functions. The by-products of MAO-mediated reactions include several chemical species with neurotoxic potential. It is widely speculated that prolonged or excessive activity of these enzymes may be conducive to mitochondrial damages and neurodegenerative disturbances. In keeping with these premises, the development of human MAO inhibitors has led to important breakthroughs in the therapy of several neuropsychiatric disorders. Areas covered in this review: This review highlights the recent MAO inhibitors related patents published from July 2005 to December 2009. It also reports on new associations of already known MAO inhibitors with other drugs, innovative therapeutic targets, MAO inhibitors obtained by plants extraction, alternative administration routes and synthetic processes. What the reader will gain: The reader will gain an overview of the main structures being investigated and their biological activities. Take home message: Several of these MAO inhibitors appear promising for further clinical development
Formazione e sviluppo professionale online degli insegnanti. Studio di un gruppo di insegnanti su Facebook
Come evidenziano importanti ricerche in ambito internazionale e nazionale (TALIS 2013, Indire 2015/2016) la partecipazione degli insegnanti italiani ad iniziative di sviluppo professionale in contesti di natura formale, quali corsi e laboratori, conferenze, seminari, è tra le più basse in Europa ed in costante decrescita, mentre emerge uno spiccato interesse per attività di ricerca individuale e in gruppo e la propensione a individuare le opportunità di sviluppo professionale all’interno di comunità di pratica che, costituendosi come occasioni di confronto tra colleghi, consentono di ancorare l’attività di formazione permanente alle peculiarità dei singoli contesti educativi e di superare una condizione di "isolamento" frequentemente denunciata nel contesto scolastico.
Diverse indagini sottolineano come tali opportunità si possano trovare oggi all’interno di spazi di socialità virtuali o online, quali ad esempio i Social Network, i forum o più in generale gli ambienti del Web 2.0 (Trentin 2004; Ellerani, 2010; Petti 2010; Ranieri & Manca, 2013; Ranieri, et al., 2012; Diggins et al., 2011; Scimeca, 2012; Munoz et al. 2013; Rehm & Notten 2016; Kelly & Antonio 2016; Fox & Bird 2017; Macià & Garcìa 2017).
Il settore di ricerca sulla partecipazione degli insegnanti in contesti di sviluppo professionale online, risulta allo stato attuale largamente alimentato dalle percezioni degli insegnanti stessi (raccolte tramite interviste, surveys, questionari).
L'analisi vuole contribuire all’avanzamento della ricerca e del dibattito sulle opportunità insite nei Social Network di sostenere e alimentare lo sviluppo professionale degli insegnanti, avvalendosi oltre che di metodologie di natura quantitativa e qualitativa, di strumenti di analisi del contenuto lessicale e testuale. In particolare lo studio indaga le dinamiche relazionali e comunicative che hanno luogo all’interno di una peculiare struttura comunitaria costituitasi su Facebook: il gruppo di insegnanti "La Classe Capovolta”
Morbid obesity in a young woman affected by advanced chronic kidney disease: an exceptional case report. Does a high dose of essential amino acids play a key role in therapeutic success?
A 38-year-old woman, obese (219 kg), diabetic, hypertensive, chronic kidney disease (CKD) stage 4, with low plasma albumin level (2.9 g dl(-1)) and marked proteinuria (22 g per day) was studied. Given the advanced-stage CKD with nephrotic proteinuria, we supplemented low-protein diet with high doses of a tailored essential amino acid mixture (AAs: 44 g per day) to improve weight reduction in the patient. After 20 months of conservative therapy, the patient lost 43 kg; despite two episodes of infection, albumin plasma levels increased up to 3.7 g per day. After a further 20 months of dialysis, the patient maintained a diet of 1800 kcal supplemented with 32 g of AAs and lost 47 kg, whereas both albumin (3.89±0.12 g dl(-1)) and C reactive protein returned to normal. During the follow-up period, anemia improved, erythropoietin was thus discontinued and insulin requirement decreased to 105 IU. This therapeutic option may be beneficial in advanced CKD patients with obesity and diabetes resulting from malnutrition
Potenzialità di TaLTaC nella anonimizzazione di sentenze della magistratura
I documenti provenienti dalla Pubblica Amministrazione sono una importante fonte di dati per l’analisi di fenomeni sociali ed economici, ma la presenza nel testo di riferimenti a persone fisiche rendono necessario disporre di procedure di anonimizzazione per rispettare le norme relative alla privacy.
I riferimenti alle persone fisiche sono di diversa natura, dipendendo anche dal tipo di documenti disponibili. Nelle sentenze della magistratura penale, per esempio, le persone fisiche coinvolte hanno ruoli anche molto diversi (imputato, parte offesa, parte civile, testimone, etc) e sono identificate da nome e cognome, luogo e data di nascita ma anche con il codice fiscale per le sentenze emesse in tempi più recenti. Nel caso di sentenze civili di divorzio, inoltre, tra le persone fisiche citate possono trovarsi anche eventuali figli, anche di età minore.
Un’ulteriore garanzia di privacy imporrebbe di rendere anonime anche le citazioni delle figure professionali (avvocati, esperti, e gli stessi giudici) inserite in qualsiasi sentenza sia civile che penale.Documents originating from the Public Administration are an important source of data for the analysis of social and economic phenomena, but the presence in the text of references to individuals make it necessary to have anonymization procedures in order to comply with privacy regulations.
References to individuals are of a different nature, depending also on the type of documents available. In the sentences of the criminal judiciary, for example, the individuals involved have very different roles (defendant, offended party, civil party, witness, etc.) and are identified by their name, place and date of birth but also with the tax code for the sentences issued in more recent times. In the case of civil judgments of divorce, moreover, among the physical persons mentioned there may also be children.
A further guarantee of privacy would impose to make anonymous the quotations of professional figures (lawyers, experts, and the same judges) included in any judgment both civil and criminal
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