Neuronal types and their specification dynamics in the autonomic nervous system

The autonomic nervous system is formed by a sympathetic and a parasympathetic division that have complementary roles in the maintenance of body homeostasis. Autonomic neurons, also known as visceral motor neurons, are tonically active and innervate virtually every organ in our body. For instance, cardiac outflow, thermoregulation and even the focusing of our eyes are just some of the plethora of physiological functions under the control of this system. Consequently, perturbation of autonomic nervous system activity can lead to a broad spectrum of disorders collectively known as dysautonomia and other diseases such as hypertension. Neuroblastoma, one of the most common and lethal infancy cancer, arises from defects during the embryonic development of sympathetic neurons. Despite its importance in everyday life and clinical relevance, little is known regarding the molecular mechanisms regulating the birth, differentiation and heterogeneity of the autonomic neurons. This PhD thesis aims at reducing this gap of knowledge. In paper I, we describe the role of the Homeobox transcription factor HMX1 and receptor signalling in directing neuronal fate during embryogenesis. We propose a new model for sympathetic specification in which mature noradrenergic and cholinergic types emerge from a common progenitor and neuronal identity is established via mechanisms involving active repression of receptors and transcription factors directing alternative cell fates. In paper II, we take advantage of high-throughput sequencing approaches to explore the heterogeneity of the sympathetic system and describe the existence of seven molecularly distinct cell types. Using a combination of retrograde and lineage tracing approaches, we describe the developmental mechanisms leading to the emergence of two specialized cell types projecting to the pilo (PEM) and nipple (NEM) erector muscles. In paper III, we show that the parasympathetic nervous system, previously thought to be originated by the Neural Crest Stem Cells (NCSCs) is derived from stem-like Schwann cell precursors (SCPs) intimately associated with the extending cranial nerves during development. All together, the data collected in this thesis provide new insights into key aspects regulating the origin and development of the autonomic nervous system and provide compelling evidence regarding the existence of specialized cell types regulating specific functions. This knowledge provides new principles on how the autonomic nervous system develops that might help to understand also its pathologies, such as neuroblastoma and dysautonomia

A.R.T. Ancient Rome Tour 2.0 Upgraded How Nero Saved Rome

[IT] La presentazione di Altair4 ad Arquelogica 2.0 consiste essenzialmente nella presentazione delle ultime produzioni su Roma Antica, attraverso la proiezione di alcune animazioni tratte da "How Nero Saved Rome" film in HD per National Geographic Channel e Il Foro Romano e i Fori Imperiali per la trasmissione RAI Ulisse. Queste produzioni si inquadrano nell'ambito del progetto pluriennale A.R.T. (Ancient Rome Tour). Il progetto nasce nel 1998 con il proposito di creare nuovi strumenti di comunicazione per la conoscenza della storia della costruzione della città di Roma e degli eventi ad essa collegati. Dopo dieci anni dalla prima pubblicazione si è deciso di operare un significativo aggiornamento dei contenuti della parte più monumentale della città, il palatino, il foro romano, i fori imperiali e la valle del colosseo, area un tempo in gran parte occupata dalla fastosa residenza dell'imperatore Nerone: La Domus Aurea. In questi dieci anni infatti si sono raccolti e analizzati i risultati di alcune importanti attività di scavo e ricerca svolte da diverse istituzioni e istituti di ricerca concretizzati in un impegnativo lavoro di sintesi visuale con gli strumenti della computer grafica 3D cercando di restituire una unità spaziale ad un'area che risulta oggi estremamente frammentata e di difficile lettura.Moretti, S.; Furlan, A. (2011). A.R.T. Ancient Rome Tour 2.0 Upgraded How Nero Saved Rome. Virtual Archaeology Review. 2(4):115-121. https://doi.org/10.4995/var.2011.4566OJS11512124CARANDINI, Andrea. "Le case del potere dai re agli imperatori". AudioLibri Laterza. Lezioni di Storia. Sulla scena di Roma - Edizione 2007 http://www.laterza.it/index.php?option=com_laterza&Itemid=97&task=schedalibro&isbn=9788849100037PANELLA, Clementina. "Archaeological Investigations & Discoveries" (2002-2009) - THE META SUDANS / THE PALATINE HILL / "Roma-Piazza del Colosseo, area della Meta Sudans; pendici nord-orientali del Palatino." La Sapienza Roma (07/2009).http://www.flickriver.com/photos/imperial_fora_of_rome/sets/72157594580930580/BESTE, Heinz. "Un palazzo imperiale. La domus aurea neroniana" . .S.S. Editorial Service System S.r.l. Forma Urbis Roma, settembre 2010F. BALL, Larry. "The Domus Aurea and The Roman Architectural Revolution". Cambridge University Press. Cambridge 2003 http://dx.doi.org/10.1017/CBO9780511666551CONTI, Cinzia, MARTINES, Giangiacomo, SINOPOLI, Anna, "Constructions Techniques of Roman Vaults: Opus Caementicium and the Octagonal Dome of the Domus Aurea". Proceedings of the Third International Congress on Construction History. Cottbus, May 2009MARTINES, Giangiacomo, "Argomenti di geometria antica a proposito della cupola del Pantheon", Quaderni dell'Istituto di storia dell'Architettura, 13 (1989)MENEGHINI Roberto, SANTANGELI VALENZANI, Riccardo. "I Fori Imperiali, Gli scavi del Comune di Roma (1991-2007)". Viviani Editore - Roma 2007TUCCI, Pier Luigi. "Nuove osservazioni sull'architettura del Templum Pacis". in Divus Vespasianus, il bimillenario dei Flavi, Electa - Roma 2009PACKER. James E."Il Foro di Traiano a Roma, Breve studio dei monumenti" Edizioni Quasar - Roma 2001LA ROCCA, Eugenio, UNGARO, Lucrezia, MENEGHINI, Roberto, "I luoghi del Consenso Imperiale, Il Foro di Augusto Il Foro di Traiano". Progetti Museali Editore - Roma 1995COARELLI. Filippo. "Il Foro Romano". Edizioni Quasar. Roma 199

Total knee arthroplasty after high tibial osteotomy. A systematic review

Background: Previous osteotomy may compromise subsequent knee replacement, but no guidelines considering knee arthroplasty after prior osteotomy have been developed. We describe a systematic review of non-randomized studies to analyze the effect of high tibial osteotomy on total knee arthroplasty. Methods: A computerized search for relevant studies published up to September 2007 was performed in Medline and Embase using a search strategy that is highly sensitive to find nonrandomized studies. Included were observational studies in which patients had total knee arthroplasty performed after prior high tibial osteotomy. Studies that fulfilled these criteria, were assessed for methodologic quality by two independent reviewers using the critical appraisal of observational studies developed by Deeks and the MINORS instrument. The study characteristics and data on the intervention, follow-up, and outcome measures, were extracted using a pre-tested standardized form. Primary outcomes were: knee range of motion, knee clinical score, and revision surgery. The grade of evidence was determined using the guidelines of the GRADE working group. Results: Of the 458 articles identified using our search strategy, 17 met the inclusion criteria. Fifteen studies were cohort study with a concurrent control group, one was a historical cohort study and one a case-control study. Nine studies scored 50% or more on both methodological quality assessments. Pooling of the results was not possible due to the heterogeneity of the studies, and our analysis could not raise the overall low quality of evidence. No significant differences between primary total knee arthroplasty and total knee arthroplasty after osteotomy were found for knee range of motion in four out of six studies, knee clinical scores in eight out of nine studies, and revision surgery in eight out of eight studies after a median follow-up of 5 years. Conclusion: Our analysis suggests that osteotomy does not compromise subsequent knee replacement. However, the low quality of evidence precludes solid clinical conclusions

A EFETIVAÇÃO DA DEMOCRACIA REPRESENTATIVA

The article initially outlined brief considerations regarding the predominance of the representative regime in the Modern States. Subsequently, the existence of universal suffrage and political parties as the main characteristics of the representative model was listed. Considerations were made as to how the right to vote is exercised, as well as the need to safeguard mechanisms for direct participation, even as a way of ensuring a higher quality of voting. In relation to the political parties, pertinent considerations were made regarding the multi-party system and its application in the present time.O artigo inicialmente traçou sucintas considerações quanto à predominância do regime representativo no âmbito dos Estados Modernos. Posteriormente elencou-se a existência do sufrágio universal e dos partidos políticos como principais características delineadoras do modelo representativo. Foram tecidas considerações quanto à forma de exercício do direito de voto, bem como quanto a necessidade do resguardo de mecanismos de participação direta como forma de assegurar-se uma maior qualidade de exercício do voto. Em relação aos partidos políticos foram feitas ponderações pertinentes quanto ao sistema pluripartidarista e sua aplicação na atualidade

O ESTADO MODERNO E O REGIME DEMOCRÁTICO

The present study draws a line of correlation between the evolution of the Modern State and the democratic regime. Initially brief considerations were made regarding the origin of the State as a political organization, with its current characteristics. Subsequently, with the necessary synthesis, we pondered on the evolution of the democratic regime, highlighting its manifestations throughout history, namely: direct, semi-direct and representative democracy. At the end of the development of the work, brief considerations were made as to the indispensable granting of confidence by the citizens of democratic institutions and their representatives, as a form of stability of the regime. Finally, the final considerations were woven.O presente estudo traçou uma linha de correlação entre a evolução do Estado Moderno e o regime democrático. Inicialmente foram tecidas breves considerações quanto à origem do Estado como organização política e suas características. Posteriormente, com a síntese necessária, ponderou-se a respeito da evolução do regime democrático dando destaque as suas modalidades de manifestação ao longo da história, a saber: democracia direta, semidireta e representativa. Encerrando-se o desenvolvimento do trabalho foram feitas breves considerações quanto a indispensável concessão de confiança por parte dos cidadãos as instituições democráticas e seus representantes, como forma de estabilidade do regime. Por fim, foram tecidas as considerações finais. &nbsp

How Biorecognition Affects the Electronic Properties of Reduced Graphene Oxide in Electrolyte‐Gated Transistor Immunosensors

Ambipolar electrolyte-gated transistors (EGTs) based on reduced graphene oxide (rGO) have been demonstrated as ultra-sensitive and highly specific immunosensors. However, the physics and chemistry ruling the device operation are still not fully unraveled. In this work, the aim is to elucidate the nature of the observed sensitivity of the device. Toward this aim, a physical–chemical model that, coupled with the experimental characterization of the rGO-EGT, allows one to quantitatively correlate the biorecognition events at the gate electrode and the electronic properties of rGO-EGT is proposed. The equilibrium of biorecognition occurring at the gate electrode is shown to determine the apparent charge neutrality point (CNP) of the rGO channel. The multiparametric analysis of the experimental transfer characteristics of rGO-EGT reveals that the recognition events modulate the CNP voltage, the excess carrier density Δn, and the quantum capacitance of rGO. This analysis also explains why hole and electron carrier mobilities, interfacial capacitance, the curvature of the transfer curve, and the transconductances are insensitive to the target concentration. The understanding of the mechanisms underlying the transistor transduction of the biorecognition events is key for the interpretation of the response of the rGO-EGT immunosensors and to guide the design of novel and more sensitive devices

Age of Onset of Mood Disorders and Complexity of Personality Traits

Objective. The aim of the present study is to evaluate the link between the age of onset of mood disorders and the complexity of the personality traits. Methods. 209 patients with major depressive or manic/hypomanic episodes were assessed using the Structured Clinical Interview for DSM Axis I diagnoses and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Results. 17.2% of the patients had no elevated MCMI-III scores, 45.9% had one peak, and 36.9% had a complex personality disorder with two or more elevated scores. Mood disorders onset of 29 years or less was the variable most related to the complexity of personality disorders as indicated from a recursive partitioning analysis. Conclusions. The relationship between mood disorders and personality traits differ in reference to age of onset of the mood disorder. In younger patients, maladaptive personality traits can evolve both in a mood disorder onset and in a complex personality disorder, while the later development of a severe mood disorder can increase the personality symptomatology. Our results suggest a threshold of mood disorder onset higher compared to previous studies. Maladaptive personality traits should be assessed not only during adolescence but also in young adults to identify and treat potential severe mood disorders