Bone Marrow Microenvironmental Control Of Hematopoietic Stem Cell Trafficking

Autologous hematopoietic stem/progenitor cells (HSPC) transplantation success depends upon adequate cell collection after G-CSF-administration that a substantial fraction of patients fails to achieve. Retrospective analysis of patient records demonstrated that diabetes correlated with lower CD34+ cell mobilization. Using mouse models, we found impaired HSPC egress from the bone marrow in either streptozotocin-induced or db/db diabetic animals. HSPC aberrantly localized within the marrow microenvironment of diabetic animals in association with abnormalities in sympathetic neuron number and function. Markedly increased sympathetic neuron density was accompanied by abnormal response to -adrenergic stimulation and a failure to generate the G-CSF-induced CXCL12 gradient in nestin-expressing mesenchymal cells associated with HSPC mobilization. Alternative mobilization by direct pharmacologic inhibition of CXCL12-CXCR4 interaction rescued the defect. These data reveal diabetes-induced changes in bone marrow physiology and microanatomy and point to a pathophysiologically based approach to overcome HSPC mobilization defects in diabetic patients

Le vittime del racket. Imprenditori e commercianti alle prese con Cosa Nostra, ‘Ndrangheta e Camorra

Il lavoro propone una ricerca su un mondo psichico fin qui ancora inesplorato: i pen-sieri, le emozioni, l’esperienza delle vittime del racket delle tre grandi organizzazioni criminali del meridione d’Italia: la Mafia, la Camorra e la ‘Ndrangheta. L’obiettivo è comprendere le multi-sfaccettate questioni psico-antropologiche e sociali sulle quali le organizzazioni criminali si sono radicate, ed in particolare quali dinamiche psico-relazionali e quali codici transculturali entrino in gioco nel complesso e controverso rapporto tra vittima e sistema criminale, tra vittima e sistemi di supporto. Con imprenditori e commer-cianti vittime della criminalità organizzata, sono stati analizzati i vissuti - in particolare la paura - e le problematiche psicologiche cui essi sono andati incontro; gli eventi e le motivazioni che hanno permesso di “rompere” il silenzio e di formulare una richiesta d’aiuto; la rappresenta-zione della rete di supporto prima e dopo l’eventuale denuncia; il tipo di aiuto offerto dai si-stemi di supporto. La dignità e il rispetto per sé stessi, la difesa della propria libertà e del proprio onore, valori profondi delle culture meridionali, quegli stessi valori che le mafie usano e radicalizzano, capovolgendoli e facendoli diventare strumenti di sopraffazione e di dominio, sembrano essere i temi portanti che guidano la ribellione alla vittimizzazione. Insieme a questo, il sostegno forte delle reti asso-ciazionistiche antiracket.This work proposes a research on a still unexplored psychical world: thoughts, emo-tions and real events experienced by racket victims of the three largest criminal organizations of the South of Italy: Mafia, Camorra and ‘Ndrangheta. The purpose is to understand the multi-faceted psycho-anthropological and social issues crimi-nal organizations have settled on, and particularly which psycho-relational dynamics and socio-cultural codes come into play in the complex and controversial relationship between victim and criminal system, between victim and support systems. With entrepreneurs and tradesmen victims of organized crime, we have analyzed lived experiences – in particular fear – and psy-chological problems they had to cope with; events and motivations which allowed them “breaking” the silence and asking for help; the representation of a support network before and after their possible pressing charges; the kind of help offered by support systems. Dignity and self respect, the defense of one’s own freedom and honor, deep values typical of south-ern cultures, those same values Mafia uses and radicalizes, turning them upside down and transforming them into tools to overpower and dominate, seem to be the main themes which lead the rebellion against victimization. Along with this, the strong support of anti-racket asso-ciations

Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation

Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse

"Lo spazio europeo di libertà, sicurezza e giustizia fondamento per una democrazia europea oltre lo Stato?" Sicurezza Diritti umani e Sovranità "condivisa" nell'Unione europea

2010 - 2011Questa ricerca è strutturata in tre parti distinte: - La Prima Parte affronta la questione chiave dei: “Mutamenti nel rapporto fra territorio e spazio nell’Europa moderna”. Un nodo teorico senza il quale non si riuscirebbe a comprendere il tentativo di costruzione di uno "spazio giuridico comune" dell’ Unione europa attuale che si deve misurare con la presenza di territori nazionali con una loro specificità geografica, storica, politica e giuridica, che ancora forniscono senso di appartenenza. Da qui' la dialettica fra territorio e spazio che mantiene e, anzi, acuisce la sua centralità come emerge dal processo costituente dell'Unione europea e in parallelo dall'esperienza derivante da sessant'anni di giurisprudenza della Corte europea dei diritti dell'Uomo. Anche da questo punto di vista, il processo di costruzione dell’Europa è intimamente dialettico, muovendo essenzialmente dalle realtà statali per intravedere la via travagliata che conduce oltre di esse: il rapporto fra Stato e territorio ha segnato la storia dello Stato e della dottrina ad esso relativa. Lo spazio comune europeo si inserisce come elemento necessario e critico di analisi. -La Seconda Parte è dedicata a: “Lo spazio di libertà, sicurezza e giustizia alla luce dei trattati dell'Unione europea”. E’ una parte necessariamente più "specialistica", che entra in un campo storico-giuridico, provando a descrivere il funzionamento dello spazio comune dell'Unione europea posto in relazione con l’insieme delle innovazioni istituzionali in cui è inserito e, quindi, cercando anche di analizzare i mutamenti morfologici in termini di sovranità e legittimazione che ne derivano. Diviene, dunque, centrale, la legittimazione attraverso i diritti, attraverso la novità del carattere vincolante della “Carta dei diritti fondamentali dell’Unione europea” e il principio di cittadinanza. -La Terza Parte si concentra su: “La legittimazione dello spazio multilaterale dell'Unione europea” e prova ad aprire lo sguardo sul rapporto fra l’Europa dello "spazio comune" e gli spazi globali, su cui tutte le entità, statali e non-statali, oggi si relazionano. In questo spazio comune, il tema della democrazia e della sovranità si trovano intimamente interconnessi. La questione centrale per sviluppare questa analisi è: quale contributo può dare l’Europa (l'Unione europea) della “sovranità condivisa” in uno spazio oltre gli Stati nazionali per la legittimazione di una visione multilaterale della governance globale. [a cura dell'autore]X n.s

Is mass loss along the red giant branch of globular clusters sharply peaked? The case of M3

There is a growing evidence that several globular clusters must contain multiple stellar generations, differing in helium content. This hypothesis has helped to interpret peculiar unexplained features in their horizontal branches. In this framework we model the peaked distribution of the RR Lyr periods in M3, that has defied explanation until now. At the same time, we try to reproduce the colour distribution of M3 horizontal branch stars. We find that only a very small dispersion in mass loss along the red giant branch reproduces with good accuracy the observational data. The enhanced and variable helium content among cluster stars is at the origin of the extension in colour of the horizontal branch, while the sharply peaked mass loss is necessary to reproduce the sharply peaked period distribution of RR Lyr variables. The dispersion in mass loss has to be <~ 0.003 Msun, to be compared with the usually assumed values of ~0.02 Msun. This requirement represents a substantial change in the interpretation of the physical mechanisms regulating the evolution of globular cluster stars.Comment: Accepted for publication in The Astrophysical Journa

Coexistence of three EGFR mutations in an NSCLC patient: A brief report

The epidermal growth factor receptor (EGFR) represents a molecular target for tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC) patients with a mutation in the EGFR gene. Mutations of the EGFR gene that occur at a single position in NSCLC tissue are found as single, whereas two or more mutations on the same allele are poorly detected and investigated

Relative Frequencies of Blue Stragglers in Galactic Globular Clusters: Constraints for the Formation Mechanisms

We discuss the main properties of the Galactic globular cluster (GC) blue straggler stars (BSS), as inferred from our new catalog containing nearly 3000 BSS. The catalog has been extracted from the photometrically homogeneous V vs. (B-V) color-magnitude diagrams (CMD) of 56 GCs, based on WFPC2 images of their central cores. In our analysis we used consistent relative distances based on the same photometry and calibration. The number of BSS has been normalized to obtain relative frequencies (F_{BSS}) and specific densities (N_S) using different stellar populations extracted from the CMD. The cluster F_{BSS} is significantly smaller than the relative frequency of field BSS. We find a significant anti-correlation between the BSS relative frequency in a cluster and its total absolute luminosity (mass). There is no statistically significant trend between the BSS frequency and the expected collision rate. F_{BSS} does not depend on other cluster parameters, apart from a mild dependence on the central density. PCC clusters act like normal clusters as far as the BSS frequency is concerned. We also show that the BSS luminosity function for the most luminous clusters is significantly different, with a brighter peak and extending to brighter luminosities than in the less luminous clusters. These results imply that the efficiency of BSS production mechanisms and their relative importance vary with the cluster mass.Comment: 12 pages, 3 figures. accepted for publication in ApJ

Influenze tra processo ed esiti: alleanza, coesione e cambiamento in un gruppo terapeutico a lungo termine

Research is currently moving in the direction of an integration between the outcome measures of the patients and the relational and/or structural factors that can facilitate their change. It is increasingly important to focus studies on the relationship between process and outcome, especially with regard to psychodynamic group therapy. These treatments, very complex and difficult to operationalize, still pose critical questions for research such as what are the main elements of the therapeutic process that are activated in these therapies?Many efforts are to be made in understanding which factors develop in groups and the conditions that positively influence the success of therapy. Important is, moreover, the work of conceptual and "operational" depth on the different constructs, to better understand their nature and differences and build tools to more easily detect their features. Therapeutic alliance and cohesion are among the most investigated process variables, because of their role on the results of therapy.This study investigates these two variables in a therapeutic group with severe patients and analyzes their associations with treatment outcomes in term of symptoms and defenses. A long-term, semi-open group meeting on a weekly basis was examined. The observation was carried out for a period of 18 months, for a total amount of 50 sessions; 11 patients with different diagnoses in Axis I and II DSM IV were examined. Outcome measures: SCL-90 - Symptom Check List; OQ-45 - Outcome Questionnaire 45.2; DSQ - Defense Style Questionnaire.Process measures: CALPAS-G: California Psychotherapy Alliance Scale-Group; GMLCS: Group/Member/Leader Cohesion Scale. The observation period was divided into 3 phases according to re-modulations of the setting (new entries, overcomes, dropout). Significant correlations between alliance, cohesion and outcomes were found in the three phases. During the phase of greater instability, the predominant role of cohesion and, more generally, dimensions related to group commitment emerge. Results offer interesting suggestions about the differentiation between Alliance and Cohesion and their different relationship with outcomes and process evolution