archives@tulane.edu / Vascular endothelial growth factor A (VEGFA) is a key contributor to the formation of new blood vessels and angiogenesis is commonly seen in wound healing, cancer, and inflammatory diseases. However, whether interleukin-17 (IL-17) can induce the expression of VEGFA in prostate cancer cells remains unknown. In this study, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis validated that expression of VEGFA in human prostate cancer LNCaP cells under IL-17 treatment was significantly higher than the untreated control group. The conditioned culture medium (CM) of LNCaP cells treated with IL-17 increased tube number, tube nodes, and tube length formed by human umbilical vein endothelial cells (HUVEC) in tube formation assays, compared with the control CM without IL-17 treatment. Collectively, these findings reveal that the expression of VEGFA is induced by IL-17 in LNCaP prostate cancer cells, which leads to increased angiogenesis of HUVEC cells. This study suggests that expression of VEGFA may be up-regulated by IL-17 in prostate cancer to enhance tumor angiogenesis. / 1 / Benyu Li

Una directriz anticipada es una declaración, oral o escrita, dirigida al personal sanitario, donde una persona expone las formas de cuidado médico que aceptaría o rechazaría en una circunstancia médica específica, o quién debería tomar las decisiones si se vuelve incapaz de expresar sus preferencias. La tesis doctoral nos muestra qué aporta la idea de sujeto en la ética del discurso de Karl-Otto Apel al debate sobre la legitimidad de estos documentos. Apel maneja una noción de sujeto como ser con competencia comunicativa, es decir, con capacidad y derecho para defender argumentativamente sus propuestas, y las directrices anticipadas ponen ante nosotros a unos sujetos irreversiblemente inconscientes a los que acompaña una hoja firmada por ellos en la que expresan cómo quieren ser tratados. ¿Debe ser considerado como interlocutor válido un paciente que ha perdido irreversiblemente la competencia comunicativa? ¿Cómo y con quién deben realizarse los diálogos sobre las cuestiones que le afectan? En la primera parte del trabajo se describen los rasgos de la idea de sujeto en Karl-Otto Apel. Se distinguen seis rasgos básicos: sentido, intersubjetividad, criterio, reflexión, moral postconvencional y corresponsabilidad. En la segunda parte se aplican esos rasgos al problema de las directrices anticipadas. Se recurre al método de la ética aplicada como hermenéutica crítica, que nos pide conocer el ámbito en el que surge el problema, y por ello se ofrece una visión internacional sobre las metas de la medicina en el final de la vida y sobre los principios de la ética biomédica. A continuación se clasifican los argumentos sobre las directrices anticipadas en tres grupos: 1) Argumentos a favor por sus aspiraciones fundamentales. 2) Argumentos a favor si se cumplen ciertas condiciones. 3) Argumentos en contra. El trabajo ofrece un amplio listado de conclusiones. Entre ellas, cabe destacar que el rasgo de la reflexión es el método seguido por el sujeto para llegar a la fundamentación última, a los enunciados con pretensión de certeza, y que un enunciado con pretensión de certeza es el siguiente: "Los sujetos deben poder expresar su voluntad anticipadamente sobre las cuestiones que les afectan". Negar esta afirmación es una autocontradicción preformativa. Las directrices anticipadas son una condición de posibilidad de la argumentación, tienen su fundamento en la lógica del lenguaje y, por lo tanto, son válidas para todas las culturas. Pero las directrices anticipadas, puesto que son realizadas en comunidades reales de comunicación, son falibles y revisables. Esta falibilidad continúa después de la pérdida de consciencia. Por ello, el representante debe poder actuar en contra de lo solicitado por el paciente en una directriz anticipada, bajo la idea de que alcanzaría un nuevo consenso con él en base a la nueva información obtenida. En este acto de interpretación debe decidirse lo que el paciente expresaría si conociera todos los datos relevantes en el momento de tomar la decisión. El trabajo concluye ofreciendo algunas condiciones para que las directrices anticipadas se realicen éticamente. Se destaca la importancia de formar al personal sanitario para conversar con los pacientes sobre la posibilidad de la muerte, y evitar la conspiración de silencio en el seno de la familia, y se dice que no debe aceptarse la fuerza legal de estos documentos si no es posible demostrar, a su vez, que se cumplieron las condiciones éticas que lo legitiman. Se incluyen amplios apéndices con referencias a códigos deontológicos de medicina y a la situación legal en diversos países, así como varios ejemplares de este tipo de documentos. / An advance directive is an oral or written statement, directed to the physician and the family, where a person exposes the forms of medical care that she would accept or would refuse in a specific medical circumstance, or who should make the decisions if she becomes unable to express her wishes. The author of this doctoral thesis shows what can provide the idea of subject in the discourse ethics of Karl-Otto Apel to the discussion on the ethical validity of these documents. Apel says that all beings capable of linguistic communication should be recognised as persons since in all their actions and expressions they are virtual speakers. But, should be considered as a communicative partner a person that has lost her communicative capacity but has written an advance directive? How should be made the dialogue on the questions that affect her? That is the problem affronted in this thesis. The author offers a classification of the arguments on advance directives following this structure: 1) Arguments for advance directives by their fundamental aspirations. 2) Arguments for them if certain requirements are fulfilled. 3) Arguments against them. Using concepts from the discourse ethics of Apel the author offers many conclusions. Among them, the author defends the universal validity of advance directives. Discourse ethics says that every person in the world share the feature of communicative competence. Because people have this competence they must recognise some logical rules of the argumentation. He defends that when a person rejects to express advance directives commits a fundamental logical mistake: performative selfcontradiction, then the fact of rejecting them is also an advance directive. These documents also reduce the asymmetries between the physician, the patient and the other people affected, and look for the consensus between them. Assuming the discourse-ethical principle of co-responsibility he also recognises what kind of changes must take place in the different societies and in the doctor-patient relationship before to authorise the legal introduction of those documents in the different countries of the world. In one of the appendixes, the author includes documents of advance directives from some countries in the world.

La labioschisi con o senza palatoschisi non-sindromica (NSCL/P) è tra le più frequenti alterazioni dello sviluppo embrionale, causata dall’interazione di fattori genetici e ambientali, moti dei quali ancora ignoti. L'obiettivo del mio progetto di Dottorato consiste nell’identificazione di fattori di rischio genetico in un processo a due stadi che prevede la selezione di geni candidati e la verifica del loro coinvolgimento nella determinazione della malformazione mediante studi di associazione. Ho analizzato alcuni polimorfismi a singolo nucleotide (SNPs) dei geni RFC1 e DHFR, appartenenti alla via metabolica dell’acido folico, evidenziando una debole associazione tra alcuni degli SNPs indagati e la NSCL/P nella popolazione italiana. Presso il laboratorio della Dott.ssa Mangold dell’Università di Bonn, ho valutato il ruolo di 15 diverse regioni cromosomiche nel determinare la suscettibilità alla malattia, evidenziando una significativa associazione per i marcatori localizzati in 8q24 e 1p22. Ho quindi rivolto la mia attenzione al ruolo del complesso Polycomb nell’insorgenza della schisi. Nell’uomo i due complessi Polycomb, PRC1 e PRC2, rimodellano la cromatina agendo da regolatori dei meccanismi trascrizionali alla base della differenziazione cellulare e dello sviluppo embrionale. Ho ipotizzato che mutazioni a carico di geni appartenenti a PRC2 possano essere considerati potenziali fattori di rischio genetico nel determinare la NSCL/P. Il razionale consiste nel fatto che JARID2, una proteina che interagisce con PRC2, è associata all’insorgenza della NSCL/P ed espressa a livello delle cellule epiteliali delle lamine palatine che si approssimano alla fusione. L’indagine condotta analizzando i geni di elementi o partner dei due complessi Polycomb, ha evidenziato un’associazione significativa con alcuni polimorfismi dei geni indagati, associazione ulteriormente confermata dall’analisi degli aplotipi. Le analisi condotte sui geni candidati mi hanno permesso di raccogliere dati interessanti sull’eziologia della malformazione. Studi indipendenti saranno necessari per poter validare l'associazione tra le varianti genetiche di questi geni candidati e la NSCL/P. / Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most frequent alterations of embryonic development; it is caused by an interaction of genetic and environmental factors. The aim of this study is identifying of genetic risk factors, selecting candidate genes and testing their involvement in the determination of the malformation through association studies. I analyzed some single nucleotide polymorphisms (SNPs) of RFC1 and DHFR genes, belonging to the folic acid metabolic cascade. I highlighted a low association for some of the SNPs investigated and NSCL/P in the Italian population. In the laboratory of Dr. Mangold of the University of Bonn, I evaluated the role of 15 different chromosomal regions in determining susceptibility to disease. I showed a significant association for the variants at 8q24 and 1p22. Attention has been given to the role of the Polycomb complex in determining NSCL/P susceptibility. In mammals, there are two main Polycomb complexes: PRC1 and 2 PRC2. Both are chromatin-remodeling multiprotein complexes. These complexes control the transcriptional mechanisms implicated in cell differentiation and in embryonic development. I hypothesized that mutations in genes belonging to PRC2 complex can be considered as potential genetic risk factors for NSCL/P. The rationale is that JARID2, protein interacts with PRC2, is associated with the onset of NSCL/P and it is expressed in epithelial cells of the palatine laminae that approach to fusion. Analysis of the polymorphisms of genes encoding elements or partners of the two Polycomb complexes, showed a significant association between some of the SNPs investigated and pathology, further confirmed by the analysis of haplotypes. The analyzes of candidate genes allowed me to collect interesting data sulla'eziologia the malformation. Independent studies will be needed to confirm the association between genetic variants of these candidate genes and NSCL/P.

L'elaborato, dopo aver esaminato le modifiche operate dalla legge n. 190 del 2012, svolge una dettagliata analisi della giurisprudenza intervenuta in seguito all'approvazione della riforma. / The paper, after examining the changes made by Law no. 190 of 2012, carried out a detailed analysis of the case law intervened following the approval of the reform.

No description available.

No description available.

No description available.

No description available.

Two major types of B cells, the antibody-producing cells of the immune system, are classically distinguished in the spleen: marginal zone (MZ) and follicular (FO). In addition, FO B cells are subdivided into FO I and FO II cells, based on the amount of surface IgM. MZ B cells, which surround the splenic follicles, rapidly produce IgM in response to blood-borne pathogens without T cell help, while T cell-dependent production of high affinity, isotype-switched antibodies is ascribed to FO I cells. The significance of FO II cells and the mechanism underlying B cell fate choices are unclear. We showed that FO II cells express more Sca1 than FO I cells and originate from a distinct B cell development program, marked by high expression of Sca1. MZ B cells can derive from the “canonical” Sca1lo pathways, as well as from the Sca1hi program, although the Sca1hi program shows a stronger MZ bias than the Sca1lo program, and extensive phenotypic plasticity exists between MZ and FO II, but not between MZ and FO I cells. The Sca1hi program is induced by hematopoietic stress and generates B cells with an Igλ-enriched repertoire. In aged mice, the canonical B cell development pathway is impaired, while the Sca1hi program is increased. Furthermore, we showed that a population of unknown function, defined as Lin-c-kit+Sca1+ (LSK-), contains early lymphoid precursors, with primarily B cell potential in vivo. Our data suggest that LSK- cells may represent a distinct precursor for the Sca1hi program in the bone marrow.

No description available.