+publisher:"Università degli Studi di Milano" +contributor:("GIANNI, ALESSANDRO")

1. V. Alari. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215883

► The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a… (more)

▼ The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a process by which acetylcholine from the vagus nerve reduces the release of the pro-inflammatory cytokine TNFα, thus allowing for a controlled response to infection. The CHRNA7 gene, in humans, is partially duplicated from exon 5-10 and forms an hybrid with four exons (D-A) of a novel gene, FAM7A. This new gene, CHRFAM7A, which is located in the opposite orientation, at 1.6 Mb, from CHRNA7, is not present on every chromosome 15 and a polymorphic variant, in linkage disequilibrium with a 2bp deletion in exon 6, in the same orientation to the CHRNA7 gene, has been described in a cohort of patients with bipolar disorders and schizophrenia. THP-1 monocytic-like cell line expresses only CHRFAM7A, which was down-regulated on treatment with LPS, by a direct transcriptional mechanism reliant on NF-kB. This effect has been confirmed in primary monocytes and macrophages cell cultures, where CHRFAM7A is expressed 200-1000 times more than CHRNA7. Here, the conventional α7 subunit was up-regulated by LPS treatment, thus suggesting the involvement of CHRFAM7A in the regulation of cell surface α7 receptors’ level (a mechanism unique to humans) and the ability of immune cells to respond to acetylcholine, released from the vagus nerve, during infection. This hypothesis seems to be supported by recent works showing that the duplicated form may have a dominant negative effect on the activity of α7 nAChR. Infact, co-expression of CHRFAM7A with α7 results in a significant reduction of the Ach-evoked currents, suggesting the presence of heteromeric non functional receptors at the plasma membrane. The promoter region that regulates the expression of CHRFAM7A is still unknown. To try to identify and characterize this region, 5'-RACE experiments were carried out to map the CHRFAM7A mRNA 5’UTR. RNA was extracted from three different cell lines: THP-1 cells, primary human macrophages and SHSY5Y neuroblastoma cell line. Multiple transcription start sites were identified, depending on the cell line used, suggesting the existence of alternative promoters. A series of constructs that recapitulate the mapping of the CHRFAM7A regulatory region, according to the transcription start sites identified, was also generated. They were cloned into a reporter vector and their functionality was tested by transient transfection both in THP-1 and SHSY5Y cell models. Through these experiments, an intronic region (-702/-208 bp from ATG codon, in exon B) and an Alu sequence (-1155/-821 bp) were identified as negative regulators of reporter gene transcription. Future experiments will allow us to identify other regulatory sites, important for proper CHRFAM7A gene expression in different tissues. Furthermore, two variants exist for CHRFAM7A gene, due to alternative splicing, that gives rise to two protein products of predicted 36 and 47 KDa, whose function is currently unknown. The N-terminally… Advisors/Committee Members: tutor:D. Fornasari, coordinatore: A. Gianni, FORNASARI, DIEGO MARIA MICHELE, GIANNI, ALESSANDRO.

Subjects/Keywords: CHRFAM7A; cholinergic anti-inflammatory pathway; CHRNA7; alpha7; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alari, V. (2013). CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215883

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/215883.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Web. 19 Jan 2021.

Vancouver:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/215883.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215883

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. E.S. Grassi. P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232400

► Thyroid cancer is the most common endocrine malignancy and his global incidence has rapidly increased in last decades. Despite the major part of thyroid cancer… (more)

▼ Thyroid cancer is the most common endocrine malignancy and his global incidence has rapidly increased in last decades. Despite the major part of thyroid cancer is represented by well differentiated hystotypes, the acquisition of additional mutations, such as p53 and β-catenin ones, causes loss of differentiation and confer high malignancy. Current treatment for undifferentiated thyroid cancers is regarded as almost ineffective, with a median survival of 3- 4 months, somewhat better in localized and worse in metastatic disease. SP600125 is a multi-kinase inhibitor that has recently been shown to be a promising anticancer drug. In the last five years it has been proved able to induce endoreduplication and subsequent polyploidization, but there are contrasting results about its intracellular actions and there is no evidence on the specific mechanism of action. Moreover, in 2012, SP600125 has been found to be the most effective against p53 deficient cells among more than 300 screened compounds. However, opposite results have also been obtained depending on cell type, concentration and time of incubation. In the current study the effects of micromolar doses of SP600125 have been characterized in six thyroid cancer cell lines with different p53 status. The results show that at low concentrations SP600125 dramatically reduces the proliferation of p53 mutated cells, with lesser effects on p53 null and no effects on the wild-type ones. In p53 mutated cells it has been proved able to induce p53 nuclear translocation and phosphorylation at serine 15; this modification resulted to be responsible of increased levels of p21. Importantly other considerable novel effects have been revealed. Firstly, SP600125 caused alterations of microtubule dynamics in p53 mutated cells, with increase of acetylation levels and loss of Microtubule Organizing Center (MTOC)-periphery organization. These effects were accompanied by alterations in cellular morphology and in late endosome/lysosome trafficking. Endoreduplication and alteration of microtubule dynamics finally resulted in aberrant mitosis and cell death. The second mechanism involves alteration of cellular motility: different kinases involved in this process are affected by SP600125 treatment and β-catenin remains at the intercellular junctions in affected cells,consistent with a failure of cell detachment (a figure consistent with inhibition of cell migration/motility). Microtubule alterations concomitantly also account for motility alterations. Both tubulin and β-catenin variations are due to HDAC6 activity alterations. This enzyme regulates the levels of acetylation of these proteins and is profoundly inhibited following SP600125 in p53 deficient cells. Alteration of HDAC6 activity is hypothesized to be the result of SP600125 direct inhibition of ROCK2, an upstream kinase regulator of HDAC6 activity. In conclusion SP600125 is a promising drug particularly active on p53-mutated cancers at concentrations unable to affect normal cell viability. The effects of SP600125 action include… Advisors/Committee Members: relatore: L. Persani, coordinatore: A. Gianni, PERSANI, LUCA, GIANNI, ALESSANDRO.

Subjects/Keywords: thyroid; cancer; p53; microtubules; endoreduplication; SP600125; Settore MED/06 - Oncologia Medica; Settore MED/13 - Endocrinologia; Settore BIO/13 - Biologia Applicata; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grassi, E. (2014). P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232400

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Grassi, E.S.. “P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232400.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Grassi, E.S.. “P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER.” 2014. Web. 19 Jan 2021.

Vancouver:

Grassi E. P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232400.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grassi E. P53 AND MICROTUBULES TARGETING AS A NOVEL STRATEGY WITH POTENTIAL FOR TREATMENT OF AGGRESSIVE POORLY DIFFERENTIATED THYROID CANCER. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232400

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. A. Crespi. THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232408

► POF1B is a candidate gene for premature ovarian failure (POF); it is mainly expressed in polarized epithelial tissues, but its function in these tissues and… (more)

▼ POF1B is a candidate gene for premature ovarian failure (POF); it is mainly expressed in polarized epithelial tissues, but its function in these tissues and the relationship with the disorder are unknown. In polarized epithelial MDCK cells the human stably expressed POF1B showed a tight junction localization that was lost by the POF1B R329Q variant associated with POF. Although the apico-basal polarity markers and ultrastructure of the tight junctions were maintained in cells expressing the mutant, tight junction assembly, as well as the organization of the monolayer appeared altered. Moreover, cells expressing the POF1B R329Q variant showed defects in ciliogenesis and cystogenesis as a result of misorientation of primary cilia and mitotic division. All of these defects were explained by interference of the mutant with the content and organization of F-actin at the junctions. Subsequently, by means of morphological and biochemical criteria we documented that POF1B is actually a desmosome- associated protein. Both in Caco-2 human intestinal cells and in stratified HaCaT keratinocyte cell lines, indeed, endogenous POF1B colocalized with desmoplakin and plakophilin 2 at the desmosomal plaque and in cytoplasmic particles aligned along intermediate filaments. POF1B co-fractionated with desmosomes and intermediate filament components and showed properties characteristic of desmosomes (i.e. detergent insolubility and calcium independence). Furthermore, POF1B was required for desmosome assembly and function, as the stable downregulation of the protein in HaCaT cells caused a decrease in desmosome number and size, and these desmosomes had very weak electron dense plaques. Among the cell-cell adhesion structures, desmosomes are the most essential for mechanical coupling. The reduced capability of POF1B-silenced keratinocytes to respond to mechanical stress revealed the protein's crucial role in these junctions. Moreover, altered desmosomes in POF1B- downregulated keratinocytes were associated with altered cell proliferation and differentiation. The localization of POF1B in simple and stratified epithelia, as well as its relocation to desmosomes in human skin tumors, further indicated the protein's role in desmosome function, and suggested its involvement in human diseases associated with impairment of these junctions. Advisors/Committee Members: tutor: G. Pietrini, coordinatore: A. Gianni, PIETRINI, GRAZIA, GIANNI, ALESSANDRO.

Subjects/Keywords: POF1B; desmosome; polarity; simple and stratified epithelia; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Crespi, A. (2014). THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232408

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Crespi, A.. “THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232408.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Crespi, A.. “THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH.” 2014. Web. 19 Jan 2021.

Vancouver:

Crespi A. THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232408.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Crespi A. THE NOVEL DESMOSOMAL PROTEIN POF1B IS ESSENTIAL FOR CELL-CELL ADHESION STRENGTH. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232408

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. V. Musella. BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215884

► ABSTRACT Breast cancer is a highly heterogeneous disease from the molecular and clinical point of view. Optimal treatment with the currently available drugs depends therefore… (more)

▼ ABSTRACT Breast cancer is a highly heterogeneous disease from the molecular and clinical point of view. Optimal treatment with the currently available drugs depends therefore on the ability to individually predict treatment. Presently available outcome prediction models are however suboptimal, single predictive variables have limited accuracy, and the actual clinical outcomes remain heterogeneous in any given prognostic group. ER status and HER-2 status are helpful in identifying patients who are not eligible for endocrine or trastuzumab therapies by virtue of their high negative predictive values (NPVs) and high sensitivities. However, only a minority of ER-positive or HER-2-positive patients respond to receptor-targeted therapy. The positive predictive values (PPVs) of these tests are <50%. Moreover, currently there are no accepted molecular predictors of response to various chemotherapeutic drugs. These limitations have driven biomarker research to develop more accurate molecular predictors of clinical outcome. In the present thesis work we report data on an innovative strategy to predict treatment response to conventional therapies by combining in a hierarchical way genomic predictors related to prognosis and to treatment sensitivity and resistance. The strategy takes into account the intrinsic molecular heterogeneity of breast tumors by distinctly developing genomic predictors for each of the three main tumor subtypes defines as: ER+/Her2-, Her2+ and ER-/Her2-. The considered genomic predictors are built based on literature data and results previously obtained at the INT (as in the case of the prognostic role of ISG genes) and are treated as metagenes mainly to facilitate cross-platform comparisons and to stick to pathways with s clear biological role. An important part of the development of the prediction strategy deals with analytical approaches which were optimized to gain more accurate information from FFPE samples. Gene expression profiles used in such approach were obtained from public database, but also from expression studies carried out at INT on two types of samples; fresh frozen and formalin fixed samples. A detailed comparative analysis of technical solutions (Illumina HT 12, Illumina Ref8, Illumina DASL and Affymetrix HG Plus2.0 chips) for optimizing gene expression profiles in FFPE samples with heavily degraded and chemically-modified RNA is reported. A new robust protocol was developed based on linear amplification of RNA under conditions minimizing rRNA amplification, and on use of the Affymetrix HG Plus 2.0 chips. The protocol was tested in a pilot study on 60 samples to estimate the actual percentage of archived FFPE clinical samples which could yield technically acceptable gene expression profiles and to evaluate the biological reliability of gene expression profiles obtained from fixed samples. Reliability was tested by comparing ER-status classifiers developed using FF-derived expression data and testing the classifier on predicting ER status in FFPE and FF dataset. Prediction accuracy… Advisors/Committee Members: coordinatore: A. Gianni, relatore: C. Carlo-Stella, tutor: V. Cappelletti, CARLO STELLA, CARMELO, GIANNI, ALESSANDRO.

Subjects/Keywords: breast; cancer; microarray; FFPE; FF; IFN; prognosis; Settore BIO/13 - Biologia Applicata

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Musella, V. (2013). BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215884

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Musella, V.. “BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/215884.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Musella, V.. “BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER.” 2013. Web. 19 Jan 2021.

Vancouver:

Musella V. BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/215884.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Musella V. BIOLOGICALLY MEANINGFUL AND CLINICALLY RELEVANT GENE EXPRESSION PROFILE FOR OPTIMAL TREATMENT PLANNING IN BREAST CANCER. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215884

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. L. Paganini. NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215885

► LSD1, the first identified Lysine specific demethylase that removes methyl groups from mono- or di-methylated Histone 3 Lys4 (H3K4), has a mammalian-restricted neuronal isoform (LSD1-E8a),… (more)

▼ LSD1, the first identified Lysine specific demethylase that removes methyl groups from mono- or di-methylated Histone 3 Lys4 (H3K4), has a mammalian-restricted neuronal isoform (LSD1-E8a), generated by the alternative inclusion of the 12-bp neurospecific exon E8a. LSD1 general function is to inhibit the expression of neuronal genes in non-neuronal cells, but LSD1-E8a isoform is characterized by a less gene repressing action. Indeed, the 4 aa coded by the exon E8a, which form a protruding loop in the LSD1 catalytic domain, contain a Threonine residue that can be phosphorylated and that is required to induce neuronal maturation, neurite outgrowth and the abrogation of LSD1-8a repressive activity. Using a Minigene reporter assay, we demonstrate that the exon E8a is surrounded by a highly conserved 800-bp intronic region that is sufficient per se to regulate exon E8a alternative splicing, containing at least in part the necessary cis-acting elements. Among them there are the binding sites for NOVA1 and nPTB, that we found to be exon E8a positive trans-acting splicing regulators. Exon E8a, indeed, is very tightly modulated and it is present only in neuronal brain tissues and not in cell line. Along with positive trans-acting factors, we identified an exon E8a complementary/inverted sequence with a very strong negative regulatory effect on exon E8a inclusion. Here we show that this sequence acts by forming a double strand pre-mRNA pairing in which exon E8a is masked. Indeed, the deletion of the 12 core nucleotides of such complementary region promotes a strong exon E8a inclusion, allowing binding of trans-acting factors that recognize single-strand cis-acting motifs. Furthermore, downstream of exon E8a we identified a new 77-bp human-restricted LSD1 alternative exon, that we called “exon E8b”. Its inclusion in mature transcripts is regulated by FOX1 and occurs in many different tissues, although these transcripts are present at a very low level. This is probably due to the fact that exon E8b, by introducing a premature STOP codon inside LSD1 mature transcripts, causes their degradation by the cellular Non-sense mRNA Mediated Decay (NMD) pathway. Exon E8b very low endogenous expression level makes it difficult to study its functional role. At the moment we can only say that its inclusion into LSD1 transcripts could be a tool at cells disposal to finely tune LSD1 RNA amount, providing a new human-restricted LSD1 level of regulation. Since the epigenetic function of the neurospecific LSD1 isoform has not been completely elucidated in-vivo, we generated a knock-out mouse model by replacing the sole LSD1 exon E8a with the Neomycin resistance cassette, flanked by two loxP sites. LSD1-E8a knockout animals are fertile, survive embryogenesis and show no histological differences as well as no obvious developmental defects. Interestingly, specific behavioral differences were detected in the exon E8a-deficient mice in response to a pharmacologically induced epileptic treatment, where they display a longer time of latency and a… Advisors/Committee Members: tutor: E. Battaglioli, coordinatore: E. Ginelli, A. M. Gianni, GINELLI, ENRICO, GIANNI, ALESSANDRO, GINELLI, ENRICO.

Subjects/Keywords: epigenetics; alternative splicing; Settore BIO/13 - Biologia Applicata

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Paganini, L. (2013). NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Paganini, L.. “NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/215885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Paganini, L.. “NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY.” 2013. Web. 19 Jan 2021.

Vancouver:

Paganini L. NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/215885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Paganini L. NEUROSPECIFIC LSD1 SPLICING ISOFORM LINKS EPIGENETICS TO MAMMALIAN BRAIN PHYSIOLOGY. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. P.A. Lonati. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215886

► IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an… (more)

▼ IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an inflammatory infiltrate is characteristic of the early phases of fibrosis development and inflammatory cells may profoundly affect the ECM production by releasing soluble products or by direct cell-to-cell interactions that modify fibroblast metabolism. Fibrosis is characteristic of many diseases, as systemic sclerosis (SSc), morphea, acrodermatitis chronica atrophicans, Shulman fasciitis and the cutaneous form of graft versus host disease (GVHD). In particular has been shown that IL-17A is present not only in the biological fluids but also in the skin of individuals affected by SSc. The aims of this study are to understand if the IL-17 isoforms are expressed in the skin of individuals affected by these diseases and which are the cells responsible for the production of IL-17A. Moreover we are interested in understanding if the treatment with Iloprost or NAC can modify the expression of the IL-17 isoforms in the skin of SSc patients and if also the cells responsible for the production of IL-17A are modified by these drugs. Bioptic material was obtained from the involved individuals affected by different fibrotic diseases and from healthy donors (HD) undergoing plastic surgery. We adopted an immunohistochemistry and immunofluorescence approach to identify and quantify in vivo the presence of cells positive for the IL-17 isoforms, the IL-17 receptors, IL-4, IL-22, INF-γ, CD3 and Tryptase. All the IL-17 isoforms are expressed in all the bioptic samples analyzed, without significant differences between the HD and the pathologic groups. IL-17A is produced by both CD3 and mast cells, and are significantly more numerous in the HD than in the SSc skin (p=0,0485). The expression of the IL-17 isoforms in the skin of SSc patients treated with Iloprost changes unevenly in all the patients. The same happens for the expression of IL-17C in the skin of SSc individuals treated with NAC, while these patients show a marked (but not significant) increase number of IL-17A and IL-17F positive cells and a decreased number of IL-17E positive cells. The treatment with Iloprost induces also the decrease in the number of both CD3 and mast cells producing IL-17A, while NAC induces the increase in the number of CD3 IL-17A producing cells. The number of mast cells producing IL-17A in patients treated with NAC changes unevenly. The number of CD3 and mast cells that produce IL-17A does not reflect the total number of IL-17A positive cells localized in the analyzed samples. This could mean that other cell types are responsible for IL-17A production. Given the role of the IL-17 isoforms in the immunity and inflammatory pathway, the presence of these cytokines in the skin of patients affected by fibrotic diseases can mean that they can be involved in the fibrotic process. This is confirmed by the modification of the expression of the IL-17 isoforms in the skin of… Advisors/Committee Members: tutor: C. Chizzolini, P. Meroni, M.O. Borghi, coordinatore: A. Gianni, MERONI, PIERLUIGI, GIANNI, ALESSANDRO.

Subjects/Keywords: interleukin 17; fibrosis; systemic sclerosis; Iloprost; Settore MED/16 - Reumatologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lonati, P. (2013). LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/215886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Web. 19 Jan 2021.

Vancouver:

Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/215886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

7. A. Cavane'. CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232417

► Il fattore trascrizionale c-Myc gioca un ruolo fondamentale nella patogenesi e nella progressione dei linfomi non-Hodgkin a cellule B (B-NHL) e la sua deregolazione è… (more)

Subjects/Keywords: c-Myc; HDAC; B-NHL; microRNA; cap-dependent translation; Settore BIO/13 - Biologia Applicata

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cavane', A. (2014). CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cavane', A.. “CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cavane', A.. “CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI.” 2014. Web. 19 Jan 2021.

Vancouver:

Cavane' A. CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cavane' A. CARATTERIZZAZIONE DELL'ATTIVITA' ANTITUMORALE DELL'INIBITORE DEGLI HDAC ITF2357 (GIVINOSTAT®) IN MODELLI PRECLINICI DI LINFOMA NON-HODGKIN A CELLULE B C-MYC POSITIVI. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

8. S. Lopa. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232420

► Osteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related… (more)

▼ Osteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related disease is increasing with population ageing and worldwide estimates indicate that 9.6% of men and 18% of women with more than 60 years present OA-related symptoms. Osteoarthritis induces the progressive damage of articular cartilage and subchondral bone and can eventually lead to the complete loss of joint functionality. Nowadays, the management of OA includes non-pharmacological, pharmacological, and surgical treatments. Non pharmacological approaches include exercise, weight loss, and physiotherapy and are used in conjunction with pharmacological treatments. The pharmacological management of OA patients is mainly based on the use of anti-inflammatory drugs for pain control. Hence, the pharmacological approach to OA patients is synptomatic, but not resolutive, since it is not able to alter the progression of the disease. These therapeutical options are not suitable for late stage OA patients, whereby the severe pain and the functional limitations caused by advanced OA degeneration are currently resolved by joint replacement. Due to the low self-repair ability of articular cartilage, untreated cartilage lesions can easily degenerate into OA. Different strategies have been developed to treat promptly chondral lesions, comprising cell-based therapies, such as autologous chondrocyte implantation (ACI). These cell-based therapies have been recently proposed also for the treatment of early OA patients in order to overcome or at least delay the need for a more invasive intervention such as joint replacement. However, major issues associated to the clinical use of autologous articular chondrocytes (ACs) are the limited number of cell harvestable from a small cartilage biopsy and the de-differentiation process occurring during the expansion phase required to achieve a clinically relevant number of cells. Furthermore, advanced age and pathological state of joints negatively affect the chondrogenic potential of ACs, representing important factors to be considered when applying chondrocyte-based therapies in particular categories of patients. In view of a possible use of autologous cell-based therapies for OA patients, we analyzed specific features of ACs as cellular yield, cell doubling rates and the dependence between these parameters and patient-related data in a set of 211 OA patients undergoing total joint replacement (Chapter 3). The patient age was not statistically correlated to the cellular yield, but was negatively correlated with the proliferation rate. No significant correlation was observed between the level of cartilage degeneration (ICRS score) and cellular yield and proliferation rates. However, in samples with the highest degree of cartilage degeneration (ICRS score 4) the cellular yield was lower compared to the other three groups (ICRS scores 1-3). In conclusion, we found that age and degenerative state of cartilage affect some… Advisors/Committee Members: tutor: M. Moretti, D. Fornasari, coordinatore: A. Gianni, FORNASARI, DIEGO MARIA MICHELE, GIANNI, ALESSANDRO.

Subjects/Keywords: osteoarthritis; cell-based therapy; cartilage; tissue engineering; prosthesis; bioreactor; chondrocytes; mesenchymal stem cells; Settore BIO/13 - Biologia Applicata; Settore BIO/14 - Farmacologia; Settore MED/33 - Malattie Apparato Locomotore

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lopa, S. (2014). BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lopa, S.. “BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lopa, S.. “BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.” 2014. Web. 19 Jan 2021.

Vancouver:

Lopa S. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lopa S. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. G. Fossati. DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232396

► Impairment of synaptic function can lead to neurological and psychiatric disorders collectively referred to as synaptopathies. SNAP-25, a SNARE protein controlling synaptic vesicle exocytosis and… (more)

▼ Impairment of synaptic function can lead to neurological and psychiatric disorders collectively referred to as synaptopathies. SNAP-25, a SNARE protein controlling synaptic vesicle exocytosis and fundamental presynaptic functions, is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. We observed that halved SNAP-25 levels at 13–14DIV not only fail to impair synaptic transmission, but instead enhance evoked glutamatergic neurotransmission. This effect is probably dependent on presynaptic voltage-gated calcium channel activity and it is not followed by changes in spontaneous quantal events or in the pool of readily releasable synaptic vesicles. Notably, synapses of neurons with reduced SNAP-25 levels show paired-pulse depression as opposed to paired-pulse facilitation occurring in their wild-type counterpart. These phenotypes disappear with synapse maturation, where instead a reduction of evoked glutamatergic transmission and mEPSC amplitude emerge in heterozygous neurons thus suggesting the onset of a postsynaptic defect. In fact, it has been recently reported that a peculiar postsynaptic SNARE complex is required for long-term potentiation; however, the role of SNAP-25 in this process is not completely understood. We recently demonstrated that acute down-regulation of SNAP-25 in vitro affects spine morphogenesis through binding to p140Cap, thus suggesting that the protein may exert a structural role at the postsynaptic level. Here we demonstrate that in vivo acute down-regulation of SNAP-25 in CA1 hippocampal neurons affects spine number and morphology and causes a specific reduction of the postsynaptic protein PSD-95. Consistently, hippocampal neurons from SNAP-25 het mice show a flawed maturation of postsynaptic specializations, reduced densities of dendritic spines and defective PSD-95 clustering. These effects do not stem from impaired presynaptic function, but as a direct consequence of reduced SNAP-25 levels in the postsynaptic compartment. By co-immunoprecipitation and LUMIER Assay, we show that SNAP-25, PSD-95 and p140Cap are part of the same molecular complex in the brain, with p140Cap being intrinsically capable to bind either to SNAP-25 and PSD-95. These data provide new mechanistic insights as to SNAP-25 involvement in synaptopathies that go beyond the protein’s known roles in presynaptic function. Advisors/Committee Members: tutor: M. Matteoli, co-tutor: E. Menna, direttore: A. Gianni, MATTEOLI, MICHELA, GIANNI, ALESSANDRO.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fossati, G. (2014). DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232396

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fossati, G.. “DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232396.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fossati, G.. “DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT.” 2014. Web. 19 Jan 2021.

Vancouver:

Fossati G. DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232396.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fossati G. DUAL ROLE OF SNAP-25 AT PRE- AND POST-SYNAPTIC LEVEL DURING DEVELOPMENT. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232396

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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