subject:(Settore BIO 11 Biologia Molecolare)

1. M. Galli. YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION.

Degree: 2017, Università degli Studi di Milano

► Haspin is a serine/threonine atypical kinase that phosphorylates histone H3-T3 during metaphase, promoting the recruitment of the chromosomal passenger complex (CPC) at kinetochores. Haspin depletion… (more)

▼ Haspin is a serine/threonine atypical kinase that phosphorylates histone H3-T3 during metaphase, promoting the recruitment of the chromosomal passenger complex (CPC) at kinetochores. Haspin depletion leads to cell arrest in mitosis and prevents proper chromosome positioning at the metaphase plate. Saccharomyces cerevisiae genome encodes for two haspin paralogues ALK1 and ALK2. We recently showed that these genes are essential to coordinate polarization and cell cycle progression, ensuring the correct positioning of several polarity factors following a transient mitotic delay. The aim of this project is to identify new processes where haspin kinase is involved. The first part of this work shows that Alk1 has a role at the G2/M transition in S. cerevisiae. These findings constitute the first evidence for Alk1-specific functions that are not shared by its paralogue Alk2. Our results indicate that cells lacking ALK1 are sensitive to Latrunculin A and complete nuclear division within the unbudded mother cells. These observations pointed toward a defect in the morphogenesis checkpoint. We also observed that in absence of ALK1 the Cdc28-Y19 phosphorylation signal decreases significantly during a morphogenetic stress. Exploring the underlying mechanism, we found that the decrease in phosphorylation is caused by a misregulation in Mih1 phosphatase activity in absence of Alk1. Therefore in budding yeast Alk1 modulates G2/M cell cycle switch by regulating Mih1 3 activity. The second part of this work is focused on exploring the role of Alk1 and Alk2 in polarisome dispersion. We show that the previously reported role of haspin in polarization relies on its ability to modulate Ras localization. Our observations are indicative for a mitotic role of Ras, which, by regulating Cdc24 redistribution, influences Cdc42 activation at polarized sites. These observations may help to shed light on alterations in cell polarity, which often constitute the molecular mechanism for cancer insurgence. Advisors/Committee Members: scientific tutor: M. Muzi-Falconi, MUZI FALCONI, MARCO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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APA (6^th Edition):

Galli, M. (2017). YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/532121

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):

Galli, M.. “YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION.” 2017. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/532121.

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

MLA Handbook (7^th Edition):

Galli, M.. “YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION.” 2017. Web. 24 Jan 2021.

Vancouver:

Galli M. YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/532121.

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

Council of Science Editors:

Galli M. YEAST HASPIN KINASE REGULATES MITOTIC CELL CYCLE EVENTS: FROM G2/M TRANSITION TO POLARISOME DISPERSION. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/532121

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

2. S. Pizzi. HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/228142

► Genome integrity is continuously jeopardized by environmental insults, such as radiations, UV light and chemicals, as well as by endogenous factors including byproducts of cellular… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Pizzi, S. (2013). HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/228142

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):

Pizzi, S.. “HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY.” 2013. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/228142.

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

MLA Handbook (7^th Edition):

Pizzi, S.. “HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY.” 2013. Web. 24 Jan 2021.

Vancouver:

Pizzi S. HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/228142.

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

Council of Science Editors:

Pizzi S. HEXO1 AND HRNASEH2: TWO NUCLEASES REQUIRED FOR MAINTENACE OF GENOME INTEGRITY. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/228142

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

3. L. Tagliabue. THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON.

Degree: 2010, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/160739

► In this PhD thesis work I investigated the expression modulation of the major adhesion factors in Escherichia coli; in particular I focused on the role… (more)

▼ In this PhD thesis work I investigated the expression modulation of the major adhesion factors in Escherichia coli; in particular I focused on the role of GGDEF and EAL proteins, on their modulation in E. coli biofilm formation in response to environmental signals and on regulation of curli fibers, cellulose and poly-N-acetylglucosamine (PNAG), the most important biofilm determinants in E. coli. E. coli is an Enterobacterium, normally living inside the mammalian gut, at temperature of 37° C and in relatively nutrient-rich environment. Once outside the host, bacteria usually face much lower temperatures (< 30°C) and a nutrient-limiting environment. The biofilm determinants studied in this thesis are all expressed in response to environmental conditions such as low temperature, low osmolarity and starvation, suggesting that E. coli bacteria switch to a biofilm mode of growth as part of their adaptation to the natural environment. In response to reduction in growth rates, E. coli seems to canalize its energy consumption into production of extracellular features such as curli or exopolysaccharides. Biofilms can be thus considered as a “resistance form” of growth able to withstand stress conditions more efficiently than cells living in a planktonic mode of growth. The CsgD protein is the master regulator of E. coli biofilm formation. It is a transcriptional factor necessary for curli genes transcription and, through the AdrA protein, for cellulose biosynthesis. Gene regulation by CsgD is tightly connected to production and sensing of cyclic di-GMP, a bacterial second messenger involved in various cellular processes, including biosynthesis of extracellular polysaccharides (Simm et al., 2004), biofilm formation (Hickman et al., 2005), and virulence (Pratt et al., 2007; Tischler and Camilli, 2005), as well as morphological and physiological differentiation (Paul et al., 2004). The CsgD-dependent adrA gene, involved in cellulose biosynthesis (Zogaj et al., 2001), encodes a cyclic di-GMP synthase (Simm et al., 2004). CsgD can also activate yoaD, whose gene product is a cyclic di-GMP phosphodiesterase, suggesting that CsgD is directly involved in feedback regulation of cyclic di-GMP intracellular levels and of cellulose biosynthesis (Brombacher et al., 2006). CsgD is also able to activate the iraP gene: IraP acts as a stabilization factor for the σs protein, an alternative sigma factor of RNA polymerase which directs transcription of genes involved in adaptation to slow growth and to cellular stresses. Here I showed that CsgD transcription activation of the iraP gene does result in a significant increase of σs intracellular concentration by positively affecting σs protein stability, thus leading to altered expression of σs-dependent genes. CsgD-mediated increase of σs cellular concentrations via the iraP gene would trigger an autoactivation loop leading to an increased production of CsgD-dependent adhesion determinants such as curli fibers and cellulose. This autoregulatory circuitry might be further fueled by σs-dependent… Advisors/Committee Members: tutor: Paolo Landini, coordinatore del dottorato: Roberto Mantovani, LANDINI, PAOLO, MANTOVANI, ROBERTO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Tagliabue, L. (2010). THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/160739

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):

Tagliabue, L.. “THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON.” 2010. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/160739.

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

MLA Handbook (7^th Edition):

Tagliabue, L.. “THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON.” 2010. Web. 24 Jan 2021.

Vancouver:

Tagliabue L. THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/160739.

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

Council of Science Editors:

Tagliabue L. THE SUBTLE BIOFILM REGULATION IN ESCHERICHIA COLI: CSGD AND THE YDDV-DOS OPERON. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/160739

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

4. F. Rusconi. HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES.

Degree: 2010, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/150096

► Myotonic Dystrophy type 2 (DM2) is caused by a DNA microsatellite expansion within the ZNF9 gene leading to an abnormal splicing pattern largely responsible for… (more)

▼ Myotonic Dystrophy type 2 (DM2) is caused by a DNA microsatellite expansion within the ZNF9 gene leading to an abnormal splicing pattern largely responsible for the pathological condition. To better define the functional changes occurring in human DM2 myotubes, we performed a quantitative proteome comparison between myotubes of DM2 and control patients using two-dimensional gel electrophoresis followed by mass spectrometry. Our results indicate that the proteins, altered in DM2 cultures, belong to two major functional categories: i) mitochondrial components, with a reduction of Elongation factor Tu (EFTu), Heat Shock Protein 60 (HSP60), Glucose Regulated Protein 75 (GRP75) and Dienoyl-CoA-Isomerase, an enzyme involved in fatty acids degradation; ii) the ubiquitin proteasome system, with increase of the 26S proteasome regulatory subunit 13 and a reduction of Proteasome subunit Apha 6 and of Rad23B homolog. Altered ubiquitin-proteasomal activity is supported by a global reduction of cytosolic ubiquitinated proteins, nonetheless the accumulation of ubiquitin-protein conjugates after proteasomal inhibitor MG-132 treatment is maintained in DM2 and control cells, suggesting a higher degradation rate for the proteasome in myoblasts from patients affected by the disease. Although future work is required to clarify how these changes affect the protein degradation machinery and mitochondrial function and to evaluate if these changes also occur in the biopsies of DM2 patients, these results identify the mitochondrial proteins and the ubiquitin-proteasomal system as candidates potentially relevant to DM2 pathogenesis. Further analysis performed in Human skin fibroblasts primary cultures, obtained from patients biopsies, revealed an Hyperpolaryzation of the mitochondrial membrane potential involving DM2 cells, indicating a putative functional issue for mitochondria. As the evaluation of the Cytocrome c release following hydrogen peroxide treatment showed a differential response to this stress inducing compound, we pointed out a functional involvement of the DM2 mitochondrial-mediated cellular response to oxidative stress. Advisors/Committee Members: tutor: Renata Zippel, Laura Popolo, supervisore: Giovanni Meola, phd program coordinator: Martino Bolognesi, ZIPPEL, RENATA, BOLOGNESI, MARTINO, MEOLA, GIOVANNI.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Rusconi, F. (2010). HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150096

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):

Rusconi, F.. “HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES.” 2010. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/150096.

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

MLA Handbook (7^th Edition):

Rusconi, F.. “HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES.” 2010. Web. 24 Jan 2021.

Vancouver:

Rusconi F. HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/150096.

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

Council of Science Editors:

Rusconi F. HUMAN MYOTONIC DYSTROPHIES: PROTEOME PROFILING AND DIFFERENTIATION STUDIES. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150096

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

5. F. Galli. IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS.

Degree: 2010, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/156499

► One way to regulate protein functions is by post-translational modification. Post-translational modifications have an important role in the regulation of biological activity of the protein… (more)

▼ One way to regulate protein functions is by post-translational modification. Post-translational modifications have an important role in the regulation of biological activity of the protein because they allow both to extend the range of functions of a protein and to monitor the activity and determine the activation or inactivation of a protein. The most common protein post-translational modifications include ubiquitylation, phosphorylation and acetylation play an essential role in cellular functions such as cellular differentiation, apoptosis, DNA repair, antigen processing, and stress response. Under particular conditions abnormal post-translational modifications were found in many diseases like: Alzheimer’s disease, Parkinson’s disease, induction of different cancer and others. These abnormal post-translational modifications are permanent and can cause loss or alteration of protein function by changing enzyme activities or capacity aggregation (Stadtman and Levine 2000; Shacter 2000). p63 protein stability is regulated by different protein modifications such phosphorylation, ubiquitylation and sumoylation. p63 is known to be degraded by ubiquitin-mediated proteasomal degradation, the E3 ubiquitin ligase NEDD4-like, ubiquitin protein ligase Itch and ubiquitin-like protein SUMO-1 have been shown to directly interact with p63 and regulate p63 protein stability (Ghioni et al. 2005; Rossi at al. 2006; Rossi et al. 2006) suggest the importance of regulating p63 to tune its biological activity. During my PhD thesis we found three novel and distinct mechanisms that are involved in the regulation of the p63 protein levels; all these mechanisms induce p63 degradation. We demonstrated that these mechanisms are relevant in different physiological contexts and that they are involved in the regulation of p63 biological function. 1. MDM2-Fbw7 pathway contribute to reduce ΔNp63α protein levels during keratinocytes differentiation and upon DNA-damage induced by UV exposure and adriamycin treatment. 2. TRIM8 plays a role in enhancing p53 anti-oncogenic activity and at the same time down-modulate oncogenic ΔNp63α activity. 3. Hipk2 phosphorylates and promotes proteasomal degradation of ΔNp63α to enable an effective DNA-damage response induced by genotoxic drugs. All these evidences indicate that regulation of p63 protein stability is a key mechanism to control p63 activities, in particular during epithelia differentiation and in response to genotoxic agents. The knowledge and the identification of the molecular mechanisms governing p63 regulation under physiological context might be fundamental for understanding the pathogenesis of human syndromes associated to p63 mutations and the mechanism by which p63 promotes disease development. We hope that future studies focusing on the mechanisms involved in p63 protein regulation might increase our knowledge on the p63 role in tumorigenicity and in response to anti-cancer therapy to improve anti-cancer therapies. Advisors/Committee Members: tutor: Luisa Guerrini, coordinatore: Roberto Mantovani, GUERRINI, LUISA FRANCESCA, MANTOVANI, ROBERTO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Galli, F. (2010). IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/156499

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):

Galli, F.. “IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS.” 2010. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/156499.

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

MLA Handbook (7^th Edition):

Galli, F.. “IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS.” 2010. Web. 24 Jan 2021.

Vancouver:

Galli F. IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/156499.

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

Council of Science Editors:

Galli F. IDENTIFICATION OF THREE NOVEL REGULATORY PATHWAYS INVOLVED IN THE DOWN-REGULATION OF P63 PROTEIN LEVELS. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/156499

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

6. A. Fossati. RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX.

Degree: 2011, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/157998

► Background. Different histone post-translational modifications (PTMs) are crucial in the regulation of chromatin, including methylations of H3 at Lysine 4 by the MLL complex. A… (more)

▼ Background. Different histone post-translational modifications (PTMs) are crucial in the regulation of chromatin, including methylations of H3 at Lysine 4 by the MLL complex. A relevant issue is how this is causally correlated to the binding of specific transcription factors (TFs) in regulatory regions. NF-Y is a TF that regulates 30% of mammalian promoters containing the widespread CCAAT element. We and others established that the presence of H3K4me3 is dependent upon the binding of NF-Y. Here, we investigate the mechanisms of H3K4me3 deposition by NF-Y. Methods. We employed Chromatin Immunoprecipitation in cells in which Ash2L and NF-Y subunits were knocked down by RNAi, to monitor the presence of histones PTMs and components of the MLL complex. We performed gene expression profiling of Ash2L-knocked down cells and analyzed the regulated genes. We performed ChIPs in leukemic cells in which MLL1 is devoid of the methyltransferase domain and fused to the AF4 gene. Results. Knock down of the Ash2L subunit of MLL leads to a decrease in global H3K4me3 with a concomitant increase in H3K79me2. Knock down of NF-Y subunits prevents promoter association of Ash2L, but not MLL1, nor WDR5, and H3K4me3 drops dramatically. Endogenous NF-Y and Ash2L specifically interact in vivo. Analysis of the promoters of Ash2L regulated genes, identified by transcriptional profiling, suggests that a handful TF binding sites are moderately enriched, among which the CCAAT box. Finally, leukemic cells carrying the MLL-AF4 translocation show a decrease of H3K4me3, absence of Ash2L and increase in H3K79me2, while NF-Y binding was not significantly affected. Conclusions. Three types of conclusions are reached: (i) H3K4 methylation is not absolutely required for NF-Y promoter association. (ii) NF-Y acts upstream of H3K4me3 deposition by recruiting Ash2L. (iii) There is a general cross-talk between H3K4me3 and H3K79me2 which is independent from the presence of MLL oncogenic fusions. Advisors/Committee Members: tutor: Roberto Mantovani, coordinatore: Roberto Mantovani, MANTOVANI, ROBERTO, MANTOVANI, ROBERTO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Fossati, A. (2011). RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/157998

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, A.. “RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX.” 2011. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/157998.

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, A.. “RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX.” 2011. Web. 24 Jan 2021.

Vancouver:

Fossati A. RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX. [Internet] [Thesis]. Università degli Studi di Milano; 2011. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/157998.

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

Council of Science Editors:

Fossati A. RELATIONSHIP BETWEEN A TRANSCRIPTION FACTOR, NF-Y AND ASH2L,A COMPONENT OF HISTONE METHYL TRANSFERASE, MLL COMPLEX. [Thesis]. Università degli Studi di Milano; 2011. Available from: http://hdl.handle.net/2434/157998

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

7. M. Fornari. ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/173417

► Nuclear factor Y (NF-Y) is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are… (more)

▼ Nuclear factor Y (NF-Y) is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as embryogenesis, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER) stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 play an important role in Arabidopsis embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos are arrested at the globular stage and that both proembryo and suspensor are characterized by a disordered cell cluster with an irregular shape, suggesting defects in the determination of the apical-basal embryo axis. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the globular-arrested nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin transport in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant regulators of the globular-heart transition that marks the acquisition of axiality during embryo development in Arabidopsis thaliana. Advisors/Committee Members: tutor: K. Petroni, coordinatore: R. Mantovani, PETRONI, KATIA, MANTOVANI, ROBERTO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Fornari, M. (2012). ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/173417

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):

Fornari, M.. “ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT.” 2012. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/173417.

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

MLA Handbook (7^th Edition):

Fornari, M.. “ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT.” 2012. Web. 24 Jan 2021.

Vancouver:

Fornari M. ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/173417.

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

Council of Science Editors:

Fornari M. ROLE OF NF-Y TRANSCRIPTION FACTORS IN ARABIDOPSIS EMBRYO DEVELOPMENT. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/173417

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

8. F. Marelli. dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/171968

► Congenital hypothyroidism (CH) is the most frequent endocrinopathy in newborn. If not promptly treated lead to a severe impairment of psychomotor development. The etiophatogenesis of… (more)

▼ Congenital hypothyroidism (CH) is the most frequent endocrinopathy in newborn. If not promptly treated lead to a severe impairment of psychomotor development. The etiophatogenesis of CH is still poorly understood; although several causative genes are identified, they can explain only a small portion of the pathological phenotypes. This scenario is further complicated if we focused on the incidence of CH in different context. In fact, epidemiological data indicate that children born prematurely have a 3-5 fold higher risk of CH. In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report that aberrant methylation patterns are associated with prematurity, intrauterine fetal development and the onset of some diseases. This project is focused on the study of DNA methylation, as predisposing factor to permanent thyroid dysfunction with neonatal onset. Using the Illumina Infinium-HumanMethylation27 technology we analyzed the global DNA methylation patterns (AVG) and selected the differentially methylated genes (DMGs) between 31 CH-cases born premature, AGA or SGA, and 28 term or preterm controls. To better understand the relationship between the DNA methylation and the premature birth, the intrauterine growth and the thyroid defect, the following groups were selected according to the gestational age at birth: 12 CH-with very preterm birth (CH-VPB<32wks) and 19 CH-with preterm birth (CH-PB 32-37wks); Controls: 9-CVPB, 6-CPB, 12-term birth (CTB>37wks). The same subjects were then analyzed according to intrauterine growth (20 CH-SGA, 11 CH-AGA than 6 C-SGA and 20 C-AGA) or the degree of CH: 19 with overt CH (OH, TSH>10 U/L) and 12 with mild CH (MH, TSH<10 U/L) than 16 CPB and 12 CTB. The global methylation analysis showed that infants born prematurely and SGA have a significant hypomethylation than term-controls. These data were confirmed by the gene-specific methylation analysis, through which we selected a large group of differentially methylated genes (DMGs) in CH-cases than term controls. Interestingly, the 95% of the DMGs are hypomethylated and the 70% of them are represented by CpG sites located in DNA non-coding regions. The gene ontology analysis revealed that genes involved in fetal growth and thyroid hormone metabolism were included among DMGs. The analysis of nine maternal genomic DNA for polymorphisms at the MTHFR revealed the possible association with folate deficiency during pregnancy and the global hypomethylation status of affected newborns. This is the first work exploring the role of epigenetic influences in the predisposition to congenital hypothyroidism. Our results suggest that genomic instability caused by global hypomethylation of non-coding regions may be related to premature birth and fetal growth delay. Under these conditions, thyroid defects are more frequent than expected and could result from the… Advisors/Committee Members: coordinatore: E. Ginelli, D. Gentilini, tutor: L. Persani, PERSANI, LUCA, GENTILINI, DAVIDE, GINELLI, ENRICO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Marelli, F. (2012). dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/171968

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):

Marelli, F.. “dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism.” 2012. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/171968.

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

MLA Handbook (7^th Edition):

Marelli, F.. “dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism.” 2012. Web. 24 Jan 2021.

Vancouver:

Marelli F. dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/171968.

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

Council of Science Editors:

Marelli F. dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/171968

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

9. E. Vergani. BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/173422

► The clinical activity of the BRAF inhibitor PLX4032 (vemurafenib) in patients with BRAFV600E mutant melanoma is limited primarily by the development of resistance leading to… (more)

▼ The clinical activity of the BRAF inhibitor PLX4032 (vemurafenib) in patients with BRAFV600E mutant melanoma is limited primarily by the development of resistance leading to tumor progression. Strategies to overcome primary and acquired resistance are required. In a panel of 27 genetically characterized patient-derived melanoma cell lines the sensitivity to PLX4032 was dependent on BRAFV600E and independent from other gene alterations that commonly occur in melanoma, such as CDKN2A, and mutations of TP53, PTEN loss, and BRAF and MITF gene amplification. To investigate the molecular basis underlying acquired resistance to BRAF inhibitor, PLX4032-resistant cells were derived from a high sensitive BRAFV600E melanoma cell line, and used as a model. The resistant variant line showed increased AKT and ERK phosphorylation and enhanced IGF-1R/PI3K signaling. Combined treatment with PLX4032 plus PI3K inhibitors resulted in significant cell growth inhibition by decreasing pAKT and pERK signaling. To explore molecular mechanisms underlying primary resistance two melanoma cell lines lacking sensitivity to PLX4032 were used as models. Resistance to PLX4032 was maintained after CRAF down-regulation by siRNA, indicating that CRAF is not involved in the activation of ERK in the resistant cell lines. Treatment with the MEK inhibitor UO126 inhibited cell growth and decreased ERK phosphorylation indicating alternative activation of MEK-ERK signaling. Genetic characterization by MLPA and analysis of pTyr signaling by MALDI-TOF mass spectrometry revealed the activation of MET and SRC signaling, associated with the amplification of MET and of CTNNB1 and CCND1 genes, respectively. Testing of co-inhibition of the MET, SRC and MAPK signaling pathways by the combined treatment with the MET inhibitor, SU11274 or the SRC inhibitor, BMS-354825 plus PLX4032 resulted in a significant inhibitory effect on melanoma cell proliferation, survival, migration and invasive capacity. These results support combinatorial approaches targeting MAPK pathway at different nodes and intercepting parallel signal transduction pathways as a strategy to override resistance to BRAF inhibitors. Advisors/Committee Members: tutor: M. Rodolfo, coordinatore: L.Guerrini, GUERRINI, LUISA FRANCESCA.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Vergani, E. (2012). BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/173422

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):

Vergani, E.. “BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA.” 2012. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/173422.

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

MLA Handbook (7^th Edition):

Vergani, E.. “BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA.” 2012. Web. 24 Jan 2021.

Vancouver:

Vergani E. BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/173422.

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

Council of Science Editors:

Vergani E. BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/173422

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

10. C. Cantoni. EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/217444

► Multiple sclerosis (MS) affects about 2.5 million people worldwide. MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and a common… (more)

▼ Multiple sclerosis (MS) affects about 2.5 million people worldwide. MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and a common cause of neurologic disability in young adults.Clinically, the course of MS can be relapsing-remitting (RRMS), primary progressive (PPMS), non-relapsing or relapsing secondary progressive (SPMS). Experimental Autoimmune Encephalomyelitis (EAE) is the prime animal model for MS study and it has been instrumental for the development of four immune modulatory MS therapies thus far. MicroRNAs (miRNAs) are a novel class of small, non-coding RNAs recently discovered to regulate gene expression post-transcriptionally. MicroRNAs are now extensively studied as possible clinical biomarkers. They also represent potential therapeutic targets as they have been implicated in the pathogenesis of several human diseases, including autoimmune diseases as MS. Dysregulation of several miRNAs has been observed in blood cells and CNS tissues of MS compared to control subjects by microarray profiling. Given these premises the aims of my work are: 1) Perform a wide gene expression analysis for miRNAs and targets mRNAs in mononuclear cells from the blood (PBMC) of MS patients and healthy controls; 2) Analyze deeply miRNAs which are known to be highly correlated in the subpopulation of CD4+ cells; 3) Determine whether serum levels of extracellular microRNAs are altered in MS; 4) Evaluate the role of miR-223 in vivo during EAE. First 104 miRNAs transcripts were found to be deregulated between MS cases and controls. Among the best hits, let-7g and miR-150 were confirmed to be deregulated using quantitative PCR in a second sample of MS and controls; genome wide mRNA expression levels of 37.794 transcripts have been obtained on the same two cohorts and correlated with miRNAs expression profile to understand their in vivo effect and to identify potential novel targets of disease. Furthermore we also found that three best characterized miRNAs in CD4+ T cells, miR-21, miR-146a and –b, were statistically significant higher expressed in the PBMCs of RRMS patients as compared with controls. In the analysis of circulating miRNAs the expression profile of 88 best characterized miRNAs was performed in a discovery cohort consisting of serum from 7 MS samples and 3 controls.The results identified three significantly downregulated miRNAs: miR-15b, miR-23a and miR-223. After data validation and replication in two independent populations, only miR-15b and miR-223 were confirmed to be significantly downregulated in MS patients versus controls. Since several lines of evidence suggest that miR-223 is involved in the MS pathogenesis we performed an active EAE experiment in miR-223 knock out (miR-223 KO) mice showing that miR-223 KO display a less severe EAE clinical course compared to littermate control mice. In conclusion, data here presented suggest that miRNAs dysregulation may contribute to the pathogenesis of MS and highlight the possibility to define different disease entities of MS with… Advisors/Committee Members: direttore della Scuola: M. Clerici, tutore: G. Comi, correlatore: D. Galimberti, COMI, GIACOMO PIETRO, CLERICI, MARIO SALVATORE.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Cantoni, C. (2013). EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/217444

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):

Cantoni, C.. “EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.” 2013. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/217444.

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

MLA Handbook (7^th Edition):

Cantoni, C.. “EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.” 2013. Web. 24 Jan 2021.

Vancouver:

Cantoni C. EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/217444.

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

Council of Science Editors:

Cantoni C. EXPRESSION AND GENETIC ANALYSIS OF MICRORNAS IN MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/217444

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

11. V. Tria. CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/217466

►

Il gene EIF3E (eukaryotic translation initiation factor 3 subunit e) è stato identificato inizialmente in topo come sito di integrazione del virus MMTV (mouse mammary… (more)

▼

Il gene EIF3E (eukaryotic translation initiation factor 3 subunit e) è stato identificato inizialmente in topo come sito di integrazione del virus MMTV (mouse mammary tumor virus). Nel genoma umano EIF3E è un gene di 45 Kb localizzato nella porzione 22-23 del braccio lungo del cromosoma 8 e codifica per un RNA messaggero di 1516 nucleotidi e una proteina di 445 amminoacidi (52 KDa). L’integrazione del virus MMTV negli introni (5, 9, 12) del gene EIF3E causa la trascrizione di RNA tronchi. L’espressione di tali trascritti tronchi è in grado di indurre un fenotipo tumorale sia in vitro che in vivo. Sebbene sia stata individuata l’esistenza di una correlazione tra il tumore mammario ed EIF3E, non è ancora noto l’esatto ruolo che il gene svolge nell’insorgenza e nella progressione del carcinoma mammario. Sono numerose le funzioni associate ad EIF3E nelle cellule eucariotiche. EIF3E è coinvolto nella regolazione dell’espressione proteica sia come subunità del complesso EIF3 (Eukaryotic translation Initiation Factor 3), sia controllando la qualità di specifici RNA messaggeri attraverso il nonsense-mediated decay (NMD) sia regolando il turnover di specifiche proteine. EIF3E è inoltre coinvolto nella regolazione dell’integrità e stabilità genomica in quanto coinvolto nel meccanismo del “DNA damage response”, nella replicazione del DNA e nella mitosi. Questo progetto di dottorato è focalizzato sullo studio del gene EIF3E ed del suo coinvolgimento nella formazione e nella progressione del tumore mammario. Abbiamo analizzato attraverso RT-qPCR l’espressione di EIF3E in diversi tessuti umani non tumorali. EIF3E ha un livello di espressione più alto nella ghiandola mammaria rispetto ad altri tessuti, questo risultato suggerisce come EIF3E possa avere una peculiare funzione nella ghiandola mammaria e sue variazioni possano essere correlate al tumore al seno. Valutando l’espressione di EIF3E in tessuti normali e tumorali della ghiandola mammaria provenienti da diversi pazienti abbiamo osservato come l’espressione di EIF3E diminuisce nel tessuto tumorale rispetto al tessuto normale. Attraverso esperimenti in vitro abbiamo dimostrato come la down-regolazione di EIF3E sia in grado di indurre un fenotipo tumorale in cellule primarie normali della ghiandola mammaria e aumentare la tumorigenicità nelle MCF7. Analizzando quale possa essere la funzione di EIF3E nella formazione e progressione tumorale abbiamo osservato come modificando l’espressione di EIF3E si causano cambiamenti nei livelli di alcuni mRNA, coinvolti in aspetti chiave della progressione tumorale .

The eukaryotic translation initiation factor 3 e-subunit (EIF3E) gene was originally identified in mouse as an integration site of the Mouse Mammary Tumour Virus (MMTV). EIF3E is a 45Kb gene localized to region q22-23 of the human chromosome 8, encodes a mRNA of 1516 nt that is translated into a 52KDa protein of 445 amino acids. Integration of MMTV into EIF3E introns (5, 9 or 12) causes the expression of truncated transcripts. These shortened EIF3E transcripts induce…

Advisors/Committee Members: direttore della Scuola: M. Clerici, tutore: S. Della Bella, co-tutore: I. Zucchi, DELLA BELLA, SILVIA ANGELA MARIA, CLERICI, MARIO SALVATORE.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Tria, V. (2013). CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/217466

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):

Tria, V.. “CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS.” 2013. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/217466.

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

MLA Handbook (7^th Edition):

Tria, V.. “CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS.” 2013. Web. 24 Jan 2021.

Vancouver:

Tria V. CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/217466.

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

Council of Science Editors:

Tria V. CHARACTERIZATION OF EIF3E TRANSCRIPT: ROLE IN MAMMARY DEVELOPMENT AND CARCINOGENESIS. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/217466

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

12. M. DE SIMONE. ¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/236980

► Pseudomonas aeruginosa is the fourth most commonly isolated hospital pathogen, multidrug resistant and potentially deadly causes of pneumonia. Patients at risk of acquiring P. aeruginosa… (more)

▼ Pseudomonas aeruginosa is the fourth most commonly isolated hospital pathogen, multidrug resistant and potentially deadly causes of pneumonia. Patients at risk of acquiring P. aeruginosa are immune-compromised , due to immunosuppressive therapies or underlying diseases such as cancer, AIDS or the hereditary disease cystic fibrosis (CF). P. aeruginosa-host interaction is driven by several factors including the bacterial phenotype and the host genetic make- up. From the bacterial side, several virulence factors have been attributed to P. aeruginosa pathogenicity while many others remain to be established. One third of the P. aeruginosa genome has no attributed homology to any previously reported sequences with only 6.7% of its genes having a function verified experimentally. To identify novel virulence genes, a genome-wide multi-host in vitro and in vivo screening was carried out. A library of 57,360 P. aeruginosa Tn-5 mutants was screened for phenotypic virulence traits (e.g. swarming, pyocyanin, and protease). A total of 404 Tn5-mutants showing pleiotropic phenotypes were tested in the C. elegans and D. melanogaster infection models and further reduced for validation in cell culture and animal models. In particular, 28 selected Tn5-mutants were tested for invasion and IL-8 production in immortalized respiratory A549 cells. Mortality, inflammation and lung pathology of eight selected mutants were scored in C57BL/6 mice and five out of eight mutants were significantly attenuated in inducing murine mortality. The Tn5 gene insertion sites were mapped and their conservation established across seven P. aeruginosa genomes by comparative sequence analysis. The Tn-5 inserted genes encoded proteins from several functional classes including hypothethical, catabolism regulation, iron uptake and quorum sensing. This screening generated a list of virulence-related genes relevant for pathogenicity in multi-hosts and favour much needed insight into the aspects of P. aeruginosa/host interaction. From the host side, the clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk including CF patients. However, risk factors for P. aeruginosa infection remain largely unknown. To characterize how the genetic background influences P. aeruginosa lung infections, nine different inbred mouse strains were infected with P. aeruginosa clinical isolate and monitored for body weight change and mortality up to seven days. Next, one of the most susceptible and resistant mouse strains were further characterized by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible mice showed a significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, and a lower inflammatory severity damage when compared to resistant ones. Our results indicated that host genetic make-up may have a role in the modulation of cell-mediated immunity playing a critical role in the control of P. aeruginosa… Advisors/Committee Members: tutor: G. Bertoni, co-tutor: A. Bragonzi, coordinator: G. Deho', DEHO', GIOVANNI.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

SIMONE, M. D. (2014). ¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/236980

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):

SIMONE, M. DE. “¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '.” 2014. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/236980.

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

MLA Handbook (7^th Edition):

SIMONE, M. DE. “¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '.” 2014. Web. 24 Jan 2021.

Vancouver:

SIMONE MD. ¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/236980.

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

Council of Science Editors:

SIMONE MD. ¿DISSECTION OF THE ROLE OF P. AERUGINOSA VIRULENCE FACTORS AND HOST GENETIC BACKGROUND DURING RESPIRATORY INFECTION '. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/236980

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

13. M. Tazzari. IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/236982

► Although designed to directly target cancer cells and tumor associated-vasculature, anti-angiogenic drugs (e.g. sunitinib), have been described to influence tumor-host interactions. Sunitinib is currently in… (more)

▼ Although designed to directly target cancer cells and tumor associated-vasculature, anti-angiogenic drugs (e.g. sunitinib), have been described to influence tumor-host interactions. Sunitinib is currently in use at our Institute for the treatment of progressive, advanced soft tissue sarcomas (STS) of different histology. However, the systemic and local immune responses and their modulation by anti-angiogenic therapies are unknown in these neoplasms, namely solitary fibrous tumors (SFTs), clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS). This thesis aims to shed light on the immunological status of these STS patients and to address the question to which extent sunitinib induces immune modulation in these patients. Thus, my research focused on the characterization of both tumor-infiltrating and circulating immune cells of STS patients. Fine analysis of the immune contexture at the tumor site in naïve and in sunitinib-treated tumors revealed that myeloid cells, namely tumor-associated macrophages, represent a key component of the tumor microenvironment and that their reprogramming is part of the response to sunitinib treatment. Immune monitoring of circulating cells in these STS patients indicated that circulating myeloid suppressor cells were associated to disease progression and were the major player in mediating the immune-suppressive status in naïve and in sunitinib-treated SFT patients. Moreover, evidence have been provided that, in sunitinib-treated SFT patients, myeloid suppressor cells may be part of acquired resistance, thus supporting the notion that myeloid cells are the most relevant hurdle in the efficacy of anti-angiogenic treatments. Collectively the results of this thesis shed light on an unappreciated phenomenon of immune dysfunction in STS patients and indicate that in SFTs sunitinib transiently relieves systemic immunosuppression and reprograms the immune microenvironment. Moreover, for the first time, an antigen-specific T cell response has been evidenced in CCS, and, this tumor-specific response has occurred in association to sunitinib-induced immune modulation. Overall, this thesis poses the rationale for the development of immune-based clinical approaches aimed at achieving a more durable disease control in these cancer patients, for which effective medical therapies are still needed. Advisors/Committee Members: tutor: C. Castelli, coordinator: G. Dehò, DEHO', GIOVANNI.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Tazzari, M. (2014). IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/236982

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):

Tazzari, M.. “IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS.” 2014. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/236982.

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

MLA Handbook (7^th Edition):

Tazzari, M.. “IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS.” 2014. Web. 24 Jan 2021.

Vancouver:

Tazzari M. IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/236982.

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

Council of Science Editors:

Tazzari M. IMMUNOLOGICAL SIGNATURE IN NAÏVE AND SUNITINIB-TREATED SOFT TISSUE SARCOMA PATIENTS: ROLE OF MYELOID CELLS. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/236982

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

14. J. Sgualdino. ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/264383

► Jmjd3 is a H3K27 demethylase that is required for the neural commitment of ESCs and controls the expression of key drivers and markers of neurulation… (more)

▼ Jmjd3 is a H3K27 demethylase that is required for the neural commitment of ESCs and controls the expression of key drivers and markers of neurulation through the demethylation of H3K27me3. Previous work from our lab has demonstrated that loss of Jmjd3 in mouse embryos causes a complex neurodevelopmental phenotype that results in perinatal death. Such lethality is due to a respiratory failure resulting from the lack of a functional pre-Bötzinger complex, a small network of neurons that is responsible for respiratory rhythm generation. Rescue experiments performed with catalytically active or inactive Jmjd3 have demonstrated that its demethylase activity is necessary for developing and maintaining the embryonic respiratory neuronal network. This unanticipated finding claims a broader role in brain development for Jmjd3, whose importance extends from early differentiation choices to the late development of neuronal networks. To investigate the effect of Jmjd3 loss on neocortical development, we analyzed Jmjd3 KO embryonic brains at different developmental stages using markers for stem cells and differentiated neurons. We found that loss of Jmjd3 causes a late-onset increase in the number of ventricular zone (VZ) neural precursor cells (NPCs) and a reduction in the cortical neuronal production. Jmjd3 KO VZ NPCs display a higher rate of cell cycle re-entry than their WT counterpart, and have an overall longer cell cycle. In order to pinpoint the mechanism by which Jmjd3 is causally linked to the lengthening of the NPC cell cycle and to the VZ expansion, we investigated the transcriptional effect of Jmjd3 loss by performing RNAseq on mRNA extracted from WT and KO cultured E13.5 primary NPCs. A detailed molecular characterization at the transcriptional level revealed that the phenotype that we observed both in vivo and in vitro in Jmjd3 KO NPCs is linked to supraphysiological activation of the Wnt/B-catenin and Notch pathways, two known regulators of the choice between self- renewal and differentiation in the VZ NPCs of the developing brains, whose upregulation has already been shown to correlate with an increased proliferative potential and hampered neuronal differentiation. Advisors/Committee Members: internal advisor: G. Natoli, external advisor: F. Guillemot, TESTA, GIUSEPPE.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Sgualdino, J. (2015). ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/264383

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):

Sgualdino, J.. “ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/264383.

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

MLA Handbook (7^th Edition):

Sgualdino, J.. “ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION.” 2015. Web. 24 Jan 2021.

Vancouver:

Sgualdino J. ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/264383.

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

Council of Science Editors:

Sgualdino J. ROLE OF THE HISTONE DEMETHYLASE JMJD3 IN CORTICAL DEVELOPMENT AND NEURAL DIFFERENTIATION. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/264383

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

15. P. Zuccolini. STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF.

Degree: 2019, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/634438

► HCN4 channels control pacemaking of the heart. They are activated by negative voltage and modulated by cAMP. Recently it had been discovered that cyclic di-nucleotides… (more)

▼ HCN4 channels control pacemaking of the heart. They are activated by negative voltage and modulated by cAMP. Recently it had been discovered that cyclic di-nucleotides bind to a second site in the channel C-terminus. This counteracts the effect of cAMP on shifting channel activation positive. A bacterial cyclase, which synthesizes c-di-GMP in response to red light, allows engineering of an optogenetic system for remote HCN4 modulation and hence for controlling the heart pace. Two cyclases were used in this work: one constitutively active (Slr1143) and one red ligh-regulated (BphS). Because the latter has some dark activity, it is co-expressed with a phosphodiesterase (YhjH). Recordings of HCN4 activity in HEK293T cells show that Slr1143 affects the voltage dependence of the channel, shifting the activation curve negative with respect to the control. Experiments with BphS show no difference in HCN4 activity between light and dark treated cells. The combined BphS-YhjH expression seemed to be unable to increase the c-di-GMP concentration in a light dependent manner. To examine the effect of light on c-di-GMP production we quantified the cyclic di-nucleotide with an established ELISA assays in HEK293T cells and with an immune-fluorescence method. The latter consisted of monitoring expression of interferon-β in BphS-YhjH expressing T cells. Cyclic di-nucleotides can activate the STING pathway, which augments synthesis of interferon-β. Both methods underlined that Slr1143 and BphS-YhjH system increased the level of c-di-GMP in cells. This activity, however, was not light regulated. The immuno-fluorescence data indicate a slightly higher expression of the constitutive compared to the light-regulated cyclase. This may explain why we observed an effect of the former but not of the latter on HCN4 gating. Eliminating YhjH did not affect the level of c-di-GMP, suggesting that the phosphodiesterase is insufficient for eliminating c-di-GMP dark production. The data confirm previous results in that c-di-GMP is able to modulate HCN4 activity. BphS is not yet suitable as an optogenetic tool because of its high dark activity. This problem may be overcome by increasing the expression/activity of the phosphodiesterase in the next iteration of engineering an optogenetic tool. Advisors/Committee Members: tutors: A. Moroni A., scientific committee: Thiel G., Schroeder I., Barbuti A., reviewers: Hansen U., Schroeder I, MORONI, ANNA, MORONI, ANNA.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Zuccolini, P. (2019). STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/634438

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):

Zuccolini, P.. “STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF.” 2019. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/634438.

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

MLA Handbook (7^th Edition):

Zuccolini, P.. “STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF.” 2019. Web. 24 Jan 2021.

Vancouver:

Zuccolini P. STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/634438.

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

Council of Science Editors:

Zuccolini P. STRATEGIES FOR AN OPTOGENETIC MODULATION OF THE PACEMAKER CURRENT IF. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/634438

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

16. C.L. Politano. TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE.

Degree: 2019, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/613244

► CD4+ Regulatory T cells (Treg cells) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. These… (more)

▼ CD4+ Regulatory T cells (Treg cells) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. These cells play a critical role in preventing autoimmunity infections, and cancer. Treg cells can infiltrate tumor tissues where they suppress anti-tumor immune responses, contributing to the development of an immunosuppressive tumor microenvironment thus promoting immune evasion and cancer progression. Tumor infiltrating Treg cells can display function heterogeneity, depending on both the tumor type and the inflammatory milieu, therefore molecular characterization of Treg cells is crucial to understand how these cells can be modulated in the tumor to unleash effective anti-tumor T cell responses. To this aim, we investigated the transcriptional blueprints of Treg cells both in tumors and in the peripheral blood of healthy donors to define both coding and non-coding transcripts that best define the identity of these cells and might therefore represent novel prognostic markers or therapeutic targets. We performed a transcriptome analysis of both CD4+ Treg cells and effector cells (Th1 and Th17) infiltrating two of the most frequent types of human cancer defining the molecular signatures of tumor-infiltrating Treg cells in these two cancer types. We found tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine enriched in tumor infiltrating Treg cells compared to both the peripheral blood of patients and healthy donors. Given the high specificity of long non-coding RNA compared to coding sequences, we also performed bioinformatic analysis to assess the expression of known and novel non-coding transcripts. With this analysis we identified specific Treg cell non-coding transcript in proximity of CTLA4 locus. Since lncRNAs are by now considered as key regulatory elements in immune cell differentiation and maintenance of their identity, we characterized the identified lncRNAs in Treg cells in healthy donors, defining their epigenetic organization, expression level, localization and whether they contributed to the established Treg cell suppressive activity. All these findings unveiled another layer of the complexity of Treg cells biology and warrants for more detailed functional studies that can fully explain the pathways and the cellular networks that are affected by the identified coding and non-coding transcripts. Advisors/Committee Members: tutor: M. Pagani, coordinatore: M. Locati, PAGANI, MASSIMILIANO, LOCATI, MASSIMO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Politano, C. (2019). TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/613244

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):

Politano, C.L.. “TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE.” 2019. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/613244.

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

MLA Handbook (7^th Edition):

Politano, C.L.. “TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE.” 2019. Web. 24 Jan 2021.

Vancouver:

Politano C. TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/613244.

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

Council of Science Editors:

Politano C. TRANSCRIPTOME ANALYSIS OF TUMOR INFILTRATING T REGULATORY CELLS UNVEILS SPECIFIC CODING AND NON CODING GENE SIGNATURE. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/613244

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

17. S. Masella. 3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/265241

► The spatial organization of the genome and its biological function are intimately linked. It is becoming evident that transcription regulation often involves multiple long-range regulatory… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Masella, S. (2015). 3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/265241

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):

Masella, S.. “3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/265241.

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

MLA Handbook (7^th Edition):

Masella, S.. “3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES.” 2015. Web. 24 Jan 2021.

Vancouver:

Masella S. 3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/265241.

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

Council of Science Editors:

Masella S. 3D GENOMIC ORGANIZATION OF MOUSE MACROPHAGES. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/265241

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

18. E. Molinari. UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/335184

► The p63 transcription factor, homolog to the p53 tumour suppressor, plays a key role in limb, epithelial and cranio-facial development. p63 activity and stability are… (more)

▼ The p63 transcription factor, homolog to the p53 tumour suppressor, plays a key role in limb, epithelial and cranio-facial development. p63 activity and stability are tightly modulated to guarantee correct development of such structures and an impairment of this regulative mechanism can result in severe malformations. The control of p63 function is achieved not only through the regulation of its gene expression but also through a complex network of post-translational modifications. Acetylation, phosphorylation and ubiquitination affect p63 half-life, the specificity and efficiency of protein-protein interactions and overall modulate the transcriptional activity of the protein. Here we describe two pathways that, by post-translationally modifying ΔNp63α protein, modulate its stability and function. One such pathway involves FGF8, c-Abl and p300 which cooperate in controlling the stability and function of ΔNp63α protein by leading to its acetylation on lysine 193 (K193). Interestingly, K193 is mutated into glutamic acid (K193E) in patients affected by Split Hand/Foot Malformation (SHFM) type 4. c-Abl kinase activity is required to transduce the signal induced by FGF8 leading to ΔNp63α stabilization and transcriptional activation, through its acetylation mediated by p300. The ΔNp63α-K193E mutant, which cannot be acetylated by this pathway, displays promoter-specific loss of DNA binding activity and consequent altered expression of development-associated ΔNp63α target genes. Our results, elucidating an important regulatory pathway activated by FGF8 and essential for ΔNp63α activation and stabilization, shed new light on the molecular mechanism that could be at the basis of the SHFM4 pathogenesis. The other pathway that we here present is a degradative pathway promoted by the teratogenic drug thalidomide that leads to proteasome-mediated degradation of ΔNp63α, resulting in a lack of activation of ΔNp63α development-related target genes. In cell lines, thalidomide treatment induces a downregulation of ΔNp63α protein via the action of GSK3 kinase and FBWX7 ubiquitin ligase. Upon thalidomide treatment, GSK3 kinase is required to phosphorylate ΔNp63α on the residues serine 383 and threonine 397. This phosphorylation is recognized as a signal by FBWX7 which in turn ubiquitinates ΔNp63α, leading to its proteasome-mediated degradation. Thalidomide treatment induces a downregulation of ΔNp63α protein levels also in vivo in zebrafish embryos, where it results in a phenotypical and molecular impairment of fin development. Importantly, the microinjection of zp63-mRNA into zebrafish embryos treated with thalidomide rescues both the phenotypical and molecular defects induced by the drug, indicating that the downregulation of ΔNp63α is, at least in part, at the bases of thalidomide-induced malformations. Our results, by demonstrating that ΔNp63α is a molecular target of thalidomide teratogenicity, provide a fundamental missing piece in the description of the drug molecular mechanism of action. Thalidomide is now used for the… Advisors/Committee Members: tutor: L.F. Guerrini, GUERRINI, LUISA FRANCESCA.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Molinari, E. (2015). UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/335184

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):

Molinari, E.. “UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/335184.

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

MLA Handbook (7^th Edition):

Molinari, E.. “UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY.” 2015. Web. 24 Jan 2021.

Vancouver:

Molinari E. UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/335184.

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

Council of Science Editors:

Molinari E. UNRAVELLING THE MOLECULAR MECHANISMS OF IMPAIRED LIMB DEVELOPMENT: ROLE OF DNP63A IN SPLIT-HAND/FOOT MALFORMATION TYPE 4 AND IN THALIDOMIDE TERATOGENICITY. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/335184

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

19. A. Guazzotti. GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/529249

► In angiosperms, efficient and successful reproductive strategies have been crucial to achieve evolutionary advantages such as genetic adaptability. However, humans, during crop domestication, selected specific… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Guazzotti, A. (2017). GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/529249

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):

Guazzotti, A.. “GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA.” 2017. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/529249.

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

MLA Handbook (7^th Edition):

Guazzotti, A.. “GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA.” 2017. Web. 24 Jan 2021.

Vancouver:

Guazzotti A. GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/529249.

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

Council of Science Editors:

Guazzotti A. GENETIC AND EPIGENETIC REGULATION OF OVULE DEVELOPMENT AND PLANT REPRODUCTION IN A. THALIANA. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/529249

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

20. M. Fazzari. NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/548108

► Alterations of CDKL5 give rise to several forms of neurological disorders generally characterised by epileptic encephalopathy, severe developmental delay, hypotonia and RTT-like features. To date… (more)

▼ Alterations of CDKL5 give rise to several forms of neurological disorders generally characterised by epileptic encephalopathy, severe developmental delay, hypotonia and RTT-like features. To date no cure exists and only secondary symptoms can be treated. About 15% of CDKL5 patients carry a nonsense mutation and might benefit of a readthrough strategy as “personalised” medicine approach. The read-through process occurs when a near-cognate aminoacyl-tRNA binds a premature stop codon (PTC), allowing its suppression and the subsequent protein elongation. This mispairing event can rarely occur, but can be facilitated using a wide range of drugs. In order to test PTC suppression, we have chosen some human pathogenic CDKL5 nonsense mutations located in the two main domains of the protein: the catalytic N-terminus (R59X, R134X) or the C-terminal tail (Q347X, E364X, R550X, S855X). We then evaluated the read-through process using aminoglycoside and non-aminoglycoside drugs in cells transfected with the mutagenized constructs. In this study, we have demonstrated that tested CDKL5 PTCs can be suppressed by gentamicin and geneticin (G418) in a dose-dependent manner and that PTC position can be critical for read-through. In particular, G418 was found to be more effective than gentamicin. Considering the known aminoglycosides toxicity, we evaluated the activity of PTC124 and GJ072 but no PTC suppression was detectable in our experimental conditions. Finally, in order to understand whether the full-length derivatives may maintain the proper function of WT CDKL5, we analysed some features of read-through products compared to the WT protein. In particular, while premature truncated proteins showed an altered subcellular localisation, read-through products demonstrated a nucleo-cytoplasmic distribution more similar to the WT one. Moreover, by evaluating the auto-phosphorylation of the TEY motif, the read-through derivatives demonstrated to recover some catalytic activity, although remaining highly hypomorphic. Nevertheless, preliminary studies on Cdkl5-null neurons transfected with R134X construct suggested that G418 treatment can ameliorate impaired neuronal morphology. Collectively, our results indicate that: (i) aminoglycosides are able to induce read-through of different CDKL5 PTCs; (ii) the read-through derivatives recover some features characterizing the WT protein; (iii) PTC position can be crucial for read-though and for rescue of a proper function and (iv) neuronal morphological defects might be rescued by small amount of a possible hypomorphic CDKL5, therefore supporting the potential validity of a read-through therapy. Advisors/Committee Members: supervisore: N. Landsberger, coordinatore: M. Locati, LANDSBERGER, NICOLETTA, LOCATI, MASSIMO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Fazzari, M. (2018). NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/548108

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):

Fazzari, M.. “NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES.” 2018. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/548108.

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

MLA Handbook (7^th Edition):

Fazzari, M.. “NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES.” 2018. Web. 24 Jan 2021.

Vancouver:

Fazzari M. NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/548108.

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

Council of Science Editors:

Fazzari M. NOVEL APPROACHES OF ¿PERSONALISED MEDICINE¿ AS PROOF-OF-PRINCIPLE FOR CDKL5-RELATED PATHOLOGIES. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/548108

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

21. G.M. Prazzoli. BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/275276

► In the last few years the introduction of novel technologies known as “next-generation sequencing” (NGS) has brought a major step forward in sequencing. These techniques… (more)

▼ In the last few years the introduction of novel technologies known as “next-generation sequencing” (NGS) has brought a major step forward in sequencing. These techniques have practically supplanted the conventional Sanger strategies that have been the principal method of sequencing DNA since the late 1970s. Different NGS platforms have been introduced, with the newest using ion-sensitive sensors to detect the incorporation of bases as opposed to the more commonly used fluorescent labelled nucleotides. Since the first techniques were introduced, both the sequencing runtime and the cost per sequenced base have dramatically decreased, and, at the current state of the art, a complete human genome can be fully sequenced in under 24 hours. On the other hand, the ever-increasing amount of short sequences (or reads) yielded per single run makes the processing of the data more difficult and challenging from a computational point of view. One of the most prominent and promising fields of application is RNA-Seq, an assay that provides a fast and reliable way to study transcriptomic variability on a whole-genome scale. Generally, in a RNA-Seq experiment, a RNA sample is converted in a cDNA library, which then undergoes several cycles of sequencing with a NGS method of choice. Usually, the resulting sequences are either mapped on the reference genome or assembled de novo without the aid of genomic sequence to produce a genome-scale transcription map, or trascriptome. The data analyzed in this thesis comes from a three year research project focused on the characterization of tissue- and individual-specific alternative splicing, and its regulation. Data consist of several RNA-Seq experiments performed on different human tissues, coming from three healthy individuals. A total of 18 sets of data (6 tissues from three individuals with 3 replicates for each) were studied. The work initially focused on the quantification of mitochondrial DNA and RNA in the six individuals, and its variability. Then, we developed a computational method for the identification of tissue- and individual- specific transcripts, able to perform a multi-sample comparison. The algorithm we implemented employs statistical test based on a variant of Shannon’s information entropy, in order to identify transcripts with an expression pattern presenting a significant bias towards one or more of the samples studied. The results obtained show the method to be robust and efficient, overcoming the need of performing pairwise comparison as with the algorithms currently available, providing a thorough and complete map of the extent of tissue-specificity of gene expression at the single individual level. Advisors/Committee Members: tutor: G. Pavesi, PAVESI, GIULIO.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Prazzoli, G. (2015). BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/275276

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):

Prazzoli, G.M.. “BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/275276.

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

MLA Handbook (7^th Edition):

Prazzoli, G.M.. “BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS.” 2015. Web. 24 Jan 2021.

Vancouver:

Prazzoli G. BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/275276.

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

Council of Science Editors:

Prazzoli G. BIOINFORMATIC TOOLS FOR NEXT GENERATION TRANSCRIPTOMICS. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/275276

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

22. S. Dusi. CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/333162

► Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of genetically defined disorders clinically characterized by progressive extrapyramidal deterioration and by iron accumulation in… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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APA (6^th Edition):

Dusi, S. (2015). CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/333162

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):

Dusi, S.. “CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/333162.

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

MLA Handbook (7^th Edition):

Dusi, S.. “CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION.” 2015. Web. 24 Jan 2021.

Vancouver:

Dusi S. CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/333162.

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

Council of Science Editors:

Dusi S. CHARACTERIZATION OF DISEASE GENES IN NEURODEGENERATION WITH BRAIN IRON ACCUMULATION. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/333162

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

23. S. Molgora. THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/347675

► Le cellule staminali della ghiandola mammaria sono un modello per lo studio dei processi molecolari che regolano lo sviluppo fisiologico dell’organo e lo sviluppo tumorale.… (more)

▼ Le cellule staminali della ghiandola mammaria sono un modello per lo studio dei processi molecolari che regolano lo sviluppo fisiologico dell’organo e lo sviluppo tumorale. Diversamente da molti organi, la ghiandola mammaria incorre in cicli di rigenerazione e involuzione associati alla gravidanza. Per questo la ghiandola mammaria è uno dei primi organi nel quale si è ipotizzata la residenza di cellule staminali. Dal concetto che le cellule staminali regolano la crescita e la differenziazione della ghiandola con l’avvento della gravidanza è stato ipotizzato che cellule tumorali con proprietà staminali possano contribuire all’eterogeneità del tumore. Al fine di scoprire come il normale sviluppo dell’architettura della ghiandola mammaria sia originata dalle cellule staminali e il ruolo delle cellule staminali tumorali nella progressione tumorale, in questo lavoro di tesi è stata indagata la funzione di IFITM3. IFITM3 è stato inizialmente identificato dal laboratorio della dott.ssa Zucchi nelle cellule LA7, cellule staminali della ghiandola mammaria di ratto capaci di differenziare in dome, strutture 2D simili agli alveoli che si formano nella ghiandola mammaria durante la gravidanza. È stato dimostrato dal gruppo Zucchi che la funzione di IFITM3 dipende dal cambio di localizzazione della proteina dal citoplasma alla membrana plasmatica, dove risiede nei lipid raft. Questo è stato il punto di partenza di questa tesi di ricerca con lo scopo di identificare se IFITM3 partecipi anche alla formazione di strutture tridimensionali complesse della ghiandola mammaria (strutture tubulo-alveolari) e se svolga una funzione nel mantenimento delle cellule staminali della ghiandola mammaria. Ho utilizzato sistemi transienti e stabili per la modulazione dei livelli di espressione di IFITM3 in cellule LA7 e in cellule MCF7, una linea cellulare umana di ghiandola mammaria. Mentre le cellule LA7 possiedono sia la capacità di generare sfere sia di differenziare morfologicamente e funzionalmente in tutti i tipi cellulari e strutture 3D della ghiandola mammaria, si ritiene che cloni MCF7 utilizzati in questo studio non possiedano proprietà di cellule staminali, non formano sfere e possono differenziare unicamente in un tipo di struttura 3D, le cisti simili agli alveoli della ghiandola mammaria. Abbattendo i livelli di espressione di IFITM3 con siRNA/oligo e tecnologia lenti virale ad RNA a forcina corta (shRNA) in cellule impiegate in saggi funzionali in condizioni di coltura 3D, ho scoperto che IFITM3 è necessario per la formazione di strutture tubulo-alveolari complesse in cellule MCF7 e per il mantenimento delle proprietà di auto-rinnovamento delle cellule staminali LA7. Dato che le mammosfere e le cisti mammarie rappresentano strutture 3D associate rispettivamente a cellule staminali o differenziate, e dato che la sotto-regolazione di IFITM3 inibisce la formazione di entrambe, possiamo ipotizzare che IFITM3 abbia una funzione diversa in base al tipo cellulare. La sotto-regolazione di IFITM3 in cellule staminali LA7 in condizioni di… Advisors/Committee Members: tutore: C. Battaglia, co-tutore: I. Zucchi, direttore del dottorato: M. Clerici, BATTAGLIA, CRISTINA.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Molgora, S. (2015). THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/347675

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):

Molgora, S.. “THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/347675.

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

MLA Handbook (7^th Edition):

Molgora, S.. “THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS.” 2015. Web. 24 Jan 2021.

Vancouver:

Molgora S. THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/347675.

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

Council of Science Editors:

Molgora S. THE ROLE OF IFITM3 IN MAMMARY GLAND DEVELOPMENT AND MAMMARY STEM CELLS. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/347675

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

24. M. Greco. TM9SF4: ROLE IN CANCER AND DEVELOPMENT.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/347447

► The tm9sf4 gene encodes a member of Transmembrane 9 Protein Superfamily, characterized by the presence of nine transmembrane domains and a high degree of evolutionary… (more)

▼ The tm9sf4 gene encodes a member of Transmembrane 9 Protein Superfamily, characterized by the presence of nine transmembrane domains and a high degree of evolutionary conservation. It was originally identified in Dictyostelium and Drosophila as a protein involved in cell adhesion and phagocytosis. More recent studies reported that tm9sf4 is expressed in metastatic melanoma cells and it is involved in the process of tumor cell cannibalism, which might be unique to metastatic cells. Tumor cells indiscriminately phagocytize both sibling tumor cells and lymphocytes, in addition to amorphous material, thereby allowing tumor cells to escape from the immune response, promoting cell survival in a hostile microenvironment with low nutrient supplies and hypoxia conditions and allowing them to remodel and migrate through the extracellular matrix. Tm9sf4 gene was brought to our attention by LA7 cells, which represent a cancer stem cell (CSC) model system. Our preliminary data showed that the expression level of tm9sf4 gene was higher in LA7 CSCs if compared to the differentiated counterpart. Tm9sf4 downregulation by RNA interference induced LA7 CSCs to trans-differentiate to mesenchymal-like cells and caused an increase of the expression level of EMT-associated markers, suggesting that the gene is involved in epithelial to mesenchymal transition (EMT). The aim of my PhD project is to identify the function of tm9sf4 in normal and cancer cells. Based on the assumption that all vertebrates share common pathways involved in biological processes including morphogenesis-associated development of branched structures, cell migration and sprouting, we investigated Tm9sf4 protein function in zebrafish (Danio rerio), to further investigate its role in normal development. Zebrafish was recently proven to be a powerful model, to study not only human diseases, but also processes associated with oncogenesis. Additionally, EMT was suggested to be the major driver of both embryonic morphogenesis and tumor progression, involving highly conserved cellular processes and signaling pathways. Tm9sf4 expression analyses were performed by both RT-PCR on RNA from embryos at different developmental stages and whole mount in situ hybridization (WISH). Histological sections of the stained embryos were performed. In addition, loss-of-function analyses were carried out by the injection of 1-4 cell stage embryos with antisense oligonucleotide morpholinos, using the zebrafish AB line (wild type) and the double transgenic line tg(gata1:dsRed)sd2/tg(flk1:EGFP)S843. The expression of specific brain markers and EMT-associated markers was assessed by WISH and Real Time PCR on embryos previously injected with morpholino oligos (morphants). We demonstrated that during zebrafish embryogenesis the gene was expressed from oocytes to 5 days post fertilization (dpf), suggesting that the expression is both maternal and zygotic. Moreover, it was found to be mainly expressed in the central nervous system (CNS). Following tm9sf4 downregulation, the embryos displayed… Advisors/Committee Members: tutore: C. Battaglia, co-tutore: I. Zucchi, coordinatore: M. Clerici, BATTAGLIA, CRISTINA, CLERICI, MARIO SALVATORE.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Greco, M. (2015). TM9SF4: ROLE IN CANCER AND DEVELOPMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/347447

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):

Greco, M.. “TM9SF4: ROLE IN CANCER AND DEVELOPMENT.” 2015. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/347447.

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

MLA Handbook (7^th Edition):

Greco, M.. “TM9SF4: ROLE IN CANCER AND DEVELOPMENT.” 2015. Web. 24 Jan 2021.

Vancouver:

Greco M. TM9SF4: ROLE IN CANCER AND DEVELOPMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/347447.

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

Council of Science Editors:

Greco M. TM9SF4: ROLE IN CANCER AND DEVELOPMENT. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/347447

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

25. S.G. Jammula. CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/366602

► ABSTRACT During my PhD tenure, I have been involved in developing a user-friendly cross-platform system capable of analyzing epigenomic data and further use it in… (more)

▼ ABSTRACT During my PhD tenure, I have been involved in developing a user-friendly cross-platform system capable of analyzing epigenomic data and further use it in understanding the role of the Polycomb Repressive Complex 2 (PRC2) in genome regulation. From current trending in epigenetics research, we can sense increasing ease of high throughput sequencing and greater interest towards genome wide epigenomic studies. As a result of which we experience an exponential flooding of epigenetic related data such as Chromatin immunoprecipitation followed by sequencing (ChIP-seq), and RNA sequencing (RNA-seq) in public domain. This creates an opportunity for crowd sourcing and exploring data outside the boundaries of specific query centered studies. Such data has to undergo standard primary analysis, which with the aid of multiple programs has been stabilized courtesy to the scientific community. Further downstream, out of many, genome wide comparative, correlative and quantitative studies have proven to be critical and helpful in deciphering key biological features. For such studies we lack platforms, which can be capable of handling, analyzing and linking multiple interdisciplinary (ChIP-seq/RNA-seq) datasets with efficient analytical methods. With this aim we developed ChIP_QC, a user-friendly standalone computational program with an ability to support numerous datasets with high/moderate sequencing depth for performing genome wide analysis. First, using ENCODE project (Consortium, 2012) data, we illustrated few applications of the program by posing different biological scenarios and showed the comfort with which some known observations can be verified and also how it can be helpful in deducing some other novel observations. Second, we were interested in understanding the functionality of the products generated through catalytic activity of PRC2. It is known that Lysine 27 of histone H3 (H3K27) undergoes posttranslational modification (PTM) and methylation is one such dominant PTM. Methylation on H3K27 can be either mono/di/tri-methylation form. Out of all three forms, it is very well demonstrated that trimethylation of H3K27 (H3K27me3) is PRC2 dependent and at the same time its role in gene repression is well characterized, but functional roles of other forms of methylation on H3K27 are still poorly characterized. For understanding this, we used mouse embryonic stem cells (mESC) as model system of our study and we were able to provide an extensive characterization of other forms of methylation, highlighting their differential deposition along the genome, their fundamental role in transcriptional regulation, and their indispensability during differentiation program. Using ChIP_QC and with other computational methods along with experimental evidences, our data demonstrated that the monomethylation of Lys27 (H3K27me1) is required for correct transcription of genes and positively correlates with trimethylated Lys36 (H3K36me3); on the other hand dimethylated Lys27 (H3K27me2), that we identified to be the principal activity… Advisors/Committee Members: Dr. Diego Pasini: immediate supervisor, Dr. Mattia Pelizzola: added supervisor, Dr. Claudia Angelini: internal adviser, Dr. Rory Johnson: external adviser, Dr. Saverio Minucci: tutor.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Jammula, S. (2016). CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/366602

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):

Jammula, S.G.. “CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES.” 2016. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/366602.

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

MLA Handbook (7^th Edition):

Jammula, S.G.. “CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES.” 2016. Web. 24 Jan 2021.

Vancouver:

Jammula S. CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/366602.

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

Council of Science Editors:

Jammula S. CHIP_QC, COMPUTATIONAL PLATFORM FOR MULTIVARIATE EPIGENETIC STUDIES AND ITS APPLICATION IN UNCOVERING ROLE OF POLYCOMB DEPENDENT METHYLATIONS STATES. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/366602

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

26. R. Quadri. HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/457676

► The atypical protein kinase haspin is conserved in all eukaryotes and promotes the correct alignment of chromosomes on the metaphase plate by recruitment of the… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Quadri, R. (2016). HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/457676

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):

Quadri, R.. “HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION.” 2016. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/457676.

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

MLA Handbook (7^th Edition):

Quadri, R.. “HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION.” 2016. Web. 24 Jan 2021.

Vancouver:

Quadri R. HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/457676.

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

Council of Science Editors:

Quadri R. HASPIN ROLE IN VESICLE DELIVERY AND POLARITY DISPERSION. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/457676

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

27. L.S. Alberio. IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/503681

► Optogenetics uses light-regulated ion channels and pumps to modulate the activity of neurons with high temporal precision. To date, inhibition of neuronal firing is obtained… (more)

▼ Optogenetics uses light-regulated ion channels and pumps to modulate the activity of neurons with high temporal precision. To date, inhibition of neuronal firing is obtained by means of hyperpolarizing pumps, and/or chloride channels. However, a light-gated potassium (K+) channel would represent a more physiological tool because of the universal role of K+ in repolarizing membrane potential in animal cells. We recently engineered a synthetic light-gated channel by fusing the LOV (light oxygen voltage) domain of the plant blue-light receptor AsPhototropin1 to the viral K+ channel Kcv-PBCV1. The resulting channel BLINK1 (Blue Light Induced K+ channel) is reversibly activated by blue light and shows K+ selectivity and high single channel conductance, when expressed in HEK 293T cells. However, BLINK1 low expression rate at the plasma membrane (PM) (less than 10% in HEK 293T cells) prevented so far its application in optogenetics. The goal of my PhD thesis has been to improve BLINK1 expression in HEK293T cells and to test it in two model systems, zebrafish and mouse. To this end, I have applied molecular and cellular approaches for modifying the trafficking and the overall folding and stability of the channel. Both the LOV domain and the pore domain have been modified by either the addition of PM anchoring motifs and structural elements (LOV domain) or the addition of trafficking motifs (Kcv). The outcome of this study, BLINK2, was obtained by adding a 14-3-3 signal peptide to the C terminus of BLINK1. It showed a moderate increase in PM expression (26% vs 10%) compared to BLINK1, but responded to light with a delay of about 90 s. We further improved BLINK2 by introducing a point mutation (Q513D) in the LOV domain that reduced the delay to about 30 s. When tested in mouse, BLINK2 Q513D efficiently inhibited spontaneous firing in brain slices. BLINK2 Q513D is currently undergoing a test in vivo in a mouse behavioral experiment. Advisors/Committee Members: scientific tutor: A. Moroni, MORONI, ANNA.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Alberio, L. (2017). IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/503681

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):

Alberio, L.S.. “IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL.” 2017. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/503681.

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

MLA Handbook (7^th Edition):

Alberio, L.S.. “IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL.” 2017. Web. 24 Jan 2021.

Vancouver:

Alberio L. IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/503681.

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

Council of Science Editors:

Alberio L. IMPROVING TRAFFICKING AND KINETICS OF A SYNTHETIC LIGHT-GATED POTASSIUM CHANNEL. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/503681

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

28. F. Rossi. ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/559145

► DNA damage response (DDR) mechanisms are crucial in all organisms to detect DNA damage and integrate its repair with cell cycle control, chromatin structure, and… (more)

▼ DNA damage response (DDR) mechanisms are crucial in all organisms to detect DNA damage and integrate its repair with cell cycle control, chromatin structure, and other adaptive changes in cell physiology. The highly conserved structural maintenance of chromosomes (SMC) complex, SMC5/6, contains both SUMO and ubiquitin ligase activities in its composition and is crucial for processing recombination structures arising during replication. Differently from related SMC complexes such as Cohesin and Condensin, the function of SMC5/6 in genome maintenance and its mode of action remain to date hardly understood. Moreover, a lack of cellular models for SMC5/6, especially in human cell lines, has hampered progress in understanding its roles in DDR in model systems most relevant for human disease. Here, we established vertebrate and human cellular models of SMC5/6 knockouts and characterized the associated phenotypes in a battery of assays. Specifically, I established (conditional) SMC5 knockout (KO) in chicken (DT40) and human (TK6) B cell lines. We generated a conditional SMC5 KO in TK6 human cell lines, and uncovered that SMC5 depletion caused apoptosis-mediated lethality, associated with increased DSBs and cohesion defects. In chicken DT40 cell lines, SMC5 KO causes a slow growth phenotype depending on the temperature condition. Second, we investigated the roles of SMC5/6 in intra- and inter-strand crosslink (ICL) repair. SMC5 shows epistasis with FA core mutations, as well as with DDX11 and RAD17, without affecting FANCD2-I ubiquitination and CHK1 phosphorylation. We propose that SMC5 is working downstream of FA and RAD17/DDX11-mediated pathways, likely in resolving the emerging recombination intermediates. Third, we are attempting to identify the principles underlying SMC5/6 roles in the establishment/maintenance of chromatin structure/cohesion and integrity of specific genomic loci such as replicating fragile sites and centromeric/peri-centromeric regions. To these ends, we have used BLISS, a genomic approach to map DSBs, and plan to employ ChIP-seq of endogenously tagged SMC5/6. Advisors/Committee Members: supervisori: J. E. Sale, D'adda di Fagagna, D. Branzei.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Rossi, F. (2018). ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/559145

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):

Rossi, F.. “ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS.” 2018. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/559145.

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

MLA Handbook (7^th Edition):

Rossi, F.. “ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS.” 2018. Web. 24 Jan 2021.

Vancouver:

Rossi F. ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/559145.

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

Council of Science Editors:

Rossi F. ROLES OF THE SMC5/6 COMPLEX IN DNA REPAIR AND CHROMOSOME INTEGRITY IN VERTEBRATE CELLS. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/559145

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

29. A. Meroni. RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/570097

► The presence of RNA in the genome of living cells is one of the emerging topics of the last two decades and has been implicated… (more)

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

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

APA (6^th Edition):

Meroni, A. (2018). RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/570097

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):

Meroni, A.. “RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY.” 2018. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/570097.

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

MLA Handbook (7^th Edition):

Meroni, A.. “RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY.” 2018. Web. 24 Jan 2021.

Vancouver:

Meroni A. RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/570097.

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

Council of Science Editors:

Meroni A. RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/570097

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

30. M.M. URUBURU GOMEZ. UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS.

Degree: 2018, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/569858

► The opportunistic pathogen Pseudomonas aeruginosa is a common agent of infectious disease in immunocompromised individuals, and a dominant pathogen in late-stage of cystic fibrosis disease.… (more)

▼ The opportunistic pathogen Pseudomonas aeruginosa is a common agent of infectious disease in immunocompromised individuals, and a dominant pathogen in late-stage of cystic fibrosis disease. P. aeruginosa represents a prototype of multidrug resistant “superbug” due to intrinsic and acquired resistance to antimicrobials agents, for which effective therapeutic options are very limited. In order to overcome the current resistance mechanisms, the identification and characterization of new cellular functions that are essential for P. aeruginosa viability could drive the development of new antibacterial compounds with novel mechanisms of action. The present PhD thesis is focused on the functional and structural characterization of the Transglutaminase protein A, TgpA, an inner membrane protein predicted to belong to the Transglutaminase-like family which contains a functional TG domain (TG180–544), localized in the periplasmic side, suggested to take part in an essential function involved in envelope structure. The protein was recently described as essential for the viability of P. aeruginosa, and a promising candidate for the design of new specific antimicrobial compounds. In Part I, the state of the art and main results are presented. First, the in vivo evaluation of the modulation of TgpA expression levels on the P. aeruginosa growth showed that, the increase of TgpA cellular levels dramatically affects the P. aeruginosa growth. On the other hand, the partial suppression of the chromosomal copy of the tgpA gene showed to compromised the envelope organization of the cells. The subsequent structural characterization of the functional TG domain allowed confirming that TgpA belongs to the poorly characterized Transglutaminase-like family, in which many of the prokaryotic members are proteases. Also, the presence of a carbohydrate-binding domain at the N-terminal portion of the protein, suggests that the binding to polysaccharides present in the cell wall might constitute a mechanism of regulation of the enzymatic activity of TgpA. Moreover, the active site of the protein shares homology with cysteine proteases and endopeptidases with described action in the maintenance/biosinthesys of the bacterial peptidoglycan, suggesting that TgpA might be involved in the cell wall metabolism. The transglutaminase and proteolytic activity of the TG domain were evaluated in vitro, showing residual activity over generic substrates. A manuscript in preparation, presented in Part II, describes in detail the characteristics found in the structure of the TG domain that are the foundations for the TgpA enzymatic activity. Finally, in the search for possible inhibitory molecules of the activity of TgpA, the results of a preliminary in silico docking analysis with in vivo results are presented in Part III. Advisors/Committee Members: co-tutor: M. Milani, E. Mastrangelo, scientific tutor: G. Bertoni, BERTONI, GIOVANNI.

Subjects/Keywords: Settore BIO/11 - Biologia Molecolare

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

GOMEZ, M. U. (2018). UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/569858

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):

GOMEZ, M.M. URUBURU. “UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS.” 2018. Thesis, Università degli Studi di Milano. Accessed January 24, 2021. http://hdl.handle.net/2434/569858.

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

MLA Handbook (7^th Edition):

GOMEZ, M.M. URUBURU. “UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS.” 2018. Web. 24 Jan 2021.

Vancouver:

GOMEZ MU. UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 24]. Available from: http://hdl.handle.net/2434/569858.

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

Council of Science Editors:

GOMEZ MU. UNRAVELLING THE ESSENTIAL ROLE OF TGPA IN THE VIABILITY OF PSEUDOMONAS AERUGINOSA: A PUTATIVE TARGET FOR NOVEL ANTIMICROBIAL AGENTS. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/569858

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

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