You searched for subject:(Settore BIO 09 Fisiologia).
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1.
A. ATTARD TREVISAN.
NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/333759 
► The doctoral thesis deals with a novel methodology of looking and processing electroencephalographic (EEG) data. The first part deals with real-time brain stimulation in the…
(more)
▼ The doctoral thesis deals with a novel methodology of looking and processing electroencephalographic (EEG) data. The first part deals with real-time brain stimulation in the form of a sonified neurofeedback therapy derived from a clinically comparable portable, 4-channel EEG system. The therapy aims to provide an effective management for symptoms of the Autism Spectrum Disorder (ASD). ASD is characterized with a high level of delta electroencephalographic waveform levels, while alpha and beta prove to be present at lower levels especially in the frontal-temporal regions. The treatment aims at lowering delta waves and promoting alpha and beta waveforms. The second part of the thesis focuses on using EEG data in the prediction of epileptic seizures. With the help of custom built algorithms and neural networks, an effective prediction of an epileptic seizure can be achieved.
Advisors/Committee Members: supervisor: P. Cavallari, coordinatore: M. Mazzanti, CAVALLARI, PAOLO, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
TREVISAN, A. A. (2015). NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/333759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
TREVISAN, A. ATTARD. “NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/333759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
TREVISAN, A. ATTARD. “NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION.” 2015. Web. 20 Jan 2021.
Vancouver:
TREVISAN AA. NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/333759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
TREVISAN AA. NOVEL COMPUTATIONAL ELECTROENCEPHALOGRAPHIC (EEG) METHODOLOGIES FOR AUTISM MANAGEMENT AND EPILEPTIC SEIZURE PREDICTION. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/333759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
2.
M. Boccazzi.
IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150164
► Several human inherited diseases are caused by mutations in chloride channels or transporters, which cause symptoms as diverse as epilepsy, startle disease, deafness, blindness, lysosomal…
(more)
▼ Several human inherited diseases are caused by mutations in chloride channels or transporters, which cause symptoms as diverse as epilepsy, startle disease, deafness, blindness, lysosomal storage and neurodegeneration, osteopetrosis, lung infections and fibrosis, male infertility, renal salt loss, and kidney stones, clearly indicating the crucial importance of anion transport in many tissues. ICln is a water-soluble protein forming a PH domain, which can be introduced into the cellular membrane to form ion channels. When expressed in cellular systems, wt-ICln ion channels mediate a chloride current resembling those activated after cell swelling (ICl,swell), suggesting a role for ICln in cell volume regulation. During the first part of my PhD program at the department of Pharmacology and Toxicology (Paracelsus Medical University of Salzburg, Austria) I was involved in the functional characterization (by Black Lipid Bilayer and Patch Clamp experiments) of a new mutant form of the ICln protein possibly implicated in a heart disease. The object of my investigation was the insertion of a Thymine in position 383 in the nucleotide sequence. This mutation produces a frameshift, leading to a scrambled sequence of 12 aminoacids (starting from the aminoacid 128) and (an earlier termination (A128FSX139) of the channel sequence. This mutation has been identified in a patient whose familiarity, symptoms and QT value suggested she was suffering from long QT syndrome (LQTS).
Black lipid Bilayer experiments showed that the mutated protein reconstituted in artificial membrane of sphingomyelin had the same electrophysiological characteristics of the wild type protein. Otherwise Patch Clamp experiments (whole cell configuration) showed that the overexpression of the mutated protein in HEK293 Phoenix cells produced a significantly reduced ICl,swell current in comparison to that obtained by hIClnWT overexpression. During the second part of my PhD program I was involved in the functional characterization of the 5`flanking region of SLC26A4. SLC26A4 (Pendrin) was cloned by positional characterization of the gene for the Pendred syndrome (OMIM274600), a recessively inherited disorder causing congenital deafness and thyroid goiter accountable for up to 10% of inherited hearing loss. The purpose of this part of my work was to identify the minimum sequence necessary for the transcription of the SLC26A4 gene and, when possible, to identify sequences important for the “tissue specific“ expression of the gene and for the recognition of responsive elements in a promoter sequence. The experiments performed in both HEK 293 Phoenix cells and in rat thyroid PC-CL3 cells showed that a sequence of only 286 base pairs is able to drive the basal expression of the pendrin gene in both cellular models. We assumed that the sequence contains all the cis-acting signals necessary for the activity of the basal transcription machinery. Moreover experiment performed in PC-CL3 cells allowed us identifying a tireoglobuline (TG) responsive element of only 205 base…
Advisors/Committee Members: tutor: Giuliano Meyer, coordinatore: Paolo Cavallari, MEYER, GIULIANO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Boccazzi, M. (2010). IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150164
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Boccazzi, M.. “IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150164.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Boccazzi, M.. “IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE.” 2010. Web. 20 Jan 2021.
Vancouver:
Boccazzi M. IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150164.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Boccazzi M. IL TRASPORTO DI CLORURO: COINVOLGIMENTO IN ALCUNE PATOLOGIE UMANE. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150164
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
3.
M. Armilli.
COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/160740
► SGLT1 (SLC5A1) is a Na+–glucose cotransporter belonging to the SLC5 family, expressed in several absorbing epithelia. Indirect evidence for a solute-coupled liquid absorption from rabbit…
(more)
▼ SGLT1 (SLC5A1) is a Na+–glucose cotransporter belonging to the SLC5 family, expressed in several absorbing epithelia. Indirect evidence for a solute-coupled liquid absorption from rabbit pleural space indicated that it should be due to a Na+/H+-Cl-/HCO3- double exchanger and a Na+-glucose cotransporter (Agostoni and Zocchi, Clin Chest Med 19:241-60, 1998). Furthermore, functional evidence of Na+-glucose cotransport in rat lung has been provided by Basset (Basset et al., J Physiol 384:325-345, 1987). By autoradiography [3H]phloridzin binding has been found confined to alveolar type II cells in mouse and rabbit lungs (Boyd, J Physiol 422: 44P, 1990). In the alveolar airspace the active Na+ transport is regulated by beta adrenergic receptors, particularly the β2 subtype (Mutlu et. al., Am J Respir Crit Care Med 170:1270–1275, 2004). Experimental data suggest that beta adrenergic agonists, working via the β2AR, accelerate clearance of excess fluid from the alveolar airspace; activation of β2AR seems to increase both Na+/K+-ATPase and ENaC function and expression (Pesce et. al., FEBS Letters 486:310-314, 2000; Chen et. al., Am J Physiol Lung Cell Mol Physiol 282:609-620, 2002). In literature there are no data regarding a beta adrenergic regulation of Na+–glucose cotransport in the respiratory system, but in two cases is reported a beta adrenergic stimulation of SGLT1, in rat small intestine (Ishikawa et al., Biochimica et Biophysica Acta 1357: 306–318, 1997) and in ruminal epithelium of sheep (Aschernbach et al., J. Nutr. 132: 1254–1257, 2002).
In this research, we first tried to obtain molecular evidence for Na+-glucose cotransporter (SGLT1) in the respiratory system, particularly in pleural and alveolar epithelia. The expression of SGLT1 was identified by Western blot assays on total protein extracts of scraped mesothelium from visceral or parietal pleura, and from alveolar cells; in all experiments we obtained SGLT1 specific bands. Immunolocalization of SGLT1 was performed examining for fluorescence the pleural surface, the alveolar epithelium and isolated alveolar cells. Confocal immunofluorescence images of lamb pleural mesothelium showed that SGLT1 is located in the apical membrane; in alveolar sections of rats and lambs most alveolar surface was stained by anti-SGLT1 antibody; furthermore also alveolar type I and type II cells isolated from rat lung were stained by anti-SGLT1 antibody, so we can assume that SGLT1 is expressed on both types of alveolar cells. After that, we concentrated on beta adrenergic regulation of SGLT1; immunofluorescence assays were performed on A549 cells (alveolar epithelial cell line) treated for different times with the beta adrenergic agonist isoproterenol. Immunolabeling images showed an increased expression of the Na+-glucose cotransporter after treatment with the β-agonist isoproterenol; this increase appears to be reversible.
These findings provide evidence at molecular level, in pleural and alveolar epithelium, for Na+-glucose cotransporter (SGLT1); in the respiratory system, it…
Advisors/Committee Members: Tutor: Luciano Zocchi, Coordinatore: Paolo Cavallari, ZOCCHI, LUCIANO ALDO MARIA, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Armilli, M. (2010). COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/160740
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Armilli, M.. “COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/160740.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Armilli, M.. “COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA.” 2010. Web. 20 Jan 2021.
Vancouver:
Armilli M. COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/160740.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Armilli M. COTRASPORTATORE NA+-GLUCOSIO NEL MESOTELIO PLEURICO E NELL'EPITELIO ALVEOLARE POLMONARE: ESPRESSIONE E CENNI DI REGOLAZIONE BETA ADRENERGICA. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/160740
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
4.
G. Carriero.
ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150049
► ABSTRACT Temporal lobe epilepsy (TLE) is the most common partial epilepsy and it is often associated with pharmacoresistance. Surgery has become the standard of care…
(more)
▼ ABSTRACT
Temporal lobe epilepsy (TLE) is the most common partial epilepsy and it is often associated with pharmacoresistance. Surgery has become the standard of care for patients with intractable temporal lobe epilepsy, Pre-surgical analyses with intracranial electrode to identify the epileptic focus reveal the presence of a characteristic high frequency low voltage activity at seizure onset. Previous work in our laboratory demonstrated that this pattern is reproducible in the model of guinea pig isolated brain perfused with bicucullin and pilocarpine (Uva et al., 2005; 2008). Intracellular recording during seizure onset reveal an intense activation of GABAergic neuron while principal cell are silent in medial entorinal cortex (Gnatkovsky et al., 2008). To confirm that ictogenesis pattern is a network property independent from the substance used to induce seizure we perfused a potassium channel blocker, 4AP, in the guinea pig brain. Furthermore, in vivo study injecting Kainic acid in the right hippocampus in anesthetized and freely moving guinea pig in acute and chronic period was performed. Both in vitro and in vivo study confirmed the presence of high frequency and low voltage signal.
Advisors/Committee Members: tutor: Marco de Curtis, coordinatore: Paolo Cavallari, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Carriero, G. (2010). ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150049
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Carriero, G.. “ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150049.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Carriero, G.. “ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE.” 2010. Web. 20 Jan 2021.
Vancouver:
Carriero G. ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150049.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Carriero G. ICTOGENESI ED EPILETTOGENESI IN UN MODELLO DI EPILESSIA DEL LOBO TEMPORALE. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150049
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
5.
B. Diamante.
PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE.
Degree: 2012, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/168386
► Control of insect pests is still mainly performed using broad spectrum chemical pesticides even though the limits of this strategy are presently well known: the…
(more)
▼ Control of insect pests is still mainly performed using broad spectrum chemical pesticides
even though the limits of this strategy are presently well known: the reduction in pest population is
associated with an unfavourable alteration of food quality and safety, with a strong impact on nontarget
species and with the rise of a widespread resistance in target insects. The most recent
approach to the Integrated Pest Management is based on the detection of new genes encoding for
polypeptides with potential insecticide activity, with a particular attention to biopesticides derived
from insect antagonists and plants (Whetstone e Hammock, 2007). However, efficient delivery
methods are essential in deploying bioinsecticides. For an effective oral delivery, it will be crucial
to develop strategies to facilitate their passage through the midgut barriers, i.e. the peritrophic
membrane (PM) and the midgut epithelium (ME). This can be achieved by altering the sieving
properties of the PM and by increasing the rate of absorption by the ME.
In the framework of a coordinated effort towards the development of new delivery strategies
my laboratory, in collaboration with other research groups, discovered that the recombinant
Chitinase A (ChiA) of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV)
determined in vitro structural alterations on lepidopteran larvae PM and a strong increase of its
permeability to molecules (Rao et al., 2004). Moreover, when this enzyme is delivered either with
artificial diet or with transgenic plants to lepidopteran larvae, a significant negative effect on insect
biological performance and survival was observed. I demonstrated that PMs isolated from fifth
instar Heliothis virescens larvae fed on transgenic tobacco plants expressing ChiA starting from the
first day of the fourth instar show an increased flux of methylene blue. The PMs were mounted in
Ussing chambers and incubated in the presence of methylene blue, a good tracer of PM
permeability, in the endoperitrophic compartment. The flux of methylene blue through the PMs
isolated from larvae reared on ChiA-expressing tobacco plants was significantly higher than that of
controls (PM isolated from larvae reared on control tobacco plants). To demonstrate that the
increased permeability was due to the hydrolytic activity of AcMNPV ChiA on the PM chitin mesh,
this enzyme was extracted and purified from ChiA-expressing tobacco plants and its activity tested
on the permeability of PMs of H. virescens larvae isolated in Ussing chambers. PM incubation with
ChiA (40 μM) in the endoperitrophyc compartment caused a significant increase of TMOF (Trypsin
Modulating Oostatic Factor) flux compared to control. Thus, the use of this enzyme, and of any
other similar enhancer, can be of great interest in the development of effective delivery strategies.
Once crossed the PM, the macromolecules have to pass the ME. They can reach the
haemocoel either through the cellular pathway, crossing the two polarized plasma membranes of the…
Advisors/Committee Members: tutor: M. Casartelli, coordinatore: G. Melone, CASARTELLI, MORENA, MELONE, GIULIO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Diamante, B. (2012). PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/168386
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Diamante, B.. “PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE.” 2012. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/168386.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Diamante, B.. “PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE.” 2012. Web. 20 Jan 2021.
Vancouver:
Diamante B. PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/168386.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Diamante B. PROPRIETA' FUNZIONALI DELLA BARRIERA INTESTINALE DI INSETTO E MODULAZIONE DELLA PERMEABILITA' PARACELLULARE. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/168386
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
6.
A. Simone.
RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA.
Degree: 2012, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/169154
► It is well known that HCN proteins, molecular correlates of the If current in the heart and Ih in neurons, interact with a system of…
(more)
▼ It is well known that HCN proteins, molecular correlates of the If current in the heart and Ih in neurons, interact with a system of proteins with regulatory activity and cytoskeleton anchoring. Among these proteins those that have been best studied to date are: caveolin 3, which influences the functionality of HCN4, filamin A which connects HCN1 to the cytoskeleton and MiRP1 that is involved in the modulation of current amplitudes and activation kinetics of HCN4 and 2.
In vitro experiments have established that the non-functionality of these proteins can have profound effects on the activity and functional properties of HCN channels.
On this basis we decided to see if mutations in the primary sequence of these proteins can be detected in patients with various heart rhythm disorders and epilepsy. Patients we considered: 38 tachycardia (IST), 107 effects by sinus bradycardia (BRA), 21 affected by sudden death syndrome (SUDS), 37 by sudden Antenatal Death Syndrome (SADS), 4 by sudden unespected infant death, 20 with paroxysmal atrial fibrillation (FAP), 110 by epilepsy (EPI) and 107 by sinus bradycardia.
So far, we have highlighted some SNPs (Single Nucleotide Polymorphisms) in Caveolin 3: five of these do not lead to changes in amino acid sequence: L9L, N33N, F41F, V57V and S68S; instead another SNP leads to an amino acid change, T78M. All these SNPs have been already published on the NCBI data-Bese. The T78M mutation has already been linked to some cases of SIDS (4), we found it in four TSI, two FAP , oneBRA, and two SADS.
The T78M mutation was not found in 418 alleles of control.
Regarding Mirp1, Q9E mutations was found in cases of SUD and M54T in a case of seizure and none of them appeared in the control group. Furthermore, two polymorphisms were found:T8A and I57T that although in the literature, along with Q9E and M54T were related to drug induced atrial fibrillation , in our case there is no statistical significance in the association to diseases when compared with the results of the control group.
The analysis of filanin A, in the same patients did not reveal significant genetic abnormalities.
The mutations were found through the analysis techniques SSCP, DHPLC and sequencing of the gene, the statistical analysis is performed by exact Fisher Test.
Later in the case of potentially interesting mutations we continued with genetic engineering techniques aimed at producing cells (HEK293) from which to draw electrophysiological data.
The experiments performed to date have focused on functional characterization of the T78M mutation to determine its clinical relevance in the context of the conditions mentioned.
Preliminary experiments of functional heterologous coexpression of HCN4 channel with caveolin-3 mutant and wild tipe, did not detect significant changes in current pacemakers. However, given the great variability of the data obtained so far, there is need for a further investigation of CAV3-T78M.
Ultimately, the presence of CAV3-T78M is characterized by high statistical significance for groups TSI,…
Advisors/Committee Members: tutor: M. Baruscotti, coordinatore: P. Cavallari, BARUSCOTTI, MIRKO, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Simone, A. (2012). RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/169154
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Simone, A.. “RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA.” 2012. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/169154.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Simone, A.. “RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA.” 2012. Web. 20 Jan 2021.
Vancouver:
Simone A. RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/169154.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Simone A. RICERCA DI MUTAZIONI IN PROTEINE ASSOCIATE AI CANALI HCN IN PAZIENTI AFFETTI DA DISTURBI DEL RITMO CARDIACO ED EPILESSIA IDIOPATICA. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/169154
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
7.
F. Sassone.
MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA.
Degree: 2013, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/215231
► CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is a chloride channel, expressed in the kidney, whose activity and localization are influenced by the cytoskeleton, in particular…
(more)
▼ CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is a chloride channel, expressed in the kidney, whose activity and localization are influenced by the cytoskeleton, in particular by actin and its polymerization state. In this study, a possible functional modification of CFTR activity and expression, led by the expression of the hypertensive mutations of adducin (G460W-S586C in humans), an actin capping protein, has been investigated.
The experiments were performed on HEK293 T cells cotransfected with CFTR and the human wild-type or mutated adducin. In whole-cell patch-clamp experiments, both the CFTR chloride current and the slope of current activation after forskolin addition were significantly higher in HEK cells overexpressing mutated adducin. A higher plasma membrane density of active CFTR channels in the presence of mutated adducin, was confirmed by cell-attached patch-clamp experiments. Western blot and biotinylation experiments demonstrated an increased CFTR expression in the plasma membrane, in the presence of the mutated adducin. FRET (Fluorescence Resonance Energy Transfer) experiments showed a significant but weak interaction between CFTR and adducin, while coimmunoprecipitation experiments failed to reveal a clear interaction between the two proteins. A higher retention of CFTR in the plasma membrane was demonstrated both by FRAP (Fluorescence Recovery After Photobleaching) and photoactivation experiments.
The present data indicate that, in HEK cells, the presence of the G460W-S586C hypertensive variant of adducin increases CFTR channel activity, possibly by altering its membrane turnover and inducing a retention of the channel in the plasma membrane. Since CFTR is known to modulate the activity of many others transport systems, the increased surface expression of the channel could have consequences on the whole network of transport in kidney cells.
Advisors/Committee Members: tutor: G. Meyer, coordinatore: P. Cavallari, MEYER, GIULIANO, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Sassone, F. (2013). MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215231
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sassone, F.. “MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA.” 2013. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/215231.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sassone, F.. “MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA.” 2013. Web. 20 Jan 2021.
Vancouver:
Sassone F. MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/215231.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sassone F. MODULAZIONE DEL CFTR DA PARTE DELLA VARIANTE IPERTENSIVA DELLA PROTEINA CITOSCHELETRICA ADDUCINA. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215231
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
F. Bolzoni.
ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT.
Degree: 2013, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/215234
► In all the experiments we investigated the relationship between the voluntary movement and the postural control. We particularly focused our attention on the role played…
(more)
▼ In all the experiments we investigated the relationship between the voluntary movement and the postural control. We particularly focused our attention on the role played by the APAs, since the general hypothesis is that the postural feed forward control of the movement is strictly bound to the voluntary movement itself in a complex and flexible way.
In the first experiment we tested the hypothesis that APAs preceding an upper-limb target reaching movement could play a role also in controlling the movement accuracy. The aim of this study was seeking a direct proof of the relationship between the APAs amplitude and the endpoint of a target reaching movement.
The aim of the second study was to determine whether a short term immobilization (12 h) interferes in parallel with both the activation of the prime mover muscle, responsible for a given movement, and the postural muscles that are recruited to stabilize the limb.
In the third experiment was aimed at verifying whether the postural activation is affected by the phenomenon of the motor resonance as well as already described for the prime mover activation.
The results of the first experiment reinforce the hypothesis that a successful on-target pointing movement relies upon a specific tuning between APAs and prime mover activation, as that obtained at the end of the adaptation phase.
The most important result of the second experiment is that, although the prime mover activation remains unchanged after the immobilization, the trajectory described by the index finger is most likely changed between the two sessions due to the modification in the postural control that led to a less effective stabilization of the proximal joint, as was suggested by the mechanical model designed by Caronni and Cavallari (2009a).
In the last experiment we demonstrated that the resonant response in resting subjects replicates, under threshold, both the primary movement and postural activity. The precocious increase in excitability observed in BB may be the expression of the anticipatory activation observed during the execution of the movement. Given that MR reflects aspects that are intrinsic to motor programming also this result strongly support the idea that primary movement and the postural command are essential components of the same neural process.
Advisors/Committee Members: tutore: P. Cavallari, coordinatore: P. Cavallari, CAVALLARI, PAOLO, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Bolzoni, F. (2013). ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215234
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Bolzoni, F.. “ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT.” 2013. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/215234.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bolzoni, F.. “ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT.” 2013. Web. 20 Jan 2021.
Vancouver:
Bolzoni F. ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/215234.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bolzoni F. ANTICIPATORY POSTURAL ADJUSTMENTS: FROM POSTURE TO MOVEMENT. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215234
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
9.
M. Ferro.
A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS.
Degree: 2013, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/215237
► An important avenue in neuroscience is represented by a more in depth analysis of cortical activity, the expectation being to find novel correlations between specific…
(more)
▼ An important avenue in neuroscience is represented by a more in depth analysis of cortical activity, the expectation being to find novel correlations between specific animal behaviours or cognitive functions and unique patterns of activity in neurons and synaptic networks. This goal can be reached thanks to the development of novel methodologies that ideally should be sensitive enough to provide quantitative information about single elements but also providing a view of the activity in the entire cortical network. In my laboratory in the last few years we have developed a series of biosensors for the investigation of synaptic activity both in vitro and in the animal in vivo. In order to develop a genetically encoded indicator of synaptic network activity, we have generated a series of reporters of synaptic vesicle re-use. These sensors have been named as the GreenZip family. These indicators report synaptic activation through the uptake of small fluorescent peptidic markers during cycles of exo-endocytosis, whose frequency is greatly enhanced by synaptic transmission and neuro-transmitter release. These new tools have been engineered by modifying the scaffold of the vesicular protein VAMP2 (Synaptobrevin2) through the insertion, at the intraluminal ending, of a "bait" domain with binding activity for a 4 kD peptide dubbed Synbond. The latter is conjugated with a fluorophore or with other detectable molecules. This pair of binders was selected for their high binding affinity (in the nM range) and the reporter gene was named GreenZip (the prefix Green indicates the presence of a GFP molecule at the N-terminal, cytosolic domain). These constructs have been shown to work in cultured neuronal networks (dissociated cultures of hippocampal neurons). The activity-dependent uptake of Synbond was characterized in detail and found to correlate well with synaptic efficacy and with the frequency of stimulation of presynaptic cells. The sensitivity is indeed very high, allowing individual active synapses to be easily visualized after just a few action potentials. To test the feasibility of this method for in vivo analysis, this family of molecules was expressed by electroporation of cDNA in brain slices (cortical, cerebellar and hippocampal cultured slices) and in vivo in the LGN thalamic nuclei (by cDNA electroporation in retinal ganglion cells). In these experiments, we demonstrated that Synbond, diffuses quickly across brain tissue and reaches synapses and an activity-dependent labeling of GreenZip-expressing that synapses can be achieved. This activity-dependent labeling of presynaptic boutons correlates with stimulus duration and light intensity and is already detectable after just a few light pulses. Therefore, this technique permits unprecedented in vivo recordings from large synaptic networks with very high spatial and temporal resolution. These experiments were run in living animals and the detection of GreenZip-expressing synapses (by GFP) and of Synbond uptake was obtained retrospectively after sacrificing the animal,…
Advisors/Committee Members: tutor: A. Malgaroli, coordinatore: P. Cavallari, CAVALLARI, PAOLO, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Ferro, M. (2013). A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215237
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ferro, M.. “A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS.” 2013. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/215237.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ferro, M.. “A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS.” 2013. Web. 20 Jan 2021.
Vancouver:
Ferro M. A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/215237.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ferro M. A NOVEL METHOD FOR FUNCTIONAL ANALYSIS OF SYNAPSES:ASSAY VALIDATION AND DESIGN OF EXPRESSION SYSTEMS FOR IN VIVO EXPERIMENTS ON BRAIN CIRCUITS. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215237
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
10.
A. Frigerio.
A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY.
Degree: 2013, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/215238
► This thesis highlights the current gold-standard surgical procedures for the rehabilitation of mimicry in individuals with facial paralysis and explores the potential application of functional…
(more)
▼ This thesis highlights the current gold-standard surgical procedures for the rehabilitation of mimicry in individuals with facial paralysis and explores the potential application of functional electrical stimulation (FES) as a novel treatment restoring the face mimicry. Closed-loop facial pacing represents an innovative solution for prosthetically assisted movements. In particular, blinking is typically symmetrical, enabling healthy eye blink on one side of the face to serve as a trigger to pace assisted blinks on the contralateral side, in case of unilateral peripheral facial palsy. The goals of this research are developing an eyeblink detection system and advancing the understanding of performing surface FES of the facial nerve in order to elicit artificial eyeblinks. The application of a biomimetic device to individuals with acute reversible facial palsy would provide immediate restoration of the periocular function and could be used until either the patient recovers sufficient function to no longer require assistance for eye closure, or the decision is made to proceed with further surgery.
Advisors/Committee Members: coordinatore: P. Cavallari, tutore: P. Cavallari, CAVALLARI, PAOLO, CAVALLARI, PAOLO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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CSE |
Export
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APA (6th Edition):
Frigerio, A. (2013). A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215238
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Frigerio, A.. “A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY.” 2013. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/215238.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Frigerio, A.. “A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY.” 2013. Web. 20 Jan 2021.
Vancouver:
Frigerio A. A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/215238.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Frigerio A. A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215238
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
S. Zoia.
I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE.
Degree: 2014, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/232732
► TITLE: I CANALI HCN E IL LORO RUOLO NELL’ECCITABILITÀ CARDIACA E NEURONALE PARTE I: CARATTERIZZAZIONE DI CELLULE “SINOATRIAL-LIKE” DA PRECURSORI CD166+ DERIVATI DA mESCs PARTE…
(more)
▼ TITLE:
I CANALI HCN E IL LORO RUOLO NELL’ECCITABILITÀ CARDIACA E NEURONALE
PARTE I: CARATTERIZZAZIONE DI CELLULE “SINOATRIAL-LIKE” DA PRECURSORI CD166+ DERIVATI DA mESCs
PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE - GENERAL INTRODUCTION
HCN channels and the related current (If/h) contribute to many important physiological processes, such as cardiac pacemaker activity and neuronal excitability, in particular setting the membrane resting potential and integrating dendritic signals. - PART I
This part of my project was aimed at developing a biological pacemaker, that is a cellular substrate able to induce ectopic spontaneous activity in the host tissue. Our strategy is based on differentiation of embryonic stem cells (ESCs) and selection of cell progenitors based on expression of the marker CD166, at day 8 of mouse ESC differentiation. CD166 is transiently co-expressed with HCN4, a marker of the cardiac pacemaker tissue, during heart development.
In culture, CD166-selected cells develop into spontaneously beating cells that express low levels of ventricular genes (Cx43, Kv4.2, HCN2, Nkx2.5) and high levels of genes involved both in SAN development (Tbx18, Tbx3, Isl-1, Shox2) and function (Cx30.2, HCN4, HCN1, CaV1.3). Furthermore CD166+ cells form an autorhythmic syncytium made of cells morphologically similar to and with the electrophysiological properties of murine SAN myocytes. Acetylcholine decreases (−23%) and isoproterenol increases (+57%) their beating rate because of the presence of both the muscarinic and β-adrenergic receptors. In co-cultures, these CD166+ cells are also able to pace neonatal ventricular myocytes at a rate faster than their own. Finally, CD166-selected cells do not express pluripotency genes and don’t induce teratomas in vivo. - PART II
Because Ih current is important in the control of neuronal excitability we have carried out a genomic screening of patients affected by temporal lobe epilepsy (TLE) in the search of rare nucleotidic alterations (SNPs) in the genes encoding for the HCN1 and HCN2 isoforms and MiRP1 (KCNE2) which contribute to native Ih. After DNA extraction from blood samples and efforts in PCR condition setting, we’ve been analyzing their sequencings.
Up to now, we’ve found 12 synonymous polymorphisms (SNPs) in hHcn2 and only a deletion in hHcn1 (del 2 gly 73-74). All these DNA variations have been already recorded in the specific database (dbSNP) and were not correlated to epilepsy. Furthermore, we’ve not found any alteration in KCNE2 sequence. - GENERAL CONCLUSIONS
Due to the importance of HCN channels in cellular excitability, they may represent important targets for therapeutic interventions. A cell-based biological pacemaker development would contribute to ameliorate decisively patient quality of life overcoming the major drawbacks associated with electronic devices. Understanding HCN-mediated epilepsy pathological mechanisms could therefore allow to discover drugs able to limit the channel alterations and thus contribute to…
Advisors/Committee Members: tutor: A.F. Barbuti, coordinatore: M. Mazzanti, BARBUTI, ANDREA FRANCESCO, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Zoia, S. (2014). I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232732
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zoia, S.. “I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE.” 2014. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/232732.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zoia, S.. “I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE.” 2014. Web. 20 Jan 2021.
Vancouver:
Zoia S. I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/232732.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zoia S. I CANALI HCN E IL LORO RUOLO NELL'ECCITABILITÀ CARDIACA E NEURONALE - PARTE I: CARATTERIZZAZIONE DI CELLULE 'SINOATRIAL-LIKE' DA PRECURSORI CD166+ DERIVATI DA MESCS - PARTE II: SCREENING GENETICO DI PAZIENTI AFFETTI DA EPILESSIA DEL LOBO TEMPORALE. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232732
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
12.
D.A. Civello.
ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN.
Degree: 2014, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/232734
► ICln è una proteina di 209 aminoacidi clonata nel 1992. Componente fondamentale del proteoma cellulare, è una proteina altamente conservata, ubiquitariamente espressa e il suo…
(more)
▼ ICln è una proteina di 209 aminoacidi clonata nel 1992. Componente fondamentale del proteoma cellulare, è una proteina altamente conservata, ubiquitariamente espressa e il suo knock-out è letale. ICln è stata inizialmente associata alla formazione della corrente IClswell, corrente di cloruro attivata in seguito a stress ipo-osmotico e fondamentale per i meccanismi omeostatici di regolazione del volume cellulare. In questi meccanismi, ICln gioca un ruolo di primo piano; infatti è stato dimostrato che anche batteri esprimenti ICln diventano altamente tolleranti a stress di natura ipo-osmotica, mentre l'inibizione della sua espressione provoca una diminuzione dell'IClswell. Nonostante risulti evidente l'importanza di ICln nella attivazione e nella regolazione della corrente, non è ancora chiaro il ruolo molecolare della proteina. In questo senso, l'impossibilità di effettuare un knock-out della proteina risulta essere un ostacolo per la sua caratterizzazione. ICln non è però coinvolta solo nei meccanismi di regolazione omeostatica del volume. Nel corso degli anni, parallelamente ad esperimenti che ne descrivevano i diversi e numerosi partner molecolari, sono state proposte nuove e più ampie funzioni per ICln, riguardanti la regolazione dello splicing e della proliferazione cellulare, della stabilità di membrana e delle interazioni cellulari. Fra le varie proteine in grado di legare con ICln, di particolare importanza sono le interazioni con le proteine citoscheletriche actina, miosina e la proteina 4.1. Quest'ultima è una proteina strutturale, multifunzionale, inizialmente individuata nei globuli rossi e associata alla regolazione della plasticità e
5
resistenza della membrana cellulare. Anche per 4.1, nel corso degli anni, sono state individuati numerosi partner molecolari e numerose funzioni. Inoltre, in aggiunta alla proteina 4.1 inizialmente identificata negli eritrociti, sono state poi individuate varie isoforme presenti in molteplici organi e tessuti. Nel laboratorio dove ho svolto la tesi, in particolare, sono state studiate le due principali isoforme della 4.1 eritrocitica (4.1R): una isoforma ad alto peso molecolare, 4.1R135 di 135 kDa, e una isoforma a basso peso molecolare, 4.1R80 di 80 kDa. Queste due isoforme sono originate dall'utilizzo di due diversi siti di inizio trascrizione e differiscono fra loro unicamente per la presenza o assenza delle regione N-terminale U1, di 209 aminoacidi. In precedenti esperimenti di FRET, coimmunoprecipitazione e western blot si è osservato che le due isoforme sono in grado di interagire con ICln. In particolare i risultati ottenuti sembrano suggerire che tale interazione è in grado di influenzare la localizzazione subcellulare della 4.1R a livello della membrana. Considerando che sia ICln che la proteina 4.1R svolgono funzioni fondamentali a livello di questo distretto subcellulare, scopo del mio lavoro è stato quello di approfondire alcuni aspetti funzionali legati all'interazione fra le due proteine. Si è quindi cercato inizialmente di approfondire…
Advisors/Committee Members: tutor: G. Meyer, coordinatore: M. Mazzanti, MEYER, GIULIANO, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Civello, D. (2014). ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232734
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Civello, D.A.. “ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN.” 2014. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/232734.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Civello, D.A.. “ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN.” 2014. Web. 20 Jan 2021.
Vancouver:
Civello D. ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/232734.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Civello D. ASPETTI FUNZIONALI DELL'INTERAZIONE TRA 4.1R E ICLN. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232734
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
13.
S. Melfi.
NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES.
Degree: 2018, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/564819
► The origin, development and maturation of Schwann cells (SCs), the main glial cells of the peripheral nervous system (PNS), are a set of complicated and…
(more)
▼ The origin, development and maturation of Schwann cells (SCs), the main glial cells of
the peripheral nervous system (PNS), are a set of complicated and intriguing processes.
These multifactorial processes take place following a precise and unique coordination
between different molecules and intracellular signaling, that interact with a complex of
endogenous and exogenous signals. Among these, there are integrins, neuregulins,
growth factors, hormones, neurotransmitters and intracellular pathway, including
protein kinase A and protein kinase C (PKA and PKC), serine/threonine kinase 1
(AKT), extracellular regulated MAPK/mitogen-activated protein kinase 1
(ERK/MAPK), Hippo, mechanistic target of rapamycin (mTOR), etc.
This thesis is focused on some novel intracellular signaling pathways involved in the
SCs development and maturation, from their origin to the acquisition of the myelinating
or repairing phenotype.
The first part of the thesis focuses on a proto-oncogene, the non-receptor tyrosine kinase
SRC (SRC), and the focal adhesion kinase (FAK), which are intermediate pathways
known to play a role in the control of adhesion, motility, and migration of SCs. It has
been investigated whether these pathways are regulated by allopregnanolone (ALLO),
a neuroactive steroid of peculiar interest for the control of SCs maturation.
The second part of this thesis focuses on the study of the Hippo signaling pathway,
known to be a key regulator of proliferation, apoptosis, control of organ size and
crucial for cancer proliferation. Hippo pathway has been studied in SCs, where it is
linked to Merlin (an oncosuppressor protein) and Yes associated protein/tafazzin
(YAP/TAZ) factors. Interestingly, these mechanisms were responsive to physical and
environmental challenges. Lastly, the third part of this thesis move on studying the role of the g-aminobutyric acid
(GABA) system in the control of peripheral myelination. In particular, the whole
expression profile was investigated in conditional knock out mice for the B1 subunit of
the GABA-B receptor (GABA-B R), with a specific deletion in SCs. By the use of
microarray technology, several genes resulted up- or downregulated in SCs, opening
new perspectives on the possible targets downstream GABA-B R in SCs.
Overall, these results highlight new aspects of the SCs biology, shedding light on
unraveled mechanisms and underlying their importance in the development and
maturation of these specialized cells of the PNS. This may be of pharmacological and
therapeutically interest, in order to identify reliable approaches for the treatment of
PNS diseases.
Advisors/Committee Members: phd school coordinator: C. Sforza, phd supervisor: V. Magnaghi, MAGNAGHI, VALERIO, SFORZA, CHIARELLA, MAGNAGHI, VALERIO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Melfi, S. (2018). NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/564819
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Melfi, S.. “NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES.” 2018. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/564819.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Melfi, S.. “NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES.” 2018. Web. 20 Jan 2021.
Vancouver:
Melfi S. NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/564819.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Melfi S. NEW SIGNALING PATHWAYS REGULATING SCHWANN CELLS OF THE PERIPHERAL NERVOUS SYSTEM: IMPLICATIONS IN PERIPHERAL NEUROPATHIES. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/564819
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
14.
M. Fecchio.
SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/338759
► The human brain is able to generate a wide repertoire of behavioral and psychological phenomena spanning from simple motor acts to cognition, from unimodal sensory…
(more)
▼ The human brain is able to generate a wide repertoire of behavioral and psychological phenomena spanning from simple motor acts to cognition, from unimodal sensory perceptions to conscious experience. All these abilities are based on two key parameters of cortico-thalamic circuits functioning: the reactivity to a direct, local stimulation (cortical excitability) and the ability to causally interact (cortical effective connectivity). Indeed, alterations of these parameters have been suggested to underlie neurologic and psychiatric conditions. Over the last ten years, high-density electroencephalography combined with transcranial magnetic stimulation (TMS/hd-EEG) has been used to non-invasively probe cortical excitability and connectivity and to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits.
A recently proposed theory suggests that consciousness depends on the brain’s ability to engage in complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). In a recent series of experiments the electroencephalographic TMS-evoked brain response was recorded in healthy subjects during wakefulness, non-rapid eyes movement sleep (NREM), under pharmacological conditions (anesthesia), and pathological conditions (severely brain-injured, vegetative state patients). Indeed, TMS/hd-EEG measurements showed that during wakefulness the brain is able to sustain long-range specific patterns of activation, while when consciousness fades in NREM sleep, anesthesia and vegetative state, the thalamo-cortical system produces either a local or a global slow wave which underlies respectively a loss of differentiation or integration.
We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS are due to bistability between periods of neuronal activity (up-state) and silence (down-state) in cortical networks. Thalamo-cortical bistability could impair the ability of thalamo-cortical circuits to sustain long-range, differentiated patterns of activation, a key theoretical requisite for consciousness. Animal studies show that the extracellular signature of the down-state is a transient suppression of high frequency (>20Hz) power in the local field potential (LFP). More recently, intracranial recordings during NREM sleep in humans have shown that a intracranial stimulations induce a widespread suppression of high frequencies (i.e. cortical down-states) that impair the ability of thalamo-cortical circuits to engage in causal interactions.
In the present thesis we use a TMS/hd-EEG approach in patients affected by disorders of consciousness such as vegetative state (VS) and minimally conscious state (MCS) to investigate whether bistability could underlie also pathological loss of consciousness. To verify this hypothesis, we recorded TMS-evoked potentials (TEPs) in awake VS and MCS patients as well as in healthy controls (HC) during wakefulness and NREM sleep. TEPs…
Advisors/Committee Members: tutor: C. E. Rosanova, coordinatore: M. Mazzanti, ROSANOVA, MARIO CARMINE EMILIANO, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Fecchio, M. (2015). SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/338759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fecchio, M.. “SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/338759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fecchio, M.. “SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS.” 2015. Web. 20 Jan 2021.
Vancouver:
Fecchio M. SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/338759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fecchio M. SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/338759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
15.
G. Puglisi.
THE ROLE OF ATTENTION IN MOTOR RESONANCE.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/340320
► Motor pathways are activated not only during the obvious task of producing voluntary movement, but also during observation of actions performed by others. Execution and…
(more)
▼ Motor pathways are activated not only during the obvious task of producing voluntary movement, but also during observation of actions performed by others. Execution and observation share a common pattern of activation, so that a subliminal "motor resonance" (MR) response is evoked, in primary motor cortex and spinal circuits, which reflects the specific motor program encoding the observed actions. There is growing evidence that MR is mediated by a parieto-frontal neural network, called the “Action Observation Network” (AON). While often described as an automatic and cognitively unmediated response, there is some experimental evidence suggesting that MR can in fact be modulated by cognitive processes. In this thesis the role of attention during the observation of a grasping action in both central and peripheral vision was investigated in three different studies. In the first study, the level of attention that 56 subjects allocated to the observation of a cyclic flexion-extension hand movement was manipulated in four different experimental conditions. MR was measured as the excitability modulation of spinal motoneurones innervating a wrist flexor muscle (flexor carpi radialis), utilizing the H-reflex technique. In the first experiment (explicit observation) 14 subjects were asked to pay attention exclusively to the cyclic oscillatory movement of a hand. In the second experiment (semi-implicit observation) the attention of 14 different subjects was partly diverted from the hand movement, since they needed to monitor hand position in order to perform a parallel task. In the third experiment (implicit observation) 14 different subjects had to complete yet a different parallel task for which the hand movement was totally irrelevant. The modulation of H-reflex amplitude, i.e. of the MR response, in these experimental conditions was compared to a baseline condition, in which 14 new subjects observed the cyclic oscillatory movement of a mechanical device, which does not evoke any motor resonant response. Results show that attention manipulation in both second and third 5 experiments dramatically decreased the amplitude of the MR response, while not affecting its muscular and temporal specificity. These results support the hypothesis that MR response is not a fully automatic process, but can be modulated by top-down influences, such as selective attention. In the second study, MR was investigated during observation of actions viewed in the peripheral field, where vision is far less accurate and where they don’t automatically receive the same level of attention as in central vision. The excitability modulation of motor pathways was recorded, this time utilizing the Transcranial Magnetic Stimulation (TMS) technique, in 40 subjects who were asked to pay attention to a central fixation point on a screen while a hand grasping action was shown at 10° in their peripheral field of vision. TMS was selected for these experiments because it allows recording from more than one muscle simultaneously. Half of the subjects observed a video…
Advisors/Committee Members: tutor: P.A. Borroni, coordinatore: M. Mazzanti, BORRONI, PAOLA ALICE, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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CSE |
Export
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Manager
APA (6th Edition):
Puglisi, G. (2015). THE ROLE OF ATTENTION IN MOTOR RESONANCE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/340320
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Puglisi, G.. “THE ROLE OF ATTENTION IN MOTOR RESONANCE.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/340320.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Puglisi, G.. “THE ROLE OF ATTENTION IN MOTOR RESONANCE.” 2015. Web. 20 Jan 2021.
Vancouver:
Puglisi G. THE ROLE OF ATTENTION IN MOTOR RESONANCE. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/340320.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Puglisi G. THE ROLE OF ATTENTION IN MOTOR RESONANCE. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/340320
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
16.
M. Angelini.
ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/268235
► Ion channels are transmembrane proteins that allow and control the flux of ions (sodium, potassium, calcium, and chloride) across the plasma membrane. They are present…
(more)
▼ Ion channels are transmembrane proteins that allow and control the flux of ions (sodium, potassium, calcium, and chloride) across the plasma membrane. They are present in all cell types and play critical roles in a variety of biological processes. Historically, ion channels have always been an attractive target for the treatment of different pathologies mainly because numerous drugs can specifically bind ion channels modifying their functional activity. My PhD thesis addresses the role of two different ion channels in the two leading causes of death in the modern society: heart disease and cancer. The first part of this PhD dissertation, developed at University of Milan under the mentorship of Prof. Michele Mazzanti, focuses on understanding the role of CLIC1 channels in glioblastoma cancer stem cells (CSCs). Glioblastoma is the most lethal among brain tumors. As other solid tumors, this cancer is composed of two cell types: a small population of cells able to self-renew and generate progeny (CSCs) and a larger population of differentiated cells (bulk cells). Glioblastomas are very aggressive tumors because of CSCs brain infiltration efficiency and resistance to chemotherapies. CLIC1 is a metamorphic protein mainly present as a soluble form in the cytoplasm that is able to translocate to the plasma membrane in response to oxidative stimuli where it acts as a Cl- channel. Several forms of glioblastomas show a high level of expression of CLIC1 compared to normal brains tissue. In electrophysiological experiments, overexpression of CLIC1 in murine CSCs were associated with a specific increase of the protein at the plasma membrane compared to normal stem cell (NSC). To study the relevance of CLIC1 we used CSCs isolated from human glioblastoma biopsies. By knocking down CLIC1 protein using siRNA viral infection (siCLIC1), we found that CLIC1-deficient cells proliferate less efficiently than control cells infected with siRNA for luciferase (siLUC). Since CLIC1 is a dimorphic protein we asked whether the reduction in proliferation was due to CLIC1 as ion channel. We performed perforated patches electrophysiological experiments for both siLUC and siCLIC1 cells. Cl- currents mediated by CLIC1 were isolated using IAA94, a CLIC1 ion channel inhibitor. The results showed that siCLIC1 cells did not display IAA94-sensitive currents, while siLUC cells presented the CLIC1-mediated chloride current. These findings strongly suggest that CLIC1 ion channel activity is required in the proliferation activity of CSCs, and therefore represents a promising target direct in the reduction of CSC gliomagenesis. To target CLIC1 ion channel, the only effective drug so far identified is IAA94 which seems to be rather specific but toxic. For this reason we sought non-toxic drugs that could interact with CLIC1 ion channel. Epidemiological and preclinical studies propose that Metformin, a first-line drug for type-2 diabetes, exerts direct antitumor activity specifically on CSCs. Although several clinical trials are ongoing, the molecular mechanisms…
Advisors/Committee Members: tutor e coordinatore: M. Mazzanti, co-tutor: R. Olcese, MAZZANTI, MICHELE, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Angelini, M. (2015). ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/268235
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Angelini, M.. “ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/268235.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Angelini, M.. “ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS.” 2015. Web. 20 Jan 2021.
Vancouver:
Angelini M. ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/268235.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Angelini M. ROLE OF CLIC1 AND L-TYPE CALCIUM CHANNELS IN THE PATHOPHYSIOLOGY OF GLIOBLASTOMA AND VENTRICULAR ARRHYTHMIAS. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/268235
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
17.
C. Corbellini.
DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/379341
► Rationale: The diaphragm pathophysiological changes occurring in chronic obstructive pulmonary disease (COPD) leads to functional inefficiency that strongly correlates to the loss of lung function.…
(more)
▼ Rationale: The diaphragm pathophysiological changes occurring in chronic obstructive pulmonary disease (COPD) leads to functional inefficiency that strongly correlates to the loss of lung function. Muscle fiber shortening follows lung hyperinflation, resulting to a chronic mechanical disadvantage, which worsens in COPD exacerbations. The diaphragmatic mobility (DM) is mostly assessed with techniques that exposes the patient to risks. The ultrasonography on M-mode is easy to use, safe and measures directly the diaphragmatic dome displacement.
Goals: to determine whether the COPD impairs the DM, and verify improvements after an inpatient pulmonary rehabilitation (PR).
Methods: ultrasonography on M-mode assessed the rest breathing and the slow deep inspiration on 52 patients and 15 healthy controls. Lung functions test, arterial blood gas analyses, six minute walk test were also performed.
Results: after initial screening, 36 COPD patients ended the PR. The DM was lower on the slow deep inspiration on COPD patients and correlated with the COPD severity (r=0.8, p<0.001). The DM on rest breathing was higher for COPD patients and also correlated to the lung disease severity (r=0.74, p<0.001). After the PR the DM on the slow deep inspiration increases from 4.58cm±1.83cm to 5.45cm±1.56cm (p<0.01).
Conclusions: ultrasonography on M-mode showed the correlation between DM impairment and COPD severity. The PR improves diaphragmatic function.
Advisors/Committee Members: tutor: L. Zocchi, coordinatore: M. Mazzanti, ZOCCHI, LUCIANO ALDO MARIA, MAZZANTI, MICHELE.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Corbellini, C. (2015). DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/379341
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Corbellini, C.. “DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/379341.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Corbellini, C.. “DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION.” 2015. Web. 20 Jan 2021.
Vancouver:
Corbellini C. DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/379341.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Corbellini C. DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND EFFECTS OF THE PULMONARY REHABILITATION. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/379341
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
18.
E. Signoretto.
ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS.
Degree: 2017, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/467800
► The present study focus attention on “Aspects of cellular iron homeostasis: NRAMP transporter function and eryptosis” combining aspects of both basic (first chapter: “Iron transporters…
(more)
▼ The present study focus attention on “Aspects of cellular iron homeostasis: NRAMP transporter function and eryptosis” combining aspects of both basic (first chapter: “Iron transporters NRAMP1 and NRAMP2 from Dictyostelium discoideum as a model of cellular iron homeostasis”) and applied physiology (second chapter: “Effects of xenobiotics on the suicidal death of erythrocytes”). Iron plays a central role in a large number of essential cellular functions but it is also potentially toxic being able to generate reactive oxygen species (ROS). SLC11 and SLC40 families are involved in iron transport and play an important role in the maintenance of iron homeostasis. The SLC11 family is comprised of two members, SLC11A1 and SLC11A2. SLC11A1 is expressed in the phagolysosome of macrophages and in the tertiary granules of neutrophils and it contributes to the innate resistance against bacterial infection. SLC11A2 (also known as DMT1) is expressed in the proximal duodenum, immature erythroid cells, brain, placenta and kidney and is a key player in iron metabolism. Intestinal iron absorption is indeed mediated by SLC11A2 at the apical membrane of enterocytes and is followed by basolateral exit via SLC40A1. D. discoideum represents a model for the study of cellular iron homeostasis, showing subcellular localization of iron transporters resembling that of macrophages. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis; in particular, D. discoideum expresses the ortholog of SLC11A1 transporter in phagolysosomes and that of SLC11A2 in the contractile vacuole. To better understand the function of Dictyostelium NRAMP proteins, they were expressed in Xenopus laevis oocytes by cRNA injection and functionally tested by radiochemical techniques and by a novel assay based on metal-induced changes in calcein fluorescence. Radiochemical assays showed that NRAMP1 induced iron transport is proton-dependent and it is inhibited by Mn2+, Cd2+, Co2+, Ni2+, Cu2+ and to a lesser extent by Zn2+. In calcein-injected oocytes expressing NRAMP1 and analyzed using confocal microscopy, Fe2+, Mn2+ and but not Fe3+ or Cu2+ led to fluorescence quenching due to their transport and accumulation into the cytoplasm of the oocytes. Therefore Dictyostelium NRAMP1 is an electrogenic proton-dependent divalent metal ion transporter with a cation selectivity comparable to that of rat DMT1. NRAMP1 colocalizes with V-ATPase in the membrane of phagolysosomes. Thus, it exploits the proton gradient maintained by the V-ATPase to mediate the efflux of iron from the phagolysosomes to the cytosol after bacterial engulfment. Preliminary studies showed that D. discoideum NRAMP2 can transport ferrous iron at neutral pH and it appears independent from proton gradient but dependent on Na+, nevertheless its transport activity is strongly reduced compared with that observed for NRAMP1. The second topic of this PhD thesis is eryptosis, the suicidal death of erythrocytes. Mutations that reduce DMT1 activity in human are associated with a severe defect in…
Advisors/Committee Members: tutor: M. Castagna, co-tutor: F. Lang, CASTAGNA, MICHELA.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Signoretto, E. (2017). ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/467800
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Signoretto, E.. “ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS.” 2017. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/467800.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Signoretto, E.. “ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS.” 2017. Web. 20 Jan 2021.
Vancouver:
Signoretto E. ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/467800.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Signoretto E. ASPECTS OF CELLULAR IRON HOMEOSTASIS: NRAMP TRANSPORTER FUNCTION AND ERYPTOSIS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/467800
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
19.
A. Leonetti.
DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE.
Degree: 2019, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/608382
► Brain tumour is an infiltrating disease harbouring within the central nervous system (CNS) causing Cognitive and Mood Disorders. The prognosis is very poor. The optimization…
(more)
▼ Brain tumour is an infiltrating disease harbouring within the central nervous system (CNS) causing Cognitive and Mood Disorders. The prognosis is very poor. The optimization of the surgical procedure with the aid of Brain Mapping Technique (BMt) allows to extending the resection of the tumour beyond its boundaries (supramarginal resection), increasing the patients’ survival while preserving the patients’ functional integrity, assuring them the best possible Health Related Quality of Life (HRQoL). However, despite the advanced surgical procedure, patients face many stressors in the course of the disease, among which the Cognitive deficits leading in Mood Disorders. Notably, Mood disorders, in turn, dramatically affect the HRQoL, the survival and other crucial aspect of care including the compliance to treatment (Litofsky et al. 2004, Maino et al. 2006). The negative influence of Cognitive and Mood Disorders on HRQoL is still a matter of debate. At present is indeed still unsolved the critical issue of whether are the clinical features related to the tumour, or rather the psychological response to the stressors secondary to the care, to be considered the main predicting factors for emergence of Mood Disorders in brain tumour patients (Madhusoodanan 2015).
Based on these premises the present PhD study investigated the association between Mood Disorders, the specific clinical and anatomical features related to the tumour itself, and the patients’ cognitive outcome with the aim of disclosing the influence of Cognitive and Mood Disorders on HRQoL before and after treatments in patients with brain tumour and, accordingly, of developing specific “interventions” aimed at improving the patient’s HRQoL.
The results of the study, conducted on 116 patients who underwent awake procedure for tumour resection, showed that Mood Disorders were not associated with the clinical features of brain tumour per se, as might be expected, but rather they were associated with the lack of recovery from Cognitive post-surgical deficits and, among the possible Cognitive deficits, specifically language, attentive/executive and visual deficits. Moreover the HRQoL turned out to be negatively affected by both the lack of cognitive recovery and by the occurrence of Mood Disorders, especially in the long run (3, 6 months after treatments).
Based on these results, in order to reduce the incidence of Mood Disorders and to improve the HRQoL of the patients affected by brain tumour, two new intraoperative tools designed to map and preserve the networks involved in the attentive/executive and visual functions were designed and tested in the intraoperative setting.
The feasibility of the new “intraoperative Stroop tools - iST” and its accuracy in preserving attentive/executive functions (EF) was assessed in 45 patients affected by glioma and candidate for tumour resection during the awake-asleep-awake surgery. The results showed that iST was successfully administered intraoperatively in all patients with high feasibility and reduced dramatically the…
Advisors/Committee Members: tutor: G. Cerri, coordinator: C. Sforza, CERRI, GABRIELLA, SFORZA, CHIARELLA.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Leonetti, A. (2019). DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/608382
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Leonetti, A.. “DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE.” 2019. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/608382.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Leonetti, A.. “DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE.” 2019. Web. 20 Jan 2021.
Vancouver:
Leonetti A. DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/608382.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Leonetti A. DETERMINANT FACTORS OF MOOD DISORDERS IN BRAIN CANCER PATIENTS:DEVELOPMENT OF NOVEL INTRAOPERATIVE TOOLS IMPACT ON PROGNOSIS AND QUALITY OF LIFE. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/608382
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
A.P. Moorhead.
THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS.
Degree: 2019, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/605781
► The mechanics of locomotion classically take into account the work done by muscle force to raise and accelerate the body center of mass and to…
(more)
▼ The mechanics of locomotion classically take into account the work done by muscle force to raise and accelerate the body center of mass and to accelerate limbs with respect to it at each step. This last component, named Internal Work (W_INT), considers only the cost to overcome segment inertia, inherently assuming frictionless joints. Thus, the unavoidable damping opposing segmental oscillation due to anatomical structures within or around the pivoting centers has never been measured so far.
The frictional coefficient (b, N.m.s.rad-1) of such a biological rotational damper has been here assessed by sampling the time course of passive oscillation (with respect to the vertical axis) of upper and lower limbs and by analyzing its motion. This experiment (straight pendulum) was performed to assess joint energy dissipation during the swing phase of locomotion. A custom mathematical model, leading to a 2nd Order Non-Linear Ordinary Differential Equation, allowed to infer b values for upper (bUU = 0.39 ± 0.08) and lower (bUL = 2.24 ± 0.56 N.m.s.rad-1) limbs in 16 healthy males. Phase planes ensured that no muscle activity was involved. In the same population, the passive swing of a lower limb, behaving as an inverted pendulum after a push (body upside-down), was also sampled while loading the leg as to replicate the compressive stress to which the hip joint is exposed during stance phase. Loads ranged from 0 N (mass of leg only) to 118 N. Damper values (b) for the inverted swing of a loaded lower limb increased with the load and ranged from 4.89 ± 1.29 to 8.92 ± 1.74 N.m.s.rad-1.
The influence on locomotion mechanics has been here evaluated. In walking, for instance, each step includes 3 'passively' swinging, unloaded segments (2 upper limbs and the swinging lower limb with joints under tensile stress) and 1 'actively' oscillating, almost fully loaded segment (stance lower limb, joint under compressive stress). The actual experimental results have been combined to provide an estimate of the internal mechanical work due to tissue and joint damping. In walking that is comparable (and should be added) to the estimate obtained by means of a kinematics-based model (Minetti, 1998) and experimental data from the literature of the traditional ‘kinematic’ W_INT. In the discussion, the potential overestimation and underestimation of those two types of internal work are presented, together with the implications of the presented additional work (and its metabolic equivalent) to the energy balance and efficiency of human locomotion.
Advisors/Committee Members: tutor: A.E. Minetti, coordinatore C. Sforza, MINETTI, ALBERTO ENRICO.
Subjects/Keywords: Settore BIO/09 - Fisiologia
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APA (6th Edition):
Moorhead, A. (2019). THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/605781
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Moorhead, A.P.. “THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS.” 2019. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/605781.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Moorhead, A.P.. “THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS.” 2019. Web. 20 Jan 2021.
Vancouver:
Moorhead A. THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS. [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/605781.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Moorhead A. THE DAMPED OSCILLATIONS OF PASSIVE LIMBS AND THEIR ROLE IN HUMAN LOCOMOTION MECHANICS. [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/605781
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
C. Zanoni.
STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150162
► ICln is a multifunctional protein that has been implicated in many cellular functions, from cell volume regulation to RNA metabolism. It interacts with many members…
(more)
▼ ICln is a multifunctional protein that has been implicated in many cellular functions, from cell volume regulation to RNA metabolism. It interacts with many members or regulators of the cytoskeleton, like the 4.1R protein, actin, myosin light chain and the JBP1 protein. This suggests that the cytoskeleton rearrangement that follows an hypotonic challenge could be involved in the translocation of the ICln protein from the cytosol to the cell membrane and in the activation of the ICl,swell. In this work we tried to elucidate the role of ICln-4.1R interaction in the context of Regulatory Volume Decrease; we focused on the in vivo interaction between ICln and the protein 4.1R by the use of the FRET technique. We used two different 4.1R isoforms for the FRET experiments: an high molecular weight (HMW) isoform (4.1 long) and a low molecular weight (LMW) one (4.1 short, without the initial 209 aa box). The strongest FRET signal was measured between ICln and 4.1Rsh, and it was significally increased by an hypotonic shock. Moreover, when the two proteins are co-expressed and interact, it seems that the two proteins change each other localization showing a decreased nuclear and, for 4.1R, membrane localization. From a functional point of view, preliminary patch-clamp experiments suggest that the over-expression of the 4.1sh isoform in HEK cells leads to an increase of the ICl,swell (the anion current that allows RVD) activation, thus confirming a role for 4.1R in cell volume regulation.
Advisors/Committee Members: tutor: Giuliano Meyer, coordinatore: Paolo Cavallari, MEYER, GIULIANO, CAVALLARI, PAOLO.
Subjects/Keywords: ICln; 4.1R; RVD; Settore BIO/09 - Fisiologia
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APA (6th Edition):
Zanoni, C. (2010). STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150162
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zanoni, C.. “STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150162.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zanoni, C.. “STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI.” 2010. Web. 20 Jan 2021.
Vancouver:
Zanoni C. STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150162.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zanoni C. STUDIO DELL'INTERAZIONE TRA LE PROTEINE CITOSCHELETRICHE 4.1R80 E 4.1R135 E LA PROTEINA ICLN: ASPETTI MOLECOLARI E FUNZIONALI. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150162
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
22.
C. Donadoni.
STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS.
Degree: 2018, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/570248
► Ion channels are membrane proteins that control crucial physiological and pathological processes in all organisms. Channels are often composed by different subunits, forming macromolecular protein…
(more)
▼ Ion channels are membrane proteins that control crucial physiological and pathological processes in all organisms. Channels are often composed by different subunits, forming macromolecular protein complexes. They include α subunits, which are the pore-forming channel subunits, and they also include β subunits, which associate to the α subunits and can regulate channel function, surface expression and trafficking (Yu et al. 2005).
Hyperpolarization-activated cyclic nucleotide gated channels (HCN1-4) are the molecular determinants of the so-called pacemaker current If/h current which controls cell excitability both in the brain and in the heart (Robinson & S. a Siegelbaum 2003).
HCN channels are dually activated by membrane hyperpolarization and cAMP binding to their cyclic nucleotide binding domain (CNBD); moreover, several regulatory β subunits have been reported to regulate HCN channels (Robinson & S. a Siegelbaum 2003), among which TRIP8b.
The cytoplasmatic tetratricopeptide repeat containing Rab8b interacting protein (TRIP8b) is an auxiliary β subunit of neuronal HCN isoforms, governing ion channel trafficking and gating. The interaction between HCN and TRIP8b proteins is already well explained in molecular details and takes place at two distinct sites: an upstream binding site where the CNBD of HCN channels interacts with an 80 aa domain in the conserved central core of TRIP8b (called miniTRIP8b); and a downstream site where the C-terminal SNL (Ser-Asn-Leu) tripeptide of the channel interacts with the tetratricopeptide repeat domain of TRIP8b (Santoro et al. 2011).
In my thesis, I identified some key residues on the CNBD important for complex formation, and finally I was able to obtain an HCN double mutant N547D/A548C unable to bind TRIP8b at the upstream binding site. This will prevent the regulation of channel activity by its β subunit without affecting the regulation of channel trafficking. This mutant represents an important tool that can be used in vivo to investigate the physiological importance of TRIP8b regulation of HCN channels in certain brain regions, such as the hippocampus.
Recently HCN channels were found to interact with Mint proteins. Less is known about this new interaction. Mints are a class of adaptor proteins which contain protein-protein interaction domains through which they mediate the assembly of functional multiprotein complexes (Rogelj et al. 2006).
The study of Mint proteins has become central in Alzheimer’s disease. Indeed, Mint proteins are known to directly bind the cytoplasmic tail of APP. This binding is important to regulate APP trafficking and notably also its cleavage, thus β-amyloid peptide (Aβ) production (Rogelj et al. 2006).
Mints were recently reported to interact with HCN channels (Saito et al. 2012; Kimura et al. 2004) but neither the nature of the binding (direct vs. indirect) nor the interaction site between the two partners is so far known. In my thesis I have performed a preliminary characterization of this new interaction by a combination of in…
Advisors/Committee Members: scientific tutor: A. Moroni, MORONI, ANNA.
Subjects/Keywords: HCN, TRIP8b, Mint; Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
Donadoni, C. (2018). STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/570248
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Donadoni, C.. “STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS.” 2018. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/570248.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Donadoni, C.. “STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS.” 2018. Web. 20 Jan 2021.
Vancouver:
Donadoni C. STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS. [Internet] [Thesis]. Università degli Studi di Milano; 2018. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/570248.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Donadoni C. STUDY OF THE INTERACTION BETWEEN HCN CHANNELS AND THEIR REGULATORY SUBUNITS TRIP8B AND MINT PROTEINS. [Thesis]. Università degli Studi di Milano; 2018. Available from: http://hdl.handle.net/2434/570248
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
23.
A.C. Saponaro.
THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM.
Degree: 2014, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/229903
► In neurons, hyperpolarization-activated cyclic nucleotide-regulated (HCN1-4) channels are the molecular determinants of the Ih current, which controls several cognitive processes. Unique among the voltage-gated ion…
(more)
▼ In neurons, hyperpolarization-activated cyclic nucleotide-regulated (HCN1-4) channels are the molecular determinants of the Ih current, which controls several cognitive processes. Unique among the voltage-gated ion channel superfamily, HCN channels are modulated by the direct binding of cAMP to their cytoplasmic cyclic nucleotide binding domain (CNBD). Thus, cyclic nucleotide-dependent conformational changes of CNBD are determinant in the regulation of HCN channel opening. The rearrangements induced by cAMP in HCN CNBD are not yet elucidated, since for this protein is known only the cAMP-bound form. HCN channels are further regulated by their association with the auxiliary protein TRIP8b, which preferentially binds to the cAMP-unbound CNBD and opposes cAMP regulation. Recently, we proposed a cyclic allosteric model to explain the mutual antagonistic effect of TRIP8b and cAMP. Here, to validate this model, we first determined the model structure of the human HCN2 CNBD in the cAMP-unbound form using NMR methodologies. By comparing the cAMP-unbound and cAMP-bound structures we highlighted all the conformational changes allosterically coupled to the channel opening transition. Subsequently, we mapped the TRIP8b binding site onto the cAMP-unbound CNBD. Our results show that cAMP and TRIP8b do not compete for the same binding region, and support our allosteric antagonistic model for the dual regulation of HCN channels by cAMP and TRIP8b.
Advisors/Committee Members: tutor: A. Moroni, MORONI, ANNA, DE MICHELIS, MARIA IDA, BELTRAME, MONICA DANIELA.
Subjects/Keywords: HCN channels; cAMP; TRIP8b; Settore BIO/10 - Biochimica; Settore BIO/09 - Fisiologia
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APA ·
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Export
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APA (6th Edition):
Saponaro, A. (2014). THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229903
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Saponaro, A.C.. “THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM.” 2014. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/229903.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Saponaro, A.C.. “THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM.” 2014. Web. 20 Jan 2021.
Vancouver:
Saponaro A. THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/229903.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Saponaro A. THE AUXILIARY SUBUNIT TRIP8B ANTAGONIZES THE BINDING OF CAMP TO HCN2 CHANNELS THROUGH AN ALLOSTERIC MECHANISM. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229903
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
24.
M. Marzagalli.
NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS.
Degree: 2015, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/340726
► Malignant melanoma represents the deadliest form of skin cancer: despite surgical resection of cutaneous in situ melanoma warrants a good prognosis, metastatic melanoma is mostly…
(more)
▼ Malignant melanoma represents the deadliest form of skin cancer: despite surgical resection of cutaneous in situ melanoma warrants a good prognosis, metastatic melanoma is mostly an incurable disease, because of the fast developing of resistance to existing therapies. For this reason, the identification of novel molecular targets and more effective antitumor compounds might be helpful in the management of the pathology.
Clinical observations indicate that estrogen receptor β (ERβ) is expressed in melanoma tissues and its expression decreases with tumor progression, suggesting its anticancer activity. Moreover, this receptor was found to mediate the antitumor effect of the vitamin E derivative δ-tocotrienol on breast cancer cell lines.
This project firstly focused on the characterization of the estrogenic system on human melanoma cell lines. ERβ is expressed in melanoma cell lines but one, and proliferation and transactivation studies indicated that specific ERβ ligands exert an antiproliferative activity inducing the classical, nuclear mechanism of action of steroid hormones receptors. This antitumor effect is due to a G1/S cell cycle blockade, evidenced by the induction of the cell cycle inhibitor p27 and the reduction of the expression of cyclin D1 and D3, rather than to the activation of apoptotic mechanisms; furthermore, the activation of the receptor can influence the DNA methylation pattern of melanoma cells, suggesting that it could also exert antitumor effects through epigenetic regulation. However, the antiproliferative activity is dependent on the specific Ras/Raf mutational status of the cells and/or the expression of specific ERβ isoforms.
MTT assays indicated that δ-tocotrienol induces a significant reduction in melanoma cell viability, independently of the specific mutational status of the cells, and the expression of ERβ. Gene-reporter assays failed to associate the antitumor activity of δ-tocotrienol and the activation of the estrogen receptor β in melanoma cells.
The molecular mechanisms underlying δ-tocotrienol activity were then analysed, evidencing a cytotoxic/apoptotic effect, through inhibition of colony-formation and cleavage of caspase-3 and PARP. Such apoptotic effect was found to be related to the activation of the endoplasmic reticulum (ER) stress pathways, as demonstrated by the induction of ER stress markers PERK, IRE1α, ATF4 and CHOP and the cleavage of caspase-4. Furthermore, the apoptotic effect was partially reverted by the ER stress inhibitor salubrinal. However, the mitochondrial apoptotic way was also activated by δ-tocotrienol, since cytochrome c release and Bax/Bcl-2 ratio increment were observed. In vivo studies were also performed, and the reduction of tumor mass and volume and the delay of tumor progression strongly support the effectiveness of this compound on melanoma.
Finally, the population of cancer stem cells was characterized in the A375 melanoma cell line, through the ability to grow on suspended melanospheres, and the expression of the melanoma stem cell…
Advisors/Committee Members: coordinatore: A. Poletti, tutor: P. LIMONTA, LIMONTA, PATRIZIA, POLETTI, ANGELO.
Subjects/Keywords: Melanoma; Estrogens; Tocotrienols; Settore BIO/13 - Biologia Applicata; Settore BIO/09 - Fisiologia
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Manager
APA (6th Edition):
Marzagalli, M. (2015). NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/340726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marzagalli, M.. “NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS.” 2015. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/340726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marzagalli, M.. “NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS.” 2015. Web. 20 Jan 2021.
Vancouver:
Marzagalli M. NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/340726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marzagalli M. NEW INSIGHTS ON ESTROGENS AND VITAMIN E DERIVATIVE TOCOTRIENOLS ON HUMAN MALIGNANT MELANOMA: TOWARDS NOVEL THERAPEUTIC INTERVENTIONS. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/340726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
25.
V. Carlini.
CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN.
Degree: 2017, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/522972
► The intracellular chloride channel 1 (CLIC1) is a metamorphic protein, belonging to a recently discovered and still largely unexplored ion channel family. It displays the…
(more)
▼ The intracellular chloride channel 1 (CLIC1) is a metamorphic protein, belonging to a recently discovered and still largely unexplored ion channel family. It displays the unique characteristic of being expressed both in a cytoplasmic and in a transmembrane form, the latter able to form a chloride selective ion channel. One of the main factors known to regulate this membrane insertion is the increase of oxidative level of the cells.
If on one hand, the transient CLIC1 functional expression in the membrane could mediate several physiological cell responses, on the other hand, its chronic membrane translocation can lead to severe pathological conditions, including cancer. In particular two tumors, prostate cancer (PCa) and colon cancer (CRC), are characterized by elevated oxidative level and growing scientific evidence have suggested the involvement of CLIC1 in the tumorigenesis of these diseases.
PCa and CRC are two of the most diffuse cancers and a leading cause of tumor fatality worldwide. Detecting the disease in a very early stage and finding a treatment able to prevent metastasis are critical clinical challenges to achieve a successful treatment for these malignancies.
This thesis was focused in the direction of understanding the possible role of CLIC1 in the development and progression of PCa and CRC.
Results obtained have shown that CLIC1 functional expression in plasma membrane occurs selectively in malignant cells, compared to benign or normal cells. Moreover, it has been demonstrated that CLIC1 membrane chloride current promotes proliferation, cell cycle progression from G1 to S phase and migration of cancer cells. All these findings suggest that CLIC1 may actively contribute to development of PCa and CRC and their progression towards a more aggressive form.
It can be reasonably hypothesize that elevated oxidative levels present in cancer cells compared to normal cells cause the chronic overexpression of CLIC1 in the plasma membrane only of malignant cells. Therefore, targeting this protein could make it possible to hit selectively the tumor cells without damaging their normal counterpart. In this scenario, CLIC1 appears not only as a promising pharmacological target but also as a suitable biomarker.
The only effective inhibitor of CLIC1 activity to date identified is highly toxic in vivo. For this reason, finding other compounds able to specifically block the channel but causing negligible side effects is necessary. In light with this purpose, our laboratory has recently proposed the anti-diabetic drug metformin as CLIC1 channel blocker.
Results obtained have demonstrated that metformin displays a significant antitumoral activity on PCa and CRC cells, inhibiting both cell proliferation and migration. This anti-neoplastic effect is dependent on the inhibition of CLIC1 channel together with other intracellular targets.
Overall these findings provide new support on the antineoplastic role of metformin and encourage the research of more specific and more effective compounds for CLIC1 channel, in order…
Advisors/Committee Members: tutor e coordinatore: M. Mazzanti, MAZZANTI, MICHELE, MAZZANTI, MICHELE.
Subjects/Keywords: CLIC1 channel; prostate cancer; colon cancer; metformin; Settore BIO/11 - Biologia Molecolare; Settore BIO/09 - Fisiologia; Settore BIO/15 - Biologia Farmaceutica
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APA (6th Edition):
Carlini, V. (2017). CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/522972
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Carlini, V.. “CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN.” 2017. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/522972.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Carlini, V.. “CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN.” 2017. Web. 20 Jan 2021.
Vancouver:
Carlini V. CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/522972.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Carlini V. CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/522972
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
26.
L.L. Ferrari.
STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/229547
► Introduction: an inherited form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 mutation in the prion protein (PrP) gene. CJD is usually characterized by…
(more)
▼ Introduction: an inherited form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 mutation in the prion protein (PrP) gene. CJD is usually characterized by motor disorders, cognitive impairment and electroencephalographic alterations but recently sleep modification have been described.
Moreover a role for PrP in sleep has been proposed on the basis of data collected in Knock-out mice.
We generated a new mouse model of CJD (Tg(CJD)) that express the murine homologue of the D178N/V129 human mutation. We used as control mice Knock-out (KO) for the PrP, mice that over-express the normal form of the PrP Tg(WT) and Wt mice.
Goals: 1) the characterization of Tg(CJD) mice 2) the study of the evolution during aging of sleep and EEG patterns in our CJD model and in KO and Tg(WT) mice 3) the study of response to sleep deprivation in all our strains.
Materials: mice were anesthetized and instrumented for chronic EEG recordings, using standard techniques. Body movements were detected by means of an infrared sensor. Mice were individually housed in soundproof rooms, and maintained on a 12 hours light:dark cycle, at an ambient temperature between 23 and 24 °C. The study of the evolution of sleep patterns over time was conducted using animals of 3 different ages for each strain (6, 12 and 18 months).
Sleep deprivation was carried out by means of gentle handling and lasted 6 hours starting from the beginning of light phase.
Results: 18 months old Tg(CJD) mice showed a striking reduction in the amount of REM sleep compared to control strains. They also showed abundance of EEG alterations that remind those described in humans and motor alterations typical of CJD. The decrease in REM sleep is already present at 12 months of age in Tg(CJD) mice. Tg(CJD) and KO mice showed a flattening of the circadianity of sleep/wake cycle at 12 and 18 months of age. Sleep deprivation analysis showed a loss of rebound of REM sleep in mice with alterations of PrP.
Conclusions: We propose that Tg(CJD) mice establish the first transgenic animal model of a genetic prion disease recapitulating cognitive, motor and neurophysiological abnormalities of the human disorder. We also propose that REM sleep decrease in Tg(CJD) mice is an early sign of CJD and could be a new tool for rapid diagnosis of this disease.
Advisors/Committee Members: tutor: L. Imeri, coordinatore: P. Cavallari, IMERI, LUCA, CAVALLARI, PAOLO.
Subjects/Keywords: prioni; Creutzfeldt-Jakob; CJD; sonno; Settore BIO/09 - Fisiologia
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APA (6th Edition):
Ferrari, L. (2010). STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229547
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ferrari, L.L.. “STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/229547.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ferrari, L.L.. “STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI.” 2010. Web. 20 Jan 2021.
Vancouver:
Ferrari L. STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/229547.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ferrari L. STUDIO DEL RUOLO DELLA PROTEINA PRIONICA NELLA REGOLAZIONE DEL SONNO MEDIANTE L'UTILIZZO DI MODELLI MURINI TRANSGENICI. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/229547
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
27.
F. Rusconi.
THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150100
► The insulin IGF1/Akt signaling pathway has recently been shown to be critical for the regulation of heart function and physiology. Indeed, compelling evidence shows activation…
(more)
▼ The insulin IGF1/Akt signaling pathway has recently been shown to be critical for the regulation of heart function and physiology. Indeed, compelling evidence shows activation of this pathway as one of the most important determinants for the enhancement of cardiac function and physiological growth in athletes, whereas its impairment is considered critical for the development of heart failure (HF). In this doctoral thesis, our aim was to determine the functional role of known and novel key-factors of this pathway to study whether their modulation might be envisaged as therapeutic tool for curing pathological cardiac hypertrophy (CH) and HF.
Physiological CH is an adaptive response of the heart to stimuli, such as developmental growth and training and differs markedly from pathological hypertrophy occurring in patients with HF. In this thesis, we demonstrated the involvement of Akt kinase in regulating heart inotropism by modulating L-Type Ca2+ Channel (LTCC) density and function. In a mouse model with inducible and cardiac specific deletion of PDK1, the upstream activator of Akt, we found that the protein stability of the LTCC pore subunit (Cavα1) can be modulated by the kinase. In particular, phosphorylation of the C-terminal coiled coil of the Cavβ2 chaperone subunit enhances LTCC protein stability by prevention of PEST-mediated Cavα1 degradation. Subsequently, to determine whether the modulation of this mechanism may be used for the treatment of HF, we studied the fine-regulation of LTCC density and activity by investigating the functional role of Akt-phosphomimetics Cavβ2 constructs. Three Akt-phosphomimetic sequences corresponding to the Cavβ2 C-terminal coiled coil were identified and shown to protect Cavα1 from protein degradation, through an increase in the number of functional LTCC. Moreover, to establish whether the Akt-dependent phosphorylation of CaVβ2 might be a trigger for the recruitment of other protein interacting partners, yeast two-hybrid screenings of human and mouse heart cDNA expression libraries revealed a fold-back interaction of the Akt-phosphorylated-Cavβ2 tail with a region of the Cavβ2 globular domain. Co-immunoprecipitation experiments confirmed this interaction, while negative results were obtained when Cavβ2-WT was used as bait. This provided the proof of concept for a mechanism of action that relies on Akt-dependent phosphorylation. Site-specific mutagenesis in the identified interacting domain confirmed this mechanism. All togheter, we found that the Akt-dependent protective effect on Cavα1 stability might relay on Cavβ2 structural rearrangements, which follow the phosphorylated C-terminal coiled coil fold back on its globular domain.
In conclusion, results from this doctoral thesis provide further insights into the role of the insulin IGF1/Akt signaling pathway and its role in the modulation of myocardial physiology and HF. These findings may lead to the development of new therapeutical tools that will be useful for the modulation of impaired cardiac contractility in HF.
Advisors/Committee Members: tutor: Dario Di Francesco, coordinatore: Paolo Cavallari, supervisor: Gianluigi Condorelli, supervisor: Daniele Catalucci, DI FRANCESCO, DARIO, CAVALLARI, PAOLO.
Subjects/Keywords: Akt; L-type Calcium channel; heart failure; Settore BIO/09 - Fisiologia
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APA ·
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MLA ·
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APA (6th Edition):
Rusconi, F. (2010). THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rusconi, F.. “THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150100.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rusconi, F.. “THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION.” 2010. Web. 20 Jan 2021.
Vancouver:
Rusconi F. THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150100.
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. THE IMPORTANT ROLE OF AKT IN THE MODULATION OF HEART INOTROPISM THROUGH L-TYPE CALCIUM CHANNELS FUNCTION. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
28.
E.S. DI CAIRANO.
GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150106
► Glutamate is the main excitatory neurotransmitter of the mammalian nervous system and is involved in neuronal plasticity, memory and learning. Emerging evidences suggest that glutamate…
(more)
▼ Glutamate is the main excitatory neurotransmitter of the mammalian nervous system and is involved in neuronal plasticity, memory and learning. Emerging evidences suggest that glutamate is also present in peripheral tissues, where it plays a role in both cellular homeostasis and in autocrine/paracrine communication as an extracellular signalling molecule [Hediger and Welbourne, 1999; Nedergaard et al., 2002]. The extracellular glutamate concentration is tightly controlled by high affinity glutamate transporters, whose expression and modulation in the peripheral tissues have been poorly investigated. In this work we analyse the high affinity glutamate transporters EAAC1 and GLT1 in epithelia and endocrine pancreas, respectively. EAAC1 was cloned from rabbit intestine [Kanai and Hediger, 1992] and its expression and function have been well characterised in absorptive epithelia, such as intestine and kidney, where it represents the major transporter for the dicarboxylic amino acids [Peghini et al., 1997]. Less is known about the molecular mechanisms that regulate its surface expression and activity. During the past few years, it has become clear that the activity of these transporters can be rapidly regulated by redistribution of proteins to and from the plasma membrane: a process that can be controlled by dynamic protein-protein interactions. Therefore, the research presented in the chapter II focuses on the molecular mechanisms which regulate EAAC1 trafficking in epithelial cells. EAAC1 has a conserved sequence present in the C-terminal domain of EAAC1, that mediates interactions with class I PDZ proteins. In the past years, we demonstrated that the PDZ-target sequence and PDZ proteins are responsible for the retention and stability of EAAC1 at the plasma membrane [D’Amico et al., 2010].
The aim of the present work is to verify whether this PDZ-target sequence is also important for the transporter’s biosynthetic delivery. Our data indicate that PDZ interactions occur early in the biosynthetic pathways and are involved in the ER-to-Golgi trafficking, as well as in Post-Golgi trafficking of EAAC1. Removal of the PDZ motif delays rather than prevents the ER export and the plasma membrane delivery of the transporter, thus indicating that PDZ interactions facilitate the ER-Golgi trafficking. Possibly, PDZ-interactions favour the transporters homo-oligomerization, a process required for the efficient ER export of EAAC1. Alternatively, PDZ domain-proteins may couple EAAC1 with protein complexes required for the efficient fusion of carrier vesicles to the appropriate target membranes. Further studies will be needed to identify the PDZ protein/s involved in the EAAC1 biosynthetic delivery. On the other hand, the presence of glutamate as an intercellular signal mediator in endocrine pancreas is well established [Moriyama and Hayashi, 2003]. In the Central Nervous System (CNS), glutamate may cause cell death by excitotoxicity, that is physiologically prevented by glutamate clearance systems [Choi et al., 1988]. The effect of…
Advisors/Committee Members: Tutor: Vellea Franca Sacchi, Tutor scientifico: Carla Perego, Coordinatore: Paolo Cavallari, SACCHI, VELLEA FRANCA, CAVALLARI, PAOLO.
Subjects/Keywords: glutamate transporters; EAAC1; GLT1; epithelia; endocrine pancreas; Settore BIO/09 - Fisiologia
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APA ·
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APA (6th Edition):
CAIRANO, E. D. (2010). GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
CAIRANO, E.S. DI. “GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
CAIRANO, E.S. DI. “GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION.” 2010. Web. 20 Jan 2021.
Vancouver:
CAIRANO ED. GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
CAIRANO ED. GLUTAMATE TRANSPORTERS IN PANCREAS AND EPITHELIA: PHYSIOLOGICAL ROLES AND DYNAMIC REGULATION. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
29.
E. Seminati.
COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150098
► The main topic of my PhD project regards the effects of the human symmetry on energetic and locomotion. The concept of symmetry, applied in many…
(more)
▼ The main topic of my PhD project regards the effects of the human symmetry on energetic and locomotion.
The concept of symmetry, applied in many and different fields, from arts to physical sciences, has been always related to beauty, balance and equilibrium. Most individuals, animals and humans as well, are characterized by an almost complete morphological bilateral symmetry, and the deviation from it caused by environmental stresses, developmental instability and genetic problems, is called Fluctuating Asymmetry (FA). In numerous studies regarding FA, it has been demonstrated that this index is related to several different features, like sexual selection, body mass, running performance in humans and in racehorses.
Similarly, symmetry plays a key role in the maintenance and design of our vehicles. They are periodically inspected, to guarantee a wheel balance/alignment and homogeneous tyre wearing. In this way the fuel consumption can be reduced.
The main aim of this project has its origin from the comparison between mechanical vehicles and the human body. In human locomotion the skeletal muscles (the motor), and the limb lever system (the machine), interact together, in order to produce the movements of the whole body system. We assume that an anatomical or structural symmetry of the human body could have effects on the dynamic asymmetry during locomotion and also could be related to some metabolic energy saving.
Several authors studied symmetry in locomotion with different methodological approaches in human, but also in animals. Different symmetry indices were found in order to classify subjects in different categories, or for pattern identification and pathologies diagnosis, but the relationships between symmetry and the Cost of Transport were poorly investigated. Gait symmetry has been defined as a perfect agreement between the actions of the lower limbs and general this assumption was adopted to simplify data collection and analysis of the lower limbs. Gait asymmetry instead, does not appear to be the consequence of abnormality, but rather reflects natural functional differences between the lower extremities.
In the present study, we tried to validate our hypothesis, investigating anatomical and, dynamical symmetries, and the cost of transport in 19 different aged and trained male runners, in order to find out significant relationships between these parameters. Subjects were divided in three categories: Occasional Runners (OR), Skilled Runners (SR) and Top Runners (TR), depending of their training/performance level.
Differently from others studies, we compare two different kinds of symmetries: the dynamic symmetry during running at different velocities (i.e. spatial differences, in Body Center of Mass (BCOM) trajectory, between two step), and the anatomical symmetry of the human lower limbs.
A Magnetic Resonance (MR) protocol was applied for each
subject, to evaluate the anatomical symmetry of three different anatomical districts Pelvis district (PD), Upper-Leg district (UD) and Lower-Leg district (LD).…
Advisors/Committee Members: tutor: Alberto E. Minetti, coordinatore: Paolo Cavallari, CAVALLARI, PAOLO.
Subjects/Keywords: cost of transport; asymmetry; dynamic of running,; Settore BIO/09 - Fisiologia
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Manager
APA (6th Edition):
Seminati, E. (2010). COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150098
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Seminati, E.. “COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150098.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Seminati, E.. “COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING.” 2010. Web. 20 Jan 2021.
Vancouver:
Seminati E. COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150098.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Seminati E. COST OF TRANSPORT, LOWER LIMBS ASIMMETRY AND THE DYNAMICS OF RUNNING. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150098
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
30.
D. Cazzola.
INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS.
Degree: 2010, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/150073
► This Thesis is organized in two parts based on two different investigations about human motion: the metabolic and mechanical analysis of ‘skyscraper running’, and the…
(more)
▼ This Thesis is organized in two parts based on two different investigations about human
motion: the metabolic and mechanical analysis of ‘skyscraper running’, and the estimation
of the visceral mass displacement in vertical jumps.
Skyscraper running is a novel sport activity, in which the athletes run on emergency stairs
of the tallest building of the world, during the ‘run up’ races of the world championship
circuit. In PART I of this Thesis, this topic has been analysed in terms of mechanical and
metabolic requirements, both at general and individual level.
Skyscraper runners’metabolic profile, has been inferred from the total mechanical power
estimated in 36 world records (48-421 m tall buildings), ranked by gender and age range.
Individual athlete’s performance (n=13) has been experimentally investigated during the
Pirelli Vertical Sprint, with data loggers for altitude and heart rate. At a general level, a
non-linear regression of Wilkie’s model relating maximal mechanical power to event
duration, revealed the gender and age differences in term of maximum aerobic power and
anaerobic energy resources particularly needed at the beginning of the race. The total
mechanical power was found to be partitioned among: the fraction devolved to raise the
body centre of mass:
W˙ STA.EXT = 80.4 ± 2.9%, the need to accelerate the limbs with respect
to the body:
W˙ STA.INT = 4.5 ± 2.1%, and running in turns between flights of stairs:
W˙ TUR =15.1 ± 2.0%. At the individual level, experiments revealed that these athletes show a
metabolic profile similar to middle-distance runners. Furthermore, best skyscraper runners
keep constant vertical speed and heart rate throughout the race, while others suddenly
decelerate, negatively affecting the race performance.
In PART II of this Thesis another interesting study has been discussed: the mechanics of
visceral mass motion in vertical jumps. This internal mass motion could occur in all the
locomotion paradigms, and also in all the movements characterized by a high centre of mass vertical displacement. Moreover, visceral mass shows significant couplings with the
respiratory system, as has been discussed in the past in famous studies on quadruped
locomotion. Here viscera motion has been analyzed in a simple and well know motor task
as the vertical jump, focusing on the effect of respiratory and muscle contractions
strategies to limit its displacement, and to improve trunk-pelvis segment stiffness.
A validated method for the estimation of visceral mass displacement has been applied during jump sequences with two different techniques: six subjects before and after a specific training period, executed the natural jump and the “controlled” jump sessions. In
that method, the simultaneous measurement of ground reaction forces and spatial
coordinates allow the estimation of the relative movement between the ‘invisible’ abdomen
content and the ‘container’, i.e. the rest of the body as described by the position of external
markers.
The results show a significantly…
Advisors/Committee Members: tutor: Alberto E. Minetti, coordinatore: Paolo Cavallari, MINETTI, ALBERTO ENRICO, CAVALLARI, PAOLO.
Subjects/Keywords: biomechanics; uphill running; energetics; viscera; jump; Settore BIO/09 - Fisiologia
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APA (6th Edition):
Cazzola, D. (2010). INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/150073
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cazzola, D.. “INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS.” 2010. Thesis, Università degli Studi di Milano. Accessed January 20, 2021.
http://hdl.handle.net/2434/150073.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cazzola, D.. “INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS.” 2010. Web. 20 Jan 2021.
Vancouver:
Cazzola D. INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2434/150073.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cazzola D. INVESTIGATING THE METABOLIC PROFILE OF RUN-UP RACES AND THE MECHANICS OF WOBBLING VISCERAL MASS IN VERTICAL JUMPS. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/150073
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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