176 results on '"Cossu A"'
Search Results
2. Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience
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Pietro Sergio, Marco Dugo, Alberto Cossu, Valentina Regazzoni, Davide Vignale, Francesco Giannini, Anna Palmisano, Francesco Moroni, Marco Toselli, Lorenzo Monti, Marco Loffi, Gianni Casella, Gianmarco Iannopollo, Alberto Monello, Raffaele Piccolo, Alberto Cereda, Gianluca Pontone, Gian Battista Danzi, Elisabetta Tonet, Francesco Monetti, Antonio Esposito, Daniele Andreini, Giuseppe Ferrillo, Gianluigi Patelli, Antonio Colombo, Ottavio Zucchetti, Gaetano Liccardo, and Elisabetta Mancini
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Male ,RNA viruses ,Viral Diseases ,Pulmonology ,Computed Tomography Angiography ,Coronaviruses ,Epidemiology ,medicine.medical_treatment ,Deep vein ,Anticoagulant Therapy ,030204 cardiovascular system & hematology ,Vascular Medicine ,Diagnostic Radiology ,0302 clinical medicine ,Medical Conditions ,Risk Factors ,Oxygen therapy ,Pulmonary angiography ,Medicine and Health Sciences ,030212 general & internal medicine ,Tomography ,Pathology and laboratory medicine ,Computed tomography angiography ,Multidisciplinary ,medicine.diagnostic_test ,Pharmaceutics ,Incidence (epidemiology) ,Incidence ,Radiology and Imaging ,Venous Thromboembolism ,Middle Aged ,Medical microbiology ,Thrombosis ,Pulmonary embolism ,Cardiovascular Therapy ,Chemistry ,medicine.anatomical_structure ,Infectious Diseases ,Italy ,Acute Disease ,Viruses ,Physical Sciences ,Medicine ,Female ,SARS CoV 2 ,Pathogens ,Research Article ,Chemical Elements ,medicine.medical_specialty ,SARS coronavirus ,Imaging Techniques ,Science ,Neuroimaging ,Research and Analysis Methods ,Microbiology ,Fibrin Fibrinogen Degradation Products ,03 medical and health sciences ,Drug Therapy ,Diagnostic Medicine ,Internal medicine ,Thromboembolism ,medicine ,Humans ,Aged ,Biology and life sciences ,business.industry ,SARS-CoV-2 ,Organisms ,Viral pathogens ,COVID-19 ,Covid 19 ,Pneumonia ,medicine.disease ,Microbial pathogens ,Computed Axial Tomography ,Oxygen ,Medical Risk Factors ,business ,Pulmonary Embolism ,Neuroscience - Abstract
Background and aims Several studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes. Methods This is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi02≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5μg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed. Results Among 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas. Conclusions Despite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas.
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- 2021
3. A randomised, double-blind, sham-controlled study of left prefrontal cortex 15 Hz repetitive transcranial magnetic stimulation in cocaine consumption and craving
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Virginia Cimino, Maenia Scarpino, C. Cossu, Fabio Fierini, Anita Ercolini, Francesco Lolli, Antonello Grippo, Matteo Innocenti, Amedeo del Vecchio, Guido Mannaioni, A. Ballerini, Brunella Occupati, M. Bastianelli, Stefano Pallanti, Giulio D’Anna, Filippo Gori, Silvia Pascolo, Giovanni Lanzo, Maya Salimova, and Nicolò Meneghin
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Male ,Physiology ,medicine.medical_treatment ,Social Sciences ,Craving ,Kaplan-Meier Estimate ,Urine ,Cocaine ,Medicine and Health Sciences ,Psychology ,Prefrontal cortex ,Depression (differential diagnoses) ,Brain Mapping ,Multidisciplinary ,Depression ,Pharmaceutics ,Brain ,Middle Aged ,Transcranial Magnetic Stimulation ,Body Fluids ,Electrophysiology ,Chemistry ,Bioassays and Physiological Analysis ,Treatment Outcome ,medicine.anatomical_structure ,Brain Electrophysiology ,Behavioral Pharmacology ,Anesthesia ,Physical Sciences ,Medicine ,Female ,Anatomy ,medicine.symptom ,Research Article ,Personality ,Adult ,Impulsivity ,Psychometrics ,Science ,Neurophysiology ,Prefrontal Cortex ,Research and Analysis Methods ,Placebo ,behavioral disciplines and activities ,Cocaine-Related Disorders ,Alkaloids ,Drug Therapy ,Double-Blind Method ,Recreational Drug Use ,Mental Health and Psychiatry ,mental disorders ,medicine ,Humans ,Transcranial Stimulation ,Pharmacology ,Personality Traits ,Mood Disorders ,business.industry ,Electrophysiological Techniques ,Chemical Compounds ,Biology and Life Sciences ,Survival Analysis ,Dorsolateral prefrontal cortex ,Transcranial magnetic stimulation ,Regimen ,business ,Neuroscience - Abstract
Background Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. Methods We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. Findings We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9–10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p Conclusions In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. Trial registration The study number on clinicalTrials.gov is NCT03607591.
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- 2021
4. The role of endoplasmic reticulum in in vivo cancer FDG kinetics
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Sommariva, Sara, primary, Scussolini, Mara, additional, Cossu, Vanessa, additional, Marini, Cecilia, additional, Sambuceti, Gianmario, additional, Caviglia, Giacomo, additional, and Piana, Michele, additional
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- 2021
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5. Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state
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Kisby, Thomas, primary, de Lázaro, Irene, additional, Stylianou, Maria, additional, Cossu, Giulio, additional, and Kostarelos, Kostas, additional
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- 2021
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6. Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience
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Loffi, Marco, primary, Regazzoni, Valentina, additional, Toselli, Marco, additional, Cereda, Alberto, additional, Palmisano, Anna, additional, Vignale, Davide, additional, Moroni, Francesco, additional, Pontone, Gianluca, additional, Andreini, Daniele, additional, Mancini, Elisabetta Maria, additional, Monello, Alberto, additional, Iannopollo, Gianmarco, additional, Casella, Gianni, additional, Monetti, Francesco, additional, Monti, Lorenzo, additional, Ferrillo, Giuseppe, additional, Liccardo, Gaetano, additional, Tonet, Elisabetta, additional, Zucchetti, Ottavio, additional, Cossu, Alberto, additional, Dugo, Marco, additional, Patelli, Gianluigi, additional, Sergio, Pietro, additional, Esposito, Antonio, additional, Colombo, Antonio, additional, Giannini, Francesco, additional, Piccolo, Raffaele, additional, and Danzi, Gian Battista, additional
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- 2021
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7. Kin discrimination and outer membrane exchange in Myxococcus xanthus: Experimental analysis of a natural population
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Cossey, Sarah M., primary, Yu, Yuen-Tsu Nicco, additional, Cossu, Laura, additional, and Velicer, Gregory J., additional
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- 2019
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8. Correction: Magic-Factor 1, a Partial Agonist of Met, Induces Muscle Hypertrophy by Protecting Myogenic Progenitors from Apoptosis
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Laura Benedetti, Vania Broccoli, Marco Cassano, Paolo M. Comoglio, Claudia Omes, Renata Boratto, Giulio Cossu, Frank N. Martin, Marcello Allegretti, Paolo Michieli, Cristina Basilico, Maurilio Sampaolesi, Gabriella De Angelis, Amanda Finan, Stefano Biressi, and Yvan Torrente
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Multidisciplinary ,Chemistry ,Apoptosis ,lcsh:R ,Magic (programming) ,lcsh:Medicine ,lcsh:Q ,Progenitor cell ,lcsh:Science ,Partial agonist ,Cell biology ,Muscle hypertrophy - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0003223.].
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- 2019
9. Correction: Magic-Factor 1, a Partial Agonist of Met, Induces Muscle Hypertrophy by Protecting Myogenic Progenitors from Apoptosis
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Cassano, Marco, primary, Biressi, Stefano, additional, Finan, Amanda, additional, Benedetti, Laura, additional, Omes, Claudia, additional, Boratto, Renata, additional, Martin, Frank, additional, Allegretti, Marcello, additional, Broccoli, Vania, additional, Cusella De Angelis, Gabriella, additional, Comoglio, Paolo M., additional, Basilico, Cristina, additional, Torrente, Yvan, additional, Michieli, Paolo, additional, Cossu, Giulio, additional, and Sampaolesi, Maurilio, additional
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- 2019
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10. VGF Peptide Profiles in Type 2 Diabetic Patients' Plasma and in Obese Mice
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Filomena D'Amato, Raffaella Isola, Irene Messana, Efisio Cossu, Barbara Noli, Gian-Luca Ferri, Michela Incani, Laura Angioni, Barbara Manconi, S. Mariotti, Cristina Cocco, and Paola Solinas
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Adult ,Male ,medicine.medical_specialty ,Spectrometry, Mass, Electrospray Ionization ,Molecular Sequence Data ,lcsh:Medicine ,Neuropeptide ,Adipose tissue ,Enzyme-Linked Immunosorbent Assay ,White adipose tissue ,Type 2 diabetes ,Diet, High-Fat ,Mice ,Tandem Mass Spectrometry ,Diabetes mellitus ,Internal medicine ,Blood plasma ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Obesity ,lcsh:Science ,Chromatography, High Pressure Liquid ,Aged ,Aged, 80 and over ,Multidisciplinary ,Chemistry ,Pancreatic islets ,lcsh:R ,Neuropeptides ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Peptide Fragments ,Endocrinology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Microscopy, Fluorescence ,lcsh:Q ,Diet-induced obese ,Research Article - Abstract
To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p
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- 2015
11. Switch to Dolutegravir plus Rilpivirine Dual Therapy in cART-Experienced Subjects: An Observational Cohort
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Capetti, Amedeo F., primary, Sterrantino, Gaetana, additional, Cossu, Maria Vittoria, additional, Orofino, GianCarlo, additional, Barbarini, Giorgio, additional, De Socio, Giuseppe V., additional, Di Giambenedetto, Simona, additional, Di Biagio, Antonio, additional, Celesia, Benedetto M., additional, Argenteri, Barbara, additional, and Rizzardini, Giuliano, additional
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- 2016
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12. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer
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Sara Ena, Maria Giuseppina Sarobba, Maria Rosaria Muroni, Luciano Murgia, Maria Rosaria De Miglio, Giovanna Pira, Francesca Sanges, Sandra Orrù, Paolo Cossu-Rocca, Alessandra Manca, Silvana Anna Maria Urru, Maria Gabriela Uras, and Giovanni Sotgiu
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Adult ,Proto-Oncogene Proteins B-raf ,MED/08 Anatomia patologica ,Class I Phosphatidylinositol 3-Kinases ,medicine.medical_treatment ,lcsh:Medicine ,Triple Negative Breast Neoplasms ,medicine.disease_cause ,Targeted therapy ,Phosphatidylinositol 3-Kinases ,Breast cancer ,medicine ,PTEN ,Humans ,lcsh:Science ,neoplasms ,PI3K/AKT/mTOR pathway ,Triple-negative breast cancer ,Aged ,Multidisciplinary ,biology ,lcsh:R ,PTEN Phosphohydrolase ,Cancer ,Middle Aged ,medicine.disease ,ErbB Receptors ,Genes, ras ,MED/04 Patologia generale ,Mutation ,Cancer research ,biology.protein ,ras Proteins ,Female ,lcsh:Q ,KRAS ,Proto-Oncogene Proteins c-akt ,Research Article ,Signal Transduction - Abstract
Background: Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. Materials and Methods: PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. Results: PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Conclusions: Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.
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- 2015
13. Detection of serum antibodies cross-reacting with Mycobacterium avium subspecies paratuberculosis and beta-cell antigen zinc transporter 8 homologous peptides in patients with high-risk proliferative diabetic retinopathy
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Francesco Blasetti, Daniela Paccagnini, Antonio Daniele Pinna, Leonardo Antonio Sechi, Davide Cossu, Irene Maiore, Speranza Masala, and Giuseppe Mameli
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Male ,lcsh:Medicine ,Type 2 diabetes ,MED/07 Microbiologia e microbiologia clinica ,Epitope ,Epitopes ,Endocrinology ,Seroepidemiologic Studies ,Insulin-Secreting Cells ,Medicine and Health Sciences ,Child ,lcsh:Science ,Cation Transport Proteins ,Multidisciplinary ,biology ,Diabetic retinopathy ,Middle Aged ,Antibodies, Bacterial ,Mycobacterium avium subspecies paratuberculosis ,Mycobacterium avium subsp. paratuberculosis ,Infectious Diseases ,Child, Preschool ,Zinc Transporter 8 ,Female ,Antibody ,Research Article ,Adult ,Adolescent ,Immunology ,Cross Reactions ,Young Adult ,Antigen ,medicine ,Humans ,MED/30 Malattie apparato visivo ,Aged ,Type 1 diabetes ,Diabetic Retinopathy ,business.industry ,lcsh:R ,Infant, Newborn ,Biology and Life Sciences ,Infant ,medicine.disease ,biology.organism_classification ,Ophthalmology ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,biology.protein ,lcsh:Q ,Peptides ,business - Abstract
Purpose: MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. Methods: Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. Results: Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference (P = 0.016). Conclusions: This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.
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- 2014
14. Switch to Dolutegravir plus Rilpivirine Dual Therapy in cART-Experienced Subjects: An Observational Cohort
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Simona Di Giambenedetto, Giuseppe Vittorio De Socio, Benedetto Maurizio Celesia, Amedeo Capetti, Giorgio Barbarini, Gaetana Sterrantino, Barbara Argenteri, Giuliano Rizzardini, Antonio Di Biagio, Maria Vittoria Cossu, and Giancarlo Orofino
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Male ,RNA viruses ,Genetics and Molecular Biology (all) ,0301 basic medicine ,Viral Diseases ,HIV Infections ,Drug resistance ,Medicine (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,Pharmacology ,Pathology and Laboratory Medicine ,Toxicology ,Biochemistry ,Piperazines ,Cohort Studies ,Drug Abuse ,chemistry.chemical_compound ,0302 clinical medicine ,Immunodeficiency Viruses ,Antiretroviral Therapy, Highly Active ,Sleep Initiation and Maintenance Disorders ,Medicine and Health Sciences ,Medicine ,Drug Interactions ,030212 general & internal medicine ,Multidisciplinary ,Headaches ,Headache ,Middle Aged ,Infectious Diseases ,Medical Microbiology ,Creatinine ,Viral Pathogens ,Rilpivirine ,Viruses ,Dolutegravir ,Cohort ,RNA, Viral ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,Female ,Pathogens ,medicine.symptom ,Heterocyclic Compounds, 3-Ring ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,Pyridones ,Science ,030106 microbiology ,Drug-Drug Interactions ,Viremia ,Settore MED/17 - MALATTIE INFETTIVE ,Microbiology ,Drug Administration Schedule ,03 medical and health sciences ,Signs and Symptoms ,Pharmacotherapy ,Diagnostic Medicine ,Microbial Control ,Internal medicine ,Drug Resistance, Viral ,Oxazines ,Retroviruses ,Humans ,HIV Integrase Inhibitors ,Microbial Pathogens ,Aged ,Behavior ,Toxicity ,business.industry ,Lentivirus ,Organisms ,Biology and Life Sciences ,HIV ,medicine.disease ,chemistry ,HIV-1 ,Antimicrobial Resistance ,business ,Follow-Up Studies - Abstract
IntroductionLittle information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap.MethodsAll HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48.ResultsOne hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months. One subject discontinued the study drug at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse. The mean age was 51.8, females 31.7% and non-caucasians 10%. Fifty-seven (43.2%) had at least one failure in their treatment history. Reasons for switching were simplification (53.0%), toxicity (34.8%), drug interactions (n = 7), persistent low-level viremia (n = 4), non-adherence (n = 3) and viral failure (n = 2). Sixty patients (45.5%) had reverse transcriptase (RT) mutations and 69 (44,7%) had protease (PR) mutations. Sixteen had baseline viral replication, 27 had < 50 HIV-1 RNA copies/mL and in 89 (67.4%) no virus was detected (NVD, 0 copies/mL). At w4, 114 (86.4%) had NVD, 15 had 1 to 49 HIV-1 RNA copies/mL and 3 had 50 to 57 copies/mL. At week 24 one subject had viral rebound without mutations due to missed drug refill, 19 had 1 to 49 copies/mL, and 112 had NVD. All 132 subjects were tested at weeks 4 and 24. Of the 50 subjects who had a 48-week follow-up, one had a treatment interruption, four had 1 to 49 copies/mL and 45 had NVD. Among the entire population, one subject had low-level, one intermediate and 4 high-level resistance to rilpivirine: none failed by week 48. Mean serum creatinine increased by +0.1 mg/dL. During the follow-up one patient reported headache and insomnia.ConclusionsRipivirine plus dolutegravir proved safe and effective in this cohort of non-naïve HIV-1 infected subjects.
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- 2016
15. Binding of sFRP-3 to EGF in the Extra-Cellular Space Affects Proliferation, Differentiation and Morphogenetic Events Regulated by the Two Molecules
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Ugo Borello, Emilio Clementi, Cesare Gargioli, Stefano Cannata, Raffaella Scardigli, Maurilio Sampaolesi, Daniela Tosoni, Clara Sciorati, Silvia Brunelli, Giulio Cossu, Scardigli, R, Gargioli, C, Tosoni, D, Borello, U, Sampaolesi, M, Sciorati, C, Cannata, S, Clementi, E, Brunelli, S, Cossu, G, and Morty, Rory Edward
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glycoprotein ,Frizzled ,Xenopus ,Cellular differentiation ,lcsh:Medicine ,animal cell ,protein binding ,heparin ,fibroblast ,Cell Biology/Cell Signaling ,ectoderm ,Mice ,Cricetinae ,Developmental Biology/Developmental Molecular Mechanisms ,Morphogenesis ,membrane protein ,animal ,lcsh:Science ,chemistry.chemical_classification ,Multidisciplinary ,hair follicle ,biology ,Settore BIO/11 ,article ,Wnt signaling pathway ,Intracellular Signaling Peptides and Proteins ,LRP6 ,LRP5 ,Cell Differentiation ,Cell biology ,Dishevelled ,Mammalia ,FRZB protein ,muscle development ,Signal transduction ,Research Article ,in vitro study ,Settore BIO/06 ,gene overexpression ,embryo ,CHO Cells ,Bovinae ,animal tissue ,Cell Line ,Cricetulus ,Animals ,controlled study ,membrane binding ,Molecular Biology ,mouse ,Cell Proliferation ,Glycoproteins ,CHO cell ,nonhuman ,secreted frizzled related protein 3 ,Epidermal Growth Factor ,lcsh:R ,BIO/13 - BIOLOGIA APPLICATA ,epidermal growth factor ,epidermal growth factor receptor ,Wnt protein ,cell differentiation ,cell proliferation ,cell structure ,embryo development ,extracellular space ,morphogenesis ,cell line ,hamster ,metabolism ,Extracellular Space ,Fibroblasts ,biology.organism_classification ,Molecular biology ,chemistry ,Wnt, EGF, sFRP-3, proliferation, differentiation ,lcsh:Q - Abstract
BACKGROUND: sFRP-3 is a soluble antagonist of Wnts, widely expressed in developing embryos. The Wnt gene family comprises cysteine-rich secreted ligands that regulate cell proliferation, differentiation, organogenesis and oncogenesis of different organisms ranging from worms to mammals. In the canonical signal transduction pathway Wnt proteins bind to the extracellular domain of Frizzled receptors and consequently recruit Dishevelled (Dsh) to the cell membrane. In addition to Wnt membrane receptors belonging to the Frizzled family, several other molecules have been described which share homology in the CRD domain and lack the putative trans-membrane domain, such as sFRP molecules (soluble Frizzled Related Protein). Among them, sFRP-3 was originally isolated from bovine articular cartilage and also as a component of the Spemann organizer. sFRP-3 blocks Wnt-8 induced axis duplication in Xenopus embryos and binds to the surface of cells expressing a membrane-anchored form of Wnt-1. Injection of sFRP-3 mRNA blocks expression of XMyoD mRNA and leads to embryos with enlarged heads and shortened trunks. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that sFRP-3 specifically blocks EGF-induced fibroblast proliferation and foci formation. Over-expression of sFRP-3 reverts EGF-mediated inhibition of hair follicle development in the mouse ectoderm while its ablation in Xenopus maintains EGF-mediated inhibition of ectoderm differentiation. Conversely, over-expression of EGF reverts the inhibition of somitic myogenesis and axis truncation in Xenopus and mouse embryos caused by sFRP-3. In vitro experiments demonstrated a direct binding of EGF to sFRP-3 both on heparin and on the surface of CHO cells where the molecule had been membrane anchored. CONCLUSIONS/SIGNIFICANCE: sFRP-3 and EGF reciprocally inhibit their effects on cell proliferation, differentiation and morphogenesis and indeed are expressed in contiguous domains of the embryo, suggesting that in addition to their canonical ligands (Wnt and EGF receptor, respectively) these molecules bind to each other and regulate their activities during embryogenesis. ispartof: PLoS One vol:3 issue:6 pages:2471- ispartof: location:United States status: published
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- 2008
16. The First Mitogenome of the Cyprus Mouflon (Ovis gmelini ophion): New Insights into the Phylogeny of the Genus Ovis
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Sanna, Daria, primary, Barbato, Mario, additional, Hadjisterkotis, Eleftherios, additional, Cossu, Piero, additional, Decandia, Luca, additional, Trova, Sandro, additional, Pirastru, Monica, additional, Leoni, Giovanni Giuseppe, additional, Naitana, Salvatore, additional, Francalacci, Paolo, additional, Masala, Bruno, additional, Manca, Laura, additional, and Mereu, Paolo, additional
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- 2015
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17. VGF Peptide Profiles in Type 2 Diabetic Patients’ Plasma and in Obese Mice
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D’Amato, Filomena, primary, Noli, Barbara, additional, Angioni, Laura, additional, Cossu, Efisio, additional, Incani, Michela, additional, Messana, Irene, additional, Manconi, Barbara, additional, Solinas, Paola, additional, Isola, Raffaella, additional, Mariotti, Stefano, additional, Ferri, Gian-Luca, additional, and Cocco, Cristina, additional
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- 2015
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18. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer
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Cossu-Rocca, Paolo, primary, Orrù, Sandra, additional, Muroni, Maria Rosaria, additional, Sanges, Francesca, additional, Sotgiu, Giovanni, additional, Ena, Sara, additional, Pira, Giovanna, additional, Murgia, Luciano, additional, Manca, Alessandra, additional, Uras, Maria Gabriela, additional, Sarobba, Maria Giuseppina, additional, Urru, Silvana, additional, and De Miglio, Maria Rosaria, additional
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- 2015
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19. Zinc transporter 8 and MAP3865c homologous epitopes are recognized at T1D onset in Sardinian children
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Leonardo Antonio Sechi, Mario Palermo, Maria Antonietta Zedda, Davide Cossu, Speranza Masala, and Carlo Ripoli
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Bacterial Diseases ,Male ,endocrine system diseases ,Epidemiology ,lcsh:Medicine ,medicine.disease_cause ,Pediatrics ,Autoantigens ,Epitope ,Autoimmunity ,Pathogenesis ,Epitopes ,Endocrinology ,immune system diseases ,Pediatric Epidemiology ,Child ,lcsh:Science ,Cation Transport Proteins ,Multidisciplinary ,biology ,Child Health ,Mycobacterium avium subspecies paratuberculosis ,Mycobacterium Avium Complex ,Antibodies, Bacterial ,Mycobacterium avium subsp. paratuberculosis ,Molecular mimicry ,Infectious Diseases ,Italy ,Child, Preschool ,Medicine ,Female ,Public Health ,Antibody ,Research Article ,endocrine system ,Adolescent ,Zinc Transporter 8 ,Cross Reactions ,Autoimmune Diseases ,Mycobacterium ,Bacterial Proteins ,medicine ,Humans ,Autoantibodies ,Diabetic Endocrinology ,lcsh:R ,Autoantibody ,nutritional and metabolic diseases ,Diabetes Mellitus Type 1 ,biology.organism_classification ,Epitope mapping ,Diabetes Mellitus, Type 1 ,Immunology ,biology.protein ,Clinical Immunology ,lcsh:Q ,Epitope Mapping - Abstract
Our group has recently demonstrated that Mycobacterium avium subspecies paratuberculosis (MAP) infection significantly associates with T1D in Sardinian adult patients. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP antibodies (Abs) in the Sardinian population, studying newly diagnosed T1D children. Therefore, we investigated the seroreactivity against epitopes derived from the ZnT8 autoantigen involved in children at T1D onset and their homologous sequences of the MAP3865c protein. Moreover, sera from all individuals were tested for the presence of Abs against: the corresponding ZnT8 C-terminal region, the MAP specific protein MptD, the T1D autoantigen GAD65 and the T1D unrelated Acetylcholine Receptor. The novel MAP3865c281–287 epitope emerges here as the major C-terminal epitope recognized. Intriguingly ZnT8186–194 immunodominant peptide was cross-reactive with the homologous sequences MAP3865c133–141, strengthening the hypothesis that MAP could be an environmental trigger of T1D through a molecular mimicry mechanism. All eight epitopes were recognized by circulating Abs in T1D children in comparison to healthy controls, suggesting that these Abs could be biomarkers of T1D. It would be relevant to investigate larger cohorts of children, followed over time, to elucidate whether Ab titers against these MAP/Znt8 epitopes wane after diagnosis.
- Published
- 2013
20. A novel splice-site mutation in angiotensin I-converting enzyme (ACE) gene, c.3691+1G>A (IVS25+1G>A), causes a dramatic increase in circulating ace through deletion of the transmembrane anchor
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Sergei M. Danilov, Alexandre Persu, A.H. Jan Danser, Leonid M. Irenge, Alexander Churbanov, Marta Cossu, Andrew B. Nesterovitch, Michel Lambert, Nathalie de Visscher, Jaap Deinum, Jérôme Ambroise, Isolda A. Popova, Jean Marc Minon, Jean-Luc Gala, Internal Medicine, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/CTMA - Centre de technologies moléculaires appliquées (plate-forme technologique), and UCL - (SLuc) Service de pathologie cardiovasculaire
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Male ,Anatomy and Physiology ,Captopril ,Gene Expression ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,medicine.disease_cause ,Cardiovascular ,Cardiovascular System ,Biochemistry ,Renin-Angiotensin System ,Nucleic Acids ,Gene expression ,Pathology ,Sequence Deletion ,Mutation ,Multidisciplinary ,Splice site mutation ,biology ,Cardiovascular diseases [NCEBP 14] ,Middle Aged ,Enzymes ,Pedigree ,Hypertension ,Medicine ,Female ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Heterozygote ,Adolescent ,Science ,Molecular Sequence Data ,Peptidyl-Dipeptidase A ,Genetic Mutation ,Vascular Biology ,Diagnostic Medicine ,Internal medicine ,Renin–angiotensin system ,medicine ,Genetics ,Humans ,Genetic Testing ,Biology ,Aged ,Base Sequence ,Proteins ,Angiotensin-converting enzyme ,Heterozygote advantage ,Human Genetics ,Dendritic Cells ,Angiotensin II ,Hormones ,Transmembrane Proteins ,Endocrinology ,Asymptomatic Diseases ,biology.protein ,RNA ,Biomarkers ,General Pathology - Abstract
Contains fulltext : 116540.pdf (Publisher’s version ) (Open Access) BACKGROUND: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. METHODS AND RESULTS: Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. CONCLUSIONS: We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. 12 p.
- Published
- 2013
21. Apricot melanoidins prevent oxidative endothelial cell death by counteracting mitochondrial oxidation and membrane depolarization
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Gianfranco Pintus, Anna Maria Sanguinetti, Amalia Piscopo, Giampiero Capobianco, Antonio Piga, Costanza Emanueli, Annalisa Cossu, Roberta Giordo, Marco Poiana, and Anna Maria Posadino
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Programmed cell death ,Phytochemistry ,Polymers ,Phytopharmacology ,Green Fluorescent Proteins ,Phytochemicals ,lcsh:Medicine ,Apoptosis ,Oxidative phosphorylation ,Mitochondrion ,Biology ,medicine.disease_cause ,Protective Agents ,RoGFP ,Cell Line ,Redox Signaling ,AGR/15 Scienze e tecnologie alimentari ,Molecular Cell Biology ,medicine ,Humans ,Signaling in Cellular Processes ,MED/40 Ginecologia e ostetricia ,lcsh:Science ,BIO/10 Biochimica ,Membrane Potential, Mitochondrial ,Multidisciplinary ,Cell Death ,lcsh:R ,Endothelial Cells ,Depolarization ,Hydrogen Peroxide ,Mitochondria ,Oxidative Stress ,Chemistry ,Biochemistry ,lcsh:Q ,Prunus ,Cellular Types ,Intracellular ,Oxidative stress ,Research Article ,Signal Transduction - Abstract
The cardiovascular benefits associated with diets rich in fruit and vegetables are thought to be due to phytochemicals contained in fresh plant material. However, whether processed plant foods provide the same benefits as unprocessed ones is an open question. Melanoidins from heat-processed apricots were isolated and their presence confirmed by colorimetric analysis and browning index. Oxidative injury of endothelial cells (ECs) is the key step for the onset and progression of cardiovascular diseases (CVD), therefore the potential protective effect of apricot melanoidins on hydrogen peroxide-induced oxidative mitochondrial damage and cell death was explored in human ECs. The redox state of cytoplasmic and mitochondrial compartments was detected by using the redox-sensitive, fluorescent protein (roGFP), while the mitochondrial membrane potential (MMP) was assessed with the fluorescent dye, JC-1. ECs exposure to hydrogen peroxide, dose-dependently induced mitochondrial and cytoplasmic oxidation. Additionally detected hydrogen peroxide-induced phenomena were MMP dissipation and ECs death. Pretreatment of ECs with apricot melanoidins, significantly counteracted and ultimately abolished hydrogen peroxide-induced intracellular oxidation, mitochondrial depolarization and cell death. In this regard, our current results clearly indicate that melanoidins derived from heat-processed apricots, protect human ECs against oxidative stress.
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- 2012
22. The First Mitogenome of the Cyprus Mouflon (Ovis gmelini ophion): New Insights into the Phylogeny of the Genus Ovis
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Piero Cossu, Daria Sanna, Laura Manca, Monica Pirastru, Salvatore Naitana, Paolo Francalacci, Sandro Trova, Paolo Mereu, Eleftherios Hadjisterkotis, Mario Barbato, Giovanni Giuseppe Leoni, Luca Decandia, and Bruno Lucio Masala
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Male ,Settore BIO/18 - GENETICA ,lcsh:Medicine ,Zoology ,Sheep, Domestic ,Genome, Mitochondrial ,Phylogeny ,Haplogroup ,Phylogenetics ,Genus ,Animals ,Humans ,lcsh:Science ,Domestication ,Domestic ,Ovis ,BIO/10 Biochimica ,Sheep ,Genome ,Multidisciplinary ,Settore AGR/17 - ZOOTECNICA GENERALE E MIGLIORAMENTO GENETICO ,biology ,Phylogenetic tree ,VET/02 Fisiologia veterinaria ,BIO/18 Genetica ,lcsh:R ,Haplotype ,biology.organism_classification ,Mitochondrial ,Mouflon ,Female ,lcsh:Q ,Research Article - Abstract
Sheep are thought to have been one of the first livestock to be domesticated in the Near East, thus playing an important role in human history. The current whole mitochondrial genome phylogeny for the genus Ovis is based on: the five main domestic haplogroups occurring among sheep (O. aries), along with molecular data from two wild European mouflons, three urials, and one argali. With the aim to shed some further light on the phylogenetic relationship within this genus, the first complete mitochondrial genome sequence of a Cypriot mouflon (O. gmelini ophion) is here reported. Phylogenetic analyses were performed using a dataset of whole Ovis mitogenomes as well as D-loop sequences. The concatenated sequence of 28 mitochondrial genes of one Cypriot mouflon, and the D-loop sequence of three Cypriot mouflons were compared to sequences obtained from samples representatives of the five domestic sheep haplogroups along with samples of the extant wild and feral sheep. The sample included also individuals from the Mediterranean islands of Sardinia and Corsica hosting remnants of the first wave of domestication that likely went then back to feral life. The divergence time between branches in the phylogenetic tree has been calculated using seven different calibration points by means of Bayesian and Maximum Likelihood inferences. Results suggest that urial (O. vignei) and argali (O. ammon) diverged from domestic sheep about 0.89 and 1.11 million years ago (MYA), respectively; and dates the earliest radiation of domestic sheep common ancestor at around 0.3 MYA. Additionally, our data suggest that the rise of the modern sheep haplogroups happened in the span of time between six and 32 thousand years ago (KYA). A close phylogenetic relationship between the Cypriot and the Anatolian mouflon carrying the X haplotype was detected. The genetic distance between this group and the other ovine haplogroups supports the hypothesis that it may be a new haplogroup never described before. Furthermore, the updated phylogenetic tree presented in this study determines a finer classification of ovine species and may help to classify more accurately new mitogenomes within the established haplogroups so far identified.
- Published
- 2015
23. Antibodies recognizing Mycobacterium avium paratuberculosis epitopes cross-react with the beta-cell antigen ZnT8 in Sardinian type 1 diabetic patients
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Leonardo Antonio Sechi, Adolfo Pacifico, Vedran Brezar, Daniela Paccagnini, Niyaz Ahmed, Speranza Masala, Roberto Mallone, and Davide Cossu
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Bacterial Diseases ,Anatomy and Physiology ,endocrine system diseases ,Paratuberculosis ,Autoimmunity ,medicine.disease_cause ,Epitope ,Pathogenesis ,Epitopes ,Endocrinology ,Insulin-Secreting Cells ,Child ,Cation Transport Proteins ,Multidisciplinary ,medicine.diagnostic_test ,Mycobacterium avium subspecies paratuberculosis ,Mycobacterium Avium Complex ,Mycobacterium avium subsp. paratuberculosis ,Molecular mimicry ,Infectious Diseases ,Italy ,Medicine ,Antibody ,Research Article ,Adult ,Adolescent ,Science ,Immunology ,Endocrine System ,Zinc Transporter 8 ,Biology ,Cross Reactions ,Autoimmune Diseases ,Young Adult ,Antigen ,medicine ,Humans ,Diabetic Endocrinology ,Antigens, Bacterial ,nutritional and metabolic diseases ,Diabetes Mellitus Type 1 ,biology.organism_classification ,medicine.disease ,Virology ,Diabetes Mellitus, Type 1 ,Immunoassay ,biology.protein ,Clinical Immunology - Abstract
The environmental factors at play in the pathogenesis of type 1 diabetes (T1D) remain enigmatic. Mycobacterium avium subspecies paratuberculosis (MAP) is transmitted from dairy herds to humans through food contamination. MAP causes an asymptomatic infection that is highly prevalent in Sardinian T1D patients compared with type 2 diabetes (T2D) and healthy controls. Moreover, MAP elicits humoral responses against several mycobacterial proteins. We asked whether antibodies (Abs) against one of these proteins, namely MAP3865c, which displays a sequence homology with the β-cell protein zinc transporter 8 (ZnT8) could be cross-reactive with ZnT8 epitopes. To this end, Ab responses against MAP3865c were analyzed in Sardinian T1D, T2D and healthy subjects using an enzymatic immunoassay. Abs against MAP3865c recognized two immunodominant transmembrane epitopes in 52-65% of T1D patients, but only in 5-7% of T2D and 3-5% of healthy controls. There was a linear correlation between titers of anti-MAP3865c and anti-ZnT8 Abs targeting these two homologous epitopes, and pre-incubation of sera with ZnT8 epitope peptides blocked binding to the corresponding MAP3865c peptides. These results demonstrate that Abs recognizing MAP3865c epitopes cross-react with ZnT8, possibly underlying a molecular mimicry mechanism, which may precipitate T1D in MAP-infected individuals.
- Published
- 2011
24. Association of Mycobacterium avium subsp. paratuberculosis with multiple sclerosis in Sardinian patients
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Leonardo Antonio Sechi, Davide Cossu, Jessica Frau, Speranza Masala, Eleonora Cocco, Daniela Paccagnini, Maria Giovanna Marrosu, and Niyaz Ahmed
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Bacterial Diseases ,Adult ,DNA, Bacterial ,Male ,Multiple Sclerosis ,Science ,Immunology ,Molecular Sequence Data ,Paratuberculosis ,Enzyme-Linked Immunosorbent Assay ,Complement receptor ,medicine.disease_cause ,Microbiology ,Polymerase Chain Reaction ,MED/07 Microbiologia e microbiologia clinica ,Autoimmune Diseases ,Immune system ,Gene mapping ,Bacterial Proteins ,Zoonoses ,Genetic predisposition ,medicine ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Biology ,Multidisciplinary ,biology ,Sequence Homology, Amino Acid ,Multiple sclerosis ,Middle Aged ,biology.organism_classification ,medicine.disease ,Mycobacterium Avium Complex ,Demyelinating Disorders ,Mycobacterium avium subsp. paratuberculosis ,Molecular mimicry ,Infectious Diseases ,Neurology ,Italy ,Medicine ,Clinical Immunology ,Female ,Mycobacterium ,Research Article - Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) infection is highly spread in the ruminant herds of Sardinia, in the Western Mediterranean. The objective of this study was to investigate prevalence of MAP infection in association with Multiple Sclerosis (MS) using clinical specimen from patients and controls. We analyzed samples for the presence of MAP specific DNA and to demonstrate humoral response to a MAP protein (MAP2694), a predicted homologue of the T-cell receptor gamma-chain/complement component 1 of the host. We found presence of MAP DNA in 42% of the MS patients and an extremely significant humoral immune response revealed by the MS patients against the MAP protein. In our opinion, this is the first report that significantly associates MAP infection with MS. Further studies will be required to confirm if MAP could be one of the triggers of MS, according to the molecular mimicry theory, in susceptible (and genetically at risk) individuals.
- Published
- 2011
25. Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples
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Podestà, Marina, primary, Bruschettini, Matteo, additional, Cossu, Claudia, additional, Sabatini, Federica, additional, Dagnino, Monica, additional, Romantsik, Olga, additional, Spaggiari, Grazia Maria, additional, Ramenghi, Luca Antonio, additional, and Frassoni, Francesco, additional
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- 2015
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26. Human Serum Albumin Increases the Stability of Green Tea Catechins in Aqueous Physiological Conditions
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Zinellu, Angelo, primary, Sotgia, Salvatore, additional, Scanu, Bastianina, additional, Forteschi, Mauro, additional, Giordo, Roberta, additional, Cossu, Annalisa, additional, Posadino, Anna Maria, additional, Carru, Ciriaco, additional, and Pintus, Gianfranco, additional
- Published
- 2015
- Full Text
- View/download PDF
27. Intention Understanding in Autism
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Giacomo Rizzolatti, Sonia Boria, Laura Sparaci, Giuseppe Cossu, Maddalena Fabbri-Destro, Erica Santelli, Corrado Sinigaglia, and Luigi Cattaneo
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medicine.medical_specialty ,Multidisciplinary ,business.industry ,Science ,lcsh:R ,Alternative medicine ,Correction ,lcsh:Medicine ,medicine.disease ,Medicine ,Autism ,lcsh:Q ,lcsh:Science ,business ,Cognitive psychology - Published
- 2009
28. Intention understanding in autism
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Giuseppe Cossu, Sonia Boria, Maddalena Fabbri-Destro, Erica Santelli, Corrado Sinigaglia, Giacomo Rizzolatti, Laura Sparaci, and Luigi Cattaneo
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genetic structures ,Neurological Disorders/Developmental and Pediatric Neurology ,media_common.quotation_subject ,actions ,autism ,lcsh:Medicine ,Context (language use) ,Intention ,Motor Activity ,Biology ,Apraxia ,Perception ,medicine ,motor control ,Humans ,movements ,Autistic Disorder ,Child ,autism, mirror neurons, motor control, actions, movements, tools, apraxia ,lcsh:Science ,Mirror neuron ,mirror neurons ,media_common ,Neuroscience/Cognitive Neuroscience ,Neuroscience/Behavioral Neuroscience ,Pediatrics and Child Health/Child and Adolescent Psychiatry ,Multidisciplinary ,lcsh:R ,Motor control ,apraxia ,medicine.disease ,Comprehension ,Neuroscience/Psychology ,Autism spectrum disorder ,Case-Control Studies ,tools ,Autism ,lcsh:Q ,Research Article ,Cognitive psychology - Abstract
When we observe a motor act (e.g. grasping a cup) done by another individual, we extract, according to how the motor act is performed and its context, two types of information: the goal (grasping) and the intention underlying it (e.g. grasping for drinking). Here we examined whether children with autistic spectrum disorder (ASD) are able to understand these two aspects of motor acts. Two experiments were carried out. In the first, one group of high-functioning children with ASD and one of typically developing (TD) children were presented with pictures showing hand-object interactions and asked what the individual was doing and why. In half of the "why" trials the observed grip was congruent with the function of the object ("why-use" trials), in the other half it corresponded to the grip typically used to move that object ("why-place" trials). The results showed that children with ASD have no difficulties in reporting the goals of individual motor acts. In contrast they made several errors in the why task with all errors occurring in the "why-place" trials. In the second experiment the same two groups of children saw pictures showing a hand-grip congruent with the object use, but within a context suggesting either the use of the object or its placement into a container. Here children with ASD performed as TD children, correctly indicating the agent's intention. In conclusion, our data show that understanding others' intentions can occur in two ways: by relying on motor information derived from the hand-object interaction, and by using functional information derived from the object's standard use. Children with ASD have no deficit in the second type of understanding, while they have difficulties in understanding others' intentions when they have to rely exclusively on motor cues.
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- 2009
29. Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis
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Marcello Allegretti, Maurilio Sampaolesi, Paolo Michieli, Gabriella Cusella De Angelis, Cristina Basilico, Marco Cassano, Giulio Cossu, Frank N. Martin, Vania Broccoli, Laura Benedetti, Paolo M. Comoglio, Renata Boratto, Yvan Torrente, Claudia Omes, Amanda Finan, Stefano Biressi, and Wölfl, Stefan
- Subjects
metabolism [Recombinant Proteins] ,analysis ,Cellular differentiation ,medicine.medical_treatment ,Biotechnology/Chemical Biology of the Cell ,metabolism [Stem Cells] ,lcsh:Medicine ,Apoptosis ,Muscular Dystrophies ,Transgenic ,Mice ,injuries [Muscles] ,Models ,Myosin ,Morphogenesis ,lcsh:Science ,injuries ,Mice, Knockout ,Multidisciplinary ,metabolism [Proto-Oncogene Proteins c-met] ,Muscles ,Stem Cells ,Cell Differentiation ,Proto-Oncogene Proteins c-met ,Recombinant Proteins ,Cell biology ,Cytokine ,Phenotype ,muscle hipertrofy ,Hepatocyte growth factor ,Tyrosine kinase ,medicine.drug ,Research Article ,Adult ,Cell Survival ,Knockout ,Mice, Transgenic ,magic-factor1 ,Biology ,Models, Biological ,myogenic progenitors ,Paracrine signalling ,Muscular Diseases ,Proto-Oncogene Proteins ,Sarcoglycans ,pathology [Muscles] ,medicine ,Animals ,Regeneration ,Autocrine signalling ,Cell Biology/Gene Expression ,Cell Proliferation ,Cell growth ,lcsh:R ,Correction ,Hypertrophy ,Biological ,Immunology ,metabolism [Sarcoglycans] ,Developmental Biology/Cell Differentiation ,Muscles: pathology ,Proto-Oncogene Proteins c-met: metabolism ,Recombinant Proteins: metabolism ,Sarcoglycans: metabolism ,Stem Cells: metabolism ,metabolism ,pathology [Adult ,Muscles] ,pathology ,lcsh:Q - Abstract
BACKGROUND: Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1) is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with alpha-sarcoglycan knock-out mice -a mouse model of muscular dystrophy- or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests. CONCLUSIONS/SIGNIFICANCE: Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major muscular diseases such as cachexia or muscular dystrophy. ispartof: PLoS One vol:3 issue:9 ispartof: location:United States status: published
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- 2008
30. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis
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Oswaldo Lorenzo-Betancor, Andrea Varrone, Henry Houlden, Pau Pastor, Paolo Barone, Orlando Graziani Povoas Barsottini, Thomas Foltynie, José Matías Arbelo, Marcelo Q. Hoexter, Giovanni Cossu, André Carvalho Felício, Kailash P. Bhatia, Joanna Herrera, Alisdair McNeill, Vincenzo Bonifati, Concepcion Isla, Sabina Pappatà, Anthony H.V. Schapira, Ruey-Meei Wu, Patricia de Carvalho Aguiar, Niccolo E. Mencacci, Maria Teresa Pellecchia, Henrique Ballalai Ferraz, Kai-Yuan Tzen, Pietro Cortelli, Rodrigo A. Bressan, Laura Silveria-Moriyama, Sevasti Bostantjopoulou, Andrew J. Lees, A. McNeill, R. Wu, K. Tzen, P. C. Aguiar, J. M. Arbelo, P. Barone, K. Bhatia, O. Barsottini, V. Bonifati, S. Bostantjopoulou, R. Bressan, G. Cossu, P. Cortelli, A. Felicio, H. B. Ferraz, J. Herrera, H. Houlden, M. Hoexter, C. Isla, A. Lee, O. Lorenzo-Betancor, N. E. Mencacci, P. Pastor, S. Pappata, M. T. Pellecchia, L. Silveria-Moriyama, A. Varrone, T. Foltynie, A. H. V, Clinical Genetics, UCL, Birmingham Womens Hosp, Natl Taiwan Univ Hosp, Hosp Israelita Albert Einstein, Hosp Univ Insular Gran Canaria, Univ Salerno, Universidade Federal de São Paulo (UNIFESP), Erasmus MC, Aristotle Univ Thessaloniki, Gen Hosp S Michele AOB G Brotzu, Univ Bologna, UCL Inst Neurol, Univ Navarra, CNR, and Karolinska Inst
- Subjects
Male ,Pathology ,Parkinson's disease ,Caudate nucleus ,lcsh:Medicine ,pathology, Female, Genotype, Humans, Male, Neuroimaging, Parkinson Disease ,genetics/pathology, Positron-Emission Tomography, Putamen ,Parkin ,Diagnostic Radiology ,Cohort Studies ,pathology, Cohort Studies, Demography, Dopamine Plasma Membrane Transport Protein ,chemistry.chemical_compound ,0302 clinical medicine ,Autosomal Recessive ,Medicine ,lcsh:Science ,Neuropathology ,0303 health sciences ,Movement Disorders ,Multidisciplinary ,Putamen ,Parkinson Disease ,LRRK2 ,Neurology ,Autosomal Dominant ,Female ,Radiology ,Research Article ,Adult ,medicine.medical_specialty ,Genotype ,Neuroimaging ,PINK1 ,03 medical and health sciences ,Diagnostic Medicine ,Humans ,Demography ,030304 developmental biology ,Clinical Genetics ,Tomography, Emission-Computed, Single-Photon ,Alpha-synuclein ,Dopamine Plasma Membrane Transport Proteins ,metabolism, Dopaminergic Neuron ,business.industry ,Dopaminergic Neurons ,lcsh:R ,Personalized Medicine ,medicine.disease ,nervous system diseases ,chemistry ,Anatomical Pathology ,Positron-Emission Tomography ,lcsh:Q ,Emission-Computed ,Nuclear Medicine ,Caudate Nucleus ,Adult, Caudate Nucleu ,pathology, Tomography ,business ,Neuroscience ,Glucocerebrosidase ,030217 neurology & neurosurgery ,Single-Photon - Abstract
Wellcome Trust/MRC Joint Call in Neurodegeneration award United Kingdom Medical Research Council Wellcome Trust Parkinson's Disease UK Kattan Trust Objectives: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. the right: left asymmetry index and striatal asymmetry index was calculated.Results: Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). the asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions: the asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss. UCL, Dept Clin Neurosci, Inst Neurol, London, England Birmingham Womens Hosp, Reg Genet Unit, Dept Clin Genet, Birmingham, W Midlands, England Natl Taiwan Univ Hosp, Coll Med, Dept Neurol, Taipei, Taiwan Natl Taiwan Univ Hosp, Coll Med, Dept Nucl Med, Taipei, Taiwan Hosp Israelita Albert Einstein, Inst Israelita Ensino & Pesquisa Albert Einstein, São Paulo, Brazil Hosp Univ Insular Gran Canaria, Dept Neurol, Parkinsons & Movement Disorders Unit, Las Palmas Gran Canaria, Spain Univ Salerno, Ctr Neurodegenerat Dis, Salerno, Fisciano Provin, Italy UCL, Inst Neurol, Sobell Dept Motor Sci, London, England Universidade Federal de São Paulo, Dept Neurol, São Paulo, Brazil Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Dept Neurol 3, GR-54006 Thessaloniki, Greece Gen Hosp S Michele AOB G Brotzu, Neurol Serv, Cagliari, Italy Gen Hosp S Michele AOB G Brotzu, Stroke Unit, Cagliari, Italy Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy Universidade Federal de São Paulo UNIFESP, EPM, Div Movement Disorders, São Paulo, Brazil UCL Inst Neurol, Dept Mol Neurosci, London, England Univ Navarra, Div Neurosci, Ctr Appl Med Res, Neurogenet Lab, E-31080 Pamplona, Spain CNR, Inst Biostruct & Bioimaging, I-80125 Naples, Italy Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden Universidade Federal de São Paulo, Dept Neurol, São Paulo, Brazil Universidade Federal de São Paulo UNIFESP, EPM, Div Movement Disorders, São Paulo, Brazil Wellcome Trust/MRC Joint Call in Neurodegeneration award: WT089698 United Kingdom Medical Research Council: G1001983 Web of Science
- Published
- 2013
31. Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples
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Claudia Cossu, Matteo Bruschettini, Marina Podestà, Grazia Maria Spaggiari, Federica Sabatini, Francesco Frassoni, Olga Romantsik, Luca Antonio Ramenghi, and Monica Dagnino
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Term Birth ,medicine.medical_treatment ,lcsh:Medicine ,Antigens, CD34 ,Biology ,Placenta cord banking ,Umbilical cord ,Andrology ,Antigens, CD ,Pregnancy ,Receptors, Transferrin ,medicine ,Humans ,Progenitor cell ,lcsh:Science ,Erythroid Precursor Cells ,Multidisciplinary ,lcsh:R ,Infant, Newborn ,Endothelial Cells ,Stem-cell therapy ,Aldehyde Dehydrogenase ,Fetal Blood ,Hematopoietic Stem Cells ,Blood Cell Count ,Haematopoiesis ,medicine.anatomical_structure ,Cord blood ,Immunology ,Premature Birth ,Female ,lcsh:Q ,Stem cell ,Infant, Premature ,Research Article - Abstract
Background Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. Methods and Results Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15–4.8) vs 0.3% (0.032–2.23) p = 0.0001 and in neonates
- Published
- 2015
32. Detection of Serum Antibodies Cross-Reacting with Mycobacterium avium Subspecies paratuberculosis and Beta-Cell Antigen Zinc Transporter 8 Homologous Peptides in Patients with High-Risk Proliferative Diabetic Retinopathy
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Pinna, Antonio, primary, Masala, Speranza, additional, Blasetti, Francesco, additional, Maiore, Irene, additional, Cossu, Davide, additional, Paccagnini, Daniela, additional, Mameli, Giuseppe, additional, and Sechi, Leonardo A., additional
- Published
- 2014
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33. Recognition of Zinc Transporter 8 and MAP3865c Homologous Epitopes by Hashimoto's Thyroiditis Subjects from Sardinia: A Common Target with Type 1 Diabetes?
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Masala, Speranza, primary, Cossu, Davide, additional, Palermo, Mario, additional, and Sechi, Leonardo Antonio, additional
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- 2014
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34. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis
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McNeill, Alisdair, primary, Wu, Ruey-Meei, additional, Tzen, Kai-Yuan, additional, Aguiar, Patricia C., additional, Arbelo, Jose M., additional, Barone, Paolo, additional, Bhatia, Kailash, additional, Barsottini, Orlando, additional, Bonifati, Vincenzo, additional, Bostantjopoulou, Sevasti, additional, Bressan, Rodrigo, additional, Cossu, Giovanni, additional, Cortelli, Pietro, additional, Felicio, Andre, additional, Ferraz, Henrique B., additional, Herrera, Joanna, additional, Houlden, Henry, additional, Hoexter, Marcelo, additional, Isla, Concepcion, additional, Lees, Andrew, additional, Lorenzo-Betancor, Oswaldo, additional, Mencacci, Niccolo E., additional, Pastor, Pau, additional, Pappata, Sabina, additional, Pellecchia, Maria Teresa, additional, Silveria-Moriyama, Laura, additional, Varrone, Andrea, additional, Foltynie, Tom, additional, and Schapira, Anthony H. V., additional
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- 2013
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35. Mitochondrial DNA Reveals Genetic Structuring of Pinna nobilis across the Mediterranean Sea
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Sanna, Daria, primary, Cossu, Piero, additional, Dedola, Gian Luca, additional, Scarpa, Fabio, additional, Maltagliati, Ferruccio, additional, Castelli, Alberto, additional, Franzoi, Piero, additional, Lai, Tiziana, additional, Cristo, Benedetto, additional, Curini-Galletti, Marco, additional, Francalacci, Paolo, additional, and Casu, Marco, additional
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- 2013
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36. Zinc Transporter 8 and MAP3865c Homologous Epitopes are Recognized at T1D Onset in Sardinian Children
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Masala, Speranza, primary, Zedda, Maria Antonietta, additional, Cossu, Davide, additional, Ripoli, Carlo, additional, Palermo, Mario, additional, and Sechi, Leonardo A., additional
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- 2013
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37. A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor
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Persu, Alexandre, primary, Lambert, Michel, additional, Deinum, Jaap, additional, Cossu, Marta, additional, de Visscher, Nathalie, additional, Irenge, Leonid, additional, Ambroise, Jerôme, additional, Minon, Jean-Marc, additional, Nesterovitch, Andrew B., additional, Churbanov, Alexander, additional, Popova, Isolda A., additional, Danilov, Sergei M., additional, Danser, A. H. Jan, additional, and Gala, Jean-Luc, additional
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- 2013
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38. Kinetic and Structural Evidences on Human Prolidase Pathological Mutants Suggest Strategies for Enzyme Functional Rescue
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Besio, Roberta, primary, Gioia, Roberta, additional, Cossu, Federica, additional, Monzani, Enrico, additional, Nicolis, Stefania, additional, Cucca, Lucia, additional, Profumo, Antonella, additional, Casella, Luigi, additional, Tenni, Ruggero, additional, Bolognesi, Martino, additional, Rossi, Antonio, additional, and Forlino, Antonella, additional
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- 2013
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39. The Interaction of Large Amplitude Internal Seiches with a Shallow Sloping Lakebed: Observations of Benthic Turbulence in Lake Simcoe, Ontario, Canada
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Cossu, Remo, primary and Wells, Mathew G., additional
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- 2013
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40. Altered Glucose Homeostasis Is Associated with Increased Serum Apelin Levels in Type 2 Diabetes Mellitus
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Cavallo, Maria Gisella, primary, Sentinelli, Federica, additional, Barchetta, Ilaria, additional, Costantino, Carmine, additional, Incani, Michela, additional, Perra, Laura, additional, Capoccia, Danila, additional, Romeo, Stefano, additional, Cossu, Efisio, additional, Leonetti, Frida, additional, Agati, Luciano, additional, and Baroni, Marco G., additional
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- 2012
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41. Ethylene Synthesis and Regulated Expression of Recombinant Protein in Synechocystis sp. PCC 6803
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Guerrero, Fernando, primary, Carbonell, Verónica, additional, Cossu, Matteo, additional, Correddu, Danilo, additional, and Jones, Patrik R., additional
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- 2012
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42. Structural Insight into Inhibitor of Apoptosis Proteins Recognition by a Potent Divalent Smac-Mimetic
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Cossu, Federica, primary, Milani, Mario, additional, Vachette, Patrice, additional, Malvezzi, Francesca, additional, Grassi, Serena, additional, Lecis, Daniele, additional, Delia, Domenico, additional, Drago, Carmelo, additional, Seneci, Pierfausto, additional, Bolognesi, Martino, additional, and Mastrangelo, Eloise, additional
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- 2012
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43. Apricot Melanoidins Prevent Oxidative Endothelial Cell Death by Counteracting Mitochondrial Oxidation and Membrane Depolarization
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Cossu, Annalisa, primary, Posadino, Anna Maria, additional, Giordo, Roberta, additional, Emanueli, Costanza, additional, Sanguinetti, Anna Maria, additional, Piscopo, Amalia, additional, Poiana, Marco, additional, Capobianco, Giampiero, additional, Piga, Antonio, additional, and Pintus, Gianfranco, additional
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- 2012
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44. Mitochondrial DNA Reveals Genetic Structuring of Pinna nobilis across the Mediterranean Sea
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Piero Franzoi, Benedetto Cristo, Daria Sanna, Piero Cossu, Paolo Francalacci, Gian Luca Dedola, Alberto Castelli, Fabio Scarpa, Marco Casu, Tiziana Lai, Ferruccio Maltagliati, and Marco Curini-Galletti
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Gene Flow ,Evolutionary Genetics ,Mediterranean climate ,Conservation of Natural Resources ,Marine ecoregions ,Molecular Sequence Data ,lcsh:Medicine ,Population genetics ,Marine Biology ,DNA, Mitochondrial ,Electron Transport Complex IV ,Evolution, Molecular ,Marine Conservation ,Mediterranean sea ,RNA, Ribosomal, 16S ,Mediterranean Sea ,Genetics ,Animals ,Cluster Analysis ,Genetic variability ,lcsh:Science ,Biology ,Ecosystem ,Phylogeny ,Evolutionary Biology ,Multidisciplinary ,Models, Genetic ,biology ,Ecology ,BIO/18 Genetica ,lcsh:R ,Genetic Variation ,Bayes Theorem ,Malacology ,biology.organism_classification ,Bivalvia ,BIO/05 Zoologia ,Genetic divergence ,Phylogeography ,Genes, Mitochondrial ,Genetics, Population ,lcsh:Q ,Animal Genetics ,Zoology ,Population Genetics ,Multilocus Sequence Typing ,Research Article ,Pinna nobilis - Abstract
Pinna nobilis is the largest endemic Mediterranean marine bivalve. During past centuries, various human activities have promoted the regression of its populations. As a consequence of stringent standards of protection, demographic expansions are currently reported in many sites. The aim of this study was to provide the first large broad-scale insight into the genetic variability of P. nobilis in the area that encompasses the western Mediterranean, Ionian Sea, and Adriatic Sea marine ecoregions. To accomplish this objective twenty-five populations from this area were surveyed using two mitochondrial DNA markers (COI and 16S). Our dataset was then merged with those obtained in other studies for the Aegean and Tunisian populations (eastern Mediterranean), and statistical analyses (Bayesian model-based clustering, median-joining network, AMOVA, mismatch distribution, Tajima’s and Fu’s neutrality tests and Bayesian skyline plots) were performed. The results revealed genetic divergence among three distinguishable areas: (1) western Mediterranean and Ionian Sea; (2) Adriatic Sea; and (3) Aegean Sea and Tunisian coastal areas. From a conservational point of view, populations from the three genetically divergent groups found may be considered as different management units.
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- 2013
45. The Interaction of Large Amplitude Internal Seiches with a Shallow Sloping Lakebed: Observations of Benthic Turbulence in Lake Simcoe, Ontario, Canada
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Remo Cossu and Mathew G. Wells
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0106 biological sciences ,Convection ,Atmospheric Science ,Environmental Engineering ,Seiche ,010504 meteorology & atmospheric sciences ,Climate ,lcsh:Medicine ,Marine and Aquatic Sciences ,Stratification (water) ,Fresh Water ,Oceanography ,Atmospheric sciences ,01 natural sciences ,Diffusion ,symbols.namesake ,Meteorology ,Water column ,Downwelling ,Limnology ,Froude number ,Hydrosphere ,lcsh:Science ,0105 earth and related environmental sciences ,Freshwater Ecology ,Ontario ,Physics ,Multidisciplinary ,Geography ,010604 marine biology & hydrobiology ,lcsh:R ,Temperature ,Physical Limnology ,Lakes ,Geophysics ,Physical Geography ,Benthic zone ,Earth Sciences ,symbols ,lcsh:Q ,Seasons ,Thermocline ,Environmental Sciences ,Research Article ,Physical Oceanography ,Environmental Monitoring - Abstract
Observations of the interactions of large amplitude internal seiches with the sloping boundary of Lake Simcoe, Canada show a pronounced asymmetry between up- and downwelling. Data were obtained during a 42-day period in late summer with an ADCP and an array of four thermistor chains located in a 5 km line at the depths where the thermocline intersects the shallow slope of the lakebed. The thermocline is located at depths of 12-14 m during the strongly stratified period of late summer. During periods of strong westerly winds the thermocline is deflected as much as 8 m vertically and interacts directly with the lakebed at depth between 14-18 m. When the thermocline was rising at the boundary, the stratification resembles a turbulent bore that propagates up the sloping lakebed with a speed of 0.05-0.15 m s(-1) and a Froude number close to unity. There were strong temperature overturns associated with the abrupt changes in temperature across the bore. Based on the size of overturns in the near bed stratification, we show that the inferred turbulent diffusivity varies by up to two orders of magnitude between up- and downwellings. When the thermocline was rising, estimates of turbulent diffusivity were high with KZ ∼10(-4) m(2)s(-1), whereas during downwelling events the near-bed stratification was greatly increased and the turbulence was reduced. This asymmetry is consistent with previous field observations and underlines the importance of shear-induced convection in benthic bottom boundary layers of stratified lakes.
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- 2013
46. Structural Insight into Inhibitor of Apoptosis Proteins Recognition by a Potent Divalent Smac-Mimetic
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Francesca Malvezzi, Martino Bolognesi, Patrice Vachette, Mario Milani, Carmelo Drago, Serena Grassi, Daniele Lecis, Pierfausto Seneci, Federica Cossu, Domenico Delia, and Eloise Mastrangelo
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Apoptosis Inhibitor ,Molecular Conformation ,lcsh:Medicine ,Plasma protein binding ,Crystallography, X-Ray ,medicine.disease_cause ,Biochemistry ,Inhibitor of Apoptosis Proteins ,Biomimetics ,Molecular Cell Biology ,Basic Cancer Research ,X-LINKED INHIBITOR ,Signaling in Cellular Processes ,lcsh:Science ,Energy-Producing Organelles ,Apoptotic Signaling Cascade ,Inhibitor of apoptosis domain ,Crystallography ,Multidisciplinary ,Cell Death ,Effector ,Intracellular Signaling Peptides and Proteins ,Antiapoptotic Signaling ,SMALL-ANGLE SCATTERING ,Signaling Cascades ,Cell biology ,XIAP ,Molecular Docking Simulation ,Molecular mimicry ,Oncology ,Caspases ,Medicine ,Signal transduction ,Protein Binding ,Research Article ,Signal Transduction ,Materials Science ,X-Linked Inhibitor of Apoptosis Protein ,Bioenergetics ,Biology ,Inhibitor of apoptosis ,Mitochondrial Proteins ,Cell Line, Tumor ,medicine ,Humans ,Protein Interactions ,lcsh:R ,Molecular Mimicry ,Proteins ,Molecular biology ,Enzyme Activation ,Proteolysis ,lcsh:Q ,Protein Multimerization ,Apoptosis Regulatory Proteins - Abstract
Genetic alterations enhancing cell survival and suppressing apoptosis are hallmarks of cancer that significantly reduce the efficacy of chemotherapy or radiotherapy. The Inhibitor of Apoptosis Protein (IAP) family hosts conserved proteins in the apoptotic pathway whose over-expression, frequently found in tumours, potentiates survival and resistance to anticancer agents. In humans, IAPs comprise eight members hosting one or more structural Baculoviral IAP Repeat (BIR) domains. Cellular IAPs (cIAP1 and 2) indirectly inhibit caspase-8 activation, and regulate both the canonical and the non-canonical NF-κB signaling pathways. In contrast to cIAPs, XIAP (X chromosome-linked Inhibitor of Apoptosis Protein) inhibits directly the effector caspases-3 and -7 through its BIR2 domain, and initiator caspase-9 through its BIR3 domain; molecular docking studies suggested that Smac/DIABLO antagonizes XIAP by simultaneously targeting both BIR2 and BIR3 domains. Here we report analytical gel filtration, crystallographic and SAXS experiments on cIAP1-BIR3, XIAP-BIR3 and XIAP-BIR2BIR3 domains, alone and in the presence of compound 9a, a divalent homodimeric Smac mimetic. 9a is shown to bind two BIR domains inter- (in the case of two BIR3) and intra-molecularly (in the case of XIAP-BIR2BIR3), with higher affinity for cIAP1-BIR3, relative to XIAP-BIR3. Despite the different crystal lattice packing, 9a maintains a right handed helical conformation in both cIAP1-BIR3 and XIAP-BIR3 crystals, that is likely conserved in solution as shown by SAXS data. Our structural results demonstrate that the 9a linker length, its conformational degrees of freedom and its hydrophobicity, warrant an overall compact structure with optimal solvent exposure of its two active moieties for IAPs binding. Our results show that 9a is a good candidate for pre-clinical and clinical studies, worth of further investigations in the field of cancer therapy.
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- 2012
47. Motor Representation of Actions in Children with Autism
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Cossu, Giuseppe, primary, Boria, Sonia, additional, Copioli, Cristiana, additional, Bracceschi, Roberta, additional, Giuberti, Virginia, additional, Santelli, Erica, additional, and Gallese, Vittorio, additional
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- 2012
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48. Hmgb3 Is Regulated by MicroRNA-206 during Muscle Regeneration
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Maciotta, Simona, primary, Meregalli, Mirella, additional, Cassinelli, Letizia, additional, Parolini, Daniele, additional, Farini, Andrea, additional, Fraro, Giulia Del, additional, Gandolfi, Francesco, additional, Forcato, Mattia, additional, Ferrari, Sergio, additional, Gabellini, Davide, additional, Bicciato, Silvio, additional, Cossu, Giulio, additional, and Torrente, Yvan, additional
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- 2012
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49. Effect of Multiple Parasitic Infections on the Tolerance to Pollutant Contamination
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Gismondi, Eric, primary, Rigaud, Thierry, additional, Beisel, Jean-Nicolas, additional, and Cossu-Leguille, Carole, additional
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- 2012
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50. Polymorphus Minutus Affects Antitoxic Responses of Gammarus Roeseli Exposed to Cadmium
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Gismondi, Eric, primary, Beisel, Jean-Nicolas, additional, and Cossu-Leguille, Carole, additional
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- 2012
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