Protein domains required for nuclear and sub-nuclear targeting of subunits of splicing factor SF3a

Le but de ma thèse a été d'identifier les signaux responsables de l'adressage du complexe de splicing SF3a vers le noyau et d'étudier les domaines de ses sous-unités qui sont importants pour une localisation correcte du complexe. J'ai démontré que l'import de SF3a120 dans le noyau est indépendant de ses interactions avec les plus petites sous-unités et j'ai identifié une séquence de localisation nucléaire. J'ai démontré l'implication d'une région de 84 acides aminés, contenant le domaine SAP, dans l'adressage de SF3a60 vers les corps de Cajal (CBs). Cette même région est également suffisante pour envoyer deux protéines reporteurs vers les CBs, ce qui prouve que la région est nécessaire et suffisante pour l'adressage du complexe SF3a entier aux CBs. D'autre part, la partie amino-terminale de la coilin montre des similitudes de séquence avec le domaine SAP, ce qui indique une fonction similaire pour les séquences communes entre SF3a60 et la coilin

Structure-function analysis of the U2 snRNP-associated splicing factor SF3a

Human splicing factor SF3a is a part of the 17 S U2 snRNP (small nuclear ribonucleoprotein), which interacts with the pre-mRNA branch site early during spliceosome formation. The SF3a subunits of 60, 66 and 120 kDa are all required for SF3a function in vitro. Depletion of individual subunits from HeLa cells by RNA interference results in a global inhibition of splicing, indicating that SF3a is a constitutive splicing factor. Structure-function analyses have defined domains necessary for interactions within the SF3a heterotrimer, association with the U2 snRNP and spliceosome assembly. Studies aimed at the identification of regions in SF3a60 and SF3a66, required for proper intracellular localization, have led to a model for the final steps in U2 snRNP biogenesis and the proposal that SF3a is incorporated into the U2 snRNP in Cajal bodies

IPOD Study: Management of Acute Left Colonic Diverticulitis in Italian Surgical Departments

BACKGROUND: In recent years, the emergency management of acute left colonic diverticulitis (ALCD) has evolved dramatically despite lack of strong evidence. As a consequence, management strategies are frequently guided by surgeon's personal preference, rather than by scientific evidence. The primary aim of IPOD study (Italian Prospective Observational Diverticulitis study) is to describe both the diagnostic and treatment profiles of patients with ALCD in the Italian surgical departments. METHODS: IPOD study is a prospective observational study performed during a 6-month period (from April 1 2015 to September 1 2015) and including 89 Italian surgical departments. All consecutive patients with suspected clinical diagnosis of ALCD confirmed by imaging and seen by a surgeon were included in the study. The study was promoted by the Italian Society of Hospital Surgeons and the World Society of Emergency Surgery Italian chapter. RESULTS: Eleven hundred and twenty-five patients with a median age of 62 years [interquartile range (IQR), 51-74] were enrolled in the IPOD study. One thousand and fifty-four (93.7%) patients were hospitalized with a median duration of hospitalization of 7 days (IQR 5-10). Eight hundred and twenty-eight patients (73.6%) underwent medical treatment alone, 13 patients had percutaneous drainage (1.2%), and the other 284 (25.2%) patients underwent surgery as first treatment. Among 121 patients having diffuse peritonitis, 71 (58.7%) underwent Hartmann's resection. However, the Hartmann's resection was used even in patients with lower stages of ALCD (36/479; 7.5%) where other treatment options could be more adequate. CONCLUSIONS: The IPOD study demonstrates that in the Italian surgical departments treatment strategies for ALCD are often guided by the surgeon's personal preference

IPOD Study: Management of Acute Left Colonic Diverticulitis in Italian Surgical Departments.

Background: In recent years, the emergency management of acute left colonic diverticulitis (ALCD) has evolved dramatically despite lack of strong evidence. As a consequence, management strategies are frequently guided by surgeon’s personal preference, rather than by scientific evidence. The primary aim of IPOD study (Italian Prospective Observational Diverticulitis study) is to describe both the diagnostic and treatment profiles of patients with ALCD in the Italian surgical departments. Methods: IPOD study is a prospective observational study performed during a 6-month period (from April 1 2015 to September 1 2015) and including 89 Italian surgical departments. All consecutive patients with suspected clinical diagnosis of ALCD confirmed by imaging and seen by a surgeon were included in the study. The study was promoted by the Italian Society of Hospital Surgeons and the World Society of Emergency Surgery Italian chapter. Results: Eleven hundred and twenty-five patients with a median age of 62 years [interquartile range (IQR), 51–74] were enrolled in the IPOD study. One thousand and fifty-four (93.7%) patients were hospitalized with a median duration of hospitalization of 7 days (IQR 5–10). Eight hundred and twenty-eight patients (73.6%) underwent medical treatment alone, 13 patients had percutaneous drainage (1.2%), and the other 284 (25.2%) patients underwent surgery as first treatment. Among 121 patients having diffuse peritonitis, 71 (58.7%) underwent Hartmann’s resection. However, the Hartmann’s resection was used even in patients with lower stages of ALCD (36/479; 7.5%) where other treatment options could be more adequate. Conclusions: The IPOD study demonstrates that in the Italian surgical departments treatment strategies for ALCD are often guided by the surgeon’s personal preference

IPOD Study: Management of Acute Left Colonic Diverticulitis in Italian Surgical Departments

Background: In recent years, the emergency management of acute left colonic diverticulitis (ALCD) has evolved dramatically despite lack of strong evidence. As a consequence, management strategies are frequently guided by surgeon’s personal preference, rather than by scientific evidence. The primary aim of IPOD study (Italian Prospective Observational Diverticulitis study) is to describe both the diagnostic and treatment profiles of patients with ALCD in the Italian surgical departments. Methods: IPOD study is a prospective observational study performed during a 6-month period (from April 1 2015 to September 1 2015) and including 89 Italian surgical departments. All consecutive patients with suspected clinical diagnosis of ALCD confirmed by imaging and seen by a surgeon were included in the study. The study was promoted by the Italian Society of Hospital Surgeons and the World Society of Emergency Surgery Italian chapter. Results: Eleven hundred and twenty-five patients with a median age of 62 years [interquartile range (IQR), 51–74] were enrolled in the IPOD study. One thousand and fifty-four (93.7%) patients were hospitalized with a median duration of hospitalization of 7 days (IQR 5–10). Eight hundred and twenty-eight patients (73.6%) underwent medical treatment alone, 13 patients had percutaneous drainage (1.2%), and the other 284 (25.2%) patients underwent surgery as first treatment. Among 121 patients having diffuse peritonitis, 71 (58.7%) underwent Hartmann’s resection. However, the Hartmann’s resection was used even in patients with lower stages of ALCD (36/479; 7.5%) where other treatment options could be more adequate. Conclusions: The IPOD study demonstrates that in the Italian surgical departments treatment strategies for ALCD are often guided by the surgeon’s personal preference