Role of sortilin in the post-endocytic trafficking of thyroglobulin

Sortilin è una proteina di ~100 KDa appartenente alla famiglia delle proteine con dominio Vps10p. Sortilin è espressa da vari tipi cellulari, principalmente nel Golgi e negli endosomi, ed è coinvolta in diversi processi, tra cui l’endocitosi e il trasporto intracellulare di proteine. Sortilin è espressa dalle cellule epiteliali tiroidee a livello intracellulare e la sua espressione è TSH-dipendente. Nel presente studio è stata valutata l’interazione tra sortilin e la tireoglobulina (Tg). Mediante surface plasmon resonance, sortilin legava la Tg con elevata affinità (Kd ~1- ~30 nM.), proporzionalmente al contenuto in T3 della Tg stessa. Il legame era resistente a valori relativamente bassi di pH ed era specifico, come dimostrato dalla dose-dipendenza e dalla inibizione da parte di specifici legandi di sortilin. Mediante gene silencing di sortilin in cellule FRTL-5 o trasfezione di sortilin in cellule COS-7 o CHO, osservavamo che l’interazione tra sortilin e Tg non avviene a livello della membrana plasmatica o durante la via biosintetica della Tg. Veniva invece osservato che la Tg esogena lega sortilin a livello intracellulare dopo endocitosi della Tg stessa. Infatti, dopo incubazione delle cellule FRTL-5 con Tg, questa co-localizzava con sortilin a livello intracellulare e veniva co-precipitata da un anticorpo anti-sortilin. Tale interazione non influenzava la degradazione della Tg né la sua transcitosi. In esperimenti in cui veniva valutato il recycling della Tg, ovvero la sua ri-secrezione dopo internalizzazione, osservavamo che tale processo veniva ridotto dal silencing di sortilin nelle cellule FRTL-5 e aumentato dalla trasfezione con sortilin delle cellule CHO. Tale dato veniva confermato mediante microscopia elettronica dopo incubazione della cellule FRTL-5 con Tg marcata con oro. Dopo la sua internalizzazione, la Tg marcata e sortilin erano presenti negli stessi endosomi, e in vescicole extracellulari come risultato del recycling. I nostri dati mostrano che sortilin è un nuovo recettore intracellulare per la Tg ed è responsabile del recycling della stessa, un processo verosimilmente necessario per l’omeostasi tiroidea

On driver behavior recognition for increased safety:A roadmap

Advanced Driver-Assistance Systems (ADASs) are used for increasing safety in the automotive domain, yet current ADASs notably operate without taking into account drivers’ states, e.g., whether she/he is emotionally apt to drive. In this paper, we first review the state-of-the-art of emotional and cognitive analysis for ADAS: we consider psychological models, the sensors needed for capturing physiological signals, and the typical algorithms used for human emotion classification. Our investigation highlights a lack of advanced Driver Monitoring Systems (DMSs) for ADASs, which could increase driving quality and security for both drivers and passengers. We then provide our view on a novel perception architecture for driver monitoring, built around the concept of Driver Complex State (DCS). DCS relies on multiple non-obtrusive sensors and Artificial Intelligence (AI) for uncovering the driver state and uses it to implement innovative Human–Machine Interface (HMI) functionalities. This concept will be implemented and validated in the recently EU-funded NextPerception project, which is briefly introduced

Prognostic Analysis of the IDH1 G105G (rs11554137) SNP in IDH-Wildtype Glioblastoma

The G105G SNP (rs11554137) in the IDH1 gene is observed in about 10–15% of patients with a diffuse glioma. Data regarding its impact on gliomas are poor and partially conflicting, possibly due to the evolving classification of CNS tumors. The aim of this study was to investigate the G105G SNP prognostic significance in a homogenous cohort of IDH-wildtype glioblastomas, in agreement with the 2021 WHO classification. The study analyzed 211 patients by collecting several clinico-pathological and molecular characteristics, including the age, lesion localization, number of involved lobes, type of surgical treatment, disease outcome and MGMT promoter methylation status. PFS and DSS curves were plotted according to the Kaplan–Meier method and statistical analyses were performed using parametric and non-parametric tests. A total of 32 patients out of 211 (15.2%) were found to be G105G SNP carriers. No significant impact of the IDH1 G105G SNP on patients’ outcomes was observed in terms of PFS and DSS, while MGMT promoter methylation and gross total resection resulted as key prognostic factors in our cohort as expected. No prognostic impact of the IDH1 G105G SNP was detected in this strict cohort of IDH-wildtype glioblastomas. Analysis of larger cohorts is warranted to address the sample size limitations

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n\u2009=\u2009305,044), while 42% of prevalent women had breast cancer (n\u2009=\u2009604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since 6515 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+\u200937% vs 2010). The largest 10-year increases are foreseen for prostate (+\u200985%) and for thyroid cancers (+\u200979%), and for long-term survivors diagnosed since 20 or more years (+\u200945%). Among the population aged 6575 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation need

Position statement on the Joint ITA–NIST–USPTO collaboration initiative regarding standards : notice of public listening and request for comments

On 11th September 2023, the US Patent and Trademark Office (USPTO), the International Trade Administration (ITA), and the National Institute for Standards and Technology (NIST) called for stakeholder input on the current state of U.S. firm participation in standard-setting, and the ability of U.S. industry to readily adopt standards to grow and compete, especially as they relate to the standardisation of critical and emerging technologies. The Centre for a Digital Society (CDS) of the European University Institute (EUI) is thankful for the opportunity to offer its comments. We would like to express our view on the legislative proposal of the European Commission (EC) for a Regulation on Standard Essential Patents (hereinafter, the Regulation) as it relates to question no. 1 of the Request for Comments on the impact of foreign IPR policies on US leadership and participation in international standard setting. Furthermore, concerning question no. 9 on possible standard-essential patents (SEP) transparency measures, we highlight the possibility of improving the USPTO patent register already in place

Position statement on the European Commission’s proposal for a SEPs regulation

On 27th April 2023, the European Commission published a proposal for a Regulation on Standard Essential Patents (hereinafter, SEPs Regulation) and allowed the public to provide feedback. The Centre for a Digital Society (CDS) of the European University Institute (EUI) is thankful for the opportunity to offer its comments and make suggestions on the proposed Regulation. Our team of researchers has significant research, policy and training experience in the areas of intellectual property, telecommunications regulation, standardisation and EU competition policy. In this Position Statement, we caution against adopting the proposed SEPs Regulation in its current form and suggest adopting guidance under Arts. 101 and 102 TFEU to clarify how SEP licensing should occur not to breach EU competition law. In the sub-optimal scenario where EU institutions would continue to pursue an immediate regulatory intervention, we provide substantial suggestions in an attempt to improve the current proposal of SEPs Regulation and limit certain negative consequences. Our constructive criticism aims to be a catalyst for the debate in the legislative process about the appropriate SEP licensing framework

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEADbox polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to 5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

BACKGROUND: Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. METHODS: 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. RESULTS: LEF ranged from 10 years for chronic lymphocytic leukaemia patients to 5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. CONCLUSIONS: Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good