University of Modena and Reggio Emilia

About: University of Modena and Reggio Emilia is a education organization based out in Modena, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 8179 authors who have published 22418 publications receiving 671337 citations. The organization is also known as: Università degli Studi di Modena e Reggio Emilia & Universita degli Studi di Modena e Reggio Emilia.

Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts.

Abstract: Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson's disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity-together with the LRR domain-to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD.

Familial aggregation of tumors in the three-year experience of a population-based colorectal cancer registry

Abstract: The familial occurrence of tumors has been investigated in 389 subjects with colorectal cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1984–1986, in the Local Health District, for malignancies of the large bowel. Among first-degree relatives of the registered patients there were 89 cases of colorectal cancer as opposed to 19 in a hospital-based control group matched for age and sex [odds ratio (OR), 7.5, P < 0.001]. This excess of neoplasms among relatives was particularly evident in siblings (60 versus 7, OR 14.7, P < 0.001) but it was observed also in parents (27 versus 12, OR 4.2, P < 0.01). Besides colorectal cancer there was no significant excess of other types of tumor in case families, whereas lung tumors tended to be more frequent in control relatives (32 versus 17). Almost half of the registered patients (182 out of 389) had one or more cases of cancer of any sites among relatives; similarly, in 68 there were one or more relatives affected by (or deceased for) colorectal cancer. Moreover, in 27 patients (7.0%) there were at least three cancers of any sites among relatives and in 15 the excess (two or more) was limited to neoplasms of the large bowel. In patients without or with only one neoplasm among relatives, cancers were mainly located in the left colon; however, cancer of the right colon became relatively more frequent in patients with two or more tumors in close relatives. In conclusion, the present study suggests that in approximately 15–20% of patients registered for colorectal cancer one or more first-degree relatives are affected by neoplasms of the large bowel. This familial occurrence of intestinal malignancies (but not of tumors of other organs) strongly suggests a genetic susceptibility to colorectal cancer in a fraction of these patients. Moreover, in a further subgroup of individuals (approximately 5% of all cases) the familial aggregation of two or more cases of colorectal cancer among relatives (besides the proband) and the frequent location of tumors in the right colon make the diagnosis of Lynch syndrome extremely probable.