59 research outputs found
Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways
Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also
between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles,
while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi
apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics
of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main
routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder
content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups
contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some
of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more
disordered (,23%) than the other two, COPI (,9%) and COPII (,8%). We show that this structural phenomenon enhances
the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other
two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its
prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest
capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific
functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for
protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of
structural disorder in vesicle trafficking and suggest major roles for this structural property in shaping the differences of
evolutionary adaptability in the three routes
The Phenotype and Genotype of Mevalonate Kinase Deficiency: A Series of 114 Cases From the Eurofever Registry
OBJECTIVE:Mevalonate kinase deficiency (MKD) is a rare metabolic disease characterized by recurrent inflammatory episodes. This study was undertaken to describe the genotype, phenotype, and response to treatment in an international cohort of MKD patients.
METHODS:All MKD cases were extracted from the Eurofever registry (Executive Agency for Health and Consumers project no. 2007332), an international, multicenter registry that retrospectively collects data on children and adults with autoinflammatory diseases.
RESULTS:The study included 114 MKD patients. The median age at onset was 0.5 years. Patients had on average 12 episodes per year. Most patients had gastrointestinal symptoms (n = 112), mucocutaneous involvement (n = 99), lymphadenopathy (n = 102), or musculoskeletal symptoms (n = 89). Neurologic symptoms included headache (n = 43), cerebellar syndrome (n = 2), and mental retardation (n = 4). AA amyloidosis was noted in 5 patients, almost twice as many as expected from findings in previous cohorts. Macrophage activation syndrome occurred in 1 patient. Patients were generally well between attacks, but 10-20% of the patients had constitutional symptoms, such as fatigue, between fever episodes. Patients with p.V377I/p.I268T compound heterozygosity had AA amyloidosis significantly more often. Patients without a p.V377I mutation more often had severe musculoskeletal involvement. Treatment with nonsteroidal antiinflammatory drugs relieved symptoms. Steroids given during attacks, anakinra, and etanercept appeared to improve symptoms and could induce complete remission in patients with MKD.
CONCLUSION:We describe the clinical and genetic characteristics of 114 MKD patients, which is the largest cohort studied so far. The clinical manifestations confirm earlier reports. However, the prevalence of AA amyloidosis is far higher than expected
Markov nets: Probabilistic models for distributed and concurrent systems
de systèmes complexe
On cyclic orders and synchronisation graphs
Theme 1 - Reseaux et systemes - Action MCRSIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.2000 n.4007 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc
Towards optimization of cyclic production systems
Theme 1 - Reseaux et systemes - Projet TRIOAvailable from INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.1999 n.3718 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc
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