1,720,969 research outputs found
Neuropatie ereditarie associate alla proteina zero della mielina (P0): dalla patologia alla patogenesi
No full textLa proteina P0 costituisce più del 50% delle proteine della mielina compatta del sistema
nervoso periferico; è una glicoproteina transmembrana sintetizzata dalle cellule di Schwann
mielinizzanti e codificata dal gene MPZ (myelin protein zero) situato sul cromosoma 1q22-23.
MPZ è diviso in 6 esoni, distribuiti in circa 7kb di DNA, codificanti per una proteina di 248
aminoacidi (aa); i primi 29 aa (codificati dall’esone 1) costituiscono il peptide segnale che viene
eliminato prima dell’inserzione della proteina P0 matura (219 aa) nella mielina (Lemke e Axel
1985, Hayasaka et al. 1993, Brown e Lemke 1997). La numerazione aminoacidica di P0
utilizzata in questo lavoro, non considera dunque i primi 29aa che non fanno parte della
proteina matura inserita nella mielina. P0 è formata da un esteso dominio extracellulare
glicosilato (P0ex) Ig-like di 124 aa, un singolo dominio transmembrana di 26 aa, con struttura
ad α-elica, ed una coda basica citoplasmatica (P0ic) di 69 aa che sembra formare 2 α-eliche. E’
una proteina altamente conservata la cui sequenza aminoacidica nell’uomo risulta essere
sovrapponibile a P0 di ratto e pollo rispettivamente per il 94% e il 75% (Uyemura e Kitamura
1991; Eichberg, 2002).
Oltre alla perdita della sequenza segnale, la catena polipeptidica in formazione va incontro a
modificazioni post-traduzionali, che consentirebbero alla proteina P0 di essere funzionale e
correttamente trasportata dal reticolo endoplasmico alla membrana plasmatica. P0 viene Nglicosilata
all’aminoacido asparagina93 (Asn93) dai carboidrati L2/HNK-1 ed L3 (Griffith et al.
1992, Filbin 1993, Filbin 1999, Sakamoto et al. 1987, Bollensen e Schachner 1987, Voshol et al.
1996, Gallego et al. 2001, Brunden 1992); inoltre è stata evidenziata la formazione di un
legame disolfuro in P0ec (cisteina21-cisteina98) che rende maggiormente stabile il dominio
immunoglobulinico e l’acilazione della cisteina153 che verosimilmente favorisce una minore
degradazione di P0 e promuove interazioni con il citoscheletro. Inoltre, durante la
mielinogenesi, la proteina P0 viene fosforilata ad opera di una protein-kinasi-C-α, in alcuni
aminoacidi, soprattutto serine ma anche tirosine (Ser197, Ser199, Ser 204, Ser208, Ser214,
Tyr191; Arg198SerThrLys201) della porzione citoplasmatica di P0 (Hilmi et al. 1995, Iyer et al.
1996, Iyer et al.2000, Xu et al. 2001; Konde e Eichberg, 2006)...Non disponibil
Primary neurolymphomatosis as clinical onset of chronic lymphocytic leukemia
Full text link[no abstract available
Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.
No full textBACKGROUND: Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B. OBJECTIVE: To assess the etiologic role of DNM2 in CMT. METHODS: We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. RESULTS: We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. CONCLUSION: Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology
Malattia di Charco-Marie-Tooth. Guida alla diagnosi molecolare.
No full textLa malattia di Charcot-Marie-Tooth (CMT) è la patologia genetica più frequente del sistema nervoso periferico. La diagnosi molecolare è essenziale per il counselling genetico, per la diagnosi differenziale con neuropatie acquisite fenotipicamente convergenti, nonché un prerequisito per terapie sperimentali mirate ai meccanismi patogenetici. Gli ultimi anni hanno registrato il moltiplicarsi dei fenotipi CMT e dei geni associati. Gli autori passano in rassegna le recenti acquisizioni della genetica ed illustrano i possibili percorsi clinici che orientino i tests molecolari
NERVE ULTRASOUND FINDINGS IN A COHORT OF PATIENTS WITH MPZ-RELATED CHARCOT-MARIE-TOOTH NEUROPATHIES
No full textN/
Parental mosaicism of a novel PMP22 mutation with a minimal neuropathic phenotype.
No full textGenetic germinal and somatic mosaicisms of dominant Charcot-Marie-Tooth disease (CMT) mutations are rarely reported and/or recognized. We describe a novel heterozygous p.Trp39Cys missense mutation in the extracellular domain of the peripheral myelin protein 22 (PMP22) associated with an early-onset demyelinating CMT type 1 E (CMT1E) in two siblings born from asymptomatic non-consanguineous parents. The 29-year-old mother, harboring approximately 20% of the mutant PMP22 allele in blood, had minor signs of distal polyneuropathy (pes cavus, decreased ankle jerk reflexes and vibration sense in legs) and slight reduction of sural nerve action potentials (SNAPs). Authors suggest that mutations of CMT-related genes which originate in post-zygotic stages may be associated with mild phenotypes of peripheral neuropathy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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