RESUMO
Mastering dissipation in graphene-based nanostructures is still the major challenge in most fundamental and technological exploitations of these ultimate mechanical nanoresonators. Although high quality factors have been measured for carbon nanotubes (>106) and graphene (>105) at cryogenic temperatures, room-temperature values are orders of magnitude lower (≃102). We present here a controlled quality factor increase of up to ×103 for these basic carbon nanostructures when externally stressed like a guitar string. Quantitative agreement is found with theory attributing this decrease in dissipation to the decrease in viscoelastic losses inside the material, an effect enhanced by tunable "soft clamping". Quality factors exceeding 25â¯000 for SWCNTs and 5000 for graphene were obtained on several samples, reaching the limits of the graphene material itself. The combination of ultralow size and mass with high quality factors opens new perspectives for atomically localized force sensing and quantum computing as the coherence time exceeds state-of-the-art cryogenic devices.
RESUMO
We present here well-defined Coulomb staircases using an original field-emission experiment on several individual in situ-grown single-wall carbon nanotubes. A unique in situ process was applied nine times to progressively shorten one single-wall carbon nanotube down to ≃10 nm, which increased the oscillations periods from 5.5 to 80 V, the temperature for observable Coulomb staircase to 1100 K and the currents to 1.8 µA. This process led to the brightest electron source ever reported [9×1011 A/(str m2 V)].
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes do Sistema Nervoso/complicações , Glutamato Descarboxilase/imunologia , Encefalite Límbica/etiologia , Adolescente , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Humanos , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/imunologia , Imageamento por Ressonância Magnética , Masculino , Convulsões/sangue , Convulsões/diagnóstico por imagem , Convulsões/etiologiaRESUMO
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels > or =7 microg/l is 46%. Therefore, selection of patients with an AFP level above 7 microg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.
Assuntos
Apraxia Ideomotora/fisiopatologia , Ataxia/complicações , Ataxia/patologia , Oftalmoplegia/fisiopatologia , Adulto , Idade de Início , Apraxia Ideomotora/genética , Ataxia/genética , Estudos de Coortes , DNA Helicases , Progressão da Doença , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Enzimas Multifuncionais , Mutação de Sentido Incorreto/genética , Oftalmoplegia/genética , Fenótipo , RNA Helicases/genética , RNA Helicases/metabolismo , Estudos Retrospectivos , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismoRESUMO
Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX). We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade. Cerebellar ataxia was progressive, slowly leading to disability which was aggravated by axonal polyneuropathy present in almost all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor apraxia (OMA) was present in 32% of the patients while convergent strabismus was present in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more severe in the eldest patients; however it may also be an early sign since it was present in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in all but two patients who presented with head tremor and writer cramp, respectively. Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker to suggest molecular studies of the SETX gene.
Assuntos
Apraxias/genética , Ataxia Cerebelar/complicações , Ataxia Cerebelar/genética , Transtornos da Motilidade Ocular/complicações , Transtornos da Motilidade Ocular/genética , RNA Helicases/genética , Adolescente , Adulto , Idade de Início , Apraxias/complicações , Apraxias/patologia , Apraxias/fisiopatologia , Atrofia , Ataxia Cerebelar/patologia , Ataxia Cerebelar/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , DNA Helicases , Análise Mutacional de DNA , Progressão da Doença , Feminino , Humanos , Masculino , Enzimas Multifuncionais , Mutação , Fibras Nervosas Mielinizadas/patologia , Condução Nervosa , Transtornos da Motilidade Ocular/patologia , Transtornos da Motilidade Ocular/fisiopatologia , Linhagem , Fenótipo , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe's disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness. Most of them die within the first year of life from cardiac and/or respiratory failure. In the majority of cases of Pompe's disease, onset of symptoms occurs after infancy, ranging widely from the first to sixth decade of life (late-onset Pompe's disease or LOPD). Progression of the disease is relentless and patients eventually progress to loss of ambulation and death due to respiratory failure. The objective of this study was to characterize the clinical presentation of 6 patients (3 with EOPD and the other 3 with LOPD) of 5 families from the East of Algeria. All our patients were diagnosed as having Pompe's disease based on biochemical confirmations of GAA deficiency by dried blood spots (DBS) and GAA gene mutations were analyzed in all patients who consented (n = 4). Our results are similar to other ethnic groups.
RESUMO
BACKGROUND: Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive and predominant spasticity of the lower limbs, in which dominant, recessive, and X-linked forms have been described. While autosomal dominant HSP has been extensively studied, autosomal recessive HSP is less well known and is considered a rare condition. OBJECTIVE: To analyze the clinical presentation in a large group of patients with autosomal recessive HSP from Portugal and Algeria to define homogeneous groups that could serve as a guide for future molecular studies. RESULTS: Clinical features in 106 patients belonging to 46 Portuguese and Algerian families with autosomal recessive HSP are presented, as well as the results of molecular studies in 23 of these families. Five phenotypes are defined: (1) pure early-onset families, (2) pure lateonset families, (3) complex families with mental retardation, (4) complex families with mental retardation and peripheral neuropathy, and (5) complex families with cerebellar ataxia. Six additional families have specific complex presentations, each of which is unique in the present series. Pyramidal signs in the upper limbs and pes cavus are frequent findings, while pseudobulbar signs, including dysarthria, dysphagia, and brisk jaw jerks, are more frequent in the complex forms. The complex forms have a poorer prognosis, while pure forms, particularly those with early onset, are more benign. One Algerian pure early-onset kindred was linked to the locus on chromosome 8, previously reported in 4 Tunisian families. Two of the Portuguese kindreds with complex forms (one with mental retardation and the other associated with hypoplasia of the corpus callosum) showed linkage to the locus recently identified on chromosome 16. CONCLUSIONS: Although autosomal recessive HSP represents a heterogeneous group of diseases, some phenotypes can be defined by analyzing a large group of patients. The fact that only one Algerian family was linked to chromosome 8 suggests that this is a rare localization even in kindreds with the same ethnic background. Linkage to chromosome 16 was found in 2 clinically diverse Portuguese kindreds, illustrating that this locus is also rare and may correspond to different phenotypes.
Assuntos
Paraplegia Espástica Hereditária/diagnóstico , Adolescente , Adulto , Idoso , Argélia , Axônios/patologia , Criança , Pré-Escolar , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 8/genética , Avaliação da Deficiência , Progressão da Doença , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Masculino , Fenótipo , Portugal , Fatores de Risco , Índice de Gravidade de Doença , Paraplegia Espástica Hereditária/genética , Cromossomo X/genéticaRESUMO
Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type I), the intermediate form (type II), the Kugelberg-Welander disease (type III), and the adult form (type IV). The gene involved in all four forms of SMA, the so-called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted in over 95% of SMA patients. Another candidate gene in SMA is the neuronal apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45-67% of type I and 20-42% of type II/type III patients. Here we studied the SMN and NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3 type IV) from 57 unrelated families, using a semiquantitative PCR approach. Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families. Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%. Conversely, the quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and the type of SMA.
RESUMO
The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.
Assuntos
Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Adolescente , Adulto , Idade de Início , Ataxia Telangiectasia/genética , Criança , Mapeamento Cromossômico , Consanguinidade , DNA/genética , Análise Mutacional de DNA , Feminino , Genótipo , Proteínas de Choque Térmico/genética , Homozigoto , Humanos , Lactente , Masculino , Repetições de Microssatélites , Mutação/genética , Doenças do Nervo Oculomotor/genética , Polimorfismo de Nucleotídeo Único , Degenerações Espinocerebelares/genética , Adulto JovemAssuntos
Radiocirurgia/métodos , Adenoma/radioterapia , Adenoma/cirurgia , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/cirurgia , Encefalopatias/patologia , Encefalopatias/radioterapia , Encefalopatias/cirurgia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Humanos , Londres , Imageamento por Ressonância Magnética , Meningioma/radioterapia , Meningioma/cirurgiaRESUMO
OBJECTIVE: Mutations in various genes of the neuromuscular junction cause congenital myasthenic syndrome (CMS). A single truncating mutation (epsilon1293insG) in the acetylcholine receptor epsilon subunit gene (CHRNE) was most often identified in CMS families originating from North Africa and was possibly a founder mutation. METHODS: Twenty-three families were studied with an early onset form of CMS and originating from Tunisia, Algeria, Morocco, and Libya. Screening for the mutation epsilon1293insG was performed by direct sequencing. Haplotype analysis was done with 9 (CA)n repeat microsatellite markers and 6 SNPs flanking epsilon1293insG on chromosome 17p13-p12. Dating was calculated using the ESTIAGE method for rare genetic diseases. RESULTS: The epsilon1293insG mutation was identified in 14 families (about 60% of the initial 23). The expression of the CMS in affected members of these families was relatively homogeneous, without fetal involvement or being life-threatening, with moderate hypotonia and oculobulbar involvement, mild and stable disease course, and good response to cholinesterase inhibitors. Haplotype analysis revealed a common conserved haplotype encompassing a distance of 63 kb. The estimated age of the founder event was at least 700 years. CONCLUSIONS: These results strongly support the hypothesis that epsilon1293insG derives from an ancient single founder event in the North African population. Identification of founder mutations in isolated or inbred populations may have important implications in the context of molecular diagnosis and genetic counseling of patients and families by detection of heterozygous carriers.