Bibliografías temáticas / SCA48

Índice

Artículos de revistas
Tesis
Capítulos de libros
Actas de conferencias

Literatura académica sobre el tema "SCA48"

Autor: Grafiati

Publicado: 10 de marzo de 2023

Crea una cita precisa en los estilos APA, MLA, Chicago, Harvard y otros

Elija tipo de fuente:

Consulte las listas temáticas de artículos, libros, tesis, actas de conferencias y otras fuentes académicas sobre el tema "SCA48".

Junto a cada fuente en la lista de referencias hay un botón "Agregar a la bibliografía". Pulsa este botón, y generaremos automáticamente la referencia bibliográfica para la obra elegida en el estilo de cita que necesites: APA, MLA, Harvard, Vancouver, Chicago, etc.

También puede descargar el texto completo de la publicación académica en formato pdf y leer en línea su resumen siempre que esté disponible en los metadatos.

Artículos de revistas sobre el tema "SCA48"

Pakdaman, Yasaman, Siren Berland, Helene J. Bustad, Sigrid Erdal, Bryony A. Thompson, Paul A. James, Kjersti N. Power et al. "Genetic Dominant Variants in STUB1, Segregating in Families with SCA48, Display In Vitro Functional Impairments Indistinctive from Recessive Variants Associated with SCAR16". International Journal of Molecular Sciences 22, n.º 11 (30 de mayo de 2021): 5870. http://dx.doi.org/10.3390/ijms22115870.

Texto completo

Resumen

Variants in STUB1 cause both autosomal recessive (SCAR16) and dominant (SCA48) spinocerebellar ataxia. Reports from 18 STUB1 variants causing SCA48 show that the clinical picture includes later-onset ataxia with a cerebellar cognitive affective syndrome and varying clinical overlap with SCAR16. However, little is known about the molecular properties of dominant STUB1 variants. Here, we describe three SCA48 families with novel, dominantly inherited STUB1 variants (p.Arg51_Ile53delinsProAla, p.Lys143_Trp147del, and p.Gly249Val). All the patients developed symptoms from 30 years of age or later, all had cerebellar atrophy, and 4 had cognitive/psychiatric phenotypes. Investigation of the structural and functional consequences of the recombinant C-terminus of HSC70-interacting protein (CHIP) variants was performed in vitro using ubiquitin ligase activity assay, circular dichroism assay and native polyacrylamide gel electrophoresis. These studies revealed that dominantly and recessively inherited STUB1 variants showed similar biochemical defects, including impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP. Our findings expand the molecular understanding of SCA48 but also mean that assumptions concerning unaffected carriers of recessive STUB1 variants in SCAR16 families must be re-evaluated. More investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Szpisjak, László, András Salamon, Viola L. Németh, Noémi Szépfalusi, Zoltán Maróti, Tibor Kalmár, Aliz Zimmermann, Dénes Zádori y Péter Klivényi. "Novel heterozygous STUB1 gene mutation causes SCA48 in a Hungarian patient". Ideggyógyászati szemle 76, n.º 1-2 (2023): 63–72. http://dx.doi.org/10.18071/isz.76.0063.

Texto completo

Resumen

Spinocerebellar ataxia type 48 (SCA48) is an autosomal dominantly inherited disease characterized by gait and limb ataxia, cerebellar dysarthria, cognitive impairment, psychiatric abnormalities and variable types of movement disorders. To date, more than 30 STUB1 gene (NM_005861.4) mutations have been described in the genetic background of SCA48. The aim of this short report was to demonstrate the first Hungarian SCA48 patient caused by a novel STUB1 missense mutation (c.788G>C, p.Arg263Pro). The characteristics of detailed neurological phenotype, brain MRI and genetic assessment are presented and compared to previously published cases. The most important neurological findings of the patient were gait ataxia, dysarthria, cognitive decline and psychiatric problems including depression, anxiety and mild impulsivity. The brain MRI demonstrated cerebellar atrophy with posterolateral predominance and frontal lobe cortical atrophy. Clinical exome sequencing examination identified the above-mentioned missense variant located in the significant ubiquitinase domain of the CHIP protein. In this paper the first Hungarian SCA48 patient was described with characteristic neuropsychiatric signs and brain MRI abnormalities, due to a novel STUB1 gene missense mutation.

Los estilos APA, Harvard, Vancouver, ISO, etc.

De Michele, Giovanna, Elena Salvatore, Sirio Cocozza, Alessandro Filla y Filippo M. Santorelli. "Of cognition and cerebellum in SCA48". neurogenetics 21, n.º 2 (3 de febrero de 2020): 145–46. http://dx.doi.org/10.1007/s10048-020-00603-8.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Mol, Merel O., Jeroen G. J. van Rooij, Esther Brusse, Annemieke J. M. H. Verkerk, Shamiram Melhem, Wilfred F. A. den Dunnen, Patrizia Rizzu, Chiara Cupidi, John C. van Swieten y Laura Donker Kaat. "Clinical and pathologic phenotype of a large family with heterozygous STUB1 mutation". Neurology Genetics 6, n.º 3 (23 de marzo de 2020): e417. http://dx.doi.org/10.1212/nxg.0000000000000417.

Texto completo

Resumen

ObjectiveTo describe the clinical and pathologic features of a novel pedigree with heterozygous STUB1 mutation causing SCA48.MethodsWe report a large pedigree of Dutch decent. Clinical and pathologic data were reviewed, and genetic analyses (whole-exome sequencing, whole-genome sequencing, and linkage analysis) were performed on multiple family members.ResultsPatients presented with adult-onset gait disturbance (ataxia or parkinsonism), combined with prominent cognitive decline and behavioral changes. Whole-exome sequencing identified a novel heterozygous frameshift variant c.731_732delGC (p.C244Yfs*24) in STUB1 segregating with the disease. This variant was present in a linkage peak on chromosome 16p13.3. Neuropathologic examination of 3 cases revealed a consistent pattern of ubiquitin/p62-positive neuronal inclusions in the cerebellum, neocortex, and brainstem. In addition, tau pathology was present in 1 case.ConclusionsThis study confirms previous findings of heterozygous STUB1 mutations as the cause of SCA48 and highlights its prominent cognitive involvement, besides cerebellar ataxia and movement disorders as cardinal features. The presence of intranuclear inclusions is a pathologic hallmark of the disease. Future studies will provide more insight into its pathologic heterogeneity.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Genis, David, Sara Ortega-Cubero, Hector San Nicolás, Jordi Corral, Josep Gardenyes, Laura de Jorge, Eva López et al. "Heterozygous STUB1 mutation causes familial ataxia with cognitive affective syndrome (SCA48)". Neurology 91, n.º 21 (31 de octubre de 2018): e1988-e1998. http://dx.doi.org/10.1212/wnl.0000000000006550.

Texto completo

Resumen

ObjectiveTo describe a new spinocerebellar ataxia (SCA48) characterized by early cerebellar cognitive-affective syndrome (CCAS) and late-onset SCA.MethodsThis is a descriptive study of a family that has been followed for more than a decade with periodic neurologic and neuropsychological examinations, MRI, brain SPECT perfusion, and genetic analysis. Whole exome sequencing was performed in 3 affected and 1 unaffected family member and subsequently validated by linkage analysis of chromosome 16p13.3.ResultsSix patients fully developed cognitive-affective and complete motor cerebellar syndrome associated with vermian and hemispheric cerebellar atrophy, suggesting a continuum from a dysexecutive syndrome slowly evolving to a complete and severe CCAS with late truncal ataxia. Three presymptomatic patients showed focal cerebellar atrophy in the vermian, paravermian, and the medial part of cerebellar lobes VI and VII, suggesting that cerebellar atrophy preceded the ataxia, and that the neurodegeneration begins in cerebellar areas related to cognition and emotion, spreading later to the whole cerebellum. Among the candidate variants, only the frameshift heterozygous c.823_824delCT STUB1 (p.L275Dfs*16) pathogenic variant cosegregated with the disease. The p.L275Dfs*16 heterozygous STUB1 pathogenic variant leads to neurodegeneration and atrophy in cognition- and emotion-related cerebellar areas and reinforces the importance of STUB1 in maintaining cognitive cerebellar function.ConclusionsWe report a heterozygous STUB1 pathogenic genetic variant causing dominant cerebellar ataxia. Since recessive mutations in STUB1 gene have been previously associated with SCAR16, these findings suggest a previously undescribed SCA locus (SCA48; MIM# 618093).

Los estilos APA, Harvard, Vancouver, ISO, etc.

Palvadeau, R., Z. E. Kaya-Güleç, G. Şimşir, A. Vural, Ö. Öztop-Çakmak, G. Genç, M. S. Aygün, O. Falay, A. Nazlı Başak y S. Ertan. "Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family". neurogenetics 21, n.º 1 (19 de noviembre de 2019): 51–58. http://dx.doi.org/10.1007/s10048-019-00595-0.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Magri, Stefania, Lorenzo Nanetti, Cinzia Gellera, Elisa Sarto, Elena Rizzo, Alessia Mongelli, Benedetta Ricci et al. "Digenic inheritance of STUB1 variants and TBP polyglutamine expansions explains the incomplete penetrance of SCA17 and SCA48". Genetics in Medicine 24, n.º 1 (enero de 2022): 29–40. http://dx.doi.org/10.1016/j.gim.2021.08.003.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Tulli, Susanna, Andrea Del Bondio, Valentina Baderna, Davide Mazza, Franca Codazzi, Tyler Mark Pierson, Alessandro Ambrosi et al. "Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation". Journal of Medical Genetics 56, n.º 8 (25 de marzo de 2019): 499–511. http://dx.doi.org/10.1136/jmedgenet-2018-105766.

Texto completo

Resumen

BackgroundSpinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date.MethodsWe derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2+/− HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2−/− murine fibroblasts.ResultsWe found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells.ConclusionOur data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2+/− cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Patturajan, Meera, Xiangyun Wei, Ronald Berezney y Jeffry L. Corden. "A Nuclear Matrix Protein Interacts with the Phosphorylated C-Terminal Domain of RNA Polymerase II". Molecular and Cellular Biology 18, n.º 4 (1 de abril de 1998): 2406–15. http://dx.doi.org/10.1128/mcb.18.4.2406.

Texto completo

Resumen

ABSTRACT Yeast two-hybrid screening has led to the identification of a family of proteins that interact with the repetitive C-terminal repeat domain (CTD) of RNA polymerase II (A. Yuryev et al., Proc. Natl. Acad. Sci. USA 93:6975–6980, 1996). In addition to serine/arginine-rich SR motifs, the SCAFs (SR-like CTD-associated factors) contain discrete CTD-interacting domains. In this paper, we show that the CTD-interacting domain of SCAF8 specifically binds CTD molecules phosphorylated on serines 2 and 5 of the consensus sequence Tyr1Ser2Pro3Thr4Ser5Pro6Ser7. In addition, we demonstrate that SCAF8 associates with hyperphosphorylated but not with hypophosphorylated RNA polymerase II in vitro and in vivo. This result suggests that SCAF8 is not present in preinitiation complexes but rather associates with elongating RNA polymerase II. Immunolocalization studies show that SCAF8 is present in granular nuclear foci which correspond to sites of active transcription. We also provide evidence that SCAF8 foci are associated with the nuclear matrix. A fraction of these sites overlap with a subset of larger nuclear speckles containing phosphorylated polymerase II. Taken together, our results indicate a possible role for SCAF8 in linking transcription and pre-mRNA processing.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Breuer, Oded, Roopesh Singh Gangwar, Mansour Seaf, Ahlam Barhoum, Eitan Kerem y Francesca Levi-Schaffer. "Evaluation of Soluble CD48 Levels in Patients with Allergic and Nonallergic Asthma in Relation to Markers of Type 2 and Non-Type 2 Immunity: An Observational Study". Journal of Immunology Research 2018 (16 de septiembre de 2018): 1–7. http://dx.doi.org/10.1155/2018/4236263.

Texto completo

Resumen

CD48 is a costimulatory receptor associated with human asthma. We aimed to assess the significance of the soluble form of CD48 (sCD48) in allergic and nonallergic asthma. Volunteer patients completed an asthma and allergy questionnaire, spirometry, methacholine challenge test, a common allergen skin prick test, and a complete blood count. sCD48, IgE, IL5, IL17A, IL33, and IFNγ were quantitated in serum by ELISA. Asthma was defined as positive methacholine challenge test or a 15% increase in FEV1 post bronchodilator in symptomatic individuals. Allergy was defined as positive skin test or IgE levels > 200 IU/l in symptomatic individuals. 137 individuals participated in the study: 82 (60%) were diagnosed with asthma of which 53 (64%) was allergic asthma. sCD48 levels were significantly elevated in patients with nonallergic asthma compared to control and to the allergic asthma cohort (median (IQR) pg/ml, 1487 (1338–1758) vs. 1308 (1070–1581), p<0.01, and 1336 (1129–1591), p=0.02, respectively). IL17A, IL33, and IFNγ levels were significantly elevated in allergic and nonallergic asthmatics when compared to control. No correlation was found between sCD48 level and other disease markers. sCD48 is elevated in nonallergic asthma. Additional studies are required for understanding the role of sCD48 in airway disease.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Más fuentes

Tesis sobre el tema "SCA48"

Wöllner, Janine [Verfasser]. "Molekulargenetische Untersuchungen zur dominant vererbten Ataxie SCA28 / Janine Wöllner". Lübeck : Zentrale Hochschulbibliothek Lübeck, 2012. http://d-nb.info/1026078172/34.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

FRACASSO, VALENTINA. "Functional analysis of AFG3L2 mutations causing spinocerebellar ataxia type 28 (SCA28)". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/20215.

Texto completo

Resumen

Autosomal dominant spinocerebellar ataxias (SCAs) are genetically heterogeneous neurological disorders characterized by cerebellar dysfunction mostly due to Purkinje cell degeneration. Here we show that AFG3L2 mutations cause SCA type 28. Along with paraplegin, which causes recessive spastic paraplegia, AFG3L2 is a component of the conserved m-AAA metalloprotease complex involved in the maintenance of the mitochondrial proteome. We identified heterozygous missense mutations in five unrelated SCA families and found that AFG3L2 is highly and selectively expressed in human cerebellar Purkinje cells. m-AAA–deficient yeast cells expressing human mutated AFG3L2 homocomplex show respiratory deficiency, proteolytic impairment and deficiency of respiratory chain complex IV. Structure homology modeling indicates that the mutations may affect AFG3L2 substrate handling. This work identifies AFG3L2 as a novel cause of dominant neurodegenerative disease and indicates a previously unknown role for this component of the mitochondrial protein quality control machinery in protecting the human cerebellum against neurodegeneration.

Los estilos APA, Harvard, Vancouver, ISO, etc.

MAGRI, STEFANIA. "Functional analysis of m-AAA homo- and heterocomplexes: the role of mitochondrial protein quality control system in spinocerebellar neurodegeneration". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/29913.

Texto completo

Resumen

Autosomal dominant spinocerebellar ataxias (SCA) are a heterogeneous group of neurological disorders characterized by cerebellar dysfunction. We recently showed that AFG3L2 mutations cause dominant ataxia SCA28. AFG3L2 and its partner protein paraplegin, which causes recessive spastic paraparesis SPG7, are components of the m-AAA complex, involved in mitochondrial protein quality control. Since yeast functional studies showed that paraplegin coexpression can modulate AFG3L2 mutations, we investigated the possible coinheritance of AFG3L2 and SPG7 mutations in patients with spinocerebellar syndromes. We identified 3 probands with heterozygous mutations in both the AFG3L2 and the SPG7 genes. Two ataxic patients carry an AFG3L2 mutation affecting highly conserved amino acids located in the ATPase or in the proteolytic domains of the protein along with the parapleginA510V. The third proband carries a de novo AFG3L2 mutation in the highly conserved SRH region of the ATPase domain along with the inherited deletion of SPG7 exons 4-6. The clinical presentation of this patient is characterized by early onset optic atrophy and a L-dopa-responsive spastic-ataxic syndrome with extrapyramidal signs. A muscle biopsy revealed an isolated complex I deficiency. Moreover, evaluation of substrates processing in patient’s fibroblasts showed abnormal processing pattern of OPA1. In conclusion, our data indicate that the presence of a loss-of-function mutation in paraplegin may act as a disease modifier for heterozygous AFG3L2 mutations. Concurrent mutations in both components of the mitochondrial m-AAA complex may result in a complex phenotype, thus expanding the clinical spectrum of AFG3L2-associated mutations. Moreover, biochemical and cell biology studies revealed a crucial role of the m-AAA complex in the processing of OPA1 and the maintenance of mitochondrial morphology.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Chuang, Wan-Chun y 莊婉君. "Molecular characterization of SCA8 inducible cell line". Thesis, 2010. http://ndltd.ncl.edu.tw/handle/59967318525036138906.

Texto completo

Resumen

碩士
國立臺灣師範大學
生命科學研究所
98
Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant late-onset neurodegenerative disease. The cause of SCA8 was originally proposed associated with CTG trinucleotide repeat at 3’UTR (untranslated region) of ATXN8OS gene, lying on chromosome 13q21. However, recent studies suggest that bidirectional transcription of ATXN8OS occurs, with its anti-strand, ataxin8 (ATXN8), which encodes a polyQ protein in the CAG orientation, and ATXN8OS transcribed into potentially pathogenic CUG transcripts. SCA8 may thus has both RNA and protein gain of function mechanisms. To understand the molecular pathogenic mechanism of SCA8, we have established inducible PC12 cells with ATXN8OS-22R (normal 22 CTG repeats) or -150R (expanded 150 CTG repeats). Our results show that the viability and neurite outgrowth were significantly reduced in cells with ATXN8OS-150R after induction. Furthermore, the proliferation rate of the cells with ATXN8OS-150R (clones 1 and 4) was obviously decreased by flow cytometry. In addition, the presence of RNA foci was identified in cells with ATXN8OS-22R and -150R. Further investigation in impairment of neurite outgrowth revealed that the neuron differenciation signal transduction pathways of PC12 cells might not be the major targets directly affected by ATXN8OS gene. Whether the mechanism of ATXN8OS gene resulted in hypoplasia of neurite outgrowth related to RNA level associated with alternative splicing needs further investigation.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Hsiang, Sheng-Weng y 項聖文. "Generation and Pathogenic Study of SCA8 Drosophila Model". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/58742825079170118029.

Texto completo

Resumen

碩士
國立臺灣師範大學
生命科學研究所
93
Abstract The spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by cerebellar dysfunction alone or in combination with other neurological abnormalities. SCA type 8 (SCA8) has been attributed to the expanded CTG repeat at 3’ end of SCA8 gene on chromosome 13q21. To unravel the pathogenic mechanisms underlying SCA8 we tried to establish SCA8 Drosophila models in this study. The photoreceptor cells were degenerated when SCA8 gene with expanded CTG repeats were expressed in the transgenic flies, suggesting the repeat sequence exhibits pathogenic effect. The repeat containing transcripts were found accumulated in nuclei as RNA foci using in situ hybridization. As sequence analysis of SCA8 gene did not reveal that SCA8 encodes any significant ORFs in previous study, suggesting that SCA8 will not encode any protein product. Nevertheless, expression constructs with EGFP fused at 3’ end of SCA8 were able to express in the eye discs of transgenic flies, suggesting that SCA8 may contain translatable ORF. Expressing the repeat containing ORF in transgenic flies cause severe degenerative phenotype. However the transcripts were aggregated in RNA foci and can not be transported to cytosol to be translated into polyLeu containing polypeptide. From these results we have learned that SCA8 can exert its cytotoxcity effect at RNA level. Previous studies demonstrated that RNA binding proteins, such as muslcle-blind and PKAAP, were associated with CUG containing transcripts to form RNA foci, which sequesters the expression level of these RNA binding proteins and enhance the pathogenic effect. We found our SCA8 fly model displayed different degenerative phenotype when placed at mbl, and PKAAP mutant background. Interestingly, the chaperone protein, Hsp70, was found alleviated SCA8 disease presentation. It is very likely that mis-folded proteins may also play a role in SCA8 pathogenesis. Since 5’ end of SCA8 is overlapped with a nearby gene KLHL1, we would like to know whether KLHL1 is also play a role in SCA8 pathogenesis. Retinal expression of KLHL1 did not cause obviously eye degeneration. Co-expression of both SCA8 and KLHL1 did not enhance the disease phenotype. This has demonstrated that KLHL1 may not participate in the pathogenesis of SCA8.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Galatolo, Daniele. "An integrated, next-generation approach to identify new genes and new pathways in hereditary ataxias". Doctoral thesis, 2020. http://hdl.handle.net/2158/1188709.

Texto completo

Resumen

The Hereditary ataxias (HAs) are a group of heterogenous neurological disorders associated with multiple genetic etiologies and encompassing a wide spectrum of phenotypes, where ataxia is the prominent feature. HAs are characterized by degeneration of Purkinje cell and/or spinocerebellar connections, often associated with defects in additional brain structures, and all patterns of inheritance may occur. Similar to other fields of medical genetics, Next Generation Sequencing (NGS) has entered the HA scenario widening our genetic and clinical knowledge of this condition, but routine NGS applications still miss genetic diagnosis in about two third of patients. In this doctoral study, we applied multi-gene panels to define the molecular basis in 259 patients with a clinical diagnosis of HA and negative to tests for pathological expansion in SCA1, 2, 3, 6, 7, 8, 12, 17 and FXN. We found a positive molecular diagnosis in 25% of patients, whereas a similar number of patients had an uncertain diagnosis due to the presence of either variants of uncertain significance or lack of biological samples to determine segregation among family members. Hence despite a higher positive diagnostic rate compared to similar studies described in literature, a half of patients lacked any indication of the genetic cause of their disease. Using exome sequencing as a second-tier approach in some families, refractory to multi-gene panel analysis, did not significantly improved our diagnostic yield. On the other hand, NGS analysis in our cohort indicated that familial cases were more easily diagnosed rather than sporadic cases, and also that combining massive sequencing with detailed clinical information and family studies increases the likelihood to reach a molecular diagnosis. Among positive patients, we could expand clinical and allelic information in a subgroup of genes offering original description of new mutations and corroborating genetic findings with functional investigations that took advantage of different in vitro or in vivo platforms. In particular, through functional studies in SPG7 knock-down models of Drosophila melanogaster, we remarked that SPG7, whose mutations cause spastic paraplegia type 7, has a critical role in neurons more than in skeletal muscle. The high frequency of p.Ala510Val mutation in SPG7 observed in our cohort as well in similar studies performed elsewhere moved us to develop a humanized knock-in fruit fly model harboring that specific mutation and prepare preliminary characterizations. Similar studies in fruit fly were performed silencing AFG3L2, the gene causing SPAX5 in a child in association with an unusual, relatively milder phenotype. Furthermore, combination of skin fibroblasts and Saccharomyces cerevisiae as models was employed in the genetic characterization of new mutations in a novel recessive HARS-related phenotype whereas primary human cells, yeast and Danio rerio models were used to functionally characterize new HA-related mutations in COQ4. Finally, we could expand the clinical presentation of rare causes of HAs describing new dominant mutations in STUB1 and biallelic variants in RFN216, COQ8A, and ATP13A2. Altogether, studies performed during this doctoral work further underlined the usefulness of NGS in HAs and highlighted how NGS technologies rely on the integrated use of family and clinical studies and different in vitro/in vivo platforms to substantiate molecular findings. The latter platform will be also a tool for future investigations to dissect pathogenesis and to improve therapies.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Lu, Chung-I. y 盧重王衣. "The Production and Composition Analysis and Application of Ropy Extracellular Adhesive Substance of Marine Bacterium Neisseria sp. strain SCA38". Thesis, 2002. http://ndltd.ncl.edu.tw/handle/3w5mns.

Texto completo

Resumen

碩士
國立海洋大學
食品科學系
90
Abstract Neisseria sp. strain SCA38 was isolated from the biofouling material suspended in sea water. Four metal ions or three buffering agents was added individually into the MSBB to testing the EAS production of strain SCA38, the results indicated that the EAS yields were increased to the range of 0.13-0.28 g/L. And as yeast extract or polypeptone/yeast extract was used to replace the original nitrogen source, the EAS yields of strain SCA38 were higher than the inorganic nitrogen replacement groups. Five monosaccharide and three disaccharides were used individually to replace the carbon source of MSBB, the results indicated that the substitution of mannose in the MSBB performed higher EAS yield (0.81 g/L) than others. In the study of incubation conditions for the maximum EAS production of strain SCA38, the results showed that while the initial pH at 8.2, shaking speed with 150 rpm, or incubation temperature at 26oC the higher EAS yields ranged from 0.71 to 0.83 g/L were observed. Strain SCA38 was cultured in the M-MPB-G with the addition of substratum such as actived carbon flake, chitin flake, wood piece, stainless steel beads, glass beads, or polypropylene beads. The EAS production results indicated that the chitin flake added to M-MPB-G performed the highest EAS yield as 0.98 ± 0.27 g/L. To test the different agitating speed on the EAS yield for strain SCA38, the higher EAS yield of this strain were observed while 200 rpm was employed. The proximate compositions of lyophilized EAS produced by strain SCA38 in various media are primarily carbohydrate 63.1-71.0%, and 8.7-15.9% the second highest content was crude protein. The results observed from gel permeation chromatography implied that the EAS derived from strain SCA38 was a complex compound with polysaccharide and protein. The solubility of rehydrated aqueous solution with strain SCA38 EAS powder was dissolved in distilled water, 1.0-4.0% NaCl, 80% formic acid, and 99% dimethyl sulphoxide. The relative viscosity (RV) of strain SCA38 EAS rehydrated aqueous solution was increased while the concentration of EAS was increased in the reacting solution. However, EAS solutions with the addition of increasing NaCl concentration were performed the decreasing RV. The 0.2% lyophilized EAS powder rehydrated is solution showed the higher and more stable RV over a pH range from 6.0 to 8.0. The RV of 0.2% lyophilized EAS powder rehydrated solution more stabled at 40oC, and then declined while the temperature is either raising or falling. The emulsion activity (EA) of EAS obtained from strain SCA38 was examined as the EAS concentration ranged from 0.2% to 0.8%, the results showed that the EAS standing among 42% to 48%. As 0.4% or 1.0% EAS was added to the testing solution, the resultant emulsion stabilities (ES) were both 53%, which is better than the rest testing groups. The EAS recovered from the cultivation of strain SCA38 in MSBB M-MPB-M, and M-MPB-G were used to test their capability on antioxidation and antimutagenicity in the concentration ranged from 10 to 50 mg/mL. The antioxidative performance of those EAS were not remarkable on the scavenging DPPH free radical, but the lyophilized EAS (derived from M-MPB-M) showed a good result on the inhibition of hemoglobin catalyzing linoleic acid. While in such 1% EAS solution, the inhibition rate could reach 93.040.58%. As to the EAS recovered from the strain SCA38 cultured MSBB and M-MPB-G, the inhibition performances on the hemoglobin catalyzing linoleic acid were ranged from 5.51% to 79.81% as the added concentration of EAS was increased. As to the antimutagenicity of EAS (5%) that produced from strain SCA38 cultured MSBB, the inhibition rate to the mutation caused by MMNG or B[a]P could be 37.1% and 5.5%, respectively. In the same testing system, the EAS of strain SCA38 that derived from M-MPB-G had inhibition rates while against the mutation caused by among 85.7-88.6% MMNG.

Los estilos APA, Harvard, Vancouver, ISO, etc.

Capítulos de libros sobre el tema "SCA48"

Hall, D. A. "SCA4". En Encyclopedia of Movement Disorders, 67–69. Elsevier, 2010. http://dx.doi.org/10.1016/b978-0-12-374105-9.00206-9.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Koob, M. D. "SCA8". En Encyclopedia of Movement Disorders, 78–80. Elsevier, 2010. http://dx.doi.org/10.1016/b978-0-12-374105-9.00210-0.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Koob, Michael D. "Spinocerebellar Ataxia 8 (SCA8)". En Genetics of Movement Disorders, 95–102. Elsevier, 2003. http://dx.doi.org/10.1016/b978-012566652-7/50012-5.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Mizusawa, Hidehiro. "Spinocerebellar Ataxia Type 4 (SCA4)". En Genetics of Movement Disorders, 71–73. Elsevier, 2003. http://dx.doi.org/10.1016/b978-012566652-7/50008-3.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Actas de conferencias sobre el tema "SCA48"

Jimenez, Chalena M., Kevin W. Richardson y Donald R. Stephens. "SCA4 — An evolved framework". En MILCOM 2012 - 2012 IEEE Military Communications Conference. IEEE, 2012. http://dx.doi.org/10.1109/milcom.2012.6415646.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Creed, Michael, Áine de Bhulbh, Diarmuid O’Connor, Eimear McMahon, Anne Doherty y Dara Byrne. "SC48 Developing a simulation-based education workshop for psychiatric emergencies for national roll-out". En Abstracts of the Association of Simulated Practice in Healthcare, 10th Annual Conference, Belfast, UK, 4–6 November 2019. The Association for Simulated Practice in Healthcare, 2019. http://dx.doi.org/10.1136/bmjstel-2019-aspihconf.85.

Texto completo

Los estilos APA, Harvard, Vancouver, ISO, etc.

Ofrecemos descuentos en todos los planes premium para autores cuyas obras están incluidas en selecciones literarias temáticas. ¡Contáctenos para obtener un código promocional único!