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1.
Inform Health Soc Care ; 45(3): 255-272, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274045

RESUMO

OBJECTIVE: In this work, we propose a new care concept for dementia patients in their own apartments: interconnected living in a quarter. We describe a technical setup that is comprised of a safety system and an activity detection system. The latter detects, processes and illustrates activities of daily living to help the quarter managers to provide appropriate interventions for persons with dementia in the quarter. PARTICIPANTS: The nine-month field study reported in this work was conducted in two quarters with eight participants. METHODS: We evaluated different possibilities to determine activity indicators with the aim of providing information that enables the quarter managers to offer exactly the level of support needed by each individual patient. To evaluate the usefulness and the perception of the technical infrastructure, qualitative interviews with the dementia patients and the quarter managers were conducted. RESULTS: The results indicate that the interconnected living concept helps to increase the safety of the dementia patients. Additionally, several activity indicators that help the quarter managers to offer the appropriate level of support to the dementia patients have been identified. CONCLUSION: The presented concept, which has been evaluated in a real-world-setting, constitutes a new holistic and cross-disciplinary dementia care approach.


Assuntos
Atividades Cotidianas , Cuidadores , Demência , Vida Independente , Gestão da Segurança/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Segurança , Apoio Social
3.
J Phys Chem Lett ; 5(2): 304-9, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-26270704

RESUMO

Peak external quantum efficiencies (EQEs) of just over 120% were observed in photovoltaic (PV) devices of CuInSe2 nanocrystals prepared with a photonic curing process. The extraction of more than one electron/hole pair as a result of the absorption of a single photon can occur if multiple excitons are generated and extracted. Multiexciton generation (MEG) in the nanocrystal films was substantiated by transient absorption spectroscopy. We propose that photonic curing leads to sufficient electronic coupling between nanocrystals to enable multiexciton extraction under typical solar illumination conditions. Under low light conditions, however, the EQE drops significantly, indicating that photonic curing-induced ligand desorption creates a significant amount of traps in the film that limit the overall power conversion efficiency of the device.

4.
J Phys Chem Lett ; 5(18): 3169-74, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26276328

RESUMO

Transient absorption spectroscopy (TAS) was used to study carrier multiplication (CM) (also called multiexciton generation (MEG)) in solvent-dispersed colloidal CuInSe2 nanocrystals with diameters as small as 4.5 nm. Size-dependent carrier cooling rates, absorption cross sections, and Auger lifetimes were also determined. The energy threshold for CM in the CuInSe2 nanocrystals was found to be 2.4 ± 0.2 times the nanocrystal energy gap (Eg) and the CM efficiency was 36 ± 6% per unit Eg. This is similar to other types of nanocrystal quantum dot materials.

5.
J Geophys Res Space Phys ; 119(2): 927-946, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26167439

RESUMO

The substorm current wedge (SCW) is a fundamental component of geomagnetic substorms. Models tend to describe the SCW as a simple line current flowing into the ionosphere toward dawn and out of the ionosphere toward dusk, linked by a westward electrojet. We use multispacecraft observations from perigee passes of the Cluster 1 and 4 spacecraft during a substorm on 15 January 2010, in conjunction with ground-based observations, to examine the spatial structuring and temporal variability of the SCW. At this time, the spacecraft traveled east-west azimuthally above the auroral region. We show that the SCW has significant azimuthal substructure on scales of 100 km at altitudes of 4000-7000 km. We identify 26 individual current sheets in the Cluster 4 data and 34 individual current sheets in the Cluster 1 data, with Cluster 1 passing through the SCW 120-240 s after Cluster 4 at 1300-2000 km higher altitude. Both spacecraft observed large-scale regions of net upward and downward field-aligned current, consistent with the large-scale characteristics of the SCW, although sheets of oppositely directed currents were observed within both regions. We show that the majority of these current sheets were closely aligned to a north-south direction, in contrast to the expected east-west orientation of the preonset aurora. Comparing our results with observations of the field-aligned current associated with bursty bulk flows (BBFs), we conclude that significant questions remain for the explanation of SCW structuring by BBF-driven "wedgelets." Our results therefore represent constraints on future modeling and theoretical frameworks on the generation of the SCW. KEY POINTS: The substorm current wedge (SCW) has significant azimuthal structureCurrent sheets within the SCW are north-south alignedThe substructure of the SCW raises questions for the proposed wedgelet scenario.

6.
ACS Appl Mater Interfaces ; 5(18): 9134-40, 2013 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-23957691

RESUMO

The power conversion efficiency of photovoltaic devices made with ink-deposited Cu(InxGa1-x)Se2 (CIGS) nanocrystal layers can be enhanced by sintering the nanocrystals with a high temperature selenization process. This process, however, can be challenging to control. Here, we report that ink deposition followed by annealing under inert gas and then selenization can provide better control over CIGS nanocrystal sintering and yield generally improved device efficiency. Annealing under argon at 525 °C removes organic ligands and diffuses sodium from the underlying soda lime glass into the Mo back contact to improve the rate and quality of nanocrystal sintering during selenization at 500 °C. Shorter selenization time alleviates excessive MoSe2 formation at the Mo back contact that leads to film delamination, which in turn enables multiple cycles of nanocrystal deposition and selenization to create thicker, more uniform absorber films. Devices with power conversion efficiency greater than 7% are fabricated using the multiple step nanocrystal deposition and sintering process.


Assuntos
Cobre/química , Gálio/química , Índio/química , Nanopartículas/química , Selênio/química , Energia Solar , Vidro/química , Temperatura
7.
ChemSusChem ; 6(3): 481-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23401465

RESUMO

Thin-film photovoltaic devices (PVs) were prepared by selenization using oleylamine-capped Cu(In,Ga)Se2 (CIGS) nanocrystals sintered at a high temperature (>500 °C) under Se vapor. The device performance varied significantly with [Ga]/[In+Ga] content in the nanocrystals. The highest power conversion efficiency (PCE) observed in the devices studied was 5.1 % under air mass 1.5 global (AM 1.5 G) illumination, obtained with [Ga]/[In+Ga]=0.32. The variation in PCE with composition is partly a result of bandgap tuning and optimization, but the main influence of nanocrystal composition appeared to be on the quality of the sintered films. The [Cu]/[In+Ga] content was found to be strongly influenced by the [Ga]/[In+Ga] concentration, which appears to be correlated with the morphology of the sintered film. For this reason, only small changes in the [Ga]/[In+Ga] content resulted in significant variations in device efficiency.


Assuntos
Cobre/química , Fontes de Energia Elétrica , Gálio/química , Índio/química , Nanopartículas/química , Selênio/química , Energia Solar , Condutividade Elétrica
8.
J Phys Chem Lett ; 4(12): 2030-4, 2013 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-26283248

RESUMO

CuInSe2 (CISe) quantum dots (QDs) were synthesized with tunable size from less than 2 to 7 nm diameter. Nanocrystals were made using a secondary phosphine selenide as the Se source, which, compared to tertiary phosphine selenide precursors, was found to provide higher product yields and smaller nanocrystals that elicit quantum confinement with a size-dependent optical gap. Photovoltaic devices fabricated from spray-cast CISe QD films exhibited large, size-dependent, open-circuit voltages, up to 849 mV for absorber films with a 1.46 eV optical gap, suggesting that midgap trapping does not dominate the performance of these CISe QD solar cells.

9.
Gesundheitswesen ; 75(1): 29-32, 2013 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-22615029

RESUMO

BACKGROUND: Effective and efficient instruments for care planning and controlling are required to optimise the nursing process and improve outcome quality despite of various lacks of quality and precarious circumstances. METHODS: A cluster randomised controlled trial was conducted to assess whether the implementation of the Resident Assessment Instrument (RAI) into home care service providers can help to improve or stabilise functional abilities (ADL, IADL) and cognitive skills (MMST), improve quality of life (EQ-5D), reduce institutionalisation and thereby increase outcome quality. RESULTS: A comparison of mean differences between the treatment and control group showed no significant effects. Although the multilevel regression results show that clients in the treatment group fared better in terms of ADL and IADL (smaller decline) and were less likely to move to nursing homes and be hospitalised, none of these effects are significant. CONCLUSIONS: The lack of significance might be due to the fact that RAI was not fully implemented and even the partial implementation lasted much longer than expected. Moreover, the number of clients included in the study was smaller than originally planned.


Assuntos
Serviços de Assistência Domiciliar/estatística & dados numéricos , Assistência de Longa Duração/estatística & dados numéricos , Avaliação em Enfermagem/métodos , Avaliação em Enfermagem/estatística & dados numéricos , Qualidade de Vida , Instituições Residenciais/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Alemanha/epidemiologia , Humanos , Masculino , Prevalência , Resultado do Tratamento
10.
ACS Appl Mater Interfaces ; 4(5): 2757-61, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22524385

RESUMO

Thin film photovoltaic devices (PVs) were fabricated with CuInSe(2) (CIS) nanocrystals capped with either oleylamine, inorganic metal chalcogenide-hydrazinium complexes (MCC), or S(2-), HS(-), and OH(-). A CIS nanocrystal layer deposited from solvent-based inks without high temperature processing served as the active light-absorbing material in the devices. The MCC ligand-capped CIS nanocrystal PVs exhibited power conversion efficiency under AM1.5 illumination (1.7%) comparable to the oleylamine-capped CIS nanocrystals (1.6%), but with significantly thinner absorber layers. S(2-)-capped CIS nanocrystals could be deposited from aqueous dispersions, but exhibited lower photovoltaic performance.

11.
J Phys Chem Lett ; 3(17): 2352-6, 2012 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-26292113

RESUMO

Pyrite-phase iron sulfide (FeS2) nanocrystals were synthesized to form solvent-based dispersions, or "solar paint," to fabricate photovoltaic devices (PVs). Nanocrystals were sprayed onto substrates as absorber layers in devices with several different architectures, including Schottky barrier, heterojunction, and organic/inorganic hybrid architectures, to explore their viability as a PV material. None of the devices exhibited PV response. XRD and Raman spectroscopy confirmed the pyrite composition and phase purity of the nanocrystals. The electrical conductivity of the nanocrystal films was about 4 to 5 S/cm, more typical of metal nanocrystal films than semiconductor nanocrystal films, and the lack of PV response appears to derive from the highly conductive surface-related defects in pyrite that have been proposed.

12.
Z Gerontol Geriatr ; 45(4): 315-22, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21769512

RESUMO

Deficits in quality, a lack of professional process management and, most importantly, neglect of outcome quality are criticized in long-term care. A cluster randomized, controlled trial was conducted to assess whether the Resident Assessment Instrument (RAI) can help to improve or stabilize functional abilities (ADL, IADL) and cognitive skills (MMST), improve quality of life (EQ-5D), and reduce institutionalization, thereby, increasing outcome quality. A total of 69 home care services throughout Germany were included and randomized. The treatment group (n = 36) received training in RAI and was supported by the research team during the study (13 months). Comparison of mean differences between the treatment and control groups (n = 33) showed no significant effect. Although the multilevel regression results show that clients in the treatment group fared better in terms of ADLs and IADLs (smaller decline) and were less likely to move to nursing homes and be hospitalized, none of these effects is significant. The lack of significance might result from the small number of clients included in the study. Moreover, RAI was not fully implemented and even partial implementation required more time than expected.


Assuntos
Doença Crônica/epidemiologia , Doença Crônica/enfermagem , Avaliação Geriátrica/métodos , Serviços de Assistência Domiciliar/classificação , Serviços de Assistência Domiciliar/estatística & dados numéricos , Avaliação em Enfermagem/métodos , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Clusia , Feminino , Humanos , Masculino
13.
Clin Genet ; 79(6): 539-45, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20560986

RESUMO

This report describes clinical characteristics in families with a Type 2A phenotype and functional properties of a novel von Hippel Lindau variant (X214L). Pedigrees were analyzed. Analysis of von Hippel Lindau (VHL) coding exons and flanking intronic sequences in DNA from a proband with pheochromocytoma and islet cell tumor was performed. Western blot assays for VHL protein (pVHL), HIFα, and Jun B were conducted using VHL null renal clear carcinoma cell lines that were engineered to produce wild-type or X214L mutant pVHL. Pedigree analysis indicated that the variant tracked with disease and the same or similar VHL point mutations were identified in several Type 2A families. The predicted 14 amino acid extended pVHL variant, when reintroduced into VHL null cells, was stable and retained the ability to downregulate HIFα in a hydroxylationdependent manner. In contrast, the variant was defective with respect to downregulation of JunB. pVHL X214L, like other pVHL variants associated with a low risk of clear cell renal carcinoma, largely preserves the ability to downregulate HIF. In contrast, this variant, like other pVHL variants linked to Type 2A disease, fails to suppress JunB. This underscores that JunB may play a role in the pathogenesis of Type 2A VHL disease.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Mutação Puntual , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adulto , Linhagem Celular Tumoral , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Adulto Jovem , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/metabolismo
14.
Acta Radiol ; 49(8): 940-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18618347

RESUMO

BACKGROUND: Osteosarcoma and chondrosarcoma are the most common nonhematopoietic primary malignancies of bone. However, unusual radiographic appearances can lead to delay in diagnosis and confusion with benign diseases. PURPOSE: To evaluate the feasibility of micro-computed tomography (CT) for the analysis of primary, nonhematopoietic human bone tumors ex vivo. MATERIAL AND METHODS: Samples from 12 human bone specimens (osteosarcoma, n=6; chondrosarcoma, n=6) obtained for diagnostic purposes were scanned using industrial X-ray film without amplifier foil and scanned with micro-CT (7- and 12-microm-cubic voxels). Trabecular bone CT "density" and tumor matrix CT "density" were determined, and results were compared with those obtained from a detailed conventional histopathologic analysis of corresponding cross-sections. The significance of differences in grayscale measurements was tested with analysis of variance. RESULTS: Micro-CT provided quantitative information on bone morphology equivalent to histopathological analysis. We established grayscale measurements by which tumor matrices of chondrosarcoma and osteosarcoma could be radiographically categorized following histological classifications (P<0.001). CONCLUSION: Micro-CT is feasible for the analysis and differentiation of human osteosarcoma and chondrosarcoma.


Assuntos
Neoplasias Ósseas/diagnóstico , Condrossarcoma/diagnóstico , Imageamento Tridimensional/métodos , Osteossarcoma/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/ultraestrutura , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Masculino , Microrradiografia/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/instrumentação
15.
J Med Genet ; 43(1): 18-27, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15937070

RESUMO

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene (FH). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African-American families with HLRCC. METHODS: Using direct sequencing analysis we identified FH germline mutations in 100% (21/21) of new families with HLRCC. RESULTS: We identified 14 germline FH mutations (10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense (L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense (S102X), one insertion (111insA), and one splice site (138+1G>C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% (13/21) had renal cancer and 76% (16/21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% (22/22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype-phenotype correlations were identified. CONCLUSIONS: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC (20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% (52/56) in families suspected of HLRCC.


Assuntos
Fumarato Hidratase/genética , Neoplasias Renais/enzimologia , Neoplasias Renais/genética , Leiomiomatose/enzimologia , Leiomiomatose/genética , Mutação/genética , Fenótipo , Negro ou Afro-Americano/genética , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Leiomioma/enzimologia , Linhagem
16.
Genet Med ; 3(2): 102-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11280946

RESUMO

PURPOSE: To report on the use of fluorescence in situ hybridization (FISH) and dosage-sensitive Southern blot analysis in the molecular diagnosis of patients with Saethre-Chotzen syndrome. METHODS: FISH and dosage-sensitive Southern blot analysis utilizing TWIST gene probes were performed on patients with Saethre-Chotzen syndrome but without an identifiable TWIST sequence variation. RESULTS: Four unrelated patients with a deletion of the TWIST gene were identified by Southern blot; one of them had a complex chromosomal rearrangement involving 7p21 and no apparent deletion by FISH, suggesting a smaller deletion in the region including the TWIST gene. A fifth patient had an abnormal TWIST gene fragment on Southern blot analysis that segregated with the disease in the family; FISH was normal in this patient, suggesting a partial deletion or rearrangement in or near the gene. CONCLUSION: FISH and dosage-sensitive Southern blot analysis are useful diagnostic tools in Saethre-Chotzen syndrome without TWIST sequence variation.


Assuntos
Acrocefalossindactilia/diagnóstico , Acrocefalossindactilia/genética , Cromossomos Humanos Par 7 , Deleção de Genes , Proteínas Nucleares , Adolescente , Adulto , Southern Blotting , Criança , Pré-Escolar , Cromossomos/ultraestrutura , Relação Dose-Resposta a Droga , Feminino , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariotipagem , Masculino , Linhagem , Análise de Sequência de DNA , Fatores de Transcrição/genética , Proteína 1 Relacionada a Twist
17.
Methods Mol Med ; 53: 193-216, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-21318797

RESUMO

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.

18.
J Biol Chem ; 275(49): 38554-60, 2000 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-10993904

RESUMO

The sarcoglycan complex in striated muscle is a heterotetrameric unit integrally associated with sarcospan in the dystrophin-glycoprotein complex. The sarcoglycans, alpha, beta, gamma, and delta, are mutually dependent with regard to their localization at the sarcolemma, and mutations in any of the sarcoglycan genes lead to limb-girdle muscular dystrophies type 2C-2F. In smooth muscle beta- and delta-sarcoglycans are associated with epsilon-sarcoglycan, a glycoprotein homologous to alpha-sarcoglycan. Here, we demonstrate that gamma-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle. First, we show the presence of gamma-sarcoglycan in a number of smooth muscle-containing organs, and we verify the existence of identical transcripts in skeletal and smooth muscle. The specificity of the expression of gamma-sarcoglycan in smooth muscle was confirmed by analysis of smooth muscle cells in culture. Next, we provide evidence for the association of gamma-sarcoglycan with the sarcoglycan-sarcospan complex by biochemical analysis and comparison among animal models for muscular dystrophy. Moreover, we find disruption of the sarcoglycan complex in the vascular smooth muscle of a patient with gamma-sarcoglycanopathy. Taken together, our results prove that the sarcoglycan complex in vascular and visceral smooth muscle consists of epsilon-, beta-, gamma-, and delta-sarcoglycans and is associated with sarcospan.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Músculo Liso/metabolismo , Proteínas de Neoplasias , Transcrição Gênica , Sequência de Aminoácidos , Animais , Proteínas do Citoesqueleto/deficiência , Proteínas do Citoesqueleto/genética , Distroglicanas , Humanos , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Camundongos Knockout , Dados de Sequência Molecular , Músculo Esquelético/metabolismo , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Sarcoglicanas
19.
Hum Mol Genet ; 9(13): 2019-27, 2000 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-10942431

RESUMO

Autosomal recessive limb girdle muscular dystrophies 2C-2F represent a family of diseases caused by primary mutations in the sarcoglycan genes. We show that sarcospan, a novel tetraspan-like protein, is also lost in patients with either a complete or partial loss of the sarcoglycans. In particular, sarcospan was absent in a gamma-sarcoglycanopathy patient with normal levels of alpha-, beta- and delta-sarcoglycan. Thus, it is likely that assembly of the complete, tetrameric sarcoglycan complex is a prerequisite for membrane targeting and localization of sarcospan. Based on our findings that sarcospan is integrally associated with the sarcoglycans, we screened >50 autosomal recessive muscular dystrophy cases for mutations in sarcospan. Although we identified three intragenic polymorphisms, we did not find any cases of muscular dystrophy associated with primary mutations in the sarcospan gene. Finally, we have identified an important case of limb girdle muscular dystrophy and cardiomyopathy with normal expression of sarcospan. This patient has a primary mutation in the gamma-sarcoglycan gene, which causes premature truncation of gamma-sarcoglycan without affecting assembly of the mutant gamma-sarcoglycan into a complex with alpha-, beta- and delta-sarcoglycan and sarcospan. This is the first demonstration that membrane expression of a mutant sarcoglycan-sarcospan complex is insufficient in preventing muscular dystrophy and cardiomyopathy and that the C-terminus of gamma-sarcoglycan is critical for the functioning of the entire sarcoglycan-sarcospan complex. These findings are important as they contribute to a greater understanding of the structural determinants required for proper sarcoglycan-sarcospan expression and function.


Assuntos
Proteínas de Transporte/metabolismo , Aberrações Cromossômicas/genética , Proteínas do Citoesqueleto/metabolismo , Distrofina/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Distrofias Musculares/genética , Proteínas de Neoplasias , Adulto , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Proteínas de Transporte/genética , Aberrações Cromossômicas/metabolismo , Transtornos Cromossômicos , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Éxons , Feminino , Imunofluorescência , Genes Recessivos , Humanos , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Distrofias Musculares/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Ligação Proteica , Sarcoglicanas
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