Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) maps to the SPG11 locus in the majority of cases. Mutations in the KIAA1840 gene, encoding spatacsin, have been shown to underlie SPG11-linked HSP-TCC. The aim of this study was to perform candidate gene analysis in HSP-TCC subjects from Asian families and to characterize disruption of spatacsin function during zebrafish development. Homozygosity mapping and direct sequencing were used to assess the ACCPN, SPG11, and SPG21 loci in four inbred kindreds originating from the Indian subcontinent. Four novel homozygous SPG11 mutations (c.442+1G>A, c.2146C>T, c.3602_3603delAT, and c.4846C>T) were identified, predicting a loss of spatacsin function in each case. To investigate the role of spatacsin during development, we additionally ascertained the complete zebrafish spg11 ortholog by reverse transcriptase PCR and 5′ RACE. Analysis of transcript expression through whole-mount in situ hybridization demonstrated ubiquitous distribution, with highest levels detected in the brain. Morpholino antisense oligonucleotide injection was used to knock down spatacsin function in zebrafish embryos. Examination of spg11 morphant embryos revealed a range of developmental defects and CNS abnormalities, and analysis of axon pathway formation demonstrated an overall perturbation of neuronal differentiation. These data confirm loss of spatacsin as the cause of SPG11-linked HSP-TCC in Asian kindreds, expanding the mutation spectrum recognized in this disorder. This study represents the first investigation in zebrafish addressing the function of a causative gene in autosomal recessive HSP and identifies a critical role for spatacsin during early neural development in vivo

Petrography of gypsum-bearing facies of the Codó Formation (Late Aptian), Northern Brazil

An original and detailed study focusing the petrography of evaporites from the Late Aptian deposits exposed in the eastern and southern São Luís-Grajaú Basin is presented herein, with the attempt of distinguishing between primary and secondary evaporites, and reconstructing their post-depositional evolution. Seven evaporites phases were recognized: 1. chevron gypsum; 2. nodular to lensoidal gypsum or anhydrite; 3. fibrous to acicular gypsum; 4. mosaic gypsum; 5. brecciated gypsum or gypsarenite; 6. pseudo-nodular anhydrite or gypsum; and 7. rosettes of gypsum. The three first phases of gypsum display petrographic characteristics that conform to a primary nature. The fibrous to acicular and mosaic gypsum were formed by replacement of primary gypsum, but their origin took place during the eodiagenesis, still under influence of the depositional setting. These gypsum morphologies are closely related to the laminated evaporites, serving to demonstrate that their formation was related to replacements that did not affect the primary sedimentary structures. The pseudo-nodular anhydrite or gypsum seems to have originated by mobilization of sulfate-rich fluids during burial, probably related to halokinesis. The rosettes of gypsum, which intercept all the other gypsum varieties, represent the latest phase of evaporite formation in the study area, resulting from either intrastratal waters or surface waters during weathering.<br>Neste trabalho, é apresentado um estudo original e detalhado enfocando os aspectos petrográficos dos evaporitos de depósitos aptianos superiores expostos no sul e leste da Bacia de São Luís-Grajaú. O objetivo é o estabelecimento de critérios que permitam distinguir entre evaporitos primários e secundários, além da reconstrução de sua evolução pós-deposicional. Sete fases de evaporitos foram reconhecidas: 1. gipsita em chevron; 2. gipsita ou anidrita nodular a lenticular; 3. gipsita fibrosa a acicular; 4. gipsita em mosaico; 5. gipsita brechada a gipsarenito; 6. anidrita ou gipsita pseudo-nodular; e 7. gipsita em rosetas. As três primeiras fases apresentam características petrográficas condizentes com origem primária. Agipsita fibrosa a acicular e a gipsita em mosaico foramformadas por substituições de gipsita primária, com origem provável nos estágios iniciais da diagenêse, portanto ainda sob influência do ambiente deposicional. Estas morfologias de gipsita estão relacionadas com a fáciesde evaporito laminado, tendo sido formadas por substituição, porém sem afetar a estruturação primária. A gipsita ou anidrita pseudo-nodular originou-se pela mobilização de soluções sulfatadas durante ou após soterramento, provavelmente associada à halocinese. A gipsita em rosetas, que intercepta todas as outras variedades de gipsita, representa o ultimo estágio de formação de evaporitos na área de estudo, tendo resultado de soluções intraestratais ou de águas superficiais durante intemperismo