Rheumatic fever and rheumatic heart disease in Africa

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Characterization of novel isoforms and evaluation of SNF2L/SMARCA1 as a candidate gene for X-linked mental retardation in 12 families linked to Xq25-26

<p>Abstract</p> <p>Background</p> <p>Mutations in genes whose products modify chromatin structure have been recognized as a cause of X-linked mental retardation (XLMR). These genes encode proteins that regulate DNA methylation (<it>MeCP2</it>), modify histones (<it>RSK2 </it>and <it>JARID1C</it>), and remodel nucleosomes through ATP hydrolysis (<it>ATRX</it>). Thus, genes encoding other chromatin modifying proteins should also be considered as disease candidate genes. In this work, we have characterized the <it>SNF2L </it>gene, encoding an ATP-dependent chromatin remodeling protein of the ISWI family, and sequenced the gene in patients from 12 XLMR families linked to Xq25-26.</p> <p>Methods</p> <p>We used an <it>in silico </it>and RT-PCR approach to fully characterize specific SNF2L isoforms. Mutation screening was performed in 12 patients from individual families with syndromic or non-syndromic XLMR. We sequenced each of the 25 exons encompassing the entire coding region, complete 5' and 3' untranslated regions, and consensus splice-sites.</p> <p>Results</p> <p>The <it>SNF2L </it>gene spans 77 kb and is encoded by 25 exons that undergo alternate splicing to generate several distinct transcripts. Specific isoforms are generated through the alternate use of exons 1 and 13, and by the use of alternate donor splice sites within exon 24. Alternate splicing within exon 24 removes a NLS sequence and alters the subcellular distribution of the SNF2L protein. We identified 3 single nucleotide polymorphisms but no mutations in our 12 patients.</p> <p>Conclusion</p> <p>Our results demonstrate that there are numerous splice variants of SNF2L that are expressed in multiple cell types and which alter subcellular localization and function. <it>SNF2L </it>mutations are not a cause of XLMR in our cohort of patients, although we cannot exclude the possibility that regulatory mutations might exist. Nonetheless, <it>SNF2L </it>remains a candidate for XLMR localized to Xq25-26, including the Shashi XLMR syndrome.</p

Characterization of novel isoforms and evaluation of SNF2L/SMARCA1 as a candidate gene for X-linked mental retardation in 12 families linked to Xq25-26

<p>Abstract</p> <p>Background</p> <p>Mutations in genes whose products modify chromatin structure have been recognized as a cause of X-linked mental retardation (XLMR). These genes encode proteins that regulate DNA methylation (<it>MeCP2</it>), modify histones (<it>RSK2 </it>and <it>JARID1C</it>), and remodel nucleosomes through ATP hydrolysis (<it>ATRX</it>). Thus, genes encoding other chromatin modifying proteins should also be considered as disease candidate genes. In this work, we have characterized the <it>SNF2L </it>gene, encoding an ATP-dependent chromatin remodeling protein of the ISWI family, and sequenced the gene in patients from 12 XLMR families linked to Xq25-26.</p> <p>Methods</p> <p>We used an <it>in silico </it>and RT-PCR approach to fully characterize specific SNF2L isoforms. Mutation screening was performed in 12 patients from individual families with syndromic or non-syndromic XLMR. We sequenced each of the 25 exons encompassing the entire coding region, complete 5' and 3' untranslated regions, and consensus splice-sites.</p> <p>Results</p> <p>The <it>SNF2L </it>gene spans 77 kb and is encoded by 25 exons that undergo alternate splicing to generate several distinct transcripts. Specific isoforms are generated through the alternate use of exons 1 and 13, and by the use of alternate donor splice sites within exon 24. Alternate splicing within exon 24 removes a NLS sequence and alters the subcellular distribution of the SNF2L protein. We identified 3 single nucleotide polymorphisms but no mutations in our 12 patients.</p> <p>Conclusion</p> <p>Our results demonstrate that there are numerous splice variants of SNF2L that are expressed in multiple cell types and which alter subcellular localization and function. <it>SNF2L </it>mutations are not a cause of XLMR in our cohort of patients, although we cannot exclude the possibility that regulatory mutations might exist. Nonetheless, <it>SNF2L </it>remains a candidate for XLMR localized to Xq25-26, including the Shashi XLMR syndrome.</p

Characterisation of solid hydrodynamics in a three-phase stirred tank reactor with positron emission particle tracking (PEPT)

It is challenging to measure the hydrodynamics of stirred tank reactors when they contain multiphase flows comprising liquid, gas bubbles and particles. Radioactive particle tracking techniques such as positron emission particle tracking (PEPT) are the only established techniques to determine internal flow behaviour due to the inherent opacity and density of fluid and the vessel walls. The profiles of solids flow are an important tool for robust reactor design and optimisation and offer insight into underlying transport processes and particle–fluid–bubble interactions for applications such as froth flotation. In this work, measurements with PEPT were performed with two tracer particles differing in surface hydrophobicity to characterise the solids hydrodynamics in a baffled vessel agitated with a Rushton turbine. The location data from PEPT were averaged with time to estimate the probability density function (PDF) of particle velocity in individual voxels. The peaks of these voxel distributions were used to produce profiles of solids flow in different azimuthal and horizontal slices. Bimodal vertical velocity distributions were observed in the impeller radial jet which suggest the particles experienced trajectory crossing effects due to inertia. Statistical tests were performed to compare the velocity distributions of the hydrophilic and hydrophobic tracer particles, which indicated similar average flow behaviour in the liquid or pulp phase of the vessel and differences near the air inlet, in the impeller discharge stream and pulp–froth interface. With tracers designed to represent gangue and valuable mineral species, the differences in velocity reveal interactions such as bubble–particle attachment and entrainment