Biomedical subjects
Publications and source records attributed to C Q Tran.
We prove that in the absence of phase singularities, a generalized Schell model partially coherent field is fully defined by its intensity in three planes. We discuss the implications of this result for the problem of characterizing wave fields.
We present an x-ray coherent diffractive imaging experiment utilizing a nonplanar incident wave and demonstrate success by reconstructing a nonperiodic gold sample at 24 nm resolution. Favorable effects of the curved beam illumination are identified.
We report a precise and spatially resolved measurement of the complex degree of coherence of a one-dimensional 1.5-keV beam produced by a third-generation synchrotron source. The method of phase-space tomography is used, which requires only measurements of the x-ray intensity. We find that the field is statistically stationary to within experimental error, the correlations are very well approximated by a Gaussian distribution, and the measured coherence length is in excellent agreement with expectations.
We compare new experimental x-ray total mass attenuation coefficients of silicon obtained with the x-ray extended-range technique (XERT) from 5 to 20 keV with theoretical calculations and earlier experimental measurements over a 5 to 50 keV energy range. The accuracy of between 0.27% and 0.5% of the XERT data allows us to probe alternate atomic and solid state wave function calculations and to test dominant scattering mechanisms. Discrepancies between experimental results and theoretical computations of the order of 5% are discussed in detail. No single theoretical computation is currently able to reproduce the experimental results over the entire 5 to 50 keV energy range investigated.
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We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing and determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. We identified 23 different disease-causing MECP2 mutations in 54 of 71 (76%) sporadic patients and in 2 of 7 (29%) familial cases. We compared electrophysiological findings, cerebrospinal fluid neurochemistry, and 13 clinical characteristics between patients carrying missense mutations and those carrying truncating mutations. Thirty-one of 34 patients (91%) with classic RTT had random XCI. Nonrandom XCI was associated with milder phenotypes, including a mitigated classic RTT caused by a rare early truncating mutation. Patients with truncating mutations have a higher incidence of awake respiratory dysfunction and lower levels of cerebrospinal fluid homovanillic acid. Scoliosis is more common in patients with missense mutations. These data indicate that different MECP2 mutations have similar phenotypic consequences, and random XCI plays an important role in producing the full phenotypic spectrum of classic RTT. The association of early truncating mutations with nonrandom XCI, along with the fact that chimeric mice lacking methyl-CpG-binding protein 2 (MeCP2) function die during embryogenesis, supports the notion that RTT is caused by partial loss of MeCP2 function.
Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
OBJECTIVES: We mapped a locus for autosomal recessive molar pregnancies with biparental genomic contribution to chromosome 19q13.4 between D19S924 and D19S890. This 5-Mb region is homologous to proximal mouse chromosome 7 and contains a cluster of Krüppel-type zinc finger genes, including the human homologue of the mouse imprinted genes: the paternally expressed gene 3 (PEG3) and the maternally expressed Zim1 genes. We analyzed the PEG3 gene for mutations in women with familial recurrent hydatidiform moles and to determine its imprinting status in humans. METHODS: We used database searches and screened cDNA libraries to find the complete genomic structure of PEG3. Polymerase chain reaction (PCR) amplification and direct sequencing of coding exons and flanking introns were performed on genomic DNA from the affected women. Allele-specific methylation and expression were studied by methylation-sensitive Southern analysis of a 5' located CpG island and by reverse-transcription PCR of total lymphoblast-derived RNA of normal individuals who were informative for two expressed polymorphisms. RESULTS: We did not detect any mutations in the coding region of PEG3 in the affected women. We observed allele-specific methylation of the CpG island and expression from the paternal allele in two independent informative pedigrees. CONCLUSION: Consistent with the findings in the mouse, the human PEG3 gene is expressed from the paternal allele. Our data support that PEG3 is not mutated in women with familial recurrent hydatidiform moles, although mutations in the regulatory regions that might affect imprinting or transcriptional level of the gene could not be evaluated.