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11.
12.
Ronald G. Munger Tsunenobu Tamura Kelley E. Johnston Marcia L. Feldkamp Roxane Pfister John C. Carey 《Birth defects research. Part A, Clinical and molecular teratology》2009,85(2):151-155
BACKGROUND: The role of maternal zinc nutrition in human oral clefts (OCs) is unclear. We measured plasma zinc concentrations (PZn) of case and control mothers to evaluate the associations between PZn and risk of OCs with and without other malformations. METHODS: Case mothers were ascertained by the Utah Birth Defects Network and control mothers were selected from Utah birth certificates by matching for child gender and delivery month and year. Maternal blood was collected >1 year after the last pregnancy. PZn was available for 410 case mothers who were divided into four subgroups: isolated cleft lip with or without cleft palate (CL/P‐I, n = 231), isolated cleft palate (CP‐I, n = 74), CL/P with other malformations (CLP‐M, n = 42), and CP with other malformations (CP‐M, n = 63). PZn was available for 447 control mothers. The mean age of children at blood sampling was 3.7 years for all cases combined and 4.3 years for controls. RESULTS: Mean PZns of all groups were similar, and low PZn (<11.0 μmol/L) was found in 59% of cases and 62% of controls. Risk of OCs did not vary significantly across PZn quartiles for the four subgroups individually and all OC groups combined. CONCLUSIONS: We previously reported that poor maternal zinc status was a risk factor for OCs in the Philippines, where OC prevalence is high and maternal PZn is low. In Utah, however, no such association was found, suggesting that poor maternal zinc status may become a risk factor only when zinc status is highly compromised. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc. 相似文献
13.
Aberrant mucin O-glycosylation often occurs in different cancers and is characterized by immature expression of simple mucin-type carbohydrates. At present, there are some controversial reports about the Tn antigen (GalNAcα-O-Ser/Thr) expression and there is a great lack of information about the [UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts)] expression in chronic lymphocytic leukemia (CLL). To gain insight in these issues we evaluated the Tn antigen expression in CLL patient samples using two Tn binding proteins with different fine specificity. We also studied the expression from 14 GalNAc-Ts genes in CLL patients by RT-PCR. Our results have provided additional information about the expression level of the Tn antigen, suggesting that a low density of Tn residues is expressed in CLL cells. We also found that GALNT11 was expressed in CLL cells and normal T cell whereas little or no expression was found in normal B cells. Based on these results, GALNT11 expression was assessed by qPCR in a cohort of 50 CLL patients. We found significant over-expression of GALNT11 in 96% of B–CLL cells when compared to normal B cells. Moreover, we confirmed the expression of this enzyme at the protein level. Finally we found that GALNT11 expression was significantly associated with the mutational status of the immunoglobulin heavy chain variable region (IGHV), [?2(1) = 18.26; P < 0.0001], lipoprotein lipase expression [?2(1) = 13.72; P = 0.0002] and disease prognosis [?2(1) = 15.49; P < 0.0001]. Our evidence suggests that CLL patient samples harbor aberrant O-glycosylation highlighted by Tn antigen expression and that the over-expression of GALNT11 constitutes a new molecular marker for CLL. 相似文献
14.
VLJ Whitehall TD Dumenil DM McKeone CE Bond ML Bettington RL Buttenshaw L Bowdler GW Montgomery LF Wockner BA Leggett 《Epigenetics》2014,9(11):1454-1460
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. 相似文献
15.
The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova and Stylonychia pustulata 总被引:17,自引:0,他引:17
We have determined the complete nucleotide sequence of the small- subunit
ribosomal RNA genes for the ciliate protozoans Stylonychia pustulata and
Oxytricha nova. The sequences are homologous and sufficiently similar that
these organisms must be closely related. In a phylogeny inferred from
comparisons of several eukaryotic small-subunit ribosomal RNAs, the
divergence of the ciliates from the eukaryotic line of descent is seen to
coincide with the radiation of the plants, the animals, and the fungi. This
radiation is preceded by the divergence of the slime mold, Dictyostelium
discoideum.
相似文献
16.
Molecular population genetics of ref(2)P, a locus which confers viral resistance in Drosophila 总被引:4,自引:0,他引:4
The ref(2)P locus (2-54.2) is polymorphic for two allelic forms in natural
populations of Drosophila melanogaster, ref(2)Po and ref(2)Pp. The latter
allele confers resistance to the rhabdovirus sigma infecting wild
populations. Previous work, based on a small sample of prescreened
restrictive (resistant) and permissive (susceptible) alleles, identified a
large number of amino acid replacement changes (7) relative to synonymous
changes (1). Such protein variability could be the result of
variation-enhancing selection. To further test the selection hypothesis, we
have examined the DNA sequences of ten randomly chosen lines of D.
melanogaster and one line of D. simulans. Nine of the ten lines are
permissive; D. simulans does not harbor the virus. The melanogaster alleles
contain 4 synonymous changes, 19 noncoding changes, and 13 amino acid
replacement changes, indicating a relatively high level of polymorphism.
Three sequenced restrictive alleles have nearly identical sequences,
indicating that they are relatively young. Compared to the permissive
alleles, they share only a complex deletion at codon 34, CAG-AAT to GGA,
which our analysis indicates to be the site conferring the restrictive
phenotype. Patterns of polymorphism and divergence differ from neutral
predictions by several criteria for the amino terminal region, which
contains the complex deletion (codons 1-91), but not the remainder of the
protein (codons 92-599). We find a higher rate of evolution on the D.
melanogaster lineage than on the D. simulans lineage. The relatively large
amount of both replacement and silent polymorphism in the permissive
alleles and the lack of divergence between permissive and restrictive
alleles suggests that the sigma virus and ref(2)P may be engaged in an
evolutionary race in which new restrictive alleles are continually arising
but are relatively short-lived.
相似文献
17.
Relationships among msx gene structure and function in zebrafish and other vertebrates 总被引:6,自引:2,他引:4
Ekker M; Akimenko MA; Allende ML; Smith R; Drouin G; Langille RM; Weinberg ES; Westerfield M 《Molecular biology and evolution》1997,14(10):1008-1022
The zebrafish genome contains at least five msx homeobox genes, msxA, msxB,
msxC, msxD, and the newly isolated msxE. Although these genes share
structural features common to all Msx genes, phylogenetic analyses of
protein sequences indicate that the msx genes from zebrafish are not
orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians.
The zebrafish msxB and msxC are more closely related to each other and to
the mouse Msx3. Similarly, although the combinatorial expression of the
zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches,
fins, and sensory organs suggests functional similarities with the Msx
genes of other vertebrates, differences in the expression patterns preclude
precise assignment of orthological relationships. Distinct duplication
events may have given rise to the msx genes of modern fish and other
vertebrate lineages whereas many aspects of msx gene functions during
embryonic development have been preserved.
相似文献
18.
1alpha,25(OH)2-vitamin D3 is a hormone which potentially stimulates bone cell growth and differentiation. TNFalpha is one possible inductor for apoptosis; apoptosis being an important regulatoring factor for bone modelling and remodelling. We examined the influence of physiological levels (0.1 nM) 1alpha,25(OH)2-vitamin D3 on TNFalpha-mediated apoptosis in human osteoblast-like cells. These human cells were obtained from bone fragments obtained during orthopedic operations on patients without systemic bone disease. Treatment with 1alpha,25(OH)2-vitamin D3 for 8 weeks resulted in a significant reduction (30%) of viable cell number compared to untreated cells. Incubation with TNFalpha (100 ng/ml for 4 hours) only had limited effects on the rate of apoptosis in control cells. After pretreatment with 1alpha,25(OH)2-vitamin D3, induction of apoptosis increased up to 10% in human osteoblast-like cells. In parallel to the induction of apoptosis, 1alpha,25(OH)2-vitamin D3 stimulated osteocalcin and alkaline phosphatase as markers of mature osteoblasts. Our data suggest that 1alpha,25(OH)2-vitamin D3 has a stimulatory effect on TNFalpha-induced apoptosis in human osteoblast-like cells as a result of 1alpha,25(OH)2-vitamin D3-induced cell differentiation. 相似文献
19.
M Schott W B Minich H S Willenberg C Papewalis J Seissler J Feldkamp A Bergmann W A Scherbaum N G Morgenthaler 《Hormones et métabolisme》2005,37(12):741-744
Recently, we demonstrated that higher levels of autoantibodies to the human TSH receptor (TBII) predict relapse of hyperthyroidism in Graves' disease (GD). The aim of this study was to extend this outcome prediction by dividing TBII into stimulating (TSAb) and blocking (TBAb) TSH receptor autoantibodies. Altogether, ninety patients (81 female, 9 male) were retrospectively analyzed; sixty-four patients (71 %) did not go into remission or relapsed, whereas twenty-six patients (29 %) went into remission (median follow-up: 17.5 months). TSAb and TBAb measurement was performed in a CHO cell bioassay with cAMP readout at the time of their first visit in our outpatient clinic (single point measurement in median 6.5 months after initial diagnosis). In the remission group, eighteen of twenty-six patients (69 %) were TSAb-positive, whereas fifty-three of sixty-four patients (83 %) were TSAb-positive in the relapse group (p = ns). The mean stimulation indices (SI) were 4.1 in the remission group and 12.9 in the relapse group, respectively (p = 0.015). By using a threshold of 10 SI, the specificity for relapse was 96.0 %, as only one in twenty patients with an SI above 10 went into remission during follow-up (PPV 95 %). Most TSAb-positive patients also had high levels of TBII. Neither group showed any difference with respect to blocking type autoantibodies, which were mostly negative in both groups. In summary, high TSAb levels are similar but not superior to TBII for predicting relapse in GD patients. In contrast, TBAb measurement does not add any valuable information in this context. In the clinical routine, TSAb/TBAb measurement may not play an important role for diagnosis or outcome prediction of GD, since sensitive 2 (nd) generation TBII assays are easier to perform and offer similar information to the clinician. Bioassays should be reserved for special clinical questions such as Graves' disease in pregnancy. 相似文献
20.
The MMS22L–TONSL heterodimer directly promotes RAD51‐dependent recombination upon replication stress
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Wojciech Piwko Karun Mutreja Lepakshi Ranjha Diana Stafa Alexander Smirnov Mia ML Brodersen Ralph Zellweger Andreas Sturzenegger Pavel Janscak Massimo Lopes Matthias Peter Petr Cejka 《The EMBO journal》2016,35(23):2584-2601
Homologous recombination (HR) is a key pathway that repairs DNA double‐strand breaks (DSBs) and helps to restart stalled or collapsed replication forks. How HR supports replication upon genotoxic stress is not understood. Using in vivo and in vitro approaches, we show that the MMS22L–TONSL heterodimer localizes to replication forks under unperturbed conditions and its recruitment is increased during replication stress in human cells. MMS22L–TONSL associates with replication protein A (RPA)‐coated ssDNA, and the MMS22L subunit directly interacts with the strand exchange protein RAD51. MMS22L is required for proper RAD51 assembly at DNA damage sites in vivo, and HR‐mediated repair of stalled forks is abrogated in cells expressing a MMS22L mutant deficient in RAD51 interaction. Similar to the recombination mediator BRCA2, recombinant MMS22L–TONSL limits the assembly of RAD51 on dsDNA, which stimulates RAD51‐ssDNA nucleoprotein filament formation and RAD51‐dependent strand exchange activity in vitro. Thus, by specifically regulating RAD51 activity at uncoupled replication forks, MMS22L–TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their HR‐mediated restart in vivo. 相似文献