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1.
F. Houben W. H. De Vos I. P. C. Krapels M. Coorens G. J. J. Kierkels M. A. F. Kamps V. L. R. M. Verstraeten C. L. M. Marcelis A. van den Wijngaard F. C. S. Ramaekers J. L. V. Broers 《Histochemistry and cell biology》2013,139(1):119-134
There is growing evidence that laminopathies, diseases associated with mutations in the LMNA gene, are caused by a combination of mechanical and gene regulatory distortions. Strikingly, there is a large variability in disease symptoms between individual patients carrying an identical LMNA mutation. This is why classical genetic screens for mutations appear to have limited predictive value for disease development. Recently, the widespread occurrence of repetitive nuclear ruptures has been described in fibroblast cultures from various laminopathy patients. Since this phenomenon was strongly correlated with disease severity, the identification of biomarkers that report on these rupture events could have diagnostic relevance. One such candidate marker is the PML nuclear body, a structure that is normally confined to the nuclear interior, but leaks out of the nucleus upon nuclear rupture. Here, we show that a variety of laminopathies shows the presence of these cytoplasmic PML particles (PML CPs), and that the amount of these protein aggregates increases with severity of the disease. In addition, between clinically healthy individuals, carrying LMNA mutations, significant differences can be found. Therefore, we postulate that detection of PML CPs in patient fibroblasts could become a valuable marker for diagnosis of disease development. 相似文献
2.
Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome 总被引:2,自引:0,他引:2
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The International IP Consortium 《American journal of human genetics》2001,69(6):1210-1217
Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation. 相似文献
3.
S. LUYSSAERT P. CIAIS S. L. PIAO E.‐D. SCHULZE M. JUNG S. ZAEHLE M. J. SCHELHAAS M. REICHSTEIN G. CHURKINA D. PAPALE G. ABRIL C. BEER J. GRACE D. LOUSTAU G. MATTEUCCI F. MAGNANI G. J. NABUURS H. VERBEECK M. SULKAVA G. R.
Van Der WERF I. A. JANSSENS members of the CARBOEUROPE‐IP SYNTHESIS TEAM 《Global Change Biology》2010,16(5):1429-1450
We present a new synthesis, based on a suite of complementary approaches, of the primary production and carbon sink in forests of the 25 member states of the European Union (EU‐25) during 1990–2005. Upscaled terrestrial observations and model‐based approaches agree within 25% on the mean net primary production (NPP) of forests, i.e. 520±75 g C m?2 yr?1 over a forest area of 1.32 × 106 km2 to 1.55 × 106 km2 (EU‐25). New estimates of the mean long‐term carbon forest sink (net biome production, NBP) of EU‐25 forests amounts 75±20 g C m?2 yr?1. The ratio of NBP to NPP is 0.15±0.05. Estimates of the fate of the carbon inputs via NPP in wood harvests, forest fires, losses to lakes and rivers and heterotrophic respiration remain uncertain, which explains the considerable uncertainty of NBP. Inventory‐based assessments and assumptions suggest that 29±15% of the NBP (i.e., 22 g C m?2 yr?1) is sequestered in the forest soil, but large uncertainty remains concerning the drivers and future of the soil organic carbon. The remaining 71±15% of the NBP (i.e., 53 g C m?2 yr?1) is realized as woody biomass increments. In the EU‐25, the relatively large forest NBP is thought to be the result of a sustained difference between NPP, which increased during the past decades, and carbon losses primarily by harvest and heterotrophic respiration, which increased less over the same period. 相似文献
4.
Nucleotide sequence of the genes for tryptophan synthase in Pseudomonas aeruginosa 总被引:17,自引:0,他引:17
We have determined the DNA sequence of the two adjacent genes for the alpha
and beta chains of tryptophan synthase in Pseudomonas aeruginosa, along
with 34 5'-flanking and 799 3'-flanking base pairs. The gene order is trpBA
as predicted from earlier genetic studies, and the two cistrons overlap by
4 bp; a ribosome binding site for the second gene is evident in the coding
sequence of the first gene. We have also determined the location of three
large deletions eliminating portions of each gene. A detailed comparison of
the deduced P. aeruginosa amino acid sequence with those published for E.
coli, Bacillus subtilis, and Saccharomyces cerevisiae shows much similarity
throughout the beta and most of the alpha subunit. Most of the residues
implicated by chemical modification or mutation as being critical for
enzymatic activity are conserved, along with many others, suggesting that
three-dimensional structure has remained largely constant during evolution.
We also report the construction of a recombinant plasmid that overproduces
a slightly modified alpha subunit from P. aeruginosa that can form a
functionally effective multimer with normal E. coli beta 2 subunit in vivo.
相似文献
5.
Krapels IP Zielhuis GA Vroom F de Jong-van den Berg LT Kuijpers-Jagtman AM van der Molen AB Steegers-Theunissen RP;Eurocran Gene-Environment Interaction Group 《Birth defects research. Part A, Clinical and molecular teratology》2006,76(8):613-620
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO) are orofacial clefts and have a multifactorial etiology. The identification of amendable parental risk factors may contribute to a reduced occurrence of these malformations in the future. METHODS: Standardized demographic and periconceptional exposure data from 284 parents of a child with CL/P, 66 parents of a child with a CPO and 222 parents of a child without congenital malformations were collected at approximately 24 months after the periconceptional period of the index child. Univariate and multivariate logistic regression analyses were used to estimate relative risks by odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Univariate results suggest that low parental education, periconceptional maternal medication use and illnesses, paternal smoking, and first-trimester maternal common cold increased CL/P risk. Pregnancy planning and periconceptional folic acid supplementation, however, reduced CL/P risk by approximately 50% (OR, 0.5; 95% CI, 0.3-0.8) and 40% (OR, 0.6; 95% CI, 0.4-0.9), respectively. Mostly comparable results were obtained for CPO. Being a boy (OR, 2.0; 95% CI, 1.4-3.0), folic acid supplementation (OR, 0.6; 95% CI, 0.4-0.9), and low paternal education (OR, 1.6; 95% CI, 1.0-2.3) mainly determined CL/P in the multivariate analyses, compared to low paternal (OR, 4.5; 95% CI, 2.1-9.4) and maternal medication use (OR, 2.0; 95% CI, 1.0-4.0) for CPO. CONCLUSIONS: Preconceptional counseling for orofacial cleft risk assessment should pay attention to maternal medication use, periconceptional folic acid supplementation, and exposures of the father. These determinants can be amended, thereby modifying orofacial cleft risk. 相似文献
6.
Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: II. Cloning and expression in Escherichia coli 总被引:7,自引:0,他引:7
Crawford IP; Wilde A; Yelverton EM; Figurski D; Hedges RW 《Molecular biology and evolution》1986,3(5):449-458
The genes for the large and small subunits of anthranilate synthase (trpE
and trpG, respectively) have been cloned from Pseudomonas aeruginosa PAC174
into E. coli by R-prime formation with the broad-host- range plasmid
R68.44. Sequential subcloning into plasmid vectors reduced the active
Pseudomonas DNA fragment to a length of 3.1 kb. We obtained evidence that
this region contains the promoter for its own expression and retains a
vestigial regulatory response to tryptophan scarcity or excess.
相似文献
7.
ANSON V. KOEHLER JOHN M. PEARCE PAUL L. FLINT J. CHRISTIAN FRANSON HON S. IP 《Molecular ecology》2008,17(21):4754-4762
The role of migratory birds in the movement of the highly pathogenic (HP) avian influenza H5N1 remains a subject of debate. Testing hypotheses regarding intercontinental movement of low pathogenic avian influenza (LPAI) viruses will help evaluate the potential that wild birds could carry Asian-origin strains of HP avian influenza to North America during migration. Previous North American assessments of LPAI genetic variation have found few Asian reassortment events. Here, we present results from whole-genome analyses of LPAI isolates collected in Alaska from the northern pintail (Anas acuta), a species that migrates between North America and Asia. Phylogenetic analyses confirmed the genetic divergence between Asian and North American strains of LPAI, but also suggested inter-continental virus exchange and at a higher frequency than previously documented. In 38 isolates from Alaska, nearly half (44.7%) had at least one gene segment more closely related to Asian than to North American strains of LPAI. Additionally, sequences of several Asian LPAI isolates from GenBank clustered more closely with North American northern pintail isolates than with other Asian origin viruses. Our data support the role of wild birds in the intercontinental transfer of influenza viruses, and reveal a higher degree of transfer in Alaska than elsewhere in North America. 相似文献
8.
9.
van den Boogaard MJ de Costa D Krapels IP Liu F van Duijn C Sinke RJ Lindhout D Steegers-Theunissen RP 《Human genetics》2008,124(5):525-534
Nonsyndromic orofacial clefts (OFC) are common birth defects caused by certain genes interacting with environmental factors.
Mutations and association studies indicate that the homeobox gene MSX1 plays a role in human clefting. In a Dutch case-control triad study (mother, father, and child), we investigated interactions
between MSX1 and the parents’ periconceptional lifestyle in relation to the risk of OFC in their offspring. We studied 181 case- and 132
control mothers, 155 case- and 121 control fathers, and 176 case- and 146 control children, in which there were 107 case triads
and 66 control triads. Univariable and multivariable logistic regression analyses were applied, and odds ratios (OR), 95%
confidence intervals (CI) were calculated. Allele 4 of the CA marker in the MSX1 gene, consisting of nine CA repeats, was the most common allele found in both the case and control triads. Significant interactions
were observed between allele 4 homozygosity of the child with maternal smoking (OR 2.7, 95% CI 1.1–6.6) and with smoking by
both parents (OR 4.9, 95% CI 1.4–18.0). Allele 4 homozygosity in the mother and smoking showed a risk estimate of OR 3.2 (95%
CI 1.1–9.0). If allele 4 homozygous mothers did not take daily folic acid supplements in the recommended periconceptional
period, this also increased the risk of OFC for their offspring (OR 2.8, 95% CI 1.1–6.7). Our findings show that, in the Dutch
population, periconceptional smoking by both parents interacts with a specific allelic variant of MSX1 to significantly increase OFC risk for their offspring. Possible underlying mechanisms are discussed.
D. de Costa and I. P. C. Krapels have equally contributed to this work. 相似文献
10.