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Severe Defects (severe + defect)
Selected AbstractsHypomineralized molars and incisors of unknown origin: treatment outcome at age 18 yearsINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2005I. MEJĀRE Summary. Objective., To assess the outcome of treatment of hypomineralized molars and incisors of unknown aetiology (MIH) in 18-year-olds. Design., A follow-up study including clinical examination, panoramic radiography and intraoral photos. Sample and method., Seventy-six individuals treated at the Eastman Dental Institute in Stockholm during 1978,2001 with the diagnosis MIH. Severity of enamel defects in molars and incisors, prevalence and distribution of extracted molars, type, quality and median duration of restorations, periradicular condition of affected molars, dental occlusion and space closure in cases of extraction, as well as the individual's satisfaction with the treatment, were assessed. Results., Severe defects with enamel surface breakdown in all four molars occurred in 42% of the individuals and 29% had at least one incisor with yellow/brown opacity in the enamel. At follow up, 42% of the individuals had at least one molar extracted; 18% had all four molars extracted. The median duration of the molar restorations (n = 153) was 5 years. Of the individuals with restored molars, 48% had at least one unacceptable restoration. Periradicular pathology was observed in three molars. The sagittal relations did not differ between individuals with and without extraction of molars. Space closure was acceptable in 87% of the individuals with extracted molars. Eighty percent were satisfied with the treatment. Conclusions., Extraction of molars with severe enamel defects gave good or acceptable results in a majority of the patients while conservative restorative treatment resulted in a need for additional treatment in approximately half of the patients. [source] Distinct roles of DNA polymerases delta and epsilon at the replication fork in Xenopus egg extractsGENES TO CELLS, Issue 3 2004Tomoyuki Fukui DNA polymerases , and , (Pol, and Pol,) are widely thought to be the major DNA polymerases that function in elongation during DNA replication in eukaryotic cells. However, the precise roles of these polymerases are still unclear. Here we comparatively analysed DNA replication in Xenopus egg extracts in which Pol, or Pol, was immunodepleted. Depletion of either polymerase resulted in a significant decrease in DNA synthesis and accumulation of short nascent DNA products, indicating an elongation defect. Moreover, Pol, depletion caused a more severe defect in elongation, as shown by sustained accumulation of both short nascent DNA products and single-stranded DNA gaps, and also by elevated chromatin binding of replication proteins that function more frequently during lagging strand synthesis. Therefore, our data strongly suggest the possibilities that Pol, is essential for lagging strand synthesis and that this function of Pol, cannot be substituted for by Pol,. [source] The RNA chaperone Hfq is essential for the virulence of Salmonella typhimuriumMOLECULAR MICROBIOLOGY, Issue 1 2007Alexandra Sittka Summary The RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Q, RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium. A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro. Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non-coding RNAs, placing Hfq at the centre of post-transcriptional regulation of virulence gene expression in Salmonella. In addition, the hfq mutation appears to cause a chronic activation of the RpoE-mediated envelope stress response which is likely due to a misregulation of membrane protein expression. [source] Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden.CONGENITAL ANOMALIES, Issue 4 2007A prospective population study ABSTRACT The use of folic acid prior to conception is generally recommended for the prevention of birth defects, notably neural tube defects. In a previous study from Sweden, based on interviews of women in early pregnancy, no such effect was found on the general malformation rate, but data for neural tube defects were scarce. Using data from the Swedish Medical Birth Register for the years 1995,2004, 20 891 women were identified who reported the use of folic acid in early pregnancy, but not of anticonvulsants. These women were compared to all other women who gave birth during the study period. Malformations in the infants born were identified from multiple sources. No reduction in the general malformation rate was seen among infants born to women who reported the use of folic acid (OR = 1.09, 95% CI 1.02,1.17) and no effect of neural tube defect rate was seen (RR = 1.35, 95% CI 0.82,2.22), based on 16 infants with neural tube defect whose mother reported the use of folic acid. No effect was seen on the rates of other malformations except for cardiac defects, where a statistically significant increased risk (notably for severe defects) was found (OR = 1.19, 95% CI 1.05,1.35). The effect of various deficiencies in data collection is discussed, but is unlikely to explain the lack of protective effect noticed. So far, it has not been possible to demonstrate a beneficial effect of folic acid supplementation on malformation risk in Sweden. A more complete ascertainment and detailed timing and dosage of folic acid use in a prospective study is recommended. [source] The lim domain only protein 7 is important in zebrafish heart developmentDEVELOPMENTAL DYNAMICS, Issue 12 2008Elisabeth B. Ott Abstract The LIM domain only protein 7 (LMO7), a member of the PDZ and LIM domain-containing protein family is a candidate gene with possible roles in embryonic development and breast cancer progression. LMO7 has been linked to actin cytoskeleton organization through nectin/afadin and to cell,cell adhesion by means of E-cadherin/catenin. In addition, LMO7 has been shown to regulate transcription of the nuclear membrane protein Emerin and other muscle relevant genes. In this study, we used in situ hybridization to investigate LMO7 expression during embryonic development in three widely used vertebrate model species: the zebrafish, the chicken and the mouse. Our temporal and spatial gene expression analysis revealed both common and distinct patterns between these species. In mouse and chicken embryos we found expression in the outflow tract, the inflow tract, the pro-epicardial organ and the second heart field, structures highly important in the developing heart. Furthermore, gene knockdown experiments in zebrafish embryos resulted in severe defects in heart development with effects on the conduction system and on heart localization. In summary, we present here the first developmental study of LMO7. We reveal the temporal and spatial expression patterns of this important gene during mouse, chicken and fish development and our findings suggest essential functions for LMO7 during vertebrate heart development. Developmental Dynamics 237:3940,3952, 2008. Š 2008 Wiley-Liss, Inc. [source] Rho1-GEFs Rgf1 and Rgf2 are involved in formation of cell wall and septum, while Rgf3 is involved in cytokinesis in fission yeastGENES TO CELLS, Issue 12 2005Tadashi Mutoh The Rho GTPase acts as a binary molecular switch by converting between a GDP-bound inactive and a GTP-bound active conformational state. The guanine nucleotide exchange factors (GEFs) are critical activators of Rho. Rho1 has been shown to regulate actin cytoskeleton and cell wall synthesis in the fission yeast Schizosaccharomyces pombe. Here we studied function of fission yeast RhoGEFs, Rgf1, Rgf2, and Rgf3. It was shown that these proteins have similar molecular structures, and function as GEFs for Rho1. Disruption of either rgf1 or rgf2 did not show a serious effect on the cell. On the other hand, disruption of rgf3 caused severe defects in contractile ring formation, F-actin patch localization, and septation during cytokinesis. Rgf1 and Rgf2 were localized to the cell ends during interphase and the septum. Rgf3 formed a ring at the division site, which was located outside the contractile ring and inside the septum where Rho1 was accumulated. In summary, Rgf1 and Rgf2 show functional redundancy, and roles of these RhoGEFs are likely to be different from that of Rgf3. Rho1 is likely to be activated by Rgf3 at the division site, and involved in contractile ring formation and/or maintenance and septation. [source] Phage-selected lipopolysaccharide mutants of Pectobacterium atrosepticum exhibit different impacts on virulenceJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2010T.J. Evans Abstract Aims:, To positively select Pectobacterium atrosepticum (Pa) mutants with cell surface defects and to assess the impact of these mutations on phytopathogenesis. Methods and Results:, Several phages were isolated from treated sewage effluent and were found to require bacterial lipopolysaccharide (LPS) for infection. Two strains with distinct mutations in LPS were obtained by transposon mutagenesis. Along with a third LPS mutant, these strains were characterized with respect to various virulence-associated phenotypes, including growth rate, motility and exoenzyme production, demonstrating that LPS mutations are pleiotropic. Two of the strains were deficient in the synthesis of the O-antigen portion of LPS, and both were less virulent than the wild type. A waaJ mutant, which has severe defects in LPS biosynthesis, was dramatically impaired in potato tuber rot assays. The infectivity of these novel phages on 32 additional strains of Pa was tested, showing that most Pa isolates were sensitive to the LPS-dependent phages. Conclusions:, Native LPS is crucial for optimal growth, survival and virulence of Pa in vivo, but simultaneously renders such strains susceptible to phage infection. Significance and Impact of the Study:, This work demonstrates the power of phages to select and identify the virulence determinants on the bacterial surface, and as potential biocontrol agents for Pa infections. [source] The Impact of Intelligence and Institutional Improvements on Economic GrowthKYKLOS INTERNATIONAL REVIEW OF SOCIAL SCIENCES, Issue 3 2002Erich Weede Standard indicators of human capital endowment , like literacy, school enrollment ratios or years of schooling , suffer from a number of defects. They are crude. Mostly, they refer to input rather than output measures of human capital formation. Occasionally, they produce implausible effects. They are not robustly significant determinants of growth. Here, they are replaced by average intelligence. This variable consistently outperforms the other human capital indicators in spite of suffering from severe defects of its own. The immediate impact of institutional improvements, i.e., more government tolerance of private enterprise or economic freedom, on growth it is in the same order of magnitude as intelligence effects are. The senior author is responsible for picking a ,politically incorrect' topic, i.e., analyzing the impact of IQ or average intelligence. The junior author has done the data compilation and the computations. [source] Kin1 is a plasma membrane-associated kinase that regulates the cell surface in fission yeastMOLECULAR MICROBIOLOGY, Issue 5 2010Angela Cadou Summary Cell morphogenesis is a complex process that depends on cytoskeleton and membrane organization, intracellular signalling and vesicular trafficking. The rod shape of the fission yeast Schizosaccharomyces pombe and the availability of powerful genetic tools make this species an excellent model to study cell morphology. Here we have investigated the function of the conserved Kin1 kinase. Kin1-GFP associates dynamically with the plasma membrane at sites of active cell surface remodelling and is present in the membrane fraction. Kin1, null cells show severe defects in cell wall structure and are unable to maintain a rod shape. To explore Kin1 primary function, we constructed an ATP analogue-sensitive allele kin1-as1. Kin1 inhibition primarily promotes delocalization of plasma membrane-associated markers of actively growing cell surface regions. Kin1 itself is depolarized and its mobility is strongly reduced. Subsequently, amorphous cell wall material accumulates at the cell surface, a phenotype that is dependent on vesicular trafficking, and the cell wall integrity mitogen-activated protein kinase pathway is activated. Deletion of cell wall integrity mitogen-activated protein kinase components reduces kin1, hypersensitivity to stresses such as those induced by Calcofluor white and SDS. We propose that Kin1 is required for a tight link between the plasma membrane and the cell wall. [source] Four conserved intramolecular disulphide linkages are required for secretion and cell wall localization of a hydrophobin during fungal morphogenesisMOLECULAR MICROBIOLOGY, Issue 1 2005Michael J. Kershaw Summary Hydrophobins are morphogenetic proteins produced by fungi during assembly of aerial hyphae, sporulation, mushroom development and pathogenesis. Eight cysteine residues are present in hydrophobins and form intramolecular disulphide bonds. Here, we show that expressing eight cysteine,alanine substitution alleles of the MPG1 hydrophobin gene from Magnaporthe grisea causes severe defects in development of aerial hyphae and spores. Immunolocalization revealed that Mpg1 hydrophobin variants, lacking intact disulphide bonds, retain the capacity to self-assemble, but are not secreted to the cell surface. This provides the first genetic evidence that disulphide bridges in a hydrophobin are dispensable for aggregation, but essential for secretion. [source] DNA gyrase requirements distinguish the alternate pathways of Mu transpositionMOLECULAR MICROBIOLOGY, Issue 2 2003Tanya D. Sokolsky Summary The MuA transposase mediates transposition of bacteriophage Mu through two distinct mechanisms. The first integration event following infection occurs through a non-replicative mechanism. In contrast, during lytic growth, multiple rounds of replicative transposition amplify the phage genome. We have examined the influence of gyrase and DNA supercoiling on these two transposition pathways using both a gyrase-inhibiting drug and several distinct gyrase mutants. These experiments reveal that gyrase activity is not essential for integration; both lysogens and recombination intermediates are detected when gyrase is inhibited during Mu infection. In contrast, gyrase inhibition causes severe defects in replicative transposition. In two of the mutants, as well as in drug-treated cells, replicative transposition is almost completely blocked. Experiments probing for formation of MuA,DNA complexes in vivo reveal that this block occurs very early, during assembly of the transposase complex required for the catalytic steps of recombination. The findings establish that DNA structure-based signals are used differently for integrative and replicative transposition. We propose that transposase assembly, the committed step for recombination, has evolved to depend on different DNA /architectural signals to control the reaction outcome during these two distinct phases of the phage life cycle. [source] A role for ethylene in the phytochrome-mediated control of vegetative developmentTHE PLANT JOURNAL, Issue 6 2006Eloise Foo Summary Members of the phytochrome family of photoreceptors play key roles in vegetative plant development, including the regulation of stem elongation, leaf development and chlorophyll accumulation. Hormones have been implicated in the control of these processes in de-etiolating seedlings. However, the mechanisms by which the phytochromes regulate vegetative development in more mature plants are less well understood. Pea (Pisum sativum) mutant plants lacking phytochromes A and B, the two phytochromes present in this species, develop severe defects later in development, including short, thick, distorted internodes and reduced leaf expansion, chlorophyll content and CAB gene transcript level. Studies presented here indicate that many of these defects in phyA phyB mutant plants appear to be due to elevated ethylene production, and suggest that an important role of the phytochromes in pea is to restrict ethylene production to a level that does not inhibit vegetative growth. Mutant phyA phyB plants produce significantly more ethylene than WT plants, and application of an ethylene biosynthesis inhibitor rescued many aspects of the phyA phyB mutant phenotype. This deregulation of ethylene production in phy-deficient plants appears likely to be due, at least in part, to the elevated transcript levels of key ethylene-biosynthesis genes. The phytochrome A photoreceptor appears to play a prominent role in the regulation of ethylene production, as phyA, but not phyB, single-mutant plants also exhibit a phenotype consistent with elevated ethylene production. Potential interactions between ethylene and secondary plant hormones in the control of the phy-deficient mutant phenotype were explored, revealing that ethylene may inhibit stem elongation in part by reducing gibberellin levels. [source] Role of the RUNX1-EVI1 fusion gene in leukemogenesisCANCER SCIENCE, Issue 10 2008Kazuhiro Maki RUNX1-EVI1 is a chimeric gene generated by t(3;21)(q26;q22) observed in patients with aggressive transformation of myelodysplastic syndrome or chronic myelogenous leukemia. RUNX1-EVI1 has oncogenic potentials through dominant-negative effect over wild-type RUNX1, inhibition of Jun kinase (JNK) pathway, stimulation of cell growth via AP-1, suppression of TGF-,-mediated growth inhibition and repression of C/EBP,. Runx1-EVI1 heterozygous knock-in mice die in uteri due to central nervous system (CNS) hemorrhage and severe defects in definitive hematopoiesis as Runx1,/, mice do, indicating that RUNX1-EVI1 dominantly suppresses functions of wild-type RUNX1 in vivo. Acute myelogenous leukemia is induced in mice transplanted with bone marrow cells expressing RUNX1-EVI1, and a Runx1-EVI1 knock-in chimera mouse developed acute megakaryoblastic leukemia. These results suggest that RUNX1-EVI1 plays indispensable roles in leukemogenesis of t(3;21)-positive leukemia. Major leukemogenic effect of RUNX1-EVI1 is mainly through histone deacetyltransferase recruitment via C-terminal binding protein. Histone deacetyltransferase could be a target in molecular therapy of RUNX1-EVI1-expressing leukemia. (Cancer Sci 2008; 99: 1878,1883) [source] | |||||||||||||