116 research outputs found

    Kinetic undercooling in solidification of a hypereutectic Al-Si alloy; Effect of solidifying within a ceramic preform composite

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    Dendrite tip temperature measurements are reported for the hypereutectic alloy Al-30% Si, directionally solidified as a bulk (non-composite) alloy, and also as the matrix of a fibrous metal matrix composite. Over the range of tip velocities studied (10-1000 mu m s) the primary Si tip undercooling in the directionally solidified bulk alloy increases slightly with increasing tip velocity, and indicates, by its large value, the presence of significant kinetic undercooling. This is in contrast with solidification of the composite, in which the primary Si tip undercooling decreases markedly with increasing tip velocity and is in quantitative agreement with theory for cellular solidification with no kinetic undercooling. These results, supported by metallographic observations, indicate that "wetting" of the alumina fibers by the growing silicon phase in the composite essentially eliminates the kinetic barrier to growth of primary Si crystals. The underlying mechanism is rationalized on the basis of macroscopic capillaric analysis at the solid/fiber/liquid juncture. This juncture is shown to be significantly more efficient in nucleating new facet planes than is are-entrant twin plane corner. (C) 1997 Acta Metallurgica Inc

    Evolution of electrospinning in liver tissue engineering

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    The major goal of liver tissue engineering is to reproduce the phenotype and functions of liver cells, especially primary hepatocytes ex vivo. Several strategies have been explored in the recent past for culturing the liver cells in the most apt environment using biological scaffolds supporting hepatocyte growth and differentiation. Nanofibrous scaffolds have been widely used in the field of tissue engineering for their increased surface-to-volume ratio and increased porosity, and their close resemblance with the native tissue extracellular matrix (ECM) environment. Electrospinning is one of the most preferred techniques to produce nanofiber scaffolds. In the current review, we have discussed the various technical aspects of electrospinning that have been employed for scaffold development for different types of liver cells. We have highlighted the use of synthetic and natural electrospun polymers along with liver ECM in the fabrication of these scaffolds. We have also described novel strategies that include modifications, such as galactosylation, matrix protein incorporation, etc., in the electrospun scaffolds that have evolved to support the long-term growth and viability of the primary hepatocytes

    Estrogen Receptor-Beta Gene Polymorphism in women with Breast Cancer at the Imam Khomeini Hospital Complex, Iran

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    ER-alpha and ER-beta genes have been proven to play a significant role in breast cancer. Epidemiologic studies have revealed that age-incidence patterns of breast cancer in Middle East differ from those in the Western countries. Two selected coding regions in the ER-β gene (exons 3 and 7) were scanned in Iranian women with breast cancer (150) and in healthy individuals (147). PCR single-strand conformation polymorphism was performed. A site of silent single nucleotide polymorphism was found only on exon 7. The SNP was found only in breast cancer patients (5.7%) (χ2 = 17.122, P = 0.01). Codon 392 (C1176G) of allele 1 was found to have direct association with the occurrence of lymph node metastasis. Our data suggest that ER-β polymorphism in exon 7 codon 392 (C1176G) is correlated with various aspects of breast cancer and lymph node metastasis in our group of patients

    Potential Role of Aromatase over Estrogen Receptor Gene Polymorphisms in Migraine Susceptibility: A Case Control Study from North India

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    BACKGROUND: The present study was undertaken to find out the role of estrogen pathway related gene polymorphisms in susceptibility to migraine in Northern Indian population. Aromatase, CYP19A1 (rs10046 and rs4646); estrogen receptors, ESR1 (rs2234693, rs1801132, rs2228480 and rs9340799) and ESR2 (rs1271572 and rs1256049) polymorphisms were selected for the present study. METHODOLOGY/PRINCIPAL FINDINGS: The patients were recruited in two cohorts - primary (207) and replicative (127) along with 200 healthy controls and genotyped for various polymorphisms. Logistic regression analysis was applied for statistical analyses. The results were validated in the replicative cohort and pooled by meta analysis using Fisher's and Mantel-Haenszel test. Furthermore, Benjamini - Hochberg false discovery rate test was used to correct for multiple comparisons. CYP19A1 rs10046 and CYP19A1 rs4646 polymorphisms were found to confer risk and protective effect, respectively. Out of four ESR1 polymorphisms, only rs2234693 variant allele was significantly associated in migraine with aura. No significant associations were observed for ESR2 polymorphisms. Significant haplotypes were identified for CYP19A1 and ESR1 polymorphisms. Gene- gene interactions of genotypes as well as haplotypes were observed for CYP19A1- ESR1 showing both risk and protective combinations. CONCLUSION: We strongly suggest CYP19A1 polymorphisms to be the major contributing factors in migraine susceptibility instead of genetic variants of estrogen receptors

    How Contemporary Human Reproductive Behaviors Influence the Role of Fertility-Related Genes: The Example of the P53 Gene

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    Studies on human fertility genes have identified numerous risk/protective alleles involved in the occurrence of reproductive system diseases causing infertility or subfertility. Investigations we carried out in populations at natural fertility seem to suggest that the clinical relevance that some fertility genes are now acquiring depends on their interaction with contemporary reproductive behaviors (birth control, delayed childbearing, and spacing birth order, among others). In recent years, a new physiological role in human fertility regulation has emerged for the tumor- suppressor p53 gene (P53), and the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans. To lend support to our previous observations, we examined the impact of Arg72Pro polymorphism on fertility in two samples of Italian women not selected for impaired fertility but collected from populations with different (premodern and modern) reproductive behaviors. Among the women at near-natural fertility (n = 98), the P53 genotypes were not associated with different reproductive efficiency, whereas among those with modern reproductive behaviors (n = 68), the P53 genotypes were associated with different mean numbers of children [Pro/Pro = 0.75<Pro/Arg = 1.7<Arg/Arg = 2, (p = 0.056)] and a significant negative relationship between the number of children and P53 Pro allele frequencies (p = 0.028) was observed. These results are consistent with those of clinical studies reporting an association between the P53 Pro allele and recurrent implantation failure. By combining these findings with previous ones, we suggest here that some common variants of fertility genes may have become “detrimental” following exposure to modern reproductive patterns and might therefore be associated with reduced reproductive success. Set within an evolutionary framework, this change could lead to the selection of a set of gene variants fitter to current reproductive behaviors as the shift to later child-bearing age in developed countries

    Effects of two common polymorphisms in the 3' untranslated regions of estrogen receptor β on mRNA stability and translatability

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    Estrogen signaling is mediated by estrogen receptors (ERs), ERα and ERβ. Aberrant estrogen signaling is involved in breast cancer development. ERα is one of the key biomarkers for diagnosis and treatment of breast cancer. Unlike ERα, ERβ is still not introduced as a marker for diagnosis and established as a target of therapy. Numerous studies suggest antiproliferative effects of ERβ, however its role remains to be fully explored. Albeit important, ERα is not a perfect marker, and some aspects of ERα function are still unclear. This thesis aims to characterize distinct molecular facets of ER action relevant for breast cancer and provide valuable information for ER-based diagnosis and treatment design. In PAPER I, we analyzed the functionality of two common single nucleotide polymorphisms in the 3’ untranslated regions of ERβ, rs4986938 and rs928554, which have been extensively investigated for association with various diseases. A significant difference in allelic expression was observed for rs4986938 in breast tumor samples from heterozygous individuals. However, no difference in mRNA stability or translatability between the alleles was observed. In PAPER II, we provided a more comprehensive understanding of ERβ function independent of ERα. A global gene expression analysis in a HEK293/ERβ cell model identified a set of ERβ-regulated genes. Gene Ontology (GO) analysis showed that they are involved in cell-cell signaling, morphogenesis and cell proliferation. Moreover, ERβ expression resulted in a significant decrease in cell proliferation. In PAPER III, using the human breast cancer MCF-7/ERβ cell model, we demonstrated, for the first time, the binding of ERα/β heterodimers to various DNA-binding regions in intact chromatin. In PAPER IV, we investigated a potential cross-talk between estrogen signaling and DNA methylation by identifying their common target genes in MCF-7 cells. Gene expression profiling identified around 150 genes regulated by both 17β- estradiol (E2) and a hypomethylating agent 5-aza-2’-deoxycytidine. Based on GO analysis, CpG island prediction analysis and previously reported ER binding regions, we selected six genes for further analysis. We identified BTG3 and FHL2 as direct target genes of both pathways. However, our data did not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes. In PAPER V, we further explored the interactions between estrogen signaling and DNA methylation, with focus on DNA methyltransferases (DNMT1, DNMT3a and DNMT3b). E2, via ERα, up-regulated DNMT1 and down-regulated DNMT3a and DNMT3b mRNA expression. Furthermore, DNMT3b interacted with ERα. siRNA-mediated DNMT3b depletion increased the expression of two genes, CDKN1A and FHL2. We proposed that the molecular mechanism underlying regulation of FHL2 and CDKN1A gene expression involves interplay of DNMT3b and ERα. In conclusion, the studies presented in this thesis contribute to the knowledge of ERβ function, and give additional insight into the cross-talk mechanisms underlying ERα signaling with ERβ and with DNA methylation pathways
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