Lambertsylvest7423

Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC.

Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.

Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.NSD1 gene (Nuclear Receptor Binding SET Domain Protein 1) encodes a methyltransferase that plays an important role in embryonic development. read more NSD1 is implicated in the transcription and methylation of histone H3 at lysine 36 (H3-K36), but the molecular mechanisms involved in these processes remain largely unknown. Pathogenic variants of NSD1 gene lead to Sotos syndrome, and have also been detected in some type of cancers, such as acute myeloid leukemia. In this study we have investigated NSD1 mRNA expression in fibroblast cell lines obtained from 14 Sotos patients and from 8 healthy controls. In addition to the expected NSD1 canonical transcript (isoform 1), we identified two additional, not yet reported, short NSD1 mRNA isoforms NSD1 Δ5Δ7 (isoform 2) and NSD1 Δ19-23 (isoform 3), both in healthy subjects and in Sotos patients. We also show that NSD1 mutations in patients can be associated with a decreased level of NSD1 mRNA, as expected. Moreover, one patient, bearing the NSD1 variant c.6010-10G > A, expressed an additional shorter transcript derived from an aberrant splicing event. These results may provide a basis to elucidate the impact of different NSD1 pathogenic variants on the heterogeneity of phenotype associated with Sotos syndrome.Iron-refractory iron deficiency anemia (IRIDA) is considered an autosomal recessive iron deficiency anemia due to mutations in the transmembrane protease serine 6 (TMPRSS6) gene. Variations in iron parameters and a higher risk of iron deficiency have been linked to the TMPRSS6 mutations. Furthermore, human genome-wide association studies (GWAS) identified a common mutation (rs855791) linked to abnormal hematological parameters, highlighting the importance of the TMPRSS6 gene in the regulation of iron homeostasis. This is the first study to investigate TMPRSS6 gene mutation in six Saudi families of probands with iron deficiency anemia unresponsive to oral iron and partially responsive to parenteral iron administration. Each participant provided a vacutainer tube with three blood samples (2.5 ml each) and analyzed based on hematological, biochemical iron profiles, and followed by genotyping by PCR. The TMPRSS6 gene was amplified, sequenced, and analyzed in all probands and family members. Statistical analysis was done using SPSS and SHEsis software. Few functional mutations in these families were suggested (p.W73X, p.E523K and p.V736A). The proband of family 6 presented numerous hematological abnormalities upon initial consultation, including normocytic anemia accompanied by low Hb, normal MCV, low serum iron, low serum ferritin, and normal TIBC. While the p.W73X variant was only found in 2 families, the p.V736A variant was found in all examined Saudi families with IRIDA. Given the evidence outlined for these six cases, future genotype-phenotype correlation studies in a large number of IRIDA patients in Saudi Arabia may be very informative for patient management, in addition to increasing knowledge of TMPRSS6 function during development as well as factors in the regulation of TMPRSS6 and its effect on iron levels in the body.E3 ligases are involved in various cellular biological processes, and their loss of function or improper targeting can induce multiple types of human diseases. F-box protein 7(FBXO7) is a unit in the SKP1-Cullin1-F-box (SCF) SCFFBXO7 E3 ligase composite, playing the role of recognizing some substrates. Additionally, FBXO7 is involved in the regulation of the proteasome complex, mitophagy, the cell cycle, cell proliferation, and germ cell differentiation. Although many articles have reviewed the pathogenesis of FBXO7, which is associated with Parkinson disease-15 (PARKIN15), a summary of the role of FBXO7 as an E3 ligase and its SCF-independent function is incomplete, as well as an overview of FBXO7 in cancer. Therefore, we summarized FBXO7-related substrates and the roles of FBXO7 in human cancers. In addition, based on previous studies, we supplemented the newly discovered FBXO7 mutations in PARKIN15 patients and some potential pathogenic mechanisms that may lead to PARKIN15. A profound exploration of the general pathophysiological mechanisms of this protein could provide potential evidence for the targeted treatment of PARKIN15 and malignant tumors.Different workers have found different bases of the spacer of the sigma 70 promoter of Escherichia coli to be important, depending on the base sequence of the two hexameric boxes of the naturally occurring promoter they were working on. Besides, there was no clue as to why particular bases worked better than others in particular positions. This necessitated a fresh look at the spacer region of a model promoter comprising all the consensus promoter elements. Randomisation of the three bases of the spacer in positions -15 to -13 with respect to the transcription initiation site, has elicited more than 50-fold variation in activity of the promoter, the highest and the lowest activities being 14,391(the three bases being GCA) and 264 Miller units (the three bases being AAA) respectively. Pairs of promoters of very similar activities were observed, even when the bases in these three positions were very different. The promoters with similar activities had similar three dimensional structures of the promoter DNA, as determined by molecular dynamics simulations. Randomisation of the three bases in positions -18 to -16 of the promoter that contained the triplet GCA in positions -15 to -13, resulted in promoters with highest activity of 15,759 (the triplet upstream of GCA being TAT) and lowest activity of 1,882 (the triplet upstream of GCA being AAA). Good correlation between the bending angles of the promoter DNAs and promoter activities could be observed, the R2 value being 0.8724. Retardation of electrophoretic mobility of the promoter DNAs correlated well with activity.PCSK9 gain-of-function (GOF) variants increase degradation of low-density lipoprotein receptor (LDLR) and are potentially associated with Familial Hypercholesterolemia (FH). This study aimed to explore the effects of PCSK9 missense variants on protein structure and interactions with LDLR using molecular modeling analyses and in vitro functional studies. Variants in FH-related genes were identified in a Brazilian FH cohort using an exon-target gene sequencing strategy. Eight PCSK9 missense variants in pro- [p.(E32K) and p.(E57K)], catalytic [p.(R237W), p.(P279T) and p.(A443T)], and C-terminal histidine-cysteine rich (CHR) [p.(R469W), p.(Q619P) and p.(R680Q)] domains were identified. Molecular dynamics analyses revealed that GOF variants p.(E32K) and p.(R469W) increased extreme motions in PCSK9 amino acid backbone fluctuations and affected Hbond and water bridge interactions between the pro-domain and CM1 region of the CHR domain. HEK293FT cells transfected with plasmids carrying p.(E32K) and p.(R469W) variants reduced LDLR expression (8.7 % and 14.8 %, respectively) compared to wild type (p less then 0.05) but these GOF variants did not affect PCSK9 expression and secretion. The missense variants p.(P279T) and p.(Q619P) also reduced protein stability and altered Hbond interactions. In conclusion, PCSK9 p.(E32K), p.(R469W), p.(P279T) and p.(Q619P) variants disrupt intramolecular interactions that are essential for PCSK9 structural conformation and biological activity and may have a potential role in FH pathogenesis.The main function of Sec61 complex is participating in the transport of polypeptide chains across the endoplasmic reticulum. The Sec61α subunit is the largest subunit of the Sec61 complex and shows high degree of conservation. In this study, we identified the NbSec61α and NbSec61γ genes in the microsporidian Nosema bombycis for the first time. Multiple sequence alignment showed that the sequence similarity between NbSec61α and homologous proteins of other microsporidia was greater than 48 %. NbSec61α contains a "plug" domain (amino acids 40-74) unique to the Sec61/SecY complex. Phylogenetic analysis based on NbSec61α and NbSec61γ indicated that the N. bombycis was closely related to Nosema granulosis, Nosema ceranae and Nosema apis. Indirect immunfluorescence assay showed that NbSec61α and NbSec61γ were mainly distributed in the perinuclear region of N. bombycis in different developmental phases. qRT-PCR results revealed that the expression level of NbSec61α gene increased in the early stage and reached the highest at 48 h, then decreased in the late stages. After knockdown of NbSec61α, the expression of NbSec61α, NbSec61γ and NbssrRNA genes were all significantly down-regulated. These results suggest that the NbSec61α and NbSec61γ may play an important role in the intracellular development of N. bombycis.Epigenetics is the science of altering gene expression without changing nucleotide sequences and may be induced by various environmental factors, including pesticides. The aim of this study was to investigate certain epigenetic changes including the methylation of CDKN2B, CDKN2A, and MGMT gene promoters and histone modifications of H3K9ac, H4K16ac, H4K20me3, and H3K4me3, as well as their association with the levels of organochlorine pesticides (OCPs) in children with acute lymphoblastic leukemia (ALL). The evaluation of OCP levels, promoter methylation, gene expression, and expression of histone modifications was performed by gas chromatography (GC), methylation-specific polymerase chain reaction (MS-PCR), reverse transcription PCR (RT-PCR), and western blotting, respectively. The results indicated that 76.2 % of CDKN2B promoters and 85.1 % of MGMT promoters were hypermethylated in children with ALL compared to healthy children. In addition, the relative expression of CDKN2B, MGMT, H4K16ac, and H3K4me3 showed a significant decrease in children with ALL compared to healthy children. Levels of OCPs in children with ALL were significantly higher than in healthy children. Furthermore, the results revealed that the rise in the OCP levels was associated with an increase in methylation at the promoter level of CDKN2B and MGMT as well as a decrease in the relative expression of H4K16ac and H3K4me3. Therefore, it can be concluded that exposure to OCPs is associated with the induction of epigenetic changes at the level of DNA and histones, which may lead to leukemia.The RAD51 gene plays an important role in DNA repair by homologous recombination, and is involved in the development and progression of multiple cancers. Single nucleotide polymorphisms in RAD51 have been previously described to impact the prognosis of patients with cancers, however, it is still unclear whether this is also true for hepatocellular carcinoma (HCC). This study therefore aimed to identify genetic variants in RAD51 and determine the effect on the survival of patients with HCC. In this study, we performed genotyping assays for RAD51 polymorphisms in a cohort of 368 patients with HCC who had underwent hepatectomy. Using multivariate cox proportional hazards model and Kaplan-Meier analyses with log-rank tests, we compared the survival of patients with HCC according to RAD51 SNP genotypes. We identified one potential functional variant, rs12593359, located in a microRNA (miRNA) binding site in the RAD51 3' untranslated region, to be an independent predictor of overall survival of patients with HCC in the dominant model.