Current Issue : January - March Volume : 2014 Issue Number : 1 Articles : 6 Articles
In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle\r\ndevelopment. The objectives of this study are (i) to characterize and compare gene expression profiles in cumulus cells (CCs)\r\nof periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii) to\r\nexamine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were\r\nupregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A) and cell-to-cell interactions (GJA5). Conversely,\r\ngenes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1). Interestingly, some\r\ngenes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH) were associated\r\nwith day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3) were related to in vitro embryo quality in\r\nboth gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality....
Radiosurgery for cerebral arteriovenous malformations (AVMs) is limited to 2-year latency. There is no early marker to monitor\r\nwhether the lesion is responsive to radiosurgery. In this study, we examined endothelial gene expression and molecular changes in\r\nresponse to radiosurgery. Gene expression of E- and P-selectin, ICAM-1, PECAM-1, VCAM-1, tissue factor, and vWF in human\r\ncerebral microvascular endothelial cells was quantified by RT-qPCR at different radiation doses and time points. Soluble E- and\r\nP-selectin, ICAM-1, VCAM-1, and tissue factor in an animal model of AVMs were quantified by ELISA at different time after\r\nradiosurgery.We found that gene expression of E- and P-selectin, ICAM-1, PECAM-1, and VCAM-1 was upregulated by radiation\r\nin a dose-dependent manner (?? < .05). Gene expression of E- and P-selectin and ICAM-1 was more sensitive to irradiation than\r\nthat of PECAM-1 andVCAM-1. Radiosurgery induced gene expression of P-selectin, ICAM-1, PECAM-1, andVCAM-1 was linearly\r\ncorrelated with time (?? < .05). Radiosurgery induced elevation of soluble E- and P-selectin, ICAM-1, VCAM-1, and tissue factor\r\nin a rat model of AVMs (?? < .05).Thus, a combination of these molecules measured at different time points may serve as an early\r\npredictor of responsiveness of AVMs to radiosurgery....
Background: Identification of expression alternations between early and late stage cancers is helpful for\r\nunderstanding cancer development and progression. Much research has been done focusing on stage-dependent\r\ngene expression profiles. In contrast, relatively fewer studies on isoform expression profiles have been performed\r\ndue to the difficulty of quantification and noisy splicing. Here we conducted both gene- and isoform-level analysis\r\non RNA-seq data of 234 stage I and 81 stage IV kidney renal clear cell carcinoma patients, aiming to uncover the\r\nstage-dependent expression signatures and investigate the advantage of isoform expression profiling for\r\nidentifying advanced stage cancers and predicting clinical outcome.\r\nResults: Both gene and isoform expression signatures are useful for distinguishing cancer stages. They provide\r\ncommon and unique information associated with cancer progression and metastasis. Combining gene and isoform\r\nsignatures even improves the classification performance and reveals additional important biological processes, such\r\nas angiogenesis and TGF-beta signaling pathway. Moreover, expression abundance of a number of genes and\r\nisoforms is predictive of the risk of cancer death in an independent dataset, such as gene and isoform expression\r\nof ITPKA, the expression of a functional important isoform of UPS19.\r\nConclusion: Isoform expression profiling provides unique and important information which cannot be detected by\r\ngene expression profiles. Combining gene and isoform expression signatures helps to identify advanced stage\r\ncancers, predict clinical outcome, and present a comprehensive view of cancer development and progression....
During growth, C. botulinum is always exposed to different environmental changes, such as temperature increase, nutrient\r\ndeprivation, and pH change; however, its corresponding global transcriptional profile is uncharacterized. This study is the first\r\ndescription of the genome-wide gene expression profile of C. botulinum in response to heat shock stress. Under heat stress\r\n(temperature shift from 37�°C to 45�°C over a period of 15 min), 176 C. botulinum ATCC 3502 genes were differentially expressed.\r\nThe response included overexpression of heat shock protein genes (dnaK operon, groESL, hsp20, and htpG) and downregulation of\r\naminoacyl-tRNA synthetase genes (valS, queA, tyrR, and gatAB) and ribosomal and cell division protein genes (ftsZ and ftsH).\r\nIn parallel, several transcriptional regulators (marR, merR, and ompR families) were induced, suggesting their involvement in\r\nreshuffling of the gene expression profile. In addition, many ABC transporters (oligopeptide transport system), energy production\r\nand conversion related genes (glpA and hupL), cell wall and membrane biogenesis related genes (fabZ, fabF, and fabG), flagellaassociated\r\ngenes (flhA, flhM, flhJ, flhS, and motAB), and hypothetical genes also showed changed expression patterns, indicating\r\nthat they may play important roles in survival under high temperatures....
Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In\r\ncontrast to 3,3??,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive\r\nmetabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a\r\nfactor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the\r\ncellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that\r\nhippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience\r\nto stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover\r\nin these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250mcg/kg in\r\nnaive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This\r\ndemonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests\r\nimportant central functions of T2, whose biological role only lately is becoming to be elucidated....
Background.The genome-wide association studies (GWAS) have been successful during the last few years. A key challenge is that\r\nthe interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data intoGWAS\r\nmay provide clues elucidating the mechanisms by which a genetic variant leads to a disease. Methods. Here, we developed a novel\r\nmediation analysis approach to identify new expression quantitative trait loci (eQTL) driving CYP2D6 activity by combining\r\ngenotype, gene expression, and enzyme activity data. Results. 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are\r\nfound strongly associated (?? < 10-5, FDR = 16.6% and 11.7%) for two different genotype platforms, namely, Affymetrix and\r\nIllumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes\r\nin the expression of distant genes by affecting major regulators or transcription factors (TFs), which would be visible as an eQTL\r\nhotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery\r\nof 64 TFs. Conclusions. Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It\r\nimproves our understanding of the functional genetic variations for the liver metabolism mechanisms....
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