Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia

In acute myeloid leukemia, there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wild-type and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures

Rapid and mobile determination of alcoholic strength in wine, beer and spirits using a flow-through infrared sensor

<p>Abstract</p> <p>Background</p> <p>Ever since Gay-Lussac's time, the alcoholic strength by volume (% vol) has been determined by using densimetric measurements. The typical reference procedure involves distillation followed by pycnometry, which is comparably labour-intensive and therefore expensive. At present, infrared (IR) spectroscopy in combination with multivariate regression is widely applied as a screening procedure, which allows one to determine alcoholic strength in less than 2 min without any sample preparation. The disadvantage is the relatively large investment for Fourier transform (FT) IR or near-IR instruments, and the need for matrix-dependent calibration. In this study, we apply a much simpler device consisting of a patented multiple-beam infrared sensor in combination with a flow-through cell for automated alcohol analysis, which is available in a portable version that allows for on-site measurements.</p> <p>Results</p> <p>During method validation, the precision of the infrared sensor was found to be equal to or better than densimetric or FTIR methods. For example, the average repeatability, as determined in 6 different wine samples, was 0.05% vol and the relative standard deviation was below 0.2%. Accuracy was ensured by analyzing 260 different alcoholic beverages in comparison to densimetric or FTIR results. The correlation was linear over the entire range from alcohol-free beers up to high-proof spirits, and the results were in substantial agreement (R = 0.99981, p < 0.0001, RMSE = 0.279% vol). The applicability of the device was further proven for the analysis of wines during fermentation, and for the determination of unrecorded alcohol (i.e. non-commercial or illicit products).</p> <p>Conclusions</p> <p>The flow-through infrared device is much easier to handle than typical reference procedures, while time-consuming sample preparation steps such as distillation are not necessary. Therefore, the alcoholic strength can be economically and quickly controlled (requiring less than 60 s per sample). The device also gives the opportunity for mobile on-site control in the context of labelling control of wine, beer and spirits, the process monitoring of fermentations, or the evaluation of unrecorded alcohols.</p

Deregulated expression of circular RNAs in acute myeloid leukemia

Circular RNAs (circRNAs) are dynamically regulated during differentiation and show cell type-specific expression, which is altered in cancer and can have a direct impact on its various hallmarks. We hypothesized that circRNA expression is deregulated in acute myeloid leukemia (AML) and that circRNA candidates might contribute to the pathogenesis of the disease. To identify leukemia-associated and differentiation-independent changes in circRNA expression, we determined the circular RNAome of 61 AML patients and 16 healthy hematopoietic stem and progenitor cell (HSPC) samples using ribosomal RNA-depleted RNA sequencing. We found hundreds of circRNAs that were differentially expressed between AML and healthy HSPCs. Gene set analysis found that many of these circRNAs were transcribed from genes implicated in leukemia biology. We discovered a circRNA derived from the T-cell transcription factor gene B cell CLL/lymphoma 11B, circBCL11B, which was exclusively expressed in AML patients, but not detected in healthy HSPCs, and associated with a T-cell-like gene expression signature. We were able to validate this finding in an independent cohort of 332 AML patients. Knockdown of circBCL11B had a negative effect on leukemic cell proliferation and resulted in increased cell death of leukemic cells, thereby suggesting circBCL11B as a novel functionally relevant candidate in AML pathogenesis. In summary, our study enables comprehensive insights into circRNA expression changes upon leukemic transformation and provides valuable information on the biology of leukemic cells and potential novel pathway dependencies that are relevant for AML therapy

Local deprivation status and seasonal influenza vaccination coverage in adults ≥ 65 years residing in the Foggia municipality, Italy, 2009-2016

Introduction: In Italy, vaccination against seasonal influenza has been recommended for the elderly since 1980, but coverage is still far below the WHO minimum target level of 75%. Effective interventions to improve influenza vaccination should take into account socioeconomic determinants of inequalities in vaccine uptake. This study aimed to assess differences in vaccination coverage, by socioeconomic status, among people ≥ 65 years of age residing in the Foggia municipality, Italy. Methods: A Socio-Economic-Health Deprivation Index (SEHDI) was constructed by using a multivariate analysis model. The resident population, for census block, was classified in 5 deprivation groups. Differences in demographic and socioeconomic indicators, the standardized mortality ratios (SMRs), and the average vaccination coverage among deprivation groups were evaluated with the linear F-test. The association between census variables and influenza vaccination coverage, in each deprivation group, was assessed using the Pearson bivariate correlation. Results: The SEHDI allowed to identify factors related to ageing, housing, household size and composition, and education. Forty percent of people residing in the Foggia municipality lived in conditions of socioeconomic and health deprivation. Belonging to families with 3 or 4 members was associated with increased coverage rates. In the most deprived group, vaccination uptake was positively associated with the dependency ratio. Conclusions: The results of this study have shown that there is still large room for improving influenza vaccination coverage among subjects belonging to the most deprived areas. Surveillance of trends in influenza vaccine uptake by socioeconomic groups is a feasible contribution to implementing effective, tailored to the frail older persons, vaccine utilization programs

Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia

In acute myeloid leukemia, there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wild-type and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures

Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia

textabstractIn acute myeloid leukemia, there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wild-type and mutated acute myeloid leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and acute myeloid leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as acute myeloid leukemia subgroup-specific circRNA signatures