RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

THE INFLUENCE OF INSETIF AND DISCIPLINE OF WORK ON EMPLOYEE PERFORMANCE IN CITANGKIL DISTRICT, CILEGON CITY

This study aims to determine the effect of incentives on work productivity, to determine the effect of work culture on work productivity and to determine the effect of incentives and work culture on work productivity in the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City. This research uses quantitative research methods, quantitative research methods can be interpreted as a research method based on the philosophy of positivism, used to research on certain populations or samples, sampling techniques are generally carried out randomly, data collection uses research instruments, data analysis is quantitative / statistics with the aim of testing the hypothesis set. As for the population in this study were as many as 6000 employees, the sample was calculated based on the Slovin formula, based on the results of these calculations with rounding, the sample was determined as many as 44 respondents / employees at the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City. Based on the research results, it is obtained that the value of Fcount is 15,983 with the decision Fcount&gt; Ftable (15,983&gt; 3,204) thus H0 is rejected and H1 is accepted, which means that there is a significant influence between incentives (X1) and work culture (X2) on work productivity (Y) in a significance level of 0.000 (0.000 &lt;0.05), it can be concluded that there is a significant influence between incentives (X1) and work culture (X2) on work productivity (Y) seaweed management in the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City. The results showed that there was a significant influence between incentives (X1) on work productivity (Y) in the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City - Banten, there is a significant influence between work culture (X2) on work productivity (Y) in the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City - Banten and there is an influence between incentives (X1) and work culture (X2) on work productivity (Y) in the Project Development Division of PT. Krakatau Steel (Persero) Cilegon City - Banten

Tumour mutations in long noncoding RNAs enhance cell fitness

Abstract Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic “driver” mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness