ADAURA update: only the end of the beginning.
Ontology highlight
ABSTRACT:
SUBMITTER: Muthusamy B
PROVIDER: S-EPMC10413021 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
Publications
ADAURA update: only the end of the beginning.
Muthusamy Bharathi B Pennell Nathan A NA
Translational lung cancer research 20230522 7
Similar Datasets
Project description: Not available
| S-EPMC5546246 | biostudies-literature
Project description: Not available
| S-EPMC9470645 | biostudies-literature
Project description:Molecular mechanisms that regulate gene expression can occur either before or after transcription. The information for post-transcriptional regulation can lie within the sequence or structure of the RNA transcript and it has been proposed that G-quadruplex nucleic acid sequence motifs may regulate translation as well as transcription. Here, we have explored the incidence of G-quadruplex motifs in and around the untranslated regions (UTRs) of mRNA. We observed a significant strand asymmetry, consistent with a general depletion of G-quadruplex-forming RNA. We also observed a positional bias in two distinct regions, each suggestive of a specific function. We observed an excess of G-quadruplex motifs towards the 5'-ends of 5'-UTRs, supportive of a hypothesis linking 5'-UTR RNA G-quadruplexes to translational control. We then analysed the vicinity of 3'-UTRs and observed an over-representation of G-quadruplex motifs immediately after the 3'-end of genes, especially in those cases where another gene is in close proximity, suggesting that G-quadruplexes may be involved in the termination of gene transcription.
| S-EPMC2577360 | biostudies-literature
Project description:Osteoporosis and disorders of bone fragility are highly heritable, but despite much effort the identities of few of the genes involved has been established. Recent developments in genetics such as genome-wide association studies are revolutionizing research in this field, and it is likely that further contributions will be made through application of next-generation sequencing technologies, analysis of copy number variation polymorphisms, and high-throughput mouse mutagenesis programs. This article outlines what we know about osteoporosis genetics to date and the probable future directions of research in this field.
| S-EPMC2592817 | biostudies-literature
Project description:Accurate biomarkers are a crucial and necessary precondition for precision medicine, yet existing ones are often unspecific and new ones have been very slow to enter the clinic. Mass spectrometry (MS)-based proteomics excels by its untargeted nature, specificity of identification, and quantification, making it an ideal technology for biomarker discovery and routine measurement. It has unique attributes compared to affinity binder technologies, such as OLINK Proximity Extension Assay and SOMAscan. In in a previous review in 2017, we described technological and conceptual limitations that had held back success. We proposed a 'rectangular strategy' to better separate true biomarkers by minimizing cohort-specific effects. Today, this has converged with advances in MS-based proteomics technology, such as increased sample throughput, depth of identification, and quantification. As a result, biomarker discovery studies have become more successful, producing biomarker candidates that withstand independent verification and, in some cases, already outperform state-of-the-art clinical assays. We summarize developments over the last years, including the benefits of large and independent cohorts, which are necessary for clinical acceptance. Shorter gradients, new scan modes, and multiplexing are about to drastically increase throughput, cross-study integration, and quantification, including proxies for absolute levels. We have found that multiprotein panels are inherently more robust than current single analyte tests and better capture the complexity of human phenotypes. Routine MS measurement in the clinic is fast becoming a viable option. The full set of proteins in a body fluid (global proteome) is the most important reference and the best process control. Additionally, it increasingly has all the information that could be obtained from targeted analysis although the latter may be the most straightforward way to enter regular use. Many challenges remain, not least of a regulatory and ethical nature, but the outlook for MS-based clinical applications has never been brighter.
| S-EPMC10388585 | biostudies-literature
Project description: Not available
| S-EPMC7398685 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) technologies are increasingly being applied to reveal cellular heterogeneity in kidney development and disease. In just the last year, multiple scRNA-seq datasets have been generated from kidney organoids, developing mouse and human kidney, adult kidney, and kidney cancer. The data generated enables a much deeper understanding of biological processes within and between cells. It has also elucidated unforeseen cell lineage relationships, defined the presence of off-target cell types in kidney organoids, and revealed a diverse inflammatory response in a human kidney allograft undergoing rejection. This review summarizes the recent rapid progress in scRNA-seq of the kidney and outlines future directions for single-cell technologies as applied to the kidney.
| S-EPMC6609508 | biostudies-literature
Project description:Accurate tracing of cell viability is critical for optimizing delivery methods and evaluating the efficacy and safety of cell therapeutics. A nanoparticle-based cell tracker is developed to image cell fate from live to dead. The particle is fabricated from two types of optically quenched polyelectrolytes, a life indicator and a death indicator, through electrostatic interactions. On incubation with cells, the fabricated bifunctional nanoprobes are taken up efficiently and the first colour is produced by normal intracellular proteolysis, reflecting the healthy status of the cells. Depending on the number of coated layers, the signal can persist for several replication cycles. However, as the cells begin dying, the second colour appears quickly to reflect the new cell status. Using this chameleon-like cell tracker, live cells can be distinguished from apoptotic and necrotic cells instantly and definitively.
| S-EPMC4852472 | biostudies-literature
Project description:Honest reporting is essential for society to function well. However, people frequently lie when asked to provide information, such as misrepresenting their income to save money on taxes. A landmark finding published in PNAS [L. L. Shu, N. Mazar, F. Gino, D. Ariely, M. H. Bazerman, Proc. Natl. Acad. Sci. U.S.A. 109, 15197-15200 (2012)] provided evidence for a simple way of encouraging honest reporting: asking people to sign a veracity statement at the beginning instead of at the end of a self-report form. Since this finding was published, various government agencies have adopted this practice. However, in this project, we failed to replicate this result. Across five conceptual replications (n = 4,559) and one highly powered, preregistered, direct replication (n = 1,235) conducted with the authors of the original paper, we observed no effect of signing first on honest reporting. Given the policy applications of this result, it is important to update the scientific record regarding the veracity of these results.
| S-EPMC7132248 | biostudies-literature
Project description:Genetic coding variants in APOL1, which encodes apolipoprotein L1 (APOL1), were identified in 2010 and are relatively common among individuals of sub-Saharan African ancestry. Approximately 13% of African Americans carry two APOL1 risk alleles. These variants, termed G1 and G2, are a frequent cause of kidney disease - termed APOL1 nephropathy - that typically manifests as focal segmental glomerulosclerosis and the clinical syndrome of hypertension and arterionephrosclerosis. Cell culture studies suggest that APOL1 variants cause cell dysfunction through several processes, including alterations in cation channel activity, inflammasome activation, increased endoplasmic reticulum stress, activation of protein kinase R, mitochondrial dysfunction and disruption of APOL1 ubiquitinylation. Risk of APOL1 nephropathy is mostly confined to individuals with two APOL1 risk variants. However, only a minority of individuals with two APOL1 risk alleles develop kidney disease, suggesting the need for a 'second hit'. The best recognized factor responsible for this 'second hit' is a chronic viral infection, particularly HIV-1, resulting in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor. Current therapies for APOL1 nephropathies are not adequate to halt progression of chronic kidney disease, and new targeted molecular therapies are in clinical trials.
| S-EPMC8877744 | biostudies-literature