Retinoic acid-induced 2 deficiency impairs genomic stability in breast cancer.

Background: Genome instability is a fundamental feature and hallmark of cancer, associated with aggressiveness, drug resistance and poor prognosis. RAI2 was initially identified as a novel metastasis suppressor protein specifically associated with the presence of disseminated tumour cells in the bone marrow of breast cancer patients, but its molecular function is largely unknown.

Methods: We analysed the consequences of RAI2 depletion on gene expression and genomic stability in luminal breast cancer cell lines, performed cytotoxicity profiling using a library of pharmacologically active compounds, and characterized a potential function of the RAI2 protein in the DNA damage response.

Growth factor independent 1B is a metabolic regulator that exerts pleiotropic effects on platelet function.

Background: Human variants in the growth factor independent 1B (GFI1B) transcription factor are associated with thrombocytopenia and a variable bleeding phenotype.

Objectives: In this study, we examined the bleeding phenotype associated with the human GFI1B variant and compared it with a mouse model of abnormal GFI1B function.

Methods: The transcriptomic and proteomic profiles of human GFI1B platelets were analyzed and compared with those of murine megakaryocytes harboring conditional deletion of Gfi1b.

Deep Sequencing of Early T Stage Colorectal Cancers Reveals Disruption of Homologous Recombination Repair in Microsatellite Stable Tumours with High Mutational Burdens.

Early T stage colorectal cancers (CRC) that invade lymph nodes (Stage IIIA) are rare and greatly under-represented in large-scale genomic mapping projects. We retrieved 10 Stage IIIA CRC cases, matched these to 16 Stage 1 CRC cases (T1 depth without lymph node metastasis) and carried out deep sequencing of 409 genes using the IonTorrent system. Tumour mutational burdens (TMB) ranged from 2.

Proteomic Analysis of Whole Blood Using Volumetric Absorptive Microsampling for Precision Medicine Biomarker Studies.

Microsampling of patient blood promises several benefits over conventional phlebotomy practices to facilitate precision medicine studies. These include at-home patient blood collection, supporting telehealth monitoring, minimal postcollection processing, and compatibility with nonrefrigerated transport and storage. However, for proteomic biomarker studies, mass spectrometry of whole blood has generally been avoided in favor of using plasma or serum obtained from venepuncture.

Identifying Circulating Urotensin II and Urotensin II-Related Peptide-Generating Enzymes in the Human Plasma Fraction Cohn IV-4.

Urotensin II (UII) and UII-related peptide (URP) are vasoactive peptide hormones causing strong vasoconstriction or vasodilation, depending on the type of blood vessel. In humans, the active forms are resulting from proteolytic cleavage of their inactive precursor protein. In blood plasma, a defined protease converting the inactive UII and URP precursors into their active forms has not been identified yet.

Molecular Features of Lymph Node Metastasis in T1/2 Colorectal Cancer from Formalin-Fixed Paraffin-Embedded Archival Specimens.

Histological risk factors for lymph node metastasis (LNM) in early-stage colorectal cancers (CRC) have been described, although the predictive utility of these factors varies. Improved LNM risk assessment based on findings in endoscopic colon and rectal excisions is necessary for optimal surgical management of CRC patients with pathologic T1- /T2-staged invasive depth (i.e.

Xenograft-derived mRNA/miR and protein interaction networks of systemic dissemination in human prostate cancer.

Background: Distant metastasis formation is the major clinical problem in prostate cancer (PCa) and the underlying mechanisms remain poorly understood. Our aim was to identify novel molecules that functionally contribute to human PCa systemic dissemination based on unbiased approaches.

Methods: We compared mRNA, microRNA (miR) and protein expression levels in established human PCa xenograft tumours with high (PC-3), moderate (VCaP) or weak (DU-145) spontaneous micrometastatic potential.

Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion.

The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB.

OmixLitMiner: A Bioinformatics Tool for Prioritizing Biological Leads from 'Omics Data Using Literature Retrieval and Data Mining.

Proteomics and genomics discovery experiments generate increasingly large result tables, necessitating more researcher time to convert the biological data into new knowledge. Literature review is an important step in this process and can be tedious for large scale experiments. An informed and strategic decision about which biomolecule targets should be pursued for follow-up experiments thus remains a considerable challenge.

Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.

Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase. Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins. Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.

Application of Displacement Chromatography to Online Two-Dimensional Liquid Chromatography Coupled to Tandem Mass Spectrometry Improves Peptide Separation Efficiency and Detectability for the Analysis of Complex Proteomes.

The complexity of mammalian proteomes is a challenge in bottom-up proteomics. For a comprehensive proteome analysis, multidimensional separation strategies are necessary. Online two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) combining strong cation exchange (SCX) in the first dimension with reversed-phase (RP) chromatography in the second dimension provides a powerful approach to analyze complex proteomes.

Multi-laboratory analysis of the variability of shipped samples for proteomics following non-cooled international transport.

Transporting biological samples such as cells or tissues is complicated by the need to maintain integrity and minimise modification and degradation, but this is economically costly as the samples must be shipped in a frozen state. This multi-laboratory study investigated sample variability introduced by non-cooled transport of dried peptide samples for proteomic analysis using mass spectrometry. Human cancer cell tryptic lysates were proteolysed and dried in Australia and shipped by air to Europe and China.

Analyzing the influence of kinase inhibitors on DNA repair by differential proteomics of chromatin-interacting proteins and nuclear phospho-proteins.

The combination of radiotherapy and pharmacological inhibition of cellular signal transduction pathways offers promising strategies for enhanced cancer cell inactivation. However, the molecular effects of kinase inhibitors especially on DNA damage detection and repair after X-irradiation have to be understood to facilitate the development of efficient and personalized treatment regimens. Therefore, we applied differential proteomics for analyzing inhibitor-induced changes in either chromatin-bound or phosphorylated nuclear proteins.

Protein species as diagnostic markers.

Unlabelled: Many diseases are associated with protein species perturbations. A prominent example of an established diagnostic marker is the glycated protein species of hemoglobin, termed HbA1c. HbA1c concentration is increased in the blood of diabetes mellitus patients due to their poor control of blood glucose levels resulting in an increased non-enzymatic glycosylation of hemoglobin producing HbA1c.

A multilingual audiometer simulator software for training purposes.

Conclusion: A set of algorithms, which allows a computer to determine the answers of simulated patients during pure tone and speech audiometry, is presented. Based on these algorithms, a computer program for training in audiometry was written and found to be useful for teaching purposes.

Objectives: To develop a flexible audiometer simulator software as a teaching and training tool for pure tone and speech audiometry, both with and without masking.