Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer.

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo.

In situ metabolomics of aldosterone-producing adenomas.

Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism.

An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics.

Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity states across 30 cell types and chart the lung proteome of young and old mice. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control.

Pollen of common ragweed (Ambrosia artemisiifolia L.): Illumina-based de novo sequencing and differential transcript expression upon elevated NO/O.

Common ragweed (Ambrosia artemisiifolia L.) is a highly allergenic annual ruderal plant and native to Northern America, but now also spreading across Europe. Air pollution and climate change will not only affect plant growth, pollen production and duration of the whole pollen season, but also the amount of allergenic encoding transcripts and proteins of the pollen.

Identification of Cadherin 2 () Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous condition caused by mutations in genes encoding desmosomal proteins in up to 60% of cases. The 40% of genotype-negative cases point to the need of identifying novel genetic substrates by studying genotype-negative ARVC families.

Methods And Results: Whole exome sequencing was performed on 2 cousins with ARVC.

Characterization of circular RNAs in human, mouse and rat hearts.

Deep sequencing techniques and advanced data analysis methods recently enabled the characterization of thousands of circular RNA isoforms (circRNAs) from a number of tissues and organisms. There is emerging evidence that some circRNAs may have important biological functions or serve as diagnostic biomarkers in disease conditions. In order to analyze circRNA expression in the heart and its changes in different conditions we performed RNA-Seq analysis of ribosome-depleted libraries from rats (neonatal and adult), mice (sham or after transverse aortic constriction, TAC) and humans (failing, non-failing).

Development of A Cell-Based Assay to Identify Small Molecule Inhibitors of FGF23 Signaling.

Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine key regulator of phosphate homeostasis. It inhibits renal tubular phosphate reabsorption by activating receptor complexes composed of FGF receptor 1c (FGFR1c) and the co-receptor Klotho. As a major signaling pathway mitogen-activated protein kinase (MAPK) pathway is employed.

Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1.

Autosomal recessive hypophosphatemic rickets 2 (ARHR2) is a rare form of renal tubular phosphate wasting disorder. Loss of function mutations of the ecto-nucleotide pyrophosphatase/pyrophosphodiesterase 1 gene (ENPP1) causes a wide spectrum of phenotypes, ranging from lethal generalized arterial calcification of infancy to hypophosphatemic rickets with hypertension. Hearing loss was not previously thought to be one of the features of the disease entities and was merely regarded as a complication rather than a part of the disease.