Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.

Background: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. We investigated the recruitment of transcription factors that underpins transcriptional rhythms in ion channels and assessed whether this mechanism was pertinent to the heart's intrinsic diurnal susceptibility to VA.

Timing of leaf removal modulates tannin composition and the level of anthocyanins and methoxypyrazines in Pinot noir grapes and wines.

This study aimed to investigate the impact of leaf removal on concentrations of anthocyanin, tannin, and methoxypyrazines (MPs) in Pinot noir grapes and wines. Leaf removal after 7 days (LR7), 30 days (LR30), and 60 days (LR60) of flowering were compared with no leaf removal control (LRC). Grapes and resultant wines were analysed for tannin and aroma composition using liquid chromatography and two-dimensional gas chromatography-mass spectrometry.

PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis.

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin.

Development of Tannins and Methoxypyrazines in Grape Skins, Seeds, and Stems of Two Pinot Noir Clones during Ripening.

Two Pinot noir clones (AM10/5 and UCD5) were analyzed for tannin and methoxypyrazines (MPs) in different grape tissues during berry development using liquid chromatography and two-dimensional gas chromatography-mass spectrometry. On a per berry basis, skin tannins reached the maximum level about 2-3 weeks after véraison, seed tannins at around véraison, and stem tannins 4 weeks before véraison. Clone AM10/5 showed significantly higher levels of seed and stem tannins on a per berry basis at harvest.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas.

Adult Age Differences in Using Information From the Eyes and Mouth to Make Decisions About Others' Emotions.

Objectives: Older adults are often less accurate than younger counterparts at identifying emotions such as anger, sadness, and fear from faces. They also look less at the eyes and more at the mouth during emotion perception. The current studies advance understanding of the nature of these age effects on emotional processing.

Navigating the Global Protein-Protein Interaction Landscape Using iRefWeb.

iRefWeb is a resource that provides web interface to a large collection of protein-protein interactions aggregated from major primary databases. The underlying data-consolidation process, called iRefIndex, implements a rigorous methodology of identifying redundant protein sequences and integrating disparate data records that reference the same peptide sequences, despite many potential differences in data identifiers across various source databases. iRefWeb offers a unified user interface to all interaction records and associated information collected by iRefIndex, in addition to a number of data filters and visual features that present the supporting evidence.

Hypoxia regulates GR function through multiple mechanisms involving microRNAs 103 and 107.

Glucocorticoids (Gcs) potently inhibit inflammation, and regulate liver energy metabolism, often acting in a hypoxic environment. We now show hypoxic conditions open a specific GR cistrome, and prevent access of GR to part of the normoxic GR cistrome. Motif analysis identified enrichment of KLF4 binding sites beneath those peaks of GR binding exclusive to normoxia, implicating KLF4 as a pioneer, or co-factor under these conditions.

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders.

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis.

Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.

A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterations is a major clinical challenge. Exploring these mechanisms of resistance, we found that EML4-ALK cells parental or resistant to crizotinib, ceritinib or alectinib are remarkably sensitive to inhibition of CDK7/12 with THZ1 and CDK9 with alvocidib or dinaciclib.

The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition.

To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the mode of HapX-DNA recognition had not been resolved.

A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity.

High-grade serous ovarian carcinoma is characterised by TP53 mutation and extensive chromosome instability (CIN). Because our understanding of CIN mechanisms is based largely on analysing established cell lines, we developed a workflow for generating ex vivo cultures from patient biopsies to provide models that support interrogation of CIN mechanisms in cells not extensively cultured in vitro. Here, we describe a "living biobank" of ovarian cancer models with extensive replicative capacity, derived from both ascites and solid biopsies.

Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.

Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA.

Caring values in undergraduate nurse students: A qualitative longtitudinal study.

Introduction: Given the emerging evidence internationally of poor care within the healthcare sector, a recent report in the United Kingdom recommended the need for education to produce nurses who are prepared both intellectually and with compassion.

Aim: This paper aims to understand the beliefs and values of caring, held by student nurses from entry to completion of their education programme.

Methods: Using a prospective qualitative longtitudinal approach, two cohorts of nursing students (February 2013 and 2014) each following a different undergraduate curriculum (the February 2013, based on a philosophy of person-centred care and the February 2014, based on the philosophy of humanisation) were followed throughout their programme leading to Registration.

The SmartTarget Biopsy Trial: A Prospective, Within-person Randomised, Blinded Trial Comparing the Accuracy of Visual-registration and Magnetic Resonance Imaging/Ultrasound Image-fusion Targeted Biopsies for Prostate Cancer Risk Stratification.

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. It is unknown whether visual-registration targeting is sufficient or augmentation with image-fusion software is needed.

Objective: To assess concordance between the two methods.

REVERBa couples the circadian clock to hepatic glucocorticoid action.

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day.

Whole Genome Sequencing, Assembly and Phenotypic Profiling for the New Budding Yeast Species .

complex consist of yeast species, which are not only important in the fermentation industry but are also model systems for genomic and ecological analysis. Here, we present the complete genome assemblies of , a newly discovered species from high altitude oaks. Phylogenetic and phenotypic analysis revealed that is more closely related to , than , and The karyotype of presents two reciprocal chromosomal translocations between chromosome VI/VII and I/XIII when compared to the genome.