A systematic approach to bowing and its application in violin playing

The aim of this research was to formulate systematic studies for the right-arm to achieve finer outcomes in violin performance. As modern violin practice involves the marking of numerical symbols on the score to indicate left-hand ‘fingerings’ it is necessary to question why no equivalent system is utilised for the training of the right-arm. Although a system for the notation of bow divisions was formulated by French violinist Lucien Capet over one hundred years ago, its use is virtually unidentified in modern violin playing and teaching. The research method adopted in this project was performance-oriented and focused on incorporating Capet’s eight-part bow division notation system into daily analytical practise allowing for core movements of the right-arm and the distribution of the bow to be documented and made habitual for the performance situation. Critical reflections on the process and specifically the application into key performance repertoire are provided in this exegesis, which contextualises the research conducted. The exegesis and folio of performances are equally weighted (50/50) for examination. The associated performance folio contains recordings of various solo and chamber works by composers Bach, Mozart, Ysaÿe, Brahms, Handel, Debussy, Franck, Strauss, Gragnani, Weber, Charlton and De Falla. The findings of this study were that setting parameters for bow distribution generated a higher level of response to address combinations of colour, timbre, mood and articulation. Notation of bow distribution is not to be understood as a rigid barrier or impediment to personal expression. On the contrary, once habitualised, it provides full awareness and control of the right arm, resulting in a refined, and highly nuanced regulation of sound to convey the desired musical expression

Fermented Goat’s Milk Consumption Improves Duodenal Expression of Iron Homeostasis Genes during Anemia Recovery

Despite the crucial roles of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferritin light chain (Ftl1), ferroportin 1 (FPN1), transferrin receptor 1 (TfR1), and hepcidin antimicrobial peptide (Hamp) in Fe metabolism, no studies have investigated the modulations of these genes during Fe repletion with fermented milks. Analysis included Fe status markers and gene and protein expression in enterocytes of control and anemic animals fed fermented milks. Fermented goat’s milk up-regulated enterocyte Dcytb, DMT1, FPN1, and Ftl1 and down-regulated TfR1 and Hamp gene expression in control and anemic animals. Anemia decreased Dcytb, DMT1, and Ftl1 in animals fed fermented cow’s milk and up-regulated TfR1 and Hamp expression. Fe overload down-regulated Dcytb and TfR1 in animals fed fermented cow’s milk and up-regulated DMT1 and FPN1 gene expression. Fermented goat’s milk increased expression of duodenal Dcytb, DMT1, and FPN1 and decreased Hamp and TfR1, improving Fe metabolism during anemia recovery

ACRATA: a novel electron transfer domain associated to apoptosis and cancer

BACKGROUND: Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. METHODS: We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. RESULTS: Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases. CONCLUSIONS: This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families

'Fat mass and obesity associated' gene (FTO): No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>We have previously identified strong association of six single nucleotide polymorphisms (SNPs) in <it>FTO </it>(fat mass and obesity associated gene) to early onset extreme obesity within the first genome wide association study (GWA) for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609) is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism.</p> <p>Methods</p> <p>We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR). For the association study (case-control approach), the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS) were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele.</p> <p>Results</p> <p>We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036). However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol.</p> <p>Conclusion</p> <p>We confirmed the rs9939609 A-allele as a risk factor for early onset obesity whereas its impact on weight loss or on serum levels of glucose, triglycerides and cholesterol could not be detected in our samples.</p> <p>Trial Registration</p> <p><b>This study is registered </b>at clinicaltrials.gov (NCT00435734).</p

The histone binding capacity of SPT2 controls chromatin structure and function in Metazoa

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.</p

The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

INTRODUCTION. HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. METHODS. We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. RESULTS. HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression were validated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment. HJURP mRNA levels were significantly correlated with CENPA mRNA levels. CONCLUSIONS. HJURP mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.National Institutes of Health, National Cancer Institute (R01 CA116481, P50 CA 5820, P30 CA 82103, U54 CA 112970); Office of Science; U.S. Department of Energy Office of Science, Office of Biological & Environmental Research (DE-AC02-05CH11231

The Chromodomain of LIKE HETEROCHROMATIN PROTEIN 1 Is Essential for H3K27me3 Binding and Function during Arabidopsis Development

Polycomb group (PcG) proteins are essential to maintain gene expression patterns during development. Transcriptional repression by PcG proteins involves trimethylation of H3K27 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2) in animals and plants. PRC1 binds to H3K27me3 and is required for transcriptional repression in animals, but in plants PRC1-like activities have remained elusive. One candidate protein that could be involved in PRC1-like functions in plants is LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), because LHP1 associates with genes marked by H3K27me3 in vivo and has a chromodomain that binds H3K27me3 in vitro. Here, we show that disruption of the chromodomain of Arabidopsis thaliana LHP1 abolishes H3K27me3 recognition, releases gene silencing and causes similar phenotypic alterations as transcriptional lhp1 null mutants. Therefore, binding to H3K27me3 is essential for LHP1 protein function

Modelling the long-term dynamics of the energy transition accounting for socioeconomic behaviour and biophysical constraints: overview of the Wiliam Energy Module

WILIAM (Within Limit Integrated Assessment Model) is a global multiregional IAM that combines economic, social, demographic, environmental, energy and material related aspects into one system dynamics model. It aims to provide stakeholders with an open source, welldocumented model to assess the feasibility, effectiveness, costs and impacts of different sustainability policy options. The adequate representation of energy production is key to assess future sustainability pathways. The main function of the developed energy module is to estimate the primary energy requirements and related GHG emissions for satisfying the economic demand. This goal was achieved by 7 major sub-modules: (1) End-use: translates the economic demand into final energy demand through a hybrid approach combining bottom-up with energy intensities for different sectors. (2) Energy transformation: maps the entire energy conversion chain from final to primary energy, including intermediary energy commodities and an allocation function for power plant utilization. (3) Energy capacity: keeps track of the current power plant capacity stock, decommissioning of expired capacities, as well as the build-up of new capacities. An allocation function for choosing the suitable technology types for new capacities stands at the core of this sub-module. (4) Computation of the EROI of green technologies (5) Variability and storage: keeps track of sub-annual time scale effects on annual energy balances depending on the current power system setup (DSM, Storage, sector coupling). (6) Consideration of techno-sustainable potentials of RES considering geographical, resource and Energy Return on Energy Investment (EROI) constraints. (7) Computation of the energy-related GHG emissions

EMF1 and PRC2 Cooperate to Repress Key Regulators of Arabidopsis Development

EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism