'Anything But Conventional' : Faith and Folk Idioms in Dvorak's Biblical Songs

<p>In the nineteenth century considerable ambiguities arose regarding sacred and secular categories in music. Although such ambiguities have often been discussed in relation to the mass, this study uses the genre of the lied - in particular, Dvorak's Biblical Songs - as a means of examining the interaction between these categories. The problems inherent in the idea of 'sacred lieder' are discussed, including case studies of Schubert's 'Die Allmacht' and Wolf's 'Nun wandre, Maria' from the Spanisches Liederbuch. The Biblical Songs are located within Dvorak's biography, to show the great extent to which they were a reflection of his personal situation. In-depth analysis of the music and texts of the songs, both individually and as a cycle, reveals that they are representative of a point of interaction between secular lieder for concert performance, and devotional lieder for a domestic context. A comparison with Brahms and his Four Serious Songs reveals two very different responses to biblical texts: whereas Brahms's solution places emphasis on secular love, Dvorak's songs show a progression from doubt and confusion about God through to faith and rejoicing. Furthermore, whereas the Four Serious Songs demonstrate a highly individualistic solution to the pessimism expressed earlier in the cycle, Dvork's use of folk idioms at key locations in the Biblical Songs places emphasis on communality and tradition. However, the cycle also reveals a more complex expression of faith than is often assumed of Dvorak.</p>

'Anything But Conventional' : Faith and Folk Idioms in Dvorak's Biblical Songs

<p>In the nineteenth century considerable ambiguities arose regarding sacred and secular categories in music. Although such ambiguities have often been discussed in relation to the mass, this study uses the genre of the lied - in particular, Dvorak's Biblical Songs - as a means of examining the interaction between these categories. The problems inherent in the idea of 'sacred lieder' are discussed, including case studies of Schubert's 'Die Allmacht' and Wolf's 'Nun wandre, Maria' from the Spanisches Liederbuch. The Biblical Songs are located within Dvorak's biography, to show the great extent to which they were a reflection of his personal situation. In-depth analysis of the music and texts of the songs, both individually and as a cycle, reveals that they are representative of a point of interaction between secular lieder for concert performance, and devotional lieder for a domestic context. A comparison with Brahms and his Four Serious Songs reveals two very different responses to biblical texts: whereas Brahms's solution places emphasis on secular love, Dvorak's songs show a progression from doubt and confusion about God through to faith and rejoicing. Furthermore, whereas the Four Serious Songs demonstrate a highly individualistic solution to the pessimism expressed earlier in the cycle, Dvork's use of folk idioms at key locations in the Biblical Songs places emphasis on communality and tradition. However, the cycle also reveals a more complex expression of faith than is often assumed of Dvorak.</p>

Transcription Factor Action Orchestrates the Complex Expression Pattern of CRABS CLAW in Arabidopsis

Angiosperm flowers are the most complex organs that plants generate, and in their center, the gynoecium forms, assuring sexual reproduction. Gynoecium development requires tight regulation of developmental regulators across time and tissues. How simple on and off regulation of gene expression is achieved in plants was described previously, but molecular mechanisms generating complex expression patterns remain unclear. We use the gynoecium developmental regulator CRABS CLAW (CRC) to study factors contributing to its sophisticated expression pattern. We combine in silico promoter analyses, global TF-DNA interaction screens, and mutant analyses. We find that miRNA action, DNA methylation, and chromatin remodeling do not contribute substantially to CRC regulation. However, 119 TFs, including SEP3, ETT, CAL, FUL, NGA2, and JAG bind to the CRC promoter in yeast. These TFs finetune transcript abundance as homodimers by transcriptional activation. Interestingly, temporal–spatial aspects of expression regulation may be under the control of redundantly acting genes and require higher order complex formation at TF binding sites. Our work shows that endogenous regulation of complex expression pattern requires orchestrated transcription factor action on several conserved promotor sites covering almost 4 kb in length. Our results highlight the utility of comprehensive regulators screens directly linking transcriptional regulators with their targets.

The SCF Complex Is Essential to Maintain Genome and Chromosome Stability

The SKP1, CUL1, F-box protein (SCF) complex encompasses a group of 69 SCF E3 ubiquitin ligase complexes that primarily modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation. These SCF complexes are distinguishable by variable F-box proteins, which determine substrate specificity. Although the function(s) of each individual SCF complex remain largely unknown, those that have been characterized regulate a wide array of cellular processes, including gene transcription and the cell cycle. In this regard, the SCF complex regulates transcription factors that modulate cell signaling and ensures timely degradation of primary cell cycle regulators for accurate replication and segregation of genetic material. SCF complex members are aberrantly expressed in a myriad of cancer types, with altered expression or function of the invariable core SCF components expected to have a greater impact on cancer pathogenesis than that of the F-box proteins. Accordingly, this review describes the normal roles that various SCF complexes have in maintaining genome stability before discussing the impact that aberrant SCF complex expression and/or function have on cancer pathogenesis. Further characterization of the SCF complex functions is essential to identify and develop therapeutic approaches to exploit aberrant SCF complex expression and function.

The Functional Composition of Sense

A central dispute in understanding Frege’s philosophy concerns how the sense of a complex expression relates to the senses of its component expressions. According to one reading, the sense of a complex expression is a whole built from the senses of the component expressions. On this interpretation, Frege is an early proponent of structured propositions. A rival reading says that senses compose by functional application: the sense of a complex expression is the value of the function denoted by its functional component for the arguments denoted by its remaining components. I argue that two non-negotiable Fregean theses entail that senses compose by functional application. One thesis is that referents compose by functional application. The other thesis is that an expression in an indirect context refers to its customary sense.

Transcription factor action orchestrates the complex expression pattern ofCRABS CLAW, a gynoecium developmental regulator in Arabidopsis

The flower of angiosperms is the most complex organ that plants generate and many transcription factors (TFs) are involved to regulate its morphogenesis in a coordinated way. In its center, the gynoecium develops consisting of specialized tissues such as secondary meristems, sites of postgenital fusion, ovules, pollen transmitting tract, all to assure successful sexual reproduction. Gynoecium development requires tight regulation of developmental regulators across time and tissues. However, while we know of several examples how simple on/off regulation of gene expression is achieved in plants, it remains unclear which regulatory processes generate complex expression patterns. Here, we use the gynoecium developmental regulatorCRABS CLAW (CRC)from Arabidopsis to study regulatory mechanisms contributing to its sophisticated expression pattern. Using a combination ofin silicopromoter analyses, global TF-DNA interaction screens, co-expression and mutant analysis we find that miRNA action, DNA methylation, and chromatin remodeling do not contribute substantially toCRCregulation. We show that a plethora of TFs bind to theCRCpromoter to fine-tune transcript abundance by activation of transcription, linkingCRCto specific developmental processes but not biotic or abiotic stress. Interestingly, the temporal-spatial aspects of regulation of expression may be under the control of redundantly acting genes and may require higher order complex formation at TF binding sites. We conclude that endogenous regulation of complex expression pattern of Arabidopsis genes requires orchestrated transcription factor action on several conserved promotor sites over almost 4 kb in length.Significance statementDifferent to genes that are simply switched on or off, depending on an environmental cue we find that genes directing development in plants often show complex expression pattern dependent on internal factors only. Here, we addressed the question how an complex expression pattern is achieved and use theCRABS CLAW (CRC)gene required for gynoecium development as an example. Combining wet lab experiments andin silicoanalysis we find that epigenetic regulation plays only a minor role and that a large number of transcription factors activates the transcription ofCRC. Single regulators may have a profound effect onCRCtranscript abundance but less so on the pattern of expression. Complex patterns most likely require the interplay of several transcription factors.

Overview of the Assays to Probe O-Linked β-N-Acetylglucosamine Transferase Binding and Activity

O-GlcNAcylation is a posttranslational modification that occurs at serine and threonine residues of protein substrates by the addition of O-linked β-d-N-acetylglucosamine (GlcNAc) moiety. Two enzymes are involved in this modification: O-GlcNac transferase (OGT), which attaches the GlcNAc residue to the protein substrate, and O-GlcNAcase (OGA), which removes it. This biological balance is important for many biological processes, such as protein expression, cell apoptosis, and regulation of enzyme activity. The extent of this modification has sparked interest in the medical community to explore OGA and OGT as therapeutic targets, particularly in degenerative diseases. While some OGA inhibitors are already in phase 1 clinical trials for the treatment of Alzheimer’s disease, OGT inhibitors still have a long way to go. Due to complex expression and instability, the discovery of potent OGT inhibitors is challenging. Over the years, the field has grappled with this problem, and scientists have developed a number of techniques and assays. In this review, we aim to highlight assays and techniques for OGT inhibitor discovery, evaluate their strength for the field, and give us direction for future bioassay methods.

Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma

Background Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC. Results The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression. Conclusions These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.