This study connects the idiosyncratic modernism of Wyndham Lewis, co-founder of the Vorticist art movement, with works of several artists from the British art rock tradition, among them Bryan Ferry, ...David Bowie, art-punk pioneers Wire and electronic pop musician John Foxx. By taking a transdisciplinary and intermedial approach to texts from two fields normally studied in isolation and staking out the elements of a shared modernist ethos, the book presents a new perspective on both fields relevant to scholars of literature, popular culture, and the visual arts alike. While the book rests on sound research from the fields of literary criticism, art history, and pop theory, the structure and writing of the book is fundamentally designed to be accessible and comprehensible to non-scholarly readers.
The structure of compacted soils is characterised by decreased (macro-)porosity, which leads to increased mechanical impedance and decreased fluid transport rates, resulting in reduced root growth ...and crop productivity. Particularly in soils with high mechanical impedance, macropores can be used by roots as pathways of least resistance. This study investigated how different soil physical states relate to whole plant growth and whether roots grow towards spots with favourable soil physical conditions. Experiments were conducted under controlled and field conditions. Soybean (Glycine max L.), wheat (Triticum aestivum L.) and maize (Zea mays L.) were grown on uncompacted soil, compacted soil and compacted soil with artificial macropores. The interactions between roots and artificial macropores were quantified using X-ray computed tomography. Active growth of roots towards artificial macropores was observed for all three species. Roots grew either into macropores (predominantly in maize) or crossed them (predominantly in wheat). The presence of artificial macropores in compacted soil enabled all three species to compensate for decreased early vigour at later developmental stages. These results show that roots sense their physical environment, enabling them to grow towards spots with favourable soil conditions. The different kinds of root-macropore interaction indicated that macropores serve as a path of least resistance and a source of oxygen, both resulting in increased crop productivity on compacted soils.
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•Artificial macropores restore certain soil physical functions of compacted soils.•Crop roots preferentially grow towards artificial macropores in compacted soil.•Artificial macropores provide different functions for roots in compacted soil.•Artificial macropores increase soil fertility and crop growth in compacted soil.
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Water is the most limiting resource for global crop production. The projected increase of dry spells due to climate change will further increase the problem of water limited crop yields. Besides low ...water abundance and availability, water limitations also occur due to restricted water accessibility. Soil penetration resistance, which is largely influenced by soil moisture, is the major soil property regulating root elongation and water accessibility. Until now the interactions between soil penetration resistance, root system properties, water uptake and crop productivity are rarely investigated. In the current study we quantified how interactive effects between soil penetration resistance, root architecture and water uptake affect water accessibility and crop productivity in the field. Maize was grown on compacted and uncompacted soil that was either tilled or remained untilled after compaction, which resulted in four treatments with different topsoil penetration resistance. Higher topsoil penetration resistance caused root systems to be shallower. This resulted in increased water uptake from the topsoil and hence topsoil drying, which further increased the penetration resistance in the uppermost soil layer. As a consequence of this feedback, root growth into deeper soil layers, where water would have been available, was reduced and plant growth decreased. Our results demonstrate that soil penetration resistance, root architecture and water uptake are closely interrelated and thereby determine the potential of plants to access soil water pools. Hence, these interactions and their feedbacks on water accessibility and crop productivity have to be accounted for when developing strategies to alleviate water limitations in cropping systems.
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•Maize root systems became shallower due to increased topsoil penetration resistance.•Shallower root systems led to increased water uptake from the topsoil.•In turn, penetration resistance further increased, which impeded deeper root growth.•This feedback eventually reduced water accessibility and crop productivity.
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Increased soil strength due to soil compaction or soil drying is a major limitation to root growth and crop productivity. Roots need to exert higher penetration force, resulting in increased ...penetration stress when elongating in soils of greater strength. This study aimed to quantify how the genotypic diversity of root tip geometry and root diameter influences root elongation under different levels of soil strength and to determine the extent to which roots adjust to increased soil strength. Fourteen wheat (Triticum aestivum) varieties were grown in soil columns packed to three bulk densities representing low, moderate, and high soil strength. Under moderate and high soil strength, smaller root tip radius-to-length ratio was correlated with higher genotypic root elongation rate, whereas root diameter was not related to genotypic root elongation. Based on cavity expansion theory, it was found that smaller root tip radius-to-length ratio reduced penetration stress, thus enabling higher root elongation rates in soils with greater strength. Furthermore, it was observed that roots could only partially adjust to increased soil strength. Root thickening was bounded by a maximum diameter, and root tips did not become more acute in response to increased soil strength. The obtained results demonstrated that root tip geometry is a pivotal trait governing root penetration stress and root elongation rate in soils of greater strength. Hence, root tip shape needs to be taken into account when selecting for crop varieties that may tolerate high soil strength.
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Zika Virus Protease: An Antiviral Drug Target Kang, CongBao; Keller, Thomas H.; Luo, Dahai
Trends in microbiology (Regular ed.),
October 2017, 2017-Oct, 2017-10-00, 20171001, Volume:
25, Issue:
10
Journal Article
Peer reviewed
Open access
The recent outbreak of Zika virus (ZIKV) infection has caused global concern due to its link to severe damage to the brain development of foetuses and neuronal complications in adult patients. A ...worldwide research effort has been undertaken to identify effective and safe treatment and vaccination options. Among the proposed viral and host components, the viral NS2B-NS3 protease represents an attractive drug target due to its essential role in the virus life cycle. Here, we outline recent progress in studies on the Zika protease. Biochemical, biophysical, and structural studies on different protease constructs provide new insight into the structure and activity of the protease. The unlinked construct displays higher enzymatic activity and better mimics the native state of the enzyme and therefore is better suited for drug discovery. Furthermore, the structure of the free enzyme adopts a closed conformation and a preformed active site. The availability of a lead fragment hit and peptide inhibitors, as well as the attainability of soakable crystals, suggest that the unlinked construct is a promising tool for drug discovery.
As an attractive antiviral drug target, the two-component NS2B-NS3 protease from Zika virus has been subjected to intensive structural and functional studies for the identification and characterization of specific inhibitors.
The unlinked protease resembles the native state of the enzyme and has higher protease activity than the covalently linked NS2B-NS3 via a glycine-rich peptide linker.
The unlinked protease adopts a closed conformation in which the NS2B cofactor is fully engaged with the NS3 protease. An empty substrate-binding site is preformed; it does not undergo further significant conformational changes upon inhibitor binding.
The linked protease can assume both open and closed conformations in solution.
Several protease–inhibitor complexes are now available. These new findings could guide the future study of the proteases from related flaviviruses.
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Genomes of invertebrates and vertebrates exhibit highly divergent patterns of DNA methylation. Invertebrate genomes tend to be sparsely methylated, and DNA methylation is mostly targeted to a subset ...of transcription units (gene bodies). In a drastic contrast, vertebrate genomes are generally globally and heavily methylated, punctuated by the limited local hypo-methylation of putative regulatory regions such as promoters. These genomic differences also translate into functional differences in DNA methylation and gene regulation. Although promoter DNA methylation is an important regulatory component of vertebrate gene expression, its role in invertebrate gene regulation has been little explored. Instead, gene body DNA methylation is associated with expression of invertebrate genes. However, the evolutionary steps leading to the differentiation of invertebrate and vertebrate genomic DNA methylation remain unresolved. Here we analyzed experimentally determined DNA methylation maps of several species across the invertebrate-vertebrate boundary, to elucidate how vertebrate gene methylation has evolved. We show that, in contrast to the prevailing idea, a substantial number of promoters in an invertebrate basal chordate Ciona intestinalis are methylated. Moreover, gene expression data indicate significant, epigenomic context-dependent associations between promoter methylation and expression in C. intestinalis. However, there is no evidence that promoter methylation in invertebrate chordate has been evolutionarily maintained across the invertebrate-vertebrate boundary. Rather, body-methylated invertebrate genes preferentially obtain hypo-methylated promoters among vertebrates. Conversely, promoter methylation is preferentially found in lineage- and tissue-specific vertebrate genes. These results provide important insights into the evolutionary origin of epigenetic regulation of vertebrate gene expression.
Targeted covalent inhibitors have re‐emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the ...structure‐based design of BCR‐ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild‐type and mutant ABL kinases, especially ABLT315I bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on molecular recognition of the non‐covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co‐crystal structures of covalent inhibitor‐ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label‐free mass spectrometry to evaluate off‐targets of our compounds at proteome‐wide level in different mammalian cells.
Using iminoboronate chemistry, we report the first successful examples of catalytic lysine‐targeting reversible covalent BCR‐ABL inhibitors which inhibited both ABLWT and ABLT315I at nanomolar potency. We also demonstrated how the study of off‐targets for this class of compounds could be performed using activity‐based protein profiling and mass spectrometry.
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The evolutionary mechanisms underlying duplicate gene maintenance and divergence remain highly debated. Epigenetic modifications, such as DNA methylation, may contribute to duplicate gene evolution ...by facilitating tissue-specific regulation. However, the role of epigenetic divergence on duplicate gene evolution remains little understood. Here we show, using comprehensive data across 10 diverse human tissues, that DNA methylation plays critical roles in several aspects of duplicate gene evolution. We first demonstrate that duplicate genes are initially heavily methylated, before gradually losing DNA methylation as they age. Within each pair, DNA methylation divergence between duplicate partners increases with evolutionary age. Importantly, tissue-specific DNA methylation of duplicates correlates with tissue-specific expression, implicating DNA methylation as a causative factor for functional divergence of duplicate genes. These patterns are apparent in promoters but not in gene bodies, in accord with the complex relationship between gene-body DNA methylation and transcription. Remarkably, many duplicate gene pairs exhibit consistent division of DNA methylation across multiple, divergent tissues: For the majority (73%) of duplicate gene pairs, one partner is always hypermethylated compared with the other. This is indicative of a common underlying determinant of DNA methylation. The division of DNA methylation is also consistent with their chromatin accessibility profiles. Moreover, at least two sequence motifs known to interact with the Sp1 transcription factor mark promoters of more hypomethylated duplicate partners. These results demonstrate critical roles of DNA methylation, as well as complex interaction between genome and epigenome, on duplicate gene evolution.
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The cytotoxicity of polyelectrolytes commonly employed for layer-by-layer deposition of polyelectrolyte multilayers (PEMUs) was assessed using rat smooth muscle A7r5 and human osteosarcoma U-2 OS ...cells. Cell growth, viability, and metabolic assays were used to compare the responses of both cell lines to poly(acrylic acid), PAA, and poly(allylamine hydrochloride), PAH, in solution at concentrations up to 10 mM and to varying thicknesses of (PAA/PAH) PEMUs. Cytotoxicity correlated with increasing concentration of solution polyelectrolytes for both cell types and was greater for the positively charged PAH than for the negatively charged PAA. While metabolism and proliferation of both cell types was slower on PEMUs than on tissue culture plastic, little evidence for direct toxicity on cells was observed. In fact, evidence for more extensive adhesion and cytoskeletal organization was observed with PAH-terminated PEMUs. Differences in cell activity and viability on different thickness PEMU surfaces resulted primarily from differences in attachment for these adhesion-dependent cell lines.
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