Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)—an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra–mass spectrometry (SWATH–MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2–2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.     

Interaction of titanium diboride/boron nitride evaporation boats with aluminium

Hexagonal boron nitride/titanium diboride composites are widely used as evaporation boats for aluminium deposition to produce functional and decorative layers on different target materials. The lifetime of such a material is limited mainly by the interaction of the metal with the ceramic substrate, but the corrosion mechanism has still not yet been thoroughly investigated and understood. In this article the corrosion mechanism for the evaporation boats used was investigated using thermodynamic calculations, FESEM, EDX and XRD phase analysis. The analysis showed that hexagonal boron nitride (hBN), which is thermodynamically less stable than TiB₂, is passivated during the application process through the formation of AlN surface layers, whereas the thermodynamically more stable TiB₂ phase dissolves and Ti-rich components precipitate in cooler regions of the evaporation boats.     

Interaction of boron suboxide with compacted graphite cast iron

The chemical interaction of boron suboxide (B₆O) with compacted graphite cast iron (CGI) was investigated using static interaction diffusion couples between B₆O and CGI at 700 °C, 900 °C and 1100 °C for 1 h. This interaction offers the possibility to evaluate the potential of B₆O as a cutting tool. The microstructures and phase compositions of the interaction zones were investigated. At 700 °C and 900 °C the chemical interaction was minimal. However, at 1100 °C, Fe₂B and SiO₂ were formed at the interface. Hence, machining at 1100 °C is likely to result in chemical wear.     

Mining the cinnabaramide biosynthetic pathway to generate novel proteasome inhibitors

The cinnabaramides and salinosporamides are mixed PKS/NRPS natural products isolated from a terrestrial streptomycete and a marine actinomycete, respectively. They interfere with the proteasome and thus potentially inhibit the growth of cancer cells. The compounds exhibit a γ-lactam-β-lactone bicyclic ring structure attached to a cyclohexenyl unit and a PKS side chain. As a first step towards improving anticancer activity and permitting genetic approaches to novel analogues, we have cloned and characterized the cinnabaramide biosynthetic genes from Streptomyces sp. JS360. In addition to the expected PKS and NRPS genes, the cluster encodes functionalities for the assembly of the hexyl side chain precursor. The corresponding enzymes exhibit relaxed substrate specificities towards a number of synthesized precursors, enabling production of novel chlorinated cinnabaramides. These were isolated and analyzed for activity, revealing that derivatives bearing a chlorine atom in the PKS side chain show higher inhibitory potentials towards the proteasome's proteolytic subunits (especially the trypsin and chymotrypsin units) and higher cytotoxicities towards human tumor cell lines than the parent cinnabaramide A. Although their activities towards the proteasome were weaker than that of salinosporamide A, the cinnabaramides were found to inhibit the growth of various fungi with greater potency.     

Influence of the Temperature on Coccolith-Containing Systems from Emiliania huxleyi Cultivations

Thermogravimetric analysis of a coccolith-containing biogenic broth showed a three-step degradation process. According to this system behavior, the biogenic broth was heated to specific temperatures and characterized in terms of its morphology, surface chemistry, and crystallinity. The elemental and organic composition of the treated samples was also evaluated and compared to the reference material. The presented results were acquired in an effort to exploit pretreatment scenarios for such a biogenic system that would improve and support a separation process.     

Syntheses of TiO2 photocatalysts by the molten salts method: Application to the photocatalytic degradation of Prosulfuron

Titania photocatalysts were synthesised by the molten salts method by reaction of a titanium precursor with three different alkali metal nitrates (LiNO₃, NaNO₃, KNO₃). The titania powders obtained have been characterised using TEM, XRD, BET and UV-Vis absorption spectroscopy. Their photoactivities were evaluated by degrading a commercial sulfonylurea herbicide, Prosulfuron^®. It has been found that the rate constants increased in the following order: Li2 prepared in KNO₃, with a rate constant 1.4 times smaller than that of P25. The effect of calcination was also studied, especially for the sample prepared in NaNO₃ (TiO₂[Na]). An improvement in photocatalytic activity was observed when TiO₂[Na] was calcined in the region of 700–800 °C. Even though the photocatalytic activities obtained did not exceed or even equal to that of Degussa P25, nevertheless, this study constitutes the first attempt to synthesise titania photocatalysts by the molten salts method.     

Synthesis and functional characterization of tridegin and its analogues: inhibitors and substrates of factor XIIIa

Tridegin, a 66‐mer peptide isolated from the leech Haementeria ghilianii, is a potent inhibitor of the coagulation factor XIIIa. This paper describes the chemical synthesis of tridegin by two different strategies—solid‐phase assembly and native chemical ligation—both followed by oxidation in solution phase. Tridegin and truncated analogues were examined for their activity and revealed a particular importance of the C‐terminal region of the parent peptide. Based on these studies a minimal sequence required for factor XIIIa inhibition could be identified. Our data revealed that the glutamine residue at position 52 (Q⁵²) of tridegin most likely binds to the active site of factor XIIIa and was therefore suggested to react with the enzyme. The function of the N‐terminal region is also discussed, as the isolated C‐terminal segment of tridegin lost its inhibitory activity rapidly in the presence of factor XIIIa, whereas this was not the case for the full‐length inhibitor.     

DNA block copolymers: functional materials for nanoscience and biomedicine

We live in a world full of synthetic materials, and the development of new technologies builds on the design and synthesis of new chemical structures, such as polymers. Synthetic macromolecules have changed the world and currently play a major role in all aspects of daily life. Due to their tailorable properties, these materials have fueled the invention of new techniques and goods, from the yogurt cup to the car seat belts. To fulfill the requirements of modern life, polymers and their composites have become increasingly complex. One strategy for altering polymer properties is to combine different polymer segments within one polymer, known as block copolymers. The microphase separation of the individual polymer components and the resulting formation of well defined nanosized domains provide a broad range of new materials with various properties. Block copolymers facilitated the development of innovative concepts in the fields of drug delivery, nanomedicine, organic electronics, and nanoscience. Block copolymers consist exclusively of organic polymers, but researchers are increasingly interested in materials that combine synthetic materials and biomacromolecules. Although many researchers have explored the combination of proteins with organic polymers, far fewer investigations have explored nucleic acid/polymer hybrids, known as DNA block copolymers (DBCs). DNA as a polymer block provides several advantages over other biopolymers. The availability of automated synthesis offers DNA segments with nucleotide precision, which facilitates the fabrication of hybrid materials with monodisperse biopolymer blocks. The directed functionalization of modified single-stranded DNA by Watson-Crick base-pairing is another key feature of DNA block copolymers. Furthermore, the appropriate selection of DNA sequence and organic polymer gives control over the material properties and their self-assembly into supramolecular structures. The introduction of a hydrophobic polymer into DBCs in aqueous solution leads to amphiphilic micellar structures with a hydrophobic polymer core and a DNA corona. In this Account, we discuss selected examples of recent developments in the synthesis, structure manipulation and applications of DBCs. We present achievements in synthesis of DBCs and their amplification based on molecular biology techniques. We also focus on concepts involving supramolecular assemblies and the change of morphological properties by mild stimuli. Finally, we discuss future applications of DBCs. DBC micelles have served as drug-delivery vehicles, as scaffolds for chemical reactions, and as templates for the self-assembly of virus capsids. In nanoelectronics, DNA polymer hybrids can facilitate size selection and directed deposition of single-walled carbon nanotubes in field effect transistor (FET) devices.