Cyclic strain has been shown to benefit tendon health. However, repetitive loading has also been implicated in the etiology of tendon overuse injuries. Recent studies demonstrated that in several cell lines cyclic strain was associated with an activation of stress-activated protein kinases (SAPKs). These SAPKs, in turn, were shown to be important upstream regulators of a variety of cell processes including apoptosis. To examine the effect of repetitive loading on SAPK activation in tendon cells in vitro, canine patellar tendon cells were cyclically strained, and the cellular stress response evaluated by measuring c-Jun N-terminal kinase (JNK) activation. The effects of strain frequency and strain magnitude as well as the role of calcium signaling in this mechanotransduction mechanism were also examined. Cyclic strain resulted in an immediate activation of JNK, which peaked at 30 min and returned to resting levels by 2 h. This activation was regulated by a magnitude-dependent but not frequency-dependent response and appeared to be mediated through a calcium-dependent mechanotransduction pathway. While transient JNK activation is associated with normal cell processes, persistent JNK activation has been linked to the initiation of the apoptotic cascade. A similar mechanism could be responsible for initiating the pathological events (localized cell death) seen in tendon overuse injury.
The oily product ZANTHIN consists of natural astaxanthin, which is manufactured from the microalgae Haematococcus pluvialis by supercritical CO(2) extraction. An HPLC method was developed to separate all of the components of the complex astaxanthin extract using a C(30) column. The separation resulted in different isomers of astaxanthin accompanied by two other carotenoids. The main component consisted of astaxanthin singly esterified with several different fatty acids. C18:3, C18:2, C18:1 and C16:0 were identified as the most commonly occurring fatty acids. Doubly esterified astaxanthin was also found, although in lower concentrations compared to singly esterified astaxanthin. After performing a detailed fatty acid analysis by GC-MS, the peaks from the extract were assigned via HPLC-MS. A trans to cis transmutation of the all-trans compound was performed by thermal treatment in order to obtain an enrichment of cis isomers as the basis for unambiguous identification via NMR experiments. The all-trans as well as the 9- and 13-cis isomers of astaxanthin were characterized in detail by UV/Vis, (1)H, and (1)H,(1)H COSY NMR spectroscopy.
The shells/coats of nuts and seeds are often very hard to crack. This is particularly the case with Macadamia seed coats, known to exhibit astoundingly high strength and toughness. We performed an extensive materials science characterization of the complex hierarchical structure of these coats, using light and scanning electron microscopy in 2D as well as microCT for 3D characterization. We differentiate nine hierarchical levels that characterize the structure ranging from the whole fruit on the macroscopic scale down to the molecular scale. From a biological viewpoint, understanding the hierarchical structure may elucidate why it is advantageous for these seed coats to be so difficult to break. From an engineering viewpoint, microstructure characterization is important for identifying features that contribute to the high strength and cracking resistance of these objects. This is essential for revealing the underlying structure-function-relationships. Such information will help us develop engineering materials and lightweight-structures with improved fracture and puncture resistance.
Novel difluoromethylenated [70]fullerene derivatives, C70(CF2 )n (n=1-3), were obtained by the reaction of C70 with sodium difluorochloroacetate. Two major products, isomeric C70(CF2 ) mono-adducts with [6,6]-open and [6,6]-closed configurations, were isolated and their homofullerene and methanofullerene structures were reliably determined by a variety of methods that included X-ray analysis and high-level spectroscopic techniques. The [6,6]-open isomer of C70(CF2 ) constitutes the first homofullerene example of a non-hetero [70]fullerene derivative in which functionalisation involves the most reactive bond in the polar region of the cage. Voltammetric estimation of the electron affinity of the C70(CF2 ) isomers showed that it is substantially higher for the [6,6]-open isomer (the 70-electron π-conjugated system is retained) than the [6,6]-closed form, the latter being similar to the electron affinity of pristine C70. In situ ESR spectroelectrochemical investigation of the C70(CF2 ) radical anions and DFT calculations of the hyperfine coupling constants provide evidence for the first example of an inter-conversion between the [6,6]-closed and [6,6]-open forms of a cage-modified fullerene driven by an electrochemical one-electron transfer. Thus, [6,6]-closed C70(CF2 ) constitutes an interesting example of a redox-switchable fullerene derivative.
Highly selective reversed phases (C(30) phases) are self-packed in 250 microm inner diameter fused-silica capillaries and employed for capillary HPLC separation of shape-constrained natural compounds (tocopherol homologues, vitamin E). Miniaturized hyphenated systems such as capillary HPLC-ESI-MS (positive ionization mode) and, with special emphasis, continuous-flow capillary HPLC- NMR are used for structural determination of the separated compounds. Despite the small amount of sample available (1.33 microg of each tocopherol), the authors have been able to monitor the capillary HPLC separation under continuous-flow (1)H NMR conditions, thus allowing an immediate peak identification. Further structural assignment was carried out in the stopped-flow NMR mode as shown, for example, by a 2D (1)H,(1)H COSY NMR spectrum of alpha-tocopherol. We demonstrate in this paper the considerable potential of hyphenated capillary separations coupled to MS and NMR for the investigation of restricted amounts of sample.
Fruit walls as well as nut and seed shells typically perform a multitude of functions. One of the biologically most important functions consists in the direct or indirect protection of the seeds from mechanical damage or other negative environmental influences. This qualifies such biological structures as role models for the development of new materials and components that protect commodities and/or persons from damage caused for example by impacts due to rough handling or crashes. We were able to show how the mechanical properties of metal foam based components can be improved by altering their structure on various hierarchical levels inspired by features and principles important for the impact and/or puncture resistance of the biological role models, rather than by tuning the properties of the bulk material. For this various investigation methods have been established which combine mechanical testing with different imaging methods, as well as with in situ and ex situ mechanical testing methods. Different structural hierarchies especially important for the mechanical deformation and failure behaviour of the biological role models, pomelo fruit (Citrus maxima) and Macadamia integrifolia, were identified. They were abstracted and transferred into corresponding structural principles and thus hierarchically structured bio-inspired metal foams have been designed. A production route for metal based bio-inspired structures by investment casting was successfully established. This allows the production of complex and reliable structures, by implementing and combining different hierarchical structural elements found in the biological concept generators, such as strut design and integration of fibres, as well as by minimising casting defects. To evaluate the structural effects, similar investigation methods and mechanical tests were applied to both the biological role models and the metallic foams. As a result an even deeper quantitative understanding of the form-structure-function relationship of the biological concept generators as well as the bio-inspired metal foams was achieved, on deeper hierarchical levels and overarching different levels.
Intravenous application of high-dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate-mediated cytotoxicity. Under normoxia and hypoxia, ascorbate IC50 values were determined on the NCI60 cancer cells. The cell cycle, the influence of cobalt chloride-induced hypoxia-inducible factor-1α (HIF-1α) and the glucose transporter 1 (GLUT-1) expression (a pro-survival HIF-1α-downstream-target) were analysed after ascorbate exposure under normoxic and hypoxic conditions. The amount of ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O2) globally increased the IC50 of ascorbate in the 60 cancer cell lines from 4.5 ± 3.6 mM to 10.1 ± 5.9 mM (2.2-fold increase, P < 0.001, Mann–Whitney t-test), thus inducing cellular resistance towards ascorbate. This ascorbate resistance depended on HIF-1α-signalling, but did not correlate with cell line-specific expression of the ascorbate transporter GLUT-1. However, under normoxic and hypoxic conditions, ascorbate treatment at the individual IC50 reduced the expression of GLUT-1 in the cancer cells. Our data show a ROS-induced, HIF-1α-and O2-dependent cytotoxicity of ascorbate on 60 different cancer cells. This suggests that for clinical application, cancer patients should additionally be oxygenized to increase the cytotoxic efficacy of ascorbate.
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