Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.     

Bandwidth limits of luminescent solar concentrators as detectors in free-space optical communication systems

Luminescent solar concentrators(LSCs)have recently emerged as a promising receiver technology in free-space optical communications due to their inherent ability to collect light from a wide field-of-view and concentrate it into small areas,thus leading to high optical gains.Several high-speed communication systems integrating LSCs in their detector blocks have already been demonstrated,with the majority of efforts so far being devoted to maximising the received optical power and the system's field-of-view.However,LSCs may pose a severe bottleneck on the bandwidth of such communication channels due to the comparably slow timescale of the fluorescence events involved,a situation further aggravated by the inherent reabsorption in these systems,and yet,an in-depth study into such dynamic effects remains absent in the field.To fill this gap,we have developed a comprehensive analytical solution that delineates the fundamental bandwidth limits of LSCs as optical detectors in arbitrary free-space optical links,and establishes their equivalence with simple RC low-pass electrical circuits.Furthermore,we demonstrate a time-domain Monte Carlo simulation platform,an indispensable tool in the multiparameter optimisation of LSC-based receiver systems.Our work offers vital insight into LSC system dynamic behaviour and paves the way to evaluate the technology for a wide range of applications,including visible light communications,high-speed video recording,and real-time biological imaging,to name a few.     

Untersuchungen zum Transfer pharmakologisch wirksamer Substanzen aus der Nutztierhaltung in Porree und Weißkohl

Investigation on the transfer of pharmacologically active substances used in animal husbandry into leek and cabbage. The potential of leek and cabbage for uptake of highly prescribed veterinary drugs (antibiotics) was tested in hydroponically grown plants. For this purpose the antibiotics sulfadiazine (SFD), enrofloxacine (ENR), tetracycline (TC), chlortetracycline (CTC) and monensine (MON) were chosen. A further aim was to gain data on the situation of vegetables grown in agricultural practise with regard to antibiotic residues. The evident effects of the antibiotics on plants grown hydroponically (each antibiotic was administered at 5 μmol/l nutrient solution) were greatly different: With regard to leek there were no visible effects (MON, SFD), a weak bleaching of the younger leaf sections (CTC), and strong effects of ENR. The (phytotoxic) effects of antibiotics on cabbage were much more distinct. CTC caused a yellowing of the plant vasculature in cabbage. MON induced lesions on some leaves and finally led to leaf wilting. With administration of ENR a nearly complete bleaching of young leaves was observed. Using LC-MS/MS-methods (low-resolution and high-resolution MS) the administered antibiotics, as well as conversion products and metabolites, were separately identified and quantified in various organs of leek (roots, young and old sections of leaves) and cabbage (roots, stalks, young and old leaves). Depending on the type of antibiotic, vegetable species, and plant organ, the detected concentrations of antibiotic residues comprised several orders of magnitude ranging from μg/kg to mg/kg of fresh weight (fw). The highest concentrations of antibiotics were found in roots of both vegetable species: CTC and TC were detected at approximately 10 mg/kg fw in cabbage roots and at approximately 20 mg/kg fw in leek roots and ENR was determined at approximately 12 mg/kg fw in cabbage roots. Low amounts of ENR were metabolised to ciprofloxacine (CIP). ENR occurred at similar concentrations of approximately 7 mg/kg fw in roots and old leaves of cabbage, indicating a high transport rate of this antibiotic in the cabbage plant. In stalks, young and old leaves of cabbage and in young and old leaf sections of leek all administered antibiotics were detected. Within these antibiotics, ENR and CTC and their conversion products, e. g. demeclocycline (DMC) and TC, occurred at the highest concentrations. SFD and MON were found in considerably lower concentrations (<100 μg/kg fw). The results of our experiments in hydroponic cultures, using defined concentrations of antibiotics in the nutrient solution, evidently demonstrate that cabbage and leek have a very high potential for uptake of a number of veterinary antibiotic drugs, especially for tetracycline and ENR.     

PBDEs in the atmosphere of three locations in western Europe

Atmospheric concentrations of PBDEs (108 samples in total) were measured at 2 rural/semirural sites in England and 1 remote site on the west coast of Ireland in the years 2001 and 2000, respectively. Detailed analysis of the factors affecting concentrations is performed. The United Kingdom (UK) has been a major producer and user of PBDEs. Concentrations of sigmaPBDEs at Mace Head (MH), Ireland ranged between 0.22 and 5.0 pg m(-3) with a mean of 2.6 pg m(-3) and were controlled primarily by advection. sigmaPBDEs concentrations at Hazelrigg (HR), northwest England, ranged between 2.8 and 37 pg m(-3) with a mean of 12 pg m(-3) and at Chilton (CH), southwest England between 3.4 and 33 pg m(-3) with a mean of 11 pg m(-3). The average mixture of PBDEs in air was similar to that of commercial penta-BDE products. Movement of air over local/regional sources influenced concentrations of PBDEs at all sites, particularly at MH. At the two English sites during the summer, concentrations of PBDEs were strongly influenced bytemperature, indicating that air-surface exchange processes play an important role. Advection became more influential during winter, particularly at CH, where a different congener profile was observed in some samples as ambient air temperatures decreased and PBDE concentrations increased. It is hypothesized that this was due to increased emissions from diffuse combustion sources.     

Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice

Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO₃)₂) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone.     

Degradation of phytate by Pichia kudriavzevii TY13 and Hanseniaspora guilliermondii TY14 in Tanzanian togwa

The fermented cereal-based gruel togwa is used as weaning food for children in Tanzania. Togwa is rich in minerals but these are often not available for uptake in the human intestine due to natural inhibitors, such as phytate (IP(6)). The yeasts Pichia kudriavzevii TY13, Hanseniaspora guilliermondii TY14 and TY20, isolated from Tanzanian togwa, and selected for high phytase activity in complex yeast medium YPD, were now studied regarding their ability to degrade IP(6) in maize-based model togwa. A modified constitutively high-phytase producing Saccharomyces cerevisiae BY80 and commercial Aspergillus ficuum phytase were included for comparison. In addition, a strain of Lactobacillus plantarum was included in the model-togwa set-up. All yeasts in the study grew and reached final cell density 1.5-2 log units higher than the start value. S. cerevisiae BY80 degraded 85% of the IP(6) in 48 h; the same degradation level as with A. ficuum phytase (89%). Of the togwa-isolated yeasts, P. kudriavzevii TY13 and H. guilliermondii TY14 showed strong phytate degradation in the model-togwa; 95% or more of the initial IP(6) was degraded after 48 h. This corresponds to a remaining level of 0.4 and 0.3μmol IP(6)/g dw. Co-inoculation with L. plantarum did not increase IP(6) degradation. Moreover, fermentation with P. kudriavzevii TY13 yielded a successive increase in inorganic phosphate (P(i)), from 0.7 to 5.4 mM, suggesting a phytase production in TY13 which is fairly insensitive to P(i) repression. The study shows that phytate in a model togwa is available for yeast phytase enzymes, and addresses the importance of strain selection for effectively degrading the phytate. Certain yeasts originating from togwa seem to have developed a natural high phytase production, and P. kudriavzevii TY13 and H. guilliermondii TY14 seem particularly well adapted to phytate degradation in togwa, and is our choice for further studies and strain improvement.     

Breaking the spores of the fungus Ganoderma lucidum by supercritical CO2

The hard sporoderm of Ganoderma lucidum spores prevents the release of bioactive components such as polysaccharides which have significant anti-tumour activity. In the present study, supercritical carbon dioxide (SC–CO₂) was used for the sporoderm breaking of G. lucidum spores, and polysaccharides were subsequently extracted and determined for evaluating the performances of SC–CO₂. The operating parameters were optimized by orthogonal array design (OAD), and the morphological status of sporoderm was observed by scanning electron microscope (SEM). The optimum operating conditions for SC–CO₂ breaking of sporoderm were as follows: pressure 35 MPa, temperature 25 °C, time 4 h, and CO₂ flow rate 10 kg/h. After SC–CO₂ processing, the extraction yield of polysaccharides reached 2.98%, which was 3-fold to that of the intact ones (0.94%). This method is fast, efficient and advanced enough to break the hard sporoderm of G. lucidum, which may provide a scientific reference for the large-scale processing of spores in the pharmaceutical and food industries.     

Chromium remediation or release? Effect of iron(II) sulfate addition on chromium(VI) leaching from columns of chromite ore processing residue

Chromite ore processing residue (COPR), derived from the so-called high lime processing of chromite ore, contains high levels of Cr(III) and Cr(VI) and has a pH between 11 and 12. Ferrous sulfate, which is used for remediation of Cr(VI) contamination in wastewater and soils via reduction to Cr(III) and subsequent precipitation of iron(III)/chromium(III) hydroxide, has also been proposed for remediation of Cr(VI) in COPR. Instead, however, addition of FeSO4 to the infiltrating solution in column experiments with COPR greatly increased leaching of Cr(VI). Leached Cr(VI) increased from 3.8 to 12.3 mmol kg(-1) COPR in 25 pore volumes with 20 mM FeSO4, reaching solution concentrations as high as 1.6 mM. Fe(II) was ineffective in reducing Cr(VI) to Cr(III) because it precipitated when it entered the column due to the high pH of COPR, while Cr(VI) in solution was transported away with the infiltrating solution. The large increase in leaching of Cr(VI) upon infiltration of sulfate, either as FeSO4 or Na2SO4, was caused by anion exchange of sulfate for chromate in the layered double hydroxide mineral hydrocalumite, a process for which scanning electron microscopy with energy-dispersive X-ray microanalysis provided direct evidence.     

Using chromium stable isotope ratios to quantify Cr(VI) reduction: lack of sorption effects

Chromium stable isotope values can be effectively used to monitor reduction of Cr(VI) in natural waters. We investigate effects of sorption during transport of Cr(VI) which may also shift Cr isotopes values, complicating efforts to quantify reduction. This study shows that Cr stable isotope fractionation caused by sorption is negligible. Equilibrium fractionation of Cr stable isotopes between dissolved Cr(VI) and Cr(VI) adsorbed onto gamma-Al2O3 and goethite is less than 0.04 per thousand (53Cr/52Cr) under environmentally relevant pH conditions. Batch experiments at pH 4.0 and pH 6.0 were conducted in series to sequentially magnify small isotope fractionations. A simple transport model suggests that adsorption may cause amplification of a small isotope fractionation along extreme fringes of a plume, leading to shifts in 53Cr/52Cr values. We therefore suggest that isotope values at extreme fringes of Cr plumes be critically evaluated for sorption effects. A kinetic effect was observed in experiments with goethite at pH 4 where apparently lighter isotopes diffuse into goethite clumps at a faster rate before eventually reaching equilibrium. This observed kinetic effect may be important in a natural system that has not attained equilibrium and is in need of further study. Cr isotope fractionation caused by speciation of Cr(VI) between HCrO4- and CrO4(2-) was also examined, and we conclude that it is not measurable. In the absence of isotope fractionation caused by equilibrium speciation and sorption, most of the variation in delta53Cr values may be attributed to reduction, and reliable estimates of Cr reduction can be made.