Imaging the In Vivo Degradation of Tissue Engineering Implants by Use of Supramolecular Radiopaque Biomaterials

For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo‐tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain‐extended polycaprolactone (PCL2000‐U4U) elastomer and a novel iodinated bisurea‐modified CA additive (I‐U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE‐grafts are prepared by simply electrospinning a solution containing PCL2000‐U4U and I‐U4U. Rats receive an aortic interposition graft, either composed of only PCL2000‐U4U (control) or of PCL2000‐U4U and I‐U4U (test). The grafts are explanted for analysis at three time points over a 1‐month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo‐tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants.     

Amiloride-sensitive channels in type I fungiform taste cells in mouse

Background  

Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na⁺ and K⁺ current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na⁺, K⁺, and Ca²⁺ currents, and make prominent synapses with afferent nerve fibers. Na⁺ salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs). In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice.     

Evidence for a role of glutamate as an efferent transmitter in taste buds

Background  

Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds.     

Progress in solid core photonic bandgap fibers

We investigate both experimentally and numerically confinement and bend losses in solid-core photonic bandgap fibers. We proposed two designs, based on the addition of air regions in the cladding, allowing these losses to be reduced significantly while keeping the optical properties of bandgap fibers. We also present and discuss numerical results on the impact of transversal defects on the fiber confinement loss in the case of a realistic low loss fiber.     

Log-robust portfolio management with parameter ambiguity

We present a robust optimization approach to portfolio management under uncertainty when randomness is modeled using uncertainty sets for the continuously compounded rates of return, which empirical research argues are the true drivers of uncertainty, but the parameters needed to define the uncertainty sets, such as the drift and standard deviation, are not known precisely. Instead, a finite set of scenarios is available for the input data, obtained either using different time horizons or assumptions in the estimation process. Our objective is to maximize the worst-case portfolio value (over a set of allowable deviations of the uncertain parameters from their nominal values, using the worst-case nominal values among the possible scenarios) at the end of the time horizon in a one-period setting. Short sales are not allowed. We consider both the independent and correlated assets models. For the independent assets case, we derive a convex reformulation, albeit involving functions with singular Hessians. Because this slows computation times, we also provide lower and upper linear approximation problems and devise an algorithm that gives the decision maker a solution within a desired tolerance from optimality. For the correlated assets case, we suggest a tractable heuristic that uses insights derived in the independent assets case.     

Synthetic studies of cystobactamids as antibiotics and bacterial imaging carriers lead to compounds with high in vivo efficacy

There is an alarming scarcity of novel chemical matter with bioactivity against multidrug-resistant Gram-negative bacterial pathogens. Cystobactamids, recently discovered natural products from myxobacteria, are an exception to this trend. Their unusual chemical structure, composed of oligomeric para-aminobenzoic acid moieties, is associated with a high antibiotic activity through the inhibition of gyrase. In this study, structural determinants of cystobactamid''s antibacterial potency were defined at five positions, which were varied using three different synthetic routes to the cystobactamid scaffold. The potency against Acinetobacter baumannii could be increased ten-fold to an MIC (minimum inhibitory concentration) of 0.06 μg mL⁻¹, and the previously identified spectrum gap of Klebsiella pneumoniae could be closed compared to the natural products (MIC of 0.5 μg mL⁻¹). Proteolytic degradation of cystobactamids by the resistance factor AlbD was prevented by an amide-triazole replacement. Conjugation of cystobactamid''s N-terminal tetrapeptide to a Bodipy moiety induced the selective localization of the fluorophore for bacterial imaging purposes. Finally, a first in vivo proof of concept was obtained in an E. coli infection mouse model, where derivative 22 led to the reduction of bacterial loads (cfu, colony-forming units) in muscle, lung and kidneys by five orders of magnitude compared to vehicle-treated mice. These findings qualify cystobactamids as highly promising lead structures against infections caused by Gram-positive and Gram-negative bacterial pathogens.

Structure–activity relationship studies of the natural product cystobactamid at four different positions led to novel imaging probes and analogs with superior antibacterial activities and in vivo efficacy.     

Development of an on-line UV decomposition system for direct coupling of liquid chromatography to atomic-fluorescence spectrometry for selenium speciation analysis

Speciation analysis of four selenium species (selenite, selenate, selenocystine, and selenomethionine) has been performed by on-line coupling of liquid chromatography (LC), UV decomposition, hydride generation (HG), and atomic-fluorescence spectrometry (AFS). Because only selenite (Se^IV) can generate hydrides, on-line conversion of organic and inorganic selenium species is discussed. Preliminary study showed that the use of only UV light was not sufficient to reduce selenate, because no absorption is observed for this compound at the main wavelength of the low-pressure mercury lamp (253.7 nm). Thus, new conditions based on addition of a reducing reagent (I⁻) were developed. Mechanisms of action are proposed to explain selenium species conversions. Because of their compatibility with on-line treatment, phosphate buffers were used for chromatographic separation on an anion exchange column (Hamilton PRP-X100). Detection limits (19–60 pg Se) and repeatability of the technique were close to those obtained by conventional quadrupole ICPMS. Applications to real samples such as water and oysters are presented and emphasize the robustness of the system.