Structure and Energetics of Ligand–Fluorine Interactions with Galectin-3 Backbone and Side-Chain Amides: Insight into Solvation Effects and Multipolar Interactions

Multipolar fluorine–amide interactions with backbone and side-chain amides have been described as important for protein–ligand interactions and have been used to improve the potency of synthetic inhibitors. In this study, fluorine interactions within a well-defined binding pocket on galectin-3 were investigated systematically using phenyltriazolyl-thiogalactosides fluorinated singly or multiply at various positions on the phenyl ring. X-ray structures of the C-terminal domain of galectin-3 in complex with eight of these ligands revealed potential orthogonal fluorine–amide interactions with backbone amides and one with a side-chain amide. The two interactions involving main-chain amides seem to have a strong influence on affinity as determined by fluorescence anisotropy. In contrast, the interaction with the side-chain amide did not influence affinity. Quantum mechanics calculations were used to analyze the relative contributions of these interactions to the binding energies. No clear correlation could be found between the relative energies of the fluorine–main-chain amide interactions and the overall binding energy. Instead, dispersion and desolvation effects play a larger role. The results confirm that the contribution of fluorine–amide interactions to protein–ligand interactions cannot simply be predicted, on geometrical considerations alone, but require careful consideration of the energetic components.     

Zn-porphyrin formation in cured meat products: Effect of added salt and nitrite

Zn-porphyrin (Zn-pp) was quantified by fluorescence spectroscopy in the cured and dry cured meat products: Parma ham, Iberian ham, dry-cured ham with added nitrite, cooked ham with added nitrite, raw ham meat, raw bacon and Karree-Speck. The highest amount of Zn-pp was found in dry-cured Parma ham and Iberian ham, while the use of nitrite as curing agent was found to inhibit completely the formation of Zn-pp in meat products. A positive correlation between both Zn content and Fe content and the logarithmic transformed Zn-pp content (measured as fluorescence intensity I_fl) was found for the different cured and dry cured meat products, with correlation coefficients of 0.79 (p < 0.001) and 0.71 (p < 0.01), respectively. Log I_fl correlates best with the Zn content, indicating that the formation of Zn-pp is proportional to the Zn content. A model system with vacuum packed pork in brine with different added levels of sodium chloride with or without nitrite and Zn acetate was investigated in order to further elucidate the mechanism of Zn-pp formation. Zn-pp increased with time (up to 42 days investigated) in non-cured meat and for meat cured solely with NaCl lower than 9%. Addition of nitrite or Zn(II) in the curing brine was found to inhibit formation of Zn-pp confirming the observations from the various cured meat products. It is suggested that a chloride anion assisted dissociation of iron from myoglobin could be rate-determining for Zn-pp formation in meat products.     

Black carbon-inclusive modeling approaches for estimating the aquatic fate of dibenzo-p-dioxins and dibenzofurans

A novel black carbon (BC) inclusive modeling tool is applied to estimate the distribution and long-term fate of dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the Norwegian Grenland Fjords. Three versions of the model were developed in which sediment-water partitioning was described using (i) an amorphous organic carbon (AOC) partitioning sorption model without BC sorption, (ii) a combined AOC and BC sorption model based on the Freundlich isotherm, and (iii) a combined BC-AOC model based on the Langmuir isotherm. The predictive ability of the three different models was evaluated for 17 PCDD/Fs by comparison of model predictions with observed organic carbon normalized sediment-water partition coefficients (K(TOC)) and with measured concentrations. All three versions of the model were able to predict concentrations that were in reasonable agreement with measured particulate concentrations (i.e., within a factor of 4 of median values). Estimated particulate concentrations were less sensitive to the model choice because the majority of the mass of these hydrophobic chemicals is associated with particulates regardless. However, for estimation of K(TOC) or dissolved water concentrations, both versions of the combined AOC and BC sorption models provided greatly improved estimates compared to the AOC-only model.     

Quantification of zinc-porphyrin in dry-cured ham products by spectroscopic methods Comparison of absorption, fluorescence and X-ray fluorescence spectroscopy

Zinc–protoporphyrin (Zn–pp), which has been identified as the major pigment in certain dry-cured meat products, was extracted with acetone/water (75%) and isolated from the following meat products: Parma ham, Iberian ham and dry-cured ham with added nitrite. The quantification of Zn–pp by electron absorption, fluorescence and X-ray fluorescence (XRF) spectroscopy was compared (concentration range used [Zn–pp] = 0.8–9.7 μM). All three hams were found to contain Zn–pp, and the results show no significant difference among the content of Zn–pp quantified by fluorescence, absorbance and X-ray fluorescence spectroscopy for Parma ham and Iberian ham. All three methods can be used for quantification of Zn–pp in acetone/water extracts of different ham types if the content is higher than 1.0 ppm. For dry-cured ham with added nitrite, XRF was not applicable due to the low content of Zn–pp (<0.1 ppm). In addition, XRF spectroscopy provides further information regarding other trace elements and can therefore be advantageous in this aspect. This study also focused on XRF determination of Fe in the extracts and as no detectable Fe was found in the three types of ham extracts investigated (limit of detection; Fe ? 1.8 ppm), it allows the conclusion that iron containing pigments, e.g., heme, do not contribute to the noticeable red colour observed in some of the extracts.     

Living lawns, dying waters: The suburban boom, nitrogenous fertilizers, and the nonpoint source pollution dilemma

The March 1963 issue of Consumer Bulletin included a four-page article titled "How to grow a better lawn", the lead paragraph of which assured readers that "one does not have to be an expert or spend large sums of money to have a good lawn. It is necessary, however, to follow certain established practices in the construction and maintenance of any lawn." These two assertions may have struck readers, as I suspect they would strike lawngrowers today, as somewhat contradictory. Given the list of established practices that followed--"the construction of the lawn base, with proper grading, drainage, and preparation of the seedbed; selection of the type of grass and spreading of the seed; and maintenance, including fertilizing, mowing, and control of weeds"--it is difficult to imagine how the homeowner could have accomplished all of this without large sums of money or expertise. In fact, building lawns in the manner described by Consumer Bulletin required tremendous amounts of both. Recognizing these established practices in lawn construction and maintenance as a technological system allows us to better understand the persistence of this grassy landscape in America.     

Mechanical properties of biaxially strained poly(l‐lactide) tubes: Strain rate and temperature dependence

Poly(l ‐lactide) (PLLA) is a bioabsorbable polymer with high stiffness and strength compared to the other commercially available bioabsorbable polymers. The properties of PLLA can be improved by straining, causing deformation‐mediated molecular orientation. PLLA tubes were biaxially strained above their T_g for improvement of their strength, in a two‐step process (sequential straining). Mechanical properties and crystal morphology were investigated as a function of processing strain rate and temperature. DSC revealed that a low processing strain rate allows molecular chain relaxation in the direction of strain and the crystallization is suppressed. Faster strain rates on the other hand suppress chain relaxation, and results in crystalline tubes. The mechanical properties are influenced by both processing strain rate and temperature. Low strain rates allow chain relaxation resulting in the lowest strength and stiffness, whereas a larger stiffness and strength is achieved by increasing strain rate and temperature. Isotropic mechanical properties are only observed at high processing strain rates. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45192.     

NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model

Restoring the control of food intake is the key to obesity management and prevention. The arcuate nucleus (ARC) of the hypothalamus is extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces food intake by its action in neuropeptide Y (NPY) neurons of the hypothalamic ARC, but the detailed mode of action observed in human neurons is missing, due to the lack of a human-neuron-based model for pharmacology testing. Here, we validated and utilized a human-neural-stem-cell-based (hNSC) model of ARC to test the effects of NPFF on cellular pathways and neuronal activity. We found that in the human neurons, decreased cAMP levels by NPFF resulted in a reduced rate of cytoplasmic calcium oscillations, indicating an inhibition of ARC NPY neurons. This suggests the therapeutic potential of NPFFR2 in obesity. In addition, we demonstrate the use of human-stem-cell-derived neurons in pharmacological applications and the potential of this model to address functional aspects of human hypothalamic neurons.     

Structural determination of ethylene‐propylene‐diene rubber (EPDM) containing high degree of controlled long‐chain branching

This work highlights an attempt to characterize the degree and nature of long‐chain branching (LCB) in an unknown sample of ethylene‐propylene‐diene rubber (EPDM). Two EPDM rubbers selected for this study were comparable in comonomer compositions but significantly different with respect to molar mass and the presence of LCB. Both rubbers contained 5‐ethylidene‐2‐norbornene (ENB) as diene. Solution cast films of pure EPDM samples were used for different characterization techniques. ¹H‐NMR, and ¹³C‐NMR were used for assessing the comonomer ratios and LCB. Size exclusion chromatography (SEC) equipped with triple detector system was used to determine the molar mass (both absolute and relative) and polydispersity index (PDI). Presence of branching was also detected using sec‐viscometry. Rheological analysis has also been used for characterizing LCB. Finally, on the basis of the experimental findings and the available theories, an attempt was made to identify the chemical nature and degree of LCB. This study reveals the possibility of detailed characterization of molecular architecture of EPDM containing LCB by comparing with an essentially linear EPDM in light of an existing theory. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Critical infrastructures and the tragedy of the commons dilemma: Implications from institutional restructuring on reliability and safety

Through the influence of neoliberal ideas, many critical infrastructures that used to be under public ownership have been opened up for market competition. Using the Swedish railway system as a case, this paper empirically explores whether such reforms have given rise to common‐pool resource problems, and discusses possible implications. The results show that institutional restructuring has created challenges related to balancing the use of the infrastructure with a sufficient level of maintenance. The paper concludes that the main value of analysing critical infrastructures from the perspective of common‐pool resources is the possibility of juxtaposing the way organizational and institutional interactions across scales generate both short‐term gains and long‐term negative side effects influencing reliability and safety.