Survey of the Chemical Defence Potential of Diatoms: Screening of Fifty Species for α,β,γ,δ-unsaturated aldehydes

In recent years a negative influence of diatom-derived ,,,-unsaturated aldehydes (PUA) on the reproductive success of copepods and invertebrates has been suggested. Since adverse chemical properties of diatoms would question the traditional view of the marine food web, this defense mechanism has been investigated in detail, but the PUA-release by test organisms has only been determined in a few cases. The observed effects were nevertheless frequently discussed from a general point of view often leading to contradictory conclusions. We have examined the PUA-production of 50 diatom species (71 isolates) in order to provide a basis for the interpretation of laboratory and field results on the influence of diatom food on the reproductive success of their consumers. PUA-production is species and strain dependent. Thirty-six percent of the investigated species (38% of the cultivated isolates) release ,,,-unsaturated aldehydes upon cell disruption in concentrations from 0.01 to 9.8 fmol per cell. Thalassiosira rotula and Thalassiosira pacifica, major spring-bloom forming diatoms isolated from Roscoff (Bretagne, English Channel, France) and Puget Sound (Washington, USA) were among the PUA-producing strains.     

Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes

Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine‐derived metabolite β‐hydroxy‐β‐methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB‐treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator‐activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP‐activated protein kinase. As a result, HMB‐treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.     

Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP (“flakka”) Derivatives

Changes in the molecular structure of synthetic cathinones has led to an increase in the number of novel emerging drugs in the illicit drug market at an unprecedented rate. Unfortunately, little is known about the neuropsychopharmacology of recently emerged halogen-substituted α-PVP derivatives. Thus, the aim of this study was to investigate the role of para- and meta-halogen (F-, Cl-, and Br-) substitutions on the in vitro, in silico, and in vivo effects of α-pyrrolidinopentiophenone (α-PVP) derivatives. HEK293 cells expressing the human dopamine or serotonin transporter (hDAT and hSERT) were used for the uptake inhibition and transporter affinity assays. Molecular docking was used to model the interaction mechanism against DAT. Swiss CD-1 mice were used for the horizontal locomotor activity, open field test, and conditioned place preference paradigm. All compounds demonstrated potent DA uptake inhibition and higher DAT selectivity than cocaine. Meta-substituted cathinones showed higher DAT/SERT ratios than their para- analogs, which correlates with an increased psychostimulant effect in vivo and with different meta- and para-in silico interactions at DAT. Moreover, all compounds induced rewarding and acute anxiogenic effects in mice. In conclusion, the present study demonstrates the role of meta- and para-halogen substitutions in the mechanism of action and provides the first evidence of the rewarding and anxiety-like properties of halogenated α-PVP derivatives.     

Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI

Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half‐life in vivo. In a rational design strategy, we obtained an X‐ray structure of lead mannosides and then designed mannosides with improved drug‐like properties. We show that cyclizing the carboxamide onto the biphenyl B‐ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2‐methyl‐4‐(1‐oxo‐1,2‐dihydroisoquinolin‐7‐yl)phenyl α‐d ‐mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N‐Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22 , as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria‐mediated hemagglutination and prevent biofilm formation by UPEC with single‐digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date.     

Direct ink writing of vancomycin-loaded polycaprolactone/ polyethylene oxide/ hydroxyapatite 3D scaffolds

Novel inks were formulated by dissolving polycaprolactone (PCL), a hydrophobic polymer, in organic solvent systems; polyethylene oxide (PEO) was incorporated to extend the range of hydrophilicity of the system. Hydroxyapatite (HAp) with a weight ratio of 55–85% was added to the polymer-based solution to mimic the material composition of natural bone tissue. The direct ink writing (DIW) technique was applied to extrude the formulated inks to fabricate the predesigned tissue scaffold structures; the influence of HAp concentration was investigated. The results indicate that in comparison to other inks containing HAp (55%, 75%, and 85%w/w), the ink containing 65% w/w HAp had faster ink recovery behavior; the fabricated scaffold had a rougher surface as well as better mechanical properties and wettability. It is noted that the 65% w/w HAp concentration is similar to the inorganic composition of natural bone tissue. The elastic modulus values of PCL/PEO/HAp scaffolds were in the range of 4–12 MPa; the values were dependent on the HAp concentration. Furthermore, vancomycin as a model drug was successfully encapsulated in the PCL/PEO/HAp composite scaffold for drug release applications. This paper presents novel drug-loaded PCL/PEO/HAp inks for 3D scaffold fabrication using the DIW printing technique for potential bone scaffold applications.     

Mechanics of lipid bilayer junctions affecting the size of a connecting lipid nanotube

In this study we report a physical analysis of the membrane mechanics affecting the size of the highly curved region of a lipid nanotube (LNT) that is either connected between a lipid bilayer vesicle and the tip of a glass microinjection pipette (tube-only) or between a lipid bilayer vesicle and a vesicle that is attached to the tip of a glass microinjection pipette (two-vesicle). For the tube-only configuration (TOC), a micropipette is used to pull a LNT into the interior of a surface-immobilized vesicle, where the length of the tube L is determined by the distance of the micropipette to the vesicle wall. For the two-vesicle configuration (TVC), a small vesicle is inflated at the tip of the micropipette tip and the length of the tube L is in this case determined by the distance between the two interconnected vesicles. An electrochemical method monitoring diffusion of electroactive molecules through the nanotube has been used to determine the radius of the nanotube R as a function of nanotube length L for the two configurations. The data show that the LNT connected in the TVC constricts to a smaller radius in comparison to the tube-only mode and that tube radius shrinks at shorter tube lengths. To explain these electrochemical data, we developed a theoretical model taking into account the free energy of the membrane regions of the vesicles, the LNT and the high curvature junctions. In particular, this model allows us to estimate the surface tension coefficients from R(L) measurements.     

Water transport in cellular tissues during thermal processing

Accurate modeling of water transport in food materials requires knowledge of how transport properties depend on the material structure. Water transport in a cellular tissue depends on its pathway (intracellular versus extracellular), which in turn depends on temperature. Using a combination of permeability measurement, pore‐size distribution analysis and bioimpedance analysis, it is shown that water in a cellular tissue (e.g., potatoes) is mostly intracellular at lower temperatures at which cell membranes are intact. During drying at high‐temperatures, cell membranes in potatoes are damaged, and the moisture transport pathway is primarily extracellular (through intercellular spaces and the lacunae created by the killed cells), with a much lower resistance to water transport. The difference in moisture diffusivity in potatoes for the two pathways has been estimated to be three orders of magnitude. Therefore, transport properties measured or predicted at low temperatures cannot be used for high temperatures because they correspond to different moisture migration pathways. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Phase and Rheological Behavior of Cetyldimethylbenzylammonium Salicylate (CDBAS) and Water

The temperature–composition phase diagram in the diluted region of the cationic surfactant cetyldimethylbenzylammonium salicylate/water system was studied with a battery of techniques. The Krafft temperature (T _k = 33 ± 1 °C) was measured by differential scanning calorimetry, polarizing microscopy, conductimetry, viscosimetry, and rheometry. The critical vesicle concentration (cvc, ~0.002 wt%) and a vesicle–micellar transition (cvm, ~0.005 wt%) was detected at a temperature of 35 °C. Below T _k and concentrations ≤2 wt%, a transparent solution is formed (I). Above 2–8.5 wt%, a lamellar (L₁) phase forms. At higher concentrations and up to 12 wt%, a second lamellar phase (L₂) is detected. From 12.4 to 15.5 wt%, an emulsion phase (E) is formed. Rheological dynamic measurements for the I phase indicate that the system exhibits a predominantly viscous behavior (G′ < G″) for concentrations lower than the overlap or entanglement concentration (C _e, ~0.75 wt%). At higher concentrations, wormlike micelles form and the elastic behavior predominates (G′ > G″). The elastic (G′) modulus collapses in a concentration–time master curve in the whole reduced frequencies range ωτ _c examined, whereas the viscous modulus (G″) collapses only at reduced frequencies lower than 0.1. Reduced stress plotted as a function of the reduced shear rate yields a good superposition of the curves at the different concentrations up to the onset of the non-linear behavior.     

(100) facets of γ-Al2O3: The Active Surfaces for Alcohol Dehydration Reactions

Abstract  

Temperature programmed desorption (TPD) of ethanol, as well as ethanol and methanol dehydration reactions were studied on γ-Al₂O₃ in order to identify the active catalytic sites for alcohol dehydration reactions. Two high temperature (>473 K) desorption features were observed following ethanol adsorption. Samples calcined at T ≤ 473 K displayed a desorption feature in the 523–533 K temperature range, while those calcined at T ≥ 673 K showed a single desorption feature at 498 K. These two high temperature desorption features correspond to the exclusive formation of ethylene on the Lewis (498 K) and Br?nsted acidic (~525 K) sites. The amount of ethylene formed under conditions where the competition between water and ethanol for adsorption sites is minimized is identical over the two surfaces. Furthermore, a nearly 1-to-1 correlation between the number of under-coordinated Al³⁺ ions on the (100) facets of γ-Al₂O₃ and the number of ethylene molecules formed in the ethanol TPD experiments on samples calcined at T ≥ 673 K was found. Titration of the penta-coordinate Al³⁺ sites on the (100) facets of γ-Al₂O₃ by BaO completely eliminated the methanol dehydration reaction activity. These results demonstrate that in alcohol dehydration reactions on γ-Al₂O₃, the (100) facets are the active catalytic surfaces. The observed activities can be linked to the same Al³⁺ ions on both hydrated and dehydrated surfaces: penta-coordinate Al³⁺ ions (Lewis acid sites), and their corresponding –OH groups (Br?nsted acid sites), depending on the calcination temperature.     

A new method of measuring and presenting the membrane fouling potential

The silt density index (SDI) and modified fouling index (MFI) characterisation methods are well known for the evaluation of membrane fouling potential of dispersed particulate matter (suspended solids, colloids) in a feed. The SDI and MFI methods, however, reduce the overall and very complex fouling phenomena into a one number value, on which the interpretation of the fouling potential of the feed is based. Considering such a one number characteristic, a significant amount of information from the fouling measurement (data) is lost. In this paper a concept is introduced in order to preserve such information and supplement the existing indexes. The proposed method measures, processes and presents data in a specific format. To illustrate the concept, some results are shown from measurements on three types of feed. Future systematic research will also include the measurement on some model feeds with, for example, well characterised dispersions for comparison purposes. However, based on the contents of this paper, a discussion on the method could be initiated.