Micelle-hosted palladium nanoparticles catalyze citral molecule hydrogenation in supercritical carbon dioxide

A new approach of employing metal particles in micelles for the hydrogenation of organic molecules in the presence of fluorinated surfactant and water in supercritical carbon dioxide has very recently been introduced. This is allegedly to deliver many advantages for carrying out catalysis including the use of supercritical carbon dioxide (scCO(2)) as a greener solvent. Following this preliminary account, the present work aims to provide direct visual evidence on the formation of metal microemulsions and to investigate whether metal located in the soft micellar assemblies could affect reaction selectivity. Synthesis of Pd nanoparticles in perfluorohydrocarboxylate anionic micelles in scCO(2) is therefore carried out in a stainless steel batch reactor at 40 degreesC and in a 150 bar CO2/H-2 mixture. Homogeneous dispersion of the microemulsion containing Pd nanoparticles in scCO(2) is observed through a sapphire window reactor at W-0 ratios (molar water-to-surfactant ratios) ranging from 2 to 30. It is also evidenced that the use of micelle assemblies as new metal catalyst nanocarriers could indeed exert a great influence on product selectivity. The hydrogenation of a citral molecule that contains three reducible groups (aldehyde, double bonds at the 2,3-position and the 6,7-position) is studied. An unusually high selectivity toward citronellal (a high regioselectivity toward the reduction of the 2,3-unsaturation) is observed in supercritical carbon dioxide. On the other hand, when the catalysis is carried out in the conventional liquid or vapor phase over the same reaction time, total hydrogenation of the two double bonds is achieved. It is thought that the high kinetic reluctance for double bond hydrogenation of the citral molecule at the hydrophobic end (the 6,7-position) is due to the unique micelle environment that is in close proximity to the metal surface in supercritical carbon dioxide that guides a head-on attack of the molecule toward the core metal particle.

High-affinity small molecule-phospholipid complex formation: Binding of siramesine to phosphatidic acid

Siramesine (SRM) is a sigma-2 receptor agonist which has been recently shown to inhibit growth of cancer cells. Fluorescence spectroscopy experiments revealed two distinct binding sites for this drug in phospholipid membranes. More specifically, acidic phospholipids retain siramesine on the bilayer surface due to a high-affinity interaction, reaching saturation at an apparent 1:1 drug-acidic phospholipid stoichiometry, where after the drug penetrates into the hydrocarbon core of the membrane. This behavior was confirmed using Langmuir films. Of the anionic phospholipids, the highest affinity, comparable to the affinities for the binding of small molecule ligands to proteins, was measured for phosphatidic acid (PA, mole fraction Of X-PA = 0.2 in phosphatidylcholine vesicles), yielding a molecular partition coefficient of 240 +/- 80 x 10(6). An MD simulation on the siramesine:PA interaction was in agreement with the above data. Taking into account the key role of PA as a signaling molecule promoting cell growth our results suggest a new paradigm for the development of anticancer drugs, viz. design of small molecules specifically scavenging phospholipids involved in the signaling cascades controlling cell behavior.

Successful manipulation of the quality and quantity of fat and carbohydrate consumed by free-living individuals using a food exchange model

Our objective in this study was to develop and implement an effective intervention strategy to manipulate the amount and composition of dietary fat and carbohydrate (CHO) in free-living individuals in the RISCK study. The study was a randomized, controlled dietary intervention study that was conducted in 720 participants identified as higher risk for or with metabolic syndrome. All followed a 4-wk run-in reference diet [high saturated fatty acids (SF)/high glycemic index (GI)]. Volunteers were randomized to continue this diet for a further 24 wk or to I of 4 isoenergetic prescriptions [high monounsaturated fatty acids (MUFA)/high GI; high MUFA/low GI; low fat (LF)/high GI; and LF/low GI]. We developed a food exchange model to implement each diet. Dietary records and plasma phospholipid fatty acids were used to assess the effectiveness of the intervention strategy. Reported fat intake from the LF diets was significantly reduced to 28% of energy (%E) compared with 38% E from the HM and LF diets. SF intake was successfully decreased in the HM and LF diets was similar to 10% E compared with 17% E in the reference diet (P = 0.001). Dietary MUFA in the HIM diets was similar to 17% E, significantly higher than in the reference (12% E) and LF diets (10% E) (P = 0.001). Changes in plasma phospholipid fatty acids provided further evidence for the successful manipulation of fat intake. The GI of the HGI and LGI arms differed by similar to 9 points (P = 0.001). The food exchange model provided an effective dietary strategy for the design and implementation across multiple sites of 5 experimental diets with specific targets for the proportion of fat and CHO. J. Nutr. 139: 1534-1540, 2009.

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

Cardiovascular risk is determined by the complex interactions between genetic and environmental factors. The apoE genotype represents the most-widely-studied single nucleotide polymorphism in relation to CVD risk, with >3600 publications cited in PubMed. Although originally described as a mediator of lipoprotein metabolism, the lipoprotein-independent functions of apoE are being increasingly recognised, with limited data available on the potential impact of genotype on these metabolic processes. Furthermore, although meta-analyses suggest that apoE4 carriers may have a 40-50% increased CVD risk, the associations reported in individual studies are highly heterogeneous and it is recognised that environmental factors such as smoking status and dietary fat composition influence genotype-phenotype associations. However, information is often derived from observational studies or small intervention trials in which retrospective genotyping of the cohort results in small group sizes in the rarer E2 and E4 subgroups. Either larger well-standardised intervention trials or smaller trials with prospective recruitment according to apoE genotype are needed to fully establish the impact of diet on genotype-CVD associations and to establish the potential of dietary strategies such as reduced total fat, saturated fat, or increased antioxidant intakes to counteract the increased CVD burden in apoE4 carriers.

Dietary manipulation of fatty acid composition in lamb meat and its effect on the volatile aroma compounds of grilled lamb

The effect on lamb muscle of five dietary supplements high in polyunsaturated fatty acids (PUFA) was measured. The supplements were linseed oil, fish oil, protected lipid (high in linoleic acid (C18:2 n-6) and alpha-linolenic acid (C18:3 n-3)), fish oil/marine algae (1:1), and protected lipid/marine algae (1:1). Eicosapentaenoic acid (C20:5 n-3) and docosahexaenoic acid (C22:6 n-3) were found in the highest amounts in the meat from lambs fed diets containing algae. Meat from lambs fed protected lipid had the highest levels of C18:2 n-6 and C18:3 n-3, due to the effectiveness of the protection system. In grilled meat from these animals, volatile compounds derived from n-3 fatty acids were highest in the meat from the lambs fed the fish oil/algae diet, whereas compounds derived from n-6 fatty acids were highest in the meat from the lambs fed the protected lipid diet. (C) 2004 Elsevier Ltd. All rights reserved.

Improved fluorescent proteins for single-molecule research in molecular tracking and co-localization

Three promising variants of autofluorescent proteins have been analyzed photophysically for their proposed use in single-molecule microscopy studies in living cells to compare their superiority to other fluorescent proteins previously reported regarding the number of photons emitted. The first variant under investigation the F46L mutant of eYFP has a 10% greater photon emission rate and > 50% slower photobleaching rate on average than the standard eYFP fluorophore. The monomeric red fluorescent protein (mRFP) has a fivefold lower photon emission rate, likely due to the monomeric content, and also a tenfold faster photobleaching rate than the DsRed fluorescent protein. In contrast, the previously reported eqfp611 has a 50% lower emission rate yet photobleaches more than a factor 2 slowly. We conclude that the F46L YFP and the eqfp611 are superior new options for single molecule imaging and tracking studies in living cells. Studies were also performed on the effects of forced quenching of multiple fluorescent proteins in sub-micrometer regions that would show the effects of dimerization at low concentration levels of fluorescent proteins and also indicate corrections to stoichiometry patterns with fluorescent proteins previously in print. We also introduce properties at the single molecule level of new FRET pairs with combinations of fluorescent proteins and artificial fluorophores.

An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro

G-protein-coupled receptors are desensitized by a two-step process. In a first step, G-protein-coupled receptor kinases (GRKs) phosphorylate agonist-activated receptors that subsequently bind to a second class of proteins, the arrestins. GRKs can be classified into three subfamilies, which have been implicated in various diseases. The physiological role(s) of GRKs have been difficult to study as selective inhibitors are not available. We have used SELEX (systematic evolution of ligands by exponential enrichment) to develop RNA aptamers that potently and selectively inhibit GRK2. This process has yielded an aptamer, C13, which bound to GRK2 with a high affinity and inhibited GRK2-catalyzed rhodopsin phosphorylation with an IC50 of 4.1 nM. Phosphorylation of rhodopsin catalyzed by GRK5 was also inhibited, albeit with 20-fold lower potency (IC50 of 79 nM). Furthermore, C13 reveals significant specificity, since almost no inhibitory activity was detectable testing it against a panel of 14 other kinases. The aptamer is two orders of magnitude more potent than the best GRK2 inhibitors described previously and shows high selectivity for the GRK family of protein kinases.

Effect of molecule branching and glycosidic linkage on the degradation of polydextrose by gut microbiota.

Polydextrose is a randomly linked complex glucose oligomer that is widely used as a sugar replacer, bulking agent, dietary fiber and prebiotic. Polydextrose is poorly utilized by the host and, during gastrointestinal transit, it is slowly degraded by intestinal microbes, although it is not known which parts of the complex molecule are preferred by the microbes. The microbial degradation of polydextrose was assessed by using a simulated model of colonic fermentation. The degradation products and their glycosidic linkages were measured by combined gas chromatography and mass spectrometry, and compared to those of intact polydextrose. Fermentation resulted in an increase in the relative abundance of non-branched molecules with a concomitant decrease in single-branched glucose molecules and a reduced total number of branching points. A detailed analysis showed a preponderance of 1,6 pyranose linkages. The results of this study demonstrate how intestinal microbes selectively degrade polydextrose, and provide an insight into the preferences of gut microbiota in the presence of different glycosidic linkages.

Force distribution in manipulation by a robot hand with equality and inequality constraints

The problem of the appropriate distribution of forces among the fingers of a four-fingered robot hand is addressed. The finger-object interactions are modelled as point frictional contacts, hence the system is indeterminate and an optimal solution is required for controlling forces acting on an object. A fast and efficient method for computing the grasping and manipulation forces is presented, where computation has been based on using the true model of the nonlinear frictional cone of contact. Results are compared with previously employed methods of linearizing the cone constraints and minimizing the internal forces.

Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells

Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI–Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). An interaction between the p85 regulatory subunit of PI3K and the scaffolding molecule Grb-2-associated binding protein-1 (Gab1), which is regulated by binding of the Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to Gab1, has been shown in other cell types to sustain PI3K activity to elicit cellular responses. Platelet endothelial cell adhesion molecule-1 (PECAM-1) functions as a negative regulator of platelet reactivity and thrombosis, at least in part by inhibiting GPVI–FcR-chain signaling via recruitment of SHP-2 to phosphorylated immunoreceptor tyrosine-based inhibitory motifs in PECAM-1. Objective: To investigate the possibility that PECAM-1 regulates the formation of the Gab1–p85 signaling complexes, and the potential effect of such interactions on GPVI-mediated platelet activation in platelets. Methods: The ability of PECAM-1 signaling to modulate the LAT signalosome was investigated with immunoblotting assays on human platelets and knockout mouse platelets. Results: PECAM-1-associated SHP-2 in collagen-stimulated platelets binds to p85, which results in diminished levels of association with both Gab1 and LAT and reduced collagen-stimulated PI3K signaling. We therefore propose that PECAM-1-mediated inhibition of GPVI-dependent platelet responses result, at least in part, from recruitment of SHP-2–p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules, such as Gab1 and LAT.

FACSGen: a tool to synthesize emotional facial expressions through systematic manipulation of facial action units

To investigate the perception of emotional facial expressions, researchers rely on shared sets of photos or videos, most often generated by actor portrayals. The drawback of such standardized material is a lack of flexibility and controllability, as it does not allow the systematic parametric manipulation of specific features of facial expressions on the one hand, and of more general properties of the facial identity (age, ethnicity, gender) on the other. To remedy this problem, we developed FACSGen: a novel tool that allows the creation of realistic synthetic 3D facial stimuli, both static and dynamic, based on the Facial Action Coding System. FACSGen provides researchers with total control over facial action units, and corresponding informational cues in 3D synthetic faces. We present four studies validating both the software and the general methodology of systematically generating controlled facial expression patterns for stimulus presentation.

The molecular structure of propylene sulphide (methylthiirane) by gas-phase electron diffraction and theoretical calculations: a molecule used in MOCVD

Gas-phase electron-diffraction (GED) data together with results from ab initio molecular orbital calculations have been used to determine the structure of propylene sulphide. Values found for the main structural parameters for the molecule are consistent with those obtained from microwave studies and are compared here with those found for similar sulphur containing rings of general formula S(CH2)n (n = 2–5). A high ring strain enthalpy was calculated for propylene sulphide which is consistent with the small C–S–C angle (48.2(6)degrees) and the relatively long C–S bond lengths (ra = 1.831(2) Å). This is thought to account for the ease of ring opening in propylene sulphide observed in MOCVD reactions and the ready polymerisation of the molecule.

Rotational symmetry of a methane molecule and the bond angle

The rotational symmetry of a methane molecule can be used to great advantage to calculate the bond angle. The problem is worked out in this article.