The article presents a new concept for vascular endoprothesis (stent). Almost all commercially available stents are made of metallic materials. A common after effect of stent implantation is ...restenosis. Several studies on metal stents coated with drug show, that the use of a drug delivery system may reduce restenosis. The purpose of this work is to develop a new stent for the drug delivery application. The shape memory properties of thermoplastic polyurethane allow to design a new fully polymeric self-expandable stent. The possibility to use the stent as a drug delivery system is described.
Bacteria possess surface properties, related to their charge, hydrophobicity and Lewis acid/base characteristics, that are involved in the attachment processes of microorganisms to surfaces. ...Fermentation bulks and food matrixes are complex heterogeneous media containing various components with different physicochemical characteristics. The aim of the present study was to investigate whether (i) bacteria present in a food matrix, interacted physicochemically at their surface level with the other constituents and (ii) the diversity of bacterial surface properties could result in a diversity of microbial adhesion to components and thus in a diversity of tolerance to toxic compounds. The surface properties of 20 lactic acid bacteria were characterized by the MATS method showing their relatively hydrophilic and various basic characteristics. The results obtained from a set of representative strains showed that (i) the strains with higher affinity for apolar solvents adsorbed more to lipids and hydrophobic compounds, (ii) the more the strains adsorbed to a toxic solvent, the less they were tolerant to this solvent. A diversity of bacterial surface properties was observed for the strains in the same species showing the importance of choosing bacteria according to their surface properties in function of technological objectives.
Bacteria possess physicochemical surface properties such as hydrophobicity, Lewis acid/base and charge which are involved in physicochemical interactions between cells and interfaces. Moreover, food ...matrices are complex and heterogeneous media, with a microstructure depending on interactions between the components in media (van der Waals, electrostatic or structural forces, etc.). Despite the presence of bacteria in fermented products, few works have investigated how bacteria interact with other food components. The objective of the present study was to determine the effects of the surface properties of lactic acid bacteria on the stability of model food emulsions. The bacteria were added to oil/water emulsions stabilized by milk proteins (sodium caseinate, whey proteins concentrate or whey proteins isolate) at different pH (from 3 to 7.5). The effect of bacteria on the emulsions stability depended on the surface properties of strains and also on the characteristics of emulsions. Flocculation and aggregation phenomena were observed in emulsion at pHs for which the bacterial surface charge was opposed to the one of the proteins. The effects of bacteria on the stability of emulsion depended also on the concentration of cations present in media such as Ca
2+. These results show that the bacteria through their surface properties could interact with other compounds in matrices, consequently affecting the stability of emulsions. The knowledge and choice of bacteria depending on their surface properties could be one of the important factors to control the stability of matrices such as fermentation media or fermented products.
The interactions between aroma compounds and other particles in foods, particularly with macromolecules, have been greatly studied in order to better understand the binding of flavors in food ...matrices. Bacteria possess many macromolecules on their cellular surface that provide them surface properties which are involved in the physicochemical interactions between cells and interfaces. However, the interactions between bacteria and aroma compounds have not received so much attention despite the presence of bacteria in many fermented products. In order to study the retention of aroma compounds by bacteria, we have investigated the retention of esters by lactic acid bacteria with static headspace techniques. Two strains of
Lactococcus lactis subsp.
lactis biov. diacetylactis reflecting the natural diversity of the bacterial surface properties and two ethyl esters generally involved in the cheese flavor (ethyl acetate and ethyl hexanoate) were chosen for the experiments. The results have shown that bacteria, through their surface physicochemical properties, can interact directly with aroma compounds or in an indirect way, by changing the emulsion characteristics. However, these effects depend on the physicochemical properties of both aroma compounds and bacterial surfaces.
In an integrative approach, we studied the role of histamine H
receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction ...in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wild-type mice. By contrast, in the same preparations from mice that overexpressed the human H
receptor in a cardiac-specific way, histamine exerted concentration- and time-dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H
receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic but not in wild-type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice and isolated perfused hearts (Langendorff preparation). Phosphorylation of phospholamban was increased in atrial and ventricular preparations from transgenic mice, but not in wild-type animals. The effects of histamine were mimicked by dimaprit and amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiologic and pathophysiologic cardiac role of the human H
receptor.
Lipids are an important source of aroma compounds. In foods, lipids are degraded or modified by enzymatic activities that are originally present in the raw materials or that develop later due to the ...growth of microorganisms. Mimicking these natural pathways, some processes have been developed to produce aroma compounds in bioreactors. In this review we describe the production of aroma compounds from different families: lactones, green notes and ionones. We focus on points that are specific to these reactions in heterogeneous media: physicochemical forces involved in the interactions between the substrate, product and biocatalyst, transfers between the phases and, as the degradation of lipids often requires an oxidation step, on the problems of oxygenation of the reactors.
Aim
Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ...ventricular tachycardia. Using a CSQ2 knockout mouse, we wanted to study also the atrial function of CSQ2.
Methods
The influence of CSQ2 on atrial function and, for comparison, ventricular function was studied in isolated cardiac preparations and by echocardiography as well as electrocardiography in mice with deletion of CSQ2.
Results
Using deletion of exon 1, we have successfully generated a constitutive knockout mouse of the calsequestrin 2 gene (CSQ2−/−). CSQ2 protein was absent in the heart (atrium, ventricle), but also in oesophagus and skeletal muscle of homozygous knockout mice. In 6‐month‐old CSQ2−/− mice, relative left atrial weight was increased, whereas relative heart weight was unchanged. The staircase phenomena in paced left atrial preparations on force of contraction and the post‐rest potentiation were different between wild type and CSQ2−/− indicative for a decreased sarcoplasmic Ca2+ load and supporting an important role of CSQ2 also in the atrium. The incidence of arrhythmias was increased in CSQ2−/−. In 2‐year‐old CSQ2−/− mice, cardiac hypertrophy and heart failure were noted possibly as a result of chronically increased cytosolic Ca2+ levels.
Conclusion
These data suggest a functional role of CSQ2 not only in the ventricle but also in the atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias, but also cardiac hypertrophy and heart failure.
The alkane-assimilating yeast
Yarrowia lipolytica degrades very efficiently hydrophobic substrates such as
n-alkanes, fatty acids, fats and oils for which it has specific metabolic pathways. An ...overview of the oxidative degradation pathways for alkanes and triglycerides in
Y. lipolytica is given, with new insights arising from the recent genome sequencing of this yeast. This includes the interaction of hydrophobic substrates with yeast cells, their uptake and transport, the primary alkane oxidation to the corresponding fatty alcohols and then by different enzymes to fatty acids, and the subsequent degradation in peroxisomal β-oxidation or storage into lipid bodies. Several enzymes involved in hydrophobic substrate utilisation belong to multigene families, such as lipases/esterases (
LIP genes), cytochromes P450 (
ALK genes) and peroxisomal acyl-CoA oxidases (
POX genes). Examples are presented demonstrating that wild-type and genetically engineered strains of
Y. lipolytica can be used for alkane and fatty-acid bioconversion, such as aroma production, for production of SCP and SCO, for citric acid production, in bioremediation, in fine chemistry, for steroid biotransformation, and in food industry. These examples demonstrate distinct advantages of
Y. lipolytica for their use in bioconversion reactions of biotechnologically interesting hydrophobic substrates.
Background
Improved Phase 2 study designs may increase success rates in late stage AD trials. Varoglutamstat (PQ912) is an oral small molecule glutaminyl cyclase inhibitor designed to address several ...key disease mechanisms. A Phase 2A study (NCT02389413) of 120 early AD patients treated for 12 weeks provided preliminary evidence of safety and tolerability, and effects on working memory, CSF biomarkers, and synaptic function (EEG theta‐power).
Objective
To design a well‐powered, safe, and efficient study of varoglutamstat in early AD incorporating adaptive dose selection in Phase 2A, a futility analysis testing pharmacological, biological and cognitive criteria, and a seamless transition to a larger Phase 2B study investigating longer‐term efficacy and safety.
Methods
An efficient and safe selection rule across 3 descending doses (600mg, 300mg, 150 mg BID) was established using a continuously monitored Pocock safety boundary targeting a set of treatment emergent AE’s of interest. Well‐powered stage‐gate criteria at a planned interim futility analysis included thresholds for target occupancy in plasma, and would detect negative effects on a cognitive composite or absence of benefit on EEG theta‐power. The Phase 2B study was powered to detect an effect size of 0.7 points on the Clinical Dementia Rating – Sum of Boxes score at 18 months, an established approvable endpoint.
Results
The on‐going Phase 2A adaptive dose‐finding trial (NCT03919162) is randomizing 180 subjects with MCI or mild probable AD, initially to 24+ weeks of 600mg varoglutamstat dose or placebo, BID. If the safety boundary is hit, the dose will be discontinued and all subjects titrated down, with similar sequential testing of lower doses as needed. The interim futility analysis will occur when the first 180 randomized subjects have been on study for at least 24 weeks. If this stage‐gate is passed, Phase 2B will enroll 234 additional patients to achieve 414 total patients treated for 72 weeks at full dose of varoglutamstat or placebo.
Conclusion
This novel study design enables adaptive dose selection, an early interim futility analysis, and longer‐term determination of cognitive and functional efficacy, and should support robust proof‐of‐concept for varoglutamstat using a total sample of 414 subjects treated for 72 weeks.
Lactobacillus pentosus is one of the few lactic acid bacteria (LAB) species capable of surviving in olive brine, and thus desirable during table olive fermentation. We have recently generated mutants ...of the efficient strain L. pentosus C11 by transposon mutagenesis and identified five mutants unable to survive and adapt to olive brine conditions. Since biofilm formation represents one of the main bacterial strategy to survive in stressful environments, in this study, the capacity of adhesion and formation of biofilm on olive skin was investigated for this strain and five derivative mutants which are interrupted in metabolic genes (enoA1 and gpi), and in genes of unknown function (“oba” genes). Confocal microscopy together with bacteria count revealed that the sessile state represented the prevailing L. pentosus C11 life-style during table olive fermentation. The characterization of cell surface properties showed that mutants present less hydrophobic and basic properties than the wild type (WT). In fact, their ability to adhere to both abiotic (polystyrene plates) and biotic (olive skin) surfaces was lower than that of the WT. Confocal microscopy revealed that mutants adhered sparsely to the olive skin instead of building a thin, multilayer biofilm. Moreover, RT-qPCR showed that the three genes enoA1, gpi and obaC were upregulated in the olive biofilm compared to the planktonic state. Thus enoA1, gpi and “oba” genes are necessary in L. pentosus to form an organized biofilm on the olive skin.
•L. pentosus C11 prevails in sessile state during olive fermentation.•Mutants were impaired in adhesion to abiotic and biotic surfaces.•oba, enoA1 and gpi genes are required for biofilm formation on the olive skin.•Olive surface is a biotic support for L. pentosus C11 adhesion and biofilm formation.
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