A health concern regarding the protein corona, aggregation and disaggregation

Nanoparticle (NP)-protein complexes exhibit the correct identity of NP in biological media. Therefore, protein-NP interactions should be closely explored to understand and to modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, the morphology of NPs and influence of medium pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of methods. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP-protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in the in vivo experiments.Comment: 40 pages, 20 figure

EFFECTS OF ORALLY ADMINISTERED ENTEROCOCCUS FAECIUM ON THE IMMUNE SYSTEMIC RESPONSE AND INTESTINAL EPITHELIAL STRUCTURE IN BALB/C MICE IMMUNIZED BY BOVINE Î’-LACTOGLOBULIN

Objective: Determine the effect of Enterococcus faecium on systemic immune response and its effect on the intestinal epithelial structure in the Balb/c mice. Methods: Thirty Balb/c mice were dispatched in three lots of 10 mice each. During an initial period of 18 days, the animals from the first lot received via an oral way suspension of 0,3 mL containing 108 ufc/mL of Enterococcus faecium,for the second and the third lot received 0,3 mL of a saline solution. In a second period of time, mice from the first and second lots were immunised via parenteral way using β-Lg. Then they were sacrified on the 50th day after the end of the first period (18 days). The level of IgG anti-β-Lg was determined in the sera by the ELISA, and histologic studies were conducted on the jejunum fragments. Results: Our results show that anti β-Lactoglobulin IgG titers were significantly reduced in immunized mice that received the Enterococcus faecium (1/280th) (***p<0,001). The histological studies of the intestinal epithelium shows long intestinal villi (53,88 ± 1,38µm) with diminished intra-epithelial lymphocytes. Conclusion: The study shows that Enterococcus faecium PC4.1 may help protect the intestinal epithelium integrity by maintaining the structure of the villi and has the ability to decrease the systemic immune response to β-lactoglobulin

Phenotypic and genotypic characterization of lactic acid bacteria isolated from Azerbaijani traditional dairy products

Studied lactic acid bacteria (LAB) were isolated from two types of final ready-to-eat artisanal dairy products (cheeses-Agdas, Sheki and yogurts-Karabakh, Ganja and Baku) manufactured in Azerbaijan. The Agdas cheese belongs to the group of semi hard cheeses whilst the Sheki cheese belongs to hard cheeses. Both of cheeses were produced from cow's milk without the addition of the starter cultures. The Karabakh and Baku yogurts were produced from bovine's milk and the Ganja yogurt from buffalo's milk. Overall 378 isolates were collected from these dairy products and 296 of them were Gram-positive and catalase-negative. It was determined using biochemical tests and molecular methods that four species of LAB were mostly present in these cheeses: Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus paraplantarum and Enterococcus faecium while in yogurts, Lactobacillus delbrueckii subsp. lactis, Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus and Enterococcus faecium dominated. Five enterococci were producers of antimicrobial compounds

The Strathclyde Evaluation of Children's Active Travel (SE-CAT): study rationale and methods

Peer reviewedPublisher PD

Higher Order Perturbation Calculation for Deformed Nuclei

The shape of the nucleus plays an important role in various nuclear phenomena. It is now generally agreed, in the nuclear shell model, that nuclei with each shell filled with nucleons have a spherical shape, and that those nuclei with some protons and neutrons missing from the last shell, deviate from a sphere. The problem of spheroidal shape has been investigated by several methods. Investigation of asymmetric nuclear deformations, which have been suggested by experimental evidence, is still in its early stages due mainly to the mathematical complexity involved in solving the wave equation for an asymmetric potential. Lee and Inglis have investigated asymmetric deformations using the spheroidal harmonic oscillator potential and a perturbation which causes a pear-shape. They were, however, unable to show that such a nucleus is stable in the second order approximation. This problem has recently been investigated further by Lee and others by employing Nilsson\u27s model where the spherical harmonic oscillator is chosen as the basic representation. It is, however, interesting to compare the results from the two procedures since the wave functions used by Lee and Inglis are correct ones, although they have ignored the spin-orbit coupling term. To further pursue the investigation of asymmetric deformations using the perturbed spheroidal harmonic oscillator, it is necessary to extend perturbation theory to include the fourth order term as given in Chapter II. In Chapter III, the matrix elements allowed by the harmonic oscillator quantum numbers are calculated. In Chapter IV the fourth order energy term resulting from the incorporation of these matrix elements is given

Ingénierie de la b-lactoglobuline bovine (étude de l'agrégation, de la stabilité et de l'interaction avec des ligands hydrophobes)

Ce travail a porté sur la production et la caractérisation de mutants de la b-lactoglobuline (BLG) bovine. Le mutant C121S a permis d'éliminer le groupe thiol libre de la BLG. Sa structure est similaire à celle de la protéine native. La mutation inhibe la dénaturation irréversible de la BLG induite par le chauffage et diminue sa stabilité: le mutant est davantage sensible à la température, aux agents réducteurs et à l'hydrolyse pepsique. La mutation semble avoir affecté la flexibilité de la protéine. Sept autres mutants ont éte choisis par modélisation moléculaire afin d'augmenter l'affinité de la BLG pour le rétinol et l'acide palmitique (modification des résidus K69 et A86). Six ont été purifiés et étaient correctement repliés. Des modifications structurales ont été mises en évidence pour deux d'entre eux. Les mutations ont permis l'augmentation de l'affinité de la BLG pour le rétinol ( 5) et l'acide palmitique ( 10). Ces résultats ont été corrélés aux prévisions par modélisation.This study was carried out on the production and characterization of bovine b-lactoglobulin (BLG) mutants. The C121S mutant allowed elimination of the free thiol group of BLG. Its structure is similar to that of native protein. The mutation inhibits the heat-induced irreversible denaturation of BLG and decreases its stability: the mutant is more sensitive to temperature, reducing agents and peptic hydrolysis. The mutation seems to have perturbed the protein flexibility. Seven other mutants were chosen by molecular modeling to increase BLG affinity for retinol and palmitic acid (substitutions of residues K69 and A86). Six mutants could be purified and were properly folded. Some structural modifications were pointed out in two of them. The mutations enhanced BLG affinity for retinol (5 fold) and palmitic acid (10 fold). These results were correlated to the previsions from molecular modeling.NANTES-BU Sciences (441092104) / SudocSudocFranceF

Clonage et caractérisation de récepteurs de type olfactif humains exprimés dans la langue

L'expression de récepteurs de type olfactif (OLRs) dans les bourgeons gustatifs de rat a été rapportée, suggérant leur implication dans la perception du goût en tant que récepteurs gustatifs. L'objectif de cette thèse était d'identifier et de caractériser des OLRs exprimés dans les tissus gustatifs humains. Neuf gènes et huit pseudogènes d'OLRs exprimés dans la langue humaine adulte et/ou fœtale ont été identifiés par RT-PCR. Leurs orthologues murins ont été déterminés : 5 sont exprimés dans la langue de souris adulte, dont 3 spécifiquement dans les papilles gustatives. Ils sont tous exprimés dans les tissus sensoriels et le cerveau, mais sont rarement détectés dans d'autres organes. L'un d'eux semble cependant présenter une expression ubiquitaire. Les expériences d'hybridation in situ, n'ont pas permis de détecter clairement l'expression de ces récepteurs dans les cellules gustatives. Un outil cellulaire visant à identifier les ligands de ces récepteurs a été construit.The expression of olfactory like receptors (OLRs) in rat taste buds has been previously described, suggesting their involvement in taste perception as gustatory receptors. The aim of this work was to identify and characterize human OLRs expressed in human gustatory tissues. Nine OLRs genes and eight pseudogenes expressed in human adult and/or foetal tongue were identified by RT-PCR. Their murine orthologs were assigned: 5 are expressed in adult mouse tongue, among which 3 are expressed specifically in gustatory papillae. The latter were detected in sensory tissues and brain, but rarely in other organs. Nevertheless, one of them seems to be ubiquitously expressed. In situ hybridization experiments did not show a clear expression of these receptors in mouse taste buds. A cellular tool was constructed in order to identify the ligands of these receptors.NANTES-BU Sciences (441092104) / SudocSudocFranceF

Proteolytic and antimicrobial activities of lactic acid bacteria isolated from traditional Azerbaijani fermented dairy products

Ce travail a été consacré à la recherche des activités protéolytiques et antibactériennes de bactéries lactiques isolées de produits laitiers fermentés traditionnels d Azerbaïdjan. Les souches étudiées ont été isolées de 46 échantillons de produits laitiers fermentés, obtenus dans différentes régions d Azerbaïdjan. Huit souches ayant une activité protéolytique notable ont été purifiées et identifiées par amplification et par séquençage de l ADN 16S comme étant Lactobacillus helveticus (1 souche), Lactobacillus paracasei subsp. paracasei (1 souche), Enterococcus faecalis (6 souches). Deux souches (1 Lactobacillus curvatus et 1 Enterococcus faecium) ayant une activité antibactérienne ont été purifiées et caractérisées. Les activités protéolytiques de ces souches ont été étudiées dans 2 systèmes: croissance dans du lait UHT et système cellulaire non prolifératif. Ces souches hydrolysent toutes les fractions de caséines ce qui démontre leur similarité avec les protéases de type PIII de Lactococcus. Les optima de température et de pH d activité protéolytique sont de 37-45 C et de pH neutre. Les effets de différents inhibiteurs sur les activités protéolytiques indiquent que les souches étudiées produisent des métallo-, sérine- et cystéine-protéases. Ces résultats ont été confirmés par l analyse des souches par PCR gène spécifique avec des amorces de protéases de bactéries lactiques. L'immuno réactivité des caséines b et aS1 mesurée par interaction avec les IgE peut être considérablement réduite par hydrolyse avec Lactobacillus helveticus A75 et Enterococcus faecalis AN1 à la suite de la destruction des épitopes linéaires des IgE. Les souches productrices de bactériocines étudiées dans ce travail inhibent la croissance des souches de bactéries lactiques étroitement liées et aussi des souches pathogènes comme Listeria monocytogenes et Bacillus cereus. La souche Lactobacillus curvatus A61 a également une activité antifongique. Le mode d action de leurs bactériocines dépendant de l organisme test utilisé était bactériostatique ou bactéricide. Enterococcus faecium AQ71 possède les gènes codant pour les enterocines P, L50A/B et A ; la souche Lactobacillus curvatus A61 présente un gène de curvacine. Les substances produites par les souches de LAB azerbaïdjanaises sont stables à la chaleur et actives dans une large gamme de pH. L'analyse des souches par des méthodes de biologie moléculaire a révélé l'absence de gènes de facteurs de virulence. Les souches étudiées ne présentaient pas de multi-résistance aux antibiotiques. Par ailleurs, les souches de LAB azerbaïdjanaises étudiées dans ce travail sont résistantes aux concentrations physiologiques de sels biliaires, ce qui est l une des caractéristiques principales des probiotiques. L ensemble de ces résultats montre que les souches de LAB azerbaïdjanaises sélectionnées, productrices de bactériocines et de protéases, peuvent être utilisées sans risque majeur comme levains ou en co-culture dans les processus de fabrication alimentaire.This thesis was devoted for the study of proteolytic and antimicrobial activities of LAB isolated from traditional Azerbaijani fermented dairy products. LAB isolation was done from 46 samples of traditional fermented dairy products obtained from different regions of Azerbaijan. As a result of the screening 10 new LAB strains were isolated, from which 8 were proteolytic and belong to the species Lactobacillus helveticus (1 strain), Lactobacillus paracasei subsp. aracasei (1 strain) and Enterococcus faecalis (6 strains). Two strains were producers of bacteriocins and belong to species Enterococcus faecium and Lactobacillus curvatus. Specificity of proteolytic activities of studied LAB strains depended on the substrate cleaved and on bacterial growth phase. Found proteolytic activities were mainly directed against caseins. The optimal hydrolysis of substrates by studied strains was observed at 37-45 and at neutral pH range. The studied strains produced several proteases, mainly metallo- and serine- proteases. The proteolysis of caseins by strains Lactobacillus helveticus 75 and Enterococcus faecalis AN1 decreased their immunoreactivity as a result of lytic destruction of IgE binding linear epitopes. The studied bacteriocinogenic strains inhibited the growth of closely related LAB strains and also pathogens such as Listeria monocytogenes, Bacillus cereus. Lactobacillus curvatus A61 also displayed antifungal activity. The mode of action of found bacteriocins was dependent on the test-organism used and was bacteriostatic or bactericidal. Enterococcus faecium AQ71 possesses genes coding enterocins , L50A/B and A. Lactobacillus curvatus A61 possesses the structural gene of curvacin A. Antimicrobial substances produced by the studied LAB strains are heat stable and active in broad pH range. The studied Azerbaijani LAB do not possess the virulence factors and multi-resistance to antibiotics. Thus they are safe for industrial application. Moreover, the studied Azerbaijani LAB strains are resistant to physiological concentrations of bile salts, what is one of the main characteristics of probiotic strains. All these results suggest that the studied bacteriocinogenic and proteolytic strains could be used safely as starter and co-cultures for the food industry.NANTES-BU Sciences (441092104) / SudocSudocFranceF