Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms

Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases.     

Quantitative risk assessment of listeriosis due to consumption of raw milk

The objectives of this study were to estimate the risk of illness for raw milk consumers due to Listeria monocytogenes in raw milk sold by permitted dealers, and the risk for people on farms who consume raw milk. Three scenarios were evaluated for raw milk sold by dealers: raw milk purchased directly from bulk tanks, from on-farm stores, and from retail. To assess the effect of mandatory testing of raw milk by regulatory agencies, the number of listeriosis cases per year was compared where no raw milk testing was done, only a screening test to issue a permit was conducted, and routine testing was conducted and milk was recalled if it was L. monocytogenes positive. The median number of listeriosis cases associated with consumption of raw milk from bulk tanks, farm stores, and retail for an intermediate-age population was 6.6 × 10(-7), 3.8 × 10(-5), and 5.1 × 10(-5) cases per year, respective ly. In populations with high susceptibility, the estimated median number of cases per year was 2.7 × 10(-7) (perinatal, i.e., pregnant women and their fetuses or newborns) and 1.4 × 10(-6) (elderly) for milk purchased from bulk tanks, 1.5 × 10(-5 ) (perinatal) and 7.8 × 10(-5) (elderly) for milk from farm stores, and 2.1 × 10(-5) (perinatal) and 1.0 × 10(-4) (elderly) for milk from retail. For raw milk consumed on farms, the median number of listeriosis cases was 1.4 × 10(-7) cases per year. A greater risk of listeriosis was associated with consumption of raw milk obtained from retail and farm stores as compared with milk obtained from bulk tanks. This was likely due to additional time-temperature combination steps in the retail and farm store models, which increased the chances for growth of L. monocytogenes in raw milk. A close relationship between prevalence of L. monocytogenes in raw milk and the values of disease incidence was observed. Hence, a reduction in the number of cases per year in all populations was observed when a raw milk-testing program was in place, especially when routine testing and recalling of milk was conducted.     

Mathematical model of Listeria monocytogenes cross-contamination in a fish processing plant

Listeriosis is a foodborne disease caused by the bacterium Listeria monocytogenes. The food industry and government agencies devote considerable resources to reducing contamination of ready-to-eat foods with L. monocytogenes. Because inactivation treatments can effectively eliminate L. monocytogenes present on raw materials, postprocessing cross-contamination from the processing plant environment appears to be responsible for most L. monocytogenes food contamination events. An improved understanding of cross-contamination pathways is critical to preventing L. monocytogenes contamination. Therefore, a plant-specific mathematical model of L. monocytogenes cross-contamination was developed, which described the transmission of L. monocytogenes contamination among food, food contact surfaces, employees' gloves, and the environment. A smoked fish processing plant was used as a model system. The model estimated that 10.7% (5th and 95th percentile, 0.05% and 22.3%, respectively) of food products in a lot are likely to be contaminated with L. monocytogenes. Sensitivity analysis identified the most significant input parameters as the frequency with which employees' gloves contact food and food contact surfaces, and the frequency of changing gloves. Scenario analysis indicated that the greatest reduction of the within-lot prevalence of contaminated food products can be achieved if the raw material entering the plant is free of contamination. Zero contamination of food products in a lot was possible but rare. This model could be used in a risk assessment to quantify the potential public health benefits of in-plant control strategies to reduce cross-contamination.     

Pep19 Has a Positive Effect on Insulin Sensitivity and Ameliorates Both Hepatic and Adipose Tissue Phenotype of Diet-Induced Obese Mice

Peptide DIIADDEPLT (Pep19) has been previously suggested to improve metabolic parameters, without adverse central nervous system effects, in a murine model of diet-induced obesity. Here, we aimed to further evaluate whether Pep19 oral administration has anti-obesogenic effects, in a well-established high-fat diet-induced obesity model. Male Swiss mice, fed either a standard diet (SD) or high-fat diet (HFD), were orally administrated for 30 consecutive days, once a day, with saline vehicle or Pep19 (1 mg/kg). Next, several metabolic, morphological, and behavioral parameters were evaluated. Oral administration of Pep19 attenuated HFD body-weight gain, reduced in approximately 40% the absolute mass of the endocrine pancreas, and improved the relationship between circulating insulin and peripheral insulin sensitivity. Pep19 treatment of HFD-fed mice attenuated liver inflammation, hepatic fat distribution and accumulation, and lowered plasma alanine aminotransferase activity. The inguinal fat depot from the SD group treated with Pep19 showed multilocular brown-fat-like cells and increased mRNA expression of uncoupling protein 1 (UCP1), suggesting browning on inguinal white adipose cells. Morphological analysis of brown adipose tissue (BAT) from HFD mice showed the presence of larger white-like unilocular cells, compared to BAT from SD, Pep19-treated SD or HFD mice. Pep19 treatment produced no alterations in mice behavior. Oral administration of Pep19 ameliorates some metabolic traits altered by diet-induced obesity in a Swiss mice model.     

In vivo assessment of the corrosion of nickel–titanium orthodontic archwires by using scanning electron microscopy and atomic force microscopy

This study was undertaken to assess in vivo the corrosion in two commercial nickel–titanium (NiTi) orthodontic archwires removed from the oral cavity of patients using fluoride mouthwashes. Five volunteers took part in this study on the corrosion behavior of two brands of NiTi archwires (3M and AO (brand of archwire)) during use of two mouthwashes with neutral sodium fluoride 1.1%, one with acidulated fluoride 1.1%, and one with placebo and a control group. Each patient used one mouthwash in three different periods of time for 1 min a day for 30 days. The archwires were assessed with scanning electron microscopy and atomic force microscopy for qualitative and quantitative analysis. The values obtained with atomic force microscopy (AFM) were submitted to normality test, two‐way analysis of variance, and Tukey's test at a significance level of 5%. The AFM images showed a gradual qualitative increase in the roughness of both types of wire between the treatments: control < placebo < neutral fluoride < acidulated fluoride. The arithmetic average of the roughness and root mean square of the roughness were similar. As for 3M archwires, only the acidulated fluoride group differed statistically from the others. As for AO archwires, the control and placebo groups did not differ from each other, but differed from the other fluoride treatments. The group using neutral fluoride also differed significantly from the acidulated fluoride group. 3M archwires were not affected by daily oral challenges. AO archwires were not affected by daily oral challenges either; their association with fluoride, either neutral or acidulated, increased their roughness.     

Light olefins dimerization to high quality gasoline components

New attractive technologies can be designed in the field of light olefins dimerization (C₃–C₅) in order to obtain products useful as gasoline blending components; the technologies are characterized both by low investment costs and by high product quality. Isobutene dimerization is a powerful alternative to MTBE production whenever the use of the latter will be forbidden in gasoline. Also the dimerization of iso-amylenes and propylene, when properly designed, can give products (both the olefins and the corresponding hydrogenated derivatives) characterized by very high octane numbers. More in general all these technologies can help to debottleneck the FCC downstream when enhanced olefins production is achieved by means of new FCC catalysts and processes.     

Detoxification in Relation to Toxin Tolerance in Desert Woodrats Eating Creosote Bush

We studied the relationship between the use of three detoxification pathways and urine pH and the tolerance of desert woodrats from two populations to a mixture of naturally occurring plant secondary metabolites (mostly phenolics) in resin from creosote bush (Larrea tridentata). The two populations of desert woodrats came from the Mojave desert (Mojave woodrats), where woodrats consume creosote bush, and from the Great Basin desert (Great Basin woodrats), where the plant species is absent. We fed woodrats alfalfa pellets containing increasing levels of the phenolic resin and measured three detoxification pathways and urine pH that are related to detoxification of allelochemicals. We found that the excretion rate of two phase II detoxification conjugates, glucuronides and sulfides, increased with increasing resin intake, whereas excretion of hippuric acid was independent of resin intake, although it differed between populations. Urine pH declined with increasing resin ingestion. The molar proportion of glucuronides in urine was three times that of the other conjugates combined. Based on an evaluation of variation in the three detoxification pathways and urine pH in relation to resin intake, we rejected the hypotheses that woodrats' tolerance to resin intake is related to capacity for amination, sulfation, or pH regulation. However, Mojave woodrats had higher maximum glucuronide excretion rates, and we accepted the hypothesis that within and between populations woodrats tolerate more resin because they have a greater capacity for glucuronide excretion.     

Toward a model of socializing project team members: An integrative approach

Project work is becoming more and more important in everyday business, as is staffing the right newcomers for the project. Recognizing that not all new project team workers possess equally important specific knowledge, skills and abilities for the success of projects, we draw on project management, human resource management, and organizational socialization literature to develop a framework on how new project team members might be socialized, depending on their strategic value for the project. We specifically draw on the socialization tactics literature and propose how four categories of new employees – Internal specialists, External specialists, External generalists and Internal generalists; based on two dimensions – work task complexity and employment mode, can be socialized more effectively. Implications for theory and practice are discussed as well.     

Physico-chemical properties and antibacterial activity of modified egg white—lysozyme

Lysozyme (N-acetyl-muramyl-hydrolase E.C. 3.2.1.17) is a low-molecular enzyme (14,400 Da) found in body secretions, systemic fluids and tissues of humans and animals. Antibacterial activity of lysozyme monomer is limited first of all to Gram-positive bacteria, which is connected with the structure of the cell wall. This enzyme catalyzes hydrolysis of β-glycoside bonds (1–4), releasing N-acetylglucosamine and N-acetylmuramic acid. The spectrum of antibacterial activity of lysozyme may be extended thanks to modifications of the enzyme. The aim of the study was to assess antibacterial activity, hydrolytic activity and surface hydrophobicity of different forms of lysozyme. Chemical and thermo-chemical modification of lysozyme was performed, and the antibacterial action of lysozyme monomer and modified preparations were compared. It was found that in comparison with monomer and the control, all modified preparations exhibit effective action against Gram (−) bacteria Pseudomonas fluorescens. A particularly effective action was found in case of lysozyme subjected to thermo-chemical modification, which was characterized by the highest proportion of oligomeric forms and the highest hydrophobicity.     

Adsorption of Cu, Cd, and Ni on goethite in the presence of natural groundwater ligands

The adsorption of copper, cadmium, and nickel on goethite was examined in natural groundwater samples from an infiltration site of the river Glatt at Glattfelden (Switzerland). Unfractionated dissolved organic matter was used at its natural concentrations. Metal concentrations were close to environmental conditions. Cu, Cd, and Ni presented the typical pH adsorption edge of cations. The major influence on metal adsorption was due to a strong organic ligand L(I), which inhibited adsorption of Cu, Cd, and Ni in the alkaline pH region. Complexation of Cu, Cd, and Ni by the natural organic ligands was described with a model defining a minimum number of discrete ligands: a strong ligand L(I) at low concentration and additional weaker ligands with higher concentrations. The adsorption of Cu, Cd, and Ni on the goethite surface in the presence of the natural organic ligands was adequately described by considering only surface complexation and complexation in solution by organic ligands. No ternary complexes had to be invoked in the model. The major effect was complexation by the strongest ligand, whereas interactions with other cations and anions had only a minor influence. Competition reactions between Cu and Ni for complexation with the same strong ligand L(I) were observed.