This work assesses the in vitro antimicrobial activity of an aqueous olive mill waste extract (AE-2) on the growth of diverse cocktails of foodborne pathogens species (Listeria monocytogenes, ...Staphylococcus aureus, Escherichia coli, and Salmonella Enterica). The effects were evaluated by Response Surface Methodology, using a two-block (D-optimal and full factorial) sequential design, with two independent variables (hydroxytyrosol concentration 0–3000 ppm and pH 3.5–6.5) and the percentage of inhibition (%I) as the dependent variable. S. Enterica and E. coli behaviours were similar but different from L. monocytogenes and S. aureus. The models predicted the complete inhibition of the four foodborne pathogen cocktails in the region defined by 3.80–3.87 pH and 1200–1314 ppm hydroxytyrosol. Within the experimental region, the model showed the best predictions for L. monocytogenes and the worst for S. Enterica, but the errors never exceeded 46%. This study could promote the use of olive by-products as natural preservatives in the food industry, especially in acidic matrices.
•Response Surface Methodology was effective to evaluate the antimicrobial effect of olive mill waste extract.•S. Enterica and E. coli behaviours were similar but different from L. monocytogenes and S. aureus.•The models predicted the complete inhibition of the four foodborne pathogen cocktails.•The model showed the best predictions for L. monocytogenes and the worst for S. Enterica.
Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that ...hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. These effects cause an imbalance between adenosine, dopamine, and serotonin receptors in HGprt deficient cells, and cells differentiated with hypoxanthine showed an increase in dopamine, adenosine and serotonin receptors expression. Hypoxanthine deregulates early neuronal differentiation increasing WNT4 and EN1 gene expression.
Inhibitors of the class I phosphoinositide 3-kinase (PI3K) isoform PI3Kα have received substantial attention for their potential use in cancer therapy. Despite the particular attraction of targeting ...PI3Kα, achieving selectivity for the inhibition of this isoform has proved challenging. Herein we report the discovery of inhibitors of PI3Kα that have selectivity over the other class I isoforms and all other kinases tested. In GDC-0032 (3, taselisib), we previously minimized inhibition of PI3Kβ relative to the other class I insoforms. Subsequently, we extended our efforts to identify PI3Kα-specific inhibitors using PI3Kα crystal structures to inform the design of benzoxazepin inhibitors with selectivity for PI3Kα through interactions with a nonconserved residue. Several molecules selective for PI3Kα relative to the other class I isoforms, as well as other kinases, were identified. Optimization of properties related to drug metabolism then culminated in the identification of the clinical candidate GDC-0326 (4).
This volume is a manifestation of the continuing interest of scholars at the University of Michigan in Philippine studies. Written by a generation of post-colonial scholars, it attempts to unravel ...some of the historical problems of the colonial era. Again and again the authors focus on the relationship of the ilustrados and the Americans, on the problems of continuity and discontinuity, and on the meaning of “modernization” in the Philippine context. As part of the Vietnam generation, these authors have looked at American imperialism with a new perspective, and yet their analysis is tempered, not strident, and reflective, not dogmatic. Perhaps the most central theme to emerge is the depth of the contradiction inherent in the American colonial experiment.
•Breeding for high WUE will not limit yield response to elevated CO2.•The high WUE cultivar showed lower leaf level photosynthetic capacity than low WUE cultivar.•The high WUE cultivar compensate the ...lower photosynthetic activity with a bigger leaf area.•High yield response to elevated CO2 was also associated with high HI.
The predicted increase in atmospheric CO2 concentration CO2 is expected to enhance photosynthesis and seed yield in crops such as soybean Glycine max (L.) Merr.. However, future breeding for high water use efficiency (WUE) could interfere with the amount of carbon (C) fixed by leaves and seed mineral composition under elevated CO2 due to lower stomatal conductance (gs). In the present study, two genotypes with contrasting WUE were grown in open top chambers (OTC) under ambient (410 ppm; aCO2) and elevated (610 ppm; eCO2). In order to test performance of both cultivars to changing CO2 conditions, growth, photosynthetic performance (leaf and canopy level) and seed mineral composition were analyzed. The low WUE genotype had a greater response to eCO2 in terms of leaf daily photosynthetic C gain due to greater gs, which was compensated in the high WUE genotype by an increase in leaf area (LA). However, in the low WUE genotype, improved daily photosynthetic C gain did not translate into greater biomass or seed yield CO2 response compared to the high WUE genotype, suggesting better assimilate partitioning by the high WUE genotype. In terms of seed composition, the high WUE genotype generally had lower mineral concentrations at eCO2 compared to aCO2, but greater total amounts of nutrient (due to higher seed yield) under eCO2 compared to the low WUE genotype. Findings presented here highlight importance of genetic variation in soybean response to future atmospheric CO2 which should be considered when breeding for future climates.
Heparan sulfate proteoglycans activate the matrix metalloproteinase-7 zymogen (proMMP-7) and recruit it in order to shed proteins from cell surfaces. This occurs in uterine and mammary epithelia, ...bacterial killing, lung healing, and tumor cell signaling. Basic tracks on proMMP-7 recognize polyanionic heparin, according to nuclear magnetic resonance and mutations disruptive of maturation. Contacts and proximity measurements guided docking of a heparin octasaccharide to proMMP-7. The reducing end fits into a basic pocket in the pro-domain while the chain continues toward the catalytic domain. Another oligosaccharide traverses a basic swath remote on the catalytic domain and inserts its reducing end into a slot formed with the basic C terminus. This latter association appears to support allosteric acceleration of proteolysis. The modes of binding account for extended, heterogeneous assemblies of proMMP-7 with heparinoids during maturation and for bridging to pro-α-defensins and proteoglycans. These associations support proteolytic release of activities at epithelial cell surfaces.
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•Heparin oligosaccharides bind two basic tracks and pockets of proMMP-7•Both modes of binding support proteolytic maturation of the zymogen•Heparin chains perturb the termini of proMMP-7•Allostery and shedding may be attributed to GAG binding remote on catalytic domain
Glycosaminoglycans recruit the protease MMP-7 to growth factors, receptors, and antibacterial proteins for maturation and shedding from cell surfaces. Fulcher et al. orient heparin chains on basic strips on the zymogen using NMR in solution and mutations that interfere in heparin-triggered maturation.
Matrix metalloproteinase-13 (MMP13) is a Zn2+-dependent protease that catalyzes the cleavage of type II collagen, the main structural protein in articular cartilage. Excess MMP13 activity causes ...cartilage degradation in osteoarthritis, making this protease an attractive therapeutic target. However, clinically tested MMP inhibitors have been associated with a painful, joint-stiffening musculoskeletal side effect that may be due to their lack of selectivity. In our efforts to develop a disease-modifying osteoarthritis drug, we have discovered MMP13 inhibitors that differ greatly from previous MMP inhibitors; they do not bind to the catalytic zinc ion, they are noncompetitive with respect to substrate binding, and they show extreme selectivity for inhibiting MMP13. By structure-based drug design, we generated an orally active MMP13 inhibitor that effectively reduces cartilage damage in vivo and does not induce joint fibroplasias in a rat model of musculoskeletal syndrome side effects. Thus, highly selective inhibition of MMP13 in patients may overcome the major safety and efficacy challenges that have limited previously tested non-selective MMP inhibitors. MMP13 inhibitors such as the ones described here will help further define the role of this protease in arthritis and other diseases and may soon lead to drugs that safely halt cartilage damage in patients.
For the first time, a database of the antioxidant capacities of both the lipophilic and hydrophilic components of foods has been developed using the modified oxygen radical absorbance capacity (ORAC
...FL) assay and a peroxyl radical generator. For lipophilic components, randomly methylated
β-cyclodextrin was used as a solubility enhancer. Four representative samples were extracted directly with the hydrophilic solvent (acetone:water:acetic acid, 70:29.5:0.5). Their ORAC
FL values were similar to that obtained for hydrophilic ORAC
FL (H-ORAC
FL) following lipophilic extraction with hexane:dichloromethane (1:1). Lipophilic ORAC values (L-ORAC
FL) were relatively low compared to H-ORAC
FL, ranging from 0.11±0.06 to 154.70±3.58
μmol TE/g of fresh or dry weight, whereas H-ORAC
FL ranged from 1.23±0.17 to 175.24±10.36
μmol TE/g of fresh or dry weight. Total antioxidant capacity (TAC) was calculated as the sum of the lipophlic and hydrophilic ORAC
FL values. L-ORAC
FL as a percentage of TAC ranged from 0.27% to 63.70%. Sampling time during the year significantly influenced lipophilic and/or hydrophilic ORAC
FL values in some food samples. In order to get an accurate total antioxidant capacity of a given food sample, both lipophilic and hydrophilic fractions need to be measured. Food processing, such as cooking or peeling, need to be considered as additional factors which can introduce variation in antioxidant capacity measurements of foods.
The aim of this paper is to analyse the long-term efficiency of different management forms for urban public transport, using a sample of 193 Spanish municipalities for the period 2014–2016. The ...analysis is performed using the order-m data panel method proposed by Garrido et al. (2018) and the concept of the meta-frontier (Battese et al., 2004). This approach is based on an analysis of panel data cost efficiency as described by Surroca et al. (2016) and provides a stable, homogeneous and comparable estimate of the efficiency obtained by different management forms in the delivery of urban public transport. The study results indicate that inter-municipal cooperation is the most efficient form of long-term management.
•Order-m data panel is implemented to obtain long-term cost efficiency in urban public transport.•Homogeneous and comparable estimates of the efficiency are obtained by different management forms.•Inter-municipal cooperation is the most efficient form of long-term management.
Blood oxygen level dependent (BOLD) contrast pharmacological magnetic resonance imaging (phMRI) is an increasingly popular technique that allows the non-invasive investigation of spatial and temporal ...changes in rat brain function in response to pharmacological stimulation in vivo. Rat brain BOLD contrast phMRI is, at present, established in few neuropharmacological laboratories, and various issues associated with the technique require attention. The present review is primarily aimed at psychopharmacologists with no previous experience of phMRI, who are interested in the practical aspects that phMRI studies entail.
Experimental and analytical considerations, including anaesthesia, physiological monitoring, drug dose and delivery, scanning protocols, statistical approaches and the interpretation of phMRI data, are discussed.
![Effects of elevated [CO2] o...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0098-8472_1873-7307/small "Effects of elevated [CO2] on photosynthesis and seed yield parameters in two soybean genotypes with contrasting water use efficiency")
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