Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.     

Application of novel extractants for actinide(III)/ lanthanide(III) separation in hollow-fibre modules

Separation tests using hollow-fibre modules were performed for the difficult selective extraction of trivalent actinides over fission lanthanides from acidic media. This article shows that with 2,6-di(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine as the extractant, up to 94% americium could be extracted from 1.0 kmol/m³ HNO₃, with minimal lanthanide co-extraction. Using a synergistic mixture of bis(chlorophenyl)dithiophosphinic acid and tri-n-octyl phosphine oxide, tests were performed on extraction, lanthanide scrubbing and stripping. In the extraction test, up to 99.99% americium could be extracted from 0.5 kmol/m³ HNO₃, with approximately one third of the lanthanides being co-extracted. Mass transfer calculations using a consistent set of input data showed good agreement with the experiments.     

Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

Crystallographic shear planes in nanocrystalline SnO2 thin films by high-resolution transmission electron microscopy

Atomic structures of crystallographic shear planes (CSPs) in nanocrystalline thin films of semiconductor SnO₂ were investigated by high-resolution electron microscopy. The films were prepared by electron beam evaporation in high vacuum (10^–6 torr) and followed by annealing in synthetic air at 700 °C for 1–2 H. CSPs with the displacement vector of [1/2 0 1/2] were observed in the planes parallel to (¯101), (110) and (¯3¯21). Most of the CPSs were found to terminate or interact with each other within SnO₂ crystallites. Partial dislocations exist at terminal places of CSPs or along intersecting lines of CSPs. CSP steps were also observed. Structural models of these defects have been proposed. Based on analysis of experimental data, it has been suggested that the Sn/O ratio at CSPs which are not parallel to their displacement vector, at cores of partial dislocations and at CSP steps, is higher than that of the perfect structure, that is, these defects are able to provide extra free electrons with the films.     

Polyamine analogue regulation of NMDA MK-801 binding: a structure-activity study

A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N1, N11-diethylnorspermine, N1,N12-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N1,N14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N1,N3-bis(4-piperidinyl)-1,3-diaminopropane, N1,N4-bis(4-piperidinyl)-1,4-diaminobutane, N1,N4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N1,N3-bis(4-pyridyl)-1,3-diaminopropane, N1,N4-bis(4-pyridyl)-1,4-diaminobutane, N1,N4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 A. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pKa's and thus different protonation, or charge, states at physiological pH. The pKa values for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.     

Multiple Na,K-ATPase Subunits Colocalize in the Brush Border of Mouse Choroid Plexus Epithelial Cells

(1) Background: The unusual accumulation of Na,K-ATPase complexes in the brush border membrane of choroid plexus epithelial cells have intrigued researchers for decades. However, the full range of the expressed Na,K-ATPase subunits and their relation to the microvillus cytoskeleton remains unknown. (2) Methods: RT-PCR analysis, co-immunoprecipitation, native PAGE, mass spectrometry, and differential centrifugation were combined with high-resolution immunofluorescence histochemistry, proximity ligase assays, and stimulated emission depletion (STED) microscopy on mouse choroid plexus cells or tissues in order to resolve these issues. (3) Results: The choroid plexus epithelium expresses Na,K-ATPase subunits α1, α2, β1, β2, β3, and phospholemman. The α1, α2, β1, and β2, subunits are all localized to the brush border membrane, where they appear to form a complex. The ATPase complexes may stabilize in the brush border membrane via anchoring to microvillar actin indirectly through ankyrin-3 or directly via other co-precipitated proteins. Aquaporin 1 (AQP1) may form part of the proposed multi-protein complexes in contrast to another membrane protein, the Na-K-2Cl cotransporter 1 (NKCC1). NKCC1 expression seems necessary for full brush border membrane accumulation of the Na,K-ATPase in the choroid plexus. (4) Conclusion: A multitude of Na,K-ATPase subunits form molecular complexes in the choroid plexus brush border, which may bind to the cytoskeleton by various alternative actin binding proteins.     

Desiderata for Languages to be Used in the Defnition of Reference Business Processes

In many modern enterprises, explicit business process de nitions facilitate the pursuit of business goals in such ways as best practice reuse, process analysis, processe ciency improvement, and automation. Most real-world business processes are large and complex. Successfully capturing, analysing, and automating these processes requires process de nition languages that capture a variety of process aspects with a wealth of details. Mostcurrent process modelling languages, such as Business Process Modelling Notation (BPMN),focus on structural control ows among activities while providing inadequate support for other process de nition needs. In this paper, we rst illustrate these inadequacies through our experiences with a collection of real-world reference business processes from the Aus-tralian lending industry. We observe that the most signi cant inadequacies include lack of resource management, exception handling, process variation, and data ow integration.These identi ed shortcomings led us to consider the Little-JIL language as a vehicle forde ning business processes. Little-JIL addresses the afore-mentioned inadequacies with a number of innovative features. Our investigation concludes that these innovative features are e ective in addressing a number of key reference business process de nition needs.     

Effects of Microbial Utilization of Phenolic Acids and their Phenolic Acid Breakdown Products on Allelopathic Interactions

Reversible sorption of phenolic acids by soils may provide some protection to phenolic acids from microbial degradation. In the absence of microbes, reversible sorption 35 days after addition of 0.5–3 mol/g of ferulic acid or p-coumaric acid was 8–14% in Cecil A_p horizon and 31–38% in Cecil B_t, horizon soil materials. The reversibly sorbed/solution ratios (r/s) for ferulic acid or p-coumaric acid ranged from 0.12 to 0.25 in A_p and 0.65 to 0.85 in B_t horizon soil materials. When microbes were introduced, the r/s ratio for both the A_p and B_t horizon soil materials increased over time up to 5 and 2, respectively, thereby indicating a more rapid utilization of solution phenolic acids over reversibly sorbed phenolic acids. The increase in r/s ratio and the overall microbial utilization of ferulic acid and/or p-coumaric acid were much more rapid in A_p than in B_t horizon soil materials. Reversible sorption, however, provided protection of phenolic acids from microbial utilization for only very short periods of time. Differential soil fixation, microbial production of benzoic acids (e.g., vanillic acid and p-hydroxybenzoic acid) from cinnamic acids (e.g., ferulic acid and p-coumaric acid, respectively), and the subsequent differential utilization of cinnamic and benzoic acids by soil microbes indicated that these processes can substantially influence the magnitude and duration of the phytoxicity of individual phenolic acids.     

Flow shop batching and scheduling with sequence-dependent setup times

This paper addresses the flow shop batching and scheduling problem where sequence-dependent family setup times are present and the objective is to minimize makespan. We consider violating the group technology assumption by dividing product families into batches. In order to reduce setup times, inconsistent batches are formed on different machines, which lead to non-permutation schedules. To the best of our knowledge, this is the first time that the splitting of job families into inconsistent batches has been considered in a flow shop system. A tabu search algorithm is developed which contains several neighbourhood functions, double tabu lists and a multilevel diversification structure. Compared to the state-of-the-art meta-heuristics for this problem, the proposed tabu search algorithm achieves further improvement when the group scheduling assumption is dropped. Also, various experiments conducted on the benchmark problem instances confirm the benefits of batching. Therefore, it will be prudent for the practitioners to consider adopting inconsistent batches and non-permutation schedules to improve their operational efficiency within a reasonable amount of computational effort.