Asthma and Human Excellence: A Coincidence or a Correlation?

Superior intelligence, creative genius, extraordinary personality, and/or social prominence have been associated with asthma often enough to raise the question of a nonrandom concurrence. With no intent to prove any developmental correlation this article presents such “case reports” (more biographical than biological) for two main reasons: to document the experience of asthma in the life of outstanding persons and to make everyone better acquainted-using asthma as an “excuse”-with the work and the times of some unique human beings.     

Exploration of the mechanism of Zisheng Shenqi decoction against gout arthritis using network pharmacology

BackgroundIn this study, the network pharmacological methods were used to predict the target of effective components of compounds in Zisheng Shenqi Decoction (ZSD, or Nourishing Kidney Qi Decoction) in the treatment of gouty arthritis (GA).MethodThe main effective components and corresponding key targets of herbs in the ZSD were discerned through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP), Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) database. UniProt database and Swiss Target Prediction (STP) database was used to rectify and unify the target names and supply the target information. The targets related to GA were obtained by using GeneCards database. After we discovered the potential common targets between ZSD and GA, the interaction network diagram of “ZSD-component-GA-target” was constructed by Cytoscape software (Version 3.7.1). Subsequently, the Protein-protein interaction (PPI) network of ZSD effective components-targets and GA-related targets was constructed by Search Tool for the Retrieval of Interacting Genes Database (STRING). Bioconductor package “org.Hs.eg.db” and “cluster profiler” package were installed in R software (Version 3.6.0) which used for Gene Ontology analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis.Results146 components and 613 targets of 11 herbal medicines in the ZSD were got from TCMSP database and BATMAN-TCM database. 987 targets of GA were obtained from GeneCards database. After intersected and removed duplications, 132 common targets between ZSD and GA were screened out by Cytoscape software (Version 3.7.1). These common targets derived from 81 effective components of 146 components, such as quercetin, stigmasterol and kaempferol. They were closely related to anti-inflammatory, analgesic and anti oxidative stress and the principal targets comprised of Purinergic receptor P2X, ligand-gated ion channel 7 (P2x7R), Nod-like receptor protein 3 (NLRP3) and IL-1β. GO enrichment analysis and KEGG pathway enrichment analysis by R software (Version 3.6.0) showed that the key target genes had close relationship with oxidative stress, reactive oxygen species (ROS) metabolic process and leukocyte migration in aspects of biological process, cell components and molecular function. It also indicated that ZSD could decrease inflammatory reaction, alleviate ROS accumulation and attenuate pain by regulating P2 × 7R and NOD like receptor signaling pathway of inflammatory reaction.ConclusionA total of 81 effective components and 132 common target genes between ZSD and GA were screened by network pharmacology. The PPI network, GO enrichment analysis and KEGG pathway enrichment analysis suggested that ZSD can exerte anti-inflammatory and analgesic effects on the treatment of GA by reducing decreasing inflammatory reaction, alleviating ROS accumulation, and attenuating pain. The possible molecular mechanism of it mainly involved multiple components, multiple targets and multiple signaling pathways, which provided a comprehensive understanding for further study. In general, the network pharmacological method applied in this study provides an alternative strategy for the mechanism of ZSD in the treatment of GA.     

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling

ObjectiveTo explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling.MethodsGene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes.ResultsIn this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway − oxidative phosphorylation.ConclusionsWe identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC.     

Über die bei hohen Ansäuerungsgraden auftretenden Polymolybdat-Typen,insbesondere zur Frage der „Dekamolybdate”︁ und „Phase C”︁-Polymolybdate

On the Polymolybdate Types Occurring at High Degrees of Acidification, with Particular Reference to the “Decamolybdates” and “Phase C” Polymolybdates It is shown that in the range of high acidification (> 1.6H⁺/MoO₄^2?) of aqueous molybdate solutions only two types of solid polymolybdates occur, namely the 36-molybdate and the “decamolybdate” types. These types can be most conveniently identified by their Raman spectra and also by some other characteristics. All the other polymolybdate types proposed in the literature for this range of acidification (“hexamolybdates”, “octamolybdates”, “dodecamolybdates”, “16-molybdates”, a 19-molybdate, the large group of polymolybdates characterized by a wide range of b in the general formula M₂O · bMoO₃ · cH₂O, “phase C” polymolybdates, a “hexagonal hydrate of molybdenum trioxide”, a “reactive molybdic acid”, “NH₃(MoO₃)₃”, and others) can be assigned to one of these two types. The most important reason for the erroneous assignments in the literature is the isomorphous exchange of varying quantities of the alkali or alkaline earth metal cations by H₃O⁺ in the crystal structure, occurring in the highly acidic solutions, particularly with the small cations. This cannot be recognized by the presently available methods of investigation and, hence, leads to the creation of new polymolybdate types. Another reason causing some of the confusion is the assignment of virtually identical X-ray diffraction data to two different types of lattices, a hexagonal and cubic lattice.     

Light scattering from polymer films having optically anisotropic rodlike texture. III. Inter-rod interference

Effects of interparticle interference on depolarized light scattering from polymer films having nonspherulitic (rodlike, disklike, or fibrous) crystalline superstructures are explored, both theoretically and experimentally. Discrepancies between the observed “rodlike scattering” and the predicted scattering based on “single-rod” theory are pointed out and accounted for in terms of various types of aggregation models for polymeric solids and solutions.     

Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

Cleft lip and/or palate (CL/P) is a common congenital malformation with a complex etiology which is not fully elucidated yet. Epidemiological studies point to different etiologies in the cleft lip and palate subgroups, isolated cleft lip (CL), isolated cleft palate (CP) and combined cleft lip and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed. Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend that future gene expression in CL/P studies should use tissue from the correct embryonic time and place if possible, to overcome the biases in the presented study.     

Gene-expression profiling in gill and liver of zebrafish exposed to produced water

The effects of produced water (a by-product of oil and gas extraction) on gene expression were studied in gills and liver tissues of zebrafish. Adult, non-breeding zebrafish were exposed to control (freshwater mixed with 5% seawater) or produced water (freshwater mixed with 5% of produced water from the Oceberg C Oil Platform in the North Sea). A zebrafish library was used to make a microarray that consisted of 15,806 unique genes. The results indicate that 27 genes in the gills and 55 genes in the liver show significantly altered expression (greater than two-fold change). More than 70% of these gene sequences have not been annotated in the Gene Ontology (GO) database, making it difficult to characterize the affected genes. CYP1A displayed the greatest upregulation in the gills (eightfold, verified with quantitative real-time PCR). This study illustrates the utility of microarray approaches in investigations of environmental effects of toxicants.     

ExplorEnz: a MySQL database of the IUBMB enzyme nomenclature

Background  

We describe the database ExplorEnz, which is the primary repository for EC numbers and enzyme data that are being curated on behalf of the IUBMB. The enzyme nomenclature is incorporated into many other resources, including the ExPASy-ENZYME, BRENDA and KEGG bioinformatics databases.     

Organization of phospholipids in biological membranes

Preferred conformations of phospholipids have been predicted through quantum-chemical techniques and classical potential functions. An essential condition for a conformation to exist in a biomembrane is that it should be possible for it to organize in the form of a bilayer. Taking into consideration the conformational flexibility of the polar head group, organization at the lipid–water interface has been considered. The biological implications of such an organization in terms of formation of “hydrophobic channels” is discussed. Quantum-mechanical investigations on the transport phenomenon have shown that the “selectivity” of biological membranes is connected with the “organization.” Calculations of the quantum-mechanical transmission coefficients for different model potential profiles indicate that minor differences in the height of potential barriers in certain regions can lead to significant changes in transmission coefficients. The “directional selectivity” of substrates (differences in transmission coefficients for flow in and out of the cell) can be explained on the basis of differences in membrane organization. These results have some important consequences in the evolutionary process in biological membranes.     

Optimisation of sulphur emission in molecular emission cavity analysis: Effects of variation in cavity position and phosphate addition

Temperature profiles are measured for hydrogen flames used for m.e.c.a. and discussed in terms of the emission intensities produced by some sulphur compounds in different regions of the flame. The effect of addition of phosphoric acid or phosphate buffers on sulphates and ammonium thiocyanate is re-examined and the enhancing effect of “residual phosphate” discussed.     

The pivotal role of high-resolution mass spectrometry in the study of grape glycosidic volatile precursors for the selection of grapevines resistant to mildews

A breeding program to produce new grape varieties tolerant to main vine fungal pathogens (Plasmopara viticola and Erysiphe necator) is carrying out by crossing Vitis vinifera cv. “Glera” with resistant genotypes such as “Solaris,” “Bronner,” and “Kunleany.” Firstly, resistance gene-based markers analyses allowed the identification of five genotypes, which have inherited the resistance loci against mildews. To select those that also inherited the phenotype as close as possible to ‘Glera’ suitable to be introduced in the Prosecco wine production protocols, the grape glycosidic derivatives were studied by UHPLC/QTOF mass spectrometry. Targeted identification of the metabolites was performed using a database expressly constructed by including the glycosidic volatile precursors previously identified in grape and wine. A total of 77 glycosidic derivatives including many aroma precursors and some variety markers, were identified. Original resistant genotypes had distinct metabolomic profiles and different to ‘Glera’, while the crossings showed varying similarity degrees to V. vinifera parent. Findings demonstrated the Glera × Bronner and Glera × Solaris crossings are more suitable to produce high-sustainable Prosecco wines. Coupling of glycosidic volatile precursors profiling to multivariate statistical analysis was effective for phenotypic characterization of grapes and to evaluate their enological potential.     

Davy Takes to the Hills: Dialogic Enquiry and the Aesthetics of the Prospect View

I discuss some of the versions of scientific enquiry used and promoted by Davy, arguing that his self-fashioning as a “genius” and “hero of science” in the years 1801–1820, paralleling the self-fashioning of his friend Wordsworth, created a public persona that tended to occlude a practice of group enquiry to which, however, he publicly returned in his last years – significantly revising it so that it became a dialogic form of writing. This form, I suggest, construed knowledge not as the production of facts – or elements – by inductive method and controlled experiment, but as a conversational process between trusted peers, in which it is not just possible but fundamental to express doubt. Requiring no absolute commitment to a single view, dialogic exploration embraced uncertainty to engender new questions and ambivalence to generate new modes of enquiry.     

A primary isotopic gas standard for sulfur in the form of SF6 with Système International d’Unités traceable values for isotopic composition and molar mass

A batch of SF₆ gas prepared by Messer (Germany) was metrologically certified for absolute isotope abundance ratios and molar mass (atomic weight) of sulfur following the ISO/BIPM Guide to the expression of uncertainties in measurements. The certification is based on the “Avogadro II Measurement Procedure” using the “Avogadro II amount comparator,” which was developed in the framework of the redetermination of the Avogadro constant. For the correction of small remaining systematic effects of unknown nature, synthetic isotope mixtures of Ag₂S converted to SF₆ were used in order to obtain “calibrated” or “absolute” values with small combined uncertainty. The values for this sulfur primary isotopic gas standard (PIGS) are traceable to the Système International d’Unités (SI) in the shortest possible way and can therefore serve as a link to SI when used in differential measurements. The PIGS is now commercially available.     

Band-broadening in packed chromatographic columns

In the past few years some problems have arisen as to the interpretation of experimental plate height data of packed chromatographic columns by means of the theory of VAN DEEMTER et al. These difficulties concern the “eddy diffusion” and “mass transfer” terms in particular. Light may be thrown on this matter by the recognition of unevenness of flow throughout the column cross-section as a major source of band-broadening. By considering the contribution to plate height resulting from the interaction between such flow profiles and various mechanisms of lateral transport of material it proved possible to solve the above-mentioned difficulties.     

Determination of the integral toxicity of water in terms of biotesting with a multisensor system sensitive to individual toxicants

Possibility of applying a multisensor potentiometric system of the type of the “electronic tongue” as a method for evaluating the toxicity of a water medium is considered. The multisensor system is preliminarily calibrated against samples with a known toxicity, determined by the biotesting method with the use of living organisms. It is shown that the thus obtained system is suitable for evaluating the quality of water samples in terms of the response of various test objects without direct use of living organisms.     

3D cell culture models and organ-on-a-chip: Meet separation science and mass spectrometry

In vitro derived simplified 3D representations of human organs or organ functionalities are predicted to play a major role in disease modeling, drug development, and personalized medicine, as they complement traditional cell line approaches and animal models. The cells for 3D organ representations may be derived from primary tissues, embryonic stem cells or induced pluripotent stem cells and come in a variety of formats from aggregates of individual or mixed cell types, self-organizing in vitro developed “organoids” and tissue mimicking chips. Microfluidic devices that allow long-term maintenance and combination with other tissues, cells or organoids are commonly referred to as “microphysiological” or “organ-on-a-chip” systems. Organ-on-a-chip technology allows a broad range of “on-chip” and “off-chip” analytical techniques, whereby “on-chip” techniques offer the possibility of real time tracking and analysis. In the rapidly expanding tool kit for real time analytical assays, mass spectrometry, combined with “on-chip” electrophoresis, and other separation approaches offer attractive emerging tools. In this review, we provide an overview of current 3D cell culture models, a compendium of current analytical strategies, and we make a case for new approaches for integrating separation science and mass spectrometry in this rapidly expanding research field.     

Radiation-induced luminescence from “dry” and hydrated DNA and related macromolecules

The radiation-induced luminescence from three types of fibrous DNA and a series of polydeoxynucleotides was measured under vacuum or in the presence of oxygen at 77 and 293 K. The “in pulse” emission spectra, generated by electrons with energies <260 keV, have been investigated in order to obtain an understanding of the effects of direct energy deposition within DNA. From a comparison of the observed emission spectra from “dry” DNA samples with different A + T/G + C ratios with those for the polydeoxynucleotides, it is inferred that the A + T/G + C ratio of DNA is an important factor in determining the wavelength dependence of the emission. The “in-pulse” emission characteristics of DNA and the polydeoxynucleotides were found to be independent of both temperature and the presence of oxygen. Investigations were extended to study the effect of hydration of DNA upon the resulting radiation induced emission spectra. It is apparent that with DNA thin films (15–20 μm) containing >50% water by wt (1.2:1 w/w, H₂O|DNA), the “in-pulse” luminescence spectrum is similar to that of “dry” DNA. These findings are discussed in terms of energy or charge migration induced in DNA upon irradiation and the possible effects of conformational changes, caused by hydration, on charge migration.     

Random Computer Generation of 3D Molecular Structures: Theoretical and Statistical Analysis

Summary: A computer program has been developed to generate three‐dimensional molecular structures randomly from a given collection of elementary chemical functional groups: the so‐called fragment database. The gradual assembly of the various fragments present in the database is performed according to a “self‐generation algorithm” (SGA). The latter is based on the covalent binding, step by step, between the unoccupied electronic valencies associated with the fragments of the database, and those of the growing molecular structure. When the number of electronic valencies of the molecular structure is zero, the growth process for this particular molecule is completed. It is shown that SGA is able to reproduce the asymmetric mass distributions of some natural colloids, like humic substances. In this article, particular attention is given to the analysis of the relationship existing between the fragment composition of the database and that of the collection of molecules generated. Mathematical expressions are derived and discussed, to understand the relationship between the proportions of the different types of fragments and the final composition of the generated molecular ensembles. For that purpose, a “pathway” formalism is proposed to describe exhaustively the whole set of generated molecules by specifying the distribution function of all of the fragments therein integrated. A statistical analysis that satisfactorily reproduces the predictions of the pathway model is extensively discussed.

Example of a three‐dimensional structure obtained with the “self‐generation algorithm” (SGA).