Inhibisie van osteoklastvorming en beenresorpsie deur poli-onversadigde vetsure in RAW 264.7 muismonosiete

Inhibition of osteoclast differentiation and bone resorption by polyunsaturated fatty acids in RAW 264.7 murine macrophages. This study investigated the effects of polyunsaturated fatty acids on osteoclast formation and bone resorption in RAW 264.7 murine pre-osteoclasts. Data obtained suggests an inhibitory effect of these compounds on osteoclastogenesis and bone resorption in the cell line tested. Beenhermodellering in volwassenes is ‘n fisiologiese proses wat die sintese van beenmatriks deur osteoblaste en die resorpsie (afbraak) van been deur osteoklaste behels. Osteoklaste ontstaan deur die samesmelting van hematopoïetiese selle van monosiet-makrofaagafkoms en speel ‘n deurslaggewende rol in beenhermodellering. Osteoklast-ooraktiwiteit kan die afbraak van been in verskeie patologiese toestande tot gevolg hê. Kliniese- en dierestudies het aangedui dat sommige poli-onversadigde vetsure ‘n voordelige effek op been kan hê. Die doel van hierdie proefstudie was om te bepaal of omega-3 en omega-6 poli-onversadigde vetsure osteoklastvorming vanaf RAW 264.7 monosiete moduleer en daardeur die aantal volwasse resorberende osteoklaste kan beïnvloed. Monosiet/makrofaag-muisselle (RAW 264.7 pre-osteoklaste) is teen 1.5x104 selle/putjie in steriele 24-put plaatjies in die aanwesigheid van 15 ng/ml muisreseptor-aktiveerder van NFκBligand (RANKL) gesaai. RANKL is noodsaaklik vir osteoklastvorming vanaf voorgangerselle. Etanol (oplosmiddelkontrole), die omega-6 poli-onversadigde vetsure aragidoonsuur en gammalinoleensuur asook die omega-3 poli-onversadigde vetsure eikosapentaënöesuur en dokosaheksaënöesuur is by die selkulture teen konsentrasies van 5–20 μg/ml gevoeg. Palmitiensuur, ‘n versadigde vetsuur, teen ‘n konsentrasie van 20 μg/ml is as positiewe kontrole vir inhibisie van osteoklastvorming gebruik. Na vyf dae inkubasie is osteoklastvorming geëvalueer deur van tartraat-weerstandigesuurfosfatase (TRAP)-kleuring gebruik te maak. TRAP-positiewe selle met vyf of meer kerne word as veelkernige osteoklaste beskou. Soortgelyke eksperimente is uitgevoer op plaatjies wat bedek is met ‘n sintetiese anorganiese beenoppervlak. Na sewe dae inkubasie is die selle afgewas en resorpsie van die oppervlak met behulp van mikroskoopfoto’s waargeneem. Die persentasie resorpsie-oppervlak is daarna met behulp van toepaslike rekenaarsagteware bepaal. Verder is RAW 264.7 selle op beenskyfies gesaai om die effek van poli-onversadigde vetsure op die degradering van organiese en anorganiese beenkomponente te evalueer. Na nege dae is die gekondisioneerde media afgetrek en die hoeveelheid Ca2+ en kollageenfragmente, beendegraderingsprodukte onderskeidelik afkomstig vanaf die anorganiese en organiese komponente van beenafbraak, deur gepaste kolorimetriese metodes bepaal. Resultate van hierdie studie het getoon dat die vorming van veelkernige osteoklaste deur die blootstelling aan poli-onversadigde vetsure by konsentrasies van 5–20 μg/ml geïnhibeer word. Blootstelling aan al die vetsure het tot inhibering van osteoklastvorming gelei met die grootste effek by die hoogste vetsuurkonsentrasies. Dokosaheksaënöesuur (omega-3) het die mees betekenisvolle inhiberende effek oor al die konsentrasies getoon en eikosapentaënöesuur die minste. Resorpsieholtes op die gesimuleerde beenplaatjies was kleiner waar die selle aan aragidoonsuur en dokosaheksaënöesuur blootgestel was in vergelyking met dié van die oplosmiddelkontrole, wat moontlik aan die laer voorkoms van volwasse veelkernige osteoklaste toegeskryf kan word. ‘n Afname in die beendegraderingsprodukte is ook waargeneem waar selle blootgestel is aan aragidoonsuur en dokosaheksaënöesuur in vergelyking met die oplosmiddelkontrole. Die resultate ondersteun die vermoede dat poli-onversadigde vetsure die vorming van volwasse osteoklaste inhibeer en daardeur ‘n beenbeskermende effek tot gevolg mag hê. Verdere navorsing is nodig om duidelikheid oor die meganismes wat hier betrokke is, te verkry. Hierdie navorsing is deur die Mediese Navorsingsraad en die Navorsings-ontwikkelingsprogram (Universiteit van Pretoria) befonds.falsefalsefalsePublishedPublishedPublishedSouth AfricaSouth AfricaSouth Afric

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease

Covalent Interaction

Reviewed in historical context, bond order emerges as a vaguely defined concept without a clear theoretical basis. As an alternative, the spherical standingwave model of the extranuclear electronic distribution on an atom provides a simple explanation of covalent bond order as arising from the constructive and destructive interference of wave patterns. A quantitative measure derives from a number pattern that relates integer and half-integer bond orders through series of Fibonacci numbers, consistent with golden-spiral optimization. Unlike any previous definition of bond order, this approach is shown to predict covalent bond length, dissociation energy and stretching force constants for homonuclear interactions that are quantitatively correct. The analysis is supported by elementary number theory and involves atomic number and the golden ratio as the only parameters. Validity of the algorithm is demonstrated for heteronuclear interactions of any order. An exhaustive comparison of calculated dissociation energies and interatomic distance in homonuclear diatomic interaction, with experimental data from critical review, is tabulated. A more limited survey of heteronuclear interactions confirms that the numerical algorithms are generally valid. The large group of heteronuclear hydrides is of particular importance to demonstrate the utility of the method, and molecular hydrogen is treated as a special case. A simple formula that describes the mutual polarization of heteronuclear pairs of atoms, in terms of valence densities derived from a spherical-wave structure of extranuclear electronic charge, is used to calculate the dipole moments of diatomic molecules. Valence density depends on the volume of the valence sphere as determined by the atomic ionization radius, and the interatomic distance is determined by the bond order of the diatomic interaction. The results are in satisfactory agreement with literature data and should provide a basis for the calculation of more complex molecular dipole moments. The diatomic CO is treated as a special case, characteristic of all interactions traditionally identified as dative bonds.http://www.springer.com/series/430hj201

Calculation of Atomic Structure

The Thomas–Fermi and Hartree–Fock calculations of non-hydrogen atomic structure rely on complicated numerical computations without a simple visualizable physical model. A new approach, based on a spherical wave structure of the extranuclear electron density on atoms, self-similar to prominent astronomical structures, simplifies the problem by orders of magnitude. It yields a normalized density distribution which is indistinguishable from the TF function and produces radial distributions, equivalent to HF results. Extended to calculate atomic ionization radii, it yields more reliable values than SCF simulation of atomic compression. All empirical parameters used in the calculation are shown to be consistent with the spherical standing-wave model of atomic electron density.http://www.springer.com/series/430hj201

All is Number

Rational numbers, which correctly describe many recognizable patterns in the physical world, are often seen to converge in the process to irrational limits or even singularities. As a common example, atomic numbers are well known as fundamental parameters in chemistry, but by demonstrating that the periodicity of atomic matter is simulated by the convergence of rational fractions, from unity to the golden ratio, the importance of limiting processes and irrational limits in the modelling of chemical systems and of phenomena such as superconduction is emphasized. Other limiting formulae feature in atomic spectral series, radioactive decay, circular measure, absolute temperature, the speed of light, structure of the solar system and gravitational collapse. In virtually all cases the convergence involves the irrational golden ratio and the golden spiral, the essential properties of which are briefly reviewed in summary of the arguments developed in this volume. The suspicion that molecular shape should have a related number basis could not be substantiated. Only in the double-helical base pairing of DNA could any correlation between molecular structure and number theory be demonstrated. It is tempting to conjecture that the ubiquitous appearance of irrational limits signals the inadequacy of the R3 number system to provide a detailed account of the four-dimensional world.http://www.springer.com/series/430hj201

Chemistry by Number Theory

Aspects of elementary number theory pertaining to the golden ratio and the golden spiral are shown to be related to and therefore of importance in the simulation of chemical phenomena. Readily derived concepts include atomic structure, electronegativity, bond order, the theory of covalent interaction and aspects of molecular chirality. The physical interpretation of the results implicates the 4D structure of space-time as a fundamental consideration. The implied classical nature of 3D molecular structure identifies molecular mechanics as an ideal method for structure optimization, and it is shown that the parameters may be related to number theory. All results point at a 4D wave structure of electrostatic charge.Alexander von Humboldt Foundationhttp://www.springer.com/series/430hb2014ai201

Molecular Shape

Molecular shape is recognized as an emergent property that complements the projection fromfour-dimensional space-time to tangent Euclidean space. Projection from hypercomplex algebra to real algebra necessitates the three-dimensional definition of concepts such as chirality, quantum uncertainty and probability density to compensate for errors of abstraction. The emergent alternative description of extranuclear charge density as spherical standing waves, optimized by a golden spiral, reveals atomic structure in line with the periodic table of the elements and underpinning the concepts of bond order, interatomic distance and stretching force constant, related to chemical interaction. The principles giving rise to molecular structure are shown to depend, like bond order, on the constructive interference of atomic wave fields, optimized by minimal adjustment to bond orders. The procedure is shown to be equivalent to the philosophy of molecular mechanics. Arguments based on the traditional interpretation of electronegativity, are presented to relate the parameters of strain-free bond lengths, dissociation energies and harmonic force constants, used in molecular mechanics, to quantum-mechanically defined ionization radii of atoms. Atomic electron densities and a bond-order function, both obtained by number-theory optimization, enable the direct calculation of interatomic distance, dissociation energy and stretching force constant for all pairwise interactions of any order. Torsional interaction determines the final shape of a molecule and presumably can only be understood as a four-dimensional effect.http://www.springer.com/series/430hj201

Effects of omega 3-and omega 6-Polyunsaturated Fatty Acids on RANKL- Induced Osteoclast Differentiation of RAW264.7 Cells: A Comparative in Vitro Study

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Publishe