Personalized loading conditions for homogenized finite element analysis of the distal sections of the radius

The microstructure of trabecular bone is known to adapt its morphology in response to mechanical loads for achieving a biomechanical homeostasis. Based on this form–function relationship, previous investigators either simulated the remodeling of bone to predict the resulting density and architecture for a specific loading or retraced physiological loading conditions from local density and architecture. The latter inverse approach includes quantifying bone morphology using computed tomography and calculating the relative importance of selected load cases by minimizing the fluctuation of a tissue loading level metric. Along this concept, the present study aims at identifying an optimal, personalized, multiaxial load case at the distal section of the human radius using in vivo HR-pQCT-based isotropic, homogenized finite element (hFE) analysis. The dataset consisted of HR-pQCT reconstructions of the 20 mm most distal section of 21 human fresh-frozen radii. We simulated six different unit canonical load cases (FX palmar–dorsal force, FY ulnar–radial force, FZ distal–proximal force, MX moment about palmar–dorsal, MY moment about ulnar–radial, MZ moment about distal–proximal) using a simplified and efficient hFE method based on a single isotropic bone phase. Once we used a homogeneous mean density (shape model) and once the original heterogeneous density distribution (shape + density model). Using an analytical formulation, we minimized the deviation of the resulting strain tensors ε(x) to a hydrostatic compressive reference strain ε₀, once for the 6 degrees of freedom (DOF) optimal (OPT) load case and for all individual 1 DOF load cases (FX, FY, FZ, MX, MY, MZ). All seven load cases were then extended in the nonlinear regime using the scaled displacements of the linear load cases as loading boundary conditions (MAX). We then compared the load cases and models for their objective function (OF) values, the stored energies and their ultimate strength using a specific torsor norm. Both shape and shape + density linear-optimized OPT models were dominated by a positive force in the z-direction (FZ). Transversal force DOFs were close to zero and mean moment DOFs were different depending on the model type. The inclusion of density distribution increased the influence and changed direction of MX and MY, while MZ was small in both models. The OPT load case had 12–15% lower objective function (OF) values than the FZ load case, depending on the model. Stored energies at the optimum were consistently 142–178% higher for the OPT load case than for the FZ load case. Differences in the nonlinear response maximum torsor norm ‖t‖ were heterogeneous, but consistently higher for OPT_MAX than FZ_MAX. We presented the proof of concept of an optimization procedure to estimate patient-specific loading conditions for hFE methods. In contrast to similar models, we included canonical load cases in all six DOFs and used a strain metric that favors hydrostatic compression. Based on a biomechanical analysis of the distal joint surfaces at the radius, the estimated load directions are plausible. For our dataset, the resulting OPT load case is close to the standard axial compression boundary conditions, usually used in HR-pQCT-based FE analysis today. But even using the present simplified hFE model, the optimized linear six DOF load case achieves a more homogeneous tissue loading and can absorb more than twice the energy than the standard uniaxial load case. The ultimate strength calculated with a torsor norm was consistently higher for the 6-DOF nonlinear model (OPT_MAX) than for the 1-DOF nonlinear uniaxial model (FZ_MAX). Defining patient-specific boundary conditions may decrease angulation errors during CT measurements and improve repeatability as well as reproducibility of bone stiffness and strength estimated by HR-pQCT-based hFE analysis. These results encourage the extension of the present method to anisotropic hFE models and their application to repeatability data sets to test the hypothesis of reduced angulation errors during measurement.

     

Exploring historical trends using taxonomic name metadata

Background  

Authority and year information have been attached to taxonomic names since Linnaean times. The systematic structure of taxonomic nomenclature facilitates the ability to develop tools that can be used to explore historical trends that may be associated with taxonomy.     

Pandemic human viruses cause decline of endangered great apes

Commercial hunting and habitat loss are major drivers of the rapid decline of great apes [1]. Ecotourism and research have been widely promoted as a means of providing alternative value for apes and their habitats [2]. However, close contact between humans and habituated apes during ape tourism and research has raised concerns that disease transmission risks might outweigh benefits [3-7]. To date only bacterial and parasitic infections of typically low virulence have been shown to move from humans to wild apes [8, 9]. Here, we present the first direct evidence of virus transmission from humans to wild apes. Tissue samples from habituated chimpanzees that died during three respiratory-disease outbreaks at our research site, C?te d'Ivoire, contained two common human paramyxoviruses. Viral strains sampled from chimpanzees were closely related to strains circulating in contemporaneous, worldwide human epidemics. Twenty-four years of mortality data from observed chimpanzees reveal that such respiratory outbreaks could have a long history. In contrast, survey data show that research presence has had a strong positive effect in suppressing poaching around the research site. These observations illustrate the challenge of maximizing the benefit of research and tourism to great apes while minimizing the negative side effects.     

Genotypic difference of potato in carbon budgeting as a mechanism of phosphorus utilization efficiency

Observed genotypic difference in P utilization efficiency in soil grown potatoes led to the present study to investigate possible mechanisms of P utilization efficiency in potato genotypes grown in nutrient solution under three P regimes (low, medium and high). For all genotypes relative growth rate (RGR), leaf P content, net assimilation rate (NAR) and leaf area ratio (LAR) increased while P utilization efficiency and leaf starch content decreased at the two higher P regimes compared to the low P regime. The P-efficient genotypes CGN 17903 and CIP 384321.3 had higher RGR compared to the P-inefficient genotypes CGN 22367 and CGN 18233, which resulted from enhanced NAR rather than from LAR. Net photosynthetic rate was similar for all genotypes. However, for P-inefficient genotype CGN 22367, the lower NAR could be explained by increased leaf dark respiration. For P-inefficient genotype CGN 18233 we speculate that increased carbon cost of root respiration or exudation or both, caused low NAR, since leaf dark respiration of this genotype was similar to that of P-efficient genotypes.     

Convergence of IL-1β and VDR Activation Pathways in Human TLR2/1-Induced Antimicrobial Responses

Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1β and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1β activity, involving the upregulation of both IL-1β and IL-1 receptor, and downregulation of the IL-1 receptor antagonist. TLR2/1L induction of IL-1β was required for upregulation of DEFB4, but not cathelicidin, whereas VDR activation was required for expression of both antimicrobial genes. The differential requirements for induction of DEFB4 and cathelicidin were reflected by differences in their respective promoter regions; the DEFB4 promoter had one vitamin D response element (VDRE) and two NF-κB sites, whereas the cathelicidin promoter had three VDREs and no NF-κB sites. Transfection of NF-κB into primary monocytes synergized with 1,25D3 in the induction of DEFB4 expression. Knockdown of either DEFB4 or cathelicidin in primary monocytes resulted in the loss of TLR2/1-mediated antimicrobial activity against intracellular mycobacteria. Therefore, these data identify a novel mechanism of host defense requiring the induction of IL-1β in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen.