The role of fabric in the large strain compressive behavior of human trabecular bone

Osteoporosis-related vertebral body fractures involve large compressive strains of trabecular bone. The small strain mechanical properties of the trabecular bone such as the elastic modulus or ultimate strength can be estimated using the volume fraction and a second order fabric tensor, but it remains unclear if similar estimations may be extended to large strain properties. Accordingly, the aim of this work is to identify the role of volume fraction and especially fabric in the large strain compressive behavior of human trabecular bone from various anatomical locations. Trabecular bone biopsies were extracted from human T12 vertebrae (n=31), distal radii (n=43), femoral head (n=44), and calcanei (n=30), scanned using microcomputed tomography to quantify bone volume fraction (BV/TV) and the fabric tensor (M), and tested either in unconfined or confined compression up to very large strains (～70%). The mechanical parameters of the resulting stress-strain curves were analyzed using regression models to examine the respective influence of BV/TV and fabric eigenvalues. The compressive stress-strain curves demonstrated linear elasticity, yielding with hardening up to an ultimate stress, softening toward a minimum stress, and a steady rehardening followed by a rapid densification. For the pooled experiments, the average minimum stress was 1.89 ± 1.77 MPa, while the corresponding mean strain was 7.15 ± 1.84%. The minimum stress showed a weaker dependence with fabric as the elastic modulus or ultimate strength. For the confined experiments, the stress at a logarithmic strain of 1.2 was 8.08 ± 7.91 MPa, and the dissipated energy density was 5.67 ± 4.42 MPa. The latter variable was strongly related to the volume fraction (R(2)=0.83) but the correlation improved only marginally with the inclusion of fabric (R(2)=0.84). The influence of fabric on the mechanical properties of human trabecular bone decreases with increasing strain, while the role of volume fraction remains important. In particular, the ratio of the minimum versus the maximum stress, i.e., the relative amount of softening, decreases strongly with fabric, while the dissipated energy density is dominated by the volume fraction. The collected results will prove to be useful for modeling the softening and densification of the trabecular bone using the finite element method.     

Sulfolobus genome: from genomics to biology

Major progress in sequencing the genome of Sulfolobus solfataricus has been closely concerted with the characterization and sequencing of many extrachromosomal genetic elements, including viruses, cryptic plasmids and conjugative plasmids, as well as mobile archaeal introns and transposons. The latter have provided a basis for developing the first generation of vectors that are now being used to study the genetics of Sulfolobus and other Archaea.     

Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes

The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are basal members of Ixodidae and have the same gene order as Limulus polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA, tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln) have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes. The tRNA(Cys) gene has translocated between the control region and the tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region is duplicated, and both copies undergo concerted evolution. Primers that flank these rearrangements confirm that this gene order is conserved in all metastriate ticks examined. Correspondence analysis of amino acid and codon use in the two ticks and in nine other arthropod mitochondrial genomes indicate a strong bias in R. sanguineus towards amino acids encoded by AT-rich codons.      

Nucleotide polymorphism at the alcohol dehydrogenase locus of pocket gophers, genus Geomys

Using the strictly neutral model as a null hypothesis, we tested for deviations from expected levels of nucleotide polymorphism at the alcohol dehydrogenase locus (Adh-1) within and among four species of pocket gophers (Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G. attwateri). The complete protein-encoding region was examined, and 10 unique alleles, representing both electromorphic and cryptic alleles, were used to test hypotheses (e.g., the neutral model) concerning the maintenance of genetic variation. Nineteen variable sites were identified among the 10 alleles examined, including 9 segregating sites occurring in synonymous positions and 10 that were nonsynonymous. Several statistical methods, including those that test for within-species variation as well as those that examine variation within and among species, failed to reject the null hypothesis that variation (both within and between species of Geomys) at the Adh locus is consistent with the neutral theory. However, there was significant heterogeneity in the ratio of polymorphism to divergence across the gene, with polymorphisms clustered in the first half of the coding region and fixed differences clustered in the second half of the gene. Two alternative hypotheses are discussed as possible explanations for this heterogeneity: an old balanced polymorphism in the first half of the gene or a recent selective sweep in the second half of the gene.      

Weighted genome trees: refinements and applications

There are many ways to group completed genome sequences in hierarchical patterns (trees) reflecting relationships between their genes. Such groupings help us organize biological information and bear crucially on underlying processes of genome and organismal evolution. Genome trees make use of all comparable genes but can variously weight the contributions of these genes according to similarity, congruent patterns of similarity, or prevalence among genomes. Here we explore such possible weighting strategies, in an analysis of 142 prokaryotic and 5 eukaryotic genomes. We demonstrate that alternate weighting strategies have different advantages, and we propose that each may have its specific uses in systematic or evolutionary biology. Comparisons of results obtained with different methods can provide further clues to major events and processes in genome evolution.     

Deduction of probable events of lateral gene transfer through comparison of phylogenetic trees by recursive consolidation and rearrangement

Background  

When organismal phylogenies based on sequences of single marker genes are poorly resolved, a logical approach is to add more markers, on the assumption that weak but congruent phylogenetic signal will be reinforced in such multigene trees. Such approaches are valid only when the several markers indeed have identical phylogenies, an issue which many multigene methods (such as the use of concatenated gene sequences or the assembly of supertrees) do not directly address. Indeed, even when the true history is a mixture of vertical descent for some genes and lateral gene transfer (LGT) for others, such methods produce unique topologies.     

Gene content and organization of a 281-kbp contig from the genome of the extremely thermophilic archaeon, Sulfolobus solfataricus P2.

The sequence of a 281-kbp contig from the crenarchaeote Sulfolobus solfataricus P2 was determined and analysed. Notable features in this region include 29 ribosomal protein genes, 12 tRNA genes (four of which contain archaeal-type introns), operons encoding enzymes of histidine biosynthesis, pyrimidine biosynthesis, and arginine biosynthesis, an ATPase operon, numerous genes for enzymes of lipopolysaccharide biosynthesis, and six insertion sequences. The content and organization of this contig are compared with sequences from crenarchaeotes, euryarchaeotes, bacteria, and eukaryotes.     

De novo Assembly of highly diverse viral populations

ABSTRACT: BACKGROUND: Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and, as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. RESULTS: We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/viral-genomics-analysis-software CONCLUSIONS: We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.