Robotic Simulation of Disc Arthroplasty Surgery: Influence of Surgical Placement on Motion Segment Dynamics

A variety of total disc replacement (TDR) designs exist for the treatment of disc pathologies. A key design parameter for a constrained ball and socket device is the location of the fixed center of rotation (COR). A previous study demonstrated that intact motion segment unit (MSU) mechanics and range of motion (ROM) were sensitive to the location of a prescribed sagittal plane rotational axis. Mal-alignment between the implant COR and the COR of the MSU may lead to an overloaded or over constrained condition. Two paradigms exist for the placement of a fixed COR TDR device relative to MSU anatomy: positioning the implant midline or posterior to midline. Presently, there are no data to indicate which paradigm may lead to better biomechanical/clinical outcome. This research attempts to evaluate changes in MSU mechanics and ROM as a result of variations in the size and placement of a simulated ball and socket TDR, like the ProDisc-L lumbar disc prosthesis. Six human cadaveric lumbar MSUs, L4-L5, were tested in flexion/extension using the Spine Robot to an end load limit of 8Nm. A fixed axis protocol was used to impose a pure rotation about a desired anatomical location. The Spine Robot was programmed to rotate the MSU about the COR of the implant. Subsequently, with the MSU held rigid, the implant was removed and rotation about the implant’s COR was repeated. Thereafter, simulated CORs were tested in different anatomical locations as defined by a customized grid pattern. The grid pattern consisted of 8 CORs which simulated the placement of a medium and large size constrained ball and socket device. Measurements of shear forces along the disc plane, axial force normal to the disc plane, segmental bending moment, and segmental ROM were analyzed at each grid point. Analysis of MSU mechanics and ROM for the ProDisc-L and Simulated Implant cases revealed that the two conditions were not comparable. Transfer of tissue pretension from the implant to the Spine Robot on removal of the implant, and dynamic contact forces at the implant surfaces were the contributing factors to the differences observed. Simulated COR testing demonstrated that the posterior tissue response was sensitive to varying placements of the simulated implant. For both implant sizes, posterior positioning of the COR required distraction of the disc space. During flexion, posterior positioning resulted in significantly higher shear and axial forces as well as a trend for reduced ROM. ROM in flexion may have been influenced by different starting positions within the neutral zone due to disc space distraction. During extension, the posterior placement of the COR reduced loading and increased rotation suggesting better alignment with, or separation of the facet joints. This novel study was able to delineate significant differences in spinal tissue response to varying simulated sizes and placements of an ideal fixed COR TDR device. The results of this study suggested that with both implant sizes the posterior placement of the COR will tend to distract the disc space and provide significantly increased ROM in extension at the expense of increased loads on posterior ligaments in flexion

Finished Genome of the Fungal Wheat Pathogen Mycosphaerella graminicola Reveals Dispensome Structure, Chromosome Plasticity, and Stealth Pathogenesis.

The plant-pathogenic fungus Mycosphaerella graminicola (asexual stage: Septoria tritici) causes septoria tritici blotch, a disease that greatly reduces the yield and quality of wheat. This disease is economically important in most wheat-growing areas worldwide and threatens global food production. Control of the disease has been hampered by a limited understanding of the genetic and biochemical bases of pathogenicity, including mechanisms of infection and of resistance in the host. Unlike most other plant pathogens, M. graminicola has a long latent period during which it evades host defenses. Although this type of stealth pathogenicity occurs commonly in Mycosphaerella and other Dothideomycetes, the largest class of plant-pathogenic fungi, its genetic basis is not known. To address this problem, the genome of M. graminicolawas sequenced completely. The finished genome contains 21 chromosomes, eight of which could be lost with no visible effect on the fungus and thus are dispensable. This eight-chromosome dispensome is dynamic in field and progeny isolates, is different from the core genome in gene and repeat content, and appears to have originated by ancient horizontal transfer from an unknown donor. Synteny plots of the M. graminicola chromosomes versus those of the only other sequenced Dothideomycete, Stagonospora nodorum, revealed conservation of gene content but not order or orientation, suggesting a high rate of intra-chromosomal rearrangement in one or both species. This observed “mesosynteny” is very different from synteny seen between other organisms. A surprising feature of the M. graminicolagenome compared to other sequenced plant pathogens was that it contained very few genes for enzymes that break down plant cell walls, which was more similar to endophytes than to pathogens. The stealth pathogenesis of M. graminicola probably involves degradation of proteins rather than carbohydrates to evade host defenses during the biotrophic stage of infection and may have evolved from endophytic ancestors

Comparative Genomics of a Plant-Pathogenic Fungus, Pyrenophora tritici-repentis, Reveals Transduplication and the Impact of Repeat Elements on Pathogenicity and Population Divergence

Pyrenophora tritici-repentis is a necrotrophic fungus causal to the disease tan spot of wheat, whose contribution to crop loss has increased significantly during the last few decades. Pathogenicity by this fungus is attributed to the production of host-selective toxins ( HST), which are recognized by their host in a genotype-specific manner. To better understand the mechanisms that have led to the increase in disease incidence related to this pathogen, we sequenced the genomes of three P. tritici-repentis isolates. A pathogenic isolate that produces two known HSTs was used to assemble a reference nuclear genome of approximately 40 Mb composed of 11 chromosomes that encode 12,141 predicted genes. Comparison of the reference genome with those of a pathogenic isolate that produces a third HST, and a nonpathogenic isolate, showed the nonpathogen genome to be more diverged than those of the two pathogens. Examination of gene-coding regions has provided candidate pathogen-specific proteins and revealed gene families that may play a role in a necrotrophic lifestyle. Analysis of transposable elements suggests that their presence in the genome of pathogenic isolates contributes to the creation of novel genes, effector diversification, possible horizontal gene transfer events, identified copy number variation, and the first example of transduplication by DNA transposable elements in fungi. Overall, comparative analysis of these genomes provides evidence that pathogenicity in this species arose through an influx of transposable elements, which created a genetically flexible landscape that can easily respond to environmental changes.This is the publisher’s final pdf. The published article is copyrighted by The Genetics Society of America and can be found at: http://www.genetics-gsa.org/Keywords: ToxB, Anastomosis, Wheat (Triticum aestivum), Copy number variation, ToxA, Histone H3 transduplicationKeywords: ToxB, Anastomosis, Wheat (Triticum aestivum), Copy number variation, ToxA, Histone H3 transduplicatio

Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens.

The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25× higher than those between inbred lines and 50× lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence

Data from: Colonization history, host distribution, anthropogenic influence and landscape features shape populations of white pine blister rust, an invasive alien tree pathogen

White pine blister rust is caused by the fungal pathogen Cronartium ribicola J.C. Fisch (Basidiomycota, Pucciniales). This invasive alien pathogen was introduced into North America at the beginning of the 20th century on pine seedlings imported from Europe and has caused serious economic and ecological impacts. In this study, we applied a population and landscape genetics approach to understand the patterns of introduction and colonization as well as population structure and migration of C. ribicola. We characterized 1,292 samples of C. ribicola from 66 geographic locations in North America using single nucleotide polymorphisms (SNPs) and evaluated the effect of landscape features, host distribution, and colonization history on the structure of these pathogen populations. We identified eastern and western genetic populations in North America that are strongly differentiated. Genetic diversity is two to five times higher in eastern populations than in western ones, which can be explained by the repeated accidental introductions of the pathogen into northeastern North America compared with a single documented introduction into western North America. These distinct genetic populations are maintained by a barrier to gene flow that corresponds to a region where host connectivity is interrupted. Furthermore, additional cryptic spatial differentiation was identified in western populations. This differentiation corresponds to landscape features, such as mountain ranges, and also to host connectivity. We also detected genetic differentiation between the pathogen populations in natural stands and plantations, an indication that anthropogenic movement of this pathogen still takes place. These results highlight the importance of monitoring this invasive alien tree pathogen to prevent admixture of eastern and western populations where different pathogen races occur

Data from: Colonization history, host distribution, anthropogenic influence and landscape features shape populations of white pine blister rust, an invasive alien tree pathogen

White pine blister rust is caused by the fungal pathogen Cronartium ribicola J.C. Fisch (Basidiomycota, Pucciniales). This invasive alien pathogen was introduced into North America at the beginning of the 20th century on pine seedlings imported from Europe and has caused serious economic and ecological impacts. In this study, we applied a population and landscape genetics approach to understand the patterns of introduction and colonization as well as population structure and migration of C. ribicola. We characterized 1,292 samples of C. ribicola from 66 geographic locations in North America using single nucleotide polymorphisms (SNPs) and evaluated the effect of landscape features, host distribution, and colonization history on the structure of these pathogen populations. We identified eastern and western genetic populations in North America that are strongly differentiated. Genetic diversity is two to five times higher in eastern populations than in western ones, which can be explained by the repeated accidental introductions of the pathogen into northeastern North America compared with a single documented introduction into western North America. These distinct genetic populations are maintained by a barrier to gene flow that corresponds to a region where host connectivity is interrupted. Furthermore, additional cryptic spatial differentiation was identified in western populations. This differentiation corresponds to landscape features, such as mountain ranges, and also to host connectivity. We also detected genetic differentiation between the pathogen populations in natural stands and plantations, an indication that anthropogenic movement of this pathogen still takes place. These results highlight the importance of monitoring this invasive alien tree pathogen to prevent admixture of eastern and western populations where different pathogen races occur

Principal component analysis using a pairwise population matrix of mean population codominant genotypic genetic distances among 66 North American populations of <i>Cronartium ribicola</i>.

<p>First and third components, accounting for 70% and 7% of the total variability. East, Midwest, Northwest and US West refer to regions in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127916#pone.0127916.s005" target="_blank">S1 Table</a>.</p

Analysis of molecular variance for <i>Cronartium ribicola</i> populations sampled across geographic regions, hosts and landscapes in North America.

<p>^aComparison among and within groups of populations arranged by geographic origin, type of stand, pine host and elevation.</p><p>^bProbability that the observed value is larger than the value calculated following permutation (**p<0.01). Φ_c<b>t</b> values were tested by permuting whole populations among groups.</p><p>^cSee <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127916#pone.0127916.s005" target="_blank">S1 Table</a> for details. Three pine species in western populations were considered: <i>P</i>. <i>monticola</i>, <i>P</i>. <i>albicaulis</i>, and <i>P</i>. <i>flexilis</i><b>.</b> Other pine species (<i>P</i>. <i>strobus</i>, <i>P</i>. <i>strobiformis</i>) would have generated confounded effect of host and geography.</p><p>Analysis of molecular variance for <i>Cronartium ribicola</i> populations sampled across geographic regions, hosts and landscapes in North America.</p

Neighbor-joining tree based on Nei’s unbiased pairwise genetic distances derived from the allele frequency at 31 SNPs among 66 North American populations of <i>Cronartium ribicola</i>.

<p>East, Midwest, Northwest and US West refer to regions in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127916#pone.0127916.s005" target="_blank">S1 Table</a>.</p

Spatial principal component analysis of western <i>Cronartium ribicola</i> populations using Delaunay triangulation as connection network.

<p>The first positive eigenvalue component of the sPCA, corresponding to global structure, was plotted on the map. Each population is represented by a blue (positive scores) or red (negative scores) circle of a size proportional to the score loading. The bar represents a barrier to gene flow identified using the Monmonier algorithm in the R package <i>Adegenet</i>.</p