Dual mobility hip arthroplasty wear measurement: Experimental accuracy assessment using radiostereometric analysis (RSA)

SummaryIntroductionThe use of dual mobility cups is an effective method to prevent dislocations. However, the specific design of these implants can raise the suspicion of increased wear and subsequent periprosthetic osteolysis.HypothesisUsing radiostereometric analysis (RSA), migration of the femoral head inside the cup of a dual mobility implant can be defined to apprehend polyethylene wear rate.Study objectivesThe study aimed to establish the precision of RSA measurement of femoral head migration in the cup of a dual mobility implant, and its intra- and interobserver variability.Material and methodsA total hip prosthesis phantom was implanted and placed under weight loading conditions in a simulator. Model-based RSA measurement of implant penetration involved specially machined polyethylene liners with increasing concentric wear (no wear, then 0.25, 0.5 and 0.75mm). Three examiners, blinded to the level of wear, analyzed (10 times) the radiostereometric films of the four liners. There was one experienced, one trained, and one inexperienced examiner. Statistical analysis measured the accuracy, precision, and intra- and interobserver variability by calculating Root Mean Square Error (RMSE), Concordance Correlation Coefficient (CCC), Intra Class correlation Coefficient (ICC), and Bland-Altman plots.ResultsOur protocol, that used a simple geometric model rather than the manufacturer's CAD files, showed precision of 0.072mm and accuracy of 0.034mm, comparable with machining tolerances with low variability. Correlation between wear measurement and true value was excellent with a CCC of 0.9772. Intraobserver reproducibility was very good with an ICC of 0.9856, 0.9883 and 0.9842, respectively for examiners 1, 2 and 3. Interobserver reproducibility was excellent with a CCC of 0.9818 between examiners 2 and 1, and 0.9713 between examiners 3 and 1.DiscussionQuantification of wear is indispensable for the surveillance of dual mobility implants. This in vitro study validates our measurement method. Our results, and comparison with other studies using different measurement technologies (RSA, standard radiographs, Martell method) make model-based RSA the reference method for measuring the wear of total hip prostheses in vivo.Level of evidenceLevel 3. Prospective diagnostic study

FrameDP: sensitive peptide detection on noisy matured sequences

Summary: Transcriptome sequencing represents a fundamental source of information for genome-wide studies and transcriptome analysis and will become increasingly important for expression analysis as new sequencing technologies takes over array technology. The identification of the protein-coding region in transcript sequences is a prerequisite for systematic amino acid-level analysis and more specifically for domain identification. In this article, we present FrameDP, a self-training integrative pipeline for predicting CDS in transcripts which can adapt itself to different levels of sequence qualities

A High-Quality Grapevine Downy Mildew Genome Assembly Reveals Rapidly Evolving and Lineage-Specific Putative Host Adaptation Genes

Downy mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high contiguity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant–pathogen interactions. Plasmopara viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species

A regulatory network-based approach dissects late maturation processes related to the acquisition of desiccation tolerance and longevity of Medicago truncatula seeds

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states

High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development

Using the latest sequencing and optical mapping technologies, we have produced a high-quality de novo assembly of the apple (Malus domestica Borkh.) genome. Repeat sequences, which represented over half of the assembly, provided an unprecedented opportunity to investigate the uncharacterized regions of a tree genome; we identified a new hyper-repetitive retrotransposon sequence that was over-represented in heterochromatic regions and estimated that a major burst of different transposable elements (TEs) occurred 21 million years ago. Notably, the timing of this TE burst coincided with the uplift of the Tian Shan mountains, which is thought to be the center of the location where the apple originated, suggesting that TEs and associated processes may have contributed to the diversification of the apple ancestor and possibly to its divergence from pear. Finally, genome-wide DNA methylation data suggest that epigenetic marks may contribute to agronomically relevant aspects, such as apple fruit development

Mycobacterium tuberculosis Exploits Asparagine to Assimilate Nitrogen and Resist Acid Stress during Infection

Mycobacterium tuberculosis is an intracellular pathogen. Within macrophages, M. tuberculosis thrives in a specialized membrane-bound vacuole, the phagosome, whose pH is slightly acidic, and where access to nutrients is limited. Understanding how the bacillus extracts and incorporates nutrients from its host may help develop novel strategies to combat tuberculosis. Here we show that M. tuberculosis employs the asparagine transporter AnsP2 and the secreted asparaginase AnsA to assimilate nitrogen and resist acid stress through asparagine hydrolysis and ammonia release. While the role of AnsP2 is partially spared by yet to be identified transporter(s), that of AnsA is crucial in both phagosome acidification arrest and intracellular replication, as an M. tuberculosis mutant lacking this asparaginase is ultimately attenuated in macrophages and in mice. Our study provides yet another example of the intimate link between physiology and virulence in the tubercle bacillus, and identifies a novel pathway to be targeted for therapeutic purposes. © 2014 Gouzy et al