DNA Slippage Occurs at Microsatellite Loci without Minimal Threshold Length in Humans: A Comparative Genomic Approach

The dynamics of microsatellite, or short tandem repeats (STRs), is well documented for long, polymorphic loci, but much less is known for shorter ones. For example, the issue of a minimum threshold length for DNA slippage remains contentious. Model-fitting methods have generally concluded that slippage only occurs over a threshold length of about eight nucleotides, in contradiction with some direct observations of tandem duplications at shorter repeated sites. Using a comparative analysis of the human and chimpanzee genomes, we examined the mutation patterns at microsatellite loci with lengths as short as one period plus one nucleotide. We found that the rates of tandem insertions and deletions at microsatellite loci strongly deviated from background rates in other parts of the human genome and followed an exponential increase with STR size. More importantly, we detected no lower threshold length for slippage. The rate of tandem duplications at unrepeated sites was higher than expected from random insertions, providing evidence for genome-wide action of indel slippage (an alternative mechanism generating tandem repeats). The rate of point mutations adjacent to STRs did not differ from that estimated elsewhere in the genome, except around dinucleotide loci. Our results suggest that the emergence of STR depends on DNA slippage, indel slippage, and point mutations. We also found that the dynamics of tandem insertions and deletions differed in both rates and size at which these mutations take place. We discuss these results in both evolutionary and mechanistic terms

Comment objectiver les moyens et outils à utiliser pour réduire l’artificialisation ?

Afin d’atteindre les objectifs de réduction de l’artificialisation, l’objectivation des tendances en cours, des moyens et outils à utiliser apparait comme une aide à la décision indispensable pour les autorités. Cet atelier fait un focus sur différents éléments mis en avant par la recherche CPDT « Intensification et requalification des centralités pour lutter contre l’étalement urbain et la dépendance à la voiture » - Volet 2. L’atelier proposé s’organise autour de trois grands axes : (i) contextualisation de la lutte contre l’artificialisation des sols, (ii) tendances et perspectives relatives à l’artificialisation et au recyclage urbain et (iii) objectivation de quelques mesures/actions/outils envisageables pour réduire l’artificialisation.recherche CPDT « Intensification et requalification des centralités pour lutter contre l’étalement urbain et la dépendance à la voiture »11. Sustainable cities and communities13. Climate action15. Life on lan

Total knee arthroplasty after opening– versus closing-wedge high tibial osteotomy. A 135-case series with minimum 5-year follow-up

INTRODUCTION: High tibial osteotomy (HTO) is effective in treating isolated medial osteoarthritis of the knee, but subsequent deterioration is inevitable, and total knee arthroplasty (TKA) is then an option. The present study sought to compare TKA following medial opening-wedge HTO (OW-HTO) versus lateral closing-wedge HTO (CW-HTO) in terms of intraoperative data and clinical results. The study hypothesis was that there is no significant difference in clinical results or complications in TKA following OW-HTO or CW-HTO. MATERIAL AND METHOD: A retrospective multicenter (9 centers) study was conducted for the French Society of Orthopedic Surgery and Traumatology (SoFCOT), including 135 TKAs following HTO (58 OW and 77 CW) at a minimum 5 years' follow-up. Mean interval between HTO and TKA was 134 months and was longer in case of CW-HTO (P<0.0001). Mean age at TKA was 65.4 years and older in case of CW-HTO (P=0.021). Tibial slope was greater in case of OW-HTO (P=0.024). Prior to TKA, 55.7% of patients could walk without canes, 98.4% found stairs difficult or impossible and only 19.1% could manage a walking distance greater than 1000m. Mean flexion was 110°; 54.2% of patients showed frontal knee stability and 87.8% sagittal stability; 60.1% had a mechanical axis in varus, without difference according to OW- or CW-HTO. RESULTS: Hardware was almost systematically removed (in 98.5% of cases): in the same step for OW-HTO (P=0.018) or often in 2 steps for CW-HTO. The primary approach was generally re-used (54.2%), but less frequently in the CW-HTO group (P=0.0004). Lateral or medial ligament release was not associated in respectively 78.2% and 79.7% of cases. The TKA implant was usually without stem (87.2%) and was fitted using a conventional technique (74.4%). At a mean 87 months' follow-up, 78.5% of patients could walk without canes, stairs were still difficult or impossible for 67%, and 74.1% could now walk further than 1000m; mean flexion was 110.5°. Overall, 91.5% of patients showed frontal knee stability and 98.2% sagittal stability, without difference according to OW- or CW-HTO. There were 15 complications within 3 months, more often in the OW-HTO group (12.3%) although not significantly, and with no difference in severity. Late complications comprised loosening (5.5%) and infection (3.6%) and were more frequent in the CW-HTO group (12%) (P<0.05). DISCUSSION: The study hypothesis was partially confirmed. The only technical differences concerned hardware removal, often performed in two steps in case of CW-HTO, and TKA approach, which differed from the primary approach in case of CW-HTO. Clinical results were comparable between OW- and CW-HTO, but late complications were more frequent in the CW-HTO group

Ten-year survival and complications of total knee arthroplasty for osteoarthritis secondary to trauma or surgery: A French multicentre study of 263 patients

BACKGROUND: Previous surgical procedures raise technical challenges in performing total knee arthroplasty (TKA) and may affect TKA outcomes. Survival rates of TKA done after trauma or surgery to the knee have not been accurately determined in large populations. The objectives of this retrospective study in 263 patients with TKA after knee trauma or surgery and a follow-up of 10 years were to assess survival, functional outcomes, and the nature and frequency of complications. HYPOTHESIS: Knee trauma or surgery before TKA increases the risk of complications and decreases implant survival. MATERIAL AND METHODS: Two hundred and sixty-three patients (122 [47%] females and 141 [53%] males) underwent TKA between 2005 and 2009 at nine centres in France. Mean age at surgery was 61 years. The patients had knee osteoarthritis secondary to a fracture (n=66), osteotomy (n=131), or ligament injury (n=66). Mean time from trauma or surgery to TKA was 145 months (range, 72-219 months). RESULTS: Major complications were infection (n=12, 4.5%), skin problems (n=8, 3%), and stiffness (n=8, 3%). Ten-year survival to implant exchange for any reason was 89%±2.8%. Flexion range increased by 2.5°±17° (p=0.02) to a mean of 110° (range, 30° to 140°); extension range increased by 4°±7° (p<0.001) to a mean of -1.19 (range, -20° to 0°). Of the 263 patients, 157 (60%) reported little or no pain at last follow-up. Mean postoperative hip-knee-ankle angle was 179°±3.2° (range, 171°-188°). CONCLUSION: TKA performed after knee injury or surgery carries a risk of specific complications (infection, skin problems, and stiffness) and may have a lower survival rate compared to primary TKA

Short- and Long-term Evolutionary Dynamics of Bacterial Insertion Sequences: Insights from Wolbachia Endosymbionts

Transposable elements (TE) are one of the major driving forces of genome evolution, raising the question of the long-term dynamics underlying their evolutionary success. Long-term TE evolution can readily be reconstructed in eukaryotes, thanks to many degraded copies constituting genomic fossil records of past TE proliferations. By contrast, bacterial genomes usually experience high sequence turnover and short TE retention times, thereby obscuring ancient TE evolutionary patterns. We found that Wolbachia bacterial genomes contain 52–171 insertion sequence (IS) TEs. IS account for 11% of Wolbachia wRi, which is one of the highest IS genomic coverage reported in prokaryotes to date. We show that many IS groups are currently expanding in various Wolbachia genomes and that IS horizontal transfers are frequent among strains, which can explain the apparent synchronicity of these IS proliferations. Remarkably, >70% of Wolbachia IS are nonfunctional. They constitute an unusual bacterial IS genomic fossil record providing direct empirical evidence for a long-term IS evolutionary dynamics following successive periods of intense transpositional activity. Our results show that comprehensive IS annotations have the potential to provide new insights into prokaryote TE evolution and, more generally, prokaryote genome evolution. Indeed, the identification of an important IS genomic fossil record in Wolbachia demonstrates that IS elements are not always of recent origin, contrary to the conventional view of TE evolution in prokaryote genomes. Our results also raise the question whether the abundance of IS fossils is specific to Wolbachia or it may be a general, albeit overlooked, feature of prokaryote genomes

Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma

International audienceBACKGROUND: We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors. METHODOLOGY/PRINCIPAL FINDINGS: Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status. CONCLUSIONS/SIGNIFICANCE: Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10(-49), Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction

Intensification et requalification des centralités pour lutter contre l'étalement urbain et la dépendance à la voiture : rapport final de la subvention 2021

Intensification et requalification des centralités pour lutter contre l’étalement urbain et la dépendance à la voiture12. Responsible consumption and production13. Climate actio

Detecting microsatellites within genomes: significant variation among algorithms

<p>Abstract</p> <p>Background</p> <p>Microsatellites are short, tandemly-repeated DNA sequences which are widely distributed among genomes. Their structure, role and evolution can be analyzed based on exhaustive extraction from sequenced genomes. Several dedicated algorithms have been developed for this purpose. Here, we compared the detection efficiency of five of them (TRF, Mreps, Sputnik, STAR, and RepeatMasker).</p> <p>Results</p> <p>Our analysis was first conducted on the human X chromosome, and microsatellite distributions were characterized by microsatellite number, length, and divergence from a pure motif. The algorithms work with user-defined parameters, and we demonstrate that the parameter values chosen can strongly influence microsatellite distributions. The five algorithms were then compared by fixing parameters settings, and the analysis was extended to three other genomes (<it>Saccharomyces cerevisiae</it>, <it>Neurospora crassa </it>and <it>Drosophila melanogaster</it>) spanning a wide range of size and structure. Significant differences for all characteristics of microsatellites were observed among algorithms, but not among genomes, for both perfect and imperfect microsatellites. Striking differences were detected for short microsatellites (below 20 bp), regardless of motif.</p> <p>Conclusion</p> <p>Since the algorithm used strongly influences empirical distributions, studies analyzing microsatellite evolution based on a comparison between empirical and theoretical size distributions should therefore be considered with caution. We also discuss why a typological definition of microsatellites limits our capacity to capture their genomic distributions.</p