Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Evolution of untranslated régions of mRNAs in primates

Until recently, functional and evolutionary studies have focused almost exclusively on protein- coding sequences, but it has become increasingly clear that noncoding genomic régions harbour a wealth of functional information. The untranslated régions (UTRs) of protein-coding mRNAs are one such example, playing an important rôle in posttranscriptional régulation, for instance translational control and efficiency, mRNA stability and mRNA subcellular localisation. Nevertheless, due to incomplète UTR annotations in non-model organisms, functional rôles of UTRs and especially their evolutionary dynamics continue to be poorly understood. In this study we focused on the primates, so we first focused improving genomic annotations, and in particular, UTR annotations across primates. To do that, we used RNA-seq information to complété the annotations of protein-coding genes, by adding new exons and new exon boundaries to existing Ensembl annotations. To compensate for différence in samples in RNA-seq data and coverage, we projected the new annotations from one species to ail other species. We were able to add thousands of new exons and new alternative splice sites, the majority being previously unannotated UTR exons. We classifïed the sequences into UTR or coding based on their evolutionary signature, and using start and stop codons as additional criteria. We sought to study how UTR exon usage differs across tissues. We detected that UTR exons are more often differentially used across tissues compared to coding exons. Moreover, différent organs exhibit différent exon usage patterns. Particularly in testis we detect l) high proportion of 5' UTR exons that are more often used in testis compared to other tissues and 2) high proportion of 3' UTR exons that are less used in testis. We detected a motif present in ail alternative promoters used specifically in testis. Also, we showed that 3' UTR sequences that are less used in testis have high number of predicted HuR protein binding sites, indicating avoidance of these binding sites. Finally, we wanted to investigate how UTR usage evolves across primates. We demonstrated that contrary to what has been shown, alternative polyadenylation usage evolves rapidly. We also detect that UTR usage is as often lineage-specific as coding exon usage and it has higher effect size of usage change. We detect higher proportion of lineage-specific tissue-specific exons in testis compared to other tissues suggesting that new isoforms might first arise in testis. Additionally, we detect conserved tissue-specific exons usage across species, and surprisingly, proportion of conserved UTRs is higher than proportion of conserved coding exons implying a spécial rôle of UTRs in tissue-dependent posttranscriptional régulation. To conclude, we created the first comparable annotations for 6 primate species and we believe these annotations will be of great value to the scientific community. Additionally, we performed the first large-scale evolutionary study of primate UTRs, discovering tissue and/or lineage spécifié UTR usage of potential functional conséquences. -- Dans le domaine de la génomique évolutive, la plupart des études se sont focalisées jusqu'à présent sur les régions qui codent pour des protéines. Cependant, il est maintenant évident que les régions non-codantes des génomes contiennent de nombreuses informations fonctionnelles. En particulier, les régions non-traduites (« untranslated régions » en anglais, d'où l'abréviation UTR) des ARNs messagers jouent des rôles importants dans le contrôle de l'expression des gènes et de la production de protéines, dans la stabilité des ARNs messagers etc. A présent, les rôles fonctionnels et en particulier la dynamique évolutive des UTRs ne sont toujours pas parfaitement compris. Le premier objectif de cette thèse était d'améliorer les annotations des UTRs dans les génomes de primates. Nous avons utilisé des données de séquençage de transcriptome pour compléter les annotations des gènes codants pour des protéines, en ajoutant de nouveaux exons ou en étendant les frontières existantes des exons. Nous avons également utilisé une approche de projection entre espèces pour améliorer la comparabilité des annotations. Nous avons utilisé la signature évolutive des séquences d'ADN pour déterminer si elles correspondent à des régions codantes pour des protéines ou, au contraire, à des éléments non-codants. Nous avons ainsi identifié de milliers de nouveaux exons, dont la majorité correspond à des UTRs. Le deuxième objectif était d'étudier les variations des UTRs entre tissus. Nous avons démontré que l'usage différentiel des UTRs présente la même quantité de variation entre tissus que l'usage différentiel d'exons codants. Les patrons d'utilisation des différents UTRs varient donc considérablement entre tissus. En particulier, nous avons détecté une proportion élevée de 5'-UTRs qui sont utilisés préférentiellement dans les testicules, et une proportion élevées de 3'-UTRs qui sont - au contraire - évités dans les testicules. Nous avons identifié un motif de fixation d'un facteur de transcription qui est commun à tous les promoteurs utilisés spécifiquement dans les testicules. Nous avons également détecté un enrichissement en motifs de fixation de la protéine HuR dans les régions 3'-UTRs évitées dans cet organe. Enfin, nous avons étudié l'évolution des UTRs chez les primates. Nous avons démontré que l'évolution de l'utilisation des sites alternatifs de polyadenylation évolue rapidement. De même, nos résultats montrent que l'utilisation différentielle des UTRs est plus souvent spécifique à une lignée ou à une espèce que l'utilisation différentielle des exons codants. La plupart des UTRs spécifiques à une lignée sont détectés dans les testicules, ce qui suggère que les nouveaux isoformes sont préférentiellement exprimés dans cet organe. Nous avons identifié de nombreux UTRs qui utilisés spécifiquement dans un organe, dans plusieurs espèces, indiquant que ces régions pourraient avoir un rôle important dans les réseaux de régulation qui définissent l'identité des organes

Universal Mosaicing using Pipe Projection

Video mosaicing is commonly used to increase the visual field of view by pasting together many video frames. Existing mosaicing methods are effective only in very limited cases where the image motion is almost a uniform translation or the camera performs a pure pan. Forward camera motion or camera zoom are very problematic for traditional mosaicing. A mosaicing methodology..

Mosaicing with Generalized Strips

Video mosaicing is commonly used to increase the effective visual field of view. Existing mosaicing methods are based on image alignment, and are effective only in very limited cases. To overcome most restrictions, mosaicing is presented in this paper as a process of collecting strips. Strips which are perpendicular to the optical flow are cut out of the images, and are warped so that within each strip the optical flow will be parallel. These strips are then pasted into the mosaic. This approach enables to define mosaicing even for cases of forward motion and for zoom. View interpolation, generating dense intermediate views, is used to overcome parallax effects. 1 Introduction An introduction and a survey of mosaicing methods can be found in [6]. We will only give a brief introduction focusing on the aspects relevant to this work. Early mosaicing methods were used for aerial and satellite images. In both cases the objects in the scene are distant from the camera, and camera motion co..

Structure of unliganded membrane-proximal domains FN4-FN5-FN6 of DCC

Ministry of Education of China; National Natural Science Foundation of China (NSFC) [81425009]; NSFC [31630028, 91632305]; NIH [HL103526]; Peking-Tsinghua Center for Life Sciences; European Research Council (ERC) under a Horizon MSCA-IF [702346]SCI(E)LETTER9701-705

Comparison of multivessel coronary angioplasty with surgical revascularization with both internal mammary arteries

To evaluate medium-term clinical results of two major methods of myocardial revascularization, we compared 80 consecutive patients with multivessel percutaneous transluminal coronary angioplasty (PTCA) with 80 consecutive patients with coronary surgery using both internal mammary arteries in all and additional venous grafts in some. Patients in the surgical group had a higher extent of coronary artery disease. In patients with PTCA a mean of 2.2 vessels per patient were attempted, and in patients with surgery 2.7 distal anastomoses per patient were performed. Primary success for PTCA and surgery was 86% vs 94% and complications occurred in 7% vs 6%, respectively. Control angiograms, done in 86% of patients (59/69) after successful PTCA, showed a recurrence in 42% (25/59). Repeat PTCA was done in 15, elective surgery in seven, and a medical treatment was pursued in 3% patients with restenosis. Recurrence of symptoms after successful surgery was found in three patients (4%). They were treated with PTCA. Clinical follow-up was available for all patients, at a mean of 12 +/- 6 months after PTCA and 16 +/- 9 months after surgery. Mean improvement was 1.5 NYHA functional classes after successful PTCA and 2.1 after surgery; 60% (48/80) vs 89% (48/80), respectively, were in class I (p less than .0001). There were fewer PTCA patients than surgical patients without antianginal drugs at follow-up (19% [11/58] vs 37% [18/48]; p less than .05), and their double product during exercise testing was inferior (272 +/- 56 vs 295 +/- 47 mm Hg X beats/min/100; p less than .05). Medium-term clinical outcome appears better after successful surgery with both internal mammary arteries than after successful multivessel PTCA