Conserved non-genic sequences - an unexpected feature of mammalian genomes.

Mammalian genomes contain highly conserved sequences that are not functionally transcribed. These sequences are single copy and comprise approximately 1-2% of the human genome. Evolutionary analysis strongly supports their functional conservation, although their potentially diverse, functional attributes remain unknown. It is likely that genomic variation in conserved non-genic sequences is associated with phenotypic variability and human disorders. So how might their function and contribution to human disorders be examined?

Optimal 3-T MRI for depiction of the finger A2 pulley: comparison between T1-weighted, fat-saturated T2-weighted and gadolinium-enhanced fat-saturated T1-weighted sequences

OBJECTIVE: To compare three spin-echo sequences, transverse T1-weighted (T1WI), transverse fat-saturated (FS) T2-weighted (T2WI), and transverse gadolinium-enhanced (Gd) FS T1WI, for the visualisation of normal and abnormal finger A2 pulley with magnetic resonance (MR) imaging at 3 tesla (T). MATERIALS AND METHODS: Sixty-three fingers from 21 patients were consecutively investigated. Two musculoskeletal radiologists retrospectively compared all sequences to assess the visibility of normal and abnormal A2 pulleys and the presence of motion or ghost artefacts. RESULTS: Normal and abnormal A2 pulleys were visible in 94% (59/63) and 95% (60/63) on T1WI sequences, in 63% (40/63) and 60% (38/63) on FS T2WI sequences, and in 87% (55/63) and 73% (46/63) on Gd FS T1WI sequences when read by the first and second observer, respectively. Motion and ghost artefacts were higher on FS T2WI sequences. Seven among eight abnormal A2 pulleys were detected, and were best depicted with Gd FS T1WI sequences in 71% (5/7) and 86% (6/7) by the first and the second observer, respectively. CONCLUSION: In 3-T MRI, the comparison between transverse T1WI, FS T2WI, and Gd FS T1WI sequences shows that transverse T1WI allows excellent depiction of the A2 pulley, that FS T2WI suffers from a higher rate of motion and ghost artefacts, and transverse Gd FS T1WI is the best sequence for the depiction of abnormal A2 pulley.

The E.coli RuvAB proteins branch migrate Holliday junctions through heterologous DNA sequences in a reaction facilitated by SSB.

During genetic recombination a heteroduplex joint is formed between two homologous DNA molecules. The heteroduplex joint plays an important role in recombination since it accommodates sequence heterogeneities (mismatches, insertions or deletions) that lead to genetic variation. Two Escherichia coli proteins, RuvA and RuvB, promote the formation of heteroduplex DNA by catalysing the branch migration of crossovers, or Holliday junctions, which link recombining chromosomes. We show that RuvA and RuvB can promote branch migration through 1800 bp of heterologous DNA, in a reaction facilitated by the presence of E.coli single-stranded DNA binding (SSB) protein. Reaction intermediates, containing unpaired heteroduplex regions bound by SSB, were directly visualized by electron microscopy. In the absence of SSB, or when SSB was replaced by a single-strand binding protein from bacteriophage T4 (gene 32 protein), only limited heterologous branch migration was observed. These results show that the RuvAB proteins, which are induced as part of the SOS response to DNA damage, allow genetic recombination and the recombinational repair of DNA to occur in the presence of extensive lengths of heterology.

Biased gene conversion and GC-content evolution in the coding sequences of reptiles and vertebrates.

Mammalian and avian genomes are characterized by a substantial spatial heterogeneity of GC-content, which is often interpreted as reflecting the effect of local GC-biased gene conversion (gBGC), a meiotic repair bias that favors G and C over A and T alleles in high-recombining genomic regions. Surprisingly, the first fully sequenced nonavian sauropsid (i.e., reptile), the green anole Anolis carolinensis, revealed a highly homogeneous genomic GC-content landscape, suggesting the possibility that gBGC might not be at work in this lineage. Here, we analyze GC-content evolution at third-codon positions (GC3) in 44 vertebrates species, including eight newly sequenced transcriptomes, with a specific focus on nonavian sauropsids. We report that reptiles, including the green anole, have a genome-wide distribution of GC3 similar to that of mammals and birds, and we infer a strong GC3-heterogeneity to be already present in the tetrapod ancestor. We further show that the dynamic of coding sequence GC-content is largely governed by karyotypic features in vertebrates, notably in the green anole, in agreement with the gBGC hypothesis. The discrepancy between third-codon positions and noncoding DNA regarding GC-content dynamics in the green anole could not be explained by the activity of transposable elements or selection on codon usage. This analysis highlights the unique value of third-codon positions as an insertion/deletion-free marker of nucleotide substitution biases that ultimately affect the evolution of proteins.

Evolution of vitellogenin genes: comparative analysis of the nucleotide sequences downstream of the transcription initiation site of four Xenopus laevis and one chicken gene.

Electron microscopic analysis of heteroduplexes between the most distantly related Xenopus vitellogenin genes (A genes X B genes) has revealed the distribution of homologous regions that have been preferentially conserved after the duplication events that gave rise to the multigene family in Xenopus laevis. DNA sequence analysis was limited to the region downstream of the transcription initiation site of the Xenopus genes A1, B1 and B2 and a comparison with the Xenopus A2 and the major chicken vitellogenin gene is presented. Within the coding regions of the first three exons, nucleotide substitutions resulting in amino acid changes accumulate at a rate similar to that observed in globin genes. This suggests that the duplication event which led to the formation of the A and B ancestral genes in Xenopus laevis occurred about 150 million years ago. Homologous exons of the A1-A2 and B1-B2 gene pairs, which formed about 30 million years ago, show a quite similar sequence divergence. In contrast, A1-A2 homologous introns seem to have evolved much faster than their B1-B2 counterparts.

Clustering and hot spot detection in socio-economic spatio-temporal data

Distribution of socio-economic features in urban space is an important source of information for land and transportation planning. The metropolization phenomenon has changed the distribution of types of professions in space and has given birth to different spatial patterns that the urban planner must know in order to plan a sustainable city. Such distributions can be discovered by statistical and learning algorithms through different methods. In this paper, an unsupervised classification method and a cluster detection method are discussed and applied to analyze the socio-economic structure of Switzerland. The unsupervised classification method, based on Ward's classification and self-organized maps, is used to classify the municipalities of the country and allows to reduce a highly-dimensional input information to interpret the socio-economic landscape. The cluster detection method, the spatial scan statistics, is used in a more specific manner in order to detect hot spots of certain types of service activities. The method is applied to the distribution services in the agglomeration of Lausanne. Results show the emergence of new centralities and can be analyzed in both transportation and social terms.

Identification of estrogen-responsive DNA sequences by transient expression experiments in a human breast cancer cell line.

The expression of a hybrid gene formed by the promoter region of the Xenopus laevis vitellogenin gene B1 and the CAT coding region is regulated by estrogen when the gene is transfected into hormone-responsive MCF-7 cells. Furthermore, the 5' flanking region of the gene B1 alone can confer inducibility to heterologous promoters, although to a varying extent depending on the promoter used. Deletion mapping of he vitellogenin hormone-responsive sequences revealed that a 13 bp element 5'-AGTCACTGTGACC-3' at position -334 is essential for estrogen inducibility. We have shown previously that this 13 bp element is present upstream of several liver-specific estrogen-inducible genes.

Athletic injuries of the extensor carpi ulnaris subsheath: MRI findings and utility of gadolinium-enhanced fat-saturated T1-weighted sequences with wrist pronation and supination

Purpose: To report the magnetic resonance imaging (MRI) findings in athletic injuries of the extensor carpi ulnaris (ECU) subsheath, assessing the utility of gadolinium-enhanced (Gd) fat-saturated (FS) T1-weighted sequences with wrist pronation and supination. Methods and Materials: Sixteen patients (13 males, 3 females; mean age 30.3 years) with athletic injuries of the ECU subsheath sustained between January 2003 and June 2009 were included in this retrospective study. Initial and follow‑up 1.5-T wrist MRIs were performed with transverse T1-weighted and STIR sequences in pronation, and Gd FS T1-weighted sequences with wrist pronation and supination. Two radiologists assessed the type of injury (A to C), ECU tendon stability, associated lesions and rated pulse sequences using a three-point scale: 1 = poor, 2 = good and 3 = excellent. Results: Gd-enhanced FS T1-weighted transverse sequences in supination (2.63) and pronation (2.56) were most valuable, compared with STIR (2.19) and T1 weighted (1.94). Nine type A, one type B and six type C injuries were found. There were trends towards diminution in size, signal intensity and enhancement of associated pouches on follow‑up MRI and tendon stabilisation within the ulnar groove. Conclusion: Gd-enhanced FS T1-weighted sequences with wrist pronation and supination are most valuable in assessing and follow‑up athletic injuries of the ECU subsheath on 1.5-T MRI.

Temporal variability of antibiotics fluxes in wastewater and contribution from hospitals.

Significant quantities of antibiotics are used in all parts of the globe to treat diseases with bacterial origins. After ingestion, antibiotics are excreted by the patient and transmitted in due course to the aquatic environment. This study examined temporal fluctuations (monthly time scale) in antibiotic sources (ambulatory sales and data from a hospital dispensary) for Lausanne, Switzerland. Source variability (i.e., antibiotic consumption, monthly data for 2006-2010) were examined in detail for nine antibiotics--azithromycin, ciprofloxacin, clarithromycin, clindamycin, metronidazole, norfloxacin, ofloxacin, sulfamethoxazole and trimethoprim, from which two main conclusions were reached. First, some substances--azithromycin, clarithromycin, ciprofloxacin--displayed high seasonality in their consumption, with the winter peak being up to three times higher than the summer minimum. This seasonality in consumption resulted in seasonality in Predicted Environmental Concentrations (PECs). In addition, the seasonality in PECs was also influenced by that in the base wastewater flow. Second, the contribution of hospitals to the total load of antibiotics reaching the Lausanne Wastewater Treatment Plant (WTP) fluctuated markedly on a monthly time scale, but with no seasonal pattern detected. That is, there was no connection between fluctuations in ambulatory and hospital consumption for the substances investigated.

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

Epileptogenic zone, electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy : a correlation study

Objectif : Etudier les résultats cliniques du traitement de patients atteints pai- une épilepsie mésiale du lobe temporal (MTLE) réfractaire, par stimulation cérébrale profonde (DBS) de l'hippocampe, en fonction de l'emplacement de l'électrode. Méthodes : Huit patients atteints de MTLE implantés dans l'hippocampe et stimulés par DBS à haute fréquence ont été inclus dans cette étude. Cinq ont subi des enregistrements invasifs avec des électrodes profondes dans le but d'estimer la localisation du foyer ictal avant de procéder à une DBS chronique. La position des contacts actifs de l'électrode a été mesurée en utilisant une imagerie post-opératoire. Les distances par rapport au foyer ictal ont été calculées, et les structures hippocampiques influencées par la stimulation ont été identifiées au moyen d'un atlas neuro-anatomique. Ces deux paramètres ont été corrélés avec la réduction de la fréquence d'apparition des crises. Résultats : Les distances entre la localisation estimée des contacts actifs de l'électrode et le foyer ictal étaient respectivement 11.0 +/- 4.3 ou 9.1 +/- 2.3 mm pour les patients présentant une réduction de > 50% ou < 50% de la fréquence des crises. Chez les patients (N = 6) montrant une réduction de > 50% de la fréquence des crises, 100% avaient des contacts actifs situés à < 3 mm du subiculum (p < 0,05). Les 2 patients ne répondant pas au traitement étaient stimulés par des contacts situés à > 3mm du subiculum. Conclusion : La diminution de l'activité épileptogène induite par DBS sur l'hippocampe dans les cas de MTLE réfractaires : 1) ne semble pas directement liée à la proximité des contacts actifs de l'électrode au foyer ictal déterminé par les enregistrements invasifs ; 2) pourrait être obtenue par une neuro-modulation du subiculum.

Reproductive allocation strategies: a long-term study on proximate factors and temporal adjustments in a viviparous lizard.

Optimisation of reproductive investment is crucial for Darwinian fitness, and detailed long-term studies are especially suited to unravel reproductive allocation strategies. Allocation strategies depend on the timing of resource acquisition, the timing of resource allocation, and trade-offs between different life-history traits. A distinction can be made between capital breeders that fuel reproduction with stored resources and income breeders that use recently acquired resources. In capital breeders, but not in income breeders, energy allocation may be decoupled from energy acquisition. Here, we tested the influence of extrinsic (weather conditions) and intrinsic (female characteristics) factors during energy storage, vitellogenesis and early gestation on reproductive investment, including litter mass, litter size, offspring mass and the litter size and offspring mass trade-off. We used data from a long-term study of the viviparous lizard, Lacerta (Zootoca) vivipara. In terms of extrinsic factors, rainfall during vitellogenesis was positively correlated with litter size and mass, but temperature did not affect reproductive investment. With respect to intrinsic factors, litter size and mass were positively correlated with current body size and postpartum body condition of the previous year, but negatively with parturition date of the previous year. Offspring mass was negatively correlated with litter size, and the strength of this trade-off decreased with the degree of individual variation in resource acquisition, which confirms theoretical predictions. The combined effects of past intrinsic factors and current weather conditions suggest that common lizards combine both recently acquired and stored resources to fuel reproduction. The effect of past energy store points out a trade-off between current and future reproduction.