Étude de la régulation de l'échangeur Na+/H+ des membranes luminales distales du néphron de lapin

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Role of HOXA7 to HOXA13 and PBX1 genes in various forms of MRKH syndrome (congenital absence of uterus and vagina)

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome refers to the congenital absence or severe hypoplasia of the female genital tract, often described as uterovaginal aplasia which is the prime feature of the syndrome. It is the second cause of primary amenorrhea after gonadal dysgenesis and occurs in ~1 in 4500 women. Aetiology of this syndrome remains poorly understood. Frequent association of other malformations with the MRKH syndrome, involving kidneys, skeleton and ears, suggests the involvement of major developmental genes such as those of the HOX family. Indeed mammalian HOX genes are well known for their crucial role during embryogenesis, particularly in axial skeleton, hindbrain and limb development. More recently, their involvement in organogenesis has been demonstrated notably during urogenital differentiation. Although null mutations of HOX genes in animal models do not lead to MRKH-like phenotypes, dominant mutations in their coding sequences or aberrant expression due to mutated regulatory regions could well account for it. Sequence analysis of coding regions of HOX candidate genes and of PBX1, a likely HOX cofactor during Müllerian duct differentiation and kidney morphogenesis, did not reveal any mutation in patients showing various forms of MRKH syndrome. This tends to show that HOX genes are not involved in MRKH syndrome. However it does not exclude that other mechanisms leading to HOX dysfunction may account for the syndrome

WASABI: a Two Million Song Database Project with Audio and Cultural Metadata plus WebAudio enhanced Client Applications

This paper presents the WASABI project, started in 2017, which aims at (1) the construction of a 2 million song knowledge base that combines metadata collected from music databases on the Web, metadata resulting from the analysis of song lyrics, and metadata resulting from the audio analysis, and (2) the development of semantic applications with high added value to exploit this semantic database. A preliminary version of the WASABI database is already online1 and will be enriched all along the project. The main originality of this project is the collaboration between the algorithms that will extract semantic metadata from the web and from song lyrics with the algorithms that will work on the audio. The following WebAudio enhanced applications will be associated with each song in the database: an online mixing table, guitar amp simulations with a virtual pedal-board, audio analysis visualization tools, annotation tools, a similarity search tool that works by uploading audio extracts or playing some melody using a MIDI device are planned as companions for the WASABI database

Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci

<p>Abstract</p> <p>Background</p> <p>Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences.</p> <p>Methods</p> <p>We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS.</p> <p>The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis.</p> <p>Results</p> <p>We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome.</p> <p>Conclusion</p> <p>Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling.</p

Identifying cost-competitive greenhouse gas mitigation potential of French agriculture

The agriculture, forestry and other land use sector are responsible for 24% (10–12 Pg CO2e per year) of anthropogenic greenhouse gas (GHG) emissions worldwide, with concomitant opportunities for mitigation. A scientific panel used deliberative methods to identify ten technical measures comprising 26 sub-measures to reduce GHG emissions from agriculture in France. Their abatement potential and cost are compared. The proposed measures concern nitrogen (N) management, management practices that increase carbon stocks in soils and biomass, livestock diets, and energy production and consumption on farms. Results show that the total abatement potential can be divided into three parts. One third of the cumulated abatement potential corresponds to sub-measures that can be implemented at a negative technical cost. These sub-measures focus on increased efficiency in input use including N fertilisers, animal feed and energy. The second third are sub-measures with moderate cost (€25 per metric Mg of avoided CO2e). These require investment with no direct financial return, the purchase of particular inputs, dedicated labour time or involve production losses. Assuming additivity, the cumulated abatement is 32.3 Tg CO2e per year in 2030, but only 10 Tg (i.e. 10% of current agricultural emissions) when calculated under current inventory rules. This study confirms that a significant abatement potential exists in the agricultural sector, with two thirds of this potential at low or even negative cost. This is likely to be an underestimated as it is based on a status quo of the current agricultural system. Results also emphasise the need to upgrade inventory rules so that efforts to reduce emissions can be accounted for

The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome

Covalently crosslinked mussel byssus protein-based materials with tunable properties

Mussels’ anchoring threads, named byssus, are collagen-rich fibers with outstanding mechanical properties. Our previous work has shown the possibility of producing a byssus protein hydrolyzate with good film-forming ability, providing a promising new avenue for the preparation of biomaterials. Materials prepared from regenerated fibrous proteins often need additional treatments to reach the performance required for targeted applications. Here, we studied the effect of covalent crosslinking, using a carbodiimide or glutaraldehyde, on the mechanical properties and enzymatic resistance of byssus-based materials. The results show that the mechanical properties of the films can be tuned, and that a higher crosslinking degree leads to increases in modulus and strength accompanied by a loss of extensibility. Structural analysis performed by infrared spectroscopy revealed that crosslinking induces an unexpected transition from aggregated strands to hydrated collagen/PPII-related helical structures. The materials were nevertheless more resistant to collagenase degradation as a result of higher crosslinking density. This new set of materials prepared in aqueous environment could find a niche in tissue engineering

Metal–ligand interactions and salt bridges as sacrificial bonds in mussel byssus-derived materials

The byssus that anchors mussels to solid surfaces is a protein-based material combining strength and toughness as well as a self-healing ability. These exceptional mechanical properties are explained in part by the presence of metal ions forming sacrificial bonds with amino acids. In this study, we show that the properties of hydrogel films prepared from a byssus protein hydrolyzate (BPH) can also be improved following the biomimetic formation of sacrificial bonds. Strengthening and toughening of the materials are both observed when treating films with multivalent ions (Ca2+ or Fe3+) or at the BPH isoelectric point (pI) as a result of the formation of metal–ligand bonds and salt bridges, respectively. These treatments also provide a self-healing behavior to the films during recovery time following a deformation. While pI and Ca2+ treatments have a similar but limited pH-dependent effect, the modulus, strength, and toughness of the films increase largely with Fe3+ concentration and reach much higher values. The affinity of Fe3+ with multiple amino acid ligands, as shown by vibrational spectroscopy, and the more covalent nature of this interaction can explain these observations. Thus, a judicious choice of treatments on polyampholyte protein-based materials enables control of their mechanical performance and self-healing behavior through the strategic exploitation of reversible sacrificial bonds