HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2

Abstract The nephron is a highly specialised segmented structure that provides essential filtration and resorption renal functions. It arises by formation of a polarised renal vesicle that differentiates into a comma-shaped body and then a regionalised S-shaped body (SSB), with the main prospective segments mapped to discrete domains. The regulatory circuits involved in initial nephron patterning are poorly understood. We report here that HNF1B, a transcription factor known to be involved in ureteric bud branching and initiation of nephrogenesis, has an additional role in segment fate acquisition. Hnf1b conditional inactivation in murine nephron progenitors results in rudimentary nephrons comprising a glomerulus connected to the collecting system by a short tubule displaying distal fates. Renal vesicles develop and polarise normally but fail to progress to correctly patterned SSBs. Major defects are evident at late SSBs, with altered morphology, reduction of a proximo-medial subdomain and increased apoptosis. This is preceded by strong downregulation of the Notch pathway components Lfng, Dll1 and Jag1 and the Irx1/2 factors, which are potential regulators of proximal and Henle’s loop segment fates. Moreover, HNF1B is recruited to the regulatory sequences of most of these genes. Overexpression of a HNF1B dominant-negative construct in Xenopus embryos causes downregulation specifically of proximal and intermediate pronephric segment markers. These results show that HNF1B is required for the acquisition of a proximo-intermediate segment fate in vertebrates, thus uncovering a previously unappreciated function of a novel SSB subcompartment in global nephron segmentation and further differentiation

REVER, le réseau français de restauration écologique

International audienceIn the past few decades, restoration has widely developed thanks to a rather favourable context, in particular legally speaking and regulatory framework-wise both at the European and French levels. Rediscovering the mitigation hierarchy "Avoid, Minimize, Restore" written in a 1976 French law, and implementing the E.U habitats directives or the E.U. water framework directive and various nation-wide or local incentive policies, thus led to the development of restoration. Restoration projects are nevertheless also confronted with administrative, socio-economic or technical barriers. The nature of restoration actions themselves implies to take into account their impacts, which can potentially be negative for biodiversity, through more or less heavy procedures. Considering local practices and perceptions is also important for the success of the restoration. Following the model of international networks, such as the SERI, the Francophone network for ecological restoration (REVER) aims at accompanying and at favouring the development of restoration by facilitating the relationships between the various stakeholders: scientists, site managers, etc., through the exchanges of knowledge and experiences. Among its actions, REVER organizes workshops. The diversity of the communications as well as of the participants illustrates the diversity of ecological restoration and restoration ecology stakeholders in France and will be presented

Misleading behavioural phenotype with adenylosuccinate lyase deficiency

Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton–Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical features might be a new presentation of adenylosuccinate lyase deficiency. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with mental retardation and a behavioural profile suggestive of Angelman syndrome

Mutation screening of MIR146A/B and BRCA1/2 3′-UTRs in the GENESIS study

International audienceAlthough a wide number of breast cancer susceptibility alleles associated with various levels of risk have been identified to date, about 50% of the heritability is still missing. Although the major BRCA1 and BRCA2 genes are being extensively screened for truncating and missense variants in breast and/or ovarian cancer families, potential regulatory variants affecting their expression remain largely unexplored. In an attempt to identify such variants, we focused our attention on gene regulation mediated by microRNAs (miRs). We screened two genes, MIR146A and MIR146B, producing miR-146a and miR-146b-5p, respectively, that regulate BRCA1, and the 3ʹ-untranslated regions (3ʹ-UTRs) of BRCA1 and BRCA2 in the GENESIS French national case/control study (BRCA1-and BRCA2-negative breast cancer cases with at least one sister with breast cancer and matched controls). We identified one rare variant in MIR146A, four in MIR146B, five in BRCA1 3ʹ-UTR and one in BRCA2 3ʹ-UTR in 716 index cases and 619 controls. Among these 11 rare variants, 7 were identified each in 1 index case. None of the three relevant MIR146A/MIR146B variants affected the pre-miR sequences. The potential causality of the four relevant BRCA1/BRCA2 3ʹ-UTRs variants was evaluated with luciferase reporter assays and co-segregation studies, as well as with bioinformatics analyses to predict miRs-binding sites, RNA secondary structures and RNA accessibility. This is the first study to report the screening of miR genes and of BRCA2 3ʹ-UTR in a large series of familial breast cancer cases. None of the variant identified in this study gave convincing evidence of potential pathogenicity

Sähkönlaadun ja energiankulutuksen tutkimus

Opinnäytetyössä tutkitaan sähkönlaadun ja energiankulutusta Raute Oyj:n rakentamissa vaneri- ja LVL-viilupalkkikoneissa. Opinnäytetyön tarkoituksena on selvittää esiintyykö Raute Oyj:n valmistamissa koneissa sähkönlaatua heikentäviä tekijöitä, kuten harmonisia yliaaltoja. Sähkönlaatua heikentävien tekijöiden lisäksi opinnäytetyössä selvitetään mahdollisuutta moottorikeskusten mitoituksessa käytettävän korjauskertoimen tarkentamiselle. Opinnäytetyön teoriaosassa esitellään sähkönlaatuun vaikuttavia tekijöitä, sekä niiden vaikutuksia sähköverkkoon ja verkonkäyttäjälle. Lisäksi teoriaosassa käydään läpi ratkaisuja, joilla esimerkiksi sähköverkossa esiintyvien yliaaltojen pitoisuutta voidaan vähentää tai poistaa kokonaan. Verkossa esiintyville häiriöille kuten harmonisille yliaalloille, taajuuden ja jännitteen vaihteluille on määritelty rajoituksia standardilla SFS-EN 50160, myös näitä rajoituksia ja niiden vaikutuksia sähkönlaatuun käydään läpi opinnäytetyön teoriaosassa. Sähkönlaatua ja energiankulutusta mitattiin kahdessa Raute Oyj:n koneessa, ja näiden mittaukseen käytettiin Fluken power quality analyzer mallia olevaa mittalaitetta. Mittaustuloksissa huomattiin sähkönlaadun olevan yleisesti hyvällä tasolla ja täyttävän standardissa SFS-EN 50160 sähkönlaadulle määritellyt raja-arvot. Tulosten perusteella huomattiin myös, että joissakin tapauksissa keskusten mitoituksessa käytettäviä korjauskertoimia pystyy tarkentamaan.The study researches the quality of electricity and the energy consumption on plywood and laminated veneer lumber (LVL) machines manufactured by Raute Plc. The Thesis aims to examine the potential existence of factors reducing the quality of electric, such as harmonic waves, on machines manufactured by Raute Plc. In addition to examine the electricity quality and consumption of energy, the thesis looks into the possibility of elaboration of motorcabin’s equalisation. The theory part of the Thesis presents factors that influence electric quality, as well as their influences on the electricity network and network’s users. Additionally, the theory part discusses solutions, which for instance reduce or eliminate harmonic waves in electric network. SFS-EN 50160 standard defines restrictions for disturbance in electric network such as harmonic waves, frequency and voltage variation, these restrictions are also presented in the theory part of the Thesis. In this study, electric quality and energy consumption were measured in two different machines manufactured by Raute Plc, and the measurements were conducted by Fluke power quality analyser measuring device. Electric quality was generally high according to the measurements, and it meets the electric quality standards defined in SFS-EN 50160. The measurements also indicated that in some cases the equalisation is possible to elaborate

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence