Integration of Myeloblastosis Associated Virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation

AIMS: Myeloblastosis Associated Virus type 1 (N) [MAV 1(N)] induces specifically nephroblastomas in 8–10 weeks when injected to newborn chicken. The MAV-induced nephroblastomas constitute a unique animal model of the pediatric Wilms' tumor. We have made use of three independent nephroblastomas that represent increasing tumor grades, to identify the host DNA regions in which MAV proviral sequences were integrated. METHODS Cellular sequences localized next to MAV-integration sites in the tumor DNAs were used to screen a Bacterial Artificial Chromosomes (BACs) library and isolate BACs containing about 150 kilobases of normal DNA corresponding to MAV integration regions (MIRs). These BACs were mapped on the chicken chromosomes by Fluorescent In Situ Hybridization (FISH) and used for molecular studies. RESULTS: The different MAV integration sites that were conserved after tumor cell selection identify genes involved in the control of cell signaling and proliferation. Syntenic fragments in human DNA contain genes whose products have been involved in normal and pathological kidney development, and several oncogenes responsible for tumorigenesis in human. CONCLUSION: The identification of putative target genes for MAV provides important clues for the understanding of the MAV pathogenic potential. These studies identified ADAMTS1 as a gene upregulated in MAV-induced nephroblastoma and established that ccn3/nov is not a preferential site of integration for MAV as previously thought. The present results support our hypothesis that the highly efficient and specific MAV-induced tumorigenesis results from the alteration of multiple target genes in differentiating blastemal cells, some of which are required for the progression to highly aggressive stages. This study reinforces our previous conclusions that the MAV-induced nephroblastoma constitutes an excellent model in which to characterize new potential oncogenes and tumor suppressors involved in the establishment and maintenance of tumors

Adaptation Strategies of Breeders Facing Global Change in Harsh Conditions

Global changes impact breed societies through complex and diverse factors such as global economics, climate change, management and degradation of rangelands, societal demands especially from youth, and new technologies including information and communication technologies. The main objective of this research developed by Livestock farming and local development network (LiFLod, http://liflod.org/) network is to better understand the mental models of local stakeholders for global change and adaptation strategies. Our hypothesis is that in harsh conditions breeders with diverse objectives adopt more or less similar strategies when faced with global change

Polymorphism of Plasmodium falciparum Na+/H+ exchanger is indicative of a low in vitro quinine susceptibility in isolates from Viet Nam

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>NA+/H+ exchanger (<it>pfnhe1</it>, gene PF13_0019) has recently been proposed to influence quinine (QN) susceptibility. However, its contribution to QN resistance seems to vary geographically depending on the genetic background of the parasites. Here, the role of this gene was investigated in <it>in vitro </it>QN susceptibility of isolates from Viet Nam.</p> <p>Method</p> <p>Ninety-eight isolates were obtained from three different regions of the Binh Phuoc and Dak Nong bordering Cambodia provinces during 2006-2008. Among these, 79 were identified as monoclonal infection and were genotyped at the microsatellite <it>pfnhe1 </it>ms4760 locus and <it>in vitro </it>QN sensitivity data were obtained for 51 isolates. Parasite growth was assessed in the field using the HRP2 immunodetection assay.</p> <p>Results</p> <p>Significant associations were found between polymorphisms at <it>pfnhe1 </it>microsatellite ms4760 and susceptibility to QN. Isolates with two or more DNNND exhibited much lower susceptibility to QN than those harbouring zero or one DNNND repeats (median IC₅₀of 682 nM <it>versus </it>median IC₅₀of 300 nM; <it>p </it>= 0.0146) while isolates with one NHNDNHNNDDD repeat presented significantly reduced QN susceptibility than those who had two (median IC₅₀of 704 nM <it>versus </it>median IC₅₀of 375 nM; p < 0.01). These QNR associated genotype features were mainly due to the over representation of profile 7 among isolates (76.5%). The majority of parasites had <it>pfcrt76T </it>and wild-type <it>pfmdr1 </it>(> 95%) thus preventing analysis of associations with these mutations. Interestingly, area with the highest median QN IC₅₀showed also the highest percentage of isolates carrying the <it>pfnhe1 </it>haplotype 7.</p> <p>Conclusions</p> <p>The haplotype 7 which is the typical Asian profile is likely well-adapted to high drug pressure in this area and may constitute a good genetic marker to evaluate the dissemination of QNR in this part of the world.</p

RÔLE DE L'OCCUPATION DU SOL VIS À VIS DE LA MODÉLISATION DES FLUX ENERGÉTIQUES ET HYDRIQUES EN MILIEU URBAIN ET PÉRIURBAIN

National audienceLe projet Rosenhy vise à étudier l’impact de l’occupation du sol sur la modélisation météorologique et hydrologique en termes de flux énergétiques et hydriques, en milieu urbain et périurbain. Trois sites appartenant aux observatoires français OTHU et ONEVU sont au centre de ce projet. Le quartier urbain hétérogène du Pin sec (Nantes), imperméabilisé à environ 45%, a fait l’objet d’une campagne expérimentale durant le mois de juin 2012, visant à estimer les flux de chaleur sensible et latente avec une haute résolution spatiale et temporelle par rapport aux mesures réalisées en continu sur ce site depuis 5 ans. Deux bassins versant périurbains (La Chézine à Nantes et l’Yzeron à Lyon), avec un taux d’imperméabilisation moins important (environ 10%) mais grandissant depuis plusieurs décennies, sont aussi étudiés. Ces deux derniers sites bénéficient d’un suivi hydrométéorologique depuis 10 ans pour la Chézine et 15 ans pour l’Yzeron. Sur ces trois sites, différentes sources de données d’occupation du sol à différentes résolutions sont disponibles :différentes bases de données géographiques communément utilisées par la communauté scientifique et les collectivités et des données télédétectées (multispectrales et hyperspectrales). L’utilisation de ces données en entrée de différents modèles météorologiques et hydrologiques implique un travail d’analyse et de classification pour adapter les informations aux besoins des modèles. Dans ce projet, les différents modèles adaptés au milieu urbain ou périrubain sont évalués et améliorés. Ainsi, les modèles hydrologiques périrubains sont en développement pour prendre en compte les différentes pratiques de gestion des eaux pluviales existantes (noues, toitures végétalisées, ...). L’utilisation conjointe des données simulées par les différents modèles aidera à déterminer le rôle de la part des surfaces naturelles et artificielles sur les bilans énergétique et hydrique en milieu plus ou moins urbanisé. Le milieu périurbain étant en évolution, le projet s’intéressera aussi à des scénarios d’urbanisation prospectifs en regardant d’une part l’impact de la densification sur les scénarios construits pour l’Yzeron lors du projet AVuPUR (ANR-VMCS, 2008-2011) et d’autre part, en réfléchissant conjointement avec Nantes Métropole, aux possibles voies d’évolution sur le bassin de la Chézine

Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

International audienceRecent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer

JWST CEERS probes the role of stellar mass and morphology in obscuring galaxies

A population of massive galaxies invisible or very faint in deep optical/near-infrared surveys, but brighter at longer wavelengths has been uncovered in the past years. However, the nature of these optically dark/faint galaxies (OFGs, among other nomenclatures) is highly uncertain. In this work, we investigate the drivers of dust attenuation in the JWST era. Particularly, we study the role of stellar mass, size, and orientation in obscuring star-forming galaxies (SFGs) at $3 < z < 7.5$, focusing on understanding why galaxies like OFGs are so faint at optical/near-infrared wavelengths. We find that stellar mass is the primary proxy of dust attenuation among those studied. Effective radius and axis ratio do not show a clear link with dust attenuation, with the effect of orientation close to random. However, there is a subset of highly dust attenuated ($A_V > 1$, typically) SFGs, of which OFGs are a specific case. For this subset, we find that the key distinctive feature is their compact size (for massive systems with $\log (M_{*}/M_{\odot}) > 10$), exhibiting 30% smaller effective radius than the average SFGs at the same stellar mass and redshift. On the contrary, they do not exhibit a preference for low axis ratios (i.e., edge-on disks). The results in this work show stellar mass as a primary proxy of dust attenuation and compact stellar light profiles behind thick dust columns obscuring typical massive SFGs.Comment: Submitted to A&A. 13 pages, 9 figure

CEERS Key Paper. V. Galaxies at 4 &lt; z &lt; 9 Are Bluer than They Appear-Characterizing Galaxy Stellar Populations from Rest-frame ∼1 μm Imaging

We present results from the Cosmic Evolution Early Release Survey on the stellar population parameters for 28 galaxies with redshifts 4 &lt; z &lt; 9 using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 μm data extend the coverage of the rest-frame spectral energy distribution to nearly 1 μm for galaxies in this redshift range. By modeling the galaxies’ SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 Å)—I-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower ratios of stellar mass to light. The MIRI data reduce the stellar masses by 〈 Δ log M * 〉 = 0.25 dex at 4 &lt; z &lt; 6 and 0.37 dex at 6 &lt; z &lt; 9. This also reduces the star formation rates (SFRs) by 〈ΔlogSFR〉 = 0.14 dex at 4 &lt; z &lt; 6 and 0.27 dex at 6 &lt; z &lt; 9. The MIRI data also improve constraints on the allowable stellar mass formed in early star formation. We model this using a star formation history that includes both a “burst” at z f = 100 and a slowly varying (“delayed-τ”) model. The MIRI data reduce the allowable stellar mass by 0.6 dex at 4 &lt; z &lt; 6 and by ≈1 dex at 6 &lt; z &lt; 9. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early Universe (z ≈ 9). Therefore, observations of rest-frame ≳1 μm are paramount for constraining the stellar-mass buildup in galaxies at very high redshifts.</p

CEERS Key Paper IV: Galaxies at 4<z<94 < z < 9 are Bluer than They Appear -- Characterizing Galaxy Stellar Populations from Rest-Frame ∼1\sim 1 micron Imaging

We present results from the Cosmic Evolution Early Release Survey (CEERS) on the stellar-population parameters for 28 galaxies with redshifts $4<z<9$ using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 $\mu$m data extend the coverage of the rest-frame spectral-energy distribution (SED) to nearly 1 micron for galaxies in this redshift range. By modeling the galaxies' SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 \r{A}) $-$ $I$-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower (stellar)-mass-to-light ratios. The MIRI data reduce the stellar masses by $\langle \Delta\log M_\ast\rangle=0.25$ dex at $4<z<6$ (a factor of 1.8) and 0.37 dex at $6<z<9$ (a factor of 2.3). This also reduces the star-formation rates (SFRs) by $\langle \Delta\log\mathrm{SFR} \rangle=0.14$ dex at $4<z<6$ and 0.27 dex at $6<z<9$. The MIRI data also improve constraints on the allowable stellar mass formed in early star-formation. We model this using a star-formation history that includes both a "burst' at $z_f=100$ and a slowly varying ("delayed-$\tau$") model. The MIRI data reduce the allowable stellar mass by 0.6 dex at $4<z< 6$ and by $\approx$1 dex at $6<z<9$. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early universe ($z\approx9$). Therefore, observations of rest-frame $\gtrsim$1 $\mu$m are paramount for constraining the stellar-mass build-up in galaxies at very high-redshifts.Comment: Updated with accepted ApJ version. Part of the CEERS Focus Issue. 27 pages, many figures (4 Figure Sets, available upon reasonable request

CEERS Key Paper V: A triality on the nature of HST-dark galaxies

The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR faint, mid-IR bright sources, HST-dark galaxies among them. We gather JWST data from the CEERS survey in the EGS, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions (SEDs) to estimate both photometric redshifts in 2 dimensions and stellar populations properties in a pixel-by-pixel basis. We select 138 galaxies with F150W-F356W>1.5 mag, F356W<27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies at 2<z<6 with masses 9<log M/M_sun<11 and a variety of specific SFRs (100 Gyr^-1); (2) 18% are quiescent/dormant (i.e., subject to reignition and rejuvenation) galaxies at 3<z<5, masses log M/M_sun~10 and post-starburst stellar mass-weighted ages (0.5-1 Gyr); and (3) 11% are strong young starbursts with indications of high-EW emission lines (typically, [OIII]+Hbeta) at 6<z<7 and log M/M_sun~9.5. The sample is dominated by disk-like galaxies with a remarkable compactness for XELG-z6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2<A(V)<5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A(V)~0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and sub-millimeter galaxies. This study implies high levels of star formation activity between z~20 and z~10, where virtually 100% of our galaxies had already formed 10^8 M_sun of their stellar content, 60% of them had assembled 10^9 M_sun, and 10% up to 10^10 M_sun (in situ or ex situ). (abridged)Comment: Published in CEERS ApJL Focus Issue, ApJL 946, L1