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In Brief Hormones secreted by muscle cells (myokines) are involved in the adaptive response to nutritional and metabolic changes. In this review, we discuss how one family of myokines may alter fertility in response to sudden changes in energy balance. Abtract Dietary stress such as obesity and short-term changes in energy balance can disrupt ovarian function leading to infertility. Adipose tissue secretes hormones (adipokines), such as leptin and adiponectin, that are known to alter ovarian function. Muscles can also secrete endocrine factors, and one such family of myokines, the eleven Fibronectin type III domain-containing (FNDC) proteins, is emerging as important for energy sensing and homeostasis. In this review, we summarize the known roles the FNDC proteins play in energy homeostasis and explore potential impacts on fertility in females. The most well-known member, FNDC5, is the precursor of the ‘exercise hormone’, irisin, secreted by both muscle and adipose tissue. The receptors for irisin are integrins, and it has recently been shown to alter steroidogenesis in ovarian granulosa cells although the effects appear to be species or context specific, and irisin may improve uterine and placental function in women and rodent models. Another member, FNDC4, is also cleaved to release a bioactive protein that modulates insulin sensitivity in peripheral tissues and whose receptor, ADGRF5, is expressed in the ovary. As obese women and farm animals in negative energy balance (NEB) both have altered insulin sensitivity, secreted FNDC4 may impact ovarian function. We propose a model in which NEB or dietary imbalance alters plasma irisin and secreted FNDC4 concentrations, which then act on the ovary through their cognate receptors to reduce granulosa cell proliferation and follicle health. Research into these molecules will increase our understanding of energy sensing and fertility and may lead to new approaches to alleviate post-partum infertility.

The Camou springs (Arbailles Massif, French Western Pyrenees) display an unusual close association of a typically cold karstic spring that drains the Urgonian western limb of the Arbailles, and a thermo-mineral spring (33.5°C; salinity 17.7 g/L). The latter gains its mineralization at the contact of Triassic evaporites mainly through a deep loop in the Apanicé syncline. The fast upflow of this deep water occurs at the cross of large active lines (the North-Pyrenean thrust located at depth, and the Saison transverse fault). Cave diving in the nearby Maddalen Cave allowed reaching the phreatic passage at the origin of the cold spring, which however also crosses the thermal body in the third sump (S3). Both water bodies are separated by a sharp thermocline. 6 pressure-temperature dataloggers were placed in both water bodies along the thermocline for 6 months. The dataloggers located downstream on either side of the thermocline show at the beginning of flood first a rise of the thermal body, then an invasion of the whole phreatic passage by the cold floodwater, controlled by head pressure changes in the karst aquifer. From observation of these mechanisms, we deduce a hydrodynamic model with a warm plume rising into the cold aquifer, without significant mixing. Such independence of water bodies is explained by the decrease of turbulent rate at the interface, due to the sharp density gradient. The relative absence of mixing does not actually require independent “watertight” routes, both water bodies can thus coexist even in the same conduit. This model locally implies the existence of unknown secondary passages close to the spring, which allow an independent draining of each water body toward separate outlets during low stage. Such type of stratified aquifer linked to density differences is common in coastal karst (Florida, French Calanques…), in the continental evaporite karst (Schlotten of the Harz in Germany, Kungur karst in Ural…), but remains poorly identified in continental carbonate karst areas, mainly because of the difficulty of access. Together with the Mescla spring in French Alpes-Maritimes, the Camou twin springs discharging in the same porch are an outstanding example, allowing a direct study of the stratification and the dynamic of highly contrasted water bodies.

This manuscript discusses the recent report “Cognate restriction of transposition bypiggyBac-like proteins” inNucleic Acids Researchby Beckermann et al and related recent publications about the inability to detect DNA transposition activity of human domesticated DNA transposase PGBD5. Measuring DNA transposition activity of transposases in human cells, where these enzymes can act on endogenous genomic substrates and induce DNA damage, is complicated by these and other cellular responses. Possible reasons for the discordant findings of Beckermann et al with prior independent reports of PGBD5 DNA transposition by Helou et al and Henssen et al and specific details of experimental methods in human cells are presented. In particular, by using independent experiments that reproduce PGBD5-mediated genomic integration, we demonstrate how supraphysiologic and ectopic overexpression of PGBD5 can cause DNA damage and cell death, and artifactual loss of apparent activity in clonogenic transposition reporter assays. While PGBD5 can support apparent DNA transposition, its cellular activity predominantly involves double-strand DNA breaks, deletions and other DNA rearrangements. We discuss the implications of this phenomenon for the interpretation of experimental assays and activities of domesticated DNA transposases.

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We present the first results of OSL-dated fluvial sands extracted from a riverside cave in the tropical Andes. The excellent agreement between the ages of the various samples allowed the calculation of a late Quaternary valley incision rate forced by ongoing uplift of an active Subandean fault-propagation fold in NE Peru. A structural cross-section was constructed to understand the relationship between the geometry of the fault-propagation fold, historical damaging earthquakes and the cave system. The calculated uplift rate is 2.3 to 2.6 mm a(-1) over the past 70 ka and can be directly linked to active propagation of west-verging basement thrusts. It is similar to uplift rates calculated from fluvial terraces in the Subandes of Colombia and Venezuela. The results will help to better assess the seismic hazard and confirm that OSL dating of fluvial sands in caves is a powerful tool to quantify uplift rates of active mountain fronts.

STUDY QUESTION What biological processes are linked to the signaling of the energy sensor 5′-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)? SUMMARY ANSWER The lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response. WHAT IS KNOWN ALREADY AMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5–20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin. STUDY DESIGN, SIZE, DURATION AMPK signaling was evaluated by analyzing differential gene expression in immortalized human granulosa cells (KGNs) with and without silencing α1AMPK using CRISPR/Cas9. In vivo studies included the use of a α1AMPK knock-out mouse model to evaluate the role of α1AMPK in folliculogenesis and fertility. Expression of α1AMPK was evaluated in primary human granulosa-luteal cells retrieved from women undergoing IVF with and without a lean PCOS phenotype (i.e. BMI: 18–25 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS α1AMPK was disrupted in KGN cells and a transgenic mouse model. Cell viability, proliferation and metabolism were evaluated. Androgen production was evaluated by analyzing protein levels of relevant enzymes in the steroid pathway by western blots, and steroid levels obtained from in vitro and in vivo models by mass spectrometry. Differential gene expression in human GC was obtained by RNA sequencing. Analysis of in vivo murine folliculogenesis was performed by histology and immunochemistry, including evaluation of the anti-Müllerian hormone (AMH) marker. The α1AMPK gene expression was evaluated by quantitative RT-PCR in primary GCs obtained from women with the lean PCOS phenotype (n = 8) and without PCOS (n = 9). MAIN RESULTS AND THE ROLE OF CHANCE Silencing of α1AMPK in KGN increased cell proliferation (P LARGE SCALE DATA The FastQ files and metadata were submitted to the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB46048. LIMITATIONS, REASONS FOR CAUTION The human KGN is a not fully differentiated, transformed cell line. As such, to confirm the role of AMPK in GC and the PCOS phenotype, this model was compared to two others: an α1AMPK transgenic mouse model and primary differentiated granulosa-lutein cells from non-obese women undergoing IVF (with and without PCOS). A clear limitation is the small number of patients with PCOS utilized in this study and that the collection of human GCs was performed after hormonal stimulation. WIDER IMPLICATIONS OF THE FINDINGS Our results reveal that AMPK is directly involved in steroid production in human GCs. In addition, AMPK signaling was associated with other processes frequently reported as dysfunctional in PCOS models, such as cell adhesion, lipid metabolism and inflammation. Silencing of α1AMPK in KGN promoted folliculogenesis, with increases in AMH. Evaluating the expression of the α1AMPK subunit could be considered as a marker of interest in infertility cases related to hormonal imbalances and metabolic disorders, including PCOS. STUDY FUNDING/COMPETING INTEREST(S) This study was financially supported by the Institut National de la Recherche Agronomique (INRA) and the national programme « FERTiNERGY » funded by the French National Research Agency (ANR). The authors report no intellectual or financial conflicts of interest related to this work. R.K. is identified as personnel of the International Agency for Research on Cancer/World Health Organization. R.K. alone is responsible for the views expressed in this article and she does not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. TRIAL REGISTRATION NUMBER N/A.

International audience; Integrative non-viral vectors such as transposons engineered to mediate targeted gene transfer into safe harbor sites in the genome may be a promising approach for the production of therapeutic proteins or for gene therapy in an efficient and secure way. In this context, we designed and evaluated two strategies for targeting the nuclear ribosomal DNA (rDNA) loci. One approach relied on the co-location of the transposase and transposon near transcriptionally active rDNA copies using a nucleolar localization signal (NoLS). Another one consisted of targeting the 18S-coding region in the rDNA loci using a NoLS-FokI-dCas9 endonuclease to perform targeted transgene knock-in. We show that integration into the rDNA of Chinese hamster ovary (CHO) cells can be achieved at a high frequency using the piggyBac transposon system, indicating that the rDNA is highly accessible for transposition. Consistently, rDNA-targeted transposition events were most frequently obtained when both the piggyBac transposon DNA and the transposase were nucleoli-targeted, yielding cells displaying stable and homogeneous expression of the transgene. This approach thus provides an alternative strategy to improve targeted transgene delivery and protein expression using CHO cells.; Les vecteurs intégratifs non viraux, tels que les transposons, conçus pour assurer le transfert ciblé de gènes dans des sites sûrs du génome, peuvent constituer une approche prometteuse pour la production de protéines thérapeutiques ou pour la thérapie génique de manière efficace et sûre. Dans ce contexte, nous avons conçu et évalué deux stratégies pour cibler les loci de l'ADN ribosomal (ADNr) nucléaire. L'une des approches repose sur la co-localisation de la transposase et du transposon à proximité de copies d'ADNr transcriptionnellement actives, à l'aide d'un signal de localisation nucléolaire (NoLS). Une autre approche consiste à cibler la région codant pour le 18S dans les loci d'ADNr à l'aide d'une endonucléase NoLS-FokI-dCas9 pour réaliser un knock-in ciblé du transgène. Nous montrons que l'intégration dans l'ADNr des cellules d'ovaire de hamster chinois (CHO) peut être réalisée à une fréquence élevée en utilisant le système de transposon piggyBac, ce qui indique que l'ADNr est très accessible pour la transposition. De manière cohérente, les événements de transposition ciblant l'ADNr ont été obtenus le plus fréquemment lorsque l'ADN du transposon piggyBac et la transposase étaient ciblés sur le nucléole, ce qui a donné des cellules présentant une expression stable et homogène du transgène. Cette approche fournit donc une stratégie alternative pour améliorer la délivrance ciblée de transgènes et l'expression de protéines en utilisant des cellules CHO.

International audience; The vertebrate piggyBac derived transposase 5 (PGBD5) encodes a domesticated transposase, which is active and able to transpose its distantly related piggyBac-like element (pble), Ifp2. This raised the question whether PGBD5 would be more effective at mobilizing a phylogenetically closely related pble element. We aimed to identify the pble most closely related to the pgbd5 gene. We updated the landscape of vertebrate pgbd genes to develop efficient filters and identify the most closely related pble to each of these genes. We found that Tcr-pble is phylogenetically the closest pble to the pgbd5 gene. Furthermore, we evaluated the capacity of two murine and human PGBD5 isoforms, Mm523 and Hs524, to transpose both Tcr-pble and Ifp2 elements. We found that both pbles could be transposed by Mm523 with similar efficiency. However, integrations of both pbles occurred through both proper transposition and improper PGBD5-dependent recombination. This suggested that the ability of PGBD5 to bind both pbles may not be based on the primary sequence of element ends, but may involve recognition of inner DNA motifs, possibly related to palindromic repeats. In agreement with this hypothesis, we identified internal palindromic repeats near the end of 24 pble sequences, which display distinct sequences.

International audience; Adipose tissue is now recognized as an active endocrine organ, which synthesizes and secretes numerous peptides factors called adipokines. In mammals, they exert pleiotropic effects affecting energy metabolism but also fertility. In mammals, secretion of adipokines is altered in adipose tissue dysfunctions and may participate to obesity-associated disorders. Thus, adipokines are promising candidates both for novel pharmacological treatment strategies and as diagnostic tools. As compared to mammals, birds exhibit several unique physiological features, which make them an interesting model for comparative studies on endocrine control of metabolism and adiposity and reproductive functions. Some adipokines such as leptin and visfatin may have different roles in avian species as compared to mammals. In addition, some of them found in mammals such as CCL2 (chemokine ligand 2), resistin, omentin and FGF21 (Fibroblast Growth factor 21) have not yet been mapped to the chicken genome model and among its annotated gene models. This brief review aims to summarize data (structure, metabolic and reproductive roles and molecular mechanisms involved) related to main avian adipokines (leptin, adiponectin, visfatin, and chemerin) and we will briefly discuss the adipokines that are still lacking in avian species.

International audience; Setmar is a gene specific to simian genomes. The function(s) of its isoforms are poorly understood and their existence in healthy tissues remains to be validated. Here we profiled SETMAR expression and its genome-wide binding landscape in colon tissue. We found isoforms V3 and V6 in healthy and tumour colon tissues as well as incell lines. In two colorectal cell lines SETMAR binds to several thousand Hsmar1 and MADE1 terminal ends, transposons mostly located in non-genic regions of active chromatin including in enhancers. It also binds to a 12-bp motifs similar to an inner motif in Hsmar1 and MADE1 terminal ends. This motif is interspersed throughout the genome and is enriched in GC-rich regions as well as in CpG islands that contain constitutive replication origins. It is also found in enhancers other than those associated with Hsmar1 and MADE1. The role of SETMAR in the expression of genes, DNA replication and in DNA repair are discussed.

The Toirano karst system is located in the Ligurian Alps (north Italy), around 4.5 km inland from the coastline and carved in Middle Triassic dolostone. It comprises five cave levels over a 154 m altitudinal range, specifically Ulivo (340 m a.s.l.), Colombo (247 m a.s.l.), Upper Santa Lucia (215 m a.s.l.), Lower Santa Lucia (201 m a.s.l.) and Basura (186 m a.s.l.) caves. The system is active at lower altitudes, as testified by the thermal spring currently located at 70 m a.s.l. along the Varatella valley. Speleogenesis was attributed to the action of epigenic processes by other authors. However, the extraordinary geodiversity of the underground morphologies and deposits are at odds with this interpretation. Accordingly, this work investigates the genesis of the Toirano karst system, in relation to the landscape evolution of the surrounding area. A detailed morphological and mineralogical investigation of cave geoforms and deposits, together with the presence of the active low thermal sulphide spring on the Varatella valley and only ~100 m below the Basura Cave, sustain the hypothesis of a hypogene origin of the caves. This work shows that most of the caves formed close to the former water table (base) level, in turn determined by the mean sea level. Geochronological analyses, including U/Th (n = 13) and cosmogenic burial (n = 1) dating, together with an estimated incision rate of the Varatella valley of around 0.1 mm y−1, have allowed to assess the age of the highest cave (Ulivo) at around 2.7 Ma, Colombo at ~1.8 Ma, Upper Santa Lucia at ~1.5 Ma, Lower Santa Lucia ~1.3 Ma and Basura at ~1.2 Ma. Estimated palaeotemperature attained through isotope analyses and fluid inclusions on speleothems suggest that the temperature of rising waters was lower than 50 °C and possibly ranging between ~12 and ~20 °C, indicating that hydrothermal fluids were not the main driver of speleogenesis, at least in the late speleogenic phases. Additionally, sulphuric acid speleogenesis by-products were not identified. Accordingly, hypogenic speleogenesis occurred because of the action of low temperature CO2-rich rising fluids. A late stage of epigenic speleogenesis has been detected because of the clear evidences of condensation-corrosion morphologies, taking place since ~150 ka (possibly earlier) when caves were finally connected to the surface because of valley enlargement. Besides uncovering the genesis of the Toirano karst system, this study demonstrates that the combination of local geology, surface vs underground geomorphological observations, climate change vs landscape evolution evaluation and geochemical data is of key importance for interpreting subsurface land-shaping processes.

International audience; DDE Transposons have been recruited at least four times as site-specific recombination activating gene allowing programmed DNA elimination in eukaryotes. The described cases are RAG in jawed vertebrates, Kat 1 and Alpha 3 in the Kluyveromyces lactis yeast and Piggymac/TPB1 TPB2 and TPB6 in ciliates. The domesticated RAG is the most known case. It constitutes the enzymatic core of the Jawed vertebrates V(D)J recombination machinery. It directs random assembly and joining of gene segments during the development of B and T cells helping in the generation of the enormous gene diversity encoding antibodies or T cell receptors. It was shown in the case of RAG that the shift from DDE transposon to site-specific recombination activating gene is an evolutionary phenomenon that did not require dramatic changes. This explains why the co-option of DDE transposon as site-specific recombination activating gene can occur in a convergent manner. As numerous genes coding for DDE transposases are widespread through numerous members of the life tree, it is expected that several of them might correspond to domesticated transposons involved in programmed DNA elimination and maybe in the generation of receptor diversity. The domestication of DDE transposon could have been and still be of an extreme importance for organisms' evolution.

International audience; Guano is a typical deposit found in caves derived from the excretions of bats and in minor cases of birds. These organic deposits decompose and form a series of acid fluids and gases that can interact with the minerals, sediments, and rocks present in the cave. Over sixty phosphates are known and described from caves, but guano decay also often leads to the formation of nitrates and sulfates. In this study twenty-two European caves were investigated for their guano-related secondary minerals. Using various analytical techniques, seventeen phosphates, along with one sulfate (gypsum), were recognized as secondary products of guano decay. Among those minerals, some are very rare and result from the interaction of guano leachates with clays, fluvial deposits, or pyrite. Some of these minerals are even found only in the studied caves (spheniscidite, robertsite). The most common minerals belong to the apatite group. The common mineral association present in fresh decaying guano is brushite-ardealite-gypsum, minerals that usually are not present in older deposits because of their higher solubility. Most minerals are in hydrated form because of the wet cave environment; however, some specific dry conditions may favor the presence of dehydrated minerals, such as berlinite, formed during guano combustion. Investigation on the acidity of guano piles shows pH values as low as 3.5 with an increase of acidity with age and depth. Finally, cave guano deposits should be better studied in the future because of their role in paleoenvironmental and paleoclimatic reconstructions and because it is important to better understand the origin of guano-related minerals, especially the phosphates and sulfates. Among all of the caves studied, Corona ’e sa Craba (Italy) and Domica-Baradla Cave (Slovakia-Hungary) are considered to be outstanding sites with respect to their phosphate mineralogy.

International audience; The Prehistoric Cave at Azé (France) was divided in two parts by calcite flowstone. This isolated the innermost parts of the cave from the entrance, which remained connected to the surface. Since the closure, bats have not been able to access the cave beyond the flowstone blockage. They have been present only in the cave entrance. The byproducts released by bats had a considerable effect on this entrance part. Gaseous exhalations have changed the composition of the surrounding atmosphere, leading to the development of dome-shaped cupolas and other wall weathering features. Guano deposits built up causing the formation of aerosols and acidic leachates. The resulting corrosion of the limestone has led to the formation of phosphate deposits and biogenic karst. The rate of retreat of the cave walls has been estimated at 5 to 7 mm/ka. Corrosion has also affected archaeological artefacts, as well as any traces left on the walls by humans or animals. Bioglyphs linked to bears as well as anthropic graffiti have completely disappeared from the part of the cave used by bats.

Efforts to elucidate the causes of biological differences between wild fowls and their domesticated relatives, the chicken, have to date mainly focused on the identification of single nucleotide mutations. Other types of genomic variations have however been demonstrated to be important in avian evolution and associated to variations in phenotype. They include several types of sequences duplicated in tandem that can vary in their repetition number. Here we report on genome size differences between the red jungle fowl and several domestic chicken breeds and selected lines. Sequences duplicated in tandem such as rDNA, telomere repeats, satellite DNA and segmental duplications were found to have been significantly re-shaped during domestication and subsequently by human-mediated selection. We discuss the extent to which changes in genome organization that occurred during domestication agree with the hypothesis that domesticated animal genomes have been shaped by evolutionary forces aiming to adapt them to anthropized environments.

Changes in gene activity through epigenetic alterations induced by early environmental challenges during embryogenesis are known to impact the phenotype, health, and disease risk of animals. Learning how environmental cues translate into persisting epigenetic memory may open new doors to improve robustness and resilience of developing animals. It has previously been shown that the heat tolerance of male broiler chickens was improved by cyclically elevating egg incubation temperature. The embryonic thermal manipulation enhanced gene expression response in muscle (P. major) when animals were heat challenged at slaughter age, 35 days post-hatch. However, the molecular mechanisms underlying this phenomenon remain unknown. Here, we investigated the genome-wide distribution, in hypothalamus and muscle tissues, of two histone post-translational modifications, H3K4me3 and H3K27me3, known to contribute to environmental memory in eukaryotes. We found 785 H3K4me3 and 148 H3K27me3 differential peaks in the hypothalamus, encompassing genes involved in neurodevelopmental, metabolic, and gene regulation functions. Interestingly, few differences were identified in the muscle tissue for which differential gene expression was previously described. These results demonstrate that the response to embryonic thermal manipulation (TM) in chicken is mediated, at least in part, by epigenetic changes in the hypothalamus that may contribute to the later-life thermal acclimation.

International audience; PiggyBac(PB)-like elements (pble) are members of a eukaryotic DNA transposon family. This family is of interest to evolutionary genomics because pble transposases have been domesticated at least 9 times in vertebrates. The amino acid sequence of pble transposases can be split into three regions: an acidic N-terminal domain (similar to 100 aa), a central domain (similar to 400 aa) containing a DD[D/E] catalytic triad, and a cysteine-rich domain (CRD; similar to 90 aa). Two recent reports suggested that a functional CRD is required for pble transposase activity. Here we found that two CRD-deficient pble transposases, a PB variant and an isoform encoded by the domesticated PB-derived vertebrate transposase gene 5 (pgbd5) trigger transposition of the Ifp2 pble. When overexpressed in HeLa cells, these CRD-deficient transposases can insert Ifp2 elements with proper and improper transposon ends, associated with deleterious effects on cells. Finally, we found that mouse CRD-deficient transposase Pgbd5, as well as PB, do not insert pbles at random into chromosomes. Transposition events occurred more often in genic regions, in the neighbourhood of the transcription start sites and were often found in genes predominantly expressed in the human central nervous system.

We report the anharmonic angstrom dynamics of self-assembled Au nanoparticles (Au:NPs) away from a nickel surface on top of which they are coupled by their near-field interaction. The deformation and the oscillatory excursion away from the surface are induced by picosecond acoustic pulses and probed at the surface plasmon resonance with femtosecond laser pulses. The overall dynamics are due to an efficient transfer of translational momentum from the Ni surface to the Au:NPs, therefore avoiding usual thermal effects and energy redistribution among the electronic states. Two modes are clearly revealed by the oscillatory shift of the Au:NPs surface plasmon resonance-the quadrupole deformation mode due to the transient ellipsoid shape and the excursion mode when the Au:NPs bounce away from the surface. We find that, contrary to the quadrupole mode, the excursion mode is sensitive to the distance between Au:NPs and Ni. Importantly, the excursion dynamics display a nonsinusoidal motion that cannot be explained by a standard harmonic potential model. A detailed modeling of the dynamics using a Hamaker-type Lennard-Jones potential between two media is performed, showing that each Au:NPs coherently evolves in a nearly one-dimensional anharmonic potential with a total excursion of ∼1 Å. This excursion induces a shift of the surface plasmon resonance detectable because of the strong near-field interaction. This general method of observing the spatiotemporal dynamics with angstrom and picosecond resolutions can be directly transposed to many nanostructures or biosystems to reveal the interaction and contact mechanism with their surrounding medium while remaining in their fundamental electronic states.

International audience; Eukaryotic cells have evolved a nuclear quality control (QC) system to monitor the co-transcriptional mRNA processing and packaging reactions that lead to the formation of export-competent ribonucleoprotein particles (mRNPs). Aberrant mRNPs that fail to pass the QC steps are retained in the nucleus and eliminated by the exonuclease activity of Rrp6. It is still unclear how the surveillance system is precisely coordinated both physically and functionally with the transcription machinery to detect the faulty events that may arise at each step of transcript elongation and mRNP formation. To dissect the QC mechanism, we previously implemented a powerful assay based on global perturbation of mRNP biogenesis in yeast by the bacterial Rho helicase. By monitoring model genes, we have shown that the QC process is coordinated by Nrd1, a component of the NNS complex (Nrd1-Nab3-Sen1) involved in termination, processing and decay of ncRNAs which is recruited by the CTD of RNAP II. Here, we have extended our investigations by analyzing the QC behaviour over the whole yeast genome. We performed high-throughput RNA sequencing (RNA-seq) to survey a large collection of mRNPs whose biogenesis is affected by Rho action and which can be rescued upon Rrp6 depletion. This genome-wide perspective was extended by generating high-resolution binding landscapes (ChIP-seq) of QC components along the yeast chromosomes before and after perturbation of mRNP biogenesis. Our results show that perturbation of mRNP biogenesis redistributes the QC components over the genome with a significant hijacking of Nrd1 and Nab3 from genomic loci producing ncRNAs to Rho-affected protein-coding genes, triggering termination and processing defects of ncRNAs.

Background More and more eukaryotic genomes are sequenced and assembled, most of them presented as a complete model in which missing chromosomal regions are filled by Ns and where a few chromosomes may be lacking. Avian genomes often contain sequences with high GC content, which has been hypothesized to be at the origin of many missing sequences in these genomes. We investigated features of these missing sequences to discover why some may not have been integrated into genomic libraries and/or sequenced. Results The sequences of five red jungle fowl cDNA models with high GC content were used as queries to search publicly available datasets of Illumina and Pacbio sequencing reads. These were used to reconstruct the leptin, TNFα, MRPL52, PCP2 and PET100 genes, all of which are absent from the red jungle fowl genome model. These gene sequences displayed elevated GC contents, had intron sizes that were sometimes larger than non-avian orthologues, and had non-coding regions that contained numerous tandem and inverted repeat sequences with motifs able to assemble into stable G-quadruplexes and intrastrand dyadic structures. Our results suggest that Illumina technology was unable to sequence the non-coding regions of these genes. On the other hand, PacBio technology was able to sequence these regions, but with dramatically lower efficiency than would typically be expected. Conclusions High GC content was not the principal reason why numerous GC-rich regions of avian genomes are missing from genome assembly models. Instead, it is the presence of tandem repeats containing motifs capable of assembling into very stable secondary structures that is likely responsible.

International audience; The chicken genome was the third vertebrate to be sequenced. To date, its sequence and feature annotations are used as the reference for avian models in genome sequencing projects developed on birds and other Sauropsida species, and in genetic studies of domesticated birds of economic and evolutionary biology interest. Therefore, an accurate description of this genome model is important to a wide number of scientists. Here, we review the location and features of a very basic element, the centromeres of chromosomes in the galGal5 genome model. Centromeres are elements that are not determined by their DNA sequence but by their epigenetic status, in particular by the accumulation of the histone-like protein CENP-A. Comparison of data from several public sources (primarily marker probes flanking centromeres using fluorescent in situ hybridization done on giant lampbrush chromosomes and CENP-A ChIP-seq datasets) with galGal5 annotations revealed that centromeres are likely inappropriately mapped in 9 of the 16 galGal5 chromosome models in which they are described. Analysis of karyology data confirmed that the location of the main CENP-A peaks in chromosomes is the best means of locating the centromeres in 25 galGal5 chromosome models, the majority of which (16) are fully sequenced and assembled. This data re-analysis reaffirms that several sources of information should be examined to produce accurate genome annotations, particularly for basic structures such as centromeres that are epigenetically determined.

International audience; L’Association française de karstologie est présentée à travers son organisation, sa vie administrative et ses activités. Celles-ci sont essentiellement l’activité éditoriale, l’organisation de rencontres annuelles de terrain et de colloques. Après quarante années d’existence, l'association a organisé 43 excursions de terrain (dont 13 à l’étranger), édité plus de 70 numéros de Karstologia (soit plus de 400 articles sur plus de 4 700 pages) et 20 numéros de Karstologia mémoires. Sachant que l’association ne dépasse pas la centaine de membres, ce bilan peut être considéré comme positif.

The ultrafast manipulation of the magnetization using femtosecond laser pulses is of utmost importance for both fundamental physics and technological applications. Here, the authors investigated the laser-induced ultrafast magnetization dynamics in a rare-earth iron garnet over a broad temperature range including the magnetization compensation point T${}_{\mathrm{M}}$. They find that the heat energy resulting from exciting the phonon-assisted $d$-$d$ transitions induces large-amplitude magnetization dynamics at temperatures slightly below T${}_{\mathrm{M}}$. They also demonstrate that the speed and the amplitude of the magnetization dynamics can be controlled by tuning either the laser energy density or the amplitude of the external magnetic field. The obtained results are explained by a magnetization reversal process across T${}_{\mathrm{M}}$.

International audience; The oxidation of hydrocarbons and sulfide sources (H2S, pyrite) produces sulfuric acid that strongly reacts with bedrock, causing limestone dissolution and complex interactions with other minerals from the bedrock or from cave fillings, mainly clays. This type of cave development, known as Sulfuric Acid Speleogenesis (SAS), is a subcategory of hypogene speleogenesis, where aggressive water rises from depth. It also produces uncommon minerals, mainly sulfates, the typical byproducts of SAS. Baume Galinière is located in Southern France, in the Vaucluse spring watershed. This small maze cave displays characteristic SAS features such as corrosion notches, calcite geodes, iron crusts, and various sulfate minerals. Sulfur isotopes of SAS byproducts (jarosite and gypsum) clearly show they derive from pyrite oxidation. Using XRD and micro-Raman spectroscopy, thirteen minerals were identified, including elemental sulfur, calcite, quartz, pyrite, goethite, gypsum, and fibroferrite, plus all of the six members of the jarosite subgroup (jarosite, argentojarosite, ammoniojarosite, hydroniumjarosite, natrojarosite, plumbojarosite). The Baume Galinière deposits are the first documented cave occurrence of argentojarosite and the second known occurrence of plumbojarosite, hydronium jarosite, ammoniojarosite, and fibroferrite. In the Vaucluse watershed, there were numerous upwellings of deep water along major faults, located at the contact of the karstic aquifer and the overlying impervious covers. The mixing of deep and meteoric waters at shallow depths caused pyrite depositions in numerous caves, including Baume Galinière. Sulfuric Acid Speleogenesis occurred later after base-level drop, when the cave was under shallow phreatic conditions then in the vadose zone, with oxidation of pyrites generating sulfuric acid. Attenuated oxidation is still occurring through condensation of moisture from incoming air. Baume Galinière Cave records the position of the semi-impervious paleo-cover and documents its retreat in relationship to valley incision caused by uplift and tilting of the Vaucluse block during the Neogene.

We show that the magnetization reversal of a Pt/Co/Pt ferromagnetic stack can be triggered by a single femtosecond laser pulse if the switched spot is comparable to the size of the intrinsic magnetic domains.

The characteristic of strongly correlated materials is the Mott transition between metal and insulator (MIT or IMT) in the same crystalline structure, indicating the presence of a gap formed by the Coulomb interaction between carriers. The physics of the transition needs to be revealed. Using VO2, as a model material, we observe the emergence of a metallic chain in the intermediate insulating monoclinic structure (M2 phase) of epitaxial strained films, proving the Mott transition involving the breakdown of the critical Coulomb interaction. It is revealed by measuring the temperature dynamics of coherent optical phonons with separated vibrational modes originated from two substructures in M2: one is the charge-density-wave, formed by electron-phonon (e-ph) interaction, and the other is the equally spaced insulator-chain with electron-electron (e-e) correlations.

Setmar is a 3-exons gene coding a SET domain fused to a Hsmar1 transposase. Its different transcripts theoretically encode 8 isoforms with SET moieties differently spliced. In vitro, the largest isoform binds specifically to Hsmar1 DNA ends and with no specificity to DNA when it is associated with hPso4. In colon cell lines, we found they bind specifically to two chromosomal targets depending probably on the isoform, Hsmar1 ends and sites with no conserved motifs. We also discovered that the isoforms profile was different between cell lines and patient tissues, suggesting the isoforms encoded by this gene in healthy cells and their functions are currently not investigated.

We report the magnetization dynamics excited by picosecond acoustic pulses confined in the acoustic cavity of freestanding nickel films. By detecting both sides of the sample we show that acoustic pulses moving back and forth inside the cavity efficiently control the magnetization precession. The multiple round trips of acoustic pulses, which survive for 12 bounces, enhance the amplitude of the magnetization precession by a factor of 4.5. Even though the conditions of total reflection are met in the freestanding film, the acoustic pulses have a large attenuation as compared to similar Ni films on $\mathrm{Si}{\mathrm{O}}_{2}$ substrate, for which we speculate that it is related to a stress induced by the substrate. Our results constitute a guideline for simple designs of acoustic cavities and for achieving a very large amplification of the magnetization precession angle. It is potentially useful for high-frequency magneto-optical modulators.

The little known impact of bats and bat guano in the late stages of cave morphogenesis. Bats are considered as symbolic caves inhabitants. The colonies, sometimes huge, may occupy caves through long periods. Large guano deposits were accumulated. Some have been mined for phosphates, either by hand or at the industrial scale. Bats impact is triple: breathing releases CO2, urine is corrosive, and guano mineralization releases acids (carbonic, nitric, sulfuric, and phosphoric). Such aggressive compounds have an effect on carbonate rock and flowstones, either by direct ground corrosion at the contact of the guano, or by condensation-corrosion on walls and ceilings. The speleogenetic impact of these late stages of cave evolution is considerable and may provoke denudation of several meters of rock. The long lasting presence of bat colonies is a major factor of the late speleogenetical stages, making specific morphologies, significant phosphate deposits, and wall reworking ranging from some centimeters to several meters. These corrosion morphologies, sometimes misinterpreted as marks of flooding, are also responsible of the destruction of many prehistoric realizations, which have been preserved only in specific conditions.

Provalata Cave (Republic of Macedonia) is a small but remarkable hypogenic cave, developed in Cambrian marbles by successive thermal carbonic and sulfuric acid speleogenesis. The cave has a thick partly corroded calcite crust, abundant gypsum deposits, with cupolas, ceiling and wall channels, feeders and replacement pockets as some of the most characteristic morphological features. Distribution of morphology and deposits suggest a hypogenic origin in two distinct speleogenetic phases: the first by thermal CO2 rich waters, the second by sulfuric acid dissolution, which were separated by complete infilling of cave passages with pyroclastic-derived clays. In the first phase of speleogenesis, cave passages were formed by dissolution along fractures due to cooling of rising carbonated thermal waters. These phreatic morphologies were later covered with a thick calcite crust deposited in a shallow phreatic environment. In Early Pleistocene the cave was completely filled with clays due to deposition of pyroclastic rocks in a lacustrine environment in the nearby Mariovo Basin. Mariovo Lake sediments were later incised by the Buturica River, which cut down into Cambrian marbles, creating its superimposed valley. Incision lowered the water table and allowed removal of the clay deposits in Provalata Cave. The second phase of speleogenesis started after introduction of H2S associated with rising thermal waters. Oxidation produced sulfuric acid, which rapidly dissolved first calcite crust, then marble host rock. Condensation-corrosion by sulfuric vapors replaced carbonate rock with gypsum producing replacement pockets as well as second generation of pockets and cupolas. The contact of sulfuric acid with the clay deposits formed alunite, jarosite, and natroalunite. 40Ar/39Ar dating gave maximum ages of 1.6 Ma (alunite) and 1.46 Ma (jarosite) for this last stage of speleogenesis, thus making it the second 40Ar/39Ar dating of a sulfuric cave in Europe (after Kraushöhle in Austria), and the first dated cave in the Republic of Macedonia.

Inteins are self-splicing proteins that occur in-frame within host-coded proteins. DNA elements coding for inteins insert specifically in highly conserved motifs of target genes. These mobile genetic elements have an uneven distribution and thus far have been found only in certain species of bacteria, archaea and fungi, a few viruses of algae and amoebozoa and in the entomopathogen, Chilo iridescent virus (CIV). Here, we report the discovery of seven new inteins parasitizing iridoviruses infecting metazoans: three within their δ DNA polymerase genes and four in genes coding for their large ribonucleotide reductase subunit. Analyses of coding sequences suggest that these inteins were acquired by ancestors shared by viruses currently classified as members of different families of viruses with large double-stranded (ds) DNA genomes and then were maintained by vertical transmission, or lost. Of significant interest is the finding that inteins present in the δ DNA polymerases of iridoviruses insert at a different location into the YGDTDS motif when compared to those found in other viruses and prokaryotes. In addition, our phylogenetic investigations suggest that inteins present in the δ DNA polymerases of these viruses might have an origin different from those found in prokaryotes. Finally, we use the sequence features of the intein insertion sites in host genes to discuss the high polymorphisms of inteins within and among viral species and the immunity of their genetic counterparts in the eukaryotic hosts of these viruses.