Biallelic non-productive enhancer-promoter interactions precede imprinted expression of Kcnk9 during mouse neural commitment.

It is only partially understood how constitutive allelic methylation at imprinting control regions (ICRs) interacts with other regulation levels to drive timely parental allele-specific expression along large imprinted domains. The Peg13-Kcnk9 domain is an imprinted domain with important brain functions. To gain insights into its regulation during neural commitment, we performed an integrative analysis of its allele-specific epigenetic, transcriptomic, and cis-spatial organization using a mouse stem cell-based corticogenesis model that recapitulates the control of imprinted gene expression during neurodevelopment. We found that, despite an allelic higher-order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts occurred on both alleles, although they were productive only on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side and suggests a more nuanced role for allelic CTCF binding at some ICRs.

Improving care safety by characterizing task interruptions during interactions between healthcare professionals: an observational study.

Few studies have investigated interruptions to the work of professionals practicing in inpatient hospitals, and even fewer take account of the functions that make up the system. Safety of care can be improved by considering avoidable interruptions during interactions between managerial and care delivery functions. The present study describes the characteristics of interruptions to the work of professionals working in the inpatient hospital sector, with respect to their typology, frequency, duration, and avoidability in the context of interactions between functions. This direct observational study of interruptions in hospital care was performed in the Pays de la Loire (west coast) area of France. A total of 23 teams (17 institutions) working in medical or surgical specialties (excluding intensive care) were included. Observations were performed between May and September 2019, and lasted seven consecutive hours per team. A pair of observers simultaneously observed the same professional for ∼30 min. Each occupational category was examined. Reported characteristics were: (i) the method and duration of the request, (ii) the location of interrupted and interrupting persons, (iii) the reaction of the interrupted person, (iv) the characteristics of the interrupting person, and (v) the classification of interrupted and interrupting tasks according to their function. An avoidable interruption was defined. Interruptions during interactions between professionals were categorised in terms of their function and avoidability. Descriptive statistical analyses (mean, standard deviation, and distribution) were run. In particular, cross-comparisons were run to highlight avoidability interruptions and interactions between managerial and care delivery functions during the working day, for different professional categories, and for the location of the request. Overall, 286 interrupted professionals were observed and 1929 interruptions were characterised. The majority of interruptions were due to a face-to-face request (58.7%), lasting ≤30 s (72.5%). Professionals engaged in the response in 49.3% of cases. A total of 57.4% of interruptions were avoidable. The average number of interruptions was 10.5 (SD = 3.2) per hour per professional. An analysis of avoidability and interactions between managerial and care delivery functions found that the period between 12:00 and 13:00 was the riskiest in terms of care safety. This study highlighted the characteristics of interruptions to the activity of professionals working in inpatient hospitals. Care teams could focus on making medical and nursing professionals much more aware of the importance of interruptions, and each team could decide how to best-manage interruptions, in the context of their specific working environment.

Reactivation of a somatic errantivirus and germline invasion in Drosophila ovaries.

Most Drosophila transposable elements are LTR retrotransposons, some of which belong to the genus Errantivirus and share structural and functional characteristics with vertebrate endogenous retroviruses. Like endogenous retroviruses, it is unclear whether errantiviruses retain some infectivity and transposition capacity. We created conditions where control of the Drosophila ZAM errantivirus through the piRNA pathway was abolished leading to its de novo reactivation in somatic gonadal cells. After reactivation, ZAM invaded the oocytes and severe fertility defects were observed. While ZAM expression persists in the somatic gonadal cells, the germline then set up its own adaptive genomic immune response by producing piRNAs against the constantly invading errantivirus, restricting invasion. Our results suggest that although errantiviruses are continuously repressed by the piRNA pathway, they may retain their ability to infect the germline and transpose, thus allowing them to efficiently invade the germline if they are expressed.

Short communication: Variability of response to feed restriction in lactating Charolais cows.

Involuntary temporary feed restriction on commercial cattle is likely to become more frequent with forage shortages in the context of climate change. If general consequences of feed restriction have been the subject of an abundant scientific literature, focus on the inter-individual variability of response is scarce. Here, we explore the response profile in terms of BW, body condition score, milk production, calf weight and cyclicity resumption of 293 lactations from 169 Charolais cows during a winter feed restriction in early lactation and its subsequent recovery at grazing using a principal component analysis followed by a hierarchical clustering on principal component. Results show a very continuous range of response profiles that was divided into three clusters: one with light animals having an intermediate response in terms of milk production and body maintenance, one with animals prioritising body maintenance and cyclicity resumption over milk production and calf weight, and the last one with animals prioritising milk production and calf weight over the rest. Among the animals performing more than one lactation, 57% remain in the same cluster on two successive lactations. This work highlights that an average group response to feed restriction may hide various resilience individual profiles. Further studies are required to determine the existence of a genetic component as well as the consequences of not taking this phenomenon into consideration with the regular use of feed restriction in commercial farms.

An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup.

Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose-normalized Cmax and AUC0-∞ was 93.7% [90% CI: 76.3-115.1] and 96.1% [91.0-101.5], respectively. For granules B it was 87.6% [81.6-94.0] and 92.5% [88.5-96.6], respectively, with slightly delayed tmax of 0.75 h [0.5-4.05] compared to syrup 0.5 h [0.3-0.8]. Tolerability visual analog scales revealed a trend for statistically non-significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar-free, tasteless, bioequivalent, and well-tolerated while enabling precise adjustment to body weight.

Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina.

The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host-pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype-phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.

Dalbavancin in Real Life: Economic Impact of Prescription Timing in French Hospitals.

INTRODUCTION: The extended half-life of dalbavancin justifies a once-a-week dosing schedule and is supposed to favour early discharge. These advantages may therefore compensate for the cost of dalbavancin, but no real-life assessment has been conducted to date. We aimed to assess the real-life budget impact of dalbavancin through its impact on the length of stay in French hospitals. METHODS: A multicentre cohort based on the French registry of dalbavancin use in 2019 was compared to the French national discharge summary database. Lengths of stay and budget impact related to the infection type, the time of introduction of dalbavancin, the type of catheter and patient subgroups were assessed. An early switch was defined when dalbavancin was administered as the first or second treatment and within less than 11 days of hospitalization. RESULTS: A total of 179 patients were identified in the registry, and 154 were included in our study. Dalbavancin was mostly used for bone and joint infections (56.0%), infective endocarditis (19.0%) and acute bacterial skin and skin structure infections (6.0%). When compared to the data for similar patients in the national database, the length of stay was almost always shorter for patients treated with dalbavancin (up to a reduction of 13 days). The budget impact for dalbavancin was heterogeneous but frequently generated savings (up to 2257.0 €). Early switching (within less than 11 days) was associated with savings (or lesser costs), with even greater benefits within 7 days of hospitalization. Patients who required a deep venous catheter as well as the most severe patients benefited the most from dalbavancin. CONCLUSION: Our study confirms that dalbavancin is associated with early discharge, which can offset its cost and generate savings. The greatest benefit is achieved with an early switch.

Development and validation of a UPLC-MS/MS method for the quantification of isothiazolinones in the composition and emissions from consumer products.

Isothiazolinones, a family of biocides, are used as preservatives for their fungicidal, bactericidal, and algacidal properties. These compounds can be found in a wide range of consumer and building products, such as paints, varnishes, shampoos, and liquid detergents. A robust analytical UPLC-MS/MS method to identify and quantify seven isothiazolinones (MIT, CMI, BIT, MBIT, BBIT, OIT, and DCOIT) in consumer products and their emissions was developed and validated according to ISO/IEC 17025. The limits of detection (LODs) ranged from 0.14 µg L-1 (BIT) to 0.54 µg L-1 (CMI). The method was applied for the quantification of the seven isothiazolinones in four types of consumer products (i.e., cosmetics, air fresheners, cleaning products, and building products) and the indoor emissions from a paint. Matrix effects were observed for the shampoo (63-74%), the shower gel (67-84%), and the ceramic glass cleaner (53-57%). All isothiazolinones indicated by the manufacturer (i.e., MIT, CMI, BIT, OIT, and DCOIT) were detected in the products and successfully quantified by the UPLC-MS/MS method.

[Knowledge of geriatric oncology in nursing homes: survey among healthcare professionals working in nursing homes in Pays-de-la-Loire.] / Connaissance de l'onco-gériatrie en Ehpad : enquête réalisée auprès des professionnels de santé dans les Ehpad des Pays-de-la-Loire.

OBJECTIVE: The increased incidence of cancer with age and rise of oral chemotherapy will affect the management of nursing home's residents. The aim of our study was to evaluate knowledge and practices in oncogeratric of nursing home's professionals from Pays-de-la-Loire and to raise awareness. METHODS: In partnership with UCOG-pl, OMEDIT and Observatoire du Cancer, we realised an observational survey from April to September 2017. Three questionnaires were sent to coordonary doctors (CD), nurses and paramedics, along with informative documents. RESULTS: In 589 nursing homes, 82 CD, 147 nurses and 240 paramedics gave an answer. The estimation of cancer's prevalence was 8,75%. Breast and prostate cancers were the most frequent. Nursing homes were an appropriate place to screen cancers by 79% of professionals. Some difficulties were reported by more than 80 % of them (coordination, residents' relationships...). At least, 20% of professionals couldn't define properly oncogeriatric. Only 73% of CD, 16% of nurses and 5% of paramedics knew about ongeriatric evaluations. Only 50% of CD knew about the G8 table, 15% of the oral cancer treatment file, 34% UCOG and 23% of the Observatoire du Cancer. Less than 5% of other professionals knew about this tool and these organisations. After information, most of the professionals think they will use them. Oral chemotherapy was already used by 90% of nurses, but the follow-up was considered inadequate. DISCUSSION: Our survey shows a low awareness about oncogeriatric by the nursing home's professionals. This misreading and under-diagnosis of cancer in nursing homes could partly explain by the lake of training, communication and coordination with oncology professionals and the distinctive characteristics of nursing home's residents. Study suggests that raising awareness of oncogeriatric and its challenges to all professionals would improve the care of the elderly with cancer.

Evolution of morphological but not aggressiveness-related traits following a major resistance breakdown in the poplar rust fungus, Melampsora larici-populina.

Crop varieties carrying qualitative resistance to targeted pathogens lead to strong selection pressure on parasites, often resulting in resistance breakdown. It is well known that qualitative resistance breakdowns modify pathogen population structure but few studies have analyzed the consequences on their quantitative aggressiveness-related traits. The aim of this study was to characterize the evolution of these traits following a resistance breakdown in the poplar rust fungus, Melampsora larici-populina. We based our experiment on three temporal populations sampled just before the breakdown event, immediately after and four years later. First, we quantified phenotypic differences among populations for a set of aggressiveness traits on a universally susceptible cultivar (infection efficiency, latent period, lesion size, mycelium quantity, and sporulation rate) and one morphological trait (mean spore volume). Then, we estimated heritability to establish which traits could be subjected to adaptive evolution and tested for evidence of selection. Our results revealed significant changes in the morphological trait but no variation in aggressiveness traits. By contrast, recent works have demonstrated that quantitative resistance (initially assumed more durable) could be eroded and lead to increased aggressiveness. Hence, this study is one example suggesting that the use of qualitative resistance may be revealed to be less detrimental to long-term sustainable crop production.

Determination of immunoglobulin concentrations and genetic parameters for colostrum and calf serum in Charolais animals.

Colostrum samples from 366 Charolais primiparous cows, as well as serum from their calves at 24 to 48 h of age, were collected to gain an overview of the situation regarding passive immune transfer in beef cattle, from both the phenotypic and genetic points of view. All samples were analyzed to quantify their G1 immunoglobulins by radial immunodiffusion (RID) and their IgG, IgA, and IgM using ELISA. The average concentrations obtained in colostrum were 84 mg/mL for RID-IgG1, and 158 mg/mL, 4.5 mg/mL and 10.8 mg/mL for ELISA-IgG, -IgA, and -IgM, respectively. The corresponding values in calf serum were 19.9, 30.6, 1.0, and 1.9 mg/mL. Apart from the general environmental effect (farm-year combination and laboratory conditions), the characteristics of the dams tested did not reveal any influence on colostrum immunoglobulin concentrations. Calving difficulty, as well as the birth weight and sex of calves, were found to be associated with serum concentrations in some cases. Heritability estimates were low to moderate, with the highest being for RID-IgG1 in colostrum (h2 = 0.28, standard error = 0.14) and serum (h2 = 0.36, standard error = 0.18). Phenotypic correlations among the different immunoglobulins were generally positive or null, and none of the genetic correlations were significant due to large standard errors. The phenotypic correlation between dam colostrum and calf serum values was 0.2 for RID-IgG1 and null for the 3 ELISA measurements. The correlation between RID-IgG1 and ELISA-IgG was, unexpectedly, null for colostrum and 0.4 for serum. Increased RID-IgG1 levels in calf serum were associated with improved survival, as well as better early growth and fewer health problems. These results thus showed that despite generally higher concentrations in beef than in dairy cattle, passive transfer was unsuccessful in a considerable number of calves. This should be brought to the attention of breeders to avoid negative effects on survival and subsequent performance. The heritability estimates were encouraging; however, obtaining phenotypes on a large scale constitutes a real limitation regarding these traits.

TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.

The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated. Here, we investigated the molecular mechanisms involved in the induction of Kdm6b expression upon neural commitment of mouse embryonic stem cells. We found that the increase in Kdm6b expression is linked to a rearrangement between two 3D configurations defined by the promoter contact with two different regions in the Kdm6b locus. This is associated with changes in 5-hydroxymethylcytosine (5hmC) levels at these two regions, and requires a functional ten-eleven-translocation (TET) 3 protein. Altogether, our data support a model whereby Kdm6b induction upon neural commitment relies on an intronic enhancer the activity of which is defined by its TET3-mediated 5-hmC level. This original observation reveals an unexpected interplay between the 5-hmC and H3K27me3 pathways during neural lineage commitment in mammals. It also questions to which extent KDM6B-mediated changes in H3K27me3 level account for the TET-mediated effects on gene expression.

Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults.

A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.

Transposon Reactivation in the Germline May Be Useful for Both Transposons and Their Host Genomes.

Transposable elements (TEs) are long-term residents of eukaryotic genomes that make up a large portion of these genomes. They can be considered as perfectly fine members of genomes replicating with resident genes and being transmitted vertically to the next generation. However, unlike regular genes, TEs have the ability to send new copies to new sites. As such, they have been considered as parasitic members ensuring their own replication. In another view, TEs may also be considered as symbiotic sequences providing shared benefits after mutualistic interactions with their host genome. In this review, we recall the relationship between TEs and their host genome and discuss why transient relaxation of TE silencing within specific developmental windows may be useful for both.

Methane and Carbon Dioxide Emission of Beef Heifers in Relation with Growth and Feed Efficiency.

Reducing enteric methane production and improving the feed efficiency of heifers on roughage diets are important selection objectives for sustainable beef production. The objective of the current study was to assess the relationship between different methane production and feed efficiency criteria of beef heifers fed ad libitum roughage diets. A total of 326 Charolais heifers aged 22 months were controlled in two farms and fed either a grass silage (n = 252) or a natural meadow hay (n = 74) diet. Methane (CH4) and carbon dioxide (CO2) emission rates (g/day) were measured with GreenFeed systems. The dry matter intake (DMI), average daily gain (ADG), CH4 and CO2 were measured over 8 to 12 weeks. Positive correlations were observed among body weight, DMI, ADG, CH4 and CO2. The residual feed intake (rwgDMI) was not related to CH4 or residual methane (rwiCH4). It was negatively correlated with methane yield (CH4/DMI): Rp = -0.87 and -0.83. Residual gain (rwiADG) and ADG/DMI were weakly and positively related to residual methane (rwiCH4): Rp = 0.21 on average. The ratio ADG/CO2 appeared to be a useful proxy of ADG/DMI (Rp = 0.64 and 0.97) and CH4/CO2 a proxy of methane yield (Rp = 0.24 and 0.33) for selecting low-emitting and efficient heifers.

Genetic parameters and genome-wide association study regarding feed efficiency and slaughter traits in Charolais cows.

Residual energy intake (REI) on two successive diets (hay and maize based) and slaughter traits, including visceral organs, were phenotyped in 584 adult purebred Charolais cows. To investigate the relationships between these traits and their genetic determinism, we first estimated the genetic parameters, including correlations, using REML modeling under WOMBAT software. The animals were then genotyped on the BovineSNP50 SNPchip before being imputed to the 600K density and genome wide association study was performed with GCTA software. We found low heritability for REI (h2 = 0.12 in each of the diet phases). Although the phenotypic correlation between the two diet phases was moderate (0.36), the genetic correlation was high (0.83), indicating a common genetic determinism for feed efficiency regardless of the diet. Correlations between REI and slaughter traits were negative regarding muscle-related traits and positive for fat-related traits, indicating that efficient animals generally had a more muscular carcass. It was also seen that feed efficiency was genetically and phenotypically correlated with smaller organs when expressed as a proportion of their empty body weight. From the GWAS analysis, seven QTLs were found to be associated with a trait at the genome-wide level of significance and 18 others at the chromosome-wide level. One important QTL was detected in BTA 2, reflecting the essential effect of the myostatin gene on both carcass composition and relative organ weight. Three QTLs were detected for REI during the maize diet phase on BTA 13, 19, and 28, the latter being significant at the genome-wide level. The QTLs on BTA 19 mapped into the TANC2 gene and the QTLs on BTA 28 into the KIF1BP gene, which are both known to interact with the same protein (KIF1A). However, no obvious functional link between these genes and feed efficiency could be made. Among the other QTLs detected, one association on BTA 4 with liver proportion mapped to the candidate gene WASL, which has previously been shown to be differentially expressed in liver cells and linked to feed restriction or cancer development. No QTLs were found to be common between feed efficiency and any slaughter traits.

Relationship between feed efficiency and slaughter traits of French Charolais bulls.

Improving feed efficiency is of interest to French beef producers so as to increase their profitability. To enable this improvement through selection, genetic correlations with production traits need to be quantified. The objective of this study was to estimate the genetic parameters for growth, feed efficiency (FE), and slaughter performance of young beef bulls of the French Charolais breed. Three feed efficiency criteria were calculated: residual feed intake (RFI), residual gain (RG), and ratio of FE. Data on feed intake, growth, and FE were available for 4,675 Charolais bulls tested in performance test stations and fed with pelleted diet. Between 1985 and 1989, 60 among 510 of these bulls were selected to procreate one generation of 1,477 progeny bulls which received the same pelleted diet at the experimental farm in Bourges. In addition to feed intake, growth, and FE traits, these terminal bulls also had slaughter traits of carcass yield, carcass composition, and weight of visceral organs collected. Genetic parameters were estimated using linear mixed animal models. Between performance test bulls and terminal bulls, the genetic correlation of RFI was 0.80 ± 0.18; it was 0.70 ± 0.21 for RG and 0.46 ± 0.20 for FE. For carcass traits, RFI was negatively correlated with carcass yield (-0.18 ± 0.14) and muscle content (-0.47 ± 0.14) and positively with fat content (0.48 ± 0.13). Conversely, RG and FE were positively correlated with carcass yield and muscle content and negatively with fat content. For the three FE criteria, efficient animals had leaner carcass. For visceral organs (as a proportion of empty body weight), RFI was genetically correlated with the proportions of the 5th quarter (0.51 ± 0.17), internal fat (0.36 ± 0.14), abomasum (0.46 ± 0.20), intestines (0.38 ± 0.17), liver (0.36 ± 0.16), and kidneys (0.73 ± 0.11). Conversely, RG and FE were negatively associated with these traits. The high-energy expenditure associated with the high-protein turnover in visceral organs may explain this opposite relationship between FE and the proportion of visceral organs. Selection for final weight and RFI increased growth and FE in progeny, and also improved carcass yield and muscle content in the carcass. To conclude, determinations of growth and feed intake in performance test stations are effective to select bulls to improve their growth, FE, and muscle content in carcass.

Pixel: a content management platform for quantitative omics data.

BACKGROUND: In biology, high-throughput experimental technologies, also referred as "omics" technologies, are increasingly used in research laboratories. Several thousands of gene expression measurements can be obtained in a single experiment. Researchers are routinely facing the challenge to annotate, store, explore and mine all the biological information they have at their disposal. We present here the Pixel web application (Pixel Web App), an original content management platform to help people involved in a multi-omics biological project. METHODS: The Pixel Web App is built with open source technologies and hosted on the collaborative development platform GitHub (https://github.com/Candihub/pixel). It is written in Python using the Django framework and stores all the data in a PostgreSQL database. It is developed in the open and licensed under the BSD 3-clause license. The Pixel Web App is also heavily tested with both unit and functional tests, a strong code coverage and continuous integration provided by CircleCI. To ease the development and the deployment of the Pixel Web App, Docker and Docker Compose are used to bundle the application as well as its dependencies. RESULTS: The Pixel Web App offers researchers an intuitive way to annotate, store, explore and mine their multi-omics results. It can be installed on a personal computer or on a server to fit the needs of many users. In addition, anyone can enhance the application to better suit their needs, either by contributing directly on GitHub (encouraged) or by extending Pixel on their own. The Pixel Web App does not provide any computational programs to analyze the data. Still, it helps to rapidly explore and mine existing results and holds a strategic position in the management of research data.

Defense Compounds Rather Than Nutrient Availability Shape Aggressiveness Trait Variation Along a Leaf Maturity Gradient in a Biotrophic Plant Pathogen.

Foliar pathogens face heterogeneous environments depending on the maturity of leaves they interact with. In particular, nutrient availability as well as defense levels may vary significantly, with opposing effects on the success of infection. The present study tested which of these factors have a dominant effect on the pathogen's development. Poplar leaf disks of eight maturity levels were inoculated with the poplar rust fungus Melampsora larici-populina using an innovative single-spore inoculation procedure. A set of quantitative fungal traits (infection efficiency, latent period, uredinia size, mycelium quantity, sporulation rate, sporulation capacity, and spore volume) was measured on each infected leaf disk. Uninfected parts of the leaves were analyzed for their nutrient (sugars, total C and N) and defense compounds (phenolics) content. We found that M. larici-populina is more aggressive on more mature leaves as indicated by wider uredinia and a higher sporulation rate. Other traits varied independently from each other without a consistent pattern. None of the pathogen traits correlated with leaf sugar, total C, or total N content. In contrast, phenolic contents (flavonols, hydroxycinnamic acid esters, and salicinoids) were negatively correlated with uredinia size and sporulation rate. The pathogen's fitness appeared to be more constrained by the constitutive plant defense level than limited by nutrient availability, as evident in the decrease in sporulation.

The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing.

Transposable elements (TEs) have invaded most genomes and constitute up to 50% of the human genome. Machinery based on small non-coding piRNAs has evolved to inhibit their expression at the transcriptional and post-transcriptional levels. Surprisingly, this machinery is weakened during specific windows of time in mice, flies or plants, allowing the expression of TEs in germline cells. The function of this de-repression remains unknown. In Drosophila, we have previously shown that this developmental window is characterized by a reduction of Piwi expression in dividing germ cells. Here, we show that the unique knock-down of Aub in these cells leads to female sterility. It correlates with defects in piRNA amplification, an increased Piwi expression and an increased silencing of transcriptionally silenced TEs. These defects are similar to those observed when Aub is depleted in the whole germline which underlies the crucial role of this developmental window for both oogenesis and TE silencing. We further show that, with age, some fertility is recovered which is concomitant to a decrease of Piwi and TE silencing. These data pinpoint the Pilp as a tremendously important step for female fertility and genome stability. They further show that such a restricted developmental niche of germ cells may sense environmental changes, such as aging, to protect the germline all along the life.