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DNA is a complex molecule carrying the instructions an organism needs to develop, live and reproduce. In 1953, Watson and Crick discovered that DNA is composed of two chains forming a double-helix. Later on, other structures of DNA were discovered and shown to play important roles in the cell, in particular G-quadruplex (G4). Following genome sequencing, several bioinformatic algorithms were developed to map G4s in vitro based on a canonical sequence motif, G-richness and G-skewness or alternatively sequence features including k-mers, and more recently machine/deep learning. Recently, new sequencing techniques were developed to map G4s in vitro (G4-seq) and G4s in vivo (G4 ChIP-seq) at few hundred base resolution. Here, we propose a novel convolutional neural network (DeepG4) to map cell-type specific active G4 regions ( e.g . regions within which G4s form both in vitro and in vivo). DeepG4 is very accurate to predict active G4 regions in different cell types. Moreover, DeepG4 identifies key DNA motifs that are predictive of G4 region activity. We found that such motifs do not follow a very flexible sequence pattern as current algorithms seek for. Instead, active G4 regions are determined by numerous specific motifs. Moreover, among those motifs, we identified known transcription factors (TFs) which could play important roles in G4 activity by contributing either directly to G4 structures themselves or indirectly by participating in G4 formation in the vicinity. In addition, we used DeepG4 to predict active G4 regions in a large number of tissues and cancers, thereby providing a comprehensive resource for researchers. Availability: https://github.com/morphos30/DeepG4 .

Ataxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved in transcription and in the maintenance of genome integrity. Here, using ChIP followed by high throughput sequencing (ChIP-seq), we report that senataxin is recruited at DNA double-strand breaks (DSBs) when they occur in transcriptionally active loci. Genome-wide mapping unveiled that RNA:DNA hybrids accumulate on DSB-flanking chromatin but display a narrow, DSB-induced, depletion near DNA ends coinciding with senataxin binding. Although neither required for resection nor for timely repair of DSBs, senataxin was found to promote Rad51 recruitment, to minimize illegitimate rejoining of distant DNA ends and to sustain cell viability following DSB production in active genes. Our data suggest that senataxin functions at DSBs in order to limit translocations and ensure cell viability, providing new insights on AOA2/ALS4 neuropathies. Recent studies suggest key roles of RNA in DNA double-strand breaks repair. Here the authors identify the helicase senataxin to be involved in DNA repair and resolve RNA:DNA hybrids forming at DNA double-strand breaks.

The repair of DNA double-strand breaks (DSBs) is essential for safeguarding genome integrity. When a DSB forms, the PI3K-related ATM kinase rapidly triggers the establishment of megabase-sized, chromatin domains decorated with phosphorylated histone H2AX (γH2AX), which act as seeds for the formation of DNA-damage response foci 1 . It is unclear how these foci are rapidly assembled to establish a ‘repair-prone’ environment within the nucleus. Topologically associating domains are a key feature of 3D genome organization that compartmentalize transcription and replication, but little is known about their contribution to DNA repair processes 2 , 3 . Here we show that topologically associating domains are functional units of the DNA damage response, and are instrumental for the correct establishment of γH2AX–53BP1 chromatin domains in a manner that involves one-sided cohesin-mediated loop extrusion on both sides of the DSB. We propose a model in which H2AX-containing nucleosomes are rapidly phosphorylated as they actively pass by DSB-anchored cohesin. Our work highlights the importance of chromosome conformation in the maintenance of genome integrity and demonstrates the establishment of a chromatin modification by loop extrusion. During the repair of double-stranded DNA breaks, cohesin mediates the extrusion of loops of DNA along which phosphorylated H2AX spreads to establish a repair zone.

Capture Hi-C analysis reveals that DNA double-strand breaks within transcriptionally active regions of the human genome form clusters that exhibit delayed repair in the G1 phase of the cell cycle. The ability of DNA double-strand breaks (DSBs) to cluster in mammalian cells has been a subject of intense debate in recent years. Here we used a high-throughput chromosome conformation capture assay (capture Hi-C) to investigate clustering of DSBs induced at defined loci in the human genome. The results unambiguously demonstrated that DSBs cluster, but only when they are induced within transcriptionally active genes. Clustering of damaged genes occurs primarily during the G1 cell-cycle phase and coincides with delayed repair. Moreover, DSB clustering depends on the MRN complex as well as the Formin 2 (FMN2) nuclear actin organizer and the linker of nuclear and cytoplasmic skeleton (LINC) complex, thus suggesting that active mechanisms promote clustering. This work reveals that, when damaged, active genes, compared with the rest of the genome, exhibit a distinctive behavior, remaining largely unrepaired and clustered in G1, and being repaired via homologous recombination in postreplicative cells.

This study investigates the microplastic contamination of both urban compartments (wastewater and total atmospheric fallout) and surface water in a continental environment (Greater Paris, France). These first investigations on urban environment confirm the presence of microplastics in sewage, freshwater and total atmospheric fallout and provide knowledge on the type and size distribution of microplastics in the [100 µm-5 000 µm] range. For the first time, the presence of microplastics, mostly fibers, is highlighted in total atmospheric fallout (29-280 particles/m2/day). High levels of fibers were found in wastewater (260-320 x103 particles/m3). In treated effluent, the contamination significantly decreases to 14-50 x103 particles/m3. In River Seine, two sampling devices are used to collect both large and small microplastic particles: i) a plankton net (80 µm mesh) and ii) a manta trawl (330 µm mesh). Sampling with the plankton net showed a predominance of fibers with concentrations ranging from 3 to 108 particles/m3. A greater diversity of both microplastic shapes and types was encountered during manta trawl sampling but at much lower concentrations (0.28-0.47 particles/m3). This combined approach could be relevant and implemented in future studies to provide an accurate overview of microplastic distribution in freshwater.

Background Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated. Results We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia . We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92–98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. Conclusions These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift.

This study aimed to define the optimal composition of three heterogeneous substrates of the anaerobic digestion process to maximize methane production. The investigated substrates were sewage sludge (SS), the organic fraction of municipal solid waste (OFMSW), and horse waste (HW). The optimal composition of these substrates was defined using the mixture design and, more specifically, the simplex–centroid mixture design. Customized methods and materials were employed to study the complex mixture design of these substrates. The findings revealed that the optimal mixture involved all three substrates with the composition 0.17 HW, 0.66 SS, and 0.17 OFMSW, which demonstrated the highest methane yield at 269 NmL·gVS−1. In addition, a mathematical model was developed to predict methane production based on a specific composition of co-substrates. The results were validated at the small pilot scale.

The effects of co-digesting sewage sludge (SS) and horse waste (HW), the composition of HW, and the ratio of HW:SS were studied using two semi-continuous digesters of 9.5 L of working volume. These digesters were operated in parallel with the mono-digestion of SS in digester 1 (D1) and the co-digestion of SS and HW in digester 2 (D2). In digester 2, there were two phases of digestion (durations of 40 and 43 weeks, respectively). The composition of HW in the first phase was 85% wheat straw (WS), 14% wood chips (WC), and 1% horse manure (HM), with 99% wheat straw (WS) and 1% horse manure (HM) in the second phase. Variable ratios of HW:SS were studied in the digesters. The co-digestion of sewage sludge (SS) and horse waste (HW) produced more biogas than the mono-digestion of SS alone, with a maximum of 15.8 L·d−1, compared to 9 L·d−1 at the end of the experiment. When comparing the results obtained in both phases, the production of methane in phase 2 was 18 NmL·gVS−1 higher than in phase 1. This slight increase in methane yield could be linked to the absence of wood chips (WC), which is considered to have a diluting effect on methane production. Therefore, this study shows that an organic loading rate (OLR) of 4.8 kgVS·m−3·d−1, a ratio of HW:SS of 3, and a composition of HW (99% WS, 1% HM) should be respected in the actual experimental conditions for a well-functioning anaerobic digestion.

Abstract Stringent discharge regulations are encouraging researchers to create innovative and sustainable wastewater treatment solutions. Urine source separation (USS) is among the potent approaches that may reduce nutrient peak loads in the influent wastewater and improve nutrient recovery. A phenomenological model was used to simulate dynamic influent properties and predict the advantages gained from implementing USS in an urban water basin. Several scenarios were investigated assuming different levels of deployment: at the entire city, or specifically in office buildings for men's urine only, or for both men and women employees. The results confirmed that all scenarios of urine source separation offered benefits at the treatment plant in terms of reducing nitrogen influent load. The economic benefits in terms of reducing energy consumption for nitrification and decreasing methanol addition for denitrification were quantified, and results confirmed environmental advantages gained from different USS scenarios. Despite larger advantages gained from a global USS rate in an entire city, implementation of a specific USS in office buildings would remain more feasible from a logistical perspective. A significant benefit in terms of reducing greenhouse gas emissions is demonstrated and this was especially due to the high level of N2O emissions avoided in nitrifying biological aerated filter.

This paper aimed to study the value of horse manure through anaerobic digestion. The study involved characterization of different components of horse waste and the evaluation of their biochemical composition, physicochemical characterization and the influence of the composition of horse waste on biochemical methane potential. More specifically, two bedding mixtures were studied: the first one was composed of wheat straw (WS), wood chips (WC) and horse manure (HM) with a volumetric composition of 85%, 14% and 1%, respectively; and the second one was a mixture of WS and HM with a volumetric composition of 99% and 1%, respectively. The analysis was carried out on the two bedding mixtures and on each substrate separately with 406 samples from May 2017 to October 2019. Biochemical methane potential tests conducted on these samples showed that the composition and structure of the substrate influenced the BMP. WS had the highest mono-digestion methane production with 176.1 NmL·gVS−1. The second bedding mixture (99% WS, 1% HM) showed a production of 189.4 NmL·gVS−1 compared to 127 NmL·gVS−1 by bedding mixture 1 (85% WS, 14% WC, 1% HM). The difference was due to a dilution effect on methane production caused by the presence of WC rich in lignin.