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See detailImaging low-mass planets within the habitable zone of α Centauri
Wagner, K.; Boehle, A.; Pathak, P. et al

in Nature Communications (2021), 12

Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we ... [more ▼]

Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, α Centauri. Based on 75-80% of the best quality images from 100 h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of α Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around α Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes. [less ▲]

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See detailOxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats.
De Moura Oliveira, Vinicius Elias ULiege; Lukas, Michael; Wolf, Hannah Nora et al

in Nature Communications (2021), 12(1), 2900

In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and ... [more ▼]

In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialysis approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), is required for aggression in female rats. Accordingly, increased activity of putative OXT receptor-positive neurons in the vLS, and decreased activity of putative AVP receptor-positive neurons in the dLS, are likely to underly aggression in female rats. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data suggest a model showing that septal release of OXT and AVP differentially affects aggression in females by modulating the inhibitory tone within LS sub-networks. [less ▲]

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See detailWobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.
Rapino, Francesca ULiege; ZHOU, ZHAOLI; RONCERO SANCHEZ, Ana Maria et al

in Nature Communications (2021), 12(1), 2170

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon ... [more ▼]

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm(5)s(2) wobble uridine tRNA modification (U(34)-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U(34)-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U(34)-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis. [less ▲]

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See detailQuality control of protein reagents for the improvement of research data reproducibility.
de Marco, Ario; Berrow, Nick; Lebendiker, Mario et al

in Nature Communications (2021), 12(1), 2795

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See detailGreater Greenland Ice Sheet contribution to global sea level rise in CMIP6
Hofer, S.; Lang, Charlotte ULiege; Amory, Charles ULiege et al

in Nature Communications (2020), 11

Future climate projections show a marked increase in Greenland Ice Sheet (GrIS) runoff during the 21st century, a direct consequence of the Polar Amplification signal. Regional climate models (RCMs) are a ... [more ▼]

Future climate projections show a marked increase in Greenland Ice Sheet (GrIS) runoff during the 21st century, a direct consequence of the Polar Amplification signal. Regional climate models (RCMs) are a widely used tool to downscale ensembles of projections from global climate models (GCMs) to assess the impact of global warming on GrIS melt and sea level rise contribution. Initial results of the CMIP6 GCM model intercomparison project have revealed a greater 21st century temperature rise than in CMIP5 models. However, so far very little is known about the subsequent impacts on the future GrIS surface melt and therefore sea level rise contribution. Here, we show that the total GrIS sea level rise contribution from surface mass loss in our high-resolution (15 km) regional climate projections is 17.8 ± 7.8 cm in SSP585, 7.9 cm more than in our RCP8.5 simulations using CMIP5 input. We identify a +1.3 °C greater Arctic Amplification and associated cloud and sea ice feedbacks in the CMIP6 SSP585 scenario as the main drivers. Additionally, an assessment of the GrIS sea level contribution across all emission scenarios highlights, that the GrIS mass loss in CMIP6 is equivalent to a CMIP5 scenario with twice the global radiative forcing. [less ▲]

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See detailAN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion
Schuster, Anne; Klein, Eliane; Neirinckx, Virginie ULiege et al

in Nature Communications (2020), 11(1), 6366

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the ... [more ▼]

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted. [less ▲]

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See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine ULiege et al

in Nature Communications (2020), 11(1), 4752

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

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See detailCircadian clock mechanism driving mammalian photoperiodism
Wood, S.H.; Hindle, M.M.; Mizoro, Yasutaka ULiege et al

in Nature Communications (2020), 11(4291),

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here ... [more ▼]

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here, light-dark cycles entrain a circadian rhythm of photosensitivity, and the expression of summer or winter biology depends on whether light coincides with the phase of high photosensitivity. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that coincidence timing takes place in the pars tuberalis of the pituitary, through a melatonin-dependent flip-flop switch between circadian transcriptional activation and repression. Long photoperiods produce short night-time melatonin signals, leading to induction of the circadian transcription factor BMAL2, in turn triggering summer biology through the eyes absent / thyrotrophin (EYA3 / TSH) pathway. Conversely, short photoperiods produce long melatonin signals, inducing circadian repressors including DEC1, in turn suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates. [less ▲]

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See detailReturn to rapid ice loss in Greenland and record loss in 2019 detected by the GRACE-FO satellites
Sasgen, I.; Wouters, B.; Gardner, A. et al

in Nature Communications (2020), 1(8),

Between 2003-2016, the Greenland ice sheet (GrIS) was one of the largest contributors to sea level rise, as it lost about 255 Gt of ice per year. This mass loss slowed in 2017 and 2018 to about 100 Gt ... [more ▼]

Between 2003-2016, the Greenland ice sheet (GrIS) was one of the largest contributors to sea level rise, as it lost about 255 Gt of ice per year. This mass loss slowed in 2017 and 2018 to about 100 Gt yr−1. Here we examine further changes in rate of GrIS mass loss, by analyzing data from the GRACE-FO (Gravity Recovery and Climate Experiment – Follow On) satellite mission, launched in May 2018. Using simulations with regional climate models we show that the mass losses observed in 2017 and 2018 by the GRACE and GRACE-FO missions are lower than in any other two year period between 2003 and 2019, the combined period of the two missions. We find that this reduced ice loss results from two anomalous cold summers in western Greenland, compounded by snow-rich autumn and winter conditions in the east. For 2019, GRACE-FO reveals a return to high melt rates leading to a mass loss of 223 ± 12 Gt month−1 during the month of July alone, and a record annual mass loss of 532 ± 58 Gt yr−1. [less ▲]

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See detailThe atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides.
Meyrath, Max Marc Roger ULiege; Szpakowska, Martyna; Zeiner, Julian et al

in Nature Communications (2020), 11(1), 3033

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7 ... [more ▼]

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7, hitherto known as an atypical scavenger receptor for chemokines, is a broad-spectrum scavenger of opioid peptides. Phylogenetically, ACKR3 is intermediate between chemokine and opioid receptors and is present in various brain regions together with classical opioid receptors. Functionally, ACKR3 is a scavenger receptor for a wide variety of opioid peptides, especially enkephalins and dynorphins, reducing their availability for the classical opioid receptors. ACKR3 is not modulated by prescription opioids, but we show that an ACKR3-selective subnanomolar competitor peptide, LIH383, can restrain ACKR3's negative regulatory function on opioid peptides in rat brain and potentiate their activity towards classical receptors, which may open alternative therapeutic avenues for opioid-related disorders. Altogether, our results reveal that ACKR3 is an atypical opioid receptor with cross-family ligand selectivity. [less ▲]

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See detailSpecific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis
wang, guangxia; Muhl, Lars; Padberg, Yvonne et al

in Nature Communications (2020)

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See detailEast Siberian Arctic inland waters emit mostly contemporary carbon
Dean, Joshua F.; Meisel, Ove H.; Martyn Rosco, Mélanie et al

in Nature Communications (2020), 11(2020), 1-10

Inland waters (rivers, lakes and ponds) are important conduits for the emission of terrestrial carbon in Arctic permafrost landscapes. These emissions are driven by turnover of contemporary terrestrial ... [more ▼]

Inland waters (rivers, lakes and ponds) are important conduits for the emission of terrestrial carbon in Arctic permafrost landscapes. These emissions are driven by turnover of contemporary terrestrial carbon and additional pre-aged (Holocene and late-Pleistocene) carbon released from thawing permafrost soils, but the magnitude of these source contributions to total inland water carbon fluxes remains unknown. Here we present unique simultaneous radiocarbon age measurements of inland water CO2, CH4 and dissolved and particulate organic carbon in northeast Siberia during summer. We show that >80% of total inland water carbon was contemporary in age, but pre-aged carbon contributed >50% at sites strongly affected by permafrost thaw. CO2 and CH4 were younger than dissolved and particulate organic carbon, suggesting emissions were primarily fuelled by contemporary carbon decomposition. Our findings reveal that inland water carbon emissions from permafrost landscapes may be more sensitive to changes in contemporary carbon turnover than the release of pre-aged carbon from thawing permafrost. [less ▲]

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See detailThe X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage
Shostak, Kateryna ULiege; Jiang, Zheshen ULiege; CHARLOTEAUX, Benoit ULiege et al

in Nature Communications (2020), 11(1),

Prolonged cell survival occur through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and ... [more ▼]

Prolonged cell survival occur through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization. [less ▲]

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See detailDual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing.
Nepal, Chirag; Hadzhiev, Yavor; Balwierz, Piotr J. et al

in Nature Communications (2020), 11(1), 168

Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry ... [more ▼]

Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5’-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5’-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs. [less ▲]

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See detailBryophytes are predicted to lag behind future climate change despite their high dispersal capacities
Zanatta, Florian ULiege; Engler, Robin; Collart, Flavien ULiege et al

in Nature Communications (2020), 11

The extent to which species can balance out the loss of suitable habitats due to climate warming by shifting their ranges is an area of controversy. Here, we assess whether highly efficient wind-dispersed ... [more ▼]

The extent to which species can balance out the loss of suitable habitats due to climate warming by shifting their ranges is an area of controversy. Here, we assess whether highly efficient wind-dispersed organisms like bryophytes can keep-up with projected shifts in their areas of suitable climate. Using a hybrid statistical-mechanistic approach accounting for spatial and temporal variations in both climatic and wind conditions, we simulate future migrations across Europe for 40 bryophyte species until 2050. The median ratios between predicted range loss vs expansion by 2050 across species and climate change scenarios range from 1.6 to 3.3 when only shifts in climatic suitability were considered, but increase to 34.7–96.8 when species dispersal abilities are added to our models. This highlights the importance of accounting for dispersal restrictions when projecting future distribution ranges and suggests that even highly dispersive organisms like bryophytes are not equipped to fully track the rates of ongoing climate change in the course of the next decades. [less ▲]

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See detailInhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
Zaninello, Marta; Palikaras, Konstantinos; Naon, Deborah et al

in Nature Communications (2020)

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See detailMultiplying the efficiency and impact of biofortification through metabolic engineering.
Van Der Straeten, Dominique; Bhullar, Navreet K.; De Steur, Hans et al

in Nature Communications (2020), 11(1), 5203

Ending all forms of hunger by 2030, as set forward in the UN-Sustainable Development Goal 2 (UN-SDG2), is a daunting but essential task, given the limited timeline ahead and the negative global health and ... [more ▼]

Ending all forms of hunger by 2030, as set forward in the UN-Sustainable Development Goal 2 (UN-SDG2), is a daunting but essential task, given the limited timeline ahead and the negative global health and socio-economic impact of hunger. Malnutrition or hidden hunger due to micronutrient deficiencies affects about one third of the world population and severely jeopardizes economic development. Staple crop biofortification through gene stacking, using a rational combination of conventional breeding and metabolic engineering strategies, should enable a leap forward within the coming decade. A number of specific actions and policy interventions are proposed to reach this goal. [less ▲]

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See detailORF Capture-Seq as a versatile method for targeted identification of full-length isoforms
Sheynkman, G. M.; Tuttle, K. S.; Laval, Florent ULiege et al

in Nature Communications (2020), 11(1),

Most human protein-coding genes are expressed as multiple isoforms, which greatly expands the functional repertoire of the encoded proteome. While at least one reliable open reading frame (ORF) model has ... [more ▼]

Most human protein-coding genes are expressed as multiple isoforms, which greatly expands the functional repertoire of the encoded proteome. While at least one reliable open reading frame (ORF) model has been assigned for every coding gene, the majority of alternative isoforms remains uncharacterized due to (i) vast differences of overall levels between different isoforms expressed from common genes, and (ii) the difficulty of obtaining full-length transcript sequences. Here, we present ORF Capture-Seq (OCS), a flexible method that addresses both challenges for targeted full-length isoform sequencing applications using collections of cloned ORFs as probes. As a proof-of-concept, we show that an OCS pipeline focused on genes coding for transcription factors increases isoform detection by an order of magnitude when compared to unenriched samples. In short, OCS enables rapid discovery of isoforms from custom-selected genes and will accelerate mapping of the human transcriptome. © 2020, The Author(s). [less ▲]

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See detail2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer.
Blomme, Arnaud ULiege; Ford, Catriona A.; Mui, Ernest et al

in Nature Communications (2020), 11(1), 2508

Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study ... [more ▼]

Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant cells and associated with perturbed glucose and lipid metabolism. To exploit this phenotype, we delineate a subset of proteins consistently associated with ARI resistance and highlight mitochondrial 2,4-dienoyl-CoA reductase (DECR1), an auxiliary enzyme of beta-oxidation, as a clinically relevant biomarker for CRPC. Mechanistically, DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises CRPC cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1 in the development of treatment resistance. [less ▲]

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See detailOccurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus.
Poncin, Katy; Roba, Agnès; Jimmidi, Ravikumar et al

in Nature Communications (2019), 10(1), 4847

It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does ... [more ▼]

It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophage infection. Genes encoding direct repair and base-excision repair pathways are required by B. abortus to face this stress in vitro and in a mouse infection model. Among these genes, ogt is found to be under the control of the conserved cell-cycle transcription factor GcrA. Our results highlight that the control of DNA repair in B. abortus displays distinct features that are not present in model organisms such as Escherichia coli. [less ▲]

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