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  • HAL (CCSd)  (22)
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  • 1
    Language: English
    In: Silence, 25 October 2011, Vol.2(1), pp.7
    Description: MicroRNAs, post-transcriptional regulators of eukaryotic gene expression, are implicated in host defense against pathogens. Viruses and bacteria have evolved strategies that suppress microRNA functions, resulting in a sustainable infection. In this work we report that Helicobacter pylori, a human stomach-colonizing bacterium responsible for severe gastric inflammatory diseases and gastric cancers, downregulates an embryonic stem cell microRNA cluster in proliferating gastric epithelial cells to achieve cell cycle arrest. Using a deep sequencing approach in the AGS cell line, a widely used cell culture model to recapitulate early events of H. pylori infection of gastric mucosa, we reveal that hsa-miR-372 is the most abundant microRNA expressed in this cell line, where, together with hsa-miR-373, it promotes cell proliferation by silencing large tumor suppressor homolog 2 (LATS2) gene expression. Shortly after H. pylori infection, miR-372 and miR-373 synthesis is highly inhibited, leading to the post-transcriptional release of LATS2 expression and thus, to a cell cycle arrest at the G1/S transition. This downregulation of a specific cell-cycle-regulating microRNA is dependent on the translocation of the bacterial effector CagA into the host cells, a mechanism highly associated with the development of severe atrophic gastritis and intestinal-type gastric carcinoma. These data constitute a novel example of host-pathogen interplay involving microRNAs, and unveil the couple LATS2/miR-372 and miR-373 as an unexpected mechanism in infection-induced cell cycle arrest in proliferating gastric cells, which may be relevant in inhibition of gastric epithelium renewal, a major host defense mechanism against bacterial infections.
    Keywords: Life Sciences ; Cellular Biology ; Life Sciences ; Development Biology ; Anatomy & Physiology;
    E-ISSN: 1758-907X
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  • 2
    Language: English
    In: Nucleic acids research, October 2010, Vol.38(19), pp.6620-36
    Description: Using an experimental approach, we investigated the RNome of the pathogen Staphylococcus aureus to identify 30 small RNAs (sRNAs) including 14 that are newly confirmed. Among the latter, 10 are encoded in intergenic regions, three are generated by premature transcription termination associated with riboswitch activities, and one is expressed from the complementary strand of a transposase gene. The expression of four sRNAs increases during the transition from exponential to stationary phase. We focused our study on RsaE, an sRNA that is highly conserved in the bacillales order and is deleterious when over-expressed. We show that RsaE interacts in vitro with the 5' region of opp3A mRNA, encoding an ABC transporter component, to prevent formation of the ribosomal initiation complex. A previous report showed that RsaE targets opp3B which is co-transcribed with opp3A. Thus, our results identify an unusual case of riboregulation where the same sRNA controls an operon mRNA by targeting two of its cistrons. A combination of biocomputational and transcriptional analyses revealed a remarkably coordinated RsaE-dependent downregulation of numerous metabolic enzymes involved in the citrate cycle and the folate-dependent one-carbon metabolism. As we observed that RsaE accumulates transiently in late exponential growth, we propose that RsaE functions to ensure a coordinate downregulation of the central metabolism when carbon sources become scarce.
    Keywords: RNA, Small Untranslated -- Metabolism ; Staphylococcus Aureus -- Genetics
    ISSN: 03051048
    E-ISSN: 1362-4962
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  • 3
    In: PLoS Genetics, 2017, Vol.13(2)
    Description: The carbon storage regulator protein CsrA regulates cellular processes post-transcriptionally by binding to target-RNAs altering translation efficiency and/or their stability. Here we identified and analyzed the direct targets of CsrA in the human pathogen Legionella pneumophila . Genome wide transcriptome, proteome and RNA co-immunoprecipitation followed by deep sequencing of a wild type and a csrA mutant strain identified 479 RNAs with potential CsrA interaction sites located in the untranslated and/or coding regions of mRNAs or of known non-coding sRNAs. Further analyses revealed that CsrA exhibits a dual regulatory role in virulence as it affects the expression of the regulators FleQ, LqsR, LetE and RpoS but it also directly regulates the timely expression of over 40 Dot/Icm substrates. CsrA controls its own expression and the stringent response through a regulatory feedback loop as evidenced by its binding to RelA-mRNA and links it to quorum sensing and motility. CsrA is a central player in the carbon, amino acid, fatty acid metabolism and energy transfer and directly affects the biosynthesis of cofactors, vitamins and secondary metabolites. We describe the first L . pneumophila riboswitch, a thiamine pyrophosphate riboswitch whose regulatory impact is fine-tuned by CsrA, and identified a unique regulatory mode of CsrA, the active stabilization of RNA anti-terminator conformations inside a coding sequence preventing Rho-dependent termination of the gap operon through transcriptional polarity effects. This allows L . pneumophila to regulate the pentose phosphate pathway and the glycolysis combined or individually although they share genes in a single operon. Thus the L . pneumophila genome has evolved to acclimate at least five different modes of regulation by CsrA giving it a truly unique position in its life cycle. Author summary The RNA binding protein CsrA is the master regulator of the bi-phasic life cycle of Legionella pneumophila governing virulence expression in this intracellular pathogen. Here, we have used deep sequencing of RNA enriched by co-immunoprecipitation with epitope-tagged CsrA to identify CsrA-associated transcripts at the genome level. We found 479 mRNAs or non-coding RNAs to be targets of CsrA. Among those major regulators including FleQ, the regulator of flagella expression, LqsR, the regulator of quorum sensing and RpoS implicated in stress response were identified. The expression of over 40 type IV secreted effector proteins important for intracellular survival and virulence are under the control of CsrA. Combined with transcriptomics, whole shotgun proteomics of a wild type and a CsrA mutant strain and functional analyses of several CsrA-targeted RNAs we identified the first riboswitch in L . pneumophila , a thiamine pyrophosphate riboswitch, and discovered a new mode of regulation by CsrA that allows L . pneumophila to regulate the pentose phosphate pathway and the glycolysis combined or individually although they share genes in a single operon. Our results further underline the indispensable role of CsrA in the life cycle of L . pneumophila and provide new insights into its regulatory roles and mechanisms.
    Keywords: Research Article ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences
    ISSN: 1553-7390
    E-ISSN: 1553-7404
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  • 4
    Language: English
    In: Frontiers in Microbiology, 2018, Vol.9, p.1929
    Description: Over the last 60 years, soil microbiologists have accumulated a wealth of experimental data showing that the usual bulk, macroscopic parameters used to characterize soils (e.g., granulometry, pH, soil organic matter and biomass contents) provide insufficient information to describe quantitatively the activity of soil microorganisms and some of its outcomes, like the emission of greenhouse gases. Clearly, new, more appropriate macroscopic parameters are needed, which reflect better the spatial heterogeneity of soils at the microscale (i.e., the pore scale). For a long time, spectroscopic and microscopic tools were lacking to quantify processes at that scale, but major technological advances over the last 15 years have made suitable equipment available to researchers. In this context, the objective of the present article is to review progress achieved to date in the significant research program that has ensued. This program can be rationalized as a sequence of steps, namely the quantification and modeling of the physical-, (bio)chemical-, and microbiological properties of soils, the integration of these different perspectives into a unified theory, its upscaling to the macroscopic scale, and, eventually, the development of new approaches to measure macroscopic soil characteristics. At this stage, significant progress has been achieved on the physical front, and to a lesser extent on the (bio)chemical one as well, both in terms of experiments and modeling. In terms of microbial aspects, whereas a lot of work has been devoted to the modeling of bacterial and fungal activity in soils at the pore scale, the appropriateness of model assumptions cannot be readily assessed because relevant experimental data are extremely scarce. For the overall research to move forward, it will be crucial to make sure that research on the microbial components of soil systems does not keep lagging behind the work on the physical and (bio)chemical characteristics. Concerning the subsequent steps in the program, very little integration of the various disciplinary perspectives has occurred so far, and, as a result, researchers have not yet been able to tackle the scaling up to the macroscopic level. Many challenges, some of them daunting, remain on the path ahead.Fortunately, a number of these challenges may be resolved by brand new measuring equipment that will become commercially available in the very near future.
    Keywords: Life Sciences ; X-Ray Computed ; Upscaling ; Biodiversity ; Soil Microbiology ; Tomography ; Single-Cell Genomics ; Nanosims Imaging ; Biology
    ISSN: 1664-302X
    E-ISSN: 1664-302X
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  • 5
    Language: English
    In: Soil Science Society of America Journal, 2013, Vol.77(2), p.403
    Description: The influence of clay content in soil-pore structure development and the relative importance of macroporosity in governing convective fluid flow are two key challenges toward better understanding and quantifying soil ecosystem functions. In this study, soil physical measurements (soil-water retention and air permeability) and x-ray computed tomography (CT) scanning were combined and used from two scales on intact soil columns (100 and 580 cm super(3)). The columns were sampled along a natural clay gradient at six locations (L1, L2, L3, L4, L5 and L6 with 0.11, 0.16, 0.21, 0.32, 0.38 and 0.46 kg kg super(-1) clay content, respectively) at a field site in Lerbjerg, Denmark. The water-holding capacity of soils markedly increased with increasing soil clay content, while significantly higher air permeability was observed for the L1 to L3 soils than for the L4 to L6 soils. Higher air permeability values observed for 580- than 100-cm super(3) soil columns implied a scale effect and relatively greater importance of macropores in convective fluid flow at larger scale. Supporting this, x-ray CT showed that both interaggregate pores and biopores (pores formed by earthworms and plant roots) were present at L1 to L3 in decreasing order, whereas only interaggre- gate pores were observed at L4 to L6. Macroporosity inferred from x-ray CT to quantify pores 1 mm decreased from 2.9 to 0.1 % from L1 to L6. A progressive improvement was observed in the linear relationship (R super(2) increasing 0.50-0.95) of air permeability with total air-filled porosity, CT-inferred macroporosity, and CT-inferred limiting macroporosity (minimum macroporosity for any quarter of soil column). The findings of this study show the immense potential in linking x-ray CT-derived soil-pore parameters with classical soil physical measurements for quantifying soil architecture and functions. [PUBLICATION]
    Keywords: Soil ; Permeability ; Earthworms ; Soil Structure ; Clay ; Porosity ; Computed Tomography ; Denmark ; Air Pollution;
    ISSN: Soil Science Society of America Journal
    E-ISSN: 0361-5995
    E-ISSN: 14350661
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  • 6
    In: eLife, Vol.6
    Description: Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can regulate the activity of these enzymes is an open question. We show that Bacillus subtilis RoxS, a major trans -acting sRNA shared with Staphylococus aureus , prevents degradation of the yflS mRNA, encoding a malate transporter. In the presence of malate, RoxS transiently escapes from repression by the NADH-sensitive transcription factor Rex and binds to the extreme 5’-end of yflS mRNA. This impairs the 5’-3’ exoribonuclease activity of RNase J1, increasing the half-life of the primary transcript and concomitantly enhancing ribosome binding to increase expression of the transporter. Globally, the different targets regulated by RoxS suggest that it helps readjust the cellular NAD + /NADH balance when perturbed by different stimuli. DOI: http://dx.doi.org/10.7554/eLife.23602.001
    Keywords: Research Article ; Genes And Chromosomes ; Microbiology And Infectious Disease ; Rna Degradation ; Ribonucleases ; Roxs ; Srna ; Malate ; Rex ; B. Subtilis
    E-ISSN: 2050-084X
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  • 7
    Language: English
    In: Environmental Earth Sciences, 2017, Vol.76(1), pp.1-25
    Description: This article provides an overview about the Bode River catchment that was selected as the hydrological observatory and main region for hydro-ecological research within the TERrestrial ENvironmental Observatories Harz/Central German Lowland Observatory. It first provides information about the general characteristics of the catchment including climate, geology, soils, land use, water quality and aquatic ecology, followed by the description of the interdisciplinary research framework and the monitoring concept with the main components of the multi-scale and multi-temporal monitoring infrastructure. It also shows examples of interdisciplinary research projects aiming to advance the understanding of complex hydrological processes under natural and anthropogenic forcings and their interactions in a catchment context. The overview is complemented with research work conducted at a number of intensive research sites, each focusing on a particular functional zone or specific components and processes of the hydro-ecological system.
    Keywords: Monitoring ; Catchment ; Water quality ; Observatory ; Water fluxes
    ISSN: 1866-6280
    E-ISSN: 1866-6299
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  • 8
    Language: English
    In: Physical review letters, 15 July 2011, Vol.107(3), pp.032302
    Description: One of the most promising probes to study deconfined matter created in high energy nuclear collisions is the energy loss of (heavy) quarks. It has been shown in experiments at the Relativistic Heavy Ion Collider that even charm and bottom quarks, despite their high mass, experience a remarkable medium suppression in the quark gluon plasma. In this exploratory investigation we study the energy loss of heavy quarks in high multiplicity proton-proton collisions at LHC energies. Although the colliding systems are smaller than compared to those at the Relativistic Heavy Ion Collider (p+p vs Au+Au), the higher energy might lead to multiplicities comparable to Cu+Cu collisions at the Relativistic Heavy Ion Collider. The interaction of charm quarks with this environment gives rise to a non-negligible suppression of high momentum heavy quarks in elementary collisions.
    Keywords: High Energy Physics - Phenomenology ; High Energy Physics - Experiment ; Nuclear Theory;
    ISSN: 00319007
    E-ISSN: 1079-7114
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  • 9
    Language: English
    In: ASA, CSSA & SSSA International Annual Meeting " Grand challenges, great solutions", 2014
    Description: absent
    Keywords: Sciences of the Universe ; Earth Sciences
    Source: Hyper Article en Ligne (CCSd)
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  • 10
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