Neogene uplift of the Tian Shan Mountains observed in the magnetic record of the Jingou River section (northwest China)

The Tian Shan Mountains constitute central Asia's longest and highest mountain range. Understanding their Cenozoic uplift history thus bears on mountain building processes in general, and on how deformation has occurred under the influence of the India-Asia collision in particular. In order to help decipher the uplift history of the Tian Shan, we collected 970 samples for magnetostratigraphic analysis along a 4571-m-thick section at the Jingou River (Xinjiang Province, China). Stepwise alternating field and thermal demagnetization isolate a linear magnetization component that is interpreted as primary. From this component, a magnetostratigraphic column composed of 67 polarity chrons are correlated with the reference geomagnetic polarity timescale between ∼1 Ma and ∼23.6 Ma, with some uncertainty below ∼21 Ma. This correlation places precise temporal control on the Neogene stratigraphy of the southern Junggar Basin and provides evidence for two significant stepwise increases in sediment accumulation rate at ∼16–15 Ma and ∼11–10 Ma. Rock magnetic parameters also undergo important changes at ∼16–15 Ma and ∼11–10 Ma that correlate with changes in sedimentary depositional environments. Together with previous work, we conclude that growth history of the modern Tian Shan Mountains includes two pulses of uplift and erosion at ∼16–15 Ma and ∼11–10 Ma. Middle to upper Tertiary rocks around the Tian Shan record very young (<∼5 Ma) counterclockwise paleomagnetic rotations, on the order of 15° to 20°, which are interpreted as because of strain partitioning with a component of sinistral shear that localized rotations in the piedmont

Etude des réseaux d'interactions protéiques impliqués dans le trafic du nickel et de l'ammoniac et de leurs rôles dans la virulence chez Helicobacter pylori

Helicobacter pyori is the only known bacterium that persistently colonizes the human stomach. Long-term infection of the gastric mucosa causes various pathologies such as peptic ulcers and adenocarcinoma. To resist acid stress encountered in its niche, H. pylori has an emergency response based on the activity of urease, an abundant and very active enzyme that synthesizes ammonia. Upon acid exposure, ammonia allows H. pylori to maintain a neutral pH in its cytoplasm.Urease and another enzyme essential for colonization, the [NiFe] hydrogenase, have a catalytic center coordinated with nickel. Because of the abundance of these two proteins and their functional importance, large amounts of nickel need to be acquired by H. pylori to establish colonization.During this PhD, we have investigated the protein interaction networks involved in the trafficking of ammonia and of nickel in H. pylori and analyzed their role in virulence. To survive, H. pylori needs to import nickel and insert it properly into the two nickel enzymes. In addition, this metal needs to be stored to prevent deleterious effects. We have studied the role of two histidine-rich proteins, Hpn and Hpn-2. We showed that these proteins interact each other and are involved in storage of nickel and control of its homeostasis. In addition, we found that they act as regulators of urease activity and are required for colonization of the animal model.We also characterized two unique systems of periplasmic hydrolysis of asparagine and glutamine that produce ammonia. These enzymes are coupled with the transport of their products, aspartate and glutamate. These deamidase/transporter couples are essential for colonization and play a role in H. pylori pathogenicity.Urease, the deamidases and other enzymes involved in the glutamine and asparagine metabolism are responsible for important ammonia production by H. pylori. Using the bacterial two-hybrid system, we found interactions between enzymes that produce ammonia and enzymes that utilize ammonia as a substrate. We propose the existence of a metabolic channeling of ammonia that functions to optimize its bioavailability and the activity of the corresponding enzymes.Our results unraveled the existence of protein interactions that optimize ammonia and nickel fluxes, two elements that are essential for H. pylori virulence.Helicobacter pylori est la seule bactérie capable de coloniser de façon persistante l’estomac humain. L’infection au long cours au contact de la muqueuse gastrique provoque diverses pathologies gastriques comme les ulcères gastroduodénaux et les cancers gastriques. Pour résister au stress acide rencontré dans sa niche, H. pylori possède une réponse d’urgence qui dépend de l’uréase. Cette enzyme abondante et très active, est responsable d’une forte production d’ammoniac. En conditions acides, l’ammoniac permet à H. pylori le maintien d’un pH neutre dans son cytoplasme.L’uréase et une autre enzyme essentielle à la colonisation, l’hydrogénase à [NiFe], possèdent des centres catalytiques à nickel. De par l’abondance de ces deux protéines, ainsi que leur importance fonctionnelle, de grandes quantités de nickel sont nécessaires à H. pylori pour établir une colonisation durable.Au cours de cette thèse, nous nous sommes intéressés aux réseaux d’interactions protéiques impliquées dans le trafic de l’ammoniac et du nickel chez H. pylori et à leurs rôles dans la pathogenèse. Pour survivre, H. pylori doit importer du nickel puis l’insérer correctement au sein des deux enzymes à nickel. De plus, ce métal doit être stocké pour éviter les effets délétères qu’il peut occasionner. Nous avons étudié le rôle de deux protéines riches en histidine, Hpn et Hpn-2. Nous avons montré que ces protéines interagissent entre elles, interviennent dans le maintien de l’homéostasie et du stockage du nickel et agissent comme régulateurs de l’activité uréasique. De plus, ces deux protéines sont essentielles à la colonisation du modèle animal.Parallèlement, nous avons caractérisé deux systèmes uniques d’hydrolyse périplasmique de l’asparagine et de la glutamine associés à la production d’ammoniac. Ces enzymes sont couplées à un import de leurs produits, l’aspartate et le glutamate dans la cellule. Ces couples déamidases/transporteurs sont essentiels à la colonisation et jouent un rôle dans la pathogénicité de H. pylori.L’uréase, les déamidases et d’autres enzymes participant au métabolisme de la glutamine et de l’asparagine sont responsables d’une importante production d’ammoniac par H. pylori. En utilisant le double hybride bactérien, des interactions entre des enzymes productrices d’ammoniac chez H. pylori et des enzymes qui l’utilisent comme substrat ont été mises en évidence. Nous proposons l’existence d’un channeling métabolique de l’ammoniac permettant d’optimiser la biodisponibilité de cette molécule et l’activité des enzymes correspondantes. Nos résultats ont révélé l’existence d’interactions protéiques qui optimisent les flux d’ammoniac et de nickel, des éléments essentiels à la virulence de H. pylori

Coupled Amino Acid Deamidase-Transport Systems Essential for Helicobacter pylori Colonization▿ †

In addition to their classical roles as carbon or nitrogen sources, amino acids can be used for bacterial virulence, colonization, or stress resistance. We found that original deamidase-transport systems impact colonization by Helicobacter pylori, a human pathogen associated with gastric pathologies, including adenocarcinoma. We demonstrated that l-asparaginase (Hp-AnsB) and γ-glutamyltranspeptidase (Hp-γGT) are highly active periplasmic deamidases in H. pylori, producing ammonia and aspartate or glutamate from asparagine and glutamine, respectively. Hp-GltS was identified as a sole and specialized transporter for glutamate, while aspartate was exclusively imported by Hp-DcuA. Uptake of Gln and Asn strictly relies on indirect pathways following prior periplasmic deamidation into Glu and Asp. Hence, in H. pylori, the coupled action of periplasmic deamidases with their respective transporters enables the acquisition of Glu and Asp from Gln and Asn, respectively. These systems were active at neutral rather than acidic pH, suggesting their function near the host epithelial cells. We showed that Hp-DcuA, the fourth component of these novel deamidase-transport systems, was as crucial as Hp-γGT, Hp-AnsB, and Hp-GltS for animal model colonization. In conclusion, the pH-regulated coupled amino acid deamidase-uptake system represents an original optimized system that is essential for in vivo colonization of the stomach environment by H. pylori. We propose a model in which these two nonredundant systems participate in H. pylori virulence by depleting gastric or immune cells from protective amino acids such as Gln and producing toxic ammonia close to the host cells

The Asexual Yeast Candida glabrata Maintains Distinct a and α Haploid Mating Types▿

The genome of the type strain of Candida glabrata (CBS138, ATCC 2001) contains homologs of most of the genes involved in mating in Saccharomyces cerevisiae, starting with the mating pheromone and receptor genes. Only haploid cells are ever isolated, but C. glabrata strains of both mating types are commonly found, the type strain being MATα and most other strains, such as BG2, being MATa. No sexual cycle has been documented for this species. In order to understand which steps of the mating pathway are defective, we have analyzed the expression of homologs of some of the key genes involved as well as the production of mating pheromones and the organism's sensitivity to artificial pheromones. We show that cells of opposite mating types express both pheromone receptor genes and are insensitive to pheromones. Nonetheless, cells maintain specificity through regulation of the α1 and α2 genes and, more surprisingly, through differential splicing of the a1 transcript

Paleoenvironnemental evolution of the northern Tianshan piedmont (Northwest China) during the Neogene: preliminary results from organic matter and rock magnetism study of fluvio-lacustrine Junggar sediments

The Tianshan range is among the Asia's largest mountain chains. It spreads over an EWdistance of 2500 km with summits higher than 7000 m. The range's geologic record attests to a complex history of Paleozoic subduction-related processes, but the living topography appears to be mainly due to a new phase of Cenozoic reactivation induced by the India-Asia collision. The Cenozoic uplift of the range has probably widely affected the Central Asia climate and environment of which the evolution might be deciphered from the sediment accumulation in the adjacent Junggar and Tarim basins. In order to better constrain the Late Tertiary environmental evolution of Central Asia, we have studied Neogene sediments at the Kuitun He section and the Jingou He section in the northern flank of the Tianshan range. Both sections exposed upper Tertiary Junggar sediments that were folded in a ramp anticline. Sediments are mainly composed of fluvio-lacustrine sandstone and conglomerate that we previously dated using magnetostratrigraphy giving an age span from 3.1 to 10.5 Ma and 8.1 to 23 Ma for the Kuitun He and the Jingou He section respectively. To track back time-transgressive changes in hydrodynamical conditions of the sedimentary record we performed a suit of rock magnetism experiments such as IRM, ARM and AMS analyses. Using the palynofacies method, we also analyzed the organic matter content of sediments that reveals the environmental evolution of both the watershed and the deposition area. Preliminary results show that around 23 My the environment of the northern Tianshan was first probably arid and becomes progressively wetter with the onset of vegetal cover. By 20 My a climatic optimum may occur marked by a lacustrine environment as shown by a high contribution of autochthonous organic matter such as algae. By 15 My the runoff seems to rapidly increase. Latter ( 11 My ?) the northern Tianshan environment records a progressive aridification with a possible acceleration by 7 My

Evolution of Helicobacter: Acquisition by Gastric Species of Two Histidine-Rich Proteins Essential for Colonization

International audienceMetal acquisition and intracellular trafficking are crucial for all cells and metal ions have been recognized as virulence determinants in bacterial pathogens. Virulence of the human gastric pathogen Helicobacter pylori is dependent on nickel, cofactor of two enzymes essential for in vivo colonization, urease and [NiFe] hydrogenase. We found that two small paralogous nickel-binding proteins with high content in Histidine (Hpn and Hpn-2) play a central role in maintaining non-toxic intracellular nickel content and in controlling its intracellular trafficking. Measurements of metal resistance, intracellular nickel contents, urease activities and interactomic analysis were performed. We observed that Hpn acts as a nickel-sequestration protein, while Hpn-2 is not. In vivo, Hpn and Hpn-2 form homo-multimers, interact with each other, Hpn interacts with the UreA urease subunit while Hpn and Hpn-2 interact with the HypAB hydrogenase maturation proteins. In addition, Hpn-2 is directly or indirectly restricting urease activity while Hpn is required for full urease activation. Based on these data, we present a model where Hpn and Hpn-2 participate in a common pathway of controlled nickel transfer to urease. Using bioinformatics and top-down proteomics to identify the predicted proteins, we established that Hpn-2 is only expressed by H. pylori and its closely related species Helicobacter acinonychis. Hpn was detected in every gastric Helicobacter species tested and is absent from the enterohepatic Helicobacter species. Our phylogenomic analysis revealed that Hpn acquisition was concomitant with the specialization of Helicobacter to colonization of the gastric environment and the duplication at the origin of hpn-2 occurred in the common ancestor of H. pylori and H. acinonychis. Finally, Hpn and Hpn-2 were found to be required for colonization of the mouse model by H. pylori. Our data show that during evolution of the Helicobacter genus, acquisition of Hpn and Hpn-2 by gastric Helicobacter species constituted a decisive evolutionary event to allow Helicobacter to colonize the hostile gastric environment, in which no other bacteria persistently thrives. This acquisition was key for the emergence of one of the most successful bacterial pathogens, H. pylori

Sequences of the Hpn and Hpn-2 proteins of <i>H</i>. <i>pylori</i> strain B128 [27,28].

<p>Histidine residues are highlighted in blue and Glutamine residues are in green. The triangle corresponds to the position at which Hpn is truncated in Hpn-∆C mutant and at which Hpn-2 is truncated in the Hpn-2∆C mutant. The black stars the positions at which the Hpn and Hpn-2 sequence are interrupted in the study of Seshadri et <i>al</i>. [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005312#ppat.1005312.ref029" target="_blank">29</a>].</p

Identification of Hpn and Hpn-2 proteins in samples prepared from different <i>Helicobacter</i> species by top-down proteomics.

<p>Identification of Hpn and Hpn-2 proteins in samples prepared from different <i>Helicobacter</i> species by top-down proteomics.</p