The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Phosphatase and tensin homologue: a therapeutic target for SMA

Spinal muscular atrophy (SMA) is one of the most common juvenile neurodegenerative diseases, which can be associated with child mortality. SMA is caused by a mutation of ubiquitously expressed gene, Survival Motor Neuron1 (SMN1), leading to reduced SMN protein and the motor neuron death. The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons. Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei, suggesting that these cells are prone to a process of cell death called apoptosis. Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system (CNS) insults is essential for widening the scope of developmental medicine. PTEN, a Phosphatase and Tensin homologue, is a tumor suppressor, which is widely expressed in CNS. PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders. It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity. Moreover, previous reports from our group demonstrated that, PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology, with significant rescue on survival rate and the body weight of the SMA mice. Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA

Enregistrement de Paléo-Mises en charge holocènes dans deux stalagmites du réseau du Rupt-du-Puits (Barrois, France). Analyses morphologiques des lamines et datations U/TH en TIMS

Le réseau souterrain du Rupt du Puits, dans l'Est de la France, est un karst couvert de bas plateau évoluant sous climat tempéré humide. Le régime des précipitations et l'organisation des circulations souterraines génèent périodiquement des mises en charges partielles outotales des conduits du système. la couverture argilo-sableuse, en cours de démentèlement, et le transit des matériaux détritiques dans le karst, induisent le dépôt d'un film agileux à chacun de ces épisodes de crue. Deux stalagmites décimétriques ont été choisies dans le réseau. Elles ont été sciées, polies puis montées en lame mince afin d'bserver en section verticale, les différentes interruptions de croissance. Elles ont fait l'objet de 14 datations U/Th en TIMS. Le principe de l'enregistrement est double. Il peut s'agir d'abord de l'intercalation de niveaux détritiques entre les lamines calcitiques. La croissance régulière du spéléothème est alors interrompue par l'ennoiement du conduit occasionnant un dépôt généralement argileux d'épaisseur variable. Ce dernier est scellé par la reprise de la croissance de la concrétion. Il peut s'agir aussi de bascukes de l'édifice stalagmitique liées à la récurrence des épisodes de mises en charge. Les datations U/Th montrent que l'échantillon R69 connaît une phase générale de pousse comprise entre 5.3 ka et environ 4.5 ka. Deux phases de bascule sont identifiées, la première vers 5 ka et la seconde comprise entre 4.7 ka et 4.4 ka. Le sommet de l'échantillon R81 est subactuel, sa base est datée 1 ka. Plusieurs couches détritiques s'intercalent dans cette chronique. On détermine ainsi quela fréquence de mises en charge enregistrées par ces objets estliée aux précipitations et aux conditions géomorphologiques locales. Sur unepériode courte (ici la fin de l'Holocène), c'est plus l'évolution des conditions morphologiques internes qui engendre ou stoppe les mises en charge, véritable expression de l'incapacité du système à drainer les eaux de crue. L'enregistrement proposé ici est donc l'expression d'une période transitoire au sein de laquelle les conditions morphologiques internes au système karstique évoluent

Intérêt de la résection complémentaire (ou « second look ») pour les carcinomes urothéliaux de vessie classés pTa haut grade

International audienc

New insights from the MIS 5 Fronte GSSP candidate Section (Taranto, Italy)

We present new data collected at the Fronte locality near Taranto, where the Upper Pleistocene marine sedimentary succession is continuously exposed. Above a fossiliferous calcarenite yielding the “Senegalese” fauna, and abundant Cladocora, the 230Th/U age of which is consistent with Marine Isotope Stage (MIS) 5, a 6.25 m thick pelitic unit is characterized by lithologically homogeneous marine sediments in which stable oxygen isotope, micropaleontological and palynological analyses suggested a long and undisturbed sedimentary interval across the Marine Isotope Stage (MIS) 5.5 peak (plateau) (Negri et al., 2015). Two cores drilled in 2015 at the top of the cliff where the section crops out, show the same lithological succession sampled in the field. These cores were investigated for the geomagnetic palaeosecular variation and relative palaeointensity recorded in these sediments. Interestingly, the Paleomagnetic record contains several brief excursions of shallowed inclination. The most significant of these reaches inclinations of below 10°, suggesting a correlation with the Blake event (Negri et al., 2016). To further clarify the age of the sedimentary succession, two branches of Cladocora recovered at the top of the fossiliferous calcarenite have been U-series dated (coral aragonite) revealing an age of about 80Ka (further refining is ongoing while we are writing this abstract) while new benthic foraminiferal analyses in the pelitic unit above it, confirmed a frankly marine microfauna. According to these new data the whole MIS 5 or so appears to be constrained by the calcarenite, This suggest a climatic change switching the sedimentation from carbonate platform to pelite. The data so far collected which are consistent with the old data reported by dai Pra and Stearns (1977) indicate that at the Fronte section a record of the Termination II and the whole MIS 5 occur. This evidences the need to detail further the time interval recorded through a new set of U/Th dating and eventually the finding of appropriate stratigraphic indicators which may strengthen the potential of the section as GSSP

A Large Paleoearthquake in the Central Apennines, Italy, Recorded by the Collapse of a Cave Speleothem

Speleoseismological research carried out in the Central Apennines (Italy) contributed to understanding the behavior of active normal faults that are potentially able to generate Mw 6.5–7 earthquakes documented by paleoseismology and by historical and instrumental seismology. Radiometric (U-Th, AMS-14C, and bulk-14C) dating of predeformation and postdeformation layers from collapsed speleothems found in Cola Cave indicates that at least three speleoseismic events occurred in the cave during the last ~12.5 ka and were ostensibly caused by seismic slip on one or more of the active faults located in the region surrounding the cave. We modeled the collapse of a tall (173 cm high) stalagmite to find a causative association of this event with one among the potential seismogenic sources. We defined the uniform hazard spectrum (UHS) for each seismogenic source at the site, and we used the calculated spectra in a deterministic approach to study the behavior of the speleothem, through a numerical finite element modeling (FEM). Although our analysis suggests the “Liri” fault as the most likely source responsible for the ground shaking recorded in the cave, the “Fucino” fault system, responsible for a Mw 7 earthquake in 1915, cannot be excluded as a potential source of speleoseismic damage. Results of this work provide new constraints on the seismotectonic history of this sector of Central Apennines and highlight the performance of integrated speleoseismological, seismic hazard, and numerical studies

Mapping soil multifunctionality for urban planning: how to deal with limited knowledge on soils?

International audienceUrban planning historically considers soils as a support for infrastructures. Hopefully, awareness is increasing on the fact that soils offer many more services than just this one, thanks to their various functions. It is therefore necessary to develop methodologies and tools that allow the urban planners to take into account the opportunities and constraints associated to soils. Considering the existing quality indexes already developed by the researchers, we faced within the MUSE project various difficulties and in particular the lack of knowledge on urban soils in France. We therefore developed a methodology to deal with limited knowledge on urban soils and tested it first on the Nantes metropolis territory (France). Our aim was to map each soil function as well as a soil multifunctionality in such a way that urban planning documents may refer to them. The aim of the multifunction map is to help protecting soils that show various functions, including patrimonial functions. We therefore considered the following functions: carbon storage, water storage and infiltration, storage and filtration of contaminants, agronomic potential, biodiversity reservoir. We did not consider the support and natural resources provision functions. According to the level of knowledge on soils (local/regional/national scales, direct/indirect), we considered three mapping approaches (statistical, global, and calculation) to build function maps, and interpreted them in terms of soil function index (SFI) map. To build the soil multifunctionality quality index (SMQI) map, we crossed the various function index maps using a ponderation according to the territorial issues. These issues derive from discussions with the urban planners of the local authority and the number of functions assessed on each part of the territory (some functions not mapped in the city center). We carried out discussions with the urban planners all along the methodological development process to ensure applicability of the index map produced. The results obtained are very satisfying considering the level of knowledge on soils. The urban planners of the local authority clearly imagine how to use both the soil function maps as well as the soil multifunctionality quality index map. We are nevertheless aware of the limits due to the use of data with different scales of validity (eg. 1 / 250 000 for pedological map; 1/10 000 for soil land-use model; statistical data on C and biodiversity at pedoclimatic scale vs national scale). The comparison with local punctual data helps verifying the degree of confidence of the maps. The methodological development is currently being adjusted and tested on other cities (in particular Marseilles and Châteauroux, France) and further discussed with urban planners at national scale. Efforts are necessary to build a wider an