A four‐dimensional analysis of the thermal structure in the Gulf of Lion

The Theoretical and Experimental Tomography in the Sea Experiment (THETIS 1) took place in the Gulf of Lion to observe the evolution of the temperature field and the process of deep convection during the 1991–1992 winter. The temperature measurements consist of moored sensors, conductivity‐temperature‐depth and expendable bathythermograph surveys, and acoustic tomography. Because of this diverse data set and since the field evolves rather fast, the analysis uses a unified framework, based on estimation theory and implementing a Kaiman filter. The resolution and the errors associated with the model are systematically estimated. Temperature is a good tracer of water masses. The time‐evolving three‐dimensional view of the field resulting from the analysis shows the details of the three classical convection phases: preconditioning, vigourous convection, and relaxation. In all phases, there is strong spatial nonuniformity, with mesoscale activity, short timescales, and sporadic evidence of advective events (surface capping, intrusions of Levantine Intermediate Water (LIW)). Deep convection, reaching 1500 m, was observed in late February; by late April the field had not yet returned to its initial conditions (strong deficit of LIW). Comparison with available atmospheric flux data shows that advection acts to delay the occurence of convection and confirms the essential role of buoyancy fluxes. For this winter, the deep mixing results in an injection of anomalously warm water (ΔT≈0.03°) to a depth of 1500 m, compatible with the deep warming previously reported

HIV-1/M+O INTERGROUP DUAL INFECTIONS AND ASSOCIATED HIV-MO RECOMBINANTS IN FRANCE FROM 2004 TO 2014

International audienc

Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae

<p>Abstract</p> <p>Background</p> <p>The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs) are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism <it>Mycobacterium smegmatis</it>, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb.</p> <p>Results</p> <p>We have recently sequenced the complete genomes of two fast-growers causing human infections, <it>Mycobacterium abscessus </it>(CIP 104536T) and <it>M. chelonae </it>(CIP 104535T). We show here that these two species contain genes corresponding to all those of the <it>M. smegmatis </it>"GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in <it>M. chelonae </it>and <it>M. abscessus</it>. One large cluster (19 genes) comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (<it>atf1 </it>and <it>atf2</it>) in <it>M. abscessus </it>and <it>M. chelonae </it>has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (<it>M. chelonae</it>, 900 kb; <it>M. abscessus</it>, 3 Mb) cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins.</p> <p>Conclusion</p> <p>Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in <it>M. smegmatis </it>represents the ancestral form and that evolution has scattered various pieces throughout the genome in <it>M. abscessus </it>and <it>M. chelonae</it>.</p

Lsr2 is an important determinant of intracellular growth and virulence in Mycobacterium abscessus

Mycobacterium abscessus, a pathogen responsible for severe lung infections in cystic fibrosis patients, exhibits either smooth (S) or rough (R) morphotypes. The S-to-R transition correlates with inhibition of the synthesis and/or transport of glycopeptidolipids (GPLs) and is associated with an increase of pathogenicity in animal and human hosts. Lsr2 is a small nucleoid-associated protein highly conserved in mycobacteria, including M. abscessus, and is a functional homologue of the heat-stable nucleoid-structuring protein (H-NS). It is essential in Mycobacterium tuberculosis but not in the non-pathogenic model organism Mycobacterium smegmatis. It acts as a master transcriptional regulator of multiple genes involved in virulence and immunogenicity through binding to AT-rich genomic regions. Previous transcriptomic studies, confirmed here by quantitative PCR, showed increased expression of lsr2 (MAB_0545) in R morphotypes when compared to their S counterparts, suggesting a possible role of this protein in the virulence of the R form. This was addressed by generating lsr2 knock-out mutants in both S (Δlsr2-S) and R (Δlsr2-R) variants, demonstrating that this gene is dispensable for M. abscessus growth. We show that the wild-type S variant, Δlsr2-S and Δlsr2-R strains were more sensitive to H2O2 as compared to the wild-type R variant of M. abscessus. Importantly, virulence of the Lsr2 mutants was considerably diminished in cellular models (macrophage and amoeba) as well as in infected animals (mouse and zebrafish). Collectively, these results emphasize the importance of Lsr2 in M. abscessus virulence

Non Mycobacterial Virulence Genes in the Genome of the Emerging Pathogen Mycobacterium abscessus

Mycobacterium abscessus is an emerging rapidly growing mycobacterium (RGM) causing a pseudotuberculous lung disease to which patients with cystic fibrosis (CF) are particularly susceptible. We report here its complete genome sequence. The genome of M. abscessus (CIP 104536T) consists of a 5,067,172-bp circular chromosome including 4920 predicted coding sequences (CDS), an 81-kb full-length prophage and 5 IS elements, and a 23-kb mercury resistance plasmid almost identical to pMM23 from Mycobacterium marinum. The chromosome encodes many virulence proteins and virulence protein families absent or present in only small numbers in the model RGM species Mycobacterium smegmatis. Many of these proteins are encoded by genes belonging to a “mycobacterial” gene pool (e.g. PE and PPE proteins, MCE and YrbE proteins, lipoprotein LpqH precursors). However, many others (e.g. phospholipase C, MgtC, MsrA, ABC Fe(3+) transporter) appear to have been horizontally acquired from distantly related environmental bacteria with a high G+C content, mostly actinobacteria (e.g. Rhodococcus sp., Streptomyces sp.) and pseudomonads. We also identified several metabolic regions acquired from actinobacteria and pseudomonads (relating to phenazine biosynthesis, homogentisate catabolism, phenylacetic acid degradation, DNA degradation) not present in the M. smegmatis genome. Many of the “non mycobacterial” factors detected in M. abscessus are also present in two of the pathogens most frequently isolated from CF patients, Pseudomonas aeruginosa and Burkholderia cepacia. This study elucidates the genetic basis of the unique pathogenicity of M. abscessus among RGM, and raises the question of similar mechanisms of pathogenicity shared by unrelated organisms in CF patients

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Observation of spiciness interannual variability in the Pacific pycnocline

International audienceMonthly gridded fields predominantly based on global Argo in situ temperature and salinity data are used to analyze the density-compensated anomaly of salinity (spiciness anomaly) in the pycnocline of the subtropical and tropical Pacific Ocean between 2004 and 2011. Interannual variability in the formation, propagation and fate of spiciness anomalies are investigated. The spiciness anomalies propagate on the isopycnal surface sq = 25.5 along the subtropical-tropical pycnocline advected by the mean currents. They reach the Pacific Western Tropics in about 5-6 years in the Southern Hemisphere and about 7-8 years in the Northern Hemisphere. Their amplitude strongly diminishes along the way and only very weak spiciness anomalies seem to reach the equator in the Western Tropics. A complex-EOF analysis of interannual salinity anomalies on sq = 25.5 highlights two dominant modes of variability at interannual scale: i) the former shows a variability of 5-7 years predominant in the Northern Hemisphere, and ii) the latter displays an interannual variability of 2 to 3 years more marked in the Southern Hemisphere. The significant correlation of this second mode with ENSO index suggests that spiciness formation in the southeastern Pacific (SEP) is affected by ENSO tropical interannual variability. A diagnosis of the mechanisms governing the interannual generation of spiciness in the SEP region leads the authors to suggest that the spiciness interannual variability in the sub-surface is linked to the equatorward migration of the isopycnal outcrop line sq = 25.5 into the area of maximum salinity. Quantitative analysis based on Turner angle reveals the dominance of the spiciness injection mechanism occurring through convective mixing at the base of mixed layer

Variability of the Heat and Salt Budget in the Subtropical Southeastern Pacific Mixed Layer between 2004 and 2010: Spice Injection Mechanism.

International audienceThe mixed layer heat and salt budget in the southeastern subtropical Pacific are estimated using 7 years (2004–10) of Argo-profiling float data, surface fluxes, precipitation, surface velocity data, and wind observations and reanalysis. In this region, the mixed layer heat budget is characterized by a strong annual cycle mainly modulated by the shortwave radiation annual cycle. During the austral fall and winter, the shortwave radiation input minimum is overwhelmed by the heat loss mainly because of the latent heat flux. The mixed layer salt budget also presents a strong annual cycle with a minimum of salt content during the late austral winter. In contrast with the heat budget, the salt budget is mainly driven by the unresolved terms computed as the residual of the budget. Among these missing terms, the most likely candidate is the vertical turbulent mixing as a result of convection caused by the heat surface buoyancy loss and the destabilizing vertical gradient of salinity at the base of the mixed layer. This downward flux of salt at the base of the mixed layer could explain the annual spiciness injection and interannual spiciness variability in the permanent thermocline in the southeastern Pacific