The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA

Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.     

Intraseasonal interaction between the Madden-Julian Oscillation and the North Atlantic Oscillation

Bridging the traditional gap between the spatio-temporal scales of weather and climate is a significant challenge facing the atmospheric community. In particular, progress in both medium-range and seasonal-to-interannual climate prediction relies on our understanding of recurrent weather patterns and the identification of specific causes responsible for their favoured occurrence, persistence or transition. Within this framework, I here present evidence that the main climate intra-seasonal oscillation in the tropics-the Madden-Julian Oscillation (MJO)-controls part of the distribution and sequences of the four daily weather regimes defined over the North Atlantic-European region in winter. North Atlantic Oscillation (NAO) regimes are the most affected, allowing for medium-range predictability of their phase far exceeding the limit of around one week that is usually quoted. The tropical-extratropical lagged relationship is asymmetrical. Positive NAO events mostly respond to a mid-latitude low-frequency wave train initiated by the MJO in the western-central tropical Pacific and propagating eastwards. Precursors for negative NAO events are found in the eastern tropical Pacific-western Atlantic, leading to changes along the North Atlantic storm track. Wave-breaking diagnostics tend to support the MJO preconditioning and the role of transient eddies in setting the phase of the NAO. I present a simple statistical model to quantitatively assess the potential predictability of the daily NAO index or the sign of the NAO regimes when they occur. Forecasts are successful in approximately 70 per cent of the cases based on the knowledge of the previous approximately 12-day MJO phase used as a predictor. This promising skill could be of importance considering the tight link between weather regimes and both mean conditions and the chances of extreme events occurring over Europe. These findings are useful for further stressing the need to better simulate and forecast the tropical coupled ocean-atmosphere dynamics, which is a source of medium-to-long range predictability and is the Achilles' heel of the current seamless prediction suites.     

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.     

Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.     

A common somitic origin for embryonic muscle progenitors and satellite cells

In the embryo and in the adult, skeletal muscle growth is dependent on the proliferation and the differentiation of muscle progenitors present within muscle masses. Despite the importance of these progenitors, their embryonic origin is unclear. Here we use electroporation of green fluorescent protein in chick somites, video confocal microscopy analysis of cell movements, and quail-chick grafting experiments to show that the dorsal compartment of the somite, the dermomyotome, is the origin of a population of muscle progenitors that contribute to the growth of trunk muscles during embryonic and fetal life. Furthermore, long-term lineage analyses indicate that satellite cells, which are known progenitors of adult skeletal muscles, derive from the same dermomyotome cell population. We conclude that embryonic muscle progenitors and satellite cells share a common origin that can be traced back to the dermomyotome.     

Le Dosage Spectrométrique du Mercure dans l'Air vers 1930

In the 1930s, atomic absorption spectroscopy replaced chemical methods for determining the amount of mercury in atmospheric air. The overall state of chemical analysis was favourable: physical instruments were moving into the chemical laboratory. This new method emerged from work in quantitative physics, and it met a need arising from the risk encountered by those who handled mercury. The new spectrometer, which originally functioned as a detector, also made precise and rapid quantitative determinations possible. This in turn encouraged industrialists to take out patents and make commercial use of the method after various improvements. This method is considered to be the ancestor of modern atomic absorption spectroscopy, which developed independently after 1960. The method developed in the 1930s could only be used for gaseous mercury, and it was not generalized as a method for quantifying other elements. The determination of mercury in air by atomic absorption spectroscopy was the first application of this technique; indeed, it was the only example of a specific use of atomic absorption. It was also part of the instrumental revolution.     

Ultrastructural and quantitative analysis of the lipid droplet clustering induced by hepatitis C virus core protein

Hepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due, at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further studies of the mechanisms involved in HCV-induced steatosis.