Adverse environmental conditions influence age-related innate immune responsiveness

Background-  

The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions.     

Isolation of Prasinoviruses of the Green Unicellular Algae Ostreococcus spp. on a Worldwide Geographical Scale

Ostreococcus spp. are extremely small unicellular eukaryotic green algae found worldwide in marine environments, and they are susceptible to attacks by a diverse group of large DNA viruses. Several biologically distinct species of Ostreococcus are known and differ in the ecological niches that they occupy: while O. tauri (representing clade C strains) is found in marine lagoons and coastal seas, strains belonging to clade A, exemplified by O. lucimarinus, are present in different oceans. We used laboratory cultures of clonal isolates of these two species to assay for the presence of viruses in seawater samples from diverse locations. In keeping with the distributions of their host strains, we found a decline in the abundance of O. tauri viruses from a lagoon in southwest France relative to the Mediterranean Sea, whereas in the ocean, no O. tauri viruses were detected. In contrast, viruses infecting O. lucimarinus were detected from distantly separated oceans. DNA sequencing, phylogenetic analyses using a conserved viral marker gene, and a Mantel test revealed no relationship between geographic and phylogenetic distances in viruses infecting O. lucimarinus.Viruses are the most abundant and genetically diverse biological entities in marine environments (48). The three ways most often used to assess eukaryotic algal virus diversity are (i) using a functional host-virus system to quantify viruses specific to one host strain (i.e., culture-based studies) (4), (ii) using PCR amplification and sequencing a conserved gene (10, 12-14, 28), and (iii) using whole-community genome sequencing (i.e., metagenomics) (6, 8, 31). Recently, the advent of sequencing techniques like shotgun sequencing or pyrosequencing (38) has led to an increase in the number of metagenomics projects. The Global Ocean Sampling (GOS) Expedition has provided a unique opportunity to investigate viral diversity in different environments within the size fraction of 0.1 to 0.8 μm (39). The GOS data revealed highly abundant viral sequences (at least 3% of the predicted proteins had a viral origin) (53). In another study, the analysis of marine viromes from four oceanic regions suggested that the composition of viral assemblages depends on their geographic locations, but these authors conclude that similar viruses are widespread throughout the oceans (2). Despite these new methods and different ways to analyze viral diversity, we still do not really know if “everything is really everywhere” (7).The present study addresses a specific part of this problem: are viruses infecting a single host strain present at geographically distant locations? If several viral strains are identified and characterized, how closely do these viruses resemble one another on a phylogenetic scale? In order to answer these questions, we focused on a microalgal (Prasinophyceae)-virus (Prasinovirus) system. The studied hosts belong to the genus Ostreococcus, a ubiquitous prasinophyte picoeukaryotic alga abundant throughout the oceanic euphotic zone (55, 56). Several strains from this genus were isolated and assigned to four distinct ecotypes according to their growth parameters under different light regimens (22, 36), which correspond to four well-defined phylogenetic clades in an internal transcribed spacer (ITS)-based phylogeny (clades A to D). The complete genome sequences of two Ostreococcus species have been described: O. tauri (19) and O. lucimarinus (35). In the present study, viruses infecting specific host species (Ostreococcus spp.) have been screened from a variety of locations around the world.Among viruses infecting Ostreococcus, the genome of a single strain (OtV5) has been fully sequenced (18), and the phylogenetic relationships among several virus strains have been investigated (4). These viruses belong to the Prasinovirus group, a genus of the Phycodnaviridae family. Many viruses infecting phytoplankton are members of the Phycodnaviridae; they have double-stranded DNA genomes and large polyhedral capsids (20). In the prasinophyte-Prasinovirus system, the hosts and viruses can be grown on solid medium and are easily maintained in the laboratory. Ostreococcus viral strains have been isolated and characterized by phylogenetic analysis based on their B-family DNA polymerase (DNA pol) partial gene sequence (4). This DNA polymerase is a useful marker for phylogenetic analyses because its sequence is well conserved in all known members of nucleocytoplasmic large DNA viruses (NCLDVs) (26), including Phycodnaviridae. Furthermore, several previous studies have examined the abundance and the genetic diversity of marine eukaryotic viruses using environmental sequencing approaches and amplified DNA pol gene fragments (11, 12, 43-46), and Monier et al. (31) used this marker to describe the taxonomic distribution of large DNA viruses from the GOS data.The first stage of this study was to isolate Ostreococcus viruses from different worldwide geographic locations, by culturing on various host strains. In a second stage, these viral strains were characterized via the sequencing of their pol sequence (encoding a part of their DNA polymerase gene), and their specificity toward different host strains was assessed in order to assess the potential host range of the viral strains isolated and to gain a better understanding of their population dynamics and distribution. Finally we compared these new Prasinovirus DNA sequences with metagenomic sequence data (obtained from sampling all around the world) and environmental sequence data identified using BLAST similarity to assess the global distribution of similar Ostreococcus viruses.     

Sequencing the genome of the Atlantic salmon (<Emphasis Type="Italic">Salmo salar</Emphasis>)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids.     

Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors

Background

Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.

Results

In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.

Conclusions

We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.     

The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment

Introduction  

Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.