Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation.

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8, leading to an I242N amino acid change in the transmembrane domain. Functional analyses establish this mutation as gain of function leading to constitutive activation of the JAK-STAT pathway and upregulation of downstream cytokine expression profiles and B cell-specific antigens. Moreover, expression of I242N mutant IL4R in a mouse xenotransplantation model conferred growth advantage in vivo. The pattern of concurrent mutations within the JAK-STAT signaling pathway suggests additive/synergistic effects of these gene mutations contributing to lymphomagenesis. Our data establish IL4R mutations as novel driver alterations and provide a strong preclinical rationale for therapeutic targeting of JAK-STAT signaling in PMBCL.

Expression of hcp in freshwater Synechococcus spp., a gene encoding a hyperconserved protein in picocyanobacteria.

Marine picoplankton of the genus Synechococcus and Prochlorococcus spp. are widely studied members of the picocyanobacterial clade, composed of unicellular cyanobacteria that dominate pelagic regions of the ocean. Less studied are the related freshwater Synechococcus spp. that similarly dominate the euphotic zone of oligotrophic lakes. Previous work has shown that marine picocyanobacteria harbor a small gene, hcp, that encodes a 62 amino acid protein 100% conserved among all strains examined. The gene is restricted exclusively to the picocyanobacterial lineage. The current study reveals that hcp is also 100% conserved in four freshwater Synechococcus spp. strains isolated from the Laurentian Great Lakes, and that the gene constitutively expressed with genes encoding a ribosomal protein and two tRNA genes. The synteny of the hcp region is also conserved between the marine and freshwater strains. Last, the hcp gene and the organization of the surrounding genetic region has been retained in the reduced genome of a picocyanobacterial endosymbiont of the amoeba Paulinella sp.

Prokaryotic community shifts during soil formation on sands in the tundra zone.

A chronosequence approach, i.e., a comparison of spatially distinct plots with different stages of succession, is commonly used for studying microbial community dynamics during paedogenesis. The successional traits of prokaryotic communities following sand fixation processes have previously been characterized for arid and semi-arid regions, but they have not been considered for the tundra zone, where the environmental conditions are unfavourable for the establishment of complicated biocoenoses. In this research, we characterized the prokaryotic diversity and abundance of microbial genes found in a typical tundra and wooded tundra along a gradient of increasing vegetation-unfixed aeolian sand, semi-fixed surfaces with mosses and lichens, and mature soil under fully developed plant cover. Microbial communities from typical tundra and wooded tundra plots at three stages of sand fixation were compared using quantitative polymerase chain reaction (qPCR) and high-throughput sequencing of 16S rRNA gene libraries. The abundances of ribosomal genes increased gradually in both chronosequences, and a similar trend was observed for the functional genes related to the nitrogen cycle (nifH, bacterial amoA, nirK and nirS). The relative abundance of Planctomycetes increased, while those of Thaumarchaeota, Cyanobacteria and Chloroflexi decreased from unfixed sands to mature soils. According to ß-diversity analysis, prokaryotic communities of unfixed sands were more heterogeneous compared to those of mature soils. Despite the differences in the plant cover of the two mature soils, the structural compositions of the prokaryotic communities were shaped in the same way. Thus, sand fixation in the tundra zone increases archaeal, bacterial and fungal abundances, shifts and unifies prokaryotic communities structure.

Spatial distribution of arable and abandoned land across former Soviet Union countries.

Knowledge of the spatial distribution of agricultural abandonment following the collapse of the Soviet Union is highly uncertain. To help improve this situation, we have developed a new map of arable and abandoned land for 2010 at a 10 arc-second resolution. We have fused together existing land cover and land use maps at different temporal and spatial scales for the former Soviet Union (fSU) using a training data set collected from visual interpretation of very high resolution (VHR) imagery. We have also collected an independent validation data set to assess the map accuracy. The overall accuracies of the map by region and country, i.e. Caucasus, Belarus, Kazakhstan, Republic of Moldova, Russian Federation and Ukraine, are 90±2%, 84±2%, 92±1%, 78±3%, 95±1%, 83±2%, respectively. This new product can be used for numerous applications including the modelling of biogeochemical cycles, land-use modelling, the assessment of trade-offs between ecosystem services and land-use potentials (e.g., agricultural production), among others.

Seasonal Expression of the Picocyanobacterial Phosphonate Transporter Gene phnD in the Sargasso Sea.

In phosphorus-limited marine environments, picocyanobacteria (Synechococcus and Prochlorococcus spp.) can hydrolyze naturally occurring phosphonates as a P source. Utilization of 2-aminoethylphosphonate (2-AEP) is dependent on expression of the phn genes, encoding functions required for uptake, and C-P bond cleavage. Prior work has indicated that expression of picocyanobacterial phnD, encoding the phosphonate binding protein of the phosphonate ABC transporter, is a proxy for the assimilation of phosphonates in natural assemblages of Synechococcus spp. and Prochlorococcus spp (Ilikchyan et al., 2009). In this study, we expand this work to assess seasonal phnD expression in the Sargasso Sea. By RT-PCR, our data confirm that phnD expression is constitutive for the Prochlorococcus spp. detected, but in Synechococcus spp. phnD transcription follows patterns of phosphorus availability in the mixed layer. Specifically, our data suggest that phnD is repressed in the spring when P is bioavailable following deep winter mixing. In the fall, phnD expression follows a depth-dependent pattern reflecting depleted P at the surface following summertime drawdown, and elevated P at depth.