Continent-scale biogeography has been extensively studied in soils and marine systems, but little is known about biogeographical patterns in non-marine sediments. We used barcode pyrosequencing to quantify the effects of local geochemical properties and geographic distance for bacterial community structure and membership, using sediment samples from 15 lakes on the Tibetan Plateau (4-1670 km apart). Bacterial communities were surprisingly diverse, and distinct from soil communities. Four of 26 phyla detected were dominant: Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria, albeit 20.2% of sequences were unclassified at the phylum level. As previously observed in acidic soil, pH was the dominant factor influencing alkaline sediment community structure, phylotype richness and phylogenetic diversity. In contrast, archaeal communities were less affected by pH. More geographically distant sites had more dissimilar communities (r=0.443, P=0.030). Variance partitioning analysis showed that geographic distance (historical contingencies) contributed more to bacterial community variation (12.2%) than any other factor, although the environmental factors explained more variance when combined (28.9%). Together, our results show that pH is the best predictor of bacterial community structure in alkaline sediments, and confirm that both geographic distance and chemical factors govern bacterial biogeography in lake sediments.

Abstract Introduction The aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE. Methods Gene expression levels in peripheral blood cells (PBLs) measured using quantitative real-time polymerase chain reaction (qPCR) were assessed for association with disease activity and the presence of specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were incubated with specific siRNAs for three days, then cells were harvested for measuring mRNA levels using qPCR, and supernatants for levels of total immunoglobulin (Ig)G and IgM as well as secreted cytokines, chemokine and antinuclear antibodies (ANA) using ELISA. Indirect immunofluorescence was also applied for ANA detection. Results OAZ gene expressions in PBLs from 40 ANA-positive SLE patients were significantly increased than those from 30 normal controls (P < 0.0001) and 18 patients with rheumatoid arthritis (P < 0.01). In SLE patients, OAZ transcripts were positively correlated with SLE disease activity index (SLEDAI) score (r = 0.72, P < 0.0001) and higher in those positive for anti-dsDNA or anti-Sm antibodies (both P < 0.05). Co-culturing with OAZ siRNAs reduced mRNA levels of OAZ by 74.6 ± 6.4% as compared to those co-cultured with non-targeting siRNA and OAZ silencing resulted in reduced total IgG, ANA, interferon (IFN)-γ, interleukin (IL)-10, IL-12 and IL-21, but elevated CCL2 levels in culture supernatants (P < 0.05). The declined ANA levels correlated with inhibited OAZ expression (r = 0.88, P = 0.05), reduced IL-21 levels (r = 0.99, P < 0.01), and elevated chemokine (C-C motif) ligand 2 levels (r = -0.98, P < 0.01). Expressions of ID1-3 were significantly down-regulated by 68.7%, 70.2% and 67.7% respectively after OAZ silence, while ID3 was also highly expressed in SLE PBLs (P < 0.0001) and associated with disease activity (r = 0.76, P < 0.0001) as well as anti-dsDNA or anti-Sm antibodies (both P < 0.05). Conclusions Elevated expression of OAZ transcripts in SLE PBLs were strongly correlated with disease activity. Suppression of OAZ expression inhibited downstream ID levels, and secretion of ANA and IL-21, implicating a role of OAZ pathway in the pathogenesis of SLE.