Interannual and (multi-)decadal variability in the sedimentary BIT index of Lake Challa, East Africa, over the past 2200 years: assessment of the precipitation proxy

The branched vs. isoprenoid tetraether (BIT) index is based on the relative abundance of branched tetraether lipids (brGDGTs) and the isoprenoidal GDGT crenarchaeol. In Lake Challa sediments the BIT index has been applied as a proxy for local monsoon precipitation on the assumption that the primary source of brGDGTs is soil washed in from the lake's catchment. Since then, microbial production within the water column has been identified as the primary source of brGDGTs in Lake Challa sediments, meaning that either an alternative mechanism links BIT index variation with rainfall or that the proxy's application must be reconsidered. We investigated GDGT concentrations and BIT index variation in Lake Challa sediments at a decadal resolution over the past 2200 years, in combination with GDGT time-series data from 45 monthly sediment-trap samples and a chronosequence of profundal surface sediments.

Our 2200-year geochemical record reveals high-frequency variability in GDGT concentrations, and therefore in the BIT index, superimposed on distinct lower-frequency fluctuations at multi-decadal to century timescales. These changes in BIT index are correlated with changes in the concentration of crenarchaeol but not with those of the brGDGTs. A clue for understanding the indirect link between rainfall and crenarchaeol concentration (and thus thaumarchaeotal abundance) was provided by the observation that surface sediments collected in January 2010 show a distinct shift in GDGT composition relative to sediments collected in August 2007. This shift is associated with increased bulk flux of settling mineral particles with high Ti / Al ratios during March–April 2008, reflecting an event of unusually high detrital input to Lake Challa concurrent with intense precipitation at the onset of the principal rain season that year. Although brGDGT distributions in the settling material are initially unaffected, this soil-erosion event is succeeded by a massive dry-season diatom bloom in July–September 2008 and a concurrent increase in the flux of GDGT-0. Complete absence of crenarchaeol in settling particles during the austral summer following this bloom indicates that no Thaumarchaeota bloom developed at that time. We suggest that increased nutrient availability, derived from the eroded soil washed into the lake, caused the massive bloom of diatoms and that the higher concentrations of ammonium (formed from breakdown of this algal matter) resulted in a replacement of nitrifying Thaumarchaeota, which in typical years prosper during the austral summer, by nitrifying bacteria. The decomposing dead diatoms passing through the suboxic zone of the water column probably also formed a substrate for GDGT-0-producing archaea. Hence, through a cascade of events, intensive rainfall affects thaumarchaeotal abundance, resulting in high BIT index values.

Decade-scale BIT index fluctuations in Lake Challa sediments exactly match the timing of three known episodes of prolonged regional drought within the past 250 years. Additionally, the principal trends of inferred rainfall variability over the past two millennia are consistent with the hydroclimatic history of equatorial East Africa, as has been documented from other (but less well dated) regional lake records. We therefore propose that variation in GDGT production originating from the episodic recurrence of strong soil-erosion events, when integrated over (multi-)decadal and longer timescales, generates a stable positive relationship between the sedimentary BIT index and monsoon rainfall at Lake Challa. Application of this paleoprecipitation proxy at other sites requires ascertaining the local processes which affect the productivity of crenarchaeol by Thaumarchaeota and brGDGTs.

Determination of multi-mycotoxin occurrence in maize based porridges from selected regions of Tanzania by liquid chromatography tandem mass spectrometry (LC-MS/MS), a longitudinal study

Residents of certain areas of Tanzania are exposed to mycotoxins through the consumption of contaminated maize based foods. In this study, 101 maize based porridge samples were collected from villages of Nyabula, Kikelelwa and Kigwa located in different agro-ecological zones of Tanzania. The samples were collected at three time points (time point 1, during maize harvest; time point 2, 6 months after harvest; time point 3, 12 months after harvest) over a 1-year period. Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to detect and quantify 9 mycotoxins: aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), fumonisin B1 (FB1), fumonisin B2 (FB2), deoxynivalenol (DON), ochratoxin A (OTA) and zearaleneone (ZEN) in the samples following a QuEChERS extraction method. Eighty two percent of samples were co-contaminated with more than one group of mycotoxins. Fumonisins (FB1 + FB2) had the highest percentage occurrence in all 101 samples (100%) whereas OTA had the lowest (5%). For all three villages the mean concentration of FB1 was lowest in samples taken from time point 2. Conversely, In Kigwa village there was a distinct trend that AFB1 mean concentration was highest in samples taken from time point 2. DON concentration did not differ greatly between time points but the percentage occurrence varied between villages, most notably in Kigwa where 0% of samples tested positive. ZEN occurrence and mean concentration was highest in Kikelelwa. The results suggest that mycotoxin contamination in maize can vary based on season and agro-ecological zones. The high occurrence of multiple mycotoxins found in maize porridge, a common weaning food in Tanzania, presents a potential increase in the risk of exposure and significant health implications in children.

Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.