Occurrence and distribution of ladderane oxidation products in different oceanic regimes

Ladderane fatty acids are commonly used as biomarkers for bacteria involved in anaerobic ammonium oxidation (anammox). These lipids have been experimentally shown to undergo aerobic microbial degradation to form short chain ladderane fatty acids. However, nothing is known of the production or the distribution of these oxic biodegradation products in the natural environment. In this study, we analysed marine water column particulate matter and sediment from three different oceanic regimes for the presence of ladderane oxidation products (C-14 ladderane fatty acids) and of original ladderane fatty acids (C-18 and C-20 ladderane fatty acids). We found that ladderane oxidation products, i.e. C-14 ladderane fatty acids, are already produced within the water column of the Arabian Sea oxygen minimum zone (OMZ) and thus only low amounts of oxygen (< 3 mu M) are needed for the beta-oxidation of original ladderane fatty acids to proceed. However, no short chain ladderane fatty acids were detected in the Cariaco Basin water column, where oxygen concentrations were below detection limit, suggesting that the beta-oxidation pathway is inhibited by the absence of molecular oxygen, or that the microbes performing the degradation are not proliferating under these conditions. Comparison of distributions of ladderane fatty acids indicates that short chain ladderane fatty acids are mostly produced in the water column and at the sediment surface, before being preserved deeper in the sediments. Short chain ladderane fatty acids were abundant in Arabian Sea and Peru Margin sediments (ODP Leg 201), often in higher concentrations than the original ladderane fatty acids. In a sediment core taken from within the Arabian Sea OMZ, short chain ladderanes made up more than 90% of the total ladderanes at depths greater than 5 cm below sea floor. We also found short chain ladderanes in higher concentrations in hydrolysed sediment residues compared to those freely occurring in lipid extracts, suggesting that they had become bound to the sediment matrix. Furthermore, these matrix-bound short chain ladderanes were found at greater sediment depths than short chain ladderanes in the lipid extract, suggesting that binding to the sediment matrix aids the preservation of these lipids. Though sedimentary degradation of short chain ladderane fatty acids did occur, it appeared to be at a slower rate than that of the original ladderane fatty acids, and short chain ladderane fatty acids were found in sediments from the Late Pleistocene (similar to 100 kyr). Together these results suggest that the oxic degradation products of ladderane fatty acids may be suitable biomarkers for past anammox activity in OMZs

Marine nitrogen cycling dynamics under altering redox conditions: Insights from deposition of sapropels S1 and the ambiguous S2 in the Eastern Mediterranean Sea

The eastern Mediterranean Sea (EMS) sedimentary record is periodically interspersed with organic-rich ‘sapropel’ layers. Sapropels are characteristic of basin-wide anoxic events, triggered by precession-forced insolation maxima. Relatively subdued insolation maxima, however, are not always expressed as distinct sapropel events. The EMS sedimentary record is thus useful to investigate feedbacks between marine anoxia and the nitrogen (N) cycle and offers an analogue for modern deoxygenation and past oceanic anoxic events. To this end, we investigated a ∼68 kyr sedimentary record from the EMS containing the well-established sapropel S1 (deposited in two phases: S1a [∼10.5–8.5 ka BP] and S1b [∼7.8–6.1 ka BP]) and sediments timed to the ambiguous S2 sapropel (∼53 ka BP). We used lipid biomarkers of microorganisms to reconstruct key N-cycle components: (1) anaerobic ammonium oxidation (anammox) using ladderanes and a stereoisomer of bacteriohopanetetrol (BHT-x), (2) dinitrogen gas (N2) fixation using heterocyte glycolipids, and (3) nitrification by Thaumarchaeota using crenarchaeol. Additionally, benthic foraminifera and trace metals (U, Mo, Mn) were used to reconstruct redox conditions. During S1a, abundances of Thaumarchaeota increased, likely promoted by elevated high-nutrient freshwater discharge. At this time, a combination of phosphorus supply and intensified loss of bioavailable N via water column anammox, may have reinforced anoxia by favoring diatom-diazotroph associations. During S1b, anammox is equally intense. Yet, no positive feedback on N2-fixation is observed, likely because diazotrophs were phosphorus limited. Instead, anammox may have provided negative feedback on anoxia by quenching primary production. Ladderanes suggest additional episodes of anammox between ∼69 to 39 cal ka BP, corresponding to brief periods of water column deoxygenation. Anoxia likely occurred at the sediment–water interface in S2-timed sediments (53–51 cal ka BP). During these episodes, ladderanes co-occur with the later eluting BHT-34R stereoisomer. δ13CBHT-34R indicate an anammox source, potentially synthesized by marine sedimentary anammox bacteria. No corresponding increase in diatom-diazotroph associations is observed, likely due to the oligotrophic conditions and the limited effect of sedimentary anammox on N-availability in the euphotic zone. Our results highlight various modes of operation of the N-cycle at different degrees of deoxygenation, which depend amongst others on nutrient-availability and the niche-segregation of N-loss and N2-fixating microorganisms

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer : long-term survival results from the STAMPEDE trial

Background STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. Methods We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. Results Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P  0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). Conclusions The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden

Chemistry of human erythrocyte polylactosamine glycopeptides (erythroglycans) as related to ABH blood group antigenic determinants.

Human erythrocytes bear carbohydrates linked to both proteins and lipids. The majority of the carbohydrates is carried on two proteins: 1) Band 3 (which carries a high molecular weight polylactosamine, variously termed Erythroglycan , poly(glycosyl)peptide or lactosaminoglycan and 2) Glycophorin A (which carries 15 O-linked tetrasaccharides and 1 triantennary N-linked structure). The remainder of carbohydrates are carried mainly by a few other glycoproteins (glycophorins B,C, the glucose transporter and others) with a minor amount carried by glycosphingolipids. This report concerns the Band 3 carbohydrate and its content of potential ABH-active sites. We have determined that an average number of two [Fuc1----2Ga11----4GlcNAc] sequences are carried by each erythroglycan , polylactosamine N-linked oligosaccharide. One such large oligosaccharide occurs on each molecule of Band 3 polypeptide of which there are 1,000,000 copies per erythrocyte. Therefore, about 2,000,000 possible ABH sites are borne by Band 3 on each erythrocyte. This approximates the number of immunologically estimated ABH sites on human erythrocytes. Thus, Band 3 carbohydrate probably carries the majority of ABH substance on human red cells, while other glycoproteins and glycosphingolipids carry a minor fraction

Lipids as paleomarkers to constrain the marine nitrogen cycle

Global climate is, in part, regulated by the effect of microbial processes on biogeochemical cycling. The nitrogen cycle, in particular, is driven by microorganisms responsible for the fixation and loss of nitrogen, and the reduction-oxidation transformations of bio-available nitrogen. Within marine systems, nitrogen availability is often the limiting factor in the growth of autotrophic organisms, intrinsically linking the nitrogen and carbon cycles. In order to elucidate the state of these cycles in the past, and help envisage present and future variability, it is essential to understand the specific microbial processes responsible for transforming bio-available nitrogen species. As most microorganisms are soft-bodied and seldom leave behind physical fossils in the sedimentary record, recalcitrant lipid biomarkers are used to unravel microbial processes in the geological past. This review emphasises the recent advances in marine nitrogen cycle lipid biomarkers, underlines the missing links still needed to fully elucidate past shifts in this biogeochemically-important cycle, and provides examples of biomarker applications in the geological past

Presence of erythroglycan on human K-562 chronic myelogenous leukemia-derived cells

Total glycopeptides from human K-562 cells, labeled metabolically with [3H]glucosamine or [3H]mannose, were prepared by extracting the cells with organic solvents to remove lipids and by digesting the residue with pronase. 3H-labeled glycopeptides were fractionated on Sephadex G-50 revealing a high molecular weight fraction (M(r) = 7,000 to 11,000), comprising approximately 10% of the [3H]glucosamine and 25% of the [3H]mannose label. Digestion of this glycopeptide fraction with endo-β-galactosidase from Escherichia freundii, specific for a repeating structure of Gal(β1 → 4)GlcNAc(β1→3), results in the following four products as resolved by Bio-Gel P-2 gel filtration: 1) a disaccharide with the structure β-2-deoxy-2-acetamidoglucosyl → β-galactose; 2) a trisaccharide with the structure β-galactosyl → β-2-deoxy-2-acetamidoglucosyl → β-galactose; 3) a tetrasaccharide with the sequence α-N-acetylneuraminyl → β-galactosyl → β-2-deoxy-2-acetamidoglucosyl → β-galactose; and 4) a larger, complex fragment which contains mannose and β-2-deoxy-2-acetamidoglucose and which is probably the protein linkage region. In addition, visualization of radiolabeled glycoproteins by fluorography on polyacrylamide gels revealed a 105,000-dalton \u27Band 3\u27-like glycoprotein and other bands that were sensitive to endo-β-galactosidase. These results indicate that the K-562 cell line bears a glycopeptide, erythroglycan, which has been found on erythrocytes, and that this polymer is expressed mainly in the fetal form as a linear chain