The Ca and Mg isotope record of the Cryogenian Trezona carbon isotope excursion

This work was supported by a grant from the Simons Foundation (SCOL 611878, ASCA) and the Carlsberg Foundation to ASCA. ASCA and CJB also acknowledge support from the Danish National Research Foundation (Grant No. DNRF53). ACM and CVR acknowledge support from NSF (EAR-0842946) for funding fieldwork on the Trezona Formation in South Australia. JAH acknowledges support from NSF (IES-1410317) and from NSF OCE CAREER Grant (1654571).The Trezona carbon isotope excursion is recorded on five different continents in platform carbonates deposited prior to the end-Cryogenian Marinoan glaciation (>635 Ma) and represents a change in carbon isotope values of 16–18‰. Based on the spatial and temporal reproducibility, the excursion previously has been interpreted as tracking the carbon isotopic composition of dissolved inorganic carbon in the global ocean before the descent into a snowball Earth. However, in modern restricted shallow marine and freshwater settings, carbon isotope values have a similarly large range, which is mostly independent from open ocean chemistry and instead reflects local processes. In this study, we combine calcium, magnesium, and strontium isotope geochemistry with a numerical model of carbonate diagenesis to disentangle the degree to which the Trezona excursion reflects changes in global seawater chemistry versus local shallow-water platform environments. Our analysis demonstrates that the most extreme carbon isotope values (∼-10‰ versus +10‰) are preserved in former platform aragonite that was neomorphosed to calcite during sediment-buffered conditions and record the primary carbon isotope composition of platform-top surface waters. In contrast, the downturn and recovery of the Trezona excursion are recorded in carbonates that were altered during early fluid-buffered diagenesis and commonly are dolomitized. We also find that the nadir of the Trezona excursion is associated with a fractional increase in siliciclastic sediments, whereas the recovery from the excursion correlates with a relative increase in carbonate. This relationship suggests that the extreme negative isotopic shift in platform aragonite occurred in concert with periods of increased input of siliciclastic sediments, changes in water depth, and possibly nutrients to platform environments. Although the process for generating extremely negative carbon isotope values in Neoproterozoic platform carbonates remains enigmatic, we speculate that these excursions reflect kinetic isotope effects associated with CO2 invasion in platform waters during periods of intense primary productivity.Publisher PDFPeer reviewe

An early diagenetic deglacial origin for basal Ediacaran “cap dolostones”

ASCA acknowledges support from The Carlsberg Foundation. JAH acknowledges support from NSF grant no. IES1410317 and from National Science Foundation OCE CAREER Grant No. 1654571. ASA and CJB acknowledges support from the Danish National Research Foundation (Grant No. DNRF53).The beginning of the Ediacaran Period (∼635 Ma) is marked by conspicuous dolostone units that cap Marinoan glacial deposits worldwide. The extent and sedimentary characteristics of the cap dolostones indicate that anomalous carbonate over-saturation coincided with deglacial sea-level rise and ocean warming. However, the geochemical variability within cap dolostones, both between continents, across single continental margins, and within individual stratigraphic sections has been difficult to reconcile with depositional models. Using a compilation of new calcium and magnesium isotope measurements in Marinoan cap dolostone successions worldwide, we show that the geochemical variability can be explained by early diagenetic dolomitization of aragonite along a spectrum of fluid- and sediment-buffered conditions. Dolostones from the outer platform formed under fluid-buffered conditions, whereas dolostones on the inner platform and foreslope environment formed under sediment-buffered conditions. This spatial pattern of dolomitizing conditions is consistent with buoyant recirculation of glacial seawater within carbonate platforms driven by the deglacial sea-level rise and development of a meltwater surface ocean. Using a numerical diagenetic model to evaluate the geochemical differences between sediment- and fluid-buffered cap dolostone units, we constrain the chemical and isotopic composition of both the dolomitizing fluid (glacial seawater [δ13C∼ 0–2‰]), the meltwater lens (δ13C∼−11‰), and the primary aragonite sediment (δ13C∼−6 to −3‰). These model end-members do not imply that primary geochemical variability did not exist but demonstrates that it is not necessary to change the chemistry of seawater to explain the global stratigraphic variability in the geochemistry of basal Ediacaran cap dolostones. Our results provide a novel framework for understanding the geochemical variability of cap dolostone units, including large excursions in carbon isotopes, and how this variability is the product of local diagenetic processes expressed globally in continental margin environments following the last Snowball Earth.PostprintPeer reviewe

Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc

Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo. Results The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creERT2Apcflx/flx and BlgCreBrca2flx/flp53flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50–95% (P < 0.01) reduction in RNA and protein expression with SL7207/c-Myc targeted strains. In vivo, following establishment of tumour tissue, a single intra-peritoneal administration of 1 × 106 CFU of SL7207/c-Myc was sufficient to permit tumour colonisation and significantly extend survival with no overt toxicity in control animals. Conclusions In summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation

A modern scleractinian coral with a two-component calcite–aragonite skeleton

Until now, all of the ca. 1,800 known modern scleractinian coral species were thought to produce skeletons exclusively of aragonite. Asymbiotic Paraconotrochus antarcticus living in the Southern Ocean is the first example of an extant scleractinian that forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. This discovery adds support to the notion that the coral skeletal formation process is strongly biologically controlled. Mitophylogenomic analysis shows that P. antarcticus represents an ancient scleractinian clade, suggesting that skeletal mineralogy/polymorph of a taxon, once established, is a trait conserved throughout the evolution of that clade.One of the most conserved traits in the evolution of biomineralizing organisms is the taxon-specific selection of skeletal minerals. All modern scleractinian corals are thought to produce skeletons exclusively of the calcium-carbonate polymorph aragonite. Despite strong fluctuations in ocean chemistry (notably the Mg/Ca ratio), this feature is believed to be conserved throughout the coral fossil record, spanning more than 240 million years. Only one example, the Cretaceous scleractinian coral Coelosmilia (ca. 70 to 65 Ma), is thought to have produced a calcitic skeleton. Here, we report that the modern asymbiotic scleractinian coral Paraconotrochus antarcticus living in the Southern Ocean forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. P. antarcticus and Cretaceous Coelosmilia skeletons share a unique microstructure indicating a close phylogenetic relationship, consistent with the early divergence of P. antarcticus within the Vacatina (i.e., Robusta) clade, estimated to have occurred in the Mesozoic (ca. 116 Mya). Scleractinian corals thus join the group of marine organisms capable of forming bimineralic structures, which requires a highly controlled biomineralization mechanism; this capability dates back at least 100 My. Due to its relatively prolonged isolation, the Southern Ocean stands out as a repository for extant marine organisms with ancient traits.Mitogenome sequences data have been deposited in GenBank (MT409109). All other study data are included in the article text and supporting information

Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

The process known as “adaptive response” allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 ± 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 Å resolution crystal structure in space group P32 that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.National Institutes of Health (U.S.) (grant R01-GM0272663)National Institutes of Health (U.S.) (grant P30-ES002109)National Science Foundation (U.S.) (grant MCB-0543833

Variations of Plasmid Content in Rickettsia felis

Background: Since its first detection, characterization of R. felis has been a matter of debate, mostly due to the contamination of an initial R. felis culture by R. typhi. However, the first stable culture of R. felis allowed its precise phenotypic and genotypic characterization, and demonstrated that this species belonged to the spotted fever group rickettsiae. Later, its genome sequence revealed the presence of two forms of the same plasmid, physically confirmed by biological data. In a recent article, Gillespie et al. ( PLoS One. 2007; 2( 3): e266.) used a bioinformatic approach to refute the presence of the second plasmid form, and proposed the creation of a specific phylogenetic group for R. felis. Methodology/ Principal Findings: In the present report, we, and five independent international laboratories confirmed unambiguously by PCR the presence of two plasmid forms in R. felis strain URRWXCal(2)(T), but observed that the plasmid content of this species, from none to 2 plasmid forms, may depend on the culture passage history of the studied strain. We also demonstrated that R. felis does not cultivate in Vero cells at 37 degrees C but generates plaques at 30 degrees C. Finally, using a phylogenetic study based on 667 concatenated core genes, we demonstrated the position of R. felis within the spotted fever group. Significance: We demonstrated that R. felis, which unambiguously belongs to the spotted fever group rickettsiae, may contain up to two plasmid forms but this plasmid content is unstable

Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature

Trace elements in hemodialysis patients: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.</p> <p>Methods</p> <p>All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.</p> <p>Results</p> <p>We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.</p> <p>Conclusion</p> <p>Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.</p