Cell surface acid-base properties of the cyanobacterium Synechococcus: Influences of nitrogen source, growth phase and N:P ratios

The distribution of many trace metals in the oceans is controlled by biological uptake. Recently, Liu et al. (2015) demonstrated the propensity for a marine cyanobacterium to adsorb cadmium from seawater, suggesting that cell surface reactivity might also play an important role in the cycling of metals in the oceans. However, it remains unclear how variations in cyanobacterial growth rates and nutrient supply might affect the chemical properties of their cellular surfaces. In this study we used potentiometric titrations and Fourier Transform Infrared (FT-IR) spectrometry to profile the key metabolic changes and surface chemical responses of a Synechococcus strain, PCC 7002, during different growth regimes. This included testing various nitrogen (N) to phosphorous (P) ratios (both nitrogen and phosphorous dependent), nitrogen sources (nitrate, ammonium and urea) and growth stages (exponential, stationary, and death phase). FT-IR spectroscopy showed that varying the growth substrates on which Synechococcus cells were cultured resulted in differences in either the type or abundance of cellular exudates produced or a change in the cell wall components. Potentiometric titration data were modeled using three distinct proton binding sites, with resulting pKa values for cells of the various growth conditions in the ranges of 4.96-5.51 (pKa1), 6.67-7.42 (pKa2) and 8.13-9.95 (pKa3). According to previous spectroscopic studies, these pKa ranges are consistent with carboxyl, phosphoryl, and amine groups, respectively. Comparisons between the titration data (for the cell surface) and FT-IR spectra (for the average cellular changes) generally indicate (1) that the nitrogen source is a greater determinant of ligand concentration than growth phase, and (2) that phosphorus limitation has a greater impact on Synechococcus cellular and extracellular properties than does nitrogen limitation. Taken together, these techniques indicate that nutritional quality during cell growth can noticeably influence the expression of cell surface ligands and their measurable densities. Given that cell surface charge ultimately affects metal adsorption, our results suggest that the cycling of metals by Synechococcus cells in the oceans may vary regionally

Design Considerations for Massively Parallel Sequencing Studies of Complex Human Disease

Massively Parallel Sequencing (MPS) allows sequencing of entire exomes and genomes to now be done at reasonable cost, and its utility for identifying genes responsible for rare Mendelian disorders has been demonstrated. However, for a complex disease, study designs need to accommodate substantial degrees of locus, allelic, and phenotypic heterogeneity, as well as complex relationships between genotype and phenotype. Such considerations include careful selection of samples for sequencing and a well-developed strategy for identifying the few “true” disease susceptibility genes from among the many irrelevant genes that will be found to harbor rare variants. To examine these issues we have performed simulation-based analyses in order to compare several strategies for MPS sequencing in complex disease. Factors examined include genetic architecture, sample size, number and relationship of individuals selected for sequencing, and a variety of filters based on variant type, multiple observations of genes and concordance of genetic variants within pedigrees. A two-stage design was assumed where genes from the MPS analysis of high-risk families are evaluated in a secondary screening phase of a larger set of probands with more modest family histories. Designs were evaluated using a cost function that assumes the cost of sequencing the whole exome is 400 times that of sequencing a single candidate gene. Results indicate that while requiring variants to be identified in multiple pedigrees and/or in multiple individuals in the same pedigree are effective strategies for reducing false positives, there is a danger of over-filtering so that most true susceptibility genes are missed. In most cases, sequencing more than two individuals per pedigree results in reduced power without any benefit in terms of reduced overall cost. Further, our results suggest that although no single strategy is optimal, simulations can provide important guidelines for study design

Earth: Atmospheric Evolution of a Habitable Planet

Our present-day atmosphere is often used as an analog for potentially habitable exoplanets, but Earth's atmosphere has changed dramatically throughout its 4.5 billion year history. For example, molecular oxygen is abundant in the atmosphere today but was absent on the early Earth. Meanwhile, the physical and chemical evolution of Earth's atmosphere has also resulted in major swings in surface temperature, at times resulting in extreme glaciation or warm greenhouse climates. Despite this dynamic and occasionally dramatic history, the Earth has been persistently habitable--and, in fact, inhabited--for roughly 4 billion years. Understanding Earth's momentous changes and its enduring habitability is essential as a guide to the diversity of habitable planetary environments that may exist beyond our solar system and for ultimately recognizing spectroscopic fingerprints of life elsewhere in the Universe. Here, we review long-term trends in the composition of Earth's atmosphere as it relates to both planetary habitability and inhabitation. We focus on gases that may serve as habitability markers (CO2, N2) or biosignatures (CH4, O2), especially as related to the redox evolution of the atmosphere and the coupled evolution of Earth's climate system. We emphasize that in the search for Earth-like planets we must be mindful that the example provided by the modern atmosphere merely represents a single snapshot of Earth's long-term evolution. In exploring the many former states of our own planet, we emphasize Earth's atmospheric evolution during the Archean, Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of potential atmospheric trajectories into the distant future, many millions to billions of years from now. All of these 'Alternative Earth' scenarios provide insight to the potential diversity of Earth-like, habitable, and inhabited worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook of Exoplanet

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The trace fossil Lepidenteron lewesiensis: a taphonomic window on diversity of Late Cretaceous fishes

The trace fossil Lepidenteron lewesiensis (Mantell 1822) provides an exceptional taphonomic window to diversity of fishes as shown for the Upper Cretaceous of Poland, in the Middle Turonian–Lower Maastrichtian deposits of the Opole Trough, Miechów Trough, Mazury-Podlasie Homocline, and SE part of the Border Synclinorium. Lepidenteron lewesiensis is an unbranched burrow lined with small fish scales and bones, without a constructed wall. It contains scales, vertebrae, and bones of the head belonging to ten taxa of teleostean fishes: two undetermined teleosteans, six undetermined Clupeocephala, one Dercetidae, and one undetermined euteleostean. The preservation of fish remains suggests that fishes were pulled down into the burrow by an animal, probably by eunicid polychaetes.Das Spurenfossil Lepidenteron lewesiensis (Mantell 1822) ermöglicht einen biostratinomischen Einblick in die Diversität von Fischen, wie Fossilmaterial aus der Oberkreide von Polen zeigt. Es stammt aus dem Mittelturonium bis Untermaastrichtium des südöstlichen Abschnittes der Grenz-Synklinale, dem Opolen-Trog, dem Miechów-Trog und der Masuren-Podlachien-Homoklinale. L. lewesiensis ist ein unverzweigter Grabgang ohne ausgekleidete Wände, dessen Ränder von kleinen Fischschuppen und—knochen gebildet werden. Diese setzen sich aus Schuppen, Wirbel und Schädelknochen von zehn Teleostei-Taxa zusammen und zwar aus zwei unbestimmte Teleosteer, sechs unbestimmten Clupeocephala, einem Dercetidae und einem unbestimmten Euteleostei. Die Erhaltung der Fischüberreste deutet darauf hin, dass die Fische von einem Tier, wahrscheinlich einem Polychaeten der Familie Eunicidae, in den Bau gezogen wurden.We are very grateful to Dr. Lionel Cavin (Geneva) and the anonymous reviewer for constructive comments on an earlier version of the manuscript. Additional support was provided by the Jagiellonian University (DS funds), National Science Center (Grant Number: PRO-2011/01/N/ST10/07717), and the Laboratory of Geology (University of Lodz) BSt Grant No. 560/844. We are grateful to Dr. Johann Egger (Wien) and Kilian Eichenseer M.Sc. (Erlangen) for help with translating the abstract into German. We are grateful to Dr. Ursula Göhlich (Wien) for access to the Dercetis specimen

Iron minerals as archives of Earth's redox and biogeochemical evolution

Iron minerals provide sedimentary repositories of chemical information pertaining to Earth’s redox and biogeochemical evolution, from before the Great Oxidation Event some 2.5 billion years ago, to more recent events occurring up to and into the Cenozoic Era. The most powerful chemical information recorded in iron minerals comes in the form of trace-element signatures, most notably their concentrations and stable isotope compositions. Here we provide an introduction to iron mineralogy and the processes responsible for the accumulation and preservation of trace-element signatures in iron minerals, focusing on the deposition of iron minerals in three key ancient sedimentary archives: banded iron formations, ferromanganese crusts and black shales. We introduce the theory and practical use of non-traditional trace-element stable-isotope systems in redox and biogeochemical research, focusing on the recent use of iron, molybdenum and chromium stable isotopes to shed light on the redox and biogeochemical information stored in iron-rich sediments. By analysing both trace-element concentrations and stableisotope compositions recorded in iron minerals, iron-rich sedimentary archives are providing a unique window into the past, where changes in trace-element signatures shed light on major transitions in Earth’s redox and biogeochemical evolution

Limited Zn and Ni mobility during simulated iron formation diagenesis

Iron formations (IF) are iron- and silica-rich chemical precipitates that were deposited during the Precambrian. Several recent studies have demonstrated how the trace metal abundances in IF can be used as proxies for the bioavailability of trace metals in ancient seawater; with the ultimate goal being to understand first-order controls on the composition of the ancient biosphere. However, the utility of IF as proxies depends on the immobilization of trace metals during diagenesis. Here, we assess the mobility of Zn and Ni from ferric oxyhydroxides (ferrihydrite) in the absence and presence of organic matter (glucose) during simulated diagenesis (170 °C, 1.2 kbar); similar to what some Precambrian IF experienced. Quantitative concentration data, coupled with X-ray diffraction analysis and electron microprobe element mapping, demonstrate that both metals are relatively immobile during simulated diagenesis. Additionally, the mechanism for initial Ni sorption is examined using X-ray adsorption spectroscopy. For the initial sorption of trace elements in abiotic ferrihydrite experiments, 93.38% Zn and 65.95% Ni were initially sorbed. In experiments utilizing biogenic ferrihydrite, 97.03% of Zn and 93.38% of Ni were initially sorbed. Following the diagenetic capsule treatments, more than 99% of Zn and more than 91.9% of Ni were retained under the varied conditions considered here. Capsule experiments suggest the strong retention of Zn and Ni following the diagenesis of either abiotic or biogenic ferrihydrite. Overall, our results indicate that paleomarine Zn and Ni concentrations are likely to be faithfully recorded in well-preserved IF deposits