Toward a Cenozoic history of atmospheric CO2.

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO2) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO2 record spanning the past 66 million years. This newly constructed record provides clearer evidence for higher Earth system sensitivity in the past and for the role of CO2 thresholds in biological and cryosphere evolution.

The PhanSST global database of Phanerozoic sea surface temperature proxy data.

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies.

An astronomically dated record of Earth's climate and its predictability over the last 66 million years.

Much of our understanding of Earth's past climate comes from the measurement of oxygen and carbon isotope variations in deep-sea benthic foraminifera. Yet, long intervals in existing records lack the temporal resolution and age control needed to thoroughly categorize climate states of the Cenozoic era and to study their dynamics. Here, we present a new, highly resolved, astronomically dated, continuous composite of benthic foraminifer isotope records developed in our laboratories. Four climate states-Hothouse, Warmhouse, Coolhouse, Icehouse-are identified on the basis of their distinctive response to astronomical forcing depending on greenhouse gas concentrations and polar ice sheet volume. Statistical analysis of the nonlinear behavior encoded in our record reveals the key role that polar ice volume plays in the predictability of Cenozoic climate dynamics.

Automation of boron chromatographic purification for δ11 B analysis of coral aragonite.

RATIONALE: To detect the small changes in past pH, the boron isotope ratio of coral carbonates, expressed as the δ11 B value, needs to be both precise and accurate (2sd <<1‰). Boron measurements by Multi-Collector Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS) require the boron to be carefully purified before analysis, which is time consuming, and requires specialist training. Here, we use the prepFAST-MC method that enables the automatic extraction of B (up to 25 ng load) from a CaCO3 matrix. METHODS: Samples were purified using the prepFAST-MC automated system with a ~25-µL column of Amberlite IRA743 resin. Boron isotope measurements were performed by MC-ICPMS. The effects of matrix load, speed of sample loading onto the column, and blank contamination were tested to evaluate the effects on the purification process. The optimised protocol was tested on various standards and samples of aragonite corals. RESULTS: The blank contribution for the approach is ~60 pg and is negligible given our sample size (<0.2% sample size). Efficiency of matrix removal is demonstrated with the addition of up to 1.6 mg of dissolved low-B calcium carbonate to NIST SRM 951 with no impact on the accuracy of δ11 B values. The Japanese Geological Survey Porites reference material JCp-1, boric acid standard NIST SRM 951, and seawater, all processed on the prepFAST-MC system, give δ11 B values within error of literature values (δ11 BJCp-1 = 24.31 ± 0.20‰ (2sd, n = 20); δ11 BNIST 951 = -0.02 ± 0.15‰ (2sd, n = 13) and δ11 BSeawater = 39.50 ± 0.06‰ (2sd, n = 2)). Results obtained from the coral Siderastrea siderea purified with the prepFAST-MC system show an average offset from the manual ion-exchange protocols of Δδ11 B = 0.01 ± 0.28‰ (2sd, n = 12). CONCLUSIONS: Our study demonstrates the capacity of the prepFAST-MC method to generate accurate and reproducible δ11 B values for a range of materials, without fractionation, with efficient matrix removal and with negligible blank contribution.

Very large release of mostly volcanic carbon during the Palaeocene-Eocene Thermal Maximum.

The Palaeocene-Eocene Thermal Maximum (PETM) was a global warming event that occurred about 56 million years ago, and is commonly thought to have been driven primarily by the destabilization of carbon from surface sedimentary reservoirs such as methane hydrates. However, it remains controversial whether such reservoirs were indeed the source of the carbon that drove the warming. Resolving this issue is key to understanding the proximal cause of the warming, and to quantifying the roles of triggers versus feedbacks. Here we present boron isotope data-a proxy for seawater pH-that show that the ocean surface pH was persistently low during the PETM. We combine our pH data with a paired carbon isotope record in an Earth system model in order to reconstruct the unfolding carbon-cycle dynamics during the event. We find strong evidence for a much larger (more than 10,000 petagrams)-and, on average, isotopically heavier-carbon source than considered previously. This leads us to identify volcanism associated with the North Atlantic Igneous Province, rather than carbon from a surface reservoir, as the main driver of the PETM. This finding implies that climate-driven amplification of organic carbon feedbacks probably played only a minor part in driving the event. However, we find that enhanced burial of organic matter seems to have been important in eventually sequestering the released carbon and accelerating the recovery of the Earth system.

Changing atmospheric CO2 concentration was the primary driver of early Cenozoic climate.

The Early Eocene Climate Optimum (EECO, which occurred about 51 to 53 million years ago), was the warmest interval of the past 65 million years, with mean annual surface air temperature over ten degrees Celsius warmer than during the pre-industrial period. Subsequent global cooling in the middle and late Eocene epoch, especially at high latitudes, eventually led to continental ice sheet development in Antarctica in the early Oligocene epoch (about 33.6 million years ago). However, existing estimates place atmospheric carbon dioxide (CO2) levels during the Eocene at 500-3,000 parts per million, and in the absence of tighter constraints carbon-climate interactions over this interval remain uncertain. Here we use recent analytical and methodological developments to generate a new high-fidelity record of CO2 concentrations using the boron isotope (δ(11)B) composition of well preserved planktonic foraminifera from the Tanzania Drilling Project, revising previous estimates. Although species-level uncertainties make absolute values difficult to constrain, CO2 concentrations during the EECO were around 1,400 parts per million. The relative decline in CO2 concentration through the Eocene is more robustly constrained at about fifty per cent, with a further decline into the Oligocene. Provided the latitudinal dependency of sea surface temperature change for a given climate forcing in the Eocene was similar to that of the late Quaternary period, this CO2 decline was sufficient to drive the well documented high- and low-latitude cooling that occurred through the Eocene. Once the change in global temperature between the pre-industrial period and the Eocene caused by the action of all known slow feedbacks (apart from those associated with the carbon cycle) is removed, both the EECO and the late Eocene exhibit an equilibrium climate sensitivity relative to the pre-industrial period of 2.1 to 4.6 degrees Celsius per CO2 doubling (66 per cent confidence), which is similar to the canonical range (1.5 to 4.5 degrees Celsius), indicating that a large fraction of the warmth of the early Eocene greenhouse was driven by increased CO2 concentrations, and that climate sensitivity was relatively constant throughout this period.

Merging high doxorubicin loading with pronounced magnetic response and bio-repellent properties in hybrid drug nanocarriers.

Hybrid magnetic drug nanocarriers are prepared via a self-assembly process of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (p(MAA-g-EGMA)) on growing iron oxide nanocrystallites. The nanocarriers successfully merge together bio-repellent properties, pronounced magnetic response, and high loading capacity for the potent anticancer drug doxorubicin (adriamicin), in a manner not observed before in such hybrid colloids. High magnetic responses are accomplished by engineering the size of the magnetic nanocrystallites (∼13.5 nm) following an aqueous single-ferrous precursor route, and through adjustment of the number of cores in each colloidal assembly. Complementing conventional magnetometry, the magnetic response of the nanocarriers is evaluated by magnetophoretic experiments providing insight into their internal organization and on their response to magnetic manipulation. The structural organization of the graft-copolymer, locked on the surface of the nanocrystallites, is further probed by small-angle neutron scattering on single-core colloids. Analysis showed that the MAA segments selectively populate the area around the magnetic nanocrystallites, while the poly(ethylene glycol)-grafted chains are arranged as protrusions, pointing towards the aqueous environment. These nanocarriers are screened at various pHs and in highly salted media by light scattering and electrokinetic measurements. According to the results, their stability is dramatically enhanced, as compared to uncoated nanocrystallites, owing to the presence of the external protective PEG canopy. The nanocarriers are also endowed with bio-repellent properties, as evidenced by stability assays using human blood plasma as the medium.

Crystallographic studies on two bioisosteric analogues, N-acetyl-beta-D-glucopyranosylamine and N-trifluoroacetyl-beta-D-glucopyranosylamine, potent inhibitors of muscle glycogen phosphorylase.

Structure-based inhibitor design has led to the discovery of a number of potent inhibitors of glycogen phosphorylase b (GPb), N-acyl derivatives of beta-D-glucopyranosylamine, that bind at the catalytic site of the enzyme. The first good inhibitor in this class of compounds, N-acetyl-beta-D-glucopyranosylamine (NAG) (K(i) = 32 microM), has been previously characterized by biochemical, biological and crystallographic experiments at 2.3 angstroms resolution. Bioisosteric replacement of the acetyl group by trifluoroacetyl group resulted in an inhibitor, N-trifluoroacetyl-beta-D-glucopyranosylamine (NFAG), with a K(i) = 75 microM. To elucidate the structural basis of its reduced potency, we determined the ligand structure in complex with GPb at 1.8 angstroms resolution. To compare the binding mode of N-trifluoroacetyl derivative with that of the lead molecule, we also determined the structure of GPb-NAG complex at a higher resolution (1.9 angstroms). NFAG can be accommodated in the catalytic site of T-state GPb at approximately the same position as that of NAG and stabilize the T-state conformation of the 280 s loop by making several favourable contacts to Asn284 of this loop. The difference observed in the K(i) values of the two analogues can be interpreted in terms of subtle conformational changes of protein residues and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interaction, and desolvation effects.

Hypertrophic and keloidal scars: an approach to polytherapy.

BACKGROUND: Cryotherapy and intralesional corticosteroids have been used separately or in combination as a treatment for hypertrophic and keloidal scars. The addition of silicone gel to the treatment schedule might be of interest. METHODS: Twenty patients with hypertrophic and keloidal scars received two 15-s cycles (in total 30 s) of cryotherapy treatments at every session (once monthly for 12 months) with intralesional injections of trimcinolone acetonide 0.1% (10-40 mg/mL, once monthly for 3 months). Topical application of silicone gel was added three times daily (for 12 months). The control group included 10 patients who received treatment with silicone sheeting. RESULTS: After 1 year there was improvement in all the parameters studied, especially in terms of symptoms, cosmetic appearance and associated signs (P < 0.0001) compared to baseline and compared to the control group. CONCLUSION: Our study suggests that polytherapy may be an effective tool in the therapy of hypertrophic and keloidal scars.