(Table 2) Oxygen and carbon isotope composition of planktonic foraminiferal species from DSDP Holes 93-603B and 93-604, and one benthic species from Hole 93-604

Holes 603C and 604 of DSDP Leg 93 were drilled on the western Atlantic continental rise at water depths of 4633 m and 2364 m, respectively. In Hole 603C, a nearly continuous, undisturbed, and complete section of Pliocene and lower Pleistocene sediments was recovered by hydraulic piston coring; in Hole 604, a section of uppermost Miocene to Pleistocene sediments was incompletely recovered by rotary coring. In order to reconstruct the Pliocene and Pleistocene history of isotopic variations, 139 oxygen and carbon isotope values were determined for planktonic and monospecific benthic foraminifer samples from these holes. Large parts of the Pleistocene history could not, however, be documented because sample intervals were large and sediments at Site 604 were redeposited. Time correlation is based on magnetostratigraphic (Hole 603C) and micropaleontologic (Hole 603C, Site 604) interpretation. Stable isotope analyses were carried out on the planktonic foraminiferal species Globigerinoides ruber, G. obliquus, and Globorotalia inflata from Hole 603C (48 analyses) and from Site 604 (48 analyses); at Site 604, the benthic foraminifer Uvigerina peregrina (43 analyses) was also studied through the section. Age calibration for Hole 603C is based on the magnetostratigraphy of Canninga et al. (1987; doi:10.2973/dsdp.proc.93.130.1987), which uses the time scale of Lowrie and Alvarez (1981).

Pliocene-Pleistocene biostratigraphic datums of ODP Site 184-1148

Based on the stable isotopic analysis of planktonic and benthic foraminifers from Ocean Drilling Program Core 1148 of the northern South China Sea (SCS), Pliocene-Pleistocene isotope stratigraphy and events have been reconstructed. The benthic foraminiferal delta18O record shows that the Pacific intermediate water had a greater influence upon the SCS or the Pacific deep water above ~2600 m was warmer before ~3.2Ma than at present. After that, the benthic delta18O conspicuously increased during the ~3.2-2.5 Ma period, in correspondence to the formation of the Northern Hemisphere ice sheet, whereas the planktonic delta18O signal suggests a stepwise overall decrease of sea surface temperature during the ~2.2-0.9 Ma period. Compared to the equatorial Pacific records, the decrease in planktonic (Globigerinoides ruber) delta13C during the ~3.2-2.2 Ma period is particularly striking, suggesting that fertility of surface water increased noticeably. According to the modern delta13C distribution of G. ruber in the northern SCS, it is inferred that the East Asian winter monsoon strengthened during this interval. Afterwards, there were several conspicuous decreases of G. ruber delta13C at ~1.7, 1.3, 0.9, 0.45 and 0.15 Ma BP, that is, about every 0.4 Ma, suggesting that the East Asian winter monsoon became episodically stronger. This is confirmed by changes in relative abundance of planktonic foraminifer species Neogloboquadrina dutertrei, a typical East Asian winter monsoon proxy. The deepwater delta13C of the SCS is close to that of the Pacific, but lighter than that of the Atlantic, implying that the pattern of deep water originating mainly from the Atlantic and through the Pacific entering the SCS existed at least since the early Pliocene. After 1.4 Ma, the benthic delta13C signal decreased conspicuously but with a periodicity of ~100 ka, suggesting that the deep-water ventilation of the SCS was reduced, probably corresponding to a decrease of the North Atlantic Deep Water and/or further isolation of the SCS deep basin from the Pacific during glaciations.

Susceptibility measurements at Gubbio sections

The complex interplay between extraterrestrial events and earth-bound processes that triggered one of the greatest biological crises of the Phanerozoic requires a high resolution timescale. Detailed magnetic susceptibility measurements at the Contessa Highway and Bottaccione sections (Italy) span the Cretaceous-Paleogene boundary and reveal clear orbital signatures in the sedimentary record. Identification of precession and 405 kyr eccentricity cycles allows an estimate of 324+/-40 kyr for the duration of the Maastrichtian part of Chron C29r. We present in the same high resolution time frame sites in Spain and the North and South Atlantic and bio-horizons, biotic changes, stable isotopic excursions and the decrease in Osmium isotopes recorded in these sections. The onset of 187 Os/ 188 Os decrease coincides with the d13 C negative excursion K-PgE1, thus suggesting a first pulse in Deccan volcanism at 66.64 Ma. The K-PgE3 d13 C negative excursion is possibly the expression of a second pulse at 66.26 Ma. Late Maastrichtian d13 C negative excursions are of low intensity and span durations of one to two eccentricity cycles, whereas early Danian excursions are brief (about 30 kyr) and acute. In Biotic response to late Maastrichtian perturbations occurred with a delay of ca. 200 kyr after the beginning of K-PgE1 shortly before K-PgE3. The biotic perturbation could be thus either a delayed response to K-PgE1, or a direct response to K-PgE3, and possibly, a threshold response to the stepwise buildup of CO2 atmospheric injections. No delay is evident in response to early Danian hyperthermal events. These differences suggest that short-lived, volcanically-derived environmental perturbations were buffered within the stable late Maastrichtian oceanic realm whereas they were amplified by the more sensitive and highly disturbed early Danian oceanic ecosystem.

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Ecosystem responses to hydrologic change and mechanisms of nitrogen sequestration in seasonally flooded tree islands of the southern Everglades

In the Florida Everglades, tree islands are conspicuous heterogeneous elements in a complex wetland landscape. I investigated the effects of increased freshwater flow in southern Everglades seasonally flooded tree islands, and characterized biogeochemical interactions among tree islands and the marsh landscape matrix, specifically examining hydrologic flows of nitrogen (N), and landscape N sequestration capacity. I utilized ecological trajectories of key ecosystem variables to differentiate effects of increased sheetflow and hydroperiod. I utilized stable isotope analyses and nutrient content of tree island ecosystem components to test the hypothesis that key processes in tree island nitrogen cycling would favor ecosystem N sequestration. I combined estimates of tree island ecosystem N standing stocks and fluxes, soil and litter N transformation rates, and hydrologic inputs of N to quantify the net sequestration of N by a seasonally flooded tree island. ^ Results show that increased freshwater flow to seasonally flooded tree islands promoted ecosystem oligotrophy, whereas reduced flows allowed some plant species to cycle P less efficiently. As oligotrophy is a defining parameter of Everglades wetlands, and likely promotes belowground production and peat development, reintroducing freshwater flow from an upstream canal had a favorable effect on ecosystem dynamics of tree islands in the study area. Important factors influencing the stable isotopic composition of nitrogen and carbon were: (1) a contribution to soil N by soil invertebrates, animal excrement, and microbes, (2) a possible NO3 source from an upstream canal and an "open" ecosystem N cycle, and (3) greater availability of phosphorus in tree islands relative to the marsh landscape, suggesting that tree island N cycling favors N sequestration. Hydrologic sources of N were dominated by surface water loads of NO3- and NH 4+, and an important soil N transformation promoting the net loss of surface water DIN was nitrate immobilization associated with soils and surficial leaf litter. The net inorganic N sequestration capacity of a seasonally flooded tree island was 50 g yr-1 m -2. Thus, tree islands likely have an important function in landscape sequestration of inorganic N, and may reduce significant anthropogenic N loads to downstream coastal systems. ^

Origin, transport and fate of organic matter in Florida Bay: A biomarker record of historical environmental changes

The Everglades are undergoing the world largest wetland restoration project with the aim of returning this system to hydrological conditions in place prior to anthropogenic modifications. Therefore, it is essential to know what these pristine conditions were. In this work, molecular marker (biomarker) distributions and carbon stable isotopic signatures in sediment samples were employed to assess historical environmental changes in Florida Bay over approximately the last 4000 years. Two biomarkers of terrestrial plants, particularly for mangroves (taraxerol and C29 n-alkane), combined with two seagrass proxies (the Paq and the C25/C 27 n-alkan-2-one ratio) revealed a sedimentary environmental shift from freshwater marshes to mangrove swamps and then to seagrass dominated marine ecosystems, likely as a result of sea-level rise in Florida Bay since the Holocene. The maximum values for the Paq and the C 25/C27 n-alkan-2-ones occurred during the 20th century, suggesting that the greatest abundance of seagrass cover is a recent rather than a historical, long-term phenomenon. The greater oscillation in frequency and amplitude for the biomarkers after 1900 potentially reflects an ecosystem under increasing anthropogenic stress. Several algal biomarkers such as C20 highly branched isoprenoids (HBIs), C 25 HBIs and dinosterol indicative of cyanobacteria, diatom and dinoflagellate organic matter inputs respectively, increased dramatically in the latter part of the 20th century and were attributed to recent anthropogenic changes in Florida Bay. ^ The highlight of this work is the development of HBIs as paleo-proxies. As biomarkers of diatoms, the C25 HBIs in the core from the central bay displayed the highest concentration at mid depth, reflecting strong historical inputs of diatom-derived sedimentary OM during that period. In fact, the depth profile of C25 HBIs coincided quite well with historical variations in diatom abundance and variations in diatom species composition in central Florida Bay based on the results of fossil diatom species analysis by microscopy. This study provides evidence that some C25 HBIs can be applied as biomarkers for certain diatom inputs in paleoenvironmental studies. The sources of C20 and C30 HBIs and their potential applicability as paleo-proxies were also investigated and their sources assessed based on their δ13C distributions. ^

Habitat use and foraging ecology of a batoid community in Shark Bay, Western Australia

Worldwide declines in populations of large elasmobranchs and the potential cascading effects on marine ecosystems have garnered considerable attention. Far less appreciated are the potential ecological impacts of changes in abundances of small to medium bodied elasmobranchs mesopredators. Crucial to elucidating the role of these elasmobranchs is an understanding of their habitat use and foraging ecology in pristine conditions. I investigated the trophic interactions and factors driving spatiotemporal variation in abundances of elasmobranch mesopredators in the relatively pristine ecosystem of Shark Bay, Australia. First, I describe the species composition and seasonal habitat use patterns of elasmobranch mesopredator on the sandflats of Shark Bay. Juvenile batoids dominated this diverse community and were extremely abundant in nearshore microhabitats during the warm season. Stomach content analysis and stable isotopic analysis revealed that there is a large degree of dietary overlap between common batoid species. Crustaceans, which tend to be found in seagrass habitats, dominated diets. Despite isotopic differences between many species, overlap in isotopic niche space was high and there was some degree of individual specialization. I then, investigated the importance of abiotic (temperature and water depth) and biotic (prey and predator abundance) factors in shaping batoid habitat use. Batoids were most abundant and tended to rest in shallow nearshore waters when temperatures were high. This pattern coincides with periods of large shark abundance suggesting batoids were seeking refuge from predators rather than selecting optimal temperatures. Finally, I used acoustic telemetry to examine batoid residency and diel use of the sandflats. Individual batoids were present on the sandflats during both the warm and cold seasons and throughout the diel cycle, suggesting lower sandflat densities during the cold season were a result of habitat shifts rather than migration out of Shark Bay. Combined, habitat use and dietary results suggest that batoids have the potential to seasonally impact sandflat dynamics through their presence, although foraging may be limited on the sandflats. Interestingly, my results suggest that elasmobranch mesopredators in pristine ecosystems probably are not regulated by food supply and their habitat use patterns and perhaps ecosystem impacts may be influenced by their predators.