David L. Fox

The Origins of C4 Grasslands: Integrating Evolutionary and Ecosystem Science

Grassland Emergence The evolution of the C4 photosynthetic pathway from the ancestral C3 pathway in grasses led to the establishment of grasslands in warm climates during the Late Miocene (8 to 3 million years ago). This was a major event in plant evolutionary history, and their high rates of foliage production sustained high levels of herbivore consumption. The past decade has seen significant advances in understanding C4 grassland ecosystem ecology, and now a wealth of data on the geological history of these ecosystems has accumulated and the phylogeny of grasses is much better known. Edwards et al. (p. 587) review this multidisciplinary research area and attempt to synthesize emerging knowledge about the evolution of grass species within the context of plant and ecosystem ecology. The evolution of grasses using C4 photosynthesis and their sudden rise to ecological dominance 3 to 8 million years ago is among the most dramatic examples of biome assembly in the geological record. A growing body of work suggests that the patterns and drivers of C4 grassland expansion were considerably more complex than originally assumed. Previous research has benefited substantially from dialog between geologists and ecologists, but current research must now integrate fully with phylogenetics. A synthesis of grass evolutionary biology with grassland ecosystem science will further our knowledge of the evolution of traits that promote dominance in grassland systems and will provide a new context in which to evaluate the relative importance of C4 photosynthesis in transforming ecosystems across large regions of Earth.

Tertiary history of C4 biomass in the Great Plains, USA

We use the carbon isotope composition of paleosols to reconstruct the history of C4 biomass on the Great Plains from ca. 23 to 1 Ma. The proportion of C4 biomass was uniform and moderate (12%‐34%) throughout the Miocene, increased between 6.4 and 4.0 Ma, and reached modern levels by 2.5 Ma. Ecological changes in Great Plains ungulates preceded the increase in C4 biomass. The contrasts in the paleosol and ungulate records may indicate initial development of C3 grasslands after the middle Miocene or a greater role for ecological interactions within communities in structuring ungulate faunas. Contrasts in paleosol records from different continents point to regional rather than global controls on the evolution of C4 grasslands.

Deciphering the role of Th17 cells in human disease

Since their identification in 2005, T helper (Th)17 cells have been proposed to play important roles in several human diseases, including various autoimmune conditions, allergy, the development and progression of tumors, and the acceptance or rejection of transplanted organs and bone marrow. Focusing on human studies, here we review recent developments regarding Th17 biology and function in each of these fields. Th17 cells actively participate in the pathogenesis of autoimmune disease, allergy and transplantation rejection. Th17 cells contribute to protective antitumor immunity in human epithelial malignancy, whereas Th17-associated cytokines may also be associated with tumor initiation and growth in the context of chronic inflammation and infection. Also discussed is how the in vivo plasticity of Th17 cells may be an important feature of Th17 cell biology in human disease.

Structural basis for RNA replication by the hepatitis C virus polymerase.

A view of the HCV polymerase at work More than 3% of the worlds population is infected with hepatitis C virus (HCV), a predisposing factor for life-threatening liver diseases such as cirrhosis and cancer. HCV encodes a polymerase called NS5B that catalyzes replication of the viral RNA genome. Drugs inhibiting NS5B have shown impressive antiviral activity in recent clinical trials. Appleby et al. (see the Perspective by Bressanelli) reveal the inner workings of HCV RNA replication by analyzing crystal structures of stalled NS5B polymerase ternary complexes during the initiation and elongation of RNA synthesis. They also define the way in which sofosbuvir, a drug with potent clinical efficacy, interacts with the NS5B active site. Science, this issue p. 771; see also p. 715 Crystal structures of hepatitis C virus RNA replication complexes reveal the molecular workings of the viral RNA polymerase. [Also see Perspective by Bressanelli] Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A β loop and a C-terminal membrane–anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3′ terminus, and vacate the active-site cavity during elongation. We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site.

Comment on the paleoenvironment of Ardipithecus ramidus.

White and colleagues (Research Articles, 2 October 2009, pp. 65–67 and www.sciencemag.org/ardipithecus) characterized the paleoenvironment of Ardipithecus ramidus at Aramis, Ethiopia, which they described as containing habitats ranging from woodland to forest patches. In contrast, we find the environmental context of Ar. ramidus at Aramis to be represented by what is commonly referred to as tree- or bush-savanna, with 25% or less woody canopy cover.

Membrane-Type I Matrix Metalloproteinase-Dependent Regulation of Rheumatoid Arthritis Synoviocyte Function

In rheumatoid arthritis, the coordinated expansion of the synoviocyte mass is coupled with a pathologic angiogenic response that leads to the destructive remodeling of articular as well as surrounding connective tissues. Although rheumatoid synoviocytes express a multiplicity of proteolytic enzymes, the primary effectors of cartilage, ligament, and tendon damage remain undefined. Herein, we demonstrate that human rheumatoid synoviocytes mobilize the membrane-anchored matrix metalloproteinase (MMP), membrane-type I MMP (MT1-MMP), to dissolve and invade type I and type II collagen-rich tissues. Though rheumatoid synoviocytes also express a series of secreted collagenases, these proteinases are ineffective in mediating collagenolytic activity in the presence of physiologic concentrations of plasma- or synovial fluid-derived antiproteinases. Furthermore, MT1-MMP not only directs the tissue-destructive properties of rheumatoid synoviocytes but also controls synoviocyte-initiated angiogenic responses in vivo. Together, these findings indentify MT1-MMP as a master regulator of the pathologic extracellular matrix remodeling that characterizes rheumatoid arthritis as well as the coupled angiogenic response that maintains the aggressive phenotype of the advancing pannus.

Stable Isotope Ecology of a Late Miocene Population of Gomphotherium productus (Mammalia, Proboscidea) from Port of Entry Pit, Oklahoma, USA

Abstract The stable carbon and oxygen isotope compositions of serial samples of enamel from tusks of Gomphotherium productus (Mammalia, Proboscidea) from Port of Entry Pit, Oklahoma (early Hemphillian North American Land Mammal Age, ca. 7.5 Ma), were measured to examine intra-annual and interannual variation. Sample series from each of six tusks spanned approximately one year of tusk growth. Carbon isotope compositions range from −11.3 to −9.2‰ (VPDB) and exhibit no pattern of seasonal variation, indicating the diet of gomphotheres at Port of Entry Pit was dominated by C3 vegetation throughout the year. Phosphate oxygen isotope composition (δ18Op) ranges from 18.9 to 22.2‰ (VSMOW); carbonate oxygen isotope composition (δ18Oc) ranges from 26.1 to 30.1‰ (VSMOW). None of the tusks exhibit seasonal variation in δ18O, and the average within-tusk range in δ18Op is 1.7‰. Neither the fluorine composition of the specimens nor the relationship between δ18Op and δ18Oc values from splits of the same samples suggest significant post-depositional alteration. The oxygen isotope data imply that Hemphillian meteoric water had δ18O values that are indistinguishable from modern values in the region today. However, because polar ice sheets were smaller and mean ocean water δ18O lower than present, the estimates of meteoric water composition from gomphothere tusk δ18Op are consistent with warmer mean annual temperatures during the Hemphillian. The within-tusk variations in δ18Op are consistent with similar or much reduced patterns of seasonal temperature variation in comparison to today, depending on air mass flow during the late Miocene. Alternative explanations include seasonal migratory behavior and reliance by the gomphotheres at Port of Entry Pit on sources of drinking water with relatively constant δ18O values.

Speleothem climate records from deep time? Exploring the potential with an example from the Permian

Speleothems are well-proven archives of terrestrial climate variation, recording mean temperature, rainfall, and surface vegetation data at subannual to millennial resolution. They also form within the generally stable environment of caves, and thus may remain remarkably well preserved for many millions of years and, most important, can be dated radiometrically to provide robust chronologies that do not rely on orbital tuning, ice-flow modeling, or estimates of sediment deposition rates. The recent adaptation of the U-Pb dating technique to speleothems has greatly extended their potential as paleoclimate recorders back into the more distant geological past, well beyond the ∼500 k.y. limit previously imposed by U-series techniques, but the opportunities presented by these new methods have yet to be fully explored. As an extreme example, here we report on samples recovered from Permian cave fills, the oldest radiometrically dated speleothems so far documented. Using state of the art analytical techniques it is possible to determine not only their age and state of preservation, but also to extract apparently nearly pristine climate proxy data. Armed with these methods, it now seems reasonable to apply the lessons learned from more recent speleothems to ancient materials, wherever they can be found, and of whatever age, to generate snapshots of paleoclimate that can be used to greatly refine the records preserved within the sediments and fossils of the time.

Pedogenic carbonate stable isotope record of environmental change during the Neogene in the southern Great Plains, southwest Kansas, USA: Carbon isotopes and the evolution of C4-dominated grasslands

Fossiliferous strata in the Meade Basin (southwest Kansas) preserve numerous superposed mammalian faunas and calcareous paleosols that range in age from the Clarendonian North American Land Mammal Age (NALMA; 12.0–9.0 Ma, early late Miocene) to the early Irvingtonian NALMA (ca. 2.5–ca. 1.0 Ma, early Pleistocene). Faunas from these sections document the evolution of the small mammal community of the modern grassland ecosystem of the region, and the stable isotope composition of paleosol carbonates provides a means by which the environmental context of the evolution of the modern ecosystem may be documented. We used the stable carbon isotope composition (δ 13 C relative to Vienna Peedee belemnite [VPDB]) of 194 pedogenic carbonates from 19 measured sections to reconstruct the history of C 4 grass abundance in the Meade Basin. Paleosol carbonate δ 13 C values reflect the proportion of C 3 (trees, shrubs, cool-climate grasses) and C 4 (warm-climate grasses) plants that grew in an ancient soil and provide a means with which to reconstruct past mammalian habitats. Paleosol carbonate δ 13 C values record a three-phase increase in the abundance of C 4 biomass during the Neogene in the Meade Basin. Late Miocene sections have mean δ 13 C values of −7.6‰ ± 0.90‰ (Clarendonian) and −6.5‰ ± 0.31‰ (Hemphillian NALMA, 9.0–4.9 Ma), consistent with 17% and 26% C 4 biomass, respectively. Miocene δ 13 C values from Meade are statistically identical to published δ 13 C values for Miocene paleosol carbonates elsewhere in the southern Great Plains, supporting the widespread presence of ∼20% C 4 biomass on average in the region throughout the Miocene. The abundance of C 4 biomass increased between the end of the Hemphillian section and the beginning of the early Blancan NALMA (5.0–3.0 Ma). Early and middle Blancan (3.0–2.5 Ma) carbonates have statistically identical δ 13 C values (−4.9‰ ± 0.90‰ and −5.0‰ ± 1.10‰, respectively), suggesting a stable ecosystem during the early Pliocene, although high δ 13 C variability in densely sampled intervals suggests a high degree of landscape-scale variation in C 4 abundance. The final phase, geochronologically controlled by two well-characterized ashes (Huckleberry Ridge, 2.10 Ma; Cerro Toledo B, 1.47–1.23 Ma) and magnetostratigraphy, is a trend to higher δ 13 C values from the late Blancan to early Irvingtonian (ca. 2.5–ca 1.0 Ma) from −4‰ at the base of the section to ∼1‰ at the top, corresponding to an increase from almost 50% to 65% C 4 biomass. The abundance of C 4 biomass first reaches modern levels for the region (78% ± 10.9%) around the level of the Cerro Toledo B ash, indicating that a modern-like grassland ecosystem first appeared in the region ca. 1.3 Ma, although δ 13 C values do not remain consistently high through the rest of the section.

Late Neogene and Early Quaternary Paleoenvironmental and Paleoclimatic Conditions in Southwestern Europe: Isotopic Analyses on Mammalian Taxa

Climatic and environmental shifts have had profound impacts on faunal and floral assemblages globally since the end of the Miocene. We explore the regional expression of these fluctuations in southwestern Europe by constructing long-term records (from ∼11.1 to 0.8 Ma, late Miocene–middle Pleistocene) of carbon and oxygen isotope variations in tooth enamel of different large herbivorous mammals from Spain. Isotopic differences among taxa illuminate differences in ecological niches. The δ13C values (relative to VPDB, mean −10.3±1.1‰; range −13.0 to −7.4‰) are consistent with consumption of C3 vegetation; C4 plants did not contribute significantly to the diets of the selected taxa. When averaged by time interval to examine secular trends, δ13C values increase at ∼9.5 Ma (MN9–MN10), probably related to the Middle Vallesian Crisis when there was a replacement of vegetation adapted to more humid conditions by vegetation adapted to drier and more seasonal conditions, and resulting in the disappearance of forested mammalian fauna. The mean δ13C value drops significantly at ∼4.2−3.7 Ma (MN14–MN15) during the Pliocene Warm Period, which brought more humid conditions to Europe, and returns to higher δ13C values from ∼2.6 Ma onwards (MN16), most likely reflecting more arid conditions as a consequence of the onset of the Northern Hemisphere glaciation. The most notable feature in oxygen isotope records (and mean annual temperature reconstructed from these records) is a gradual drop between MN13 and the middle Pleistocene (∼6.3−0.8 Ma) most likely due to cooling associated with Northern Hemisphere glaciation.