Carbon isotope ratios of soil organic matter and their use in assessing community composition changes in Curlew Valley,Utah

Summary Stable carbon isotope ratios of roots and soil organic matter were measured in Curlew Valley, Utah to determine if changes in the relative dominance of two shrub species had occurred in this salt-desert community. Measurements were made on soil cores along transects stretching from monospecific stands of Ceratoides lanata, a C₃ shrub, to monospecific stands of Atriplex confertifolia, a C₄ shrub. ¹³C values of roots and soil organic matter under Ceratoides cover appeared to be in equilibrium with the current plant community. By contrast, ¹³C values of roots and soils under Atriplex portions of the transects were more negative than would be expected for a C₄-dominated community. These results indicate that a change in relative C₃/C₄ dominance has occurred, and suggest that the C₄ shrub Atriplex confertifolia is increasing in importance in this salt-desert community.     

Water use by woody plants on contrasting soils in a savanna parkland: assessment with δ2H and δ18O

In savanna parklands of southern Texas, patches of grassland and discrete clusters of small trees and shrubs occur on sandy loam surface soils underlain by an argillic horizon (claypan) at 40 cm. Large trees and shrubs in groves occur on deep (2 m) sandy loam soils without an argillic horizon. 2H and 18O of rainfall, groundwater, and soil and plant water were measured to: (1) determine if coexistence in woody patches occurs via vertical stratification of soil water uptake; (2) document differences in plant water acquisition on contrasting soil types; and (3) evaluate recharge and evaporative losses of soil moisture from grassland vs. wooded landscape elements. Groundwater was isotopically similar to weighted rainfall, suggesting local recharge at this site. Linear regressions of soil water 2H on 18O yielded slopes less than the meteoric water line, indicating significant evaporative losses of soil moisture in all landscape elements. Interspecific differences in root density distribution were significant; some woody species had roots well below 1.6 m, while others had few roots below 0.8 m. 2H and 18O values of stem water from all plants in groves were lower than those of soil water in the upper 1.5 m of the profile, suggesting all species obtained their water from depths >1.5 m. Deep roots of trees and shrubs at this savanna parkland site thus appeared to have a functional significance that was not revealed by biomass or density determinations. Root densities of species in discrete clusters (claypan present) were typically greater than those of the same species in groves (claypan absent), especially in the upper 80 cm of the soil profile. Consistent with rooting profiles, 2H and 18O values of plant water indicated that trees and shrubs in discrete clusters with fine- textured subsoils obtained most of their water at depths <1.5 m. As with groves, there was no indication of water resource partitioning between species. In summary, we saw no isotopic evidence that co- occurring woody plants at this savanna parkland site were partitioning soil moisture vertically during late summer/early fall, despite marked differences in their root density distributions. This supports other lines of evidence which indicate that species interactions in tree/shrub clumps are competitive, and that species composition is therefore unstable in those landscape elements.     

Binding-site identification and genotypic profiling of hepatitis C virus polymerase inhibitors

The search for hepatitis C virus polymerase inhibitors has resulted in the identification of several nonnucleoside binding pockets. The shape and nature of these binding sites differ across and even within diverse hepatitis C virus genotypes. These differences confront antiviral drug discovery with the challenge of finding compounds that are capable of inhibition in variable binding pockets. To address this, we have established a hepatitis C virus mutant and genotypic recombinant polymerase panel as a means of guiding medicinal chemistry through the elucidation of the site of action of novel inhibitors and profiling against genotypes. Using a genotype 1b backbone, we demonstrate that the recombinant P495L, M423T, M414T, and S282T mutant enzymes can be used to identify the binding site of an acyl pyrrolidine analog. We assess the inhibitory activity of this analog and other nonnucleoside inhibitors with our panel of enzyme isolates generated from clinical sera representing genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a.     

Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Whole-body protein metabolism in lactating and nonlactating women

The adaptive responses of body protein metabolism to lactation were characterized in women at 1, 5, and 12 mo postpartum and in nulliparous controls during a controlled diet of measured protein and energy intakes by nitrogen balance, a constant infusion of [13C]bicarbonate, and a primed constant infusion of [1-13C]leucine and [alpha-15N]-lysine. Dietary energy intakes in the lactating women were 27% greater than those in the nulliparous controls. Despite these differences, lactating women had significantly lower nitrogen balances compared with the nonlactating women (-4.0 +/- 37.8 vs. +44.7 +/- 30.8 mg.kg-1.day-1). No significant differences in amino acid flux, oxidation, or incorporation into protein were detected during fasting conditions in the two groups of women. However, significantly positive associations were noted between dietary intakes and the variables of protein metabolism in the lactating women. A more complete understanding of the mechanisms that regulate the disposition of dietary nutrients into maternal body stores or milk production will enhance the determination of nutrient requirements in lactating women.     

Vegetation dynamics in a Quercus‐Juniperus savanna: An isotopic assessment

Abstract. Woody plants are increasing in many grassland and savanna ecosystems around the world. As a case in point, the Edwards Plateau of Texas, USA, is a vast region (93 000 km²) in which rapid woody encroachment appears to be occurring. The native vegetation (prior to the Anglo‐European settlement 150–200 yr ago) and the biogeochemical consequences of woody encroachment in this region, however, are poorly understood. To assess these matters we measured plant and soil δ¹³C, soil organic C and soil N content from grasslands and two important woody patch types (mature Quercus virginiana clusters and Juniperus ashei woodlands) in this region. Soil δ¹³C values showed that relative productivity of C₃ species has increased in grassland and both woody habitats in recent times. δ¹³C of SOC in grasslands and Q. virginiana clusters increased with depth from the litter layer to 30 cm (grasslands =?21 to ?13‰Q. virginiana clusters =?27 to ?17‰) and were significantly different between habitats at all depths, indicating that Q. virginiana has been a long‐term component of the landscape. In J. ashei woodlands, soil δ¹³C values (at 20–30 cm depth) near the woodland edge (‐13‰) converged with those of an adjacent grassland (‐13‰) while those from the woodland interior (‐15‰) remained distinct, indicating that the woodland has been present for many years but has recently expanded. Concentrations and densities of SOC and total N were generally greater in woody patches than in grasslands. However, differences in the amount of SOC and N stored beneath the two woody patch types indicates that C and N sequestration potentials are species dependent.     

Spatial variation of the stable nitrogen isotope ratio of woody plants along a topoedaphic gradient in a subtropical savanna

Variation in the stable N isotope ratio (δ¹⁵N) of plants and soils often reflects the influence of environment on the N cycle. We measured leaf δ¹⁵N and N concentration ([N]) on all individuals of Prosopis glandulosa (deciduous tree legume), Condalia hookeri (evergreen shrub), and Zanthoxylum fagara (evergreen shrub) present within a belt transect 308 m long × 12 m wide in a subtropical savanna ecosystem in southern Texas, USA in April and August 2005. Soil texture, gravimetric water content (GWC), total N and δ¹⁵N were also measured along the transect. At the landscape scale, leaf δ¹⁵N was negatively related to elevation for all the three species along this topoedaphic sequence. Changes in soil δ¹⁵N, total N, and GWC appeared to contribute to this spatial pattern of leaf δ¹⁵N. In lower portions of the landscape, greater soil N availability and GWC are associated with relatively high rates of both N mineralization and nitrification. Both soil δ¹⁵N and leaf [N] were positively correlated with leaf δ¹⁵N of non-N₂ fixing plants. Leaf δ¹⁵N of P. glandulosa, an N₂-fixing legume, did not correlate with leaf [N]; the δ¹⁵N of P. glandulosa’s leaves were closer to atmospheric N₂ and significantly lower than those of C. hookeri and Z. fagara. Additionally, at smaller spatial scales, a proximity index (which reflected the density and distance of surrounding P. glandulosa trees) was negatively correlated with leaf δ¹⁵N of C. hookeri and Z. fagara, indicating the N₂-fixing P. glandulosa may be important to the N nutrition of nearby non-N₂-fixing species. Our results indicate plant ¹⁵N natural abundance can reflect the extent of N retention and help us better understand N dynamics and plant-soil interactions at ecosystem and landscape scales.     

Targeting the cell cycle in breast cancer: towards the next phase

Deregulation of the cell cycle is a hallmark of cancer that enables limitless cell division. To support this malignant phenotype, cells acquire molecular alterations that abrogate or bypass control mechanisms in signaling pathways and cellular checkpoints that normally function to prevent genomic instability and uncontrolled cell proliferation. Consequently, therapeutic targeting of the cell cycle has long been viewed as a promising anti-cancer strategy. Until recently, attempts to target the cell cycle for cancer therapy using selective inhibitors have proven unsuccessful due to intolerable toxicities and a lack of target specificity. However, improvements in our understanding of malignant cell-specific vulnerabilities has revealed a therapeutic window for preferential targeting of the cell cycle in cancer cells, and has led to the development of agents now in the clinic. In this review, we discuss the latest generation of cell cycle targeting anti-cancer agents for breast cancer, including approved CDK4/6 inhibitors, and investigational TTK and PLK4 inhibitors that are currently in clinical trials. In recognition of the emerging population of ER+ breast cancers with acquired resistance to CDK4/6 inhibitors we suggest new therapeutic avenues to treat these patients. We also offer our perspective on the direction of future research to address the problem of drug resistance, and discuss the mechanistic insights required for the successful implementation of these strategies.     

Contribution of flexible allocation priorities to herbivory tolerance in C4 perennial grasses: an evaluation with 13C labeling

The ability of plants to rapidly replace photosynthetic tissues following defoliation represents a resistance strategy referred to as herbivory tolerance. Rapid reprioritization of carbon allocation to regrowing shoots at the expense of roots following defoliation is a widely documented tolerance mechanism. An experiment was conducted in a controlled environment to test the hypothesis that herbivory-sensitive perennial grasses display less flexibility in reprioritizing carbon allocation in response to defoliation than do grasses possessing greater herbivory tolerance. An equivalent proportion of shoot biomass (60% dry weight) was removed from two C₄ perennial grasses recognized as herbivory-sensitive, Andropogon gerardii and Schizachyrium scoparium, and two C₄ perennial grasses recognized as herbivory-tolerant, Aristida purpurea and Bouteloua rigidiseta. Both defoliated and undefoliated plants were exposed to ¹³CO₂ for 30 min, five plants per species were harvested at 6, 72 and 168 h following labeling, and biomass was analyzed by isotope ratio mass spectrometry. The tallgrass, A. geraiddii, exhibited inflexible allocation priorities while the shortgrass, B. rigidiseta, exhibited flexible allocation priorities in response to defoliation which corresponded with their initial designations as herbivory-sensitive and herbivory-tolerant species, respectively. A. gerardii had the greatest percentage and concentration of ¹³C within roots and lowest percentage of ¹³C within regrowth of the four species evaluated. In contrast, B. rigidiseta had a greater percentage of ¹³C within regrowth than did A. gerardii, the greatest percentage of ¹³C within new leaves of defoliated plants, and the lowest concentration of ¹³C within roots follwing defoliation. Although both midgrasses, S. scoparium and A. purpurea, demonstrated flexible allocation priorities in response to defoliation, they were counter to those stated in the initial hypothesis. The concentration of ¹³C within new leaves of S. scoparium increased in response to a single defoliation while the percentage and concentration of ¹³C within roots was reduced. A. purpurea was the only species in which the percentate of ¹³C within new leaves decreased while the percentage of ¹³C within roots increased following defoliation. The most plausible alternative hypothesis to explain the inconsistency between the demonstrated responsiveness of allocation priorities to defoliation and the recognized herbivory resistance of S. scoparium and A. purpurea is that the relative ability of these species to avoid herbivory may make an equal or greater contribution to their overall herbivory resistance than does herbivory tolerance. Selective herbivory may contribute to S. scoparium's designation as a herbivorysensitive species even though it possesses flexible allocation priorities in response to defoliation. Alternatively, the recognized herbivory resistance of A. purpurea may be a consequence of infrequent and/or lenient herbivory associated with the expression of avoidance mechanisms, rather than the expression of tolerance mechanisms. A greater understanding of the relative contribution of tolerance and avoidance strategies of herbivory resistance are required to accurately interpret how herbivory influences plant function, competitive interactions, and species abundance in grazed communities.