Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Amaranth Productivity and Nutrient Composition in Central Georgia

Amaranth (Amaranthus spp.) may have potential as a forage for summer grazing in the southeastern United States (US). Six accessions of amaranth were harvested at bud stage in two successive growing seasons to evaluate growth characteristics, yield, and forage quality parameters. The accessions, three genotypes of A. tricolor (Hinchoy VL, RRC-701, RRC-1186) and one each of A. hybridus (RRC-843), A. cruentus (RRC-1034), and A. dubius (RRC-1186) were evaluated in 1994 and 1995 on a Dothan sandy loam (fine loamy, siliceous, thermic, Plinthic Paleudult) soil at the Fort Valley State University Research Station, Fort Valley, Georgia. The plots were planted in mid- June in each year as a randomized complete block with four replications. Plants were harvested approximately 40 d after germination. Plant height and total dry matter (DM) yield determinations were made at harvest. Percentage leaf and stem were determined by hand separation of 5 randomly selected plants from each plot. Leaf material for the 1994 growing season was analyzed for neutral detergent fiber (NDF), acid detergent fiber (ADF), and crude protein (CP) content. Protein content ranged from 240-260 g/kg, while NDF and ADF ranged from 523-587 g/kg and 187-293 g/kg, respectively. The accessions ranged in height from 41-74 cm and total DM and leaf DM yield from 0.83-1.30 Mg/ha and 0.52-0.79 Mg/ha, respectively. All the accessions were over 50% leaf. With adequate yields and high leaf protein, amaranth has potential as a summer forage crop for livestock grazing in the southeastern US

Police Criminal Charging Decisions: An Examination of Post-Arrest Decision-Making

Scholars have encouraged studies of police decision-making to move beyond the arrest decision into research that broadens the understanding of police behavior. The criminal charge placed by officers against offenders is largely an untouched area of study. Examining criminal charging decisions goes beyond simple dichotomous decisions, such as arrest, but instead explores the area of police leniency or punitiveness. Randomly constructed vignettes describing a domestic violence incident were given to officers from four agencies. Officers indicated the criminal charges they would likely list against an offender if they were to make an arrest. Serious criminal charges were often supported by additional, but less serious, charges. Victim injury and an uncooperative offender were related to the decision to charge a misdemeanor offense. There was a significant negative relationship between the number of charges listed and more experienced officers and officers working in smaller agencies. The implications of this study and directions for future research are discussed

Tomographic X‐ray scattering based on invariant reconstruction: analysis of the 3D nanostructure of bovine bone

Small-angle X-ray scattering (SAXS) is an effective characterization technique for multi-phase nanocomposites. The structural complexity and heterogeneity of biological materials require the development of new techniques for the 3D characterization of their hierarchical structures. Emerging SAXS tomographic methods allow reconstruction of the 3D scattering pattern in each voxel but are costly in terms of synchrotron measurement time and computer time. To address this problem, an approach has been developed based on the reconstruction of SAXS invariants to allow for fast 3D characterization of nanostructured inhomogeneous materials. SAXS invariants are scalars replacing the 3D scattering patterns in each voxel, thus simplifying the 6D reconstruction problem to several 3D ones. Standard procedures for tomographic reconstruction can be directly adapted for this problem. The procedure is demonstrated by determining the distribution of the nanometric bone mineral particle thickness (T parameter) throughout a macroscopic 3D volume of bovine cortical bone. The T parameter maps display spatial patterns of particle thickness in fibrolamellar bone units. Spatial correlation between the mineral nano­structure and microscopic features reveals that the mineral particles are particularly thin in the vicinity of vascular channels

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Preference of Goats for Cool-Season Annual Clovers in the Southern United States

In the southern U.S.A., annual clovers provide high-quality winter and spring grazing for beef cattle and sheep. New Zealand data on white clover (Trifolium repens L.) suggests that goats do not prefer this plant as much as sheep (Clark et al., 1982) but little data are available on willingness of goats to consume different clover types in the USA

Spinodal-assisted crystallization in polymer melts

Recent experiments in some polymer melts quenched below the melting temperature have reported spinodal kinetics in small-angle x-ray scattering before the emergence of a crystalline structure. To explain these observations we propose that the coupling between density and chain conformation induces a liquid-liquid binodal within the equilibrium liquid-crystalline solid coexistence region. A simple phenomenological theory is developed to illustrate this idea, and several experimentally testable consequences are discussed. Shear is shown to enhance the kinetic role of the hidden binodal

Concentration and Bioactivity of Condensed Tannins and Total Phenolics of \u3cem\u3eLespedeza\u3c/em\u3e Species From a Germplasm Collection

Interest in ‘AU-Grazer’ sericea lespedeza (Lespedeza cuneata) as an anti-parasitic bioactive forage has been growing in the United States, but the concentration and bioactivity of tannins and other phenolics from additional accessions of L. cuneata, as well as other Lespedeza species, have not been evaluated. A study was completed to determine the concentration of extractable condensed tannins (ECT), total CT (TCT), total phenolics (TP), and protein-precipitable phenolics (PPP) of 32 accessions of L. cuneata and 16 additional Lespedeza species from a germplasm collection. The plants were established in small pots in a greenhouse and then transplanted into small field plots at the Fort Valley State University Agricultural Research Station in Georgia. Once established in the field, samples from each plot were collected, freeze-dried, and ground for analysis. The ECT and TCT for L. cuneata accessions averaged 6.6 ± 1.4% and 9.1 ± 1.8%, respectively, while TP were 114.8 ± 33.2 mg/g plant material and PPP averaged 81.5 ± 25.3 mg binding CT/g plant material. For other Lespedeza species, ECT ranged from 3.7 ± 1.3 (L. striate) to 8.8 ± 1.3 (L. frutescens) and TCT from 6.0 ± 0.5 (L. japonica) to 10.8 ± 1.3 (L. frutescens). Total phenolics ranged from 45.3 ± 24.0 (L. striate) to 185.8 ± 43.9 (L. virgata), and PPP from 22.1 ± 71 (L. tomentosa) to 89.0 ± 23.6 (L. virginica). All Lespedeza species evaluated in this study had relatively high levels of CT, with several species as high or higher in TP and PPP (bioactivity) than L. cuneata, suggesting potential increased use of these plants as nutraceutical forages for animals

Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases