An immunodominant La/SSB autoantibody proteome derives from public clonotypes

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.The La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren’s Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3- 43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigendriven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein–RNA complexes are mediated by public sets of autoreactive B cell clonotypes.This work was supported by an Australian National Health and Medical Research Council grant 1041900 to T. P. Gordon and T. K. Chataway

Effects of Three Modest Levels of Proximal Loading on Marathon Pace Running Economy

International Journal of Exercise Science 13(7): 1120-1131, 2020. This study examined the effect of modest increases in proximal body mass on running economy expressed as metabolic cost (MC). External loads of 1.6 (L), 2.4 (M), and 3.2 kg (H) were added to the anterior and posterior torso region of male (n = 18) and female (n = 18) runners using a double-layered compression garment with gel inserts. MC was evaluated using stoichiometry equations of data collected via indirect calorimetry. Data was collected during four, 5-min running bouts at marathon pace for the 3 load levels and an unloaded state (CON). When data from both sexes were combined, MC for CON (13.2 ± 2.7) was lower (p \u3c 0.05) versus L (13.5 ± 2.6), M (13.6 ± 2.6), and H (13.7 ± 2.6 kcal/min), but L did not differ from CON when data was analyzed for each sex. Male runners exhibited stepped increases in MC across loads and a weak-moderate relationship (r = 0.37; p \u3c 0.01) between percentage change in absolute MC and increased percent body mass. A prediction model for MC (∆% kcal/min = 0.98(∆% body mass) – 0.91; SEE = ± 2.5%) was developed. For female runners, L increased MC by ~3.5% above CON, but no differentiation was found among L, M, and H, limiting the development of a prediction equation for females. Modest increases in body mass can produce detectable and potentially important levels of running economy impairment, but the relationship between changes in body mass and RE are complex, particularly in regards to sex

Foundations of Translational Ecology

Ecologists who specialize in translational ecology (TE) seek to link ecological knowledge to decision making by integrating ecological science with the full complement of social dimensions that underlie today\u27s complex environmental issues. TE is motivated by a search for outcomes that directly serve the needs of natural resource managers and decision makers. This objective distinguishes it from both basic and applied ecological research and, as a practice, it deliberately extends research beyond theory or opportunistic applications. TE is uniquely positioned to address complex issues through interdisciplinary team approaches and integrated scientist–practitioner partnerships. The creativity and context-specific knowledge of resource managers, practitioners, and decision makers inform and enrich the scientific process and help shape use-driven, actionable science. Moreover, addressing research questions that arise from on-the-ground management issues – as opposed to the top-down or expert-oriented perspectives of traditional science – can foster the high levels of trust and commitment that are critical for long-term, sustained engagement between partners

Complete Genome Sequences of Chop, DelRio, and GrandSlam, Three Gordonia Phages Isolated from Soil in Central Arkansas

Chop, DelRio, and GrandSlam are phage with a Siphoviridae morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage

Taking the steps towards sustainable livestock: our multidisciplinary global farm platform journey

Implications The Global Farm Platform was conceived and established to explore multidisciplinary strategies for optimising the sustainability of ruminant livestock systems around the world. International sustainability issues are common, but the solutions are often region-specific; therefore, our farms, situated across all major agroclimatic zones, are a unique resource worldwide. Each farm is following ?steps to sustainable livestock? to improve their production system(s), thereby developing robust metrics to progress economic, environmental and social viability. The consortium works collaboratively to improve the sustainability of ruminants, which we argue are a vital component of global food systems, delivering both human and planetary health