Oceanic mafic magmatism in the Siletz terrane, NW North America: Fragments of an Eocene oceanic plateau?

The Siletz terrane, a predominantly mafic accreted oceanic terrane, is located in the Cascadia Forearc region of Oregon, Washington and Vancouver Island. The terrane represents a late Paleocene – Eocene large igneous province that consists of pillow lavas, massive flows and intrusive sheets. Previously it has been proposed that the Siletz terrane represents either an accreted oceanic plateau, hotspot island chain, backarc basin, island arc, or a sequence of slab window volcanics. A province-wide geochemical reassessment of the terrane, including new high precision Sr-Pb-Nd-Hf isotope, has been used to assess the validity of the proposed tectonomagmatic models for the Siletz terrane. The trace element data show little evidence of crustal contamination, or an arc signature, and the samples have rare earth element (REE) patterns that are flat to light REE enriched. These features are similar to other oceanic plateaus such as the Ontong Java and the Caribbean. Initial isotope ratios range from 206Pb/204 Pb: 18.751 to 19.668, 207Pb/204Pb: 15.507–15.661, 207Pb/204Pb: 38.294–39.2128, 176Hf/177Hf: 0.28300–0.28316 (εHf: 9.0 to 14.5), 143Nd/144Nd: 0.51282–0.51299 (εNd: 5.0 to 8.1) and 87Sr/86Sr: 0.70302–0.70380. These data are consistent with a mantle source of the Siletz terrane that appears to have been heterogeneous and slightly enriched. The enriched signature has characteristics of both EM2 and HIMU components and this, combined with a calculated mantle potential temperature well above ambient mantle, indicates derivation of the Siletz magmatism from a mantle plume, possibly the Yellowstone Hotspot. We therefore conclude that the Siletz terrane represents an accreted oceanic plateau

SUMO chain formation is required for response to replication arrest in S. pombe

SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

RAD51 foci as a biomarker predictive of platinum chemotherapy response in ovarian cancer

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if \u3e10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P \u3c 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P \u3c 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P \u3c 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P \u3c 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P \u3c 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials

The relationship between early neural responses to emotional faces at age 3 and later autism and anxiety symptoms in adolescents with autism

Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14. Faster ERPs to neutral faces predicted greater ASD symptom improvement over time, lower ASD severity in adolescence, and lower anxiety in adolescence. Early individual differences in processing of emotional stimuli likely reflect a unique predictive contribution from social brain circuitry early in life

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Multi-institutional analysis of pancreatic adenocarcinoma demonstrating the effect of diabetes status on survival after resection

The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201