Development of rapid diagnostic techniques for idiopathic blindness in the American lobster, Homarus americanus, from eastern Long Island Sound

Idiopathic blindness is a condition that afflicts approximately 50% of the lobsters, Homarus americanus H. Milne-Edwards, 1837, in Long Island Sound (LIS). The condition occurs in lobsters from LIS and Narragansett Bay, but has lower prevalence levels in the Gulf of Maine. Grossly, the condition presents as patches of cloudy, gray-colored regions in the eyes of afflicted animals. Histologically, the ommatidia show signs of altered pigment distribution, necrosis of the optic nerves and rhabdoms, and hemocyte infiltration through the protective basement membrane separating the ommatidia from the optic nerves. Severe lesions show areas with necrotic ommatidia and nearly complete loss of the underlying associated optic nerves. We assessed a rapid, nondestructive, diagnostic technique for determining blindness in lobsters. We compared the use of an otolaryngoscope (o-scope) with stereomicroscopy on live, frozen, and histologically-fixed eyes. Live lobsters from Narragansett Bay, Rhode Island, and off southern Massachusetts were assessed with the o-scope. Right eyes were analyzed via standard histological procedures. Left eyes were frozen and stored at –80 °C, and later thawed and reassessed for blindness. The o-scope had good sensitivity and specificity in diagnosing blindness in the laboratory with good inter-observer comparisons among trained staff. Initial results indicate that the etiological agent of idiopathic blindness is present throughout a large portion of the sound, and that lobsters are probably continually exposed to it. The use of the o-scope as a diagnostic tool will help us better understand the distribution of idiopathic blindness in lobsters from the New England region

Degradation of biological macromolecules supports uncultured microbial populations in Guaymas Basin hydrothermal sediments

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Castro, S. P., Borton, M. A., Regan, K., de Angelis, I. H., Wrighton, K. C., Teske, A. P., Strous, M., & Ruff, S. E. Degradation of biological macromolecules supports uncultured microbial populations in Guaymas Basin hydrothermal sediments. Isme Journal. (2021), https://doi.org/10.1038/s41396-021-01026-5.Hydrothermal sediments contain large numbers of uncultured heterotrophic microbial lineages. Here, we amended Guaymas Basin sediments with proteins, polysaccharides, nucleic acids or lipids under different redox conditions and cultivated heterotrophic thermophiles with the genomic potential for macromolecule degradation. We reconstructed 20 metagenome-assembled genomes (MAGs) of uncultured lineages affiliating with known archaeal and bacterial phyla, including endospore-forming Bacilli and candidate phylum Marinisomatota. One Marinisomatota MAG had 35 different glycoside hydrolases often in multiple copies, seven extracellular CAZymes, six polysaccharide lyases, and multiple sugar transporters. This population has the potential to degrade a broad spectrum of polysaccharides including chitin, cellulose, pectin, alginate, chondroitin, and carrageenan. We also describe thermophiles affiliating with the genera Thermosyntropha, Thermovirga, and Kosmotoga with the capability to make a living on nucleic acids, lipids, or multiple macromolecule classes, respectively. Several populations seemed to lack extracellular enzyme machinery and thus likely scavenged oligo- or monomers (e.g., MAGs affiliating with Archaeoglobus) or metabolic products like hydrogen (e.g., MAGs affiliating with Thermodesulfobacterium or Desulforudaceae). The growth of methanogens or the production of methane was not observed in any condition, indicating that the tested macromolecules are not degraded into substrates for methanogenesis in hydrothermal sediments. We provide new insights into the niches, and genomes of microorganisms that actively degrade abundant necromass macromolecules under oxic, sulfate-reducing, and fermentative thermophilic conditions. These findings improve our understanding of the carbon flow across trophic levels and indicate how primary produced biomass sustains complex and productive ecosystems.We are grateful to the captain and crew of the R/V Atlantis AT37-06 as well as the crew of the human occupied vehicle Alvin for their tireless support. Sampling at Guaymas Basin was supported by NSF (OCE-1357238)

Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas

AbstractReduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73% of patients having partial responses or stable disease. EPOCH-F depleted host CD4+ T cells from a median of 235 cells/μL to 56 cells/μL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT. © 2003 American Society for Blood and Marrow TransplantationBiology of Blood and Marrow Transplantation 9:162-169 (2003

Spin Relaxation in Single Layer Graphene with Tunable Mobility

Graphene is an attractive material for spintronics due to theoretical predictions of long spin lifetimes arising from low spin-orbit and hyperfine couplings. In experiments, however, spin lifetimes in single layer graphene (SLG) measured via Hanle effects are much shorter than expected theoretically. Thus, the origin of spin relaxation in SLG is a major issue for graphene spintronics. Despite extensive theoretical and experimental work addressing this question, there is still little clarity on the microscopic origin of spin relaxation. By using organic ligand-bound nanoparticles as charge reservoirs to tune mobility between 2700 and 12000 cm2/Vs, we successfully isolate the effect of charged impurity scattering on spin relaxation in SLG. Our results demonstrate that while charged impurities can greatly affect mobility, the spin lifetimes are not affected by charged impurity scattering.Comment: 13 pages, 5 figure

Evaluation of different recall periods for the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Aims—The U.S. National Cancer Institute recently developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g., nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-week, 2-week, 3-week, and 4-week recall periods, using daily reporting as the reference. Methods—English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four U.S. cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-week, 2-week, 3-week, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g., maximum of daily scores over 7 days vs. 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results—127 subjects completed questionnaires (57% male; median age 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size), was −0.20 (−0.20) for 1-week recall; −0.36 (−0.31) for 2-week recall; −0.45 (−0.39) for 3-week recall; and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82); 2-week recall: 0.74 (range: 0.58–0.83); 3-week recall: 0.72 (range: 0.61–0.84); and 4-week recall: 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusions—1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss

Macrophage metabolic reprogramming presents a therapeutic target in lupus nephritis.

IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis

Cancer Care Delivery Research: Building the Evidence Base to Support Practice Change in Community Oncology

Understanding how health care system structures, processes, and available resources facilitate and/or hinder the delivery of quality cancer care is imperative, especially given the rapidly changing health care landscape. The emerging field of cancer care delivery research (CCDR) focuses on how organizational structures and processes, care delivery models, financing and reimbursement, health technologies, and health care provider and patient knowledge, attitudes, and behaviors influence cancer care quality, cost, and access and ultimately the health outcomes and well-being of patients and survivors. In this article, we describe attributes of CCDR, present examples of studies that illustrate those attributes, and discuss the potential impact of CCDR in addressing disparities in care. We conclude by emphasizing the need for collaborative research that links academic and community-based settings and serves simultaneously to accelerate the translation of CCDR results into practice. The National Cancer Institute recently launched its Community Oncology Research Program, which includes a focus on this area of research

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts