Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses

Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes.Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity

Effects of Elevated Temperature and Carbon Dioxide on the Growth and Survival of Larvae and Juveniles of Three Species of Northwest Atlantic Bivalves

Rising CO2 concentrations and water temperatures this century are likely to have transformative effects on many coastal marine organisms. Here, we compared the responses of two life history stages (larval, juvenile) of three species of calcifying bivalves (Mercenaria mercenaria, Crassostrea virginica, and Argopecten irradians) to temperatures (24 and 28°C) and CO2 concentrations (∼250, 390, and 750 ppm) representative of past, present, and future summer conditions in temperate estuaries. Results demonstrated that increases in temperature and CO2 each significantly depressed survival, development, growth, and lipid synthesis of M. mercenaria and A. irradians larvae and that the effects were additive. Juvenile M. mercenaria and A. irradians were negatively impacted by higher temperatures while C. virginica juveniles were not. C. virginica and A. irradians juveniles were negatively affected by higher CO2 concentrations, while M. mercenaria was not. Larvae were substantially more vulnerable to elevated CO2 than juvenile stages. These findings suggest that current and future increases in temperature and CO2 are likely to have negative consequences for coastal bivalve populations

Better Regional Ocean Observing Through Cross-National Cooperation: A Case Study From the Northeast Pacific

The ocean knows no political borders. Ocean processes, like summertime wind-driven upwelling, stretch thousands of kilometers along the Northeast Pacific (NEP) coast. This upwelling drives marine ecosystem productivity and is modulated by weather systems and seasonal to interdecadal ocean-atmosphere variability. Major ocean currents in the NEP transport water properties such as heat, fresh water, nutrients, dissolved oxygen, pCO2, and pH close to the shore. The eastward North Pacific Current bifurcates offshore in the NEP, delivering open-ocean signals south into the California Current and north into the Gulf of Alaska. There is a large and growing number of NEP ocean observing elements operated by government agencies, Native American Tribes, First Nations groups, not-for-profit organizations, and private entities. Observing elements include moored and mobile platforms, shipboard repeat cruises, as well as land-based and estuarine stations. A wide range of multidisciplinary ocean sensors are deployed to track, for example, upwelling, downwelling, ocean productivity, harmful algal blooms, ocean acidification and hypoxia, seismic activity and tsunami wave propagation. Data delivery to shore and observatory controls are done through satellite and cell phone communication, and via seafloor cables. Remote sensing from satellites and land-based coastal radar provide broader spatial coverage, while numerical circulation and biogeochemical modeling complement ocean observing efforts. Models span from the deep ocean into the inland Salish Sea and estuaries. NEP ocean observing systems are used to understand regional processes and, together with numerical models, provide ocean forecasts. By sharing data, experiences and lessons learned, the regional ocean observatory is better than the sum of its parts

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

Integrated Ocean Carbon Research: A Summary of Ocean Carbon Research, and Vision of Coordinated Ocean Carbon Research and Observations for the Next Decade

The Integrated Ocean Carbon Research (IOC-R) programme is a formal working group of the Intergovernmental Oceanographic Commission (IOC) that was formed in 2018 in response to the United Nations (UN) Decade of Ocean Science for Sustainable Development (2021-2030), “the Decade.” The IOC-R will contribute to the science elements of the overarching Implementation Plan for the Decade1. The Implementation Plan is a high-level framework to guide actions by which ocean science can more effectively deliver its contribution and co-development with other entities to achieve the societal outcomes outlined in the Decade plan and the sustainable development goals (SDGs) of the UN.UNESC