Quality of T-cell responses versus reduction in viral load: results from an exploratory phase II clinical study of Vacc-4x, a therapeutic HIV vaccine

Background Immunization with Vacc-4x, a peptide-based therapeutic vaccine for HIV-1, has shown a statistically significant reduction in viral load set point compared to placebo during treatment interruption in an exploratory phase II clinical study enrolling 135 subjects (NCT00659789). This vaccine aims to induce sustained cell-mediated immune responses to conserved domains on HIV p24. Methods After 6 immunizations on ART over 28 weeks, treatment was interrupted for up to 24 weeks (Vacc-4x n=88; placebo n=38). Immunological analyses (ELISPOT, proliferation, intracellular cytokine staining (ICS)) to HIV p24 were carried out at central laboratories. The HLA class I profile (Vacc-4x n=73, placebo n=32) was also determined. Results For subjects that remained off ART until week 52 (Vacc-4x n=56, placebo n=25), there was a log 0.44 reduction in viral load set point between the Vacc-4x and placebo groups (p=0.0397). There was a similar distribution of HLA class I alleles in the two treatment arms, with the exception of the B35 allele (27% of Vacc-4x subjects versus 8% placebo subjects). The viral load of ELISPOT positive Vacc-4x subjects was significantly lower than that of placebo subjects (p=0.023). There was no significant difference in T-cell proliferation responses between Vacc-4x and placebo groups, however, the percentage of subjects showing proliferative CD4 and CD8 T-cell responses to Vacc-4x peptides increased over time only for the Vacc-4x group. ICS analysis showed a predominance of CD8-mediated T-cell responses to p24 that were significantly increased from baseline for the Vacc-4x group (p<0.043) but not for the placebo group(p>0.05). There was also a trend towards higher numbers of polyfunctional T-cells in the Vacc-4x group compared to the placebo group (p=0.188). Conclusion These findings suggest Vacc-4x immunization can influence the quality of immune responses to HIV-1 p24 irrespective of HLA status, and contribute to a reduction in viral load

Role of Mesoscale Eddies in Cross-Frontal Transport of Heat and Biogeochemical Tracers in the Southern Ocean

This study examines the role of processes transporting tracers across the Polar Front (PF) in the depth interval between the surface and major topographic sills, which this study refers to as the “PF core.” A preindustrial control simulation of an eddying climate model coupled to a biogeochemical model [GFDL Climate Model, version 2.6 (CM2.6)– simplified version of the Biogeochemistry with Light Iron Nutrients and Gas (miniBLING) 0.1° ocean model] is used to investigate the transport of heat, carbon, oxygen, and phosphate across the PF core, with a particular focus on the role of mesoscale eddies. The authors find that the total transport across the PF core results from a ubiquitous Ekman transport that drives the upwelled tracers to the north and a localized opposing eddy transport that induces tracer leakages to the south at major topographic obstacles. In the Ekman layer, the southward eddy transport only partially compensates the northward Ekman transport, while below the Ekman layer, the southward eddy transport dominates the total transport but remains much smaller in magnitude than the near-surface northward transport. Most of the southward branch of the total transport is achieved below the PF core, mainly through geostrophic currents. This study finds that the eddy-diffusive transport reinforces the southward eddy-advective transport for carbon and heat, and opposes it for oxygen and phosphate. Eddy-advective transport is likely to be the leading-order component of eddy-induced transport for all four tracers. However, eddy-diffusive transport may provide a significant contribution to the southward eddy heat transport due to strong along-isopycnal temperature gradients

US SOLAS Science Report

The article of record may be found at https://doi.org/10.1575/1912/27821The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G).This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

US SOLAS Science Report

The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

Melatonin Induces Follicle Maturation in Danio rerio

Most organisms modulate their reproductive activity responding to day length by the nocturnal release of melatonin by the pineal gland. This hormone is also responsible for synchronizing reproduction with specific external environment stimuli in order to optimize reproductive success

Mechanisms of decadal variability in the Labrador Sea and the wider North Atlantic in a high-resolution climate model

A necessary step before assessing the performance of decadal predictions is the evaluation of the processes that bring memory to the climate system, both in climate models and observations. These mechanisms are particularly relevant in the North Atlantic, where the ocean circulation, related to both the Subpolar Gyre and the Meridional Overturning Circulation (AMOC), is thought to be important for driving significant heat content anomalies. Recently, a rapid decline in observed densities in the deep Labrador Sea has pointed to an ongoing slowdown of the AMOC strength taking place since the mid 90s, a decline also hinted by in-situ observations from the RAPID array. This study explores the use of Labrador Sea densities as a precursor of the ocean circulation changes, by analysing a 300-year long simulation with the state-of-the-art coupled model HadGEM3-GC2. The major drivers of Labrador Sea density variability are investigated, and are characterised by three major contributions. First, the integrated effect of local surface heat fluxes, mainly driven by year-to-year changes in the North Atlantic Oscillation, which accounts for 62% of the total variance. Additionally, two multidecadal-to-centennial contributions from the Greenland-Scotland Ridge outflows are quantified; the first associated with freshwater exports via the East Greenland Current, and the second with density changes in the Denmark Strait Overflow. Finally, evidence is shown that decadal trends in Labrador Sea densities are followed by important atmospheric impacts. In particular, a negative winter NAO response appears to follow the positive Labrador Sea density trends, and provides a phase reversal mechanism

Global perspectives on observing ocean boundary current systems

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Todd, R. E., Chavez, F. P., Clayton, S., Cravatte, S., Goes, M., Greco, M., Ling, X., Sprintall, J., Zilberman, N., V., Archer, M., Aristegui, J., Balmaseda, M., Bane, J. M., Baringer, M. O., Barth, J. A., Beal, L. M., Brandt, P., Calil, P. H. R., Campos, E., Centurioni, L. R., Chidichimo, M. P., Cirano, M., Cronin, M. F., Curchitser, E. N., Davis, R. E., Dengler, M., deYoung, B., Dong, S., Escribano, R., Fassbender, A. J., Fawcett, S. E., Feng, M., Goni, G. J., Gray, A. R., Gutierrez, D., Hebert, D., Hummels, R., Ito, S., Krug, M., Lacan, F., Laurindo, L., Lazar, A., Lee, C. M., Lengaigne, M., Levine, N. M., Middleton, J., Montes, I., Muglia, M., Nagai, T., Palevsky, H., I., Palter, J. B., Phillips, H. E., Piola, A., Plueddemann, A. J., Qiu, B., Rodrigues, R. R., Roughan, M., Rudnick, D. L., Rykaczewski, R. R., Saraceno, M., Seim, H., Sen Gupta, A., Shannon, L., Sloyan, B. M., Sutton, A. J., Thompson, L., van der Plas, A. K., Volkov, D., Wilkin, J., Zhang, D., & Zhang, L. Global perspectives on observing ocean boundary current systems. Frontiers in Marine Science, 6, (2010); 423, doi: 10.3389/fmars.2019.00423.Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.RT was supported by The Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. FC was supported by the David and Lucile Packard Foundation. MGo was funded by NSF and NOAA/AOML. XL was funded by China’s National Key Research and Development Projects (2016YFA0601803), the National Natural Science Foundation of China (41490641, 41521091, and U1606402), and the Qingdao National Laboratory for Marine Science and Technology (2017ASKJ01). JS was supported by NOAA’s Global Ocean Monitoring and Observing Program (Award NA15OAR4320071). DZ was partially funded by the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement NA15OAR4320063. BS was supported by IMOS and CSIRO’s Decadal Climate Forecasting Project. We gratefully acknowledge the wide range of funding sources from many nations that have enabled the observations and analyses reviewed here