Spatial and seasonal patterns of FMD primary outbreaks in cattle in Zimbabwe between 1931 and 2016

Foot and mouth disease (FMD) is an important livestock disease impacting mainly intensive production systems. In southern Africa, the FMD virus is maintained in wildlife and its control is therefore complicated. However, FMD control is an important task to allow countries access to lucrative foreign meat market and veterinary services implement drastic control measures on livestock populations living in the periphery of protected areas, negatively impacting local small-scale livestock producers. This study investigated FMD primary outbreak data in Zimbabwe from 1931 to 2016 to describe the spatio-temporal distribution of FMD outbreaks and their potential drivers. The results suggest that: (i) FMD outbreaks were not randomly distributed in space across Zimbabwe but are clustered in the Southeast Lowveld (SEL); (ii) the proximity of protected areas with African buffalos was potentially responsible for primary FMD outbreaks in cattle; (iii) rainfall per se was not associated with FMD outbreaks, but seasons impacted the temporal occurrence of FMD outbreaks across regions; (iv) the frequency of FMD outbreaks increased during periods of major socio-economic and political crisis. The differences between the spatial clusters and other areas in Zimbabwe presenting similar buffalo/cattle interfaces but with fewer FMD outbreaks can be interpreted in light of the recent better understanding of wildlife/livestock interactions in these areas. The types of wildlife/livestock interfaces are hypothesized to be the key drivers of contacts between wildlife and livestock, triggering a risk of FMD inter-species spillover. The management of wildlife/livestock interfaces is therefore crucial for the control of FMD in southern Africa

Diel and seasonal methane dynamics in the shallow and turbulent Wadden Sea

The Wadden Sea is a coastal system along the fringe of the land–sea borders of Denmark, Germany and the Netherlands. The Wadden Sea is extremely productive and influenced by strong variations in physical and biological forcing factors that act on timescales of hours to seasons. Productive coastal seas are known to dominate the ocean's methane emission to the atmosphere, but knowledge of controls and temporal variations in methane dynamics in these vastly dynamic systems is scarce. Here we address this knowledge gap by measuring methane inventories and methanotrophic activity at a temporal resolution of 1 h over a period of 2 d, repeatedly during four successive seasons in the central Dutch Wadden Sea. We found that methane dynamics varied between colder and warmer seasons, with generally higher water column methane concentrations and methanotrophic activity in the warmer seasons. The efflux of methane to the atmosphere was, on the other hand, lower in the warmer seasons because of lower wind speeds. On a diel scale, tides controlled methanotrophic activity, which increased ∼40 % at low tide compared to high tide. We estimate that methane oxidizing bacteria reduce the methane budget of the Dutch Wadden Sea by only 2 %, while escapes to the atmosphere and are flushed out into the open North Sea at ebb tide. Our findings indicate that tides play a key role in controlling methane dynamics and methanotrophic activity and highlight the importance of high-resolution and repeated sampling strategies to resolve methane dynamics in fast-changing coastal systems

Plastic photodegradation under simulated marine conditions

Ocean plastic pollution is a problem of increasing magnitude; yet, the amount of plastic at the sea surface is much lower than expected. Solar ultraviolet (UV) radiation can induce photodegradation, but its importance in determining the longevity of floating plastic remains unconstrained. Here, we measured photodegradation rates of different plastic types slightly larger than microplastics (virgin polymers and floating plastic debris) under simulated marine conditions. UV irradiation caused all plastic types to leach dissolved organic carbon, and to a lesser degree carbon dioxide, carbon monoxide, methane, and other hydrocarbon gases. The release of photodegradation products translates to degradation rates of 1.7–2.3 % yr−1 of the tested plastic particles normalized to conditions as found in the subtropical surface ocean. Modelling the accumulation of floating plastic debris, our results show that solar UV radiation could already have degraded 7 to 22 % of all floating plastic that has ever been released to the sea

Preclinical development of HIvax: human survivin Highly Immunogenic vaccines

Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers

Diel and seasonal methane dynamics in the shallow and turbulent Wadden Sea

The Wadden Sea is a coastal system along the fringe of the land-sea borders of Denmark, Germany and the Netherlands. The Wadden Sea is extremely productive and influenced by strong variations in physical and biological forcing factors that act on timescales of hours to seasons. Productive coastal seas are known to dominate the ocean's methane emission to the atmosphere, but knowledge of controls and temporal variations in methane dynamics in these vastly dynamic systems is scarce. Here we address this knowledge gap by measuring methane inventories and methanotrophic activity at a temporal resolution of 1h over a period of 2d, repeatedly during four successive seasons in the central Dutch Wadden Sea. We found that methane dynamics varied between colder and warmer seasons, with generally higher water column methane concentrations and methanotrophic activity in the warmer seasons. The efflux of methane to the atmosphere was, on the other hand, lower in the warmer seasons because of lower wind speeds. On a diel scale, tides controlled methanotrophic activity, which increased g1/440% at low tide compared to high tide. We estimate that methane oxidizing bacteria reduce the methane budget of the Dutch Wadden Sea by only 2%, while 1/41/3 escapes to the atmosphere and 1/42/3 are flushed out into the open North Sea at ebb tide. Our findings indicate that tides play a key role in controlling methane dynamics and methanotrophic activity and highlight the importance of high-resolution and repeated sampling strategies to resolve methane dynamics in fast-changing coastal systems

Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models

Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment

Expansion in CD39(+) CD4(+) Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4(+) T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. the CD39 ectonucleotidase receptor is expressed on CD4(+) T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39(+)CD25(+)) and effector (CD39(+)CD25(-)) function. Here, we investigated the expression of CD39 on CD4(+) T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. the frequency of CD39(+)CD4(+) T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39(+)CD25(-) CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39(+)CD25(+) regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39(-)CD25(+) T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4(+) T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4(+) T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.National Institute of Allergies and Infectious DiseasesNational Institutes of HealthUniversity of CaliforniaSan Francisco-Gladstone Institute of Virology & Immunology Center for AIDS ResearchFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)John E. Fogarty International CenterNational Center for Research ResourcesNational Institute of General Medical Sciences from the National Institutes of HealthUniv Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA 94143 USAUniv Hawaii, John A Burns Sch Med, Dept Trop Med, Hawaii Ctr AIDS, Honolulu, HI 96822 USAUniv São Paulo, Sch Med, Deparment Infect Dis, São Paulo, BrazilUniv São Paulo, Sch Med, Div Clin Immunol & Allergy, São Paulo, BrazilFuncacao Prosangue, Hemoctr São Paulo, Mol Biol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilSan Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research: P30 AI027763FAPESP: 04/15856-9/KallasFAPESP: 2010/05845-0/KallasFAPESP: 11/12297-2/SanabaniJohn E. Fogarty International Center: D43 TW00003National Center for Research Resources: 5P20RR016467-11National Institute of General Medical Sciences from the National Institutes of Health: 8P20GM103466-11Web of Scienc