Naoki H. Kumagai

Xenogeneic thymokidney and thymic tissue transplantation in a pig-to-baboon model: I. Evidence for pig-specific T-cell unresponsiveness.

Background. The potential of xenotransplantation for clinical application will require overcoming barriers of humoral and cellular rejection, through strategies using immune suppression or tolerance induction. This laboratory has previously reported the induction of tolerance in the discordant xenogeneic model of pig-to-rodent thymic transplantation. We also have described a miniature swine model of fully mismatched allogeneic composite vascularized thymokidney transplantation that induced transplantation tolerance. We tested a combination of these approaches in a clinically relevant pig-to-primate model of xenotransplantation. Methods. Composite thymokidney grafts were prepared 40 to 80 days before transplantation by the autologous implantation of thymic tissue under the renal capsule of human decay-accelerating factor transgenic swine. Baboons received xenotransplants of both human decay-accelerating factor composite thymokidneys and omental implants of thymic tissue. Recipients were treated with an immunosuppressive-conditioning regimen including thymectomy or thymic irradiation, extracorporeal immunoadsorption of anti-&agr;Gal antibodies and T-cell depletion. Recipients were followed for indicators of xenograft rejection, T-cell depletion and reconstitution, anti-&agr;Gal antibody levels, and mixed lymphocyte responses. Immunologic responses were studied in those animals that survived for more than 3 weeks. Results. Thymokidney xenografts survived for up to 30 days, with evidence of viable thymic epithelium and Hassall’s corpuscles under the renal capsule and in the omental implants, and with evidence of few host lymphocytes. Three animals demonstrated donor-specific unresponsiveness, while maintaining normal alloresponses, in mixed–lymphocyte-response assays performed after immunosuppression had been stopped. Rejected grafts demonstrated humoral damage without evidence of cellular infiltrates. After graftectomy, one animal maintained donor-specific cellular unresponsiveness and stable anti-&agr;Gal antibody levels for more than 2 months. Conclusions. We concluded that composite thymokidney and thymic-tissue xenotransplantation from swine to baboons can induce donor-specific cellular unresponsiveness and stable anti-&agr;Gal antibody levels, suggesting avoidance of sensitization after xenotransplantation. The presence of viable donor-swine thymic epithelium could have a role in the development of donor-specific T-cell tolerance. Further strategies to address humoral rejection could prolong graft survival and result in long-term tolerance to xenografts.

Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis.

Background. Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine. Methods. Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74–12–4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells. Results. Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60. Conclusions. Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.

Negative effects of ocean acidification on two crustose coralline species using genetically homogeneous samples

We evaluated acidification effects on two crustose coralline algal species common to Pacific coral reefs, Lithophyllum kotschyanum and Hydrolithon samoense. We used genetically homogeneous samples of both species to eliminate misidentification of species. The growth rates and percent calcification of the walls of the epithallial cells (thallus surface cells) of both species decreased with increasing pCO₂. However, elevated pCO₂ more strongly inhibited the growth of L. kotschyanum versus H. samoense. The trend of decreasing percent calcification of the cell wall did not differ between these species, although intercellular calcification of the epithallial cells in L. kotschyanum was apparently reduced at elevated pCO₂, a result that might indicate that there are differences in the solubility or density of the calcite skeletons of these two species. These results can provide knowledge fundamental to future studies of the physiological and genetic mechanisms that underlie the response of crustose coralline algae to environmental stresses.

Responses of calcification of massive and encrusting corals to past, present, and near-future ocean carbon dioxide concentrations

In this study, we report the acidification impact mimicking the pre-industrial, the present, and near-future oceans on calcification of two coral species (Porites australiensis, Isopora palifera) by using precise pCO2 control system which can produce acidified seawater under stable pCO2 values with low variations. In the analyses, we performed Bayesian modeling approaches incorporating the variations of pCO2 and compared the results between our modeling approach and classical statistical one. The results showed highest calcification rates in pre-industrial pCO2 level and gradual decreases of calcification in the near-future ocean acidification level, which suggests that ongoing and near-future ocean acidification would negatively impact coral calcification. In addition, it was expected that the variations of parameters of carbon chemistry may affect the inference of the best model on calcification responses to these parameters between Bayesian modeling approach and classical statistical one even under stable pCO2 values with low variations.

Projecting the impacts of rising seawater temperatures on the distribution of seaweeds around Japan under multiple climate change scenarios.

Seaweed beds play a key role in providing essential habitats and energy to coastal areas, with enhancements in productivity and biodiversity and benefits to human societies. However, the spatial extent of seaweed beds around Japan has decreased due to coastal reclamation, water quality changes, rising water temperatures, and heavy grazing by herbivores. Using monthly mean sea surface temperature (SST) data from 1960 to 2099 and SST-based indices, we quantitatively evaluated the effects of warming seawater on the spatial extent of suitable versus unsuitable habitats for temperate seaweed Ecklonia cava, which is predominantly found in southern Japanese waters. SST data were generated using the most recent multiple climate projection models and emission scenarios (the Representative Concentration Pathways or RCPs) used in the Coupled Model Intercomparison Project phase 5 (CMIP5). In addition, grazing by Siganus fuscescens, an herbivorous fish, was evaluated under the four RCP simulations. Our results suggest that continued warming may drive a poleward shift in the distribution of E. cava, with large differences depending on the climate scenario. For the lowest emission scenario (RCP2.6), most existing E. cava populations would not be impacted by seawater warming directly but would be adversely affected by intensified year-round grazing. For the highest emission scenario (RCP8.5), previously suitable habitats throughout coastal Japan would become untenable for E. cava by the 2090s, due to both high-temperature stress and intensified grazing. Our projections highlight the importance of not only mitigating regional warming due to climate change, but also protecting E. cava from herbivores to conserve suitable habitats on the Japanese coast.

An improved estimation of the poleward expansion of coral habitats based on the inter-annual variation of sea surface temperatures

The poleward expansion of coral habitats has been observed along the Japanese coast since the 1930s. Previous modeling studies have projected a poleward expansion using decadal-mean sea surface temperatures (SSTs) in the coldest months. However, this poleward expansion could be affected by the inter-annual variation of SST in the coldest months, which has not been considered before. In this study, the simulated pattern of poleward expansion was compared between cases where coral mortality was considered based on the inter-annual variation of SST and the decadal-mean SST in the coldest months. Modeled monthly mean SSTs for historical and future global warming simulations from the most recent climate projection model (MIROC4h) were used. The poleward expansion of corals simulated by considering mortality based on the inter-annual variation of SST in the coldest months better reproduced the observed poleward expansion speed compared to the simulations without such a consideration. Our results show the importance of considering coral mortality based on the inter-annual variation of seawater temperature to produce a more realistic poleward expansion of coral habitats.

Habitat-forming seaweeds in Japan (fucoids and temperate kelps)

This paper describes the flora of habitat-forming seaweeds (fucoids and temperate kelps) at 7673 sites of the Japanese coast encompassing its warm to cold temperate zone, recorded from 1887 to 2014. The data set includes 86 species (21,168 presence and 20,845 absence records), compiled from 355 literature sources, most of which were written in Japanese and published as grey literature in local journals or individual reports. Scientific names were consolidated under currently-accepted nomenclature based on Algaebase (http://www.algaebase.org). The data set compiled the seaweed flora at each study site each year, the geographical location and the scientific names. Additionally, three supporting data sets were created respectively including name of each site, synonyms of the seaweeds, and the corresponding literature list. This rich collection of data can be used to study the biogeography and long-term changes of particular species and the diversity of habitat-forming seaweeds of the Japanese coast.

Author Correction: Declaration of local chemical eradication of the Argentine ant: Bayesian estimation with a multinomial-mixture model

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Ocean currents and herbivory drive macroalgae-to-coral community shift under climate warming

Significance Global degradation of coral reefs and macroalgal beds can have ecosystem-wide implications for biodiversity, ecological functioning, and ocean resources. However, recent studies in warm temperate zones have documented community shifts from macroalgae to corals, signaling a potential mechanism for coral conservation under climate warming. Here, we present evidence that warming, aided by the dominant poleward-flowing current system, is facilitating the expansion of tropical corals and herbivorous fishes into existing temperate Japanese macroalgae communities, which are contracting faster than they are expanding. Furthermore, our results suggest future climate change may exacerbate this process, potentially compromising the long-term stability of these communities. Future conservation of these communities might require of a more proactive management toward climate adaptation. Coral and macroalgal communities are threatened by global stressors. However, recently reported community shifts from temperate macroalgae to tropical corals offer conservation potential for corals at the expense of macroalgae under climate warming. Although such community shifts are expanding geographically, our understanding of the driving processes is still limited. Here, we reconstruct long-term climate-driven range shifts in 45 species of macroalgae, corals, and herbivorous fishes from over 60 years of records (mainly 1950–2015), stretching across 3,000 km of the Japanese archipelago from tropical to subarctic zones. Based on a revised coastal version of climate velocity trajectories, we found that prediction models combining the effects of climate and ocean currents consistently explained observed community shifts significantly better than those relying on climate alone. Corals and herbivorous fishes performed better at exploiting opportunities offered by this interaction. The contrasting range dynamics for these taxa suggest that ocean warming is promoting macroalgal-to-coral shifts both directly by increased competition from the expansion of tropical corals into the contracting temperate macroalgae, and indirectly via deforestation by the expansion of tropical herbivorous fish. Beyond individual species’ effects, our results provide evidence on the important role that the interaction between climate warming and external forces conditioning the dispersal of organisms, such as ocean currents, can have in shaping community-level responses, with concomitant changes to ecosystem structure and functioning. Furthermore, we found that community shifts from macroalgae to corals might accelerate with future climate warming, highlighting the complexity of managing these evolving communities under future climate change.

High-resolution modeling of thermal thresholds and environmental influences on coral bleaching for local and regional reef management

Coral reefs are one of the world’s most threatened ecosystems, with global and local stressors contributing to their decline. Excessive sea-surface temperatures (SSTs) can cause coral bleaching, resulting in coral death and decreases in coral cover. A SST threshold of 1 °C over the climatological maximum is widely used to predict coral bleaching. In this study, we refined thermal indices predicting coral bleaching at high-spatial resolution (1 km) by statistically optimizing thermal thresholds, as well as considering other environmental influences on bleaching such as ultraviolet (UV) radiation, water turbidity, and cooling effects. We used a coral bleaching dataset derived from the web-based monitoring system Sango Map Project, at scales appropriate for the local and regional conservation of Japanese coral reefs. We recorded coral bleaching events in the years 2004–2016 in Japan. We revealed the influence of multiple factors on the ability to predict coral bleaching, including selection of thermal indices, statistical optimization of thermal thresholds, quantification of multiple environmental influences, and use of multiple modeling methods (generalized linear models and random forests). After optimization, differences in predictive ability among thermal indices were negligible. Thermal index, UV radiation, water turbidity, and cooling effects were important predictors of the occurrence of coral bleaching. Predictions based on the best model revealed that coral reefs in Japan have experienced recent and widespread bleaching. A practical method to reduce bleaching frequency by screening UV radiation was also demonstrated in this paper.