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The coral-algal symbiosis is the biological engine that drives one of the most spectacular structures on Earth: the coral reef. Here, living coral microhabitats are engineered using 3D bioprinting, as biomimetic model system of the coral-algal symbiosis. Various bioinks for the encapsulation of coral photosymbiotic microalgae (Breviolum psygmophilum) are developed and coral mass transfer phenomena are mimicked by 3D bioprinting coral tissue and skeleton microscale features. At the tissue–seawater interface, the biomimetic coral polyp and connective tissue structures successfully replicate the natural build-up of the O2 diffusive boundary layer. Inside the bioprinted construct, coral-like microscale gastric cavities are engineered using a multi-material bioprinting process. Underneath the tissue, the constructs mimic the porous architecture of the coral aragonite skeleton at the micrometer scale, which can be manipulated to assess the effects of skeletal architecture on stress-related hydrogen peroxide (H2O2) production. The bioprinted living coral microhabitats replicate the diffusion-related phenomena that underlie the functioning and breakdown of the coral-algal symbiosis and can be exploited for the additive manufacturing of synthetic designer corals.

Background\ud \ud Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO.\ud \ud \ud \ud Results\ud \ud We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice.\ud \ud \ud \ud Conclusions\ud \ud The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease.

Background. Ebolavirus and Marburgvirus cause severe hemorrhagic fever with high mortality and are potential bioterrorism agents. There are no available vaccines or therapeutic agents. Previous clinical trials evaluated transmembrane-deleted and point-mutation Ebolavirus glycoproteins (GPs) in candidate vaccines. Constructs evaluated in this trial encode wild-type (WT) GP from Ebolavirus Zaire and Sudan species and the Marburgvirus Angola strain expressed in a DNA vaccine. Methods. The VRC 206 study evaluated the safety and immunogenicity of these DNA vaccines (4 mg administered intramuscularly by Biojector) at weeks 0, 4, and 8, with a homologous boost at or after week 32. Safety evaluations included solicited reactogenicity and coagulation parameters. Primary immune assessment was done by means of GP-specific enzyme-linked immunosorbent assay. Results. The vaccines were well tolerated, with no serious adverse events; 80% of subjects had positive enzymelinked immunosorbent assay results (≥30) at week 12. The fourth DNA vaccination boosted the immune responses. Conclusions. The investigational Ebolavirus and Marburgvirus WT GP DNA vaccines were safe, well tolerated, and immunogenic in this phase I study. These results will further inform filovirus vaccine research toward a goal of inducing protective immunity by using WT GP antigens in candidate vaccine regimens. Clinical Trials Registration. NCT00605514.

Malaria Sporozoite Vaccine Each year, hundreds of millions of people are infected with Plasmodium falciparum, the mosquito-borne parasite that causes malaria. A preventative vaccine is greatly needed. Seder et al. (p. 1359, published online 8 August; see the Perspective by Good) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole, attenuated sporozoite vaccine. Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection. Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received, suggesting that both arms of the adaptive immune response may have participated in the observed protection. Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and wel-tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards. Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good] Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good]

Fire is an integral component of many ecosystems worldwide. Many plant species require fire-related cues, primarily heat and smoke, to trigger germination. Despite the importance of this process, the responses of many Australian species to these cues are unknown. Without this knowledge fire management strategies may be developed that are inappropriate for individual species and vegetation communities. In this study we examined the responses of a dry sclerophyll forest seed bank to heat and smoke germination cues. Analysis was possible for 48 taxa within the soil seedbank with 34 of these showing a response to one or both of the germination cues. 10 species responded to the heat treatment, 11 species responded to the smoke treatment and 13 species responded to both the heat and smoke treatments. Germination cues acted independently for all species considered. Results in this study were consistent with published reports for most species, although some differences were seen at the species and genus level. The study highlights the importance of fire-related cues in enhancing germination of a large proportion of the species occurring in dry sclerophyll forests.

This study investigates the performances of four major global Leaf Area Index (LAI) products at 1/11.2 degrees spatial sampling and a monthly time step: ECOCLIMAP climatology, GLOBCARBON (from SPOT/VEGETATION and ATSR/AATSR), CYCLOPES (from SPOT/VEGETATION) and MODIS Collection 4 (main algorithm, from MODIS/TERRA). These products were intercompared during the 2001 - 2003 period over the BELMANIP network of sites. Their uncertainty was assessed by comparison with 56 LAI reference maps derived from ground measurements. CYCLOPES and MODIS depict realistic spatial variations at continental scale, while ECOCLIMAP poorly captures surface spatial heterogeneity, and GLOBCARBON tends to display erratic variations. ECOCLIMAP and GLOBCARBON show the highest frequency of successful retrievals while MODIS and CYCLOPES retrievals are frequently missing in winter over northern latitudes and over the equatorial belt. CYCLOPES and MODIS describe consistent temporal profiles over most vegetation types, while ECOCLIMAP does not show any interannual variations, and GLOBCARBON can exhibit temporal instability during the growing season over forests. The CYCLOPES, MODIS, and GLOBCARBON LAI values agree better over croplands and grasslands than over forests, where differences in vegetation structure representation between algorithms and surface reflectance uncertainties lead to substantial discrepancies between products. CYCLOPES does not reach high enough LAI values to properly characterize forests. In contrast, the other products have sufficient dynamic range of LAI to describe the global variability of LAI. Overall, CYCLOPES is the most similar product to the LAI reference maps. However, more accurate ground measurements and better representation of the global and seasonal variability of vegetation are required to refine this result.