Cities, biodiversity and health: we need healthy urban microbiome initiatives

Current evidence suggests that biodiverse environmental microbiomes contribute positively to human health and could account for known associations between urban green space and improved health. We summarise the state of knowledge that could inform the development of healthy urban microbiome initiatives (HUMI) to re-connect urban populations to biodiverse microbial communities

Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY) ligand-binding motif and the CTLA-4 (GVYVKM) inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based switch motifs (ITSMs) in genes and protein domains that have not been previously reported in any species. This checkpoint molecule analysis and review of salient features for each of the molecules presented here can serve as road map for the development of a Tasmanian devil facial tumor disease immunotherapy. Finally, the strategies can be used as a guide for veterinarians, ecologists, and other researchers willing to venture into the nascent field of wild immunology

An oral bait vaccination approach for the Tasmanian devil facial tumor diseases

Introduction: The Tasmanian devil (Sarcophilus harrisii) is the largest extant carnivorous marsupial. Since 1996, its population has declined by 77% primarily due to a clonal transmissible tumor, known as devil facial tumor (DFT1) disease. In 2014, a second transmissible devil facial tumor (DFT2) was discovered. DFT1 and DFT2 are nearly 100% fatal.Areas covered: We review DFT control approaches and propose a rabies-style oral bait vaccine (OBV) platform for DFTs. This approach has an extensive safety record and was a primary tool in large-scale rabies virus elimination from wild carnivores across diverse landscapes. Like rabies virus, DFTs are transmitted by oral contact, so immunizing the oral cavity and stimulating resident memory cells could be advantageous. Additionally, exposing infected devils that already have tumors to OBVs could serve as an oncolytic virus immunotherapy. The primary challenges may be identifying appropriate DFT-specific antigens and optimization of field delivery methods.Expert opinion: DFT2 is currently found on a peninsula in southern Tasmania, so an OBV that could eliminate DFT2 should be the priority for this vaccine approach. Translation of an OBV approach to control DFTs will be challenging, but the approach is feasible for combatting ongoing and future disease threats

Toward Cloning of the Magnetotactic Metagenome: Identification of Magnetosome Island Gene Clusters in Uncultivated Magnetotactic Bacteria from Different Aquatic Sediments

In this report, we describe the selective cloning of large DNA fragments from magnetotactic metagenomes from various aquatic habitats. This was achieved by a two-step magnetic enrichment which allowed the mass collection of environmental magnetotactic bacteria (MTB) virtually free of nonmagnetic contaminants. Four fosmid libraries were constructed and screened by end sequencing and hybridization analysis using heterologous magnetosome gene probes. A total of 14 fosmids were fully sequenced. We identified and characterized two fosmids, most likely originating from two different alphaproteobacterial strains of MTB that contain several putative operons with homology to the magnetosome island (MAI) of cultivated MTB. This is the first evidence that uncultivated MTB exhibit similar yet differing organizations of the MAI, which may account for the diversity in biomineralization and magnetotaxis observed in MTB from various environments

Role of LAG-3 in Regulatory T Cells

AbstractRegulatory T cells (Tregs) limit autoimmunity but also attenuate the magnitude of antipathogen and antitumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Tregs in vivo requires identification of Treg-selective receptors. A comparative analysis of gene expression arrays from antigen-specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related molecule that binds MHC class II. Antibodies to LAG-3 inhibit suppression by induced Tregs both in vitro and in vivo. Natural CD4+CD25+ Tregs express LAG-3 upon activation, which is significantly enhanced in the presence of effector cells, whereas CD4+CD25+ Tregs from LAG-3−/− mice exhibit reduced regulatory activity. Lastly, ectopic expression of LAG-3 on CD4+ T cells significantly reduces their proliferative capacity and confers on them suppressor activity toward effector T cells. We propose that LAG-3 marks regulatory T cell populations and contributes to their suppressor activity

Multispecies Sustainability

The sustainability concept in its current form suffers from reductionism. The common interpretation of ‘meeting the needs of the present without compromising the ability of future generations to meet their own needs’ fails to explicitly recognize their interdependence with needs of current and future non-human generations. Here, we argue that the focus of sustainability on human well-being – a purely utilitarian view of nature as a resource for humanity – limits its conceptual and analytical power, as well as real-world sustainability transformation efforts. We propose a broadened concept of ‘multispecies sustainability’ by acknowledging interdependent needs of multiple species’ current and future generations. We develop the concept in three steps: (1) discussing normative aspects, fundamental principles underlying the con- cept, and potential visual models, (2) showcasing radically diverging futures emerging from a scenario thought experiment based on the axes sustainable-unsustainable and multispecies-anthropocentric, and (3) exploring how multispecies sustainability can be applied to research and policy-making through two case studies (a multispecies stakeholder framework and the Healthy Urban Microbiome Initiative)

City-size bias in knowledge on the effects of urban nature on people and biodiversity

The evidence base for the benefits of urban nature for people and biodiversity is strong. However, cities are diverse and the social and environmental contexts of cities are likely to influence the observed effects of urban nature, and the application of evidence to differing contexts. To explore biases in the evidence base for the effects of urban nature, we text-matched city names in the abstracts and affiliations of 14 786 journal articles, from separate searches for articles on urban biodiversity, the health and wellbeing impacts of urban nature, and on urban ecosystem services. City names were found in 51% of article abstracts and 92% of affiliations. Most large cities were studied many times over, while only a small proportion of small cities were studied once or twice. Almost half the cities studied also had an author with an affiliation from that city. Most studies were from large developed cities, with relatively few studies from Africa and South America in particular. These biases mean the evidence base for the effects of urban nature on people and on biodiversity does not adequately represent the lived experience of the 41% of the world’s urban population who live in small cities, nor the residents of the many rapidly urbanising areas of the developing world. Care should be taken when extrapolating research findings from large global cities to smaller cities and cities in the developing world. Future research should encourage research design focussed on answering research questions rather than city selection by convenience, disentangle the role of city size from measures of urban intensity (such as population density or impervious surface cover), avoid gross urban-rural dualisms, and better contextualise existing research across social and environmental contexts