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Microbial sensors play an essential role in maintaining cellular homeostasis. Our knowledge is limited on how microbial sensing helps in differential immune response and its link to inflammatory diseases. Recently, we have shown that cytosolic sensor ELMO1 (Engulfment and Cell Motility Protein-1) binds to effectors from pathogenic bacteria and controls intestinal inflammation. Here, we show that ELMO1 interacts with another sensor, NOD2 (Nucleotide-binding oligomerization domain-containing protein 2), that recognizes bacterial cell wall component muramyl dipeptide (MDP). The polymorphism of NOD2 is linked to Crohn’s disease (CD) pathogenesis. Interestingly, we found that overexpression of ELMO1 and mutant NOD2 (L1007fs) were not able to clear the CD-associated adherent invasive E. coli (AIEC-LF82). To understand the interplay of microbial sensing of ELMO1-NOD2 in epithelial cells and macrophages, we used enteroid-derived monolayers (EDMs) from ELMO1 and NOD2 KO mice and ELMO1 and NOD2-depleted murine macrophage cell lines. The infection of murine EDMs with AIEC-LF82 showed higher bacterial load in ELMO1-KO, NOD2 KO EDMs, and ELMO1 KO EDMs treated with NOD2 inhibitors. The murine macrophage cells showed that the downregulation of ELMO1 and NOD2 is associated with impaired bacterial clearance that is linked to reduced pro-inflammatory cytokines and reactive oxygen species. Our results indicated that the crosstalk between microbial sensors in enteric infection and inflammatory diseases impacts the fate of the bacterial load and disease pathogenesis.

The Anthropocene has seen declining biodiversity inextricably linked to our societies, values, and choices. This requires ecologists to engage with the public in ecosystems such as cities to learn from and help inform their values and experiences regarding their role in urban nature. This article presents a transdisciplinary citizen science project on spontaneous urban vegetation in the context of urban botany, art-science, and participatory research that engages with the ecology of cities. We address the interdependence of ecological and social networks, suggesting how plant ecology can become more relevant for society in the Anthropocene, while presenting a specific methodology for engaging the public with urban botany. Summary: Cities are socio-ecological systems that require new ways of thinking and engagement to successfully conserve biodiversity. In this article, we present the citizen science project Where Seeds Fall which was undertaken in the city of Zurich, Switzerland. It was developed in an “ecology with” cities approach seeking to conduct research with the humans living in the ecosystem while learning from and helping inform their values. Our project brings together the perspectives of ecologists, artists, and planners on the three themes of urban wastelands, spontaneous vegetation, and ecological connectivity. It is placed in the context of urban botany, environmental arts and participatory research. Volunteers placed trays of bare soil (without seeds) in their gardens and balconies and monitored what plants arrived and germinated. They then were able to share information about their trays (images, species lists) with one another through a spatially explicit web platform. The project was accompanied by public outreach events and artistic interventions in public space. This article presents the methodology of the project so that it can be replicated elsewhere. Based on the experiences with the project we discuss evolving transdisciplinary perspectives on wild plant biodiversity in cities., Plants, People, Planet, 3 (4), ISSN:2572-2611

The conservation and promotion of biodiversity in urban spaces has become a core concern in urban greening. As cities continue to densify, however, urban green spaces are becoming smaller and more isolated. Many hope that wildflowers, and with them also faunistic biodiversity, can be maintained through networks of small informal green spaces. Currently, there are little data available for city planners to answer the questions of how patch size and ecological connectivity affect the population persistence of wildflowers in small vegetation patches. To address these concerns, we surveyed all vegetation patches greater than 1 m2 in public spaces across seven 1 km2 quadrats distributed across the city of Zurich, Switzerland. Our survey focused on a list of 166 herbaceous vascular plant species. We analyzed vegetation patch topologies (frequency distributions of size and connectivity) and related it to alpha and beta species diversity. Dispersal traits of investigated species were used to interpret connectivity patterns. Over 75 % of patches were

This paper introduces an implementation of a robot elaborated with Raspberry Pi that accompanies the mentoring of the programming courses given at Universidad Tecnológica de Bolívar as a pedagogic element. This robotic prototype was designed to support the learning of the students who have shortcomings and gaps in knowledges they acquire in their master classes. It describes how it was carried out, as well as important details that append value to the robot. © 2018 IEEE.

1. Habitat loss and modification are hallmarks of anthropogenic ecosystems, but the consequences for ecosystem functioning and service provisioning often remain unclear. Understanding these links in cities is complicated by strong but fine‐scale differences in habitat structure among green space patches, and a high variance in habitat amount across urban landscapes. 2. We used airborne laser scanning data to disentangle the effects of 3D woody habitat heterogeneity of urban home gardens, and woody habitat amount at four landscape spatial scales (50, 100, 250, and 500 m), on the predation risk of artificial sentinel prey by birds and arthropods. 3. In both predator groups, and at all the investigated spatial scales, cross‐scale interactive effects between garden habitat heterogeneity and habitat amount in the urban landscape were the main drivers of predation. Risk of predation by birds was highest in heterogeneous garden habitats, but only in densely built urban landscapes where habitat amount was low to intermediate (10%–20%) at large spatial scales (250–500 m). It dropped independently of garden habitat heterogeneity when habitat amount became too low (

Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3–6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3–5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson’s trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.

Differentiation of CD4(+) T cells into type 1 or type 2 subsets is mediated by the expression of the opposing lineage defining transcription factors T-bet and GATA-3. However, the existence of GATA-3(+) T-bet(+) CD4(+) T cells in mice suggests functional plasticity of these subsets. Little is known about type 1 and type 2 plasticity of human T-cell subsets in vivo. Here, we show that in the xenogeneic environment of humanized mice, which lacks a functional immune-regulatory network, human CD4(+) and, notably, CD8(+) T cells preferentially differentiate into interleukin (IL)-4(+) GATA-3(+) and IL-4(+) interferon-γ(+) GATA-3(+) T-bet(+) subsets. Treatment with recombinant human IL-12 or expansion of IL-12-producing human dendritic cells in vivo reverted this phenotype and led to the down-regulation of GATA-3 expression. These changes also correlated with improved antiviral immune responses in humanized mice. In conclusion, our study shows the capacity of human CD4(+) and CD8(+) T cells for stable co-expression of GATA-3 and T-bet in humanized mice and reveals a critical role for IL-12 in regulating this phenotype.

Humanized mice have emerged as a promising model to study human immunity in vivo. Although they are susceptible to many pathogens exhibiting an almost exclusive human tropism, human immune responses to infection remain functionally impaired. It has recently been demonstrated that the expression of HLA molecules improves human immunity to lymphotropic virus infections in humanized mice. However, little is known about the extent of functional human immune responses in nonlymphoid tissues, such as in the liver, and the role of HLA expression in this context. Therefore, we analyzed human antiviral immunity in humanized mice during a hepatotropic adenovirus infection. We compared immune responses of conventional humanized NOD SCID IL-2Rγ–deficient (NSG) mice to those of a novel NOD SCID IL-2Rγ–deficient strain transgenic for both HLA-A*0201 and a chimeric HLA-DR*0101 molecule. Using a firefly luciferase–expressing adenovirus and in vivo bioluminescence imaging, we demonstrate a human T cell–dependent partial clearance of adenovirus-infected cells from the liver of HLA-transgenic humanized mice. This correlated with liver infiltration and activation of T cells, as well as the detection of Ag-specific humoral and cellular immune responses. When infected with a hepatitis C virus NS3–expressing adenovirus, HLA-transgenic humanized mice mounted an HLA-A*0201–restricted hepatitis C virus NS3-specific CD8+ T cell response. In conclusion, our study provides evidence for the generation of partial functional antiviral immune responses against a hepatotropic pathogen in humanized HLA-transgenic mice. The adenovirus reporter system used in our study may serve as simple in vivo method to evaluate future strategies for improving human intrahepatic immune responses in humanized mice.

In most exposed individuals, hepatitis C virus (HCV) establishes a chronic infection; this long-term infection in turn contributes to the development of liver diseases such as cirrhosis and hepatocellular carcinoma. The role of antibodies directed against HCV in disease progression is poorly understood. Neutralizing antibodies (nAbs) can prevent HCV infection in vitro and in animal models. However, the effects of nAbs on an established HCV infection are unclear. We demonstrate that three broadly nAbs-AR3A, AR3B, and AR4A-delivered with adeno-associated viral vectors can confer protection against viral challenge in humanized mice. Furthermore, we provide evidence that nAbs can abrogate an ongoing HCV infection in primary hepatocyte cultures and in a human liver chimeric mouse model. These results showcase a therapeutic approach to interfere with HCV infection by exploiting a previously unappreciated need for HCV to continuously infect new hepatocytes to sustain a chronic infection.