Addressing technical, social and economic constraints to rice fish culture in Laos, emphasising women’s involvement: DFID Aquaculture Research Programme Project R6380Cb, final technical report

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Growth: Expanding the Nature of Cities

This thesis aims to define and explore why it is absolutely necessary for cities to accommodate higher densities of people and incorporate the natural environment within the built environment. As urban populations continue to grow at rapid rates, the threat of losing our ties to the natural environment looms on the horizon, but presents architects with an opportunity to help combat this problem. This thesis aims to critically examine strategies for rethinking the architecture of cities, strategies that include both accommodating higher numbers of people and presenting people with the opportunity for frequent exposure to nature within the context of urban environments. Under the Supervision of Professor Mark Hoista

Struktur und Funktion von TcdA1 und TcdB2-TccC3 eines Tc-Toxinkomplexes aus Photorhabdus luminescens

Das Bakterium Photorhabdus luminescens lebt in einer mutualistischen Symbiose mit Nematoden der Gattung Heterorhabditis. Die Nematoden dringen in das Hämozöl und den Gastrointestinaltrakt verschiedener Insektenarten ein und sondern dort über ihre Körperausgänge die Bakterien ab. Um die Immunabwehr des Insekts zu umgehen und das Insekt zu töten, sekretiert Photorhabdus luminescens eine Vielzahl von Virulenzfaktoren, insbesondere Tc-Toxine. Tc-Toxine sind aus jeweils einer A-, B- und C-Komponente aufgebaut, die einen 1,7 Megadalton großen Holotoxinkomplex bilden. Dieser Komplex enthält ein toxisches Enzym, das nach Übertragung in die Wirtszelle durch Modifikation von Proteinen zum Zelltod führt. In der hier vorliegenden Arbeit wurden die dreidimensionalen Strukturen der pentameren AKomponente (TcdA1-Präpore aus Photorhabdus luminescens) und des Heterodimers der Bund C-Komponente (TcdB2-TccC3 aus Photorhabdus luminescens) mittels Röntgenkristallographie bestimmt. Das TcdB2-TccC3-Heterodimer bildet eine kokonähnliche Struktur und enthält im C-terminalen Bereich von TccC3 eine intrinsische Aspartatproteasedomäne. Diese Domäne spaltet den C-Terminus von TccC3 ab, der als ADPRibosyltransferase C3 die eigentlich toxische Komponente bildet, die wahrscheinlich in einem entfalteten Zustand im Kokon vorliegt. Desweiteren verschließt ein unsymmetrischer β-Propeller den Kokon in TcdB2. Die TcdA1-Struktur zeigt ein Pentamer, das aus einer äußeren Hülle und einem zentralen Translokationskanal aufgebaut ist. Die äußere Hülle enthält Insertionen, die sich in rezeptorbindende Domänen und in ein neuraminidaseähnliches Pentamer falten. Aufgrund der Homologie zu Sialidasen könnte dieses Pentamer Glykoproteine in der Wirtszelle enzymatisch spalten. Die rezeptorbindenden Domänen zeigen Homologien zu Interleukin- und Interferon- Rezeptoruntereinheiten. Durch Interaktionen mit Mitgliedern dieser Zytokinrezeptorfamilie könnte das TcdA1-Pentamer an der Wirtszellmembran stabilisiert und die Penetration der Membran durch den TcdA1-Translokationskanal bei einer Konformationsänderung unterstützt werden

5 steps to buying meat direct from the farm

Written by Jennifer Lutes (Field Specialist in Agricultural Business), Kyle Whittaker (County Engagement Specialist in Agriculture and Environment), Eric Meusch (Field Specialist in Livestock), Rachel Hopkins, (County Engagement Specialist in Agriculture and Environment), Amie Breshears (County Engagement Specialist in Agriculture and Environment)."If you plan to buy an animal to have processed into packaged meat, then the process can present some learning curves. This publication can help you navigate that process in five steps. Identify desired meat products. Purchase animal from livestock producer. Find a processor that fits your needs. Understand your costs. Consider timing."--Page 1.Jennifer Lutes (Field Specialist in Agricultural Business), Kyle Whittaker (County Engagement Specialist in Agriculture and Environment), Eric Meusch (Field Specialist in Livestock), Rachel Hopkins (County Engagement Specialist in Agriculture and Environment), Amie Breshears (County Engagement Specialist in Agriculture and Environment)New 5/22Includes bibliographical reference

Safety Interventions For Houseless Pedestrians

In 2016, the City of Portland adopted the Vision Zero Action Plan with the goal of eliminating traffic deaths and serious injuries on Portland’s streets. The Portland Bureau of Transportation (PBOT) also makes a commitment in all of its plans to create a more equitable transportation system by prioritizing areas of the city with a disproportionate number of BIPOC community members and people with lower incomes, all of whom face a greater risk from traffic violence. To achieve its Vision Zero goals, the City and PBOT have undertaken a number of actions, including redesigning streets through traffic calming and traffic management, and outreach and education. While progress has been made since the Vision Zero plan’s adoption, there has recently been an alarming increase in traffic crashes and fatalities, particularly among people experiencing houselessness. The PBOT Vision Zero team partnered with Street Perspective—the Portland State University Master of Urban and Regional Planning student Workshop team—to examine how to mitigate the risk of traffic-related harm to people experiencing houselessness. Through this project, Street Perspective has developed a report of existing conditions, promising practices, site-specific analysis, outreach, and a toolkit of recommendations to better understand and address the needs and vulnerabilities of people experiencing houselessness in Portland

Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis

The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine

Conformational changes during pore formation by the perforin-related protein pleurotolysin

Membrane attack complex/perforin-like (MACPF) proteins comprise the largest superfamily of pore-forming proteins, playing crucial roles in immunity and pathogenesis. Soluble monomers assemble into large transmembrane pores via conformational transitions that remain to be structurally and mechanistically characterised. Here we present an 11 Å resolution cryo-electron microscopy (cryo-EM) structure of the two-part, fungal toxin Pleurotolysin (Ply), together with crystal structures of both components (the lipid binding PlyA protein and the pore-forming MACPF component PlyB). These data reveal a 13-fold pore 80 Å in diameter and 100 Å in height, with each subunit comprised of a PlyB molecule atop a membrane bound dimer of PlyA. The resolution of the EM map, together with biophysical and computational experiments, allowed confident assignment of subdomains in a MACPF pore assembly. The major conformational changes in PlyB are a ~70° opening of the bent and distorted central β-sheet of the MACPF domain, accompanied by extrusion and refolding of two α-helical regions into transmembrane β-hairpins (TMH1 and TMH2). We determined the structures of three different disulphide bond-trapped prepore intermediates. Analysis of these data by molecular modelling and flexible fitting allows us to generate a potential trajectory of β-sheet unbending. The results suggest that MACPF conformational change is triggered through disruption of the interface between a conserved helix-turn-helix motif and the top of TMH2. Following their release we propose that the transmembrane regions assemble into β-hairpins via top down zippering of backbone hydrogen bonds to form the membrane-inserted β-barrel. The intermediate structures of the MACPF domain during refolding into the β-barrel pore establish a structural paradigm for the transition from soluble monomer to pore, which may be conserved across the whole superfamily. The TMH2 region is critical for the release of both TMH clusters, suggesting why this region is targeted by endogenous inhibitors of MACPF function

Abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels

Bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (SOX) bacteria that provide them with nutrition. We sequenced the SOX symbiont genomes from two Bathymodiolus species. Comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer. Many of the genes specific to the symbionts were homologs of virulence genes. We discovered an abundant and diverse array of genes similar to insecticidal toxins of nematode and aphid symbionts, and toxins of pathogens such as Yersinia and Vibrio. Transcriptomics and proteomics revealed that the SOX symbionts express the toxin-related genes (TRGs) in their hosts. We hypothesize that the symbionts use these TRGs in beneficial interactions with their host, including protection against parasites. This would explain why a mutualistic symbiont would contain such a remarkable 'arsenal' of TRG

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Functional and phenotypic heterogeneity of Th17 cells in health and disease

Background Th17 cells have nonredundant roles in maintaining immunity, particularly at mucosal surfaces. These roles are achieved principally through the production of cytokines and the recruitment of other immune cells to maintain the integrity of mucosal barriers and prevent the dissemination of microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of plasticity. This allows these cells to respond to changing environmental challenges. However, Th17 cells also play pro‐inflammatory roles in chronic autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic autoimmune diseases remain unclear. Design In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting IL‐17 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases. Results The report sheds light on likely triggers that initiate or perpetuate Th17 responses that promote chronic inflammation and autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17 cells in inducing autoreactive B cells, leading to autoantibody production. Pathogenic bacterial species can change Th17 cell phenotype and responses. These findings provide insights into how Th17 cells could be induced to promoting autoimmune disease pathogenesis. Conclusion This article provides an overview of the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces and in skin mucosa and how their functional flexibility could be linked with chronic inflammation in autoimmune rheumatic diseases