Mus musculus deficient for secretory antibodies show delayed growth with an altered urinary metabolome

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and aged mice (up to 18 months of age), and the observed immunopathology in pIgR -/- mice was further characterised using flow cytometry. Urinary metabolites were analysed using gas chromatography-mass spectrometry (GC-MS), which revealed changes in metabolites that correlated with age-related increase in gut permeability in pIgR -/- mice. Results: We observed that pIgR -/- mice exhibited delayed growth, and this phenomenon is associated with low-grade gut inflammation that increased with ageing. The gross intraepithelial lymphocytic (IEL) infiltration characteristic of pIgR -/- mice was redefined as CD8α+αβ+ T cells, the majority of which expressed high levels of CD103 and CD69 consistent with tissue resident memory T cells (TRM). Comparison of the urinary metabolome between pIgR -/- and wild-type mice revealed key changes in urinary biomarkers fucose, glycine and Vitamin B5, suggestive of altered mucosal permeability. A significant increase in gut permeability was confirmed by analysing the site-specific uptake of sugar probes in different parts of the intestine. Conclusion: Our data show that loss of the secretory antibody system in mice results in enhanced accumulation of inflammatory IELs in the gut, which likely reflects ongoing inflammation in reaction to gut microbiota or food antigens, leading to delayed growth in pIgR -/- mice. We demonstrate that this leads to the presence of a unique urinary metabolome profile, which may provide a biomarker for altered gut permeability

Effects of sand burial and overstory tree age on seedling establishment in coastal Pinus thunbergii forests in the northern Shandong Peninsula, China

Coastal Pinus thunbergii (Japanese black pine) forests in the northern Shandong Peninsula of China recently experienced widespread natural regeneration failure. This study identifies critical factors that affect natural regeneration of P. thunbergii. Seeds from trees of various ages (13-32 years) were used to investigate the effects of age and burial depth in sand on germination and seedling establishment. Results show that seed density in 2-5 cm soil decreased with increased distance from the shoreline. Sand burial decreased seed germination but did not affect the relative growth rate of seedlings at depths from 0.5 to 3 cm. Germination, leaf mass ratio, and relative growth rates were higher with seedlings originating from older trees, all of which enhanced seedling resistance to sand burial. Tree age and seed burial were found to be determining factors for natural regeneration of the coastal P. thunbergii forest. Silvicultural treatments that promote quality of seed sources and mitigation of sand burial can be used in the future to improve the regeneration of these coastal forests

Comparison of soil erosion models used to study the Chinese Loess Plateau

The Loess Plateau suffers from severe soil erosion that leads to a series of ecological and economic problems such as reduced land productivity, exacerbated rural poverty, decreased biodiversity and sedimentation of the riverbed in the lower reaches of the Yellow River. Soil erosion models are commonly used on the Loess Plateau to help target sustainable land management strategies to control soil erosion. In this study, we compared eleven soil erosion models that were previously used on the Loess Plateau. We studied their prediction accuracy, process representation, data and calibration requirements, and potential application in scenario studies. The selected models consisted of a broad range of model types, structures and scales. The comparison showed that process-based and empirical models did not necessarily yield more accurate results over one another for the Loess Plateau. Among the process-based models, Si’ model, WEPP and MMF had the highest prediction accuracy. However, some of the selected models were tested with total sediment load while others were tested with suspended sediment load (i.e. bedload is not included), which is subject to several drawbacks. Research questions that each of the models can address on the Loess Plateau were suggested. Further improvement of soil erosion models for the Loess Plateau should concentrate on enhancing the quality of data for model implementation and testing, incorporating key processes into process-based models according to their aims and scales, comparing models that address the same research questions, and implementing internal and spatial model testing

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Transit-Oriented Development in China: How can it be planned in complex urban systems?

In recent years most of the Chinese cities have shown a rapid decline in modal split of public transport as a consequence of rapid urbanization and motorization in the “socialist market economy”. It has been witnessed that cars flood into streets; road congestion, air pollution and traffic safety have become major problems in urban China. To ameliorate this situation and to promote sustainable urban traffic, many Chinese metropolises consider the concept of Transit-Oriented Development (TOD), which is a model with worldwide successful experience in promoting public transport through integrating urban traffic with land use and creating a mobility environment where public transport is a much more respectable alternative to automobile travel. However, as the municipal governments embrace the concept, they were not aware of the fact that the realization of TOD requires fulfilling a number of preconditions, including a high level of land use diversity and density, beautiful urban design and cityscape, constraints on automobile use, good transit service qualities, good urban governance, and a real estate market that provides affordable and mixed types of housing. Even if the governments are informed of these conditions and seriously intend to meet these conditions, they are bound to deliberately enact comprehensive targeted policies and to mobilize substantial resources and support. However, after decades of economic reforms the Chinese cities have grown from comparatively simple systems that heavily depend on artificial intervention to complex and self-organizing systems that seem to be unplannable. In other words, it is very likely nowadays for the deliberate design for TOD to become dashed in complex cities. Therefore, rather than focusing on providing policy instruments and implementation recommendations of TOD for the Chinese local governments, this study sought to understand how cities are structured, what makes cities work, how to perceive cities as complex systems, and with such a perception how to plan cities (with respect to TOD). Accordingly, this book aims to pry open the complex urban systems firstly by formulating a conceptual model of cities and establishing 36 city parameters; and secondly by applying this framework into the case area, the Dalian city that is one of the most prosperous cities located in the eastern coastal region of China and has officially adopted TOD, whereby the empirical scores of the parameters are obtained. Based on the empirical scores, we draw lessons as to how the city parameters operate, how complex urban systems self-organize, and then what the implications are for deliberate design. The purpose of the lessons is to show elite politicians, policy analysts, public officials, legalists and also the wider public how TOD can be planned in contemporary cities in China.Policy, Organization, Law & GamingTechnology, Policy and Managemen

Public-Private Partnership and the Manageement of Expressways in China: An Agency Theory Approach

Technology, Policy and Managemen

Swarm intelligence in engineering

Electrical Engineering, Mathematics and Computer Scienc

A Tale of Two Chinese Transit Metropolises and the Implementation of Their Policies: Shenyang and Dalian (Liaoning Province, China)

To promote sustainable urbanization and combat the economic, environmental, energy and safety issues that go with rapid motorization, the Ministry of Transport in China has introduced the “Transit Metropolis” program with a substantive amount of funds devoted to the implementation of the program in local governments. This represents the largest ever central government-led effort addressing transit metropolis development in the world. How has the program been implemented locally? Have the selected demonstration cities followed the same principle or taken comparable measures to implement their version of the transit metropolis? What is their performance? These questions remain unknown in the current literature. This article answers the above questions through a literature review, interviews and comparative case studies in Shenyang and Dalian, two large cities in Liaoning Province. It shows that both cities have successfully achieved the target levels for building a transit metropolis. Similarities between the two cities can be found their absence of any policies on automobile restriction and the presence of enormous efforts in transit network expansion and optimization. Differences lie in the fact that Shenyang has been more conventional in developing the transit metropolis, while Dalian has been more innovative and flexible in policy implementation. When comparing our empirical findings with the experience of creating transit metropolis elsewhere in China and in foreign countries, we find that policies and regulations restricting car use and calming traffic are not necessary conditions for successful transit metropolises; however, the attractiveness of transit infrastructure, combined with aesthetic and well-decorated street network is essential for a modal shift for transit. We also find that the perception on the transit metropolis in China more emphasizes transit service improvement, while the concept in Western countries more focuses on the shift of land use patterns that lean more towards influencing transit behavior.Organisation and Governanc

Strategic Use of Analytical Information in Transport Planning in China: How Is It Different from Western Democracies?

Theory on the strategic use of knowledge in planning large infrastructure projects is comparatively well-developed in the fields of public policy and urban/transport planning for Western democracies. But how policymakers make use of knowledge and what position policy analysts hold in non-Western countries still remains largely unknown territory in the literature. This article begins to explore this topic by studying two urban transport projects in the Chinese city of Dalian. Based on empirical evidence, the article concludes with a number of preliminary but notable differences between Western countries and China in terms of the administrative mechanisms underlying the strategic use of knowledge in policymaking. We found that Chinese institutional incentives with regard to cadre evaluation and promotion channels largely constitute the motivation of politicians to use knowledge strategically. Additionally, the wider social and administrative cultures in China, including a command-and-control tradition and a high level of power distance create a basis for the strategic use of information as well as the manipulation of analytical data.Accepted Author ManuscriptTransport and LogisticsOrganisation and Governanc

A Typology of Strategic Behaviour in PPPs for Expressways: Lessons from China and Implications for Europe

In line with governance trends around the world, a growing number of expressways in the People’s Republic of China are managed as Public-Private Partnerships (PPPs). The tremendous growth in demand for mobility in newly emerging economies has led to a gap between investment needs and available public funding. Using private funds is potentially helpful in closing this gap and accommodating the social and economic needs of motorization. By some, it is also hoped that contracting-out and involvement of the private sector will lead to higher transparency and accountability. However, in line with what has been found in various transport infrastructure modes, during uncertain and hazy transition periods that arise after infrastructure reforms, many forms of potentially pernicious strategic behaviour can pop up. Strategic behaviour emerges from information a-symmetry between private and public players, where the former act as agents and the latter as principals. In this article, China’s evidence on various types of strategic behaviour in the management of expressways is found. Several PPP projects for expressways in China are investigated empirically. And conclusions are drawn as to what possible cures are effective countermeasures of strategic behaviour, and what are the implications for Europe.Multi Actor SystemsTechnology, Policy and Managemen