Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD

Intestinal Microbiota Composition of Interleukin-10 Deficient C57BL/6J Mice and Susceptibility to Helicobacter hepaticus-Induced Colitis

The mouse pathobiont Helicobacter hepaticus can induce typhlocolitis in interleukin-10-deficient mice, and H. hepaticus infection of immunodeficient mice is widely used as a model to study the role of pathogens and commensal bacteria in the pathogenesis of inflammatory bowel disease. C57BL/6J Il10[superscript −/−] mice kept under specific pathogen-free conditions in two different facilities (MHH and MIT), displayed strong differences with respect to their susceptibilities to H. hepaticus-induced intestinal pathology. Mice at MIT developed robust typhlocolitis after infection with H. hepaticus, while mice at MHH developed no significant pathology after infection with the same H. hepaticus strain. We hypothesized that the intestinal microbiota might be responsible for these differences and therefore performed high resolution analysis of the intestinal microbiota composition in uninfected mice from the two facilities by deep sequencing of partial 16S rRNA amplicons. The microbiota composition differed markedly between mice from both facilities. Significant differences were also detected between two groups of MHH mice born in different years. Of the 119 operational taxonomic units (OTUs) that occurred in at least half the cecum or colon samples of at least one mouse group, 24 were only found in MIT mice, and another 13 OTUs could only be found in MHH samples. While most of the MHH-specific OTUs could only be identified to class or family level, the MIT-specific set contained OTUs identified to genus or species level, including the opportunistic pathogen, Bilophila wadsworthia. The susceptibility to H. hepaticus-induced colitis differed considerably between Il10[superscript −/−] mice originating from the two institutions. This was associated with significant differences in microbiota composition, highlighting the importance of characterizing the intestinal microbiome when studying murine models of IBD.National Institutes of Health (U.S.) (Grant NIH P01-CA26731)National Institutes of Health (U.S.) (Grant NIH P30ES0026731)National Institutes of Health (U.S.) (Grant NIH R01-OD011141

Global Changes in Staphylococcus aureus Gene Expression in Human Blood

Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

Can organization change: eviromenta: protection, citizen partipation and the corps of engineers/ Mazmanian

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State Leadership in US Climate Change and Energy Policy: The California Experience

It is a long-held belief among scholars and practitioners that the State of California is a notable subnational leader in environmental and climate change policy. This article focuses primarily on four essential contextual factors that explain why and how within the United States’ federal system of government California has become such an important leader, performing far in excess of the national government and most other states. These essential factors are preferences, authority, capacity, and effectiveness. The article then moves to the multifaceted implementation strategy California policy makers have employed to realize their environmental goals. Finally, despite the history of strong leadership, the state continues to face a host of significant challenges in realizing its ambitious climate change goals for the coming decades

The Paradox of “Acting Globally While Thinking Locally”: Discordance in Climate Change Adaption Policy

The paradox motivating this article is why California has acted globally by enacting a comprehensive mitigation policy to reduce the emissions of Greenhouse gases, a true public good since the benefits will be shared across the planet, but has not mustered the will to act locally through the adoption of an equally comprehensive adaptation policy for the state to protect its own public and private assets and interests. We attempt to explain the paradox by identifying what it is that differentiates climate change adaptation from mitigation, both substantively and politically. The paradox notwithstanding, we identify several imaginable adaptation policies and strategies that would be commensurate with individual and collective self-interested behavior

The governance of adaptation:choices, reasons, and effects. Introduction to the Special Feature

The governance of climate adaptation involves the collective efforts of multiple societal actors to address problems, or to reap the benefits, associated with impacts of climate change. Governing involves the creation of institutions, rules and organizations, and the selection of normative principles to guide problem solution and institution building. We argue that actors involved in governing climate change adaptation, as climate change governance regimes evolve, inevitably must engage in making choices, for instance on problem definitions, jurisdictional levels, on modes of governance and policy instruments, and on the timing of interventions. Yet little is known about how and why these choices are made in practice, and how such choices affect the outcomes of our efforts to govern adaptation. In this introduction we review the current state of evidence and the specific contribution of the articles published in this Special Feature, which are aimed at bringing greater clarity in these matters, and thereby informing both governance theory and practice. Collectively, the contributing papers suggest that the way issues are defined has important consequences for the support for governance interventions, and their effectiveness. The articles suggest that currently the emphasis in adaptation governance is on the local and regional levels, while underscoring the benefits of interventions and governance at higher jurisdictional levels in terms of visioning and scaling-up effective approaches. The articles suggest that there is a central role of government agencies in leading governance interventions to address spillover effects, to provide public goods, and to promote the long-term perspectives for planning. They highlight the issue of justice in the governance of adaptation showing how governance measures have wide distributional consequences, including the potential to amplify existing inequalities, access to resources, or generating new injustices through distribution of risks. For several of these findings, future research directions are suggested.</p

PV-BILD: A Life Cycle Environmental and Economic Assessment Tool for Building-Integrated Photovoltaic Installations

An elegant application of photovoltaic (PV) technology is in building-integrated designs (BIPV), in which the PV modules become an integral part of the building envelope. BIPV systems perform the traditional architectural functions of walls and roofs (weather protection, structural, and aesthetic) while performing the additional function of generating electricity. BIPV systems displace conventional building materials and utility-generated electricity and do not require additional land area or supplementary support structures. A life cycle environmental and economic model and software tool were developed to assist in the evaluation and design of building-integrated photovoltaic installations. This tool, called the Photovoltaic-Building Integrated Lifecycle Design tool or PV-BILD, calculates a set of life-cycle environmental impacts and benefits associated with a specified BIPV system while also evaluating the combination of conventional electricity and building materials that the BIPV system displaces. The environmental data categories investigated include energy, air pollutant emissions, water use, and waste generated. PV-BILD also calculates system energy performance metrics and system economic parameters. PV-BILD currently includes data for two BIPV products (a shingle product and standing-seam metal roofing) and one inverter, as well as insolation and electric utility parameters for 15 cities around the United States. Results were generated for a reference BIPV system (2kWp shingle system with a 20 year life) for the 15 cities in PV-BILD. The electricity production efficiency (electricity output/total primary energy input excluding insolation) for a reference system ranged from 3.42 in Portland, OR to 5.57 in Phoenix, AZ indicating a significant return on energy investment. The energy performance of this BIPV system is dramatically better than conventional electricity generation. The pollution prevention benefits of displaced conventional building material were negligible compared to the benefits from displacing conventional electricity generation for the reference system. The reference system had the greatest air pollution prevention benefits in cities with conventional electricity generation mixes dominated by coal and natural gas, not necessarily in cities where the insolation and displaced conventional electricity were greatest. Detroit had the highest mass of pollution prevention for all air emissions except methane and carbon monoxide. The life cycle economic analysis determined the value of the air pollution prevention achieved by the BIPV system. The value of avoided air pollution without regulation of carbon emissions ranged from 1.8 cents/kWh in Detroit to 0.5 cents/kWh in Boston based on the unit damage costs incorporated in the model. With carbon regulation, the value of avoided air pollution ranged from 4.4 cents/kWh in Detroit to 1.3 cents/kWh in Boston based on a carbon compliance cost of $130/ton. The cost for the BIPV reference system was 32 cents/kWh in Detroit based on a 20 year service life. Even when avoided damage costs are included, the reference system is not economically competitive with conventional grid electricity. It should be noted that many other environmental costs associated with conventional electricity generation such as oil spills, nuclear wastes, and habitat destruction from hydroelectric dams were not included in this analysis. Even considering these factors, consumers motivated primarily by economic arguments are not likely to deploy BIPV systems until system cost comes down substantially or the cost of conventional electricity rises.http://deepblue.lib.umich.edu/bitstream/2027.42/192099/1/css99-02r2.pdfDescription of css99-02r2.pdf : ReportSEL