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Description

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

ContributorsKang, Dae Wook (Author) / Park, Jin (Author) / Ilhan, Zehra (Author) / Wallstrom, Garrick (Author) / LaBaer, Joshua (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2013-06-03
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Description

n public planning processes for sustainable urban development, planners and experts often face the challenge of engaging a public that is not familiar with sustainability principles or does not subscribe to sustainability values. Although there are calls to build the public’s sustainability literacy through social learning, such efforts require sufficient

n public planning processes for sustainable urban development, planners and experts often face the challenge of engaging a public that is not familiar with sustainability principles or does not subscribe to sustainability values. Although there are calls to build the public’s sustainability literacy through social learning, such efforts require sufficient time and other resources that are not always available. Alternatively, public participation processes may be realigned with the sustainability literacy the participants possess, and their capacity can modestly be built during the engagement. Asking what tools might successfully align public participation with participants’ sustainability literacy, this article describes and evaluates a public participation process in Phoenix, Arizona, in which researchers, in collaboration with city planners, facilitated sustainability conversations as part of an urban development process. The tool employed for Visually Enhanced Sustainability Conversation (VESC) was specifically designed to better align public participation with stakeholders’ sustainability literacy. We tested and evaluated VESC through interviews with participants, city planners, and members of the research team, as well as an analysis of project reports. We found that the use of VESC successfully facilitated discussions on pertinent sustainability issues and embedded sustainability objectives into the project reports. We close with recommendations for strengthening tools like VESC for future public engagements.

ContributorsCohen, Matthew (Author) / Wiek, Arnim (Author) / Kay, Braden (Author) / Harlow, John (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2015-07-03
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Description

Successful careers in sustainability are determined by positive real-world change towards sustainability. This success depends heavily on professional skills in effective and compassionate communication, collaborative teamwork, or impactful stakeholder engagement, among others. These professional skills extend beyond content knowledge and methodical expertise. Current sustainability programs do not sufficiently facilitate students’

Successful careers in sustainability are determined by positive real-world change towards sustainability. This success depends heavily on professional skills in effective and compassionate communication, collaborative teamwork, or impactful stakeholder engagement, among others. These professional skills extend beyond content knowledge and methodical expertise. Current sustainability programs do not sufficiently facilitate students’ acquisition of such skills. This article presents a brief summary of professional skills, synthesized from the literature, and why they are relevant for sustainability professionals. Second, it presents how these skills have been taught in an undergraduate course in sustainability at Arizona State University, USA. Third, it critically discusses the effectiveness and challenges of that exemplary course. Finally, the article concludes with outlining the lessons learned that should be incorporated into future course offerings.

Created2017-03-07
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Description

Resilience can have desirable and undesirable consequences. Thus, resilience should not be viewed as a normative desirable goal, but as a descriptor of complex systems dynamics. From this perspective, we apply resilience thinking concepts to assess the dynamics of inequality, spatial segregation, and sustainability in Chile’s capital city of Santiago.

Resilience can have desirable and undesirable consequences. Thus, resilience should not be viewed as a normative desirable goal, but as a descriptor of complex systems dynamics. From this perspective, we apply resilience thinking concepts to assess the dynamics of inequality, spatial segregation, and sustainability in Chile’s capital city of Santiago. Chile’s economy boosted since democracy was restored in 1990, but continuity of neoliberal reforms and transformations of Pinochet’s dictatorship (1973–1990) seem to have locked Chilean cities in resilient, albeit unsustainable, patterns of uneven development. Socio-economic data from Santiago shows highly resilient patterns of urban inequality and segregation from 1992 to 2009 despite democratic efforts, political agendas and discourses packed with calls for reducing poverty and inequality. We present a conceptual model based on the notion of stability landscapes to explore potential trade-offs between resilience and sustainable development. We mapped Santiago’s spatio-temporal inequality trends and explored if these patterns support an inequality-resilience stability landscape. Analysis of temporal and spatial distribution of development assets across four human development dimensions (i.e., income, education, health, democracy) revealed potential socio-political and spatial feedbacks supporting the resilience of inequality and segregation in Santiago. We argue that urban sustainability may require breaking this resilience, a process where bottom-up stressors such as social movements could play a key role.

Created2016-08-19
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Description

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complex to modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.

ContributorsSkibinski, Adam (Author) / Breindel, Jerrica L. (Author) / Prat, Aleix (Author) / Galvan, Patricia (Author) / Smith, Elizabeth (Author) / Rolfs, Andreas (Author) / Gupta, Piyush B. (Author) / LaBaer, Joshua (Author) / Kuperwasser, Charlotte (Author) / Biodesign Institute (Contributor)
Created2014-03-27
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Description

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

ContributorsWang, Wei (Author) / Yin, Linliang (Author) / Gonzalez-Malerva, Laura (Author) / Wang, Shaopeng (Author) / Yu, Xiaobo (Author) / Eaton, Seron (Author) / Zhang, Shengtao (Author) / Chen, Hong-Yuan (Author) / LaBaer, Joshua (Author) / Tao, Nongjian (Author) / Biodesign Institute (Contributor)
Created2014-10-14
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Description

In order to improve the efficiency of government spending, it is necessary for the decentralized irrigation management to gain support from local institutions. Efficient institutions take on several distinct configurations in different irrigation districts. In this research, we upgrade Tang’s (1992) framework focusing on incentives, to a framework that includes

In order to improve the efficiency of government spending, it is necessary for the decentralized irrigation management to gain support from local institutions. Efficient institutions take on several distinct configurations in different irrigation districts. In this research, we upgrade Tang’s (1992) framework focusing on incentives, to a framework that includes institutional incentives and coordination. Within the framework, we then classify 5 institutional variables: water pricing reform (P), government funding (F), coordination by administration (C), having formal monitors (M) and self-organized management (S). This article processes the data obtained through a field survey (2009–2011) in 20 of China’s southern counties, where they implement the “Small-scale Irrigation and Water Conservancy Key Counties Construction (Key Counties Construction)”, a national project supported by the central government. Next, it applies Data Envelopment Analysis (DEA) to measure the efficiency of government spending and uses Qualitative Comparative Analysis (QCA) to extract efficient institutional configurations. It concludes that there are generally three types of institutional configurations able to improve the efficiency of government spending, which are respectively: “government funding combined with coordination by administration”, “water pricing reform combined with self-organized management and coordination by administration or water pricing reform combined with self-organized management and government funding and formal monitors” and “self-organized management”. Among these, the second configuration is a mixed governance structure with multiple institutions coexisting, and this configuration occurs in the most efficient key counties. For that reason, it is viewed as the mainstream irrigation management approach, and we expect it to be the development trend in the future. Although Chinese irrigation policies are formalizing effective local institutions, they are still not sufficient. Future policies are needed to 1) promote institutions of government support for water laws in order to build stable expectations for both water user associations (WUAs) and farmers, 2) guide water pricing reform by ensuring farmers’ water rights and regulating water markets, and 3) provide opportunities for hiring professional monitors and crafting formal rules.

Created2016-02-01
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Description

Many population centers in the American West rely on water from the Colorado River Basin, which has faced shortages in recent years that are anticipated to be exacerbated by climate change. Shortages to urban water supplies related to climate change will not be limited to cities dependent on the Colorado

Many population centers in the American West rely on water from the Colorado River Basin, which has faced shortages in recent years that are anticipated to be exacerbated by climate change. Shortages to urban water supplies related to climate change will not be limited to cities dependent on the Colorado River. Considering this, addressing sustainable water governance is timely and critical for cities, states, and regions facing supply shortages and pollution problems. Engaging in sustainability transitions of these hydro-social systems will increase the ability of such systems to meet the water needs of urban communities. In this paper, we identify historical transitions in water governance and examine their context for three sites in the Colorado River Basin (Denver, Colorado, Las Vegas, Nevada, and Phoenix, Arizona) to provide insight for intentional transitions towards sustainable, or “water sensitive” cities. The comparative historical approach employed allows us to more fully understand differences in present-day water governance decisions between the sites, identify past catalysts for transitions, and recognize emerging patterns and opportunities that may impact current and future water governance in the Colorado River Basin and beyond.

ContributorsSullivan, Abigail (Author) / White, Dave (Author) / Larson, Kelli (Author) / Wutich, Amber (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2017-05-06
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Description

Nucleic Acid Programmable Protein Arrays (NAPPA) have emerged as a powerful and innovative technology for the screening of biomarkers and the study of protein-protein interactions, among others possible applications. The principal advantages are the high specificity and sensitivity that this platform offers. Moreover, compared to conventional protein microarrays, NAPPA technology

Nucleic Acid Programmable Protein Arrays (NAPPA) have emerged as a powerful and innovative technology for the screening of biomarkers and the study of protein-protein interactions, among others possible applications. The principal advantages are the high specificity and sensitivity that this platform offers. Moreover, compared to conventional protein microarrays, NAPPA technology avoids the necessity of protein purification, which is expensive and time-consuming, by substituting expression in situ with an in vitro transcription/translation kit. In summary, NAPPA arrays have been broadly employed in different studies improving knowledge about diseases and responses to treatments. Here, we review the principal advances and applications performed using this platform during the last years.

ContributorsDiez, Paula (Author) / Gonzalez-Gonzalez, Maria (Author) / Lourido, Lucia (Author) / Degano, Rosa M. (Author) / Ibarrola, Nieves (Author) / Casado-Vela, Juan (Author) / LaBaer, Joshua (Author) / Fuentes, Manuel (Author) / Biodesign Institute (Contributor)
Created2015-04-24
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Description

Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays.

Methods: In this work, we developed the Multiplexed Nucleic

Rationale: Cell-free protein microarrays display naturally-folded proteins based on just-in-time in situ synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays.

Methods: In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot.

Results: Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform. Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA.

Conclusion: All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research.

ContributorsYu, Xiaobo (Author) / Song, Lusheng (Author) / Petritis, Brianne (Author) / Bian, Xiaofang (Author) / Wang, Haoyu (Author) / Viloria, Jennifer (Author) / Park, Jin (Author) / Bui, Hoang (Author) / Li, Han (Author) / Wang, Jie (Author) / Liu, Lei (Author) / Yang, Liuhui (Author) / Duan, Hu (Author) / McMurray, David N. (Author) / Achkar, Jacqueline M. (Author) / Magee, Mitch (Author) / Qiu, Ji (Author) / LaBaer, Joshua (Author) / Biodesign Institute (Contributor)
Created2017-09-20