Faculty and Staff

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.

We present a microarray nonlinear calibration (MiNC) method for quantifying antibody binding to the surface of protein microarrays that significantly increases the linear dynamic range and reduces assay variation compared with traditional approaches. A serological analysis of guinea pig Mycobacterium tuberculosis models showed that a larger number of putative antigen targets were identified with MiNC, which is consistent with the improved assay performance of protein microarrays. MiNC has the potential to be employed in biomedical research using multiplex antibody assays that need quantitation, including the discovery of antibody biomarkers, clinical diagnostics with multi-antibody signatures, and construction of immune mathematical models.

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated. The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies. However, the overall progress of viral ORF cloning has been slow. To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system. Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays. The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies. These valuable plasmid resources will be available to the research community to enable continued viral functional studies.

Rho GTPases are frequent targets of virulence factors as they are keystone signaling molecules. Herein, we demonstrate that AMPylation of Rho GTPases by VopS is a multifaceted virulence mechanism that counters several host immunity strategies. Activation of NFκB, Erk, and JNK kinase signaling pathways were inhibited in a VopS-dependent manner during infection with Vibrio parahaemolyticus. Phosphorylation and degradation of IKBα were inhibited in the presence of VopS as was nuclear translocation of the NFκB subunit p65. AMPylation also prevented the generation of superoxide by the phagocytic NADPH oxidase complex, potentially by inhibiting the interaction of Rac and p67. Furthermore, the interaction of GTPases with the E3 ubiquitin ligases cIAP1 and XIAP was hindered, leading to decreased degradation of Rac and RhoA during infection. Finally, we screened for novel Rac1 interactions using a nucleic acid programmable protein array and discovered that Rac1 binds to the protein C1QA, a protein known to promote immune signaling in the cytosol. Interestingly, this interaction was disrupted by AMPylation. We conclude that AMPylation of Rho Family GTPases by VopS results in diverse inhibitory consequences during infection beyond the most obvious phenotype, the collapse of the actin cytoskeleton.

This paper presents a Bayesian framework for evaluative classification. Current education policy debates center on arguments about whether and how to use student test score data in school and personnel evaluation. Proponents of such use argue that refusing to use data violates both the public’s need to hold schools accountable when they use taxpayer dollars and students’ right to educational opportunities. Opponents of formulaic use of test-score data argue that most standardized test data is susceptible to fatal technical flaws, is a partial picture of student achievement, and leads to behavior that corrupts the measures.

A Bayesian perspective on summative ordinal classification is a possible framework for combining quantitative outcome data for students with the qualitative types of evaluation that critics of high-stakes testing advocate. This paper describes the key characteristics of a Bayesian perspective on classification, describes a method to translate a naïve Bayesian classifier into a point-based system for evaluation, and draws conclusions from the comparison on the construction of algorithmic (including point-based) systems that could capture the political and practical benefits of a Bayesian approach. The most important practical conclusion is that point-based systems with fixed components and weights cannot capture the dynamic and political benefits of a reciprocal relationship between professional judgment and quantitative student outcome data.

This is a brief text intended for use in undergraduate school-and-society classes. Your class may also be titled “Social foundations of education.” “Social foundations of education” is an interdisciplinary field that includes both humanities and social-science perspectives on schooling. It thus includes study of the philosophy and history of education as well as sociological, economic, anthropological, and political perspectives on schooling.

The core of most social foundations classes lies in the relationship between formal schooling and broader society. This emphasis means that while some parts of psychology may be related to the core issues of social foundations classes—primarily social psychology—the questions that are asked within a social-foundations class are different from the questions raised in child development, educational psychology, and most teaching-methods classes. For example, after finishing the first chapter of this text, you should be able to answer the question, “Why does the federal government pay public schools to feed poor students at breakfast and lunch?” Though there is some psychology research tying nutrition to behavior and learning, the policy is based on much broader expectations of schools. In this case, “Children learn better if they are well-fed” both is based on research and also is an incomplete answer.

The current debate over graduate rate calculations and results has glossed over the relationship between student migration and the accuracy of various graduation rates proposed over the past five years. Three general grade-based graduation rates have been proposed recently, and each has a parallel version that includes an adjustment for migration, whether international, internal to the U.S., or between different school sectors. All of the adjustment factors have a similar form, allowing simulation of estimates from real data, assuming different unmeasured net migration rates. In addition, a new age-based graduation rate, based on mathematical demography, allows the simulation of estimates on a parallel basis using data from Virginia's public schools.

Both the direct analysis and simulation demonstrate that graduation rates can only be useful with accurate information about student migration. A discussion of Florida's experiences with longitudinal cohort graduation rates highlights some of the difficulties with the current status of the oldest state databases and the need for both technical confidence and definitional clarity. Meeting the No Child Left Behind mandates for school-level graduation rates requires confirmation of transfers and an audit of any state system for accuracy, and basing graduation rates on age would be a significant improvement over rates calculated using grade-based data.

The spread of academic testing for accountability purposes in multiple countries has obscured at least two historical purposes of academic testing: community ritual and management of the social structure. Testing for accountability is very different from the purpose of academic challenges one can identify in community “examinations” in 19th century North America, or exams’ controlling access to the civil service in Imperial China. Rather than testing for ritual or access to mobility, the modern uses of testing are much closer to the state-building project of a tax census, such as the Domesday Book of medieval Britain after the Norman Invasion, the social engineering projects described in James Scott's Seeing like a State (1998), or the “mapping the world” project that David Nye described in America as Second Creation (2004). This paper will explore both the instrumental and cultural differences among testing as ritual, testing as mobility control, and testing as state-building.