Characterization of the Human Host Gut Microbiome with an Integrated Genomics / Proteomics Approach

The new field of ‘omics’ has spawned the development of metaproteomics, an approach that has the ability to identify and decipher the metabolic functions of a proteome derived from a microbial community that is largely uncultivable. With the development and availabilities of high throughput proteomics, high performance liquid chromatography coupled to mass spectrometry (MS) has been leading the field for metaproteomics. MS-based metaproteomics has been successful in its’ investigations of complex microbial communities from soils to the human body. Like the environment, the human body is host to a multitude of microorganisms that reside within the skin, oral cavity, vagina, and gastrointestinal tract, referred to as the human microbiome. The human microbiome is made up of trillions of bacteria that outnumber human genes by several orders of magnitude. These microbes are essential for human survival with a significant dependence on the microbes to encode and carryout metabolic functions that humans have not evolved on their own. Recently, metaproteomics has emerged as the primary technology to understand the metabolic functional signature of the human microbiome. Using a newly developed integrated approach that combines metagenomics and metaproteomics, we attempted to address the following questions: i) do humans share a core functional microbiome and ii) how do microbial communities change in response to disease. This resulted in a comprehensive identification and characterization of the metaproteome from two healthy human gut microbiomes. These analyses have resulted in an extended application to characterize how Crohn’s disease affects the functional signature of the microbiota. Contrary to measuring highly complex and representative gut metaproteomes is a less complex, controlled human-derived microbial community present in the gut of gnotobiotic mice. This human gut model system enhanced the capability to directly monitor fundamental interactions between two dominant phyla, Bacteroides and Firmicutes, in gut microbiomes colonized with two or more phylotypes. These analyses revealed membership abundance and functional differences between phylotypes when present in either a binary or 12-member consortia. This dissertation aims to characterize host microbial interactions and develop MS-based methods that can provide a better understanding of the human gut microbiota composition and function using both approaches

Evaluating American Rainwater Harvesting Policy: A Case Study of Three U.S. Cities

In spite of increasing support for rainwater harvesting by public agencies, environmental organizations and well-defined industry guidelines, the researchers found a strikingly limited number of municipalities with formal rainwater harvesting policies and programs. With literature on rainwater harvesting limited to mostly instructional material, the researchers were compelled to examine the feasibility of rainwater harvesting guidelines and practices. International and domestic rainwater harvesting guidelines were considered. The researchers surveyed municipalities which have implemented rainwater harvesting policies and ordinances to determine the extent to which industry prescribed guidelines are feasible. The subject jurisdictions commonly regulated rainwater harvesting through ancillary city codes or programs though one enacted a stand-alone rainwater harvesting ordinance. The respondents evaluated system performance primarily through water conservation. The jurisdictions studied also concurred that identification of acceptable end-uses of rainwater and public education were the most feasible industry guidelines. System costs were identified as the main barrier to implementing rainwater harvesting. Economic subsidies and comprehensive planning policies were associated with program success

Attitude Accessiblity as a Determinant of Object Construal and Evaluation

Attitude accessibility, the ease with which a given attitude comes to mind, has been demonstrated to affect attention. The current experiments focus on the construal of multiply-categorizable objects. They seek to provide evidence that (a) construals toward which individuals have more accessible attitudes, i.e., those that are more attitude-evoking, are more likely to influence the evaluation of related objects and that (b) this effect of attitude accessibility on construal processes can be extended to a whole series of objects which vary along multiple dimensions. Experiment 1 provides evidence that construals whose related attitudes were made more accessible via attitude rehearsal were more likely to influence the evaluation of a related target. Experiments 2 and 3 extend these findings to the domain of foods, which vary along two potential construal continua (healthiness versus tastiness), and demonstrate that if participant attitudes toward fitness are made more accessible, participants’ judgments about eating a variety of specific foods are guided more by the healthiness of the foods

Review essays

Kenneth Joel Shapiro, Animal models of human psychology: critique o f science, ethics, and policy, 328pp., Hogrefe & Huber Publishers, Seattle, 1998 / Georges Chapouthier and Jean-Claude Nouet, eds. The Universal Declaration of Animal Rights: Comments and Intentions, 93pp., Ligue Frangaise des Droits de VAnimal, Paris 1998 / Mark A. Michael, editor, Preserving Nature: An International Perspective, 307pp., Humanity Books, New York, 2000

Hearing handicap and quality of life: Reports by cochlear implantees and their frequent communication partners

“Copyright 2001, Speech Pathology Association of Australia Ltd (https://www.speechpathologyaustralia.org.au/) . Published version of the paper reproduced here with permission from the publisher.”Questionnaires concerning communication, hearing handicap and quality of life were posted to all 55 adult cochlear implantees known to be resident in South Australia. Parallel questionnaires were included for completion by a chosen frequent communication partner. This interim analysis focuses on replies from 34/55 (61.8%) of recipients currently received on two scales included in the questionnnaire; the Hearing Handicap Inventory for the Elderly (HHIE - Ventry & Weinstein, 1982), and the SF-36 (Ware, Snow, Kosinski & Gandek, 1993). The main results indicate that: (a) implantees and their frequent communication partners substantially agree in their assessment of the hearing handicap remaining post-implantation, and (b) implantees’ ratings of aspects of quality of life are similar to those of the general population in South Australia. These results indicate both the complimentary and confirmatory nature of these two scales. Implications for assessment and intervention for this population are discussed in light of these findings

A comparative genomics approach to identifying the plasticity transcriptome

BACKGROUND: Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function. RESULTS: We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors. CONCLUSION: These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties

Beyond peer observation of teaching

OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs, based on promoting lifestyle change to prevent type 2 diabetes in real-world settings and to examine whether adherence to international guideline recommendations is associated with effectiveness. RESEARCH DESIGN AND METHODS Bibliographic databases were searched up to July 2012. Included studies had a follow-up of ≥12 months and outcomes comparing change in body composition, glycemic control, or progression to diabetes. Lifestyle interventions aimed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs. Data were combined using random-effects meta-analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines. RESULTS Twenty-five studies met the inclusion criteria. The primary meta-analysis included 22 studies (24 study groups) with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta-analysis shows that lifestyle interventions resulted in a mean weight loss of 2.12 kg (95% CI -2.61 to -1.63; I(2) = 91.4%). Adherence to guidelines was significantly associated with a greater weight loss (an increase of 0.3 kg per point increase on a 12-point guideline-adherence scale). CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective. Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence. However, more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects