The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
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Independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae)

Phytochemical diversity is thought to result from coevolutionary cycles as specialization in herbivores imposes diversifying selection on plant chemical defenses. Plants in the speciose genus Erysimum (Brassicaceae) produce both ancestral glucosinolates and evolutionarily novel cardenolides as defenses. Here we test macroevolutionary hypotheses on co-expression, co-regulation, and diversification of these potentially redundant defenses across this genus. We sequenced and assembled the genome of E. cheiranthoides and foliar transcriptomes of 47 additional Erysimum species to construct a phylogeny from 9868 orthologous genes, revealing several geographic clades but also high levels of gene discordance. Concentrations, inducibility, and diversity of the two defenses varied independently among species, with no evidence for trade-offs. Closely related, geographically co-occurring species shared similar cardenolide traits, but not glucosinolate traits, likely as a result of specific selective pressures acting on each defense. Ancestral and novel chemical defenses in Erysimum thus appear to provide complementary rather than redundant functions.Austrian Science Fund (FWF) PZ00P3-161472National Science Foundation (NSF) 1811965 1645256Triad FoundationGerman Research Foundation (DFG) DFG-PE 2059/3-1Agencia Estatal de Investigacion CGL2017-86626-C2-2-PLOEWE Program Insect Biotechnology and BioresourcesJunta de Andalucía A-RNM505-UGR1

Algorithmic support for commodity-based parallel computing systems.

The Computational Plant or Cplant is a commodity-based distributed-memory supercomputer under development at Sandia National Laboratories. Distributed-memory supercomputers run many parallel programs simultaneously. Users submit their programs to a job queue. When a job is scheduled to run, it is assigned to a set of available processors. Job runtime depends not only on the number of processors but also on the particular set of processors assigned to it. Jobs should be allocated to localized clusters of processors to minimize communication costs and to avoid bandwidth contention caused by overlapping jobs. This report introduces new allocation strategies and performance metrics based on space-filling curves and one dimensional allocation strategies. These algorithms are general and simple. Preliminary simulations and Cplant experiments indicate that both space-filling curves and one-dimensional packing improve processor locality compared to the sorted free list strategy previously used on Cplant. These new allocation strategies are implemented in Release 2.0 of the Cplant System Software that was phased into the Cplant systems at Sandia by May 2002. Experimental results then demonstrated that the average number of communication hops between the processors allocated to a job strongly correlates with the job's completion time. This report also gives processor-allocation algorithms for minimizing the average number of communication hops between the assigned processors for grid architectures. The associated clustering problem is as follows: Given n points in {Re}d, find k points that minimize their average pairwise L{sub 1} distance. Exact and approximate algorithms are given for these optimization problems. One of these algorithms has been implemented on Cplant and will be included in Cplant System Software, Version 2.1, to be released. In more preliminary work, we suggest improvements to the scheduler separate from the allocator

Extracting heuristics from experienced instructional designers

Experienced instructional design practitioners often use personal rules of thumb (heuristics) when engaged in the instructional design problem-solving process. It could be beneficial for novices to know which heuristics experienced instructional designers use as one way to make their problem-solving processes more efficient. Thus, this two-phase study investigated instructional design heuristics used by experienced instructional designers. Phase A included interviews with experienced instructional designers, during which each participant told a story about a complex instructional design project on which he/she had worked. From these stories we extracted a set of heuristics that guided their practice. In Phase B, Delphi surveys were conducted with a panel of experienced instructional designers, which allowed for corroboration and consensus of the heuristics found in Phase A. Interviews resulted in 8 categories of heuristics. Categories included communication, management, learner/audience, solutions/deliverables/outcomes, design process, design team, design problem, and client. Within each category multiple heuristics were identified. The Delphi process resulted in 61 instructional design heuristics classified into the same eight categories. Within each category, multiple heuristics were again identified and also rank-ordered based on the calculated mean of each heuristic’s ratings. Discussion centers on the incorporation of heuristics in novice instructional design education. Because instructional design is a problem-solving process, novices need to understand what practicing instructional designers do, rather than just memorizing procedures in instructional design models. Based on the results of this study, instructional design educators should consider teaching business, project management, and communication skills (in addition to the basic ID skills), which most instructional design models fail to include

Virtual Classroom Extension for Effective Distance Education

We present the design, implementation, and initial results of a system for remote lecture attendance based on extending on-campus classrooms to accommodate remotely located students. A remote student is modeled with a real-time video sprite. The sprites are integrated into a geometric model that ~rovides a virtual extension of the classroom. The A-virtual extension is rendered and projected onto the back wall of the classroom. The remote students are displayed at a natural location within the field of view of the instructor, who can conveniently get a sense of their body language and of their facial expression. The system has been deployed in a first classroom and a pilot study indicates that the system promises to deliver quality education remotely. The system relies exclusively on commodity components, therefore it can be deployed in any classroom to allow any course to offer distance education seats. Keywords I.3.6.d Interaction techniques, I.3.7.g Virtual reality, I.3.2.a Distributed/network graphics

Pre-service teachers\u27 motivation to use technology and the impact of authentic learning exercises

In this quasi-experimental study, the authors explored the impact of authentic learning exercises on pre-service teachers\u27 motivational beliefs to integrate technology, as well as the ability of those beliefs to predict intentions to integrate. A questionnaire was used to assess 104 pre-service teachers\u27 motivational beliefs, namely intrinsic and extrinsic goal orientations, task value, self-efficacy, and control of learning in relation to technology integration. Results indicated authentic learning exercises might have enhanced motivational beliefs, particularly self-efficacy and intrinsic goal-orientation. Also, motivational beliefs predicted their intentions to integrate technology into future instruction, with task value predicting significantly. The chapter concludes with implications for practice

Usability Services An Introduction to Web Accessibility

Slides for a workshop taught by Teal Anderson and Cynthia York for the Welch Library course series

Impact of meningococcal vaccination on carriage and disease transmission: A review of the literature

Colonization of the human nasopharyngeal tract by the bacterium Neisseria meningitidis is usually asymptomatic, but life-threatening meningococcal disease with a clinical presentation of meningitis, septicemia, or more rarely, gastrointestinal symptoms, can develop. Invasive meningococcal disease (IMD) can be fatal within 24 hours, but IMD is vaccine-preventable. Vaccines used to protect against IMD caused by 5 of the 6 most common serogroups (A, B, C, W, and Y) may also influence carriage prevalence in vaccinated individuals. Lower carriage among vaccinated people may reduce transmission to nonvaccinated individuals to provide herd protection against IMD. This article reviews observational and clinical studies examining effects of vaccination on N. meningitidis carriage prevalence in the context of mass vaccination campaigns and routine immunization programs. Challenges associated with carriage studies are presented alongside considerations for design of future studies to assess the impact of vaccination on carriage