Linking Old Librarianship to New: Aligning 5-Steps of The Innovator's DNA in Creating Thematic Discovery Systems for the Everglades

This poster presentation from the May 2015 Florida Library Association Conference, along with the Everglades Explorer discovery portal at http://ee.fiu.edu, demonstrates how traditional bibliographic and curatorial principles can be applied to: 1) selection, cross-walking and aggregation of metadata linking end-users to wide-spread digital resources from multiple silos; 2) harvesting of select PDFs, HTML and media for web archiving and access; 3) selection of CMS domains, sub-domains and folders for targeted searching using an API. Choosing content for this discovery portal is comparable to past scholarly practice of creating and publishing subject bibliographies, except metadata and data are housed in relational databases. This new and yet traditional capacity coincides with: Growth of bibliographic utilities (MarcEdit); Evolution of open-source discovery systems (eXtensible Catalog); Development of target-capable web crawling and archiving systems (Archive-it); and specialized search APIs (Google). At the same time, historical and technical changes – specifically the increasing fluidity and re-purposing of syndicated metadata – make this possible. It equally stems from the expansion of freely accessible digitized legacy and born-digital resources. Innovation principles helped frame the process by which the thematic Everglades discovery portal was created at Florida International University. The path -- to providing for more effective searching and co-location of digital scientific, educational and historical material related to the Everglades -- is contextualized through five concepts found within Dyer and Christensen’s “The Innovator’s DNA: Mastering the five skills of disruptive innovators (2011). The project also aligns with Ranganathan’s Laws of Library Science, especially the 4th Law -- to "save the time of the user.”

Bioinformatic analysis for exploring relationships between genes and gene products

To carry out their specific roles in the cell, genes and gene products often work together in groups, forming many relationships among themselves and with other molecules. Such relationships include physical protein-protein interaction relationships, regulatory relationships, metabolic relationships, genetic relationships, and much more. With advances in science and technology, some high throughput technologies have been developed to simultaneously detect tens of thousands of pairwise protein-protein interactions and protein-DNA interactions. However, the data generated by high throughput methods are prone to noise. Furthermore, the technology itself has its limitations, and cannot detect all kinds of relationships between genes and their products. Thus there is a pressing need to investigate all kinds of relationships and their roles in a living system using bioinformatic approaches, and is a central challenge in Computational Biology and Systems Biology. This dissertation focuses on exploring relationships between genes and gene products using bioinformatic approaches. Specifically, we consider problems related to regulatory relationships, protein-protein interactions, and semantic relationships between genes. A regulatory element is an important pattern or "signal", often located in the promoter of a gene, which is used in the process of turning a gene "on" or "off". Predicting regulatory elements is a key step in exploring the regulatory relationships between genes and gene products. In this dissertation, we consider the problem of improving the prediction of regulatory elements by using comparative genomics data. With regard to protein-protein interactions, we have developed bioinformatics techniques to estimate support for the data on these interactions. While protein-protein interactions and regulatory relationships can be detected by high throughput biological techniques, there is another type of relationship called semantic relationship that cannot be detected by a single technique, but can be inferred using multiple sources of biological data. The contributions of this thesis involved the development and application of a set of bioinformatic approaches that address the challenges mentioned above. These included (i) an EM-based algorithm that improves the prediction of regulatory elements using comparative genomics data, (ii) an approach for estimating the support of protein-protein interaction data, with application to functional annotation of genes, (iii) a novel method for inferring functional network of genes, and (iv) techniques for clustering genes using multi-source data.

Theoretical Investigation of Intra- and Inter-cellular Spatiotemporal Calcium Patterns in Microcirculation

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined. Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.

Comparative reproductive biology of two Florida pawpaws Asimina reticulata Chapman and Asimina tetramera Small

I investigated the phenology and breeding systems of two Florida endemic pawpaws, Asimina reticulata, widespread in peninsular Florida, and A. tetramera, a federally endangered species limited to two counties on the Atlantic Coastal Ridge. The purpose of this study was to determine if differences contribute to the rarity of Asimina tetramera compared with A. reticulata. The study was conducted in sand pine scrub sites with the largest populations of A. tetramera in the two counties. Flowering seasons differ for the two species. Both species are hermaphroditic and strongly protogynous. Pollination experiments show that neither species is autogamous and the primary breeding mechanism is outcrossing, although low levels of geitonogamous pollination occur in mature scrub habitats. High levels of inbreeding depression were noted in both species at both sites but inbreeding depression was relaxed the first year post-fire. Fruit set in mature habitats may be pollinator limited. ^ I studied insects associated with the flowers in sand pine scrub habitat in southeastern Florida from 1994–1996. The most commonly represented orders were Coleoptera (25 spp.), Lepidoptera. (3 spp.) and Hymenoptera. (3 spp.). All Coleoptera. were flower visitors; one species, Euphoria sepulchralis (Fabricius)(Scarabeaidae), visited flowers of the two Asimina species at both sites. Eurytides marcellus (Cramer) (Lepidoptera: Papilionidae) eggs and larvae were observed on both species of Asimina during each year of the study. ^ Resource management techniques were applied to a mature sand pine scrub community in Jonathan Dickinson State Park in southeastern Florida for the management of Asimina tetramera. Manipulations conducted in 1996 included combinations of fire and mechanical treatments. I measured effects of these treatments on flowering and fruit set on A. tetramera and found cutting and burning was most effective in increasing flowering, followed by burning. Mechanical cutting and mulching had no significant effect. ^

Molecular markers and human history: A tale of two haplogroup systems

To chronicle demographic movement across African Asian corridors, a variety of molecular (sequence analysis, restriction mapping and denaturing high performance liquid chromatography etc.) and statistical (correspondence analysis, AMOVA, calculation of diversity indices and phylogenetic inference, etc.) techniques were employed to assess the phylogeographic patterns of mtDNA control region and Y chromosomal variation among 14 sub-Saharan, North African and Middle Eastern populations. The patterns of genetic diversity revealed evidence of multiple migrations across several African Asian passageways as well within the African continent itself. The two-part analysis uncovered several interesting results which include the following: (1) a north (Egypt and Middle East Asia) to south (sub-Saharan Africa) partitioning of both mtDNA and Y chromosomal haplogroup diversity, (2) a genetic diversity gradient in sub-Saharan Africa from east to west, (3) evidence in favor of the Levantine Corridor over the Horn of Africa as the major genetic conduit since the Last Glacial Maximum, (4) a substantially higher mtDNA versus Y chromosomal sub-Saharan component in the Middle East collections, (5) a higher representation of East versus West African mtDNA haplotypes in the Arabian Peninsula populations versus no such bias in the Levant groups and lastly, (6) genetic remnants of the Bantu demographic expansion in sub-Saharan Africa. ^

Does landscape context affect habitat value? The importance of seascape ecology in back-reef systems

Seascape ecology provides a useful framework from which to understand the processes governing spatial variability in ecological patterns. Seascape context, or the composition and pattern of habitat surrounding a focal patch, has the potential to impact resource availability, predator-prey interactions, and connectivity with other habitats. For my dissertation research, I combined a variety of approaches to examine how habitat quality for fishes is influenced by a diverse range of seascape factors in sub-tropical, back-reef ecosystems. In the first part of my dissertation, I examined how seascape context can affect reef fish communities on an experimental array of artificial reefs created in various seascape contexts in Abaco, Bahamas. I found that the amount of seagrass at large spatial scales was an important predictor of community assembly on these reefs. Additionally, seascape context had differing effects on various aspects of habitat quality for the most common reef species, White grunt Haemulon plumierii. The amount of seagrass at large spatial scales had positive effects on fish abundance and secondary production, but not on metrics of condition and growth. The second part of my dissertation focused on how foraging conditions for fish varied across a linear seascape gradient in the Loxahatchee River estuary in Florida, USA. Gray snapper, Lutjanus griseus, traded food quality for quantity along this estuarine gradient, maintaining similar growth rates and condition among sites. Additional work focused on identifying major energy flow pathways to two consumers in oyster-reef food webs in the Loxahatchee. Algal and microphytobenthos resource pools supported most of the production to these consumers, and body size for one of the consumers mediated food web linkages with surrounding mangrove habitats. All of these studies examined a different facet of the importance of seascape context in governing ecological processes occurring in focal habitats and underscore the role of connectivity among habitats in back-reef systems. The results suggest that management approaches consider the surrounding seascape when prioritizing areas for conservation or attempting to understand the impacts of seascape change on focal habitat patches. For this reason, spatially-based management approaches are recommended to most effectively manage back-reef systems.

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.

Does Landscape Context Affect Habitat Value? The Importance of Seascape Ecology in Back-reef Systems

Seascape ecology provides a useful framework from which to understand the processes governing spatial variability in ecological patterns. Seascape context, or the composition and pattern of habitat surrounding a focal patch, has the potential to impact resource availability, predator-prey interactions, and connectivity with other habitats. For my dissertation research, I combined a variety of approaches to examine how habitat quality for fishes is influenced by a diverse range of seascape factors in sub-tropical, back-reef ecosystems. In the first part of my dissertation, I examined how seascape context can affect reef fish communities on an experimental array of artificial reefs created in various seascape contexts in Abaco, Bahamas. I found that the amount of seagrass at large spatial scales was an important predictor of community assembly on these reefs. Additionally, seascape context had differing effects on various aspects of habitat quality for the most common reef species, White grunt Haemulon plumierii. The amount of seagrass at large spatial scales had positive effects on fish abundance and secondary production, but not on metrics of condition and growth. The second part of my dissertation focused on how foraging conditions for fish varied across a linear seascape gradient in the Loxahatchee River estuary in Florida, USA. Gray snapper, Lutjanus griseus, traded food quality for quantity along this estuarine gradient, maintaining similar growth rates and condition among sites. Additional work focused on identifying major energy flow pathways to two consumers in oyster-reef food webs in the Loxahatchee. Algal and microphytobenthos resource pools supported most of the production to these consumers, and body size for one of the consumers mediated food web linkages with surrounding mangrove habitats. All of these studies examined a different facet of the importance of seascape context in governing ecological processes occurring in focal habitats and underscore the role of connectivity among habitats in back-reef systems. The results suggest that management approaches consider the surrounding seascape when prioritizing areas for conservation or attempting to understand the impacts of seascape change on focal habitat patches. For this reason, spatially-based management approaches are recommended to most effectively manage back-reef systems.

Understanding ten-eleven translocation-2 in hematological and nervous systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. ^ In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. ^ In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.^