Knowledge Integration and Good Marine Governance: A Multidisciplinary Analysis and Critical Synopsis

Human Ecology - Our research addresses knowledge integration for the good governance of the environment and the oceans: (a) through a comprehensive legal, political science, and anthropological...     

GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge

Method

Genome-wide expression profiling is a widely used approach for characterizing heterogeneous populations of cells, tissues, biopsies, or other biological specimen. The exploratory analysis of such data typically relies on generic unsupervised methods, e.g. principal component analysis (PCA) or hierarchical clustering. However, generic methods fail to exploit prior knowledge about the molecular functions of genes. Here, I introduce GO-PCA, an unsupervised method that combines PCA with nonparametric GO enrichment analysis, in order to systematically search for sets of genes that are both strongly correlated and closely functionally related. These gene sets are then used to automatically generate expression signatures with functional labels, which collectively aim to provide a readily interpretable representation of biologically relevant similarities and differences. The robustness of the results obtained can be assessed by bootstrapping.

Results

I first applied GO-PCA to datasets containing diverse hematopoietic cell types from human and mouse, respectively. In both cases, GO-PCA generated a small number of signatures that represented the majority of lineages present, and whose labels reflected their respective biological characteristics. I then applied GO-PCA to human glioblastoma (GBM) data, and recovered signatures associated with four out of five previously defined GBM subtypes. My results demonstrate that GO-PCA is a powerful and versatile exploratory method that reduces an expression matrix containing thousands of genes to a much smaller set of interpretable signatures. In this way, GO-PCA aims to facilitate hypothesis generation, design of further analyses, and functional comparisons across datasets.     

A Spatial Framework for Understanding Population Structure and Admixture

Geographic patterns of genetic variation within modern populations, produced by complex histories of migration, can be difficult to infer and visually summarize. A general consequence of geographically limited dispersal is that samples from nearby locations tend to be more closely related than samples from distant locations, and so genetic covariance often recapitulates geographic proximity. We use genome-wide polymorphism data to build “geogenetic maps,” which, when applied to stationary populations, produces a map of the geographic positions of the populations, but with distances distorted to reflect historical rates of gene flow. In the underlying model, allele frequency covariance is a decreasing function of geogenetic distance, and nonlocal gene flow such as admixture can be identified as anomalously strong covariance over long distances. This admixture is explicitly co-estimated and depicted as arrows, from the source of admixture to the recipient, on the geogenetic map. We demonstrate the utility of this method on a circum-Tibetan sampling of the greenish warbler (Phylloscopus trochiloides), in which we find evidence for gene flow between the adjacent, terminal populations of the ring species. We also analyze a global sampling of human populations, for which we largely recover the geography of the sampling, with support for significant histories of admixture in many samples. This new tool for understanding and visualizing patterns of population structure is implemented in a Bayesian framework in the program SpaceMix.     

A Framework for Managing Core Facilities within the Research Enterprise

Core facilities represent increasingly important operational and strategic components of institutions'' research enterprises, especially in biomolecular science and engineering disciplines. With this realization, many research institutions are placing more attention on effectively managing core facilities within the research enterprise. A framework is presented for organizing the questions, challenges, and opportunities facing core facilities and the academic units and institutions in which they operate. This framework is intended to assist in guiding core facility management discussions in the context of a portfolio of facilities and within the overall institutional research enterprise.     

A Sero-epidemiological Approach to Explore Transmission of Mycobacterium ulcerans

The debilitating skin disease Buruli ulcer (BU) is caused by infection with Mycobacterium ulcerans. While various hypotheses on potential reservoirs and vectors of M. ulcerans exist, the mode of transmission has remained unclear. Epidemiological studies have indicated that children below the age of four are less exposed to the pathogen and at lower risk of developing BU than older children. In the present study we compared the age at which children begin to develop antibody responses against M. ulcerans with the age pattern of responses to other pathogens transmitted by various mechanisms. A total of 1,352 sera from individuals living in the BU endemic Offin river valley of Ghana were included in the study. While first serological responses to the mosquito transmitted malaria parasite Plasmodium falciparum and to soil transmitted Strongyloides helminths emerged around the age of one and two years, sero-conversion for M. ulcerans and for the water transmitted trematode Schistosoma mansoni occurred at around four and five years, respectively. Our data suggest that exposure to M. ulcerans intensifies strongly at the age when children start to have more intense contact with the environment, outside the small movement range of young children. Further results from our serological investigations in the Offin river valley also indicate ongoing transmission of Treponema pallidum, the causative agent of yaws.     

Ethnobotanical Knowledge and Crop Diversity in Swidden Fields: A Study in a Native Amazonian Society

Crop diversity protects food consumption in poor households within developing nations. Here we estimate the association between crop diversity on swidden fields and ethnobotanical knowledge. We conducted research among 215 male household heads from a native Amazonian society. Using multivariate regressions, we found higher crop diversity among households that depend on agricultural production for household consumption. We also found a statistically significant and positive, but low, association between the ethnobotanical knowledge of the male household head and crop diversity. Doubling the stock of ethnobotanical knowledge of the male household head is associated with a 9% increase in the number of crops sown by a household. The association remained after we controlled for the household level of market exposure, but vanished after we controlled for the social capital of the male household head. Future research should compare the association between ethnobotanical knowledge and crop diversity across different agricultural systems (i.e., home gardens, fallow fields).     

Voices of Our Past: Using Oral History to Explore Funds of Knowledge within a Puerto Rican Family

This article presents an educational rationale for using oral history to teach students that there are multiple sources of knowledge and ways to seek valid information. A case study to explore the funds of knowledge within an extended Puerto Rican family is used illustratively. The study describes the leadership role played by one grandmother as the family participated in multiple migrations, describes creative ways employed by her and other women to reestablish the community, and challenges some stereotypes of Latinas.     

Broadening the Genetic Base of Soybean: A Multidisciplinary Approach

Soybean [Glycine max (L.) Merr.] is an economically important legume with 2n = 40 chromosomes, whose seeds contain an average of 40% protein and 20% oil, and its plants enrich the soil by fixing nitrogen in symbiosis with nitrogen-fixing bacteria. World soybean production has doubled in the past twenty years to over 220 million metric tons in 2006; the producing countries are U.S.A., Brazil, Argentina, China, and India. Soybean was domesticated in East Asia from its wild annual progenitor G. soja Sieb. & Zucc. (2n = 40). There are 26 wild perennial species, indigenous to Australia, of the subgenus Glycine but a common progenitor with 2n = 20 chromosomes has not been identified, and it may be extinct. It has been demonstrated that Glycine species are of either of allo-or auto-tetraploid origin. The cytogenetic knowledge of soybean lags far behind that of other model important crops (rice, maize, wheat, tomato), because it's somatic chromosomes are symmetrical, and only one pair of satellite chromosomes can be identified. Pachytene chromosome analysis created a chromosome map that has laid the foundation for producing primary trisomics. Several molecular linkage maps have been developed, but only 11 of the 20 molecular linkage groups (MLGs) have been associated with specific chromosomes. The genetic base of modern soybean cultivars is narrow and soybean breeders are confined to crossing within the primary gene pool (GP-1). Soybean does not have secondary gene pool (GP-2). Exploitation of the tertiary and quaternary gene pools (GP-3, GP-4) has been attempted but ended at the amphidiploid stage. A methodology for producing fertile lines derived from G. max and G. tomentella (2n = 78) cross has been developed, thereby making introgression of useful genes from GP-3. Genetic transformation has produced Roundup Ready® Soybeans, resistant to glyphosate herbicide.     

Evaluation of Urinary Protein Precipitation Protocols for the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network

Standardization of sample collection, shipping, and storage has been a major focus of biorepositories servicing large, multi-institute studies. The standardization of total protein concentration measurements may also provide an important metric for characterizing biospecimens. The measurement of total protein concentration in urine is challenging because of widely variable sample dilutions obtained in the clinic and the lack of a reference matrix for use with a standard curve and blank subtraction. Urinary proteins are therefore typically precipitated and reconstituted in a reference solution before quantitation. We have tested three different methods for protein precipitation and evaluated them using variability in total protein concentration measurement as a metric. The methods were tested on four urine samples ranging from very concentrated to very dilute. A method using a commercially available kit provided the most reproducible results, with average coefficients of variation <10%. Addition of a freeze/thaw did not lead to significant protein loss or additional variability. Samples were titrated and the measurements obtained appeared to be linearly correlated with sample starting volume. This method was applied to analysis of 77 urine biorepository samples and provided reproducible results when the same sample was assayed on different microwell plates.     

Multidisciplinary Research: Strategies for Assessing Chemical Mixtures to Reduce Risk of Exposure and Disease

The Precautionary Principle is founded on the use of comprehensive, coordinated research to protect human health in the face of uncertain risks. Research directed at key data gaps may significantly reduce the uncertainty underlying the complexities of assessing risk to mixtures. The National Institute of Environmental Health Sciences (NIEHS) has taken a leadership rôle in building the scientific infrastructure to address these uncertainties. The challenge is to incorporate the objectives as defined by the Precautionary Principle with the knowledge gained in understanding the multifactorial nature of gene-environment interactions. Through efforts such as the National Center for Toxicogenomics, the National Toxicology Program, and the Superfund Basic Research Program, NIEHS is translating research findings into public health prevention strategies using a 3-pronged approach: (1) identify/evaluate key deviations from additivity for mixtures; (2) develop/apply/link advanced technologies and bioinformatics to quantitative tools for an integrated science-based approach to chemical mixtures; (3) translate/disseminate these technologies into useable, practical means to reduce exposure and the risk of disease. Preventing adverse health effects from environmental exposures requires translation of research findings to affected communities and must include a high level of public involvement. Integrating these approaches are necessary to advance understanding of the health relevance of exposure to mixtures.     

A Chicken's Egg as a Reaction Vessel to Explore Biomineralization

Natural composites, formed through biomineralization, have highly ordered structures which have been aptly explored for functional applications. Though the role of organic phases has been well understood in biomineralization, not enough attention has been paid to the role of bio-membranes which are often found encapsulating the chamber in which mineralization occurs.We have used the natural protein and semi-permeable membrane of chicken eggs to grow different materials such as ceramics,semi-metals and metals to understand the role of bio-membranes in biomineralization. We here report the successful biomimetic synthesis of calcite, cadmium sulphide, and silver having homogeneous morphologies. We have found that the membrane operates like a tuned gateway, playing a significant role in controlling the morphology of the inorganic crystals formed during biomineralization.     

A Multidisciplinary Approach to Assess the Welfare of Weaned Pigs During Transport at Three Space Allowances

Transport can be a stressful experience for pigs, especially in pigs simultaneously experiencing weaning stress. The objective of this study was to use a multidisciplinary approach to assess the welfare of weaned pigs during transport at 3 space allowances. A commercial semitrailer, fitted with compartments, provided 0.05, 0.06, and 0.07 m²/pig. The study recorded frequency of standing, lying, sitting, and standing-rearing on another pig during the entire duration of transport. Blood samples, body weights, and lesion scores were collected from a subset of pigs (n = 48 per space allowance) in each experimental compartment. Transport time for the pigs was 148.0 ± 10.0 min to the wean-to-finishing site. Total white blood cell counts, cortisol, and several blood chemistry values increased (p < .05) after transport regardless of space allowance. Glucose and body weight decreased (p < .05) after transport regardless of space allowance. Space allowance influenced stand-rearing, sitting, standing, and lying behaviors in pigs. Combining behavioral and physiological measures of stress provides a robust picture of piglet welfare during transport at different space allowances.     

Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. FMD virus (FMDV) shows a strong tropism for epithelial cells, and FMD is characterised by cell lysis and the development of vesicular lesions in certain epithelial tissues (for example, the tongue). By contrast, other epithelial tissues do not develop lesions, despite being sites of viral replication (for example, the dorsal soft palate). The reasons for this difference are poorly understood, but hypotheses are difficult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial differential equation model of FMDV infection in bovine epithelial tissues and used it to explore a range of hypotheses about epithelium structure which could be driving differences in lytic behaviour observed in different tissues. Our results demonstrate that, based on current parameter estimates, epithelial tissue thickness and cell layer structure are unlikely to be determinants of FMDV-induced cell lysis. However, differences in receptor distribution or viral replication amongst cell layers could influence the development of lesions, but only if viral replication rates are much lower than current estimates.     

A Bayesian Computational Approach to Explore the Optimal Duration of a Cell Proliferation Assay

Cell proliferation assays are routinely used to explore how a low-density monolayer of cells grows with time. For a typical cell line with a doubling time of 12 h (or longer), a standard cell proliferation assay conducted over 24 h provides excellent information about the low-density exponential growth rate, but limited information about crowding effects that occur at higher densities. To explore how we can best detect and quantify crowding effects, we present a suite of in silico proliferation assays where cells proliferate according to a generalised logistic growth model. Using approximate Bayesian computation we show that data from a standard cell proliferation assay cannot reliably distinguish between classical logistic growth and more general non-logistic growth models. We then explore, and quantify, the trade-off between increasing the duration of the experiment and the associated decrease in uncertainty in the crowding mechanism.