BSim: an agent-based tool for modeling bacterial populations in systems and synthetic biology.

Open Access ArticleLarge-scale collective behaviors such as synchronization and coordination spontaneously arise in many bacterial populations. With systems biology attempting to understand these phenomena, and synthetic biology opening up the possibility of engineering them for our own benefit, there is growing interest in how bacterial populations are best modeled. Here we introduce BSim, a highly flexible agent-based computational tool for analyzing the relationships between single-cell dynamics and population level features. BSim includes reference implementations of many bacterial traits to enable the quick development of new models partially built from existing ones. Unlike existing modeling tools, BSim fully considers spatial aspects of a model allowing for the description of intricate micro-scale structures, enabling the modeling of bacterial behavior in more realistic three-dimensional, complex environments. The new opportunities that BSim opens are illustrated through several diverse examples covering: spatial multicellular computing, modeling complex environments, population dynamics of the lac operon, and the synchronization of genetic oscillators. BSim is open source software that is freely available from http://bsim-bccs.sf.net and distributed under the Open Source Initiative (OSI) recognized MIT license. Developer documentation and a wide range of example simulations are also available from the website. BSim requires Java version 1.6 or higher.Engineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Biosocial life-course factors associated with women's early marriage in rural India: The prospective longitudinal Pune Maternal Nutrition Study

Objectives: By convention, women's early marriage is considered a sociocultural decision sensitive to factors acting during adolescence such as poverty, early menarche, and less education. Few studies have examined broader risk factors in the natal household prior to marriage. We investigated whether biosocial markers of parental investment through the daughters' life-course were associated with early marriage risk in rural India. We used an evolutionary perspective to interpret our findings. / Materials and Methods: A prospective cohort recruited mothers at preconception. Children were followed from birth to age 21 years. Multivariable logistic regression models estimated odds ratios of marrying early (<19 years) associated first with wealth, age at menarche and education, and then with broader markers of maternal phenotype, natal household characteristics, and girls' growth trajectories. Models adjusted for confounders. / Results: Of 305 girls, 71 (23%) had married early. Early married girls showed different patterns of growth compared to unmarried girls. Neither poverty nor early menarche predicted early marriage. Girls' non-completion of lower secondary school predicted early marriage, explaining 19% of the variance. Independent of girls' lower schooling, nuclear household, low paternal education, shorter gestation, and girls' poor infant weight gain were associated with marrying early, explaining in combination 35% of the variance. / Discussion: Early marriage reflects “future discounting,” where reduced parental investment in daughters' somatic and educational capital from early in her life favors an earlier transition to the life-course stage when reproduction can occur. Interventions initiated in adolescence may occur too late in the life-course to effectively delay women's marriage

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

The genomic evolution of human prostate cancer.

Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The Distances of the Magellanic Clouds

The present status of our knowledge of the distances to the Magellanic Clouds is evaluated from a post-Hipparcos perspective. After a brief summary of the effects of structure, reddening, age and metallicity, the primary distance indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring, Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived via these methods are weighted and combined to produce final "best" estimates for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in pres