Exploring modularity in biological networks

Network theoretical approaches have shaped our understanding of many different kinds of biological modularity. This essay makes the case that to capture these contributions, it is useful to think about the role of network models in exploratory research. The overall point is that it is possible to provide a systematic analysis of the exploratory functions of network models in bioscientific research. Using two examples from molecular and developmental biology, I argue that often the same modelling approach can perform one or more exploratory functions, such as introducing new directions of research, offering a complementary set of concepts, methods and algorithms for individuating important features of natural phenomena, generating proofs of principle demonstrations and potential explanations for phenomena of interest and enlarging the scope of certain research agendas. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'

Shifting Attention From Theory to Practice in Philosophy of Biology

Traditional approaches in philosophy of biology focus attention on biological concepts, explanations, and theories, on evidential support and inter-theoretical relations. Newer approaches shift attention from concepts to conceptual practices, from theories to practices of theorizing, and from theoretical reduction to reductive retooling. In this article, I describe the shift from theory-focused to practice-centered philosophy of science and explain how it is leading philosophers to abandon fundamentalist assumptions associated with traditional approaches in philosophy of science and to embrace scientific pluralism. This article comes in three parts, each illustrating the shift from theory-focused to practice-centered epistemology. The first illustration shows how shifting philosophical attention to conceptual practice reveals how molecular biologists succeed in identifying coherent causal strands within systems of bewildering complexity. The second illustration suggests that analyzing how a multiplicity of alternative models function in practice provides an illuminating approach for understanding the nature of theoretical knowledge in evolutionary biology. The third illustration demonstrates how framing reductionism in terms of the reductive retooling of practice offers an informative perspective for understanding why putting DNA at the center of biological research has been incredibly productive throughout much of biology. Each illustration begins by describing how traditional theory-focused philosophical approaches are laden with fundamentalist assumptions and then proceeds to show that shifting attention to practice undermines these assumptions and motivates a philosophy of scientific pluralism

Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics\ud

Objective: To investigate the impact of upper extremity deficit in subjects with tetraplegia.\ud \ud Setting: The United Kingdom and The Netherlands.\ud \ud Study design: Survey among the members of the Dutch and UK Spinal Cord Injury (SCI) Associations.\ud \ud Main outcome parameter: Indication of expected improvement in quality of life (QOL) on a 5-point scale in relation to improvement in hand function and seven other SCI-related impairments.\ud \ud Results: In all, 565 subjects with tetraplegia returned the questionnaire (overall response of 42%). Results in the Dutch and the UK group were comparable. A total of 77% of the tetraplegics expected an important or very important improvement in QOL if their hand function improved. This is comparable to their expectations with regard to improvement in bladder and bowel function. All other items were scored lower.\ud \ud Conclusion: This is the first study in which the impact of upper extremity impairment has been assessed in a large sample of tetraplegic subjects and compared to other SCI-related impairments that have a major impact on the life of subjects with SCI. The present study indicates a high impact as well as a high priority for improvement in hand function in tetraplegics.\ud \u

Adoption and use of social media among public health departments

<p>Abstract</p> <p>Background</p> <p>Effective communication is a critical function within any public health system. Social media has enhanced communication between individuals and organizations and has the potential to augment public health communication. However, there is a lack of reported data on social media adoption within public health settings. The purposes of this study were to assess: 1) the extent to which state public health departments (SHDs) are using social media; 2) which social media applications are used most often; and 3) how often social media is used interactively to engage audiences.</p> <p>Methods</p> <p>This was a non-experimental, cross sectional study of SHD social media sites. Screen capture software Snag-It^®was used to obtain screenshots of SHD social media sites across five applications. These sites were coded for social media presence, interactivity, reach, and topic.</p> <p>Results</p> <p>Sixty percent of SHDs reported using at least one social media application. Of these, 86.7% had a Twitter account, 56% a Facebook account, and 43% a YouTube channel. There was a statistically significant difference between average population density and use of social media (p = .01). On average, SHDs made one post per day on social media sites, and this was primarily to distribute information; there was very little interaction with audiences. SHDs have few followers or friends on their social media sites. The most common topics for posts and tweets related to staying healthy and diseases and conditions. Limitations include the absence of a standard by which social media metrics measure presence, reach, or interactivity; SHDs were only included if they had an institutionally maintained account; and the study was cross sectional.</p> <p>Conclusions</p> <p>Social media use by public health agencies is in the early adoption stage. However, the reach of social media is limited. SHDs are using social media as a channel to distribute information rather than capitalizing on the interactivity available to create conversations and engage with the audience. If public health agencies are to effectively use social media then they must develop a strategic communication plan that incorporates best practices for expanding reach and fostering interactivity and engagement.</p

Enterococcus faecalis Endocarditis Severity in Rabbits Is Reduced by IgG Fabs Interfering with Aggregation Substance

Background: Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the heart endothelium leading to vegetation formation (microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue). Our previous research determined that enterococcal aggregation substance (AS) is an important virulence factor in causation of endocarditis, although endocarditis may occur in the absence of AS production. Production of AS by E. faecalis causes the organism to form aggregates through AS binding to enterococcal binding substance. In this study, we assessed the ability of IgGs and IgG Fabs against AS to provide protection against AS + E. faecalis endocarditis. Methodology/Principal Findings: When challenged with AS + E. faecalis, 10 rabbits actively immunized against AS + E. faecalis developed more significant vegetations than 9 animals immunized against AS 2 E. faecalis, and 9/10 succumbed compared to 2/9 (p,0.005), suggesting enhanced aggregation by IgG contributes significantly to disease. IgG antibodies against AS also enhanced enterococcal aggregation as tested in vitro. In contrast, Fab fragments of IgG from rabbits immunized against purified AS, when passively administered to rabbits (6/group) immediately before challenge with AS + E. faecalis, reduced total vegetation (endocarditis lesion) microbial counts (7.9610 6 versus 2.0610 5, p = 0.02) and size (40 mg versus 10, p = 0.05). In vitro, the Fabs prevented enterococcal aggregation. Conclusions/Significance: The data confirm the role of AS in infective endocarditis formation and suggest that use of Fab

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism