Degeneracy: a link between evolvability, robustness and complexity in biological systems

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability

Graded structure in sexual definitions: categorizations of having “had sex” and virginity loss among homosexual and heterosexual men and women

Definitions of sexual behavior display a robust hierarchy of agreement regarding whether or not acts should be classed as, for example, sex or virginity loss. The current research offers a theoretical explanation for this hierarchy, proposing that sexual definitions display graded categorical structure, arising from goodness of membership judgments. Moderation of this graded structure is also predicted, with the focus here on how sexual orientation identity affects sexual definitions. A total of 300 18- to 30-year-old participants completed an online survey, rating 18 behaviors for how far each constitutes having “had sex” and virginity loss. Participants fell into one of four groups: heterosexual male or female, gay male or lesbian. The predicted ratings hierarchy emerged, in which bidirectional genital acts were rated significantly higher than unidirectional or nonpenetrative contact, which was in turn rated significantly higher than acts involving no genital contact. Moderation of graded structure was also in line with predictions. Compared to the other groups, the lesbian group significantly upgraded ratings of genital contact that was either unidirectional or nonpenetrative. There was also evidence of upgrading by the gay male sample of anal intercourse ratings. These effects are theorized to reflect group-level variation in experience, contextual perspective, and identity-management. The implications of the findings in relation to previous research are discussed. It is suggested that a graded structure approach can greatly benefit future research into sexual definitions, by permitting variable definitions to be predicted and explained, rather than merely identified

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Sleep quality, the neglected outcome variable in clinical studies focusing on locomotor system; a construct validation study

Background: In addition to general health and pain, sleep is highly relevant to judging the well-being of an individual. Of these three important outcome variables, however, sleep is neglected in most outcome studies. Sleep is a very important resource for recovery from daily stresses and strains, and any alteration of sleep will likely affect mental and physical health, especially during disease. Sleep assessment therefore should be standard in all population-based or clinical studies focusing on the locomotor system. Yet current sleep assessment tools are either too long or too specific for general use. Methods: Based on a literature review and subsequent patient-based rating of items, an expert panel designed a four-item questionnaire about sleep. Construct validation of the questionnaire in a random sample of the German-speaking Swiss population was performed in 2003. Reliability, correlation, and tests for internal consistency and validity were analyzed. Results: Overall, 16,634 (70%) out of 23,763 eligible individuals participated in the study. Test-retest reliability coefficients ranged from 0.72 to 0.87, and a Cronbach’s alpha of 0.83 indicates good internal consistency. Results show a moderate to good correlation between sleep disturbances and health perception, and between sleep disturbances and overall pain. Conclusions: The Sleep Standard Evaluation Questionnaire (SEQ-Sleep) is a reliable and short tool with confirmed construct validity for sleep assessment in population-based observational studies. It is easy to administer and therefore suitable for postal surveys of the general population. Criterion validity remains to be determined

Herpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes

Whether all the infectious herpesvirus particles entering a cell are able to replicate and/or express their genomes is not known. Here, we developed a general method to determine the number of viral genomes expressed in an infected cell. We constructed and analysed fluorophore expression from a recombinant pseudorabies virus (PRV263) carrying a Brainbow cassette (Cre-conditional expression of different fluorophores). Using three isogenic strains derived from PRV263, each expressing a single fluorophore, we analysed the colour composition of cells infected with these three viruses at different multiplicities. We estimate that fewer than seven incoming genomes are expressed per cell. In addition, those templates that are expressed are the genomes selected for replication and packaging into virions. This finite limit on the number of viral genomes that can be expressed is an intrinsic property of the infected cell and may be influenced by viral and cellular factors

Optogenetic acidification of synaptic vesicles and lysosomes

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes

The Depletion of Nuclear Glutathione Impairs Cell Proliferation in 3t3 Fibroblasts

BACKGROUND:Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate. PRINCIPAL FINDINGS:We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM) and buthionine sulfoximine (BSO), and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation. CONCLUSIONS:Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle

Recruitment Constraints in Singapore's Fluted Giant Clam (Tridacna squamosa) Populations - A Dispersal Model Approach

10.1371/journal.pone.0058819PLoS ONE83

Disseminating research findings: what should researchers do? A systematic scoping review of conceptual frameworks

Background: Addressing deficiencies in the dissemination and transfer of research-based knowledge into routine clinical practice is high on the policy agenda both in the UK and internationally. However, there is lack of clarity between funding agencies as to what represents dissemination. Moreover, the expectations and guidance provided to researchers vary from one agency to another. Against this background, we performed a systematic scoping to identify and describe any conceptual/organising frameworks that could be used by researchers to guide their dissemination activity.Methods: We searched twelve electronic databases (including MEDLINE, EMBASE, CINAHL, and PsycINFO), the reference lists of included studies and of individual funding agency websites to identify potential studies for inclusion. To be included, papers had to present an explicit framework or plan either designed for use by researchers or that could be used to guide dissemination activity. Papers which mentioned dissemination (but did not provide any detail) in the context of a wider knowledge translation framework, were excluded. References were screened independently by at least two reviewers; disagreements were resolved by discussion. For each included paper, the source, the date of publication, a description of the main elements of the framework, and whether there was any implicit/explicit reference to theory were extracted. A narrative synthesis was undertaken.Results: Thirty-three frameworks met our inclusion criteria, 20 of which were designed to be used by researchers to guide their dissemination activities. Twenty-eight included frameworks were underpinned at least in part by one or more of three different theoretical approaches, namely persuasive communication, diffusion of innovations theory, and social marketing.Conclusions: There are currently a number of theoretically-informed frameworks available to researchers that can be used to help guide their dissemination planning and activity. Given the current emphasis on enhancing the uptake of knowledge about the effects of interventions into routine practice, funders could consider encouraging researchers to adopt a theoretically-informed approach to their research dissemination