Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

The concept of mindfulness in information systems research: A multi-dimensional analysis

The concept of mindfulness has garnered increasing attention during the last decade. Initially proposed within the scope of Information Systems (IS) research as a means of creating a deeper knowledge foundation for decision making regarding information technology (IT) innovations, it soon became broadly applied throughout IS research. To gain a better understanding of the evolved diversity of this concept, this paper reviews and analyzes extant IS research by means of (a) the investigated IS themes, (b) the purpose of using the concept, (c) the level of application of the concept, and (d) the tendency to focus either on mindfulness, mindlessness, or both. By synthesizing research findings, we derive a high-level IS mindfulness theory. We then propose future research opportunities, such as the explanation of the relationships between different levels of mindfulness, applying mindfulness to bridge the different phases of the software development process, and identification of guidelines for designing information systems that facilitate mindfulness. As the first review on the application of mindfulness in IS research, we contribute to the overall understanding of mindfulness and address the four abovementioned dimensions from which mindfulness emerges in order to demonstrate that mindfulness provides a meaningful platform for generating knowledge

SDSS-IV MaNGA: A serendipitous observation of a potential gas accretion event

The nature of warm, ionized gas outside of galaxies may illuminate several key galaxy evolutionary processes. A serendipitous observation by the MaNGA survey has revealed a large, asymmetric H$\alpha$ complex with no optical counterpart that extends ≈8″ (≈6.3 kpc) beyond the effective radius of a dusty, starbursting galaxy. This H$\alpha$ extension is approximately three times the effective radius of the host galaxy and displays a tail-like morphology. We analyze its gas-phase metallicities, gaseous kinematics, and emission-line ratios and discuss whether this H$\alpha$ extension could be diffuse ionized gas, a gas accretion event, or something else. We find that this warm, ionized gas structure is most consistent with gas accretion through recycled wind material, which could be an important process that regulates the low-mass end of the galaxy stellar mass function.Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. SDSS-IV is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration. D.B. is supported by grant RSCF-14-22-00041. A.W. acknowledges support from a Leverhulme Early Career Fellowship. J.H.K. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under grant number AYA2013-41243-P and thanks the Astrophysics Research Institute of Liverpool John Moores University for their hospitality, and the Spanish Ministry of Education, Culture and Sports for financial support of his visit there, through grant number PR2015-00512

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Mapping transcription mechanisms from multimodal genomic data

Background Identification of expression quantitative trait loci (eQTLs) is an emerging area in genomic study. The task requires an integrated analysis of genome-wide single nucleotide polymorphism (SNP) data and gene expression data, raising a new computational challenge due to the tremendous size of data. Results We develop a method to identify eQTLs. The method represents eQTLs as information flux between genetic variants and transcripts. We use information theory to simultaneously interrogate SNP and gene expression data, resulting in a Transcriptional Information Map (TIM) which captures the network of transcriptional information that links genetic variations, gene expression and regulatory mechanisms. These maps are able to identify both cis- and trans- regulating eQTLs. The application on a dataset of leukemia patients identifies eQTLs in the regions of the GART, PCP4, DSCAM, and RIPK4 genes that regulate ADAMTS1, a known leukemia correlate. Conclusions The information theory approach presented in this paper is able to infer the dependence networks between SNPs and transcripts, which in turn can identify cis- and trans-eQTLs. The application of our method to the leukemia study explains how genetic variants and gene expression are linked to leukemia.National Human Genome Research Institute (U.S.) (R01HG003354)National Institute of Allergy and Infectious Diseases (U.S.) (U19 AI067854-05)National Heart, Lung, and Blood Institute (grant T32 HL007427-28)National Institutes of Health (U.S.) (grant K99 LM009826

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Recent emergence and worldwide spread of the red tomato spider mite, [i]Tetranychus evansi[/i]: genetic variation and multiple cryptic invasions

Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699Plant biosecurity is increasingly challenged by emerging crop pests. The spider mite Tetranychus evansi has recently emerged as a new threat to solanaceous crops in Africa and the Mediterranean basin, with invasions characterized by a high reproductive output and an ability to withstand a wide range of temperatures. Mitochondrial (868 bp of COI) and nuclear (1,137 bp of ITS) loci were analyzed in T. evansi samples spanning the current geographical distribution to study the earliest stages of the invasive process. The two sets of markers separate the samples into two main clades that are only present together in South America and Southern Europe. The highest COI diversity was found in South America, consistent with the hypothesis of a South American origin of T. evansi. Among the invaded areas, the Mediterranean region displayed a high level of genetic diversity similar to that present in South America, that is likely the result of multiple colonization events. The invasions of Africa and Asia by T. evansi are characterized by a low genetic variation associated with distinct introductions. Genetic data demonstrate two different patterns of invasions: (1) populations in the Mediterranean basin that are a result of multiple cryptic introductions and (2) emerging invasions of Africa and Asia, each likely the result of propagules from one or limited sources. The recent invasions of T. evansi illustrate not only the importance of human activities in the spread of agricultural pests, but also the limits of international quarantine procedures, particularly for cryptic invasion

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM