Differential Gene Repertoire in Mycobacterium ulcerans Identifies Candidate Genes for Patho-Adaptation

The emerging human disease Buruli ulcer, caused by Mycobacterium ulcerans, is of increasing challenge for public health systems in many countries, mainly in West and Central sub-Saharan Africa. Genetic differentiation of patient isolates, a prerequisite for scientific studies on and intervention of disease transmission and dispersal, is hampered by an exceptional lack of genetic diversity within this species. Comparative genomics on M. ulcerans of worldwide geographical origin has already allowed for distinguishing several haplotypes separated into two distinct lineages. Differences in prevalence and incidence of Buruli ulcer were already suspected, but biological relevance for this was unclear. Here, we show newly identified hot spot regions of genomic instability, a biased silencing of coding sequences belonging to distinct functional groups, and a differential gene repertoire across M. ulcerans strains. Gene inactivation mediated by different mechanisms in M. ulcerans adds to the concept of anti-virulence genes observed in an increasing number of bacterial species. According to this concept, loss of such genes—in addition to gain of function—may confer a selective advantage for a pathogen radiating into a new niche. In the case of M. ulcerans, a distinct set of disrupted genes may enhance virulence, particularly in the classical lineage

A LOFAR DETECTION of the LOW-MASS YOUNG STAR T TAU at 149 MHz

© 2017 Published by Elsevier B.V. Radio observations of young stellar objects (YSOs) enable the study of ionized plasma outflows from young protostars via their free-free radiation. Previous studies of the low-mass young system T Tau have used radio observations to model the spectrum and estimate important physical properties of the associated ionized plasma (local electron density, ionized gas content, and emission measure). However, without an indication of the low-frequency turnover in the free-free spectrum, these properties remain difficult to constrain. This paper presents the detection of T Tau at 149 MHz with the Low Frequency Array (LOFAR)-the first time a YSO has been observed at such low frequencies. The recovered total flux indicates that the free-free spectrum may be turning over near 149 MHz. The spectral energy distribution is fitted and yields improved constraints on local electron density ((7.2 ± 2.1) × 103 cm-3), ionized gas mass ( ± × -1.0 1.8 10-6Ṁ), and emission measure ((1.67 ± 0.14) × 105 pc cm-6)

On identifiability for chemical systems from measurable variables

The final publication is available at Springer via http://dx.doi.org/10.1007/s10910-013-0149-4The dynamics of the composition of chemical species in reacting systems can be characterized by a set of autonomous differential equations derived from mass conservation principles and some elementary hypothesis related to chemical reactivity. These sets of ordinary differential equations are basically non-linear, their complexity grows as much increases the number of substances present in the reacting media an can be characterized by a set of phenomenological constants which contains all the relevant information about the physical system. The determination of these kinetic constants is critical for the design or control of chemical systems from a technological point of view but the non-linear nature of the equations implies that there are hidden correlations between the parameters which maybe can be revealed with a identifiability analysis.This work has been partially supported by MTM2010-18228.Cantó Colomina, B.; Coll, C.; Sánchez, E.; Cardona Navarrete, SC.; Navarro-Laboulais, J. (2014). On identifiability for chemical systems from measurable variables. Journal of Mathematical Chemistry. 52(4):1023-1035. https://doi.org/10.1007/s10910-013-0149-4S10231035524M.J. Almendral, A. Alonso, M.S. Fuentes, Development of new methodologies for on-line determination of the bromate. J. Environ. Monit. 11, 1381–1388 (2009)A. Ben-Zvi, P.J. McLellan, K.B. McAuley, Identifiability of linear time-invariant differential-algebraic systems. I. The generalized Markov parameter approach. Ind. Eng. Chem. Res. 42, 6607–6618 (2003)T.P. Bonacquisti, A drinking water utility’s perspective on bromide, bromate, and ozonation. Toxicology 221, 145–148 (2006)R. Butler, A. Godley, L. Lytton, E. Cartmell, Bromate environmental contamination: review of impact and possible treatment. Crit. Rev. Environ. Sci. Tech. 35, 193–217 (2005)R. Butler, L. Lytton, A.R. Godley, I.E. Tothill, E. Cartmell, Bromate analysis in groundwater and wastewater samples. J. Environ. Monit. 7, 999–1006 (2005)B. Cantó, S.C. Cardona, C. Coll, J. Navarro-Laboulais, E. Sánchez, Dynamic optimization of a gas-liquid reactor. J. Math. Chem. 50, 381–393 (2012)B. Cantó, C. Coll and E. Sánchez, Identifiability of a class of discretized linear partial differential algebraic equations, Math. Problems Eng. 2011, 1–12 (2011)A. Constantinides, N. Mostoufi, Numerical Methods for Chemical Engineers with MATLAB Applications, Alkis Constantinides and Navid Mostoufi, Upper Saddle River (Prentice Hall, New Jersey, 1999)P. Englezos, N. Kalogerakis, Applied Parameter Estimation for Chemical Engineers (Marcel Dekker, New York, 2001)U. von Gunten, Ozonation of drinking water. Part II. Disinfection and by-product formation in presence of bromide, iodide or chlorine. Water Res. 37, 1469–1487 (2003)B. Legube, B. Parinet, K. Gelinet, F. Berne, J-Ph Croue, Modeling of bromate formation by ozonation of surface waters in drinking water treatment. Water Res. 38, 2185–2195 (2004)Q. Liu, L.M. Schurter, C.E. Muller, S. Aloisio, J.S. Francisco, D.W. Margerum, Kinetics and mechanisms of aqueous ozone reactions with bromide, sulfite, hydrogen sulfite, iodide, and nitrite ions. Inorg. Chem. 40, 4436–4442 (2001)J.B. Rawling, J.G. Ekerdt, Chemical Reactor Analysis and Design Fundamentals (Nob Hill Pub, Madison, 2002)W.E. Stewart, M. Caracotsios, Computer Aided Modelling of Reactive Systems (John Wiley and Sons, New York, 2008)P. Westerhoff, R. Song, G. Amy, R. Minear, Numerical kinetic models for bromide oxidation to bromine and bromate. Water Res. 32, 1687–1699 (1998)World Health Organization, Bromate in Drinking-water, Document WHO/SDE/WSH/05.08/78, http://www.who.int/water_sanitation_health/dwq/chemicals/en/ (accesed 26/07/12

An Early Cambrian Rift to Post-Rift Transition in the Cordillera of Western North America

The upper Proterozoic and lower Palaeozoic wedge of miogeoclinal strata in the North American Cordillera is widely regarded as evidence for a proto-Pacific passive margin. The rifting history of this margin appears to have been protracted, possibly spanning more than 200 Myr in a tectonic setting that is not well understood. Quantitative subsidence analyses of lower Palaeozoic strata between British Columbia and Utah, however, provide indirect evidence that the transition from rifting to post-rift cooling occurred within a relatively short interval of time, although probably not synchronously, between 600 and 555 Myr. This age is significantly younger than that implied in previous studies. We describe here new field data, which, together with published geological data, provide direct evidence of a latest Proterozoic or early Cambrian age for the rift to post-rift transition. The data support recent arguments for widespread initiation of passive margins around the edge of the North American craton close to the Cambrian-Precambrian boundary

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI)

Introduction It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g., OLS linear, random effects, mean, robust, spline, quadratic). Results A total of 245 participants completed utility interviews (51.4% female; mean age =45.3y). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g., R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE =0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions The recommended scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Single nucleotide polymorphisms unravel hierarchical divergence and signatures of selection among Alaskan sockeye salmon (Oncorhynchus nerka) populations

<p>Abstract</p> <p>Background</p> <p>Disentangling the roles of geography and ecology driving population divergence and distinguishing adaptive from neutral evolution at the molecular level have been common goals among evolutionary and conservation biologists. Using single nucleotide polymorphism (SNP) multilocus genotypes for 31 sockeye salmon (<it>Oncorhynchus nerka</it>) populations from the Kvichak River, Alaska, we assessed the relative roles of geography (discrete boundaries or continuous distance) and ecology (spawning habitat and timing) driving genetic divergence in this species at varying spatial scales within the drainage. We also evaluated two outlier detection methods to characterize candidate SNPs responding to environmental selection, emphasizing which mechanism(s) may maintain the genetic variation of outlier loci.</p> <p>Results</p> <p>For the entire drainage, Mantel tests suggested a greater role of geographic distance on population divergence than differences in spawn timing when each variable was correlated with pairwise genetic distances. Clustering and hierarchical analyses of molecular variance indicated that the largest genetic differentiation occurred between populations from distinct lakes or subdrainages. Within one population-rich lake, however, Mantel tests suggested a greater role of spawn timing than geographic distance on population divergence when each variable was correlated with pairwise genetic distances. Variable spawn timing among populations was linked to specific spawning habitats as revealed by principal coordinate analyses. We additionally identified two outlier SNPs located in the major histocompatibility complex (MHC) class II that appeared robust to violations of demographic assumptions from an initial pool of eight candidates for selection.</p> <p>Conclusions</p> <p>First, our results suggest that geography and ecology have influenced genetic divergence between Alaskan sockeye salmon populations in a hierarchical manner depending on the spatial scale. Second, we found consistent evidence for diversifying selection in two loci located in the MHC class II by means of outlier detection methods; yet, alternative scenarios for the evolution of these loci were also evaluated. Both conclusions argue that historical contingency and contemporary adaptation have likely driven differentiation between Kvichak River sockeye salmon populations, as revealed by a suite of SNPs. Our findings highlight the need for conservation of complex population structure, because it provides resilience in the face of environmental change, both natural and anthropogenic.</p