BLM and RMI1 alleviate RPA inhibition of topoIIIα decatenase activity

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA

Synthesis of global satellite observations of magmatic and volcanic deformation: implications for volcano monitoring & the lateral extent of magmatic domains

Global Synthetic Aperture Radar (SAR) measurements made over the past decades provide insights into the lateral extent of magmatic domains, and capture volcanic process on scales useful for volcano monitoring. Satellite-based SAR imagery has great potential for monitoring topographic change, the distribution of eruptive products and surface displacements (InSAR) at subaerial volcanoes. However, there are challenges in applying it routinely, as would be required for the reliable operational assessment of hazard. The deformation detectable depends upon satellite repeat time and swath widths, relative to the spatial and temporal scales of volcanological processes. We describe the characteristics of InSAR-measured volcano deformation over the past two decades, highlighting both the technique’s capabilities and its limitations as a monitoring tool. To achieve this, we draw on two global datasets of volcano deformation: the Smithsonian Institution Volcanoes of the World database and the Centre for the Observation and Modelling of Earthquakes, Volcanoes and Tectonics volcano deformation catalogue, as well as compiling some measurement characteristics and interpretations from the primary literature. We find that a higher proportion of InSAR observations capture non-eruptive and non-magmatic processes than those from ground-based instrument networks, and that both transient ( 5 years) deformation episodes are under-represented. However, satellite radar is already used to assess the development of extended periods of unrest and long-lasting eruptions, and improved spatial resolution and coverage have resulted in the detection of previously unrecognised deformation at both ends of the spatial scale (~ 10 to > 1000 km²). ‘Baseline’ records of past InSAR measurements, including ‘null’ results, are fundamental for any future interpretation of interferograms in terms of hazard‚ both by providing information about past deformation at an individual volcano, and for assessing the characteristics of deformation that are likely to be detectable (and undetectable) using InSAR. More than half of all InSAR deformation signals attributed to magmatic processes have sources in the shallow crust (< 5 km depth). While the depth distribution of InSAR-derived deformation sources is affected by measurement limitations, their lateral distribution provides information about the extent of active magmatic domains. Deformation is common (24% of all potentially magmatic events) at loci ≥5 km away from the nearest active volcanic vent. This demonstrates that laterally extensive active magmatic domains are not exceptional, but can comprise the shallowest part of trans-crustal magmatic systems in a range of volcanic settings

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Acquired constriction ring syndrome as a cause of inconsolable cry in a child: a case report

Acute constriction ring syndrome (ACRS) is a rare clinical condition characterized by formation of a circumferential constriction ring around an appendage or genitalia. Cases are mostly reported in infants and young children. Early recognition and a definitive treatment are of paramount importance in order to avoid irreversible ischemia and possible auto-amputation. We describe a case of a 14-month-old child presented to casualty with a history of refusal to feed and inconsolable cry. Parents noticed a recent swelling of left third toe. On careful examination the child was found to have an acquired constriction ring secondary to a tightly wrapped hair around left third toe. An urgent surgical decompression was done by the orthopaedic team with complete resolution of symptoms. We summarized the pathophysiology of ACRS underlining the need of awareness in treating physicians. The possible medico legal implications should be kept in mind bearing a suggested link with non-accidental injury

Physicians' use of the 5As in counseling obese patients: is the quality of counseling associated with patients' motivation and intention to lose weight?

<p>Abstract</p> <p>Background</p> <p>Physicians are encouraged to counsel obese patients to lose weight, but studies measuring the quality of physicians' counseling are rare. We sought to describe the quality of physicians' obesity counseling and to determine associations between the quality of counseling and obese patients' motivation and intentions to lose weight, key predictors of behavior change.</p> <p>Methods</p> <p>We conducted post-visit surveys with obese patients to assess physician's use of 5As counseling techniques and the overall patient-centeredness of the physician.. Patients also reported on their motivation to lose weight and their intentions to eat healthier and exercise. One-way ANOVAs were used to describe mean differences in number of counseling practices across levels of self-rated intention and motivation. Logistic regression analyses were conducted to assess associations between number of 5As counseling practices used and patient intention and motivation.</p> <p>Results</p> <p>137 patients of 23 physicians were included in the analysis. While 85% of the patients were counseled about obesity, physicians used only a mean of 5.3 (SD = 4.6) of 18 possible 5As counseling practices. Patients with higher levels of motivation and intentions reported receiving more 5As counseling techniques than those with lower levels. Each additional counseling practice was associated with higher odds of being motivated to lose weight (OR 1.31, CI 1.11-1.55), intending to eat better (OR 1.23, CI 1.06-1.44), and intending to exercise regularly (OR 1.14, CI 1.00-1.31). Patient centeredness of the physician was also positively associated with intentions to eat better (OR 2.96, CI 1.03-8.47) and exercise (OR 26.07, CI 3.70-83.93).</p> <p>Conclusions</p> <p>Quality of physician counseling (as measured using the 5As counseling framework and patient-centeredness scales) was associated with motivation to lose weight and intentions to change behavior. Future studies should determine whether higher quality obesity counseling leads to improved behavioral and weight outcomes.</p

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Optimal iterative methods for finding multiple roots of nonlinear equations using free parameters

[EN] In this paper, we propose a family of optimal eighth order convergent iterative methods for multiple roots with known multiplicity with the introduction of two free parameters and three univariate weight functions. Also numerical experiments have applied to a number of academical test functions and chemical problems for different special schemes from this family that satisfies the conditions given in convergence result.This research was partially supported by Ministerio de Economia y Competitividad MTM2014-52016-C02-2-P and Generalitat Valenciana PROMETEO/2016/089.Zafar, F.; Cordero Barbero, A.; Quratulain, R.; Torregrosa Sánchez, JR. (2018). Optimal iterative methods for finding multiple roots of nonlinear equations using free parameters. Journal of Mathematical Chemistry. 56(7):1884-1901. https://doi.org/10.1007/s10910-017-0813-1S18841901567R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, On developing fourth-order optimal families of methods for multiple roots and their dynamics. Appl. Math. Comput. 265(15), 520–532 (2015)R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, V. Kanwar, An optimal fourth-order family of methods for multiple roots and its dynamics. Numer. Algor. 71(4), 775–796 (2016)R. Behl, A. Cordero, S.S. Motsa, J.R. Torregrosa, An eighth-order family of optimal multiple root finders and its dynamics. Numer. Algor. (2017). doi: 10.1007/s11075-017-0361-6F.I. Chicharro, A. Cordero, J. R. Torregrosa, Drawing dynamical and parameters planes of iterative families and methods. Sci. World J. ID 780153 (2013)A. Constantinides, N. Mostoufi, Numerical Methods for Chemical Engineers with MATLAB Applications (Prentice Hall PTR, New Jersey, 1999)J.M. Douglas, Process Dynamics and Control, vol. 2 (Prentice Hall, Englewood Cliffs, 1972)Y.H. Geum, Y.I. Kim, B. Neta, A class of two-point sixth-order multiple-zero finders of modified double-Newton type and their dynamics. Appl. Math. Comput. 270, 387–400 (2015)Y.H. Geum, Y.I. Kim, B. Neta, A sixth-order family of three-point modified Newton-like multiple-root finders and the dynamics behind their extraneous fixed points. Appl. Math. Comput. 283, 120–140 (2016)J.L. Hueso, E. Martınez, C. Teruel, Determination of multiple roots of nonlinear equations and applications. J. Math. Chem. 53, 880–892 (2015)L.O. Jay, A note on Q-order of convergence. BIT Numer. Math. 41, 422–429 (2001)S. Li, X. Liao, L. Cheng, A new fourth-order iterative method for finding multiple roots of nonlinear equations. Appl. Math. Comput. 215, 1288–1292 (2009)S.G. Li, L.Z. Cheng, B. Neta, Some fourth-order nonlinear solvers with closed formulae for multiple roots. Comput. Math. Appl. 59, 126–135 (2010)B. Liu, X. Zhou, A new family of fourth-order methods for multiple roots of nonlinear equations. Nonlinear Anal. Model. Control 18(2), 143–152 (2013)M. Shacham, Numerical solution of constrained nonlinear algebraic equations. Int. J. Numer. Method Eng. 23, 1455–1481 (1986)M. Sharifi, D.K.R. Babajee, F. Soleymani, Finding the solution of nonlinear equations by a class of optimal methods. Comput. Math. Appl. 63, 764–774 (2012)J.R. Sharma, R. Sharma, Modified Jarratt method for computing multiple roots. Appl. Math. Comput. 217, 878–881 (2010)F. Soleymani, D.K.R. Babajee, T. Lofti, On a numerical technique forfinding multiple zeros and its dynamic. J. Egypt. Math. Soc. 21, 346–353 (2013)F. Soleymani, D.K.R. Babajee, Computing multiple zeros using a class of quartically convergent methods. Alex. Eng. J. 52, 531–541 (2013)R. Thukral, A new family of fourth-order iterative methods for solving nonlinear equations with multiple roots. J. Numer. Math. Stoch. 6(1), 37–44 (2014)R. Thukral, Introduction to higher-order iterative methods for finding multiple roots of nonlinear equations. J. Math. Article ID 404635 (2013)X. Zhou, X. Chen, Y. Song, Constructing higher-order methods for obtaining the muliplte roots of nonlinear equations. J. Comput. Math. Appl. 235, 4199–4206 (2011)X. Zhou, X. Chen, Y. Song, Families of third and fourth order methods for multiple roots of nonlinear equations. Appl. Math. Comput. 219, 6030–6038 (2013

Comparison of Whole Blood and Peripheral Blood Mononuclear Cell Gene Expression for Evaluation of the Perioperative Inflammatory Response in Patients with Advanced Heart Failure

Background: Heart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP) was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC) transcriptomes obtained from patients’ blood samples. Whole blood (WB) samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined. Methods: We collected blood samples from 31 HF patients (57¡15 years old) undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively) (25–75% IQR 7–14 days) and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA) score was used to characterize the severity of MOD into low (# 4 points), intermediate (5–11), and high ($ 12) risk categories correlating with GEP. Results: Results indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO) analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups. Conclusion: GEP analysis of WB has the potential to become a clinical tool for immune-monitoring in patients with MO