bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer dynamics of Tn6648, a composite integrative conjugative element generated by tandem accretion of Tn5801 and Tn6647 in Enterococcus faecalis
Authors: León-Sampedro Ricardo , Fernández-de-Bobadilla Miguel D , San Millán Álvaro , Baquero Fernando , Coque Teresa M 
Published: June 2019

Abstract

Background
Tn5801 [tet(M)], a Tn916-like element with site-specific affinity for the 3′ end of the housekeeping gene guaA, may integrate at different chromosomal sites.

Objectives
To characterize the genetic context of Tn5801 to define its transfer dynamics and impact on the evolution of Enterococcus faecalis (Efs).

Methods
WGS (Illumina HiSeq 2500) was performed on the Efs clinical strain Ef1 and primary and secondary transconjugants of Efs strains JH2-2 [which naturally contains Tn5801.B23, an unusual variant that lacks tet(M)], OG1RF and OG1SS carrying different copies of Tn5801-like elements. The transposon structures were analysed using a range of bioinformatics tools allowing us to identify the context of Tn5801-like elements. Growth rates at different tetracycline concentrations (0.5–20 mg/L) were estimated using a Synergy HTX plate reader.

Results
Tn5801.B15 [tet(M), 20.3 kb] exists and can be transferred either singly or within Tn6648 (53.2 kb), a composite element that comprises Tn5801.B15 and Tn6647, a newly identified 32.8 kb transposon that contains the prgABCT operon of pheromone-responsive plasmids. These transposons are able to integrate at specific 11 nt sequences at the 3′ end of guaA and at other chromosomal sites in Efs genomes, thus being able to generate tandem accretions. These events may increase the number of tet(M) copies, enhancing tetracycline resistance in the recipient strain.

Conclusions
This study describes Tn6647 and Tn6648 (comprising Tn6647 and Tn5801.B15) and highlights the diversity of mechanisms for conjugative mobilization and chromosomal insertion of these elements, which can result in tandem accretion. This strategy would facilitate the adaptation of Efs clones to environmental challenges.
Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis
Authors: Boutrot Maxime , Azougagh Khalid , Guinard Jérôme , Boulain Thierry , Barbier François 
Published: June 2019

Abstract

Background
Intestinal colonization resistance is mainly exerted by commensal anaerobes.

Objectives
To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients.

Patients and methods
All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition.

Results
Among the 352 included patients [median ICU stay 16 (9–30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12–13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46–12.63, P = 0.01). Exposure to other antimicrobials—especially ceftriaxone and imipenem/meropenem—exerted no independent impact on the likelihood of CFR-GNB acquisition.

Conclusions
Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.
The Political Economy of Program Enforcement: Evidence from Brazil
Authors: Brollo Fernanda , Kaufmann Katja , La Ferrara Eliana 
Published: June 2019

AbstractDo politicians manipulate the enforcement of conditional welfare programs to influence electoral outcomes? We study the Bolsa Familia Program (BFP) in Brazil, which provides a monthly stipend to poor families conditional on school attendance. Repeated failure to comply with this requirement results in increasing penalties. First, we exploit random variation in the timing when beneficiaries learn about penalties for noncompliance around the 2008 municipal elections. We find that the vote share of candidates aligned with the president is lower in zip codes where more beneficiaries received penalties shortly before (as opposed to shortly after) the elections. Second, we show that politicians strategically manipulate enforcement. Using a regression discontinuity design, we find weaker enforcement before elections in municipalities where mayors from the presidential coalition can run for reelection. We provide evidence that manipulation occurs through misreporting school attendance, particularly in municipalities with a higher fraction of students in schools with politically connected principals.
Analogues of the fundamental and secondary theorems of selection, assuming a log-normal distribution of expected fitness
Authors: Morrissey Michael B , Bonnet Timothée 
Published: June 2019

Abstract
It is increasingly common for studies of evolution in natural populations to infer the quantitative genetic basis of fitness (e.g., the additive genetic variance for relative fitness), and of relationships between traits and fitness (e.g., the additive genetic covariance of traits with relative fitness). There is a certain amount of tension between the theory that justifies estimating these quantities, and methodological considerations relevant to their empirical estimation. In particular, the additive genetic variances and covariances involving relative fitness are justified by the fundamental and secondary theorems of selection, which pertain to relative fitness on the scale that it is expressed. However, naturally-occurring fitness distributions lend themselves to analysis with generalized linear mixed models (GLMMs), which conduct analysis on a different scale, typically on the scale of the logarithm of expected values, from which fitness is expressed. This note presents relations between evolutionary change in traits, and the rate of adaptation in fitness, and log quantitative genetic parameters of fitness, potentially reducing the discord between theoretical and methodological considerations to the operationalization of the secondary and fundamental theorems of selection.
Damselfly (Odonata: Calopterygidae) Population Decline in an Urbanizing Watershed
Authors: Córdoba-Aguilar Alex , Rocha-Ortega Maya 
Published: June 2019

Abstract
Reduction of terrestrial vegetation and degradation of water quality are among the factors driving insect population decline in growing cities. In this study, we investigated the extent of habitat deterioration, behavioral and physiological responses, and fitness of a damselfly [Hetaerina americana (F.)] population in a semitropical region in central Mexico. The study population was located in a riverine area that crosses a small urban area (Tehuixtla city). We related two habitat variables (tree/shrub covered area and numbers of wastewater outlets) to presumable damselfly responses (larval and adult abundance, duration of adults exposed directly to sunlight, lipid content and muscle mass, and egg survival) over the years 2002 and 2016. We detected a reduction in terrestrial vegetation cover, an increase in wastewater outlets, and a decrease in larval and adult abundance. Adults were more exposed to sunlight in 2016 than in 2002 and showed a reduced lipid content and muscle mass in 2016. Egg survival also decreased. Although correlative, these results suggest impairment of damselfly condition (via lipid and muscle reduction) and fitness as urbanization increases.
Boundaries of eliminated heterochromatin of Tetrahymena are positioned by the DNA-binding protein Ltl1
Authors: Jaspan Vita N , Taye Marta E , Carle Christine M , Chung Joyce J , Chalker Douglas L 
Published: June 2019

AbstractDuring differentiation of the Tetrahymena thermophila somatic nucleus, its germline-derived DNA undergoes extensive reorganization including the removal of ∼50 Mb from thousands of loci called internal eliminated sequences (IESs). IES-associated chromatin is methylated on lysines 9 and 27 of histone H3, marking newly formed heterochromatin for elimination. To ensure that this reorganized genome maintains essential coding and regulatory sequences, the boundaries of IESs must be accurately defined. In this study, we show that the developmentally expressed protein encoded by Lia3-Like 1 (LTL1) (Ttherm_00499370) is necessary to direct the excision boundaries of particular IESs. In ΔLTL1 cells, boundaries of eliminated loci are aberrant and heterogeneous. The IESs regulated by Ltl1 are distinct from those regulated by the guanine-quadruplex binding Lia3 protein. Ltl1 has a general affinity for double stranded DNA (Kd ∼ 350 nM) and binds specifically to a 50 bp A+T rich sequence flanking each side of the D IES (Kd ∼ 43 nM). Together these data reveal that Ltl1 and Lia3 control different subsets of IESs and that their mechanisms for flanking sequence recognition are distinct.
Integrative construction of regulatory region networks in 127 human reference epigenomes by matrix factorization
Authors: Liu Dianbo , Davila-Velderrain Jose , Zhang Zhizhuo , Kellis Manolis 
Published: June 2019

Abstract
Despite large experimental and computational efforts aiming to dissect the mechanisms underlying disease risk, mapping cis-regulatory elements to target genes remains a challenge. Here, we introduce a matrix factorization framework to integrate physical and functional interaction data of genomic segments. The framework was used to predict a regulatory network of chromatin interaction edges linking more than 20 000 promoters and 1.8 million enhancers across 127 human reference epigenomes, including edges that are present in any of the input datasets. Our network integrates functional evidence of correlated activity patterns from epigenomic data and physical evidence of chromatin interactions. An important contribution of this work is the representation of heterogeneous data with different qualities as networks. We show that the unbiased integration of independent data sources suggestive of regulatory interactions produces meaningful associations supported by existing functional and physical evidence, correlating with expected independent biological features.
The nucleosome position-encoding WW/SS sequence pattern is depleted in mammalian genes relative to other eukaryotes
Authors: Wright Gregory M , Cui Feng 
Published: June 2019

AbstractNucleosomal DNA sequences generally follow a well-known pattern with ∼10-bp periodic WW (where W is A or T) dinucleotides that oscillate in phase with each other and out of phase with SS (where S is G or C) dinucleotides. However, nucleosomes with other DNA patterns have not been systematically analyzed. Here, we focus on an opposite pattern, namely anti-WW/SS pattern, in which WW dinucleotides preferentially occur at DNA sites that bend into major grooves and SS (where S is G or C) dinucleotides are often found at sites that bend into minor grooves. Nucleosomes with the anti-WW/SS pattern are widespread and exhibit a species- and context-specific distribution in eukaryotic genomes. Unlike non-mammals (yeast, nematode and fly), there is a positive correlation between the enrichment of anti-WW/SS nucleosomes and RNA Pol II transcriptional levels in mammals (mouse and human). Interestingly, such enrichment is not due to underlying DNA sequence. In addition, chromatin remodeling complexes have an impact on the abundance but not on the distribution of anti-WW/SS nucleosomes in yeast. Our data reveal distinct roles of cis- and trans-acting factors in the rotational positioning of nucleosomes between non-mammals and mammals. Implications of the anti-WW/SS sequence pattern for RNA Pol II transcription are discussed.
A novel histone H4 variant H4G regulates rDNA transcription in breast cancer
Authors: Long Mengping , Sun Xulun , Shi Wenjin , Yanru An , Leung Sophia T C , Ding Dongbo , Cheema Manjinder S , MacPherson Nicol , Nelson Christopher J , Ausio Juan , Yan Yan , Ishibashi Toyotaka 
Published: June 2019

AbstractHistone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.
Association between dietary zinc intake and abdominal aortic calcification in US adults
Authors: Chen Wei , Eisenberg Ruth , Mowrey Wenzhu B , Wylie-Rosett Judith , Abramowitz Matthew K , Bushinsky David A , Melamed Michal L 
Published: June 2019

Abstract

Background
In animal studies, zinc supplementation inhibited phosphate-induced arterial calcification. We tested the hypothesis that higher intake of dietary zinc was associated with lower abdominal aortic calcification (AAC) among adults in the USA. We also explored the associations of AAC with supplemental zinc intake, total zinc intake and serum zinc level.

Methods
We performed cross-sectional analyses of 2535 participants from the National Health and Nutrition Examination Survey 2013–14. Dietary and supplemental zinc intakes were obtained from two 24-h dietary recall interviews. Total zinc intake was the sum of dietary and supplemental zinc. AAC was measured using dual-energy X-ray absorptiometry in adults ≥40 years of age and quantified using the Kauppila score system. AAC scores were categorized into three groups: no AAC (AAC = 0, reference group), mild–moderate (AAC &gt;0–≤6) and severe AAC (AAC &gt;6).

Results
Dietary zinc intake (mean ± SE) was 10.5 ± 0.1 mg/day; 28% had AAC (20% mild–moderate and 8% severe), 17% had diabetes mellitus and 51% had hypertension. Higher intake of dietary zinc was associated with lower odds of having severe AAC. Per 1 mg/day higher intake of dietary zinc, the odds of having severe AAC were 8% lower [adjusted odds ratio 0.92 (95% confidence interval 0.86–0.98), P = 0.01] compared with those without AAC, after adjusting for demographics, comorbidities and laboratory measurements. Supplemental zinc intake, total zinc intake and serum zinc level were not associated with AAC.

Conclusions
Higher intake of dietary zinc was independently associated with lower odds of having severe AAC among noninstitutionalized US adults.
Imaging the kidney: from light to super-resolution microscopy
Authors: Angelotti Maria Lucia , Antonelli Giulia , Conte Carolina , Romagnani Paola 
Published: June 2019

Abstract
The important achievements in kidney physiological and pathophysiological mechanisms can largely be ascribed to progress in the technology of microscopy. Much of what we know about the architecture of the kidney is based on the fundamental descriptions of anatomic microscopists using light microscopy and later by ultrastructural analysis provided by electron microscopy. These two techniques were used for the first classification systems of kidney diseases and for their constant updates. More recently, a series of novel imaging techniques added the analysis in further dimensions of time and space. Confocal microscopy allowed us to sequentially visualize optical sections along the z-axis and the availability of specific analysis software provided a three-dimensional rendering of thicker tissue specimens. Multiphoton microscopy permitted us to simultaneously investigate kidney function and structure in real time. Fluorescence-lifetime imaging microscopy allowed to study the spatial distribution of metabolites. Super-resolution microscopy increased sensitivity and resolution up to nanoscale levels. With cryo-electron microscopy, researchers could visualize the individual biomolecules at atomic levels directly in the tissues and understand their interaction at subcellular levels. Finally, matrix-assisted laser desorption/ionization imaging mass spectrometry permitted the measuring of hundreds of different molecules at the same time on tissue sections at high resolution. This review provides an overview of available kidney imaging strategies, with a focus on the possible impact of the most recent technical improvements.
Meta-analysis of the Smoker’s Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment
Authors: Zhang Peng , Guo Zhen-Ni , Sun Xin , Zhao Yingkai , Yang Yi 
Published: June 2019

Abstract

Introduction
The existence of the smoker’s paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT).

Methods
This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies.

Results
Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36–1.60) after IVT and 2.10 (95% CI: 1.47–3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81–1.59]).

Conclusion
Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis.

Implications
The existence of the smoker’s paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.
Postural Control and Interceptive Skills in Children With Autism Spectrum Disorder
Authors: Chen Li-Chiou , Su Wan-Chun , Ho Tzu-Lin , Lu Lu , Tsai Wen-Che , Chiu Yen-Nan , Jeng Suh-Fang 
Published: June 2019

Abstract

Background
Increasing evidence shows common motor deficits associated with autism spectrum disorder (ASD) that can relate to impaired planning and control processes of the sensorimotor system. Catching is a fundamental motor skill that requires coordination between vision, posture, and arm movements. Although postural control and ball catching have been shown to be impaired in children with ASD, previous studies have not investigated how these components are integrated.

Objective
The objective of this study was to investigate the sensorimotor control of arm movements and postural adjustments during ball catching in children with and without ASD.

Design
This study employed a cross-sectional design.

Methods
Fifteen children with ASD (mean [SD] age = 8.8 [1.2] years; 12 boys) and 15 age- and sex-matched typically developing children participated in this study. Children were asked to catch a ball rolling down a ramp in 6 test conditions in which visual inputs and ramp direction were manipulated to provide different sensory conditions and postural demands.

Results
Compared with their typically developing peers, children with ASD had increased difficulties catching balls, especially those from lateral directions. They less often used visual information to plan for catching motion, demonstrated fewer and delayed anticipatory postural adjustments, and exhibited increased corrective control.

Limitations
The sample excluded children with intellectual disability and attention deficit and hyperactivity disorders that might reduce the generalizability to the whole ASD population.

Conclusions
Our results suggest that motor difficulties present in children with ASD can result from compromised sensorimotor integration in planning and control of movements.
The Formalization of Banking Supervision in Japan and Sweden
Authors: HOTORI Eiji , WENDSCHLAG Mikael 
Published: June 2019

AbstractThis study examines the formalization of banking supervision in Japan and Sweden that occurred in the decades around 1900. Using an incremental change approach, we examine the respective cases along three dimensions: (a) the legal framework, (b) the banking supervisory agency, and (c) bank supervisory activities. Through this comparative analysis, we find several similarities and differences. The most important similarity we find is that financial crises—generally considered to be a primary driver of major regulatory and supervisory reforms—did not play a main role in the formalization of supervision in either Japan or Sweden. Rather, formalization was an incremental change process closely linked to the organic development of the banking sector, the general public’s increasing exposure to the banks as deposit holders and borrowers, and the increased need for professionalization of the banking sector. This finding suggests that our approach is applicable to any country where the formalization of supervision took place without being prompted by a specific event such as a financial crisis.