bluuebunny/crossref_metadata_2025 huggingface dataset:
SYSTEMIC PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVITREAL AFLIBERCEPT, BEVACIZUMAB, AND RANIBIZUMAB
Authors: Avery Robert L. , Castellarin Alessandro A. , Steinle Nathan C. , Dhoot Dilsher S. , Pieramici Dante J. , See Robert , Couvillion Stephen , Nasir Ma'an A. , Rabena Melvin D. , Maia Mauricio , Van Everen Sherri , Le Kha , Hanley William D.
Published: January 2017

Purpose:

To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO).

Methods:

Prospective, open-label, nonrandomized clinical trial of patients with AMD, DME, or RVO who were antivascular endothelial growth factor (VEGF) naïve or had not received anti-VEGF for ≥4 months. Patients received 3 monthly intravitreal injections of aflibercept 2.0 mg, bevacizumab 1.25 mg, or ranibizumab (0.5 mg for AMD/RVO, 0.3 mg for DME). The main outcome measures were serum PKs and plasma free-VEGF concentrations after the first and third injections.

Results:

A total of 151 patients were included. In AMD/DME/RVO, systemic exposure to each drug was highest with bevacizumab, then aflibercept, and lowest with ranibizumab. Ranibizumab cleared from the bloodstream more quickly than bevacizumab or aflibercept. Aflibercept treatment resulted in the greatest reductions in plasma free-VEGF relative to baseline levels, whereas ranibizumab treatment resulted in the smallest decreases in plasma free-VEGF.

Conclusion:

The three anti-VEGF treatments examined in this analysis demonstrated notable differences in systemic PKs. Generally, the reduction in plasma free-VEGF levels correlated with elevated levels of circulating anti-VEGF agents, with the reduction in free-VEGF levels greatest with aflibercept and least with ranibizumab.
SUBFOVEAL CHOROIDAL THICKNESS AND VASCULAR DIAMETER IN ACTIVE AND RESOLVED CENTRAL SEROUS CHORIORETINOPATHY
Authors: Chung Yoo-Ri , Kim Jong Wan , Choi Shin-Young , Park Sung Wook , Kim Jeong Hun , Lee Kihwang
Published: January 2017

Purpose:

To determine the subfoveal choroidal thickness and analyze Haller's layer, Sattler's layer, and large choroidal vessel diameter in eyes with active central serous chorioretinopathy (CSC) and after resolution of CSC.

Methods:

Ocular and clinical features of 32 eyes with CSC were analyzed retrospectively from October 2014 to September 2015. Subfoveal choroidal thickness and thicknesses of Haller's layer and Sattler's layer were measured in the active and resolved states. The diameter of the subfoveal choroidal hyporeflective lumen (i.e., the large choroidal vessel in Haller's layer) was also measured.

Results:

The mean subfoveal choroidal thickness, mean thickness of Haller's layer, and mean choroidal vessel diameter were significantly less after the resolution of CSC (P < 0.001). However, the thickness of Sattler's layer did not change after the resolution of CSC (P = 0.731). There were no significant differences among the different treatment modalities.

Conclusion:

After the resolution of CSC, the subfoveal choroidal thickness and thickness of Haller's layer declined, but the reduced diameter of subfoveal choroidal vessels accounted for only about half of the total thickness changes in the choroid. These results suggest that nonvascular smooth muscle cells might play a role in the thickening of the choroid during CSC and possibly in the pathogenesis and progression of CSC.
ASSOCIATION STUDY BETWEEN POLYMORPHISMS OF THE p53 AND LYMPHOTOXIN ALPHA (LTA) GENES AND THE RISK OF PROLIFERATIVE VITREORETINOPATHY/RETINAL DETACHMENT IN A MEXICAN POPULATION
Authors: Quiroz-Casian Natalia , Lozano-Giral David , Miranda-Duarte Antonio , Garcia-Montalvo Ivan , Rodriguez-Loaiza Jose L. , Zenteno Juan C.
Published: January 2017

Purpose:

To report the results of an association study between single-nucleotide polymorphisms of the p53 and LTA genes and the risk of proliferative vitreoretinopathy (PVR)/retinal detachment (RD) in a Mexican cohort.

Methods:

A total of 380 unrelated subjects were studied, including 98 patients with primary rhegmatogenous RD without PVR, 82 patients with PVR after RD surgery, and 200 healthy, ethnically matched subjects. Genotyping of single-nucleotide polymorphisms rs1042522 (p53 gene) and rs2229094 (LTA gene) was performed by direct nucleotide sequencing. Allele frequencies, genotype frequencies, and Hardy–Weinberg equilibrium were assessed with HaploView software.

Results:

No significant differences in the allelic distributions of the previously identified risk C allele for LTA rs2229094 were observed between RD subjects and controls (odds ratio [95% confidence interval] = 0.8 [0.5–1.2]; P = 0.3). Conversely, the C allele for rs1042522 in p53 was positively associated with an increased risk for RD (odds ratio [95% confidence interval] = 1.4 [1.01–1.9]; P = 0.04). No significant differences were observed when the subgroup of 82 RD + PVR subjects was compared with the subgroup of 98 patients with RD.

Conclusion:

The C allele for rs1042522 in p53 was genetically associated with a higher risk for RD but not for PVR in this cohort. This is the first association study attempting replication of PVR-associated risk alleles in a nonwhite population.
How mice are indispensable for understanding obesity and diabetes genetics
Authors: Attie Alan D. , Churchill Gary A. , Nadeau Joseph H.
Published: January 2017

Purpose of review

The task of cataloging human genetic variation and its relation to disease is rapidly approaching completion. The new challenge is to discover the function of disease-associated genes and to understand the pathways that lead to human disease. We propose that achieving this new level of understanding will increasingly rely on the use of model organisms. We discuss the advantages of the mouse as a model organism to our understanding of human disease.

Recent findings

The collection of available mouse strains represents as much genetic and phenotypic variation as is found in the human population. However, unlike humans, mice can be subjected to experimental breeding protocols and the availability of tissues allows for a far greater and deeper level of phenotyping. New methods for gene editing make it relatively easy to create mouse models of known human mutations. The distinction between genetic and epigenetic inheritance can be studied in great detail. Various experimental protocols enable the exploration of the role of the microbiome in physiology and disease.

We propose that there will be an interdependence between human and model organism research. Technological advances and new genetic screening platforms in the mouse have greatly improved the path to gene discovery and mechanistic studies of gene function.
Non-parametric test for connectivity detection in multivariate autoregressive networks and application to multiunit activity data
Authors: Gilson M , Campo A Tauste , Chen X , Thiele A , Deco G
Published: January 2017

Directed connectivity inference has become a cornerstone in neuroscience to analyze multivariate data from neuroimaging and electrophysiological techniques. Here we propose a non-parametric significance method to test the non-zero values of multivariate autoregressive model to infer interactions in recurrent networks. We use random permutations or circular shifts of the original time series to generate the null-hypothesis distributions. The underlying network model is the same as used in multivariate Granger causality, but our test relies on the autoregressive coefficients instead of error residuals. By means of numerical simulation over multiple network configurations, we show that this method achieves a good control of false positives - type 1 error - and detects existing pairwise connections more accurately than using the standard parametric test for the ratio of error residuals. In practice, our method aims to detect temporal interactions in real neuronal networks with nodes possibly exhibiting redundant activity. As a proof of concept, we apply our method to multiunit activity (MUA) recorded from Utah electrode arrays in a monkey and examine detected interactions between 25 channels. We show that during stimulus presentation our method detects a large number of interactions that cannot be solely explained by the increase in the MUA level.
The stress-inducible peroxidaseTSA2 enables Chromosome IV duplication to be conditionally beneficial inSaccharomyces cerevisiae
Authors: Linder Robert A. , Greco John P. , Seidl Fabian , Matsui Takeshi , Ehrenreich Ian M.
Published: January 2017

Although chromosomal duplications are often deleterious, in some cases they enhance cells’ abilities to tolerate specific genetic or environmental challenges. Identifying the genes that cause particular chromosomal duplications to confer these conditionally beneficial effects can improve our understanding of the genetic and molecular mechanisms that enable certain aneuploidies to persist in cell populations and contribute to disease and evolution. Here, we perform a screen for spontaneous mutations that improve the tolerance of haploidSaccharomyces cerevisiaeto hydrogen peroxide. Chromosome IV duplication is the most frequent mutation, as well as the only change in chromosomal copy number, seen in the screen. Using a genetic mapping strategy that involves systematically deleting segments of a duplicated chromosome, we show that the Chromosome IV duplication’s effect is largely due to the generation of a second copy of the stress-inducible cytoplasmic thioredoxin peroxidaseTSA2. This finding is consistent with a growing literature indicating that the conditionally beneficial effects of chromosomal duplications tend to reflect the contributions of small numbers of genes that enhance tolerance to specific stresses when their copy number is increased.

Article summary

Changes in karyotype play an important role in evolution and health. Although these aneuploidization events are usually deleterious, in some instances they show conditionally beneficial effects by enabling cells to tolerate specific mutations or environmental stresses. The mechanisms underlying these protective effects of aneuploidization are not fully understood. To provide insights into this problem, we identify and characterize a conditionally beneficial chromosomal duplication that makes haploid yeast more tolerant to oxidative stress. We determine that the effect of the chromosomal duplication on oxidative stress tolerance is largely explained by duplication of a single stress-inducible gene.
Efficient and flexible strategies for gene cloning and vector construction using overlap PCR
Authors: Liu Zhongtian , Zhang Tingting , Xu Kun
Published: January 2017

Gene cloning and vector construction are basic technologies in modern molecular biology for gene functional study. Here, we present flexible and efficient strategies for gene cloning and vector construction using overlap PCR. We firstly cloned the open reading frames (ORFs) of the porcineMSTN, chickenOVAand humanα-glucosidasegenes by overlap PCR-based assembling of their exons, which could be amplified with genomic DNAs as the templates without RNA extraction and RT-PCR reaction. Secondly, we generated additionally three designed functional cassettes by overlap PCR-based assembling of different DNA elements, which facilitated the construction their expression vectors greatly. Moreover, we further developed an interesting overlap-circled PCR method for fast plasmid vector construction without any cutting and ligating procedure. These advanced applications of overlap PCR provide useful alternative tools for gene cloning and vector construction.
Fragile dynamics enable diverse genomic determinants to influence arrhythmia propensity
Authors: Kamerzell Tim J , Sobie Eric A , Yang Kai-Chen , Nerbonne Jeanne M , MacRae Calum A , Iyengar Ravi
Published: January 2017

Genotype-phenotype relationships are determinants of human diseases. Often, we know little about why so many genes are involved in complex common diseases. We hypothesized that this multigene effect arises from the relationship between genes and physiological dynamics. We tested this hypothesis for arrhythmias as physiological dynamics define this disease. We integrated graph theory analysis of genomic and protein-protein interaction networks with dynamical models of ion channel function to identify the physiological dynamics of genome wide variation for five different arrhythmias. Regulatory networks for the cardiac conduction system and arrhythmias were constructed from GWAS and known disease genes. Electrophysiological models of myocyte action potentials were used to conduct extensive parameter variations to identify robust and fragile kinetic parameters that were then, using regulatory networks, associated with genomic determinants. We find that genome-wide determinants of arrhythmias that represent many cellular processes are selectively associated with fragile physiological dynamics of ion channel kinetics. This association predicts disease propensity. Deep RNA sequencing from human left ventricular tissue of arrhythmia and control subjects confirmed the predictive relationship. Taken together these studies show that the varied multigene effects of arrhythmias arises because of associations with fragile kinetic parameters of cardiac electrophysiology.

Significance Statement

Our understanding of the genetics of common diseases has advanced exponentially over the past decade. We now know that differences and variation in multiple genes contribute to disease susceptibility with significant heterogeneity in the phenotype. However, how genetic variation contributes to disease phenotypes remains unknown. We hypothesized that the relationships between physiological dynamics and genetic architecture is a fundamental determinant of disease susceptibility and genetic heterogeneity. To test our hypothesis, we integrated mathematical models of cardiac electrophysiology with genetic network models of cardiac arrhythmias. We found that disease related genome variants were selectively associated with fragile kinetic parameters that predict disease propensity and identified several novel cellular processes associated with arrhythmogenesis.
Promoter-Enhancer Interactions Identified from Hi-C Data using Probabilistic Models and Hierarchical Topological Domains
Authors: Ron Gil , Moran Dror , Kaplan Tommy
Published: January 2017

Proximity-ligation methods as Hi-C allow us to map physical DNA-DNA interactions along the genome, and reveal its organization in topologically associating domains (TADs). As Hi-C data accumulate, computational methods were developed for identifying domain borders in multiple cell types and organisms.

Here, we present PSYCHIC, a computational approach for analyzing Hi-C data and identifying Promoter-Enhancer interactions. We use a unified probabilistic model to segment the genome into domains, which we merge hierarchically and fit the Hi-C interaction map with a local background model. This allows us to estimate the expected number of interactions for every DNA-DNA pair, thus identifying over-represented interactions across the genome.

By analyzing published Hi-C data in human and mouse, we identified hundreds of thousands of putative enhancers and their target genes in multiple cell types, and compiled an extensive genome-wide catalog of gene regulation in human and mouse.
Automated Detection of Records in Biological Sequence Databases that are Inconsistent with the Literature
Authors: Bouadjenek Mohamed Reda , Verspoor Karin , Zobel Justin
Published: January 2017

We investigate and analyse the data quality of nucleotide sequence databases with the objective of automatic detection of data anomalies and suspicious records. Specifically, we demonstrate that the published literature associated with each data record can be used to automatically evaluate its quality, by cross-checking the consistency of the key content of the database record with the referenced publications. Focusing on GenBank, we describe a set of quality indicators based on the relevance paradigm of information retrieval (IR). Then, we use these quality indicators to train an anomaly detection algorithm to classify records as“confident”or“suspicious”.

Our experiments on the PubMed Central collection show assessing the coherence between the literature and database records, through our algorithms, is an effective mechanism for assisting curators to perform data cleansing. Although fewer than 0.25% of the records in our data set are known to be faulty, we would expect that there are many more in GenBank that have not yet been identified. By automated comparison with literature they can be identified with a precision of up to 10% and a recall of up to 30%, while strongly outperforming several baselines. While these results leave substantial room for improvement, they reflect both the very imbalanced nature of the data, and the limited explicitly labelled data that is available. Overall, the obtained results show promise for the development of a new kind of approach to detecting low-quality and suspicious sequence records based on literature analysis and consistency. From a practical point of view, this will greatly help curators in identifying inconsistent records in large-scale sequence databases by highlighting records that are likely to be inconsistent with the literature.
Systematic analysis of the effects of the DNA damage response network in telomere defective budding yeast
Authors: Holstein Eva-Maria , Ngo Greg , Lawless Conor , Banks Peter , Greetham Matthew , Wilkinson Darren , Lydall David
Published: January 2017

Functional telomeres are critically important to eukaryotic genetic stability. Budding yeast is a powerful model organism for genetic analysis and yeast telomeres are maintained by very similar mechanisms to human telomeres. Scores of proteins and pathways are known to affect telomere function. Here, we report a series of related genome-wide genetic interaction screens performed on budding yeast cells with acute or chronic telomere defects. We examined genetic interactions in cells defective in Cdc13 and Stn1, affecting two components of CST, a single stranded DNA (ssDNA) binding complex that binds telomeric DNA. We investigated genetic interactions in cells with defects in Rfa3, affecting the major ssDNA binding protein, RPA, which has overlapping functions with CST at telomeres. We also examined genetic interactions in cells lackingEXO1orRAD9,affecting different aspects of the DNA damage response in acdc13-1background. Comparing fitness profiles across the data sets allows us build up a picture of the specific responses to different types of dysfunctional telomeres. Our results show that there is no universal response to telomere defects. To help others engage with the large volumes of data we make the data available via two interactive web-based tools: Profilyzer and DIXY. Among numerous genetic interactions we found thechk1Δ mutation improved fitness ofcdc13-1 exo1Δ cells more than other checkpoint mutations (ddc1Δ,rad9Δ,rad17Δ,rad24Δ), whereas incdc13-1cells the effects of all checkpoint mutations were similar. We find that Chk1 stimulates resection at defective telomeres, revealing a new role for Chk1 in the eukaryotic DNA damage response network.
Targeted gene correction ofFKRPby CRISPR/Cas9 restores functional glycosylation of α-dystroglycan in cortical neurons derived from human induced pluripotent stem cells
Authors: Lana Beatrice , Kim Jihee , Ryan David , Konstantinidis Evangelos , Louzada Sandra , Fu Beiyuan , Yang Fengtang , Stemple Derek L. , Liu Pentao , Muntoni Francesco , Lin Yung-Yao
Published: January 2017

Mutations in genes required for functional glycosylation of α-dystroglycan cause a group of congenital muscular dystrophies associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic, physiology-relevant human cellular models has limited our understanding of the cortical abnormalities in dystroglycanopathies. Here we generate induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous mutations in the ribitol-5-phosphate transferase gene,FKRP. We carry out targeted gene correction in FKRP-iPSCs using CRISPR/Cas9-mediated genome editing. We characterise the directed differentiation of FKRP- and corrected-iPSCs to neural stem cells, cortical progenitors and cortical neurons. Importantly, we show that targeted gene correction ofFKRPrestores functional glycosylation of α-dystroglycan in iPSC-derived cortical neurons. We independently validate this result by showing targeted gene mutation ofFKRPdisrupts functional glycosylation of α-dystroglycan. This work demonstrates the feasibility of using CRISPR/Cas9-engineered human iPSCs for modelling dystroglycanopathies and provides a foundation for therapeutic development.

Highlights

Generation of FKRP-iPSCs for modelling cortical abnormalities in dystroglycanopathies

Precise gene correction by CRISPR/Cas9-mediated genome editing

Directed differentiation of isogenic control and FKRP-iPSC to cortical neurons

Functional glycosylation of α-dystroglycan is restored in cortical neurons derived from CRISPR/Cas9-corrected iPSCs

Targeted gene mutation of FKRP disrupts functional glycosylation of α-dystroglycan in cortical neurons
Wilm’s tumor 1 promotes memory flexibility
Authors: Mariottini Chiara , Munari Leonardo , Gunzel Ellen , Seco Joseph M. , Tzavaras Nikos , Hansen Jens , Stern Sarah A. , Gao Virginia , Aleyasin Hossein , Azeloglu Evren U. , Hodes Georgia E. , Russo Scott J. , Huff Vicki , Birtwistle Marc , Blitzer Robert D. , Alberini Cristina M. , Iyengar Ravi
Published: January 2017

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilm’s Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.
Genome Graphs
Authors: Novak Adam M. , Hickey Glenn , Garrison Erik , Blum Sean , Connelly Abram , Dilthey Alexander , Eizenga Jordan , Elmohamed M. A. Saleh , Guthrie Sally , Kahles André , Keenan Stephen , Kelleher Jerome , Kural Deniz , Li Heng , Lin Michael F. , Miga Karen , Ouyang Nancy , Rakocevic Goran , Smuga-Otto Maciek , Zaranek Alexander Wait , Durbin Richard , McVean Gil , Haussler David , Paten Benedict
Published: January 2017

There is increasing recognition that a single, monoploid reference genome is a poor universal reference structure for human genetics, because it represents only a tiny fraction of human variation. Adding this missing variation results in a structure that can be described as a mathematical graph: a genome graph. We demonstrate that, in comparison to the existing reference genome (GRCh38), genome graphs can substantially improve the fractions of reads that map uniquely and perfectly. Furthermore, we show that this fundamental simplification of read mapping transforms the variant calling problem from one in which many non-reference variants must be discovered de-novo to one in which the vast majority of variants are simply re-identified within the graph. Using standard benchmarks as well as a novel reference-free evaluation, we show that a simplistic variant calling procedure on a genome graph can already call variants at least as well as, and in many cases better than, a state-of-the-art method on the linear human reference genome. We anticipate that graph-based references will supplant linear references in humans and in other applications where cohorts of sequenced individuals are available.
Multiplexed dynamic imaging of genomic loci in single cells by combined CRISPR imaging and DNA sequential FISH
Authors: Takei Yodai , Shah Sheel , Harvey Sho , Qi Lei S. , Cai Long
Published: January 2017

Visualization of chromosome dynamics allows the investigation of spatiotemporal chromatin organization and its role in gene regulation and other cellular processes. However, current approaches to label multiple genomic loci in live cells have a fundamental limitation in the number of loci that can be labelled and uniquely identified. Here we describe an approach we call “track first and identify later” for multiplexed visualization of chromosome dynamics by combining two techniques: CRISPR labeling and DNA sequential fluorescencein situhybridization (DNA seqFISH). Our approach first labels and tracks chromosomal loci in live cells with the CRISPR system, then barcodes those loci by DNA seqFISH in fixed cells and resolves their identities. We demonstrate our approach by tracking telomere dynamics, identifying 12 unique subtelomeric regions with variable detection efficiencies, and tracking back the telomere dynamics of respective chromosomes in mouse embryonic stem cells.
UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy
Authors: Smith Tom , Heger Andreas , Sudbery Ian
Published: January 2017

Unique Molecular Identifiers (UMIs) are random oligonucleotide barcodes that are increasingly used in high-throughput sequencing experiments. Through a UMI, identical copies arising from distinct molecules can be distinguished from those arising through PCR amplification of the same molecule. However, bioinformatic methods to leverage the information from UMIs have yet to be formalized. In particular, sequencing errors in the UMI sequence are often ignored or else resolved in an ad hoc manner. We show that errors in the UMI sequence are common and introduce network-based methods to account for these errors when identifying PCR duplicates. Using these methods, we demonstrate improved quantification accuracy both under simulated conditions and real iCLIP and single-cell RNA-seq data sets. Reproducibility between iCLIP replicates and single-cell RNA-seq clustering are both improved using our proposed network-based method, demonstrating the value of properly accounting for errors in UMIs. These methods are implemented in the open source UMI-tools software package.
Nanoscale stability of two- and three-dimensional defects in Cu/Ag–Mo thin films
Authors: Csiszár G. , Makvandi A. , Mittemeijer E. J.
Published: January 2017

A comparative study of the thermal stability of nanocrystalline Cu–Mo and Ag–Mo alloy thin films was performed. Phase decomposition, texture evolution, grain coarsening and segregation of Mo to planar faults of both films, before and after heat treatment, were studied using X-ray diffraction measurements and (high-resolution) transmission electron microscopy with energy-dispersive spectroscopy. The evolution of stress/strain in the thin films was traced by in situ X-ray diffraction measurements. The segregation of Mo solute atoms at twin boundaries in both films already occurs at room temperature. By first segregation and then precipitation of Mo atoms at grain boundaries, the columnar grain microstructure is preserved upon heat treatment. In the case of Ag–Mo thin films, the twin boundaries are also more or less preserved at elevated temperature, but in the case of Cu–Mo thin films the annihilation of twin boundaries takes place concomitantly with the precipitation of Mo in columnar grain interiors.
Expression and crystallographic studies ofD-glycero-β-D-manno-heptose-1-phosphate adenylyltransferase fromBurkholderia pseudomallei
Authors: Park Jimin , Kim Hyojin , Kim Suwon , Lee Daeun , Shin Dong Hae
Published: January 2017

The Gram-negative bacteriumBurkholderia pseudomalleiis the causative agent of melioidosis. D-glycero-β-D-manno-Heptose-1-phosphate adenylyltransferase (HldC) is the fourth enzyme of the ADP-L-glycero-β-D-manno-heptose biosynthesis pathway, which produces an essential carbohydrate comprising the inner core of lipopolysaccharide. Therefore, HldC is a potential target of antibiotics against melioidosis. In this study, HldC fromB. pseudomalleihas been cloned, expressed, purified and crystallized. Synchrotron X-ray data from a selenomethionine-substituted HldC crystal were also collected to 2.8 Å resolution. The crystal belonged to the primitive triclinic space groupP1, with unit-cell parametersa= 74.0,b= 74.0,c= 74.9 Å, α = 108.4, β = 108.4, γ = 108.0°. Eight protomers are present in the unit cell and three out of five selenomethionines were found in each protomer using thePHENIXsoftware suite. A full structural determination is in progress to elucidate the structure–function relationship of the protein.
The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch‐up vaccine programme: a two‐centre observational study
Authors: Munro A , Gillespie C , Cotton S , Busby‐Earle C , Kavanagh K , Cuschieri K , Cubie H , Robertson C , Smart L , Pollock K , Moore C , Palmer T , Cruickshank ME
Published: January 2017

Objective

To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy.

Design

A two‐centre observational study including vaccinated and unvaccinated women.

Setting

Colposcopy clinics serving two health regions in Scotland, UK.

Population

A total of 361 women aged 20–25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening.

Methods

Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi‐square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features.

Main outcome measures

Colposcopic features, HPV genotypes, mRNA expression, and cervical histology.

Results

The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated).

Conclusions

In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch‐up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines.

Tweetable abstract

Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.
Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes
Authors: Laugesen Caroline Schmidt , Ostri Christoffer , Brynskov Troels , Lund‐Andersen Henrik , Larsen Michael , Vorum Henrik , Sørensen Torben L.
Published: January 2017

Purpose

There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti‐VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes.

Methods

A nationwide retrospective review of medical records from 2010 to 2013.

Results

We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow‐up was 323 days (interquartile range 72–1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI 0.13–1.01) before injections. After an average of 4.7 injections (range 1–15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13–0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI −0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision was unchanged (gain or loss of 0–0.05 logMAR), and in nine eyes (27%), vision decreased 0.1 logMAR or more. Mean central foveal thickness (CFT) on optical coherence tomography (OCT) scan was 412 μm (95% CI 390–434 μm) before injections. After injections, the mean CFT decreased to 352 μm (95% CI 334–370 μm). The mean reduction in CFT was 14% (95% CI 4–24%, p = 0.01). Sixteen eyes (48.5%) became devoid of oedema on the last OCT scan. Despite the significant reduction in CFT, the visual acuity remained unchanged.

Conclusion

Intravitreal ranibizumab can be effective in previously vitrectomized eyes with diabetic macular oedema. However, the response is variable and should be carefully monitored.
Sleep and diabetic retinopathy
Authors: Jee Donghyun , Keum Nana , Kang Seungbum , Arroyo Jorge G.
Published: January 2017

Purpose

To investigate the association between sleep duration and diabetic retinopathy (DR).

Methods

A population‐based cross‐sectional study using a nation‐wide, systemically stratified, multistage, clustered sampling method included a total of 1670 subjects aged ≥40 years with diabetes who participated in the Korean National Health and Nutrition Examination Survey during 2008–2012. All participants performed standardized interviews, including self‐reported sleep duration, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. Diabetic retinopathy (DR) was graded and classified as any DR and vision‐threatening DR. Participants were stratified into men and women.

Results

The mean sleep duration was 6.71 hr/day. In men, adjusted OR of any DR was 1.88 [95% confidence interval (OR), 1.01–3.59] in those with ≤5 hr sleep, and 2.19 (95% CI, 1.01–4.89) in those with ≥9 hr sleep, compared to in subjects with 6–8 hr sleep, after adjusting for potential confounders including age, body mass index (BMI), diabetes duration, fasting glucose level, haemoglobin A1c levels and hypertension. In women, however, no significant association between sleep duration and DR was found. The vision‐threatening DR was not significantly associated with sleep duration in either men or women.

Conclusions

Short and long sleep was associated with high prevalence of DR in men. Sleep deprivation may be involved in the pathogenesis of DR development.
Self‐Control in Childhood: A Synthesis of Perspectives and Focus on Early Development
Authors: Gagne Jeffrey R.
Published: January 2017

In this article, I describe three prominent developmental science perspectives on self‐control in childhood, discuss differences and areas of consensus, and suggest a comprehensive, early integrative approach to research on this topic. The self‐control perspectives are the self‐regulatory concepts of delay of gratification and willpower, the cognitive neuroscience executive functioning construct of inhibitory control (IC), and the behavioral and emotional temperament dimensions of effortful control and IC. The primary focus of these approaches is similar, and differences are based largely on theory, methods, and the age of the children studied. Therefore, I agree with a synthesis of these perspectives championed by other developmental scientists, and propose comprehensive, multitheoretical, multimethod empirical study that begins when self‐control emerges in toddlerhood.
Neglected issues in using weather and climate information in ecology and biogeography
Authors: Baker David J. , Hartley Andrew J. , Pearce‐Higgins James W. , Jones Richard G. , Willis Stephen G.
Published: January 2017

Anthropogenic climate change is already impacting ecological systems. Understanding how organisms respond to weather (short‐term) and climate (long‐term) variability, and the population and ecosystem‐wide consequences of climate change, is a research priority. The appropriate use of information on past and potential future weather and climate conditions is crucial for such research, but uncertainties and biases in this information are seldom given full consideration, with important consequences for assessing the potential impacts of climate change on the conservation of biodiversity. Here, we highlight three important neglected issues pertaining to the major applications of weather and climate information in ecological and biogeographical studies. These are as follows: (1) the uncertainty associated with historical weather and climate information; (2) the selection of ensembles of simulated future climate conditions derived from general circulation models (GCM); and (3) the uncertainty and assumptions associated with downscaling GCM simulations to ecologically relevant spatial scales. Broadly, in order to improve the use of weather and climate information in ecological studies, we propose that ecologists must: (1) use weather and climate products that are appropriate for their intended purpose; (2) explore the consequences of uncertainty in these products for ecological conclusions; and (3) seek greater integration of ecological and climate research to create products that reflect both the requirements of ecologists and the limits of climatology. This will enable more effective research into the likely responses of ecological systems to future climate change.
The Discounted Euler Equation: A Note
Authors: McKay Alisdair , Nakamura Emi , Steinsson Jón
Published: January 2017

We present a simple model with income risk and borrowing constraints that yields a ‘discounted Euler equation’. This feature of the model mutes the extent to which news about far future real interest rates (i.e. forward guidance) affects current outcomes. We show that this simple model approximates the outcomes of a rich model with uninsurable income risk and borrowing constraints in response to a forward guidance shock. The model is simple enough to be easily incorporated into simple New Keynesian models. We illustrate this with an application to the zero lower bound.
Parr dispersal between streams via a marine environment: A novel mechanism behind straying for anadromous brown trout?
Authors: Taal Imre , Rohtla Mehis , Saks Lauri , Kesler Martin , Jürgens Kristiina , Svirgsden Roland , Matetski Lagle , Verliin Aare , Paiste Päärn , Vetemaa Markus
Published: January 2017

Otolith Sr:Ca profiles demonstrated that juvenile anadromous brown trout (ABT) Salmo trutta may descend to the brackish waters of the Baltic Sea from their natal streams as parr or fry and then migrate into non‐natal streams before transforming into smolt. To our knowledge, no such published documentation exists for ABT. The ecological significance of this life‐history strategy is presently not clear. However, stream shifting through the marine environment should to be considered with regard to stock management and the assessment and restoration of salmonid populations and their potential habitats.
Effect of wind turbulence on gas transport in porous media: experimental method and preliminary results
Authors: Pourbakhtiar A. , Poulsen T. G. , Wilkinson S. , Bridge J. W.
Published: January 2017

We demonstrate a novel experimental arrangement for measuring wind turbulence‐induced gas transport in dry porous media under controlled conditions. This equipment was applied to assess the effect of wind turbulence on gas transport (quantified as a dispersion coefficient) as a function of distance to the surface of the porous medium exposed to wind. Two different strategies for the measurement of wind‐induced gas transport were compared. Experiments were carried out with O2 and CO2 as tracer gases with average vertical wind speeds of 0.02–1.06 m s−1. Oxygen breakthrough curves as a function of distance to the wind‐exposed surface of the porous medium were analysed numerically with a finite‐difference‐based model to assess gas transport. We showed that wind turbulence‐induced gas transport is an important transport mechanism that can be 20–70 times larger than molecular diffusion‐induced transport. Wind conditions and properties of the porous medium had strong controlling effects on this relationship. Importantly, we show that even though wind‐induced gas transport is greatest near to the wind‐exposed surface, it can have marked effects on the variation in gas concentration at much greater depths.

Highlights

We explored the effect of atmospheric wind turbulence on gas transport in porous media.

We measured the depth relation of wind‐induced dispersion in porous media for real wind conditions.

Wind‐induced gas dispersion coefficients were 20–70 times larger than molecular diffusion.

Wind turbulence can potentially have a considerable effect on gas transport in porous media.
Low‐Income and Never‐Married Families: Service and Support at the Intersection of Family Court and Child Support Agency Systems
Authors: Boggess Jacquelyn L.
Published: January 2017

State child support enforcement agencies facilitate the legal establishment of paternity for children born outside of marriage and enforce the payment of child support by noncustodial parents. They are directed to move cash resources from a nonresident parent to the home of his/her child. Ideally, this income transfer provides financial support for children and security for custodial families. This article describes how the agency is challenged in the fulfillment of this responsibility by the adversarial nature of its own process and by the intractable poverty and unemployment (among other barriers to economic security) of a significant portion of its caseload.
Delivery Outcomes of Patients with Acute Migraine in Pregnancy: A Retrospective Study
Authors: Grossman Tracy B. , Robbins Matthew S. , Govindappagari Shravya , Dayal Ashlesha K.
Published: January 2017

Objective

To describe labor and delivery outcomes in pregnant patients presenting to the hospital setting with an acute severe migraine headache attack earlier in the same gestation.

Methods

We retrospectively reviewed pregnancy and delivery records from a database of consecutive inpatient neurology consultations for acute headache in pregnant women over a 5 year period.

Results

We identified 86 pregnant women with acute migraine. The mean age was 29.3 (±6.4) years. Nearly half had migraine with aura (35/86 [40.7%]), 12.8% (12/86) had chronic migraine, and 31.4% (27/86) presented in status migrainosus. Complication rates included 54.7%([41/75], 95% CI 29.87, 52.13) for at least one adverse outcome, 28.0% ([21/75], 95% CI 11.78, 30.22) for preterm delivery, 21.3% ([16/75], 95% CI 7.7, 24.3) for preeclampsia, 30.6% ([23/75] 95% CI 13.48, 32.52) for cesarean delivery, and 18.7% ([14/75] 95% CI 6.15, 21.85) for low birthweight.

Conclusions

Pregnant women seeking treatment for acute migraine headache experienced a higher rate of preterm delivery, preeclampsia, and low birthweight but a lower rate of cesarean delivery than the local and general populations. More than half (54.7% [41/75] 95% CI 29.87, 52.13) of the study patients experienced some type of adverse birth outcome, suggesting that pregnancies in migraine patients presenting to an acute care setting may benefit from more intense surveillance.
Impact of land‐use change on flower‐visiting insect communities on an oceanic island
Authors: Picanço Ana , Rigal François , Matthews Thomas J. , Cardoso Pedro , Borges Paulo A. V.
Published: January 2017

Land‐use change has profoundly impacted pollinator communities throughout the world. However, the processes through which it acts on pollinator diversity and composition are still poorly understood, especially in highly vulnerable island ecosystems.

In this study, we investigated the distribution, abundance, richness and composition of flower‐visiting insects to assess their response to land‐use change in Terceira Island (Azores).

Flower‐visiting insects were sampled over 2 years using a standardised protocol along 50 transects across five different habitats corresponding to a land‐use gradient. Insect species were classified as indigenous or exotics. We assessed changes across habitats using multiple diversity indices, species abundance distribution models (SAD) and species composition metrics (β‐diversity), along with plant species composition.

We observed that indigenous flower‐visiting insects were dominant, both in abundance and species richness, across the entire land‐use gradient. Species diversity varied only slightly across the gradient. SADs were lognormal in all habitats, with very few truly common and rare flower‐visiting insects and a prevalence of species of intermediate abundance. Species replacement was significantly higher mainly between the two most contrasting habitats (i.e. natural forests and intensive pastures) but was significantly correlated with species replacement of host plant species across the gradient.

Our results revealed that the Azorean flower‐visiting insect communities were highly simplified across the entire gradient with little difference between habitats. In the absence of strong exotic competitors, indigenous flower‐visiting insects expand their range and occupy new anthropogenic habitats, also facilitating the expansion of a large number of exotic plant species.
Structural and redox features of La0.7Bi0.3Mn1−xCoxO3 nanoperovskites for ethane combustion and CO oxidation
Authors: Gholizadeh Ahmad , Malekzadeh Azim
Published: January 2017

In this work, structural and catalytic properties of La0.7Bi0.3Mn1−xCoxO3 nanocatalysts with x=0.00, 0.25, 0.50, 0.75, and 1.00 prepared by citrate method are investigated. The structural characterization using X'Pert package and Fullprof program is an evidence for structural phase transition. The values of refined unit cell volume obtained from the Rietveld analysis show decreasing and increasing tendencies for values of x≤0.5 and x>0.5, respectively. The catalytic performance tests of the catalysts show that the samples x=0.00 and 0.25 have lower temperature of CO oxidation and C2H6 combustion, respectively.