bluuebunny/crossref_metadata_2025 huggingface dataset:
On the design and fabrication of W‐band stabilised‐pattern dual‐polarised horn antennas with DMLS and CNC
Authors: Al‐Tarifi Muhannad A. , Filipovic Dejan S.
Published: June 2017

A square horn antenna with rotationally‐stable radiation patterns that are also nearly invariant with frequency across the entire W band (75–110 GHz) is demonstrated. The flaring is designed such that the horn can support two perpendicular linear polarisations with very similar radiation patterns. The antenna is fabricated in two ways; by assembling two computer numerical control (CNC) machined split blocks, and by metallic 3D printing using direct metal laser sintering (DMLS). All fabricated antennas (one CNC aluminium, one DMLS aluminium, and one DMLS stainless steel) have similar performances that agree well with theory. Effect of surface roughness with the DMLS antennas is found to be electrically insignificant which is desired for fast prototyping and many current and emerging applications.
Machine learning approach for optimal determination of wave parameter relationships
Authors: Barker Aaron , Murphy Jimmy
Published: June 2017

Wave parameter relationships have long been determined using methods that give non‐standard and often inaccurate results. With increased commercial activity in the marine sector, the importance of accurate wave parameter relationship determination has become increasingly apparent. The outputs of many numerical models and buoy datasets do not include all requisite wave parameters, and a typical approach is to use a constant conversion factor or relationship based on defined spectra such as the Bretschneider or the joint North Sea wave observation project (JONSWAP) spectrum to determine these parameters. Given that relationships between wave parameters vary significantly over both hourly and seasonal and annual timescales, the currently employed methods are lacking, as subtleties are missed by the simpler approach. This paper addresses the determination of wave parameter relationships using a machine learning (ML)‐based model, identifying and selecting the optimal method for the conversion of wave parameters (Te, T01) in coastal Irish Waters. This approach is then validated at two sites on the West coast of Ireland. The aim is to highlight the utility of ML in approximating the relationship between wave parameters; using both buoy and modelled data, and mapping the predicted outcomes for a wave energy converter based on a variety of ML and measure correlate predict approaches.
Cervical Spine Deformity—Part 2: Management Algorithm and Anterior Techniques
Authors: Tan Lee A. , Riew K. Daniel , Traynelis Vincent C.
Published: June 2017

A sound operative plan based on solid understanding of the pathology and biomechanics is the most important part of cervical deformity correction. Many different surgical options exist for operative management of cervical spine deformities. However, selecting the correct approach that ensures the optimal clinical outcome can be challenging and often controversial. In Part 2 of this three-part review series, we discuss the pre-operative planning, management algorithm, and anterior surgical techniques for cervical deformity correction.
Mitochondrial genome ofPlasmodium vivax/simiumdetected in an endemic region for malaria in the Atlantic Forest of Espírito Santo state, Brazil: do mosquitoes, simians and humans harbor the same parasite?
Authors: Buery JC , Rodrigues PT , Natal L , Salla LC , Loss AC , Vicente CR , Rezende HR , Duarte AMCR , Fux B , Malafronte RS , Falqueto A , Cerutti C.
Published: June 2017

Background

The transmission of malaria in the extra-Amazonian regions of Brazil, although interrupted in the 1960s, has persisted to the present time in some areas of dense Atlantic Forest, with reports of cases characterized by particular transmission cycles and clinical presentations. Bromeliad-malaria, as it is named, is particularly frequent in the state of Espírito Santo, withPlasmodium vivaxbeing the parasite commonly recognized as the etiologic agent of human infections. With regard to the spatial and temporal distances between cases reported in this region, the transmission cycle does not fit the traditional malaria cycle. The existence of a zoonosis, with infected simians participating in the epidemiology, is therefore hypothesized. In the present study, zoonotic transmission of bromeliad-malaria in Espírito Santo is investigated, based on the complete mitochondrial genome of DNA extracted from isolates ofPlasmodiumspecies which had infected humans, a simian from the genusAllouata, andAnophelesmosquitoes.Plasmodium vivax/simiumwas identified in the samples by both nested-PCR and real-time PCR. After amplification, the mitochondrial genome was completely sequenced and compared in a haplotype network, including all sequences ofP. vivax/simiummitochondrial genomes sampled from humans and simians from all regions in Brazil.

Results

The haplotype network demonstrates that humans and simians from the Atlantic Forest share the same haplotype, but some isolates from humans are not identical to the simian isolate. In addition, the plasmodial DNA extracted from mosquitoes revealed sequences different from those obtained from simians, but similar to two isolates from humans.

Conclusions

These findings reinforce the hypothesis that in the Atlantic Forest, and especially in the state with the highest frequency of bromeliad-malaria in Brazil, the same parasite species is shared by humans and simians, at least in part. The difference between the sequences of mosquitoes and simians raises two hypotheses: (1) two distinct transmission cycles for human malaria exist in the study area, one of them involving simians and the other exclusive to human hosts, or (2) there is only one transmission cycle involving humans and simians, but the identification of variations among simians was not possible due to a lack of other samples.
Genome-wide analysis reveals distinct genetic mechanisms of diet-dependent lifespan and healthspan inD. melanogaster
Authors: Wilson Kenneth A. , Nelson Christopher S. , Beck Jennifer N. , Brem Rachel B. , Kapahi Pankaj
Published: June 2017

Dietary restriction (DR) robustly extends lifespan and delays age-related diseases across species. An underlying assumption in aging research has been that DR mimetics extend both lifespan and healthspan jointly, though this has not been rigorously tested in different genetic backgrounds. Furthermore, nutrient response genes important for lifespan or healthspan extension remain underexplored, especially in natural populations. To address these gaps, we utilized over 150 DGRP strains to measure nutrient-dependent changes in lifespan and age-related climbing ability to measure healthspan. DR extended lifespan and delayed decline in climbing ability on average, but there was no evidence of correlation between these traits across individual strains. Through GWAS, we then identified and validatedjugheadandFerredoxinas determinants of diet-dependent lifespan, andDaedalusfor diet-dependent physical activity. Modulating these genes produced independent effects on lifespan and climbing ability, further suggesting that these age-related traits are likely to be regulated through distinct genetic mechanisms.
Structure and misfolding of the flexible tripartite coiled coil domain of glaucoma-associated myocilin
Authors: Hill Shannon E. , Nguyen Elaine , Donegan Rebecca K. , Hazel Anthony , Gumbart James C. , Lieberman Raquel L.
Published: June 2017

Glaucoma-associated myocilin is a member of the olfactomedins, a protein family broadly involved in neuronal development and human disease. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a disulfide-linked, parallel dimer-of-dimers Y-shaped molecule, with distinct tetramer and dimer regions. The structure of the C-terminal 7-heptad dimer elucidates an unexpected repeat pattern involving electrostatic inter-strand stabilization. Molecular dynamics simulations reveal an alternate conformation in which the terminal inter-strand disulfide bond limits the extent of unfolding and results in a kinked configuration. Taken together, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of extracellular coiled coils for protein design and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.

Highlights

Glaucoma-causing extracellular protein associated with amyloid forming propensity

Structural studies confirm tripartite parallel dimer-of-dimers coiled coil

Leucine zipper exhibits non-canonical heptad repeat pattern with disulfide cap

Glaucoma-associated variants in tetramer alter structure but not stability

eTOC blurb

Hill et al describe the structure of the coiled-coil region of myocilin, the extracellular olfactomedin family member closely associated with the ocular disorder glaucoma. Myocilin’s coiled coil adopts a unique Y-shaped parallel dimer-of-timers employing an unusual heptad repeat pattern. Selected disease variants alter quaternary structure.
RNA interference pathways display high rates of adaptive protein evolution across multiple invertebrates
Authors: Palmer William H. , Hadfield Jarrod , Obbard Darren J.
Published: June 2017

Conflict between organisms can lead to reciprocal adaptation that manifests itself as an increased evolutionary rate in the genes mediating the conflict. This adaptive signature has been observed in RNA interference (RNAi) pathway genes involved in the suppression of viruses and transposable elements inDrosophila melanogaster, suggesting that a subset ofDrosophilaRNAi genes may be locked into an arms race with these parasites. However, it is not known whether rapid evolution of RNAi genes is a general phenomenon across invertebrates, or which RNAi genes generally evolve adaptively. Here we use population genomic data from eight invertebrate species to infer rates of adaptive sequence evolution, and to test for past and ongoing selective sweeps in RNAi genes. We assess rates of adaptive protein evolution across species by using a formal meta-analytic framework to combine data across species, and by implementing a multispecies generalised linear mixed model of mutation counts. In all species, we find that RNAi genes display a greater rate of adaptive protein substitution than other genes, and that this is primarily mediated by positive selection acting on the subset of genes that are most likely to defend against viruses and transposable elements. In contrast, evidence for recent selective sweeps is broadly spread across functional classes of RNAi genes and differs substantially among species. Finally, we identify genes that exhibit elevated adaptive evolution across the analysed insect species combined, perhaps due to concurrent parasite-mediated arms races.
A Deep Learning Approach to Estimate Collagenous Tissue Nonlinear Anisotropic Stress-Strain Responses from Microscopy Images
Authors: Liang Liang , Liu Minliang , Sun Wei
Published: June 2017

Biological collagenous tissues comprised of networks of collagen fibers are suitable for a broad spectrum of medical applications owing to their attractive mechanical properties. In this study, we developed a noninvasive approach to estimate collagenous tissue elastic properties directly from microscopy images using Machine Learning (ML) techniques. Glutaraldehyde-treated bovine pericardium (GLBP) tissue, widely used in the fabrication of bioprosthetic heart valves and vascular patches, was chosen as a representative collagenous tissue. A Deep Learning model was designed and trained to process second harmonic generation (SHG) images of collagen networks in GLBP tissue samples, and directly predict the tissue elastic mechanical properties. The trained model is capable of identifying the overall tissue stiffness with a classification accuracy of 84%, and predicting the nonlinear anisotropic stress-strain curves with average regression errors of 0.021 and 0.031. Thus, this study demonstrates the feasibility and great potential of using the Deep Learning approach for fast and noninvasive assessment of collagenous tissue elastic properties from microstructural images.
Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection
Authors: Hoytema van Konijnenburg David P. , Reis Bernardo S. , Pedicord Virginia , Farache Julia , Victora Gabriel D. , Mucida Daniel
Published: June 2017

Intestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit distinct location and movement patterns in the epithelial compartment that were microbiota-dependent and quickly altered upon enteric infections. These infection-induced changes included increased inter-epithelial cell (EC) scanning, anti-microbial gene expression and glycolysis. Direct modulation of glycolysis was sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Both γδ IEL behavioral and metabolic changes were dependent on EC pathogen sensing. Our results uncover a coordinated EC–IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier.
The chromatin factor Gon4l regulates embryonic axis extension by promoting mediolateral cell polarity and notochord boundary formation through negative regulation of cell adhesion
Authors: Williams Margot L K , Sawada Atsushi , Budine Terin , Yin Chunyue , Gontarz Paul , Krezel Lilianna Solnica-
Published: June 2017

Anteroposterior axis extension during vertebrate gastrulation requires cell proliferation, embryonic patterning, and morphogenesis to be spatiotemporally coordinated, but the underlying genetic mechanisms remain poorly understood. Here we define a role for the conserved chromatin factor Gon4l, encoded byugly duckling (udu),in coordinating tissue patterning and axis extension during zebrafish gastrulation. Although identified as a recessive enhancer of short axis phenotypes in planar cell polarity (PCP) mutants, we found that Gon4l functions in a genetically independent, partially overlapping fashion with PCP signaling to regulate mediolateral cell polarity underlying axis extension in part by promoting notochord boundary formation. We identified direct genomic targets of Gon4l and found that it acts as both a positive and negative regulator of gene expression, including limiting expression of the cell-cell and cell-matrix adhesion molecules EpCAM and Integrinα3b. Excessepcamoritga3bin wild-type gastrulae phenocopied notochord boundary defects ofudumutants, while downregulation ofitga3bsuppressed them. By promoting formation of this anteroposteriorly aligned boundary and associated cell polarity, Gon4l cooperates with PCP signaling to coordinate morphogenesis with the anteroposterior embryonic axis.
Estimates of introgression as a function of pairwise distances
Authors: Pfeifer Bastian , Kapan Durrell D
Published: June 2017

Background

Research over the last 10 years highlights the increasing importance of hybridization between species as a major force structuring the evolution of genomes and potentially providing raw material for adaptation by natural and/or sexual selection. Fueled by research in a few model systems where phenotypic hybrids are easily identified, research into hybridization and introgression (the flow of genes between species) has exploded with the advent of whole-genome sequencing and emerging methods to detect the signature of hybridization at the whole-genome or chromosome level. Amongst these are a general class of methods that utilize patterns of single-nucleotide polymorphisms (SNPs) across a tree as markers of hybridization. These methods have been applied to a variety of genomic systems ranging from butterflies to Neanderthal’s to detect introgression, however, when employed at a fine genomic scale these methods do not perform well to quantify introgression in small sample windows.

Results

We introduce a novel method to detect introgression by combining two widely used statistics: pairwise nucleotide diversitydxyand Patterson’sD. The resulting statistic, theBasic distance fraction(Bdf), accounts for genetic distance across possible topologies and is designed to simultaneously detect and quantify introgression. We also relate our new method to the recently publishedfdand incorporate these statistics into the powerful genomics R-package PopGenome, freely available on GitHub (pievos101/PopGenome). The supplemental material contains a wide range of simulation studies and a detailed manual how to perform the statistics within the PopGenome framework.

Conclusion

We present a new distance based statisticBdfthat avoids the pitfalls of Patterson’sDwhen applied to small genomic regions and accurately quantifies the fraction of introgression (f) for a wide range of simulation scenarios.
Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS
Authors: Çetiner Uğur , Sukharev Sergei
Published: June 2017

Adaptive desensitization and inactivation are common properties of most ion channels and receptors. The mechanosensitive channel of small conductance MscS, which serves as a low-threshold osmolyte release valve in most bacteria, is unusual because it slowly inactivates not from the open, but from the resting state under moderate tensions. The manifestation of this mechanism is the channel’s ability to discriminate the rate of tension application, i.e., to ignore slow tension ramps but fully respond to abruptly applied stimuli. In this work, we present a reconstruction of the landscape for tension-dependent MscS transitions based on patch current kinetics recorded under specially designed pressure protocols. The data are analyzed with a three-state continuous time Markov model of gating, where the tension-dependent transition rates are governed by Arrhenius-type relations. The analysis provides assignments to the intrinsic opening, closing, inactivation, and recovery rates as well as their tension dependencies. These parameters, which define the spatial (areal) distances between the energy wells and the positions of barriers, describe the tension-dependent distribution of the channel population between the three states and quantitatively predict the experimentally observed dynamic pulse and ramp responses. Our solution also provides an analytic expression for the area of the inactivated state in terms of two experimentally accessible parameters: the tension at which inactivation probability is maximized, γ*, and the midpoint tension for activation, γ0.5. The analysis initially performed onEscherichia coliMscS shows its applicability to the previously uncharacterized MscS homolog fromPseudomonas aeruginosa. MscS inactivation minimizes metabolic losses during osmotic permeability response and thus contributes to the environmental fitness of bacteria.
Multivariate Heteroscedasticity Models for Functional Brain Connectivity
Authors: Seiler Christof , Holmes Susan
Published: June 2017

Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI). We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP) comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.
Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants
Authors: Kerr Shona M. , Campbell Archie , Marten Jonathan , Vitart Veronique , McIntosh Andrew , Porteous David J. , Hayward Caroline
Published: June 2017

This paper provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records in particular represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets including cancer, mental health and maternity inpatient information is also possible through the same straightforward and transparent application process. The Electronic Health Record linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index (CHI) number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genome-wide genetic information.
Patterns of conservation and diversification in the fungal polarization network
Authors: Diepeveen Eveline T. , Pourquié Valérie , Gehrmann Thies , Abeel Thomas , Laan Liedewij
Published: June 2017

The combined actions of proteins in networks underlie all fundamental cellular functions. Deeper insights into the dynamics of network composition across species and their functional consequences are crucial to fully understand protein network evolution. Large-scale comparative studies with high phylogenetic resolution are now feasible through the recent rise in available genomic datasets of both modelandnon-model species. Here we focus on the polarity network, which is universally essential for cell proliferation and studied in great detail in the model organism,Saccharomyces cerevisiae. We examine 34 proteins, directly related to cell polarization, across 200 fungal strains/species to determine evolution of the composition of the network and patterns of conservation and diversification.

We observe strong protein conservation for a group of 16 core proteins: 95% of all strains/species possess at least 75% of these proteins, albeit in varying compositions. We find high levels of variation in prevalence and sequence identity in the remaining 18 proteins, resulting in distinct lineage-specific compositions of the network in the majority of strains/species. We test if the observed diversification in network composition correlates with potential underlying factors and find that lineage, lifestyle, and genetic distance co-vary with network size. Yeast, filamentous and basal unicellular fungi form distinctive groups based on these analyses, with substantial differences to their polarization network. Our study shows that evolution of the fungal polarization network is highly dynamic, even between closely related species, and that functional conservation is achieved by varying structural conservation of the fungal polarization proteins.

Data Deposition

Sequence alignments used are available upon request.
A convergent depression vulnerability pathway encoded by emergent spatiotemporal dynamics
Authors: Hultman Rainbo , Ulrich Kyle , Sachs Benjamin D. , Blount Cameron , Carlson David E. , Ndubuizu Nkemdilim , Bagot Rosemary C. , Parise Eric , Vu Mai-Anh T. , Wang Joyce , Silva Alcino J. , Deisseroth Karl , Mague Stephen , Caron Marc G. , Nestler Eric J. , Carin Lawrence , Dzirasa Kafui
Published: June 2017

Fluctuations in brain local field potential (LFP) oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these LFP oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional processes at the network level. Here we use machine learning to integrate LFP activity acquired concurrently from seven cortical and subcortical brain regions into an analytical model that predicts the emergence of depression-related behavioral dysfunction across individual mice subjected to chronic social defeat stress. We uncover a spatiotemporal dynamic network in which activity originates in prefrontal cortex (PFC) and nucleus accumbens (NAc, ventral striatum), relays through amygdala and ventral tegmental area (VTA), and converges in ventral hippocampus (VHip). The activity of this network correlates with acute threat responses and brain-wide cellular firing, and it is enhanced in three independent molecular-, physiological-, and behavioral-based models of depression vulnerability. Finally, we use two antidepressant manipulations to demonstrate that this vulnerability network is biologically distinct from the networks that signal behavioral dysfunction after stress. Thus, corticostriatal to VHip-directed spatiotemporal dynamics organized at the network level are a novel convergent depression vulnerability pathway.
mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces potentially functional transcripts
Authors: Anderson Jennifer L , Mulligan Timothy S , Shen Meng-Chieh , Wang Hui , Scahill Catherine M , Du Shao J , Busch-Nentwich Elisabeth M , Farber Steven A
Published: June 2017

As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, allow frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes. We analyzed mRNA processing in seven zebrafish lines with mutations expected to disrupt gene function, generated by CRISPR/Cas9 or ENU mutagenesis methods. Five of the seven lines showed evidence of genomic compensation by means of altered mRNA processing: one through a skipped exon that did not lead to a frame shift, one through nonsense-associated splicing that did not lead to a frame shift, and three through the use of cryptic splice sites. These results highlight the need for a methodical analysis of the mRNA produced in mutant lines before making conclusions or embarking on studies that assume loss of function as a result of a given genomic change. Furthermore, recognition of the types of genomic adaptations that can occur may inform the strategies of mutant generation.

Author summary

The recent rise of reverse genetic, gene targeting methods has allowed researchers to readily generate mutations in any gene of interest with relative ease. Should these mutations have the predicted effect on the mRNA and encoded protein, we would expect many more abnormal phenotypes than are typically being seen in reverse genetic screens. Here we set out to explore some of the reasons for this discrepancy by studying seven separate mutations in zebrafish. We present evidence that thorough cDNA sequence analysis is a key step in assessing the likelihood that a given mutation will produce hypomorphic or null alleles. This study reveals that alternative mRNA processing in the mutant background often produces transcripts that escape nonsense-mediated decay, thereby potentially preserving gene function. By understanding the ways that cells avoid the deleterious consequences of mutations, researchers can better design reverse genetic strategies to increase the likelihood of gene disruption.
Dual functions of Discoidin domain receptor coordinate cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors
Authors: Bernadskaya Yelena Y. , Brahmbhatt Saahil , Gline Stephanie E. , Wang Wei , Christiaen Lionel
Published: June 2017

Integrated analyses of regulated effector genes, cellular processes, and extrinsic signals are required to understand how transcriptional networks coordinate fate specification and cell behavior during embryogenesis. Migratory pairs of cardiac progenitors in the tunicateCionaprovide the simplest model of collective migration in chordate embryos. Ciona cardiopharyngeal progenitors (aka trunk ventral cells, TVCs) polarize as leader and trailer cells, and migrate between the ventral epidermis and trunk endoderm, which influences collective polarity. Using functional perturbations and quantitative analyses, we show that the TVC-specific and collagen-binding Discoidin-domain receptor (Ddr) cooperates with Integrin-β1 to promote cell-matrix adhesion to the epidermis. We found that endoderm cells secrete a collagen, Col9-a1, that is deposited in the basal epidermal matrix and activates Ddr at the ventral membrane of migrating TVCs. A functional antagonism between Ddr/Intβ1-mediated cell-matrix adhesion and Vegfr signaling appears to modulate the position of cardiopharyngeal progenitors between the endoderm and epidermis. Finally, we show that Ddr activity promotes leader-trailer-polarized BMP-Smad signaling independently of its role in cell-matrix adhesion. We propose that dual functions of Ddr act downstream of cardiopharyngeal-specific transcriptional inputs to coordinate subcellular processes underlying collective polarity and directed migration.
Distinct Solubility and Cytotoxicity Regimes of Paclitaxel-Loaded Cationic Liposomes at Low and High Drug Content Revealed by Kinetic Phase Behavior and Cancer Cell Viability Studies
Authors: Steffes Victoria M. , Murali Meena M. , Park Yoonsang , Fletcher Bretton J. , Ewert Kai K. , Safinya Cyrus R.
Published: June 2017

Lipid-based particles are used worldwide in clinical trials as carriers of hydrophobic paclitaxel (PTXL) for cancer chemotherapy, albeit with little improvement over the standard-of-care. Improving efficacy requires an understanding of intramembrane interactions between PTXL and lipids to enhance PTXL solubilization and suppress PTXL phase separation into crystals. We studied the solubility of PTXL in cationic liposomes (CLs) composed of positively charged 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP) and neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) as a function of PTXL membrane content and its relation to efficacy. Time-dependent kinetic phase diagrams were generated from observations of PTXL crystal formation by differential-interference-contrast microscopy. Furthermore, a new Synchrotron small-angle x-ray scattering in situ methodology applied to DOTAP/DOPC/PTXL membranes condensed with DNA enabled us to detect the time-dependent depletion of PTXL from membranes by measurements of variations in the membrane interlayer and DNA interaxial spacings. Our results revealed three regimes with distinct time scales for PTXL membrane solubility: hours for > 3 mol% PTXL (low), days for ≈ 3 mol% PTXL (moderate), and ≥ 20 days for < 3 mol% PTXL (long-term). Cell viability experiments on human cancer cell lines using CLPTXLnanoparticles (NPs) in the distinct CLPTXLsolubility regimes reveal an unexpected nonmonotonic dependence of efficacy on PTXL content in NPs delivered at short time scales (hours) after liposome hydration, where we see two distinct high-efficacy regimes at low (< 2 mol%) and high (9 mol%) drug loading. These newly identified high-efficacy regimes flank the membrane solubility limit (≈ 3 mol%, where efficacy declines), which has been the focus of most previous physicochemical studies (and clinical trials) of PTXL-loaded CLs. At longer times scales (days), CLPTXLNPs with ≥ 3 mol% PTXL lose efficacy while formulations with 1–2 mol% PTXL maintain high efficacy. Our findings underscore the importance of understanding the relationship of the kinetic phase behavior and physicochemical properties of CLPTXLNPs to efficacy.
The impact of a novel transendometrial approach for caesarean myomectomy on obstetric outcomes of subsequent pregnancy: a longitudinal panel study
Authors: Huang SY , Shaw SW , Su SY , Li WF , Peng HH , Cheng PJ
Published: June 2017

Objective

To evaluate the obstetric and surgical outcomes of a novel transendometrial approach for myomectomy during caesarean section in subsequent pregnancies.

Design

Longitudinal panel study.

Setting

Chang Gung Memorial Hospital, Taiwan, with approximately 5000 births per annum.

Population

Pregnant women complicated with uterine myoma.

Method

Sixty‐three pregnant women who received transendometrial myomectomy during the first caesarean delivery reported a subsequent live pregnancy and planned an elective repeat caesarean delivery.

Main outcome measures

Obstetric outcomes consisted of gestational age at birth, newborn weight, Apgar score, birthweight adequacy, uterine rupture, placental abruption, placenta praevia, placenta accreta, spontaneous preterm birth and preterm premature rupture of membranes. Surgical outcomes consisted of surgical time, blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score.

Result

The mean gestational age at birth and newborn weight at the subsequent caesarean section were superior to those at the first caesarean delivery. Spontaneous preterm birth, small‐for‐gestational‐age infants and preterm premature rupture of membranes occurred more often in the first pregnancy than in the subsequent pregnancy. The mean surgical time was shorter for the subsequent caesarean delivery than for the first caesarean delivery combined with myomectomy. The other surgical composite outcomes of blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score were similar across the two stages of caesarean deliveries.

Conclusion

The novel transendometrial approach for caesarean myomectomy may improve the obstetric outcomes of subsequent pregnancy without causing any additional immediate and long‐term adverse surgical outcomes.

Tweetable abstract

Transendometrial caesarean myomectomy may improve future obstetric outcomes.
Risk factors for severe respiratory depression from prescription opioid overdose
Authors: Fox Lindsay M. , Hoffman Robert S. , Vlahov David , Manini Alex F.
Published: June 2017

Background and aims

Prescription opioid overdose is a leading cause of injury‐related morbidity and mortality in the United States. We aimed to identify characteristics associated with clinical severity in emergency department patients with prescription opioid overdose.

Design

This was a secondary data analysis of adult prescription opioid overdoses from a large prospective cohort of acute overdoses. We examined elements of a typical emergency department evaluation using a multivariable model to determine which characteristics were associated with clinical severity, specifically severe respiratory depression (SRD).

Setting

This study was conducted at two urban academic emergency departments in New York City, USA.

Participants

Adult patients who presented with acute prescription opioid overdose between 2009 and 2013 were included in the current study. We analyzed 307 patients (mean age = 44.7, 42% female, 2.0% mortality).

Measurements

Patient demographics, reported substances ingested, suspected intent for ingesting the substance, vital signs, laboratory data, treatments including antidotes and intubation and outcome of death were recorded by trained research assistants. Intent was categorized into four mutually exclusive categories: suicide, misuse, therapeutic error and undetermined. The primary outcome was SRD, defined as administration of either (a) naloxone or (b) endotracheal intubation (ETI).

Findings

A total of 109 patients suffered SRD with 90 patients receiving naloxone alone, nine ETI alone and 10 both naloxone and ETI. The most common opioids were oxycodone (n = 124) and methadone (n = 116). Mean age was higher in patients with SRD (51.1 versus 41.1,P < 0.001). Opioid misuse was associated with SRD in the multivariable analysis [odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.21–3.55]. The unadjusted relative risk of SRD was high for fentanyl (83.3% SRD) and lowest for codeine (3.6% SRD).

Conclusion

In emergency department patients in the United States with prescription opioid overdose, worse clinical severity was associated with opioid misuse, increased with age and was widely variable, depending on the specific opioid medication involved.
PIN, Adjusted PIN, and PSOS: Difference of Opinion in the Korean Stock Market
Authors: Eom Kyong Shik , Kang Jangkoo , Kwon Kyung Yoon
Published: June 2017

Duarte and Young (2009) decompose the probability of information‐based trading PIN into adjusted PIN (AdjPIN) and probability of trading caused by symmetric order flow shocks (PSOS). We explore sources of PSOS in the Korean stock market and examine the relation between PSOS and stock returns. Using transaction data with trader types and initiator information, we find that AdjPIN is not priced, while PSOS is negatively priced, a finding that Lai et al. (2014) label “puzzling.” We find that the negative price of PSOS comes from differences of opinion among domestic individual investors on the significance of public news.
Pathways to arithmetic fact retrieval and percentage calculation in adolescents
Authors: Träff Ulf , Skagerlund Kenny , Olsson Linda , Östergren Rickard
Published: June 2017

Background

Developing sufficient mathematical skills is a prerequisite to function adequately in society today. Given this, an important task is to increase our understanding regarding the cognitive mechanisms underlying young people's acquisition of early number skills and formal mathematical knowledge.

Aims

The purpose was to examine whether the pathways to mathematics model provides a valid account of the cognitive mechanisms underlying symbolic‐number processing and mathematics in adolescents. The pathways model states that the three pathways should provide independent support to symbolic‐number skill. Each pathway's unique contribution to formal mathematics varies depending on the complexity and demand of the tasks.

Sample

The study used a sample of 114 adolescents (71 girls). Their mean age was 14.60 years (SD = 1.00).

Methods

The adolescents were assessed on tests tapping the three pathways and general cognitive abilities (e.g., working memory). A structural equation path analysis was computed.

Results

Symbolic‐number comparison was predicted by the linguistic pathway, the quantitative pathway, and processing speed. The linguistic pathway, quantitative pathways, and symbolic‐number comparison predicted arithmetic fact retrieval. The linguistic pathway, working memory, visual analogies, and symbolic‐number comparison predicted percentage calculation.

Conclusions

There are both similarities and differences in the cognitive mechanisms underlying arithmetic fact retrieval and percentage calculation in adolescents. Adolescents’ symbolic‐number processing, arithmetic fact retrieval, and percentage calculation continue to rely on the linguistic pathways, whereas the reliance upon the spatial pathway has ceased. The reliance upon the quantitative pathway varies depending on the task.
Does Guaranteed employment promote resilience to climate change? The case of India's Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA)
Authors: Godfrey‐Wood Rachel , Flower Benjamin C. R.
Published: June 2017

India's Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) is the largest labour guarantee scheme in the world, offering 100 days of paid labour to every rural household. This article reviews the growing evidence base, assessing the extent to which the scheme can be said to contribute to resilience to climate change, based on its effectiveness as a safety net and driver of household accumulation, its ability to create assets which build collective resilience, and its support for transformations of exploitative social relations. The article concludes that the MGNREGA has already made a major contribution to resilience, but requires improvements in governance and state capacity to maximize its contribution.
The impact of media on behaviour: Evidence from television coverage expansion and declining fertility in Indonesia
Authors: Dewi Rika Kumala , Suryadarma Daniel , Suryahadi Asep
Published: June 2017

The media is increasingly recognized as playing an important role in affecting the behaviour of individuals. In this article, we examine the effect of an expansion of private television broadcast on fertility in Indonesia. Our district fixed effects estimation results show that increasing the share of population with access to private television by one‐standard deviation—from a 78% coverage to a universal coverage—reduces crude birth rate by 6.2%, equivalent to 190,000 fewer births. We find evidence that television causes an increase in the use of modern contraceptives, but no change in the use of traditional contraceptives. The finding that expanding television coverage increases the demand for modern contraceptives shows that policy‐makers need to ensure that modern contraceptive is easily accessible.
Prognostic relevance of oxidative stress measurement in chronic lymphocytic leukaemia
Authors: D'Arena Giovanni , Vitale Candida , Perbellini Omar , Coscia Marta , La Rocca Francesco , Ruggieri Vitalba , Visco Carlo , Di Minno Nicola Matteo Dario , Innocenti Idanna , Pizza Vincenzo , Deaglio Silvia , Di Minno Giovanni , Giudice Aldo , Calapai Gioacchino , Musto Pellegrino , Laurenti Luca , Iorio Eugenio Luigi
Published: June 2017

Objective

To evaluate the prognostic significance of oxidative stress (OS) and antioxidant defence status measurement in patients with chronic lymphocytic leukaemia (CLL).

Methods

d‐ROMs test and BAP test were evaluated at diagnosis of 165 patients with CLL and correlated with clinical‐biological features and prognosis.

Results

An increased oxidative damage (d‐ROMs test) and a reduced antioxidant potential (BAP test) were found in CLL patients than normal controls (P<.0001). CLL patients with higher d‐ROMs values had higher number of circulating white blood cells and lymphocytes, and higher values of β2‐microglobulin. Higher d‐ROMs values were found in female (P=.0003), in patients with unmutated IgVH (P=.04), unfavourable cytogenetics (P=.002) and more advanced clinical stage (P=.002). Higher BAP test values were found in patients expressing CD49d (P=.01) and with more advanced clinical stage (P=.004). At a median follow‐up of 48 months, CLL patients with d‐ROMs ≥418 CARR U were found to have a shorter time to first treatment (TFT) (P=.0002), and a reduced survival (P=.006) than others. CLL patients with BAP test values ≥2155 μmol/L had a shorter TFT (P=.008) and a shorter survival (P=.003).

Conclusions

OS can affect CLL patients by concomitantly increasing reactive oxygen metabolites production and decreasing antioxidant defences.
Retrospective analysis of distal limb conformation and lameness in mature horses after desmotomy of the accessory ligament of the deep digital flexor tendon for management of a flexural deformity
Authors: Tracey A. , McClure S. R.
Published: June 2017

Mature horses that present with flexural deformity of the distal interphalangeal joint and lameness isolated to the foot may obtain long‐term benefits from desmotomy of the accessory ligament of the deep digital flexor tendon (ALDDFT). This retrospective analysis of medical records and radiographs included 13 horses, aged ≥2 years, presented for lameness isolated to the hoof region and diagnosed with flexural deformity of the distal interphalangeal joint. Radiographic angles of the hoof and distal interphalangeal joint and lameness scores were compared before and after desmotomy of the ALDDFT. Follow‐up data including the ability to perform the intended use were obtained at least one year after surgery. There was improvement in the angle between the dorsal aspect of the third phalanx and the weightbearing surface of the hoof, improved alignment between the dorsal hoof wall and dorsal aspect of the third phalanx, and improved alignment of the distal interphalangeal joint. Lameness was decreased in 9/13 horses and 10/13 horses were performing at their level of intended use. Evidence of improved hoof conformation and lameness following desmotomy of the ALDDFT in lame horses with flexural deformity of the distal interphalangeal joint would indicate this procedure should be considered in mature horses.
Notalgia paresthetica: factors associated with its perceived severity, duration, side, and localization
Authors: Pagliarello Calogero , Fabrizi Giuseppe , De Felici Beatrice , Casanova Dahiana , Feliciani Claudio , Di Nuzzo Sergio
Published: June 2017

Background

Notalgia paresthetica (NP) is a disorder characterized by pruritus localized to the patient's back. Little is known about predictors of severity, duration, side, and localization.

Objective

To identify factors associated with perceived severity, duration, side, and localization of NP.

Methods

In a cross‐sectional study, disease severity, duration, side, and localization were compared among the considered variables. Multivariate analysis was used to assess each variable contribution in predicting disease severity and its duration.

Results

Sixty‐five patients were recruited. Disease involved more female than male patients (Female/Male: 1.6) and after adjusting for all potential confounders, it was perceived as more severe in females (OR = 7.3, 95% CI = 2–26.3, P < 0.01). NP was reported more frequently on the right side among patients sleeping on the left side and conversely (P < 0.05). A higher disease duration was significantly linked to a higher body mass index (OR = 4.8, 95% CI = 1.3–17.1, P < 0.05).

Conclusion

Our study linked female gender to worse disease severity, a higher body mass index to longer disease duration, and prevailing sleep position to NP side expression. The sleeping position should be considered a possible target for treating the disease.