bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of social contact surveys to inform transmission models of close contact infections
Authors: Hoang Thang Van , Coletti Pietro , Melegaro Alessia , Wallinga Jacco , Grijalva Carlos , Edmunds W. John , Beutels Philippe , Hens Niel
Published: April 2018

Social contact data are increasingly being used to inform models for infectious disease spread with the aim of guiding effective policies on disease prevention and control. In this paper, we undertake a systematic review of the study design, statistical analyses and outcomes of the many social contact surveys that have been published. Our primary focus is to identify the designs that have worked best and the most important determinants and to highlight the most robust ﬁndings.

Two publicly accessible online databases were systematically searched for articles regarding social contact surveys. PRISMA guidelines were followed as closely as possible. In total, 64 social contact surveys were identiﬁed. These surveys were conducted in 24 countries, and more than 80% of the surveys were conducted in high-income countries. Study settings included general population (58%), schools/universities (37%) and health care/conference/research institutes (5%). The majority of studies did not focus on a speciﬁc age group (38%), whereas others focused on adults (32%) or children (19%). Retrospective and prospective designs were used mostly (45% and 41% of the surveys, respectively) with 6% using both for comparison purposes. The deﬁnition of a contact varied among surveys, e.g. a non-physical contact may require conversation, close proximity or both. Age, time schedule (e.g., weekday/weekend) and household size were identiﬁed as relevant determinants for contact pattern across a large number of studies. The surveys present a wide range of study designs. Throughout, we found that the overall contact patterns were remarkably robust for the study details. By considering the most common approach in each aspect of design (e.g., sampling schemes, data collection, deﬁnition of contact), we could identify a common practice approach that can be used to facilitate comparison between studies and for benchmarking future studies.
Natural selection on gene-specific codon usage bias is common across eukaryotes
Authors: Peng Zhen , Zaher Hani , Ben-Shahar Yehuda
Published: April 2018

Although the actual molecular evolutionary forces that shape differences in codon usage across species remain poorly understood, majority of synonymous mutations are assumed to be functionally neutral because they do not affect protein sequences. However, empirical studies suggest that some synonymous mutations can have phenotypic consequences. Here we show that in contrast to the current dogma, natural selection on gene-specific codon usage bias is common across Eukaryota. Furthermore, by using bioinformatic and experimental approaches, we demonstrate that specific combinations of rare codons contribute to the spatial and sex-related regulation of some protein-coding genes inDrosophila melanogaster.Together, these data indicate that natural selection can shape gene-specific codon usage bias, which therefore, represents an overlooked genomic feature that is likely to play an important role in the spatial and temporal regulation of gene functions. Hence, the broadly accepted dogma that synonymous mutations are in general functionally neutral should be reconsidered.
The organization of intracortical connections by layer and cell class in the mouse brain
Authors: Harris Julie A. , Mihalas Stefan , Hirokawa Karla E. , Whitesell Jennifer D. , Knox Joseph E. , Bernard Amy , Bohn Phillip , Caldejon Shiella , Casal Linzy , Cho Andrew , Feng David , Gaudreault Nathalie , Gerfen Charles R. , Graddis Nile , Groblewski Peter A. , Henry Alex , Ho Anh , Howard Robert , Kuan Leonard , Lecoq Jerome , Luviano Jennifer , McConoghy Stephen , Mortrud Marty T. , Naeemi Maitham , Ng Lydia , Oh Seung W. , Ouellette Benjamin , Sorensen Staci A. , Wakeman Wayne , Wang Quanxin , Williford Ali , Phillips John W. , Jones Allan , Koch Christof , Zeng Hongkui
Published: April 2018

The mammalian cortex is a laminar structure composed of many cell types densely interconnected in complex ways. Recent systematic efforts to map the mouse mesoscale connectome provide comprehensive projection data on interareal connections, but not at the level of specific cell classes or layers within cortical areas. We present here a significant expansion of the Allen Mouse Brain Connectivity Atlas, with ∼1,000 new axonal projection mapping experiments across nearly all isocortical areas in 49 Cre driver lines. Using 13 lines selective for cortical layer-specific projection neuron classes, we identify the differential contribution of each layer/class to the overall intracortical connectivity patterns. We find layer 5 (L5) projection neurons account for essentially all intracortical outputs. L2/3, L4, and L6 neurons contact a subset of the L5 cortical targets. We also describe the most common axon lamination patterns in cortical targets. Most patterns are consistent with previous anatomical rules used to determine hierarchical position between cortical areas (feedforward, feedback), with notable exceptions. While diverse target lamination patterns arise from every source layer/class, L2/3 and L4 neurons are primarily associated with feedforward type projection patterns and L6 with feedback. L5 has both feedforward and feedback projection patterns. Finally, network analyses revealed a modular organization of the intracortical connectome. By labeling interareal and intermodule connections as feedforward or feedback, we present an integrated view of the intracortical connectome as a hierarchical network.
Manipulation of the unfolded protein response: a pharmacological strategy against coronavirus infection
Authors: Echavarría-Consuegra Liliana , Cook Georgia M. , Busnadiego Idoia , Lefèvre Charlotte , Keep Sarah , Brown Katherine , Doyle Nicole , Dowgier Giulia , Franaszek Krzysztof , Moore Nathan A. , Siddell Stuart G. , Bickerton Erica , Hale Benjamin G. , Firth Andrew E. , Brierley Ian , Irigoyen Nerea
Published: April 2018

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release ∼1,000-fold. Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.

Author Summary

SARS-CoV-2 is the novel coronavirus responsible for the COVID-19 pandemic which has resulted in over 100 million cases since the end of 2019. Most people infected with the virus will experience mild to moderate respiratory illness and recover without any special treatment. However, older people, and those with underlying medical problems like chronic respiratory disease are more likely to develop a serious illness. So far, more than 2 million people have died of COVID-19. Unfortunately, there is no specific medication for this viral disease.

In order to produce viral proteins and to replicate their genetic information, all coronaviruses use a cellular structure known as the endoplasmic reticulum or ER. However, the massive production and modification of viral proteins stresses the ER and this activates a compensatory cellular response that tries to reduce ER protein levels. This is termed the unfolded protein response or UPR. We believe that coronaviruses take advantage of the activation of the UPR to enhance their replication.

The UPR is also activated in some types of cancer and neurodegenerative disorders and UPR inhibitor drugs have been developed to tackle these diseases. In this work, we have tested some of these compounds in human lung cells infected with SARS-CoV-2 and found that virus production was reduced 1000-fold in human lung cells.
Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells
Authors: Miraldi Emily R. , Pokrovskii Maria , Watters Aaron , Castro Dayanne M. , Veaux Nicholas De , Hall Jason A. , Lee June-Yong , Ciofani Maria , Madar Aviv , Carriero Nick , Littman Dan R. , Bonneau Richard
Published: April 2018

Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to influence gene expression modeling. We rigorously test our methods in the context of T Helper Cell Type 17 (Th17) differentiation, generating new ATAC-seq data to complement existing Th17 genomic resources (plentiful gene expression data, TF knock-outs and ChIP-seq experiments). In this resource-rich mammalian setting, our extensive benchmarking provides quantitative, genome-scale evaluation of TRN inference combining ATAC-seq and RNA-seq data. We refine and extend our previous Th17 TRN, using our new TRN inference methods to integrate all Th17 data (gene expression, ATAC-seq, TF KO, ChIP-seq). We highlight newly discovered roles for individual TFs and groups of TFs (“TF-TF modules”) in Th17 gene regulation. Given the popularity of ATAC-seq, which provides high-resolution with low sample input requirements, we anticipate that application of our methods will improve TRN inference in new mammalian systems, especially in vivo, for cells directly from humans and animal models.
CD56 expression of intravascular trophoblasts defines a class of vasculopathy in preeclampsia and other pregnancy complications
Authors: Zhang Peilin
Published: April 2018

We have discovered the expression of CD56 on the intravascular trophoblasts in the maternal spiral artery at implantation sites, and we have also found the similar phenotypic switch of intravascular trophoblasts in the decidual vasculopathy in preeclampsia. Currently we have examined 124 placentas from the patients with preeclampsia and 84 placentas from patients with other pregnancy associated complications without preeclampsia. CD56 expression on the intravascular trophoblasts can be seen in classic decidual vasculopathy such as fibrinoid medial necrosis and acute atherosis. In addition, partial involvement of the decidual vessels with classic vasculopathy can also be identified by CD56 expression. The cellular components of the classic vasculopathy in preeclampsia showed immunoreactivity to cytokeratin and CD68, in addition to CD56 expression, indicating the fetal trophoblastic cell origin. The classic decidual vasculopathy including acute atherosis and fibrinoid medial necrosis can be unified and designated as CD56-related vasculopathy. The CD56 related vasculopathy is associated not only to preeclampsia but also to other pregnancy related complications, such as gestational diabetes, placental infarcts, intervillous thrombosis and other fetal distress syndromes. Our study defined a spectrum of decidual vasculopathy spanning from the classic preeclampsia to other complications important to pregnancy that can be highlighted by CD56 expression, pointing to different direction of pathogenesis of preeclampsia and other pregnancy associated complications.
NRG1-mediated recognition of HopQ1 reveals a link between PAMP- and Effector-triggered Immunity
Authors: Brendolise Cyril , Martinez-Sanchez Marcela , Morel Arry , Chen Ronan , Dinis Romain , Deroles Simon , Peeters Nemo , Rikkerink Erik H. A. , Montefiori Mirco
Published: April 2018

Members of the hopQ1/XopQ family of effectors are conserved amongst pathogenic bacteria suggesting an important function in virulence. Therefore, the identification of R proteins recognising members of this family is potentially of high value to achieve broad-spectrum resistance in crops.

Recent studies demonstrated that HopQ1/XopQ recognition is EDS1-dependant and is mediated by the TIR-NB-LRR protein Roq1. Using our recently described R gene RNAi library, we have investigated the mechanism of HopQ1 recognition and the other components of its signalling network.

We show that silencing of the CCR-NB-LRR helper protein N Requirement Gene 1 (NRG1) prevents HopQ1 recognition in N. benthamiana and that NRG1 expression confers recognition of HopQ1 and restricts Pto DC3000 proliferation in the otherwise susceptible host Arabidopsis. Moreover NRG1 expression is briefly but strongly induced at a very early stage of the plant innate response, establishing a strong dependency link between PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI).

Overall we demonstrate that in addition to Roq1, HopQ1 recognition in N. benthamiana requires the CCR-NB-LRR protein NRG1 and propose a model based on the dual requirement of a CCR-NB-LRR and a TIR-NB-LRR that could extend beyond HopQ1 detection and possibly be used to recognize other pathogen effectors.
Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells induces dedifferentiated liposarcoma potency
Authors: Kim Yu Jin , Sung Minjung , Yu Dan Bi , Kim Mingi , Song Ji-Young , Song Kyoung , Jung Kyungsoo , Choi Yoon-La
Published: April 2018

Amplification and overexpression of MDM2 and CDK4 are well-known diagnostic criteria of well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). Although it was reported that depletion of MDM2 or CDK4 decreased proliferation in DDLPS cell lines, it remains unclear whether MDM2 and CDK4 induce WDLPS/DDLPS tumorigenesis. We examined whether MDM2 and/or CDK4 produce WDLPS/DDLPS using transformed human bone marrow stem cells (BMSCs), 2H and 5H, with five oncogenic hits (overexpression of hTERT, TP53 degradation, RB inactivation, c-MYC stabilization, and overexpression of HRASv12). In vitro functional experiments revealed that co-overexpression of MDM2 and CDK4 plays key roles in tumorigenesis by increasing cell growth and migration and inhibiting adipogenic differentiation potency compared to sole expression of MDM2 or CDK4. Using mouse xenograft models, we found that co-overexpression of MDM2 and CDK4 in 5H cells with five additional oncogenic mutations can develop proliferative DDLPS in vivo. Our results suggest that co-overexpression of MDM2 and CDK4 induces DDLPS tumour potency in transformed human BMSCs by accelerating cell growth and migration and blocking adipogenetic potential incooperation with multiple genetic factors.
Chronic exposure to a neonicotinoid pesticide and a synthetic pyrethroid in full-sized honey bee colonies
Authors: Odemer Richard , Rosenkranz Peter
Published: April 2018

In the last decade, the use of neonicotinoid insecticides increased significantly in the agricultural landscape and meanwhile considered a risk to honey bees. Besides the exposure to pesticides, colonies are treated frequently with various acaricides that beekeepers are forced to use against the parasitic mite Varroa destructor. Here we have analyzed the impact of a chronic exposure to sublethal concentrations of the common neonicotinoid thiacloprid (T) and the widely used acaricide τ-fluvalinate (synthetic pyrethroid, F) - applied alone or in combination - to honey bee colonies under field conditions. The population dynamics of bees and brood were assessed in all colonies according to the Liebefeld method. Four groups (T, F, F+T, control) with 8-9 colonies each were analyzed in two independent replications, each lasting from spring/summer until spring of the consecutive year. In late autumn, all colonies were treated with oxalic acid against Varroosis. We could not find a negative impact of the chronic neonicotinoid exposure on the population dynamics or overwintering success of the colonies, irrespective of whether applied alone or in combination with τ-fluvalinate. This is in contrast to some results obtained from individually treated bees under laboratory conditions and confirms again an effective buffering capacity of the honey bee colony as a superorganism. Yet, the underlying mechanisms for this social resilience remain to be fully understood.
Native DNA electronics: the Nuclear Aggregates of Polyamines possible role
Authors: D’Agostino L.
Published: April 2018

The genomic DNA is enveloped by nanotubes formed by the Nuclear Aggregates of Polyamines (NAPs) that induce DNA conformational changes, and provides protection and increased interactive abilities for the double strands. In a physiologic environment, the nanotube arrangement initiates with the spontaneous interaction among the terminal amino groups of polyamines and the phosphate ions, with the consequent formation of cyclic monomers that hook at DNA grooves. The polymer thus formed has the morphological features of an organic semiconductor and, therefore, can be considered able to conduce electric charges. Phosphate ions positioned on NAP external surface could regulate, as in a physical electric circuit, both protein linear and rotational (histones) motion, in accordance with the basilar principles of the electronics. A model of a carrier system for proteins motion along the polymer wrapping the DNA strands, based on the phosphate-phosphate complexation, is proposed.
Toward a model-free feedback control synthesis for treating acute inflammation
Authors: Bara Ouassim , Fliess Michel , Join Cédric , Day Judy , Djouadi Seddik M.
Published: April 2018

An effective and patient-specific feedback control synthesis for inflammation resolution is still an ongoing research area. A strategy consisting of manipulating a pro and anti-inflammatory mediator is considered here as used in some promising model-based control studies. These earlier studies, unfortunately, suffer from the difficultly of calibration due to the heterogeneity of individual patient responses even under similar initial conditions. We exploit a new model-free control approach and its corresponding “intelligent” controllers for this biomedical problem. A crucial feature of the proposed control problem is as follows: the two most important outputs which must be driven to their respective desired states are sensorless. This difficulty is overcome by assigning suitable reference trajectories to the other two outputs that do have sensors. A mathematical model, via a system of ordinary differential equations, is nevertheless employed as a “virtual” patient forin silicotesting. We display several simulation results with respect to the most varied situations, which highlight the effectiveness of our viewpoint.
Visualizing conformational dynamics of proteins in solution and at the cell membrane
Authors: Gordon Sharona E. , Munari Mika , Zagotta William N.
Published: April 2018

Conformational dynamics underlie enzyme function, yet are generally inaccessible via traditional structural approaches. FRET has the potential to measure conformational dynamicsin vitroand in intact cells, but technical barriers have thus far limited its accuracy, particularly in membrane proteins. Here, we combine amber codon suppression to introduce a donor fluorescent noncanonical amino acid with a new, biocompatible approach for labeling proteins with acceptor transition metals in a method called ACCuRET (Anap Cyclen-Cu2+resonance energy transfer). We show that ACCuRET measures absolute distances and distance changes with high precision and accuracy using maltose binding protein as a benchmark. Using cell unroofing, we show that ACCuRET can accurately measure rearrangements of proteins in native membranes. Finally, we implement a computational method for correcting the measured distances for the distance distributions observed in proteins. ACCuRET thus provides a flexible, powerful method for measuring conformational dynamics in both soluble proteins and membrane proteins.
GET_PHYLOMARKERS, a software package to select optimal orthologous clusters for phylogenomics and inferring pan-genome phylogenies, used for a critical geno-taxonomic revision of the genusStenotrophomonas
Authors: Vinuesa Pablo , Ochoa-Sánchez Luz Edith , Contreras-Moreira Bruno
Published: April 2018

The massive accumulation of genome-sequences in public databases promoted the proliferation of genome-level phylogenetic analyses in many areas of biological research. However, due to diverse evolutionary and genetic processes, many loci have undesirable properties for phylogenetic reconstruction. These, if undetected, can result in erroneous or biased estimates, particularly when estimating species trees from concatenated datasets. To deal with these problems, we developed GET_PHYLOMARKERS, a pipeline designed to identify high-quality markers to estimate robust genome phylogenies from the orthologous clusters, or the pan-genome matrix (PGM), computed by GET_HOMOLOGUES. In the first context, a set of sequential filters are applied to exclude recombinant alignments and those producing anomalous or poorly resolved trees. Multiple sequence alignments and maximum likelihood (ML) phylogenies are computed in parallel on multi-core computers. A ML species tree is estimated from the concatenated set of top-ranking alignments at the DNA or protein levels, using either FastTree or IQ-TREE (IQT). The latter is used by default due to its superior performance revealed in an extensive benchmark analysis. In addition, parsimony and ML phylogenies can be estimated from the PGM.

We demonstrate the practical utility of the software by analyzing 170Stenotrophomonasgenome sequences available in RefSeq and 10 new complete genomes of environmentalS. maltophiliacomplex (Smc) isolates reported herein. A combination of core-genome and PGM analyses was used to revise the molecular systematics of the genus. An unsupervised learning approach that uses a goodness of clustering statistic identified 20 groups within the Smc at a core-genome average nucleotide identity of 95.9% that are perfectly consistent with strongly supported clades on the core- and pan-genome trees. In addition, we identified 14 misclassified RefSeq genome sequences, 12 of them labeled asS. maltophilia, demonstrating the broad utility of the software for phylogenomics and geno-taxonomic studies. The code, a detailed manual and tutorials are freely available for Linux/UNIX servers under the GNU GPLv3 license athttps://github.com/vinuesa/get_phylomarkers. A docker image bundling GET_PHYLOMARKERS with GET_HOMOLOGUES is available athttps://hub.docker.com/r/csicunam/get_homologues/, which can be easily run on any platform.
CagY-dependent regulation of type IV secretion inHelicobacter pyloriis associated with alterations in integrin binding
Authors: Skoog Emma C. , Morikis Vasilios A. , Martin Miriam E. , Foster Greg A. , Cai Lucy P. , Hansen Lori M. , Li Beibei , Gaddy Jennifer A. , Simon Scott I. , Solnick Jay V.
Published: April 2018

Strains ofHelicobacter pylorithat cause ulcer or gastric cancer typically express a type IV secretion system (T4SS) encoded by thecagpathogenicity island (PAI). CagY is an ortholog of VirB10 that, unlike other VirB10 orthologs, has a large middle repeat region (MRR) with extensive repetitive sequence motifs, which undergo CD4+ T cell-dependent recombination during infection of mice. Recombination in the CagY MRR reduces T4SS function, diminishes the host inflammatory response, and enables the bacteria to colonize at a higher density. Since CagY is known to bind human α5β1integrin, we tested the hypothesis that recombination in the CagY MRR regulates T4SS function by modulating binding to α5β1integrin. Using a cell-free microfluidic assay, we found thatH. pyloribinding to α5β1integrin under shear flow is dependent on the CagY MRR, but independent of the presence of the T4SS pili, which are only formed whenH. pyloriis in contact with host cells. Similarly, expression of CagY in the absence of other T4SS genes was necessary and sufficient for whole bacterial cell binding to α5β1integrin. Bacteria with variantcagYalleles that reduced T4SS function showed comparable reduction in binding to α5β1integrin, though CagY was still expressed on the bacterial surface. We speculate thatcagY-dependent modulation ofH. pyloriT4SS function is mediated by alterations in binding to α5β1integrin, which in turn regulates the host inflammatory response so as to maximize persistent infection.

IMPORTANCE

Infection withH. pylorican cause peptic ulcers, and is the most important risk factor for gastric cancer, the third most common cause of cancer death worldwide. The majorH. pylorivirulence factor that determines whether infection causes disease or asymptomatic colonization is the type IV secretion system (T4SS), a sort of molecular syringe that injects bacterial products into gastric epithelial cells and alters host cell physiology. We previously showed that recombination in CagY, an essential T4SS component, modulates the function of the T4SS. Here we found that these recombination events produce parallel changes in specific binding to α5β1integrin, a host cell receptor that is essential for T4SS-dependent translocation of bacterial effectors. We propose that CagY-dependent binding to α5β1integrin acts like a molecular rheostat that alters T4SS function and modulates the host immune response to promote persistent infection.
Uncertainty quantification, propagation and characterization by Bayesian analysis combined with global sensitivity analysis applied to dynamical intracellular pathway models
Authors: Eriksson Olivia , Jauhiainen Alexandra , Sasane Sara Maad , Kramer Andrei , Nair Anu G , Sartorius Carolina , Kotaleski Jeanette Hellgren
Published: April 2018

Motivation

Dynamical models describing intracellular phenomena are increasing in size and complexity as more information is obtained from experiments. These models are often over-parameterized with respect to the quantitative data used for parameter estimation, resulting in uncertainty in the individual parameter estimates as well as in the predictions made from the model. Here we combine Bayesian analysis with global sensitivity analysis in order to give better informed predictions; to point out weaker parts of the model that are important targets for further experiments, as well as give guidance on parameters that are essential in distinguishing different qualitative output behaviours.

Results

We used approximate Bayesian computation (ABC) to estimate the model parameters from experimental data, as well as to quantify the uncertainty in this estimation (inverse uncertainty quantification), resulting in a posterior distribution for the parameters. This parameter uncertainty was next propagated to a corresponding uncertainty in the predictions (forward uncertainty propagation), and a global sensitivity analysis was performed on the prediction using the posterior distribution as the possible values for the parameters. This methodology was applied on a relatively large and complex model relevant for synaptic plasticity, using experimental data from several sources. We could hereby point out those parameters that by themselves have the largest contribution to the uncertainty of the prediction as well as identify parameters important to separate between qualitatively different predictions.This approach is useful both for experimental design as well as model building.
All-in-One Adeno-associated Virus Delivery and Genome Editing by Neisseria meningitidis Cas9 in vivo
Authors: Ibraheim Raed , Song Chun-Qing , Mir Aamir , Amrani Nadia , Xue Wen , Sontheimer Erik J.
Published: April 2018

Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo genome engineering applications: SpyCas9, SauCas9 and CjeCas9. However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome. Here, we present an additional in vivo editing platform using Neisseria meningitidis Cas9 (NmeCas9). NmeCas9 is compact, edits with high accuracy, and possesses a distinct PAM, making it an excellent candidate for safe gene therapy applications. We find that NmeCas9 can be used to target the Pcsk9 and Hpd genes in mice. Using tail vein hydrodynamic-based delivery of NmeCas9 plasmid to target the Hpd gene, we successfully reprogrammed the tyrosine degradation pathway in Hereditary Tyrosinemia Type I mice. More importantly, we delivered NmeCas9 with its single-guide RNA in a single recombinant adeno-associated vector (rAAV) to target Pcsk9, resulting in lower cholesterol levels in mice. This all-in-one vector yielded >35% gene modification after two weeks of vector administration, with minimal off-target cleavage in vivo. Our findings indicate that NmeCas9 can facilitate future efforts to correct disease-causing mutations by expanding the targeting scope of RNA-guided nucleases.
Supply chain network optimization with consideration of raw material and final product substitutions driven by price and carbon emissions
Authors: Wang Chuanxu , Li Yanbing , Wang Zhengcai
Published: April 2018

Purpose

This paper aims to develop a bi-objective mixed integer non-linear programing model to optimize the supply chain networks consisting of raw material providers, final product manufacturers and distribution centers. Raw material substitution caused by varying raw material supply amounts, prices and carbon emissions and final product substitution due to different product prices and carbon emissions are considered.

Design/methodology/approach

The proposed model aims to achieve total profit maximization and total carbon emission minimization. The objective function of carbon emissions is converted into a maximization problem by changing minimum to maximum. The composite objective function is the weighted sum of the bias value of each objective function. The model is then solved using software Lingo12.

Findings

Numerical analysis results show that an increase in the number of alternate raw materials for original raw material helps improve supply chain network performance, and variation in that number causes detectable but not significant changes in downstream final product substitution results.

Originality/value

The major differences between this work and existing research are as follows: first, although previous research considered carbon emissions in supply chain network optimization, it has not considered the substitution effects of products or raw materials. This paper considers the substitution of both raw material and productions. Second, the item substitution considered by previous research is derived from inventory shortage or price difference of original items. However, the substitution considered in the present paper is a response to differences in purchase price, production cost and carbon emissions for items.
Remote chemical sensing: a review of techniques and recent developments
Authors: Bogue Robert
Published: April 2018

Purpose

This paper aims to provide technical details of the techniques used for the remote detection of chemical compounds in a number of applications and also to highlight key research themes.

Design/methodology/approach

Following a short introduction, this first considers remote gas detection using the DIAL technique. Remote gas cloud imaging is then discussed, and this is followed by a review of chemical warfare agent detection technologies. A selection of research activities and product developments aimed at remotely detecting explosives are considered and, finally, brief concluding comments are drawn.

Findings

Remote gas sensing is now a practical reality, and products are available which can remotely detect, identify, quantify and in some cases visualise a wide range of toxic and environmentally threatening gases. These satisfy numerous industrial, environmental and military applications. Remotely detecting explosives poses a significant technological challenge, and despite some commercialisation, it remains the topic of an extensive research effort, much involving LIBS and Raman techniques. Importantly, much of this work also has potential in non-military applications, with several developments being shown to detect various industrially important compounds.

Originality/value

This provides a technical insight into the techniques and products used in a range of remote chemical sensing applications.
Parents of children referred to a sleep laboratory for disordered breathing reported anxiety, daytime sleepiness and poor sleep quality
Authors: Cadart Marion , De Sanctis Livio , Khirani Sonia , Amaddeo Alessandro , Ouss Lisa , Fauroux Brigitte
Published: April 2018

Aim

We evaluated the impact that having a child with sleep‐disordered breathing had on their parents, including their own sleep quality.

Methods

Questionnaires were completed by 96 parents of 86 children referred for a sleep study or control of continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) at the sleep laboratory of the Necker Hospital, Paris, France, between October 2015 and January 2016. The questionnaires evaluated anxiety and depression, family functioning, the parents’ quality of life, daytime sleepiness and sleep quality.

Results

The children had a mean age of seven ±five years and most of the responses (79%) came from their mothers. These showed that 26% of parents showed moderate‐to‐severe anxiety, 8% moderate‐to‐severe depression, 6% complex family cohesion, 59% moderate‐to‐severe daytime sleepiness and 54% poor sleep quality. Anxiety was higher in mothers than in fathers (p < 0.001). The questionnaire scores did not differ according to the child's age, the results of the sleep studies or the CPAP or NIV treatment. The symptoms seem to be more commonly related to the child's underlying disease than their sleep‐disordered breathing.

Conclusion

The parents of children referred to a sleep laboratory reported frequent anxiety, daytime sleepiness and poor sleep quality.
Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro‐BNP performance
Authors: Berrington JE , Clarke P , Embleton ND , Ewer AK , Geethanath R , Gupta S , Lal M , Oddie S , Shafiq A , Vasudevan C , Bührer C
Published: April 2018

Aim

Urinary N‐terminal B‐type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants.

Methods

Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development.

Results

Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28).

Conclusion

The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.
Piecing Together the American Voting Puzzle: How Voters’ Personalities and Judgments of Issue Importance Mattered in the 2016 Presidential Election
Authors: Blankenship Benjamin T. , Savaş Özge , Frederick Jennifer K. , Stewart Abigail J.
Published: April 2018

In the wake of the 2016 election, which surprised pundits and voters on both the left and the right, there has been renewed interest in understanding what predicts American voters’ choices. In this article, we investigate the roles of personality and issue importance in how people voted in the 2016 U.S. election. In this longitudinal study of 403 MTurk workers who voted in the election, we assessed the relations between personality (openness, social dominance orientation, and national identity importance) and issue importance (group rights and social justice, economic rights, and individual and national rights), and voting for Clinton or Trump. Our results indicate that both individual differences and issue importance as measured in July 2016 predicted votes in November. We also found that the links between personality and voting were mediated by issue importance. Implications for political psychology and the study of personality, campaign issues, and voting behavior are discussed.
PRICE AND QUANTITY COMPETITION WITH ASYMMETRIC COSTS IN A MIXED DUOPOLY: A TECHNICAL NOTE
Authors: Choi Kangsik
Published: April 2018

We consider a mixed duopoly in which private and public firms can choose to strategically set prices or quantities when the public firm is less efficient than the private firm. Thus, even with cost asymmetry, we obtain exactly the same result (i.e., Bertrand competition) of Matsumura and Ogawa (2012) if Singh and Vives’ (1984) assumption of positive primary outputs holds. However, compared to endogenous determination of the type of contract without cost asymmetry, our main finding is that in the wider range of cost asymmetry, different type(s) of equilibrium related to or not related to the limit‐pricing strategy of the private firm can be sustained. Thus, when considering an implication on privatization, we may overestimate the welfare gain of privatization because Cournot competition takes place after privatization even though cost asymmetry exists between firms. While the result of Matsumura and Ogawa (2012) holds true if the goods are complements, we find the novel results in the case of substitutes.
Patient experience of centralized acute stroke care pathways
Authors: Perry Catherine , Papachristou Iliatha , Ramsay Angus I.G. , Boaden Ruth J. , McKevitt Christopher , Turner Simon J. , Wolfe Charles D.A. , Fulop Naomi J.
Published: April 2018

Background

In 2010, Greater Manchester (GM) and London centralized acute stroke care services into a reduced number of hyperacute stroke units, with local stroke units providing on‐going care nearer patients’ homes.

Objective

To explore the impact of centralized acute stroke care pathways on the experiences of patients.

Design

Qualitative interview study. Thematic analysis was undertaken, using deductive and inductive approaches. Final data analysis explored themes related to five chronological phases of the centralized stroke care pathway.

Setting and participants

Recruitment from 3 hospitals in GM (15 stroke patients/8 family members) and 4 in London (21 stroke patients/9 family members).

Results

Participants were impressed with emergency services and initial reception at hospital: disquiet about travelling further than a local hospital was allayed by clear explanations. Participants knew who was treating them and were involved in decisions. Difficulties for families visiting hospitals a distance from home were raised. Repatriation to local hospitals was not always timely, but no detrimental effects were reported. Discharge to the community was viewed less positively.

Discussion and conclusions

Patients on the centralized acute stroke care pathways reported many positive aspects of care: the centralization of care pathways can offer patients a good experience. Disadvantages of travelling further were perceived to be outweighed by the opportunity to receive the best quality care. This study highlights the necessity for all staff on a centralized care pathway to provide clear and accessible information to patients, in order to maximize their experience of care.
Time to abandon the loss of dispersal ability hypothesis in island plants: A comment on García‐Verdugo, Mairal, Monroy, Sajeva and Caujapé‐Castells (2017)
Authors: Burns K.C.
Published: April 2018

García‐Verdugo et al. (2017) recently tested the loss of dispersal ability hypothesis in a wind‐dispersed shrub from Southern Europe. Although the hypothesis has guided research for over 150 years, García‐Verdugo et al. (2017) results failed to substantiate its central prediction—the loss of seed dispersal potential in island populations. Here, I highlight several additional limitations of the hypothesis. First, García‐Verdugo et al. (2017) results are not unusual. Empirical support for the hypothesis is equivocal. Second, when reduced dispersal potential is documented, it may often evolve as a passive by‐product of selection for large seeds, for reasons that are wholly unrelated to their dispersal. Third, the hypothesis does not readily apply to all plant dispersal modes, particularly plants that produce fleshy fruits. These issues advocate a fresh approach to the study of how selection shapes the evolution of dispersal potential on islands.
Radiofrequency Thermocoagulation of the Ganglion Impar for Coccydynia Management: Long‐Term Effects
Authors: Kırcelli Atilla , Demirçay Emre , Özel Ömer , Çöven Ilker , Işık Semra , Civelek Erdinç , Kabataş Serdar
Published: April 2018

Objective

To investigate the short‐ and long‐term effects of ganglion impar radiofrequency thermocoagulation (RFT) treatment in patients with chronic coccydynia.

Methods

We retrospectively analyzed the medical records of patients who underwent RFT of the ganglion impar between 2009 and 2011. Pain intensity visual numeric scale (VNS) scores and Euroqol 5D (EQ‐5D) index scores were recorded pre‐intervention and post‐intervention at the first, sixth, and twelfth months. The differences between pre‐procedural VNS scores and post‐procedural VNS scores at the first, sixth, and twelfth months were evaluated. The success of the intervention was recorded as the percentage difference between the pre‐intervention VNS scores and post‐intervention VNS scores at the first, sixth, and twelfth months.

Results

The mean age of the patients, including 11 females (55%) and 8 males (45%), was 48.7 ± 14.3 years. The average follow‐up duration was 17.3 ± 2.9 months. Statistically significant differences were observed between the pre‐ and post‐procedure VNS scores (P < 0.0001). Improvements in VNS scores were correlated with improvements in EQ‐5D index scores. Mid‐term (sixth month) and long‐term (twelfth month) evaluations after the intervention revealed that 67.4% and 61.1% of the patients had successful outcomes, respectively.

Conclusion

Our data suggested that RFT of the ganglion impar in patients with chronic coccydynia resulted in effective outcomes, and patients who responded to RFT had significantly lower post‐RFT pain scores.
Social goals moderate the associations between peer status and behavior in middle school
Authors: Mayeux Lara , Kraft Caroline
Published: April 2018

This study investigated the associations among popularity, agentic and communal social goals, and overt and relational aggression in adolescence, with a focus on social goals as moderators of the association between aggression and popularity. Three hundred eighteen sixth‐, seventh‐, and eighth‐grade students completed a sociometric assessment of overt and relational aggression, prosocial behavior, and popularity, and the Interpersonal Goals Inventory for Children (IGI‐C; Ojanen, Grönroos, & Salmivalli, Developmental Psychology, 41(5), 699–710, 2005). Endorsing agentic goals moderated the association between popularity and both overt aggression and prosocial behavior. Adolescents who were both popular and who endorsed agentic goals were particularly high in overt aggression and prosocial behavior. Communal goals also moderated the popularity‐aggression link, but in different ways depending on the type of aggression being analyzed. We also found evidence that, among adolescents who endorse both types of goals, agentic goals may overshadow communal values. Some of these interactions were further qualified by gender.
The Examination of the Possible Relationship Between Reality Shock Expectations and Teacher Self-Efficacy Levels of the Prospective Teachers Attending Pedagogical Formation Certificate Program
Authors: Sezen-Gultekin Gozde , Nartgun Senay Sezgin
Published: April 2018

The aim of this study is to determine the possible relationship between the reality shock expectations and teacher self-efficacy levels of the prospective teachers attending pedagogical formation certificate program. In accordance with this purpose, the study was designed in correlational model among relational survey models, and the study sample was composed of 293 prospective teachers who were attending the Pedagogical Formation Certificate Program in 2016-2017 academic year by selected through convenience sampling. According to the analysis of the obtained data from this sample, it was seen that the prospective teachers’ reality shock expectation levels were generally higher in the possible problems with professional differences, while the teacher self-efficacy levels were lower in the situations regarding individual differences. On the other hand, it was observed that the reality shock expectations and teacher self-efficacy levels did not show difference according to gender, education level and graduated field variables, while only the teacher self-efficacy towards teaching strategies sub-dimension had a difference in terms of education level variable. This difference was in favor of teacher candidates receiving postgraduate training. When the main prupose of the study was examined, it was determined that there was no statistically significant relationship between the teacher's self-efficacy and reality shock expectations of the prospective teachers attending to the pedagogical formation certificate program.
The Examination of the Social Integration Perceptions of Undergraduate Students
Authors: Özgan Habib , Akşab Şahabettin
Published: April 2018

This study was aimed to determine the social integration perceptions of undergraduate students and to examine them in terms of certain variables. It was a descriptive study with survey methodology. The data were obtained using the Social Integration Scale. The study group consisted of 545 undergraduate students during the fall semester of 2016-2017 academic year. The research sample was determined using probability-based sampling techniques. SPSS 20.0 software package was used in data analysis. Mann Whitney U and Kruskal Wallis H-Tests were conducted to research data. According to the research results, it was revealed that undergraduate students had higher social integration perceptions in general. The research findings indicated that undergraduate students’ perceptions of integration with the social environment differ significantly according to their departments, ages and income; their local integration perceptions according to the geographical region they reside and the occupation of mother; their educational integration perceptions according to their departments, ages and income; their normative-moral integration perceptions according to their departments and the educational degrees of parents.