bluuebunny/crossref_metadata_2025 huggingface dataset:
The individual functional connectome is unique and stable over months to years
Authors: Horien Corey , Shen Xilin , Scheinost Dustin , Constable R. Todd
Published: December 2017

Functional connectomes computed from fMRI provide a means to characterize individual differences in the patterns of BOLD synchronization across regions of the entire brain. Using four resting-state fMRI datasets with a wide range of ages, we show that individual differences of the functional connectome are stable across three months to three years. Medial frontal and frontoparietal networks appear to be both unique and stable, resulting in high ID rates, as did a combination of these two networks. We conduct analyses demonstrating that these results are not driven by head motion. We also show that the edges demonstrating the most individualized features tend to connect nodes in the frontal and parietal cortices, while edges contributing the least tend to connect cross-hemispheric homologs. Our results demonstrate that the functional connectome is stable across years and is not an idiosyncratic aspect of a specific dataset, but rather reflects stable individual differences in the functional connectivity of the brain.

Research highlights

Whole-brain functional connectivity profiles obtained from four resting-state fMRI datasets are unique and stable across 3 months-3 years in adolescents, young adults, and older adults

Medial frontal and frontoparietal networks tended to be both unique and stable

Individual edges in the frontal and parietal cortices tended to be most discriminative of individual subjects
Active site alanine substitutions can convert deubiquitinating enzymes into avid ubiquitin-binding domains
Authors: Morrow Marie , Morgan Michael , Clerici Marcello , Growkova Katerina , Yan Ming , Komander David , Simicek Michal , Sixma Titia , Wolberger Cynthia
Published: December 2017

A common strategy for studying the biological role of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight-binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30-fold higher affinity of Ubp8C146A for ubiquitin. We show that an alternative option, substituting the active site cysteine with arginine, can inactivate DUBs while also decreasing the affinity for ubiquitin.
Hydrogen production bySulfurospirillumspp. enables syntrophic interactions of Epsilonproteobacteria
Authors: Kruse Stefan , Goris Tobias , Westermann Martin , Adrian Lorenz , Diekert Gabriele
Published: December 2017

Hydrogen-producing bacteria are of environmental and biotechnological importance in anoxic environments, since hydrogen is an important electron donor for prokaryotes and of interest as an alternative energy source. Epsilonproteobacteria, inhabiting ecologically, clinically or biotechnologically relevant environments, are currently considered to be hydrogen-oxidizing bacteria exclusively. Here, we report hydrogen production for a genus of free-living Epsilonproteobacteria,Sulfurospirillumspp. inhabiting sediments, wastewater plants, bioelectrodes, oil reservoirs, contaminated areas, or marine habitats. The amount of hydrogen production was largely different in two subgroups ofSulfurospirillumspp., represented byS. cavoleiandS. multivorans. The former is shown to be the more potent hydrogen producer and excretes acetate as sole organic acid, while the latter exhibited a more flexible fermentation, producing additionally lactate and succinate. The observed hydrogen production could be assigned to a group 4 hydrogenase similar to Hydrogenase 4 (Hyf) inE. coli. We propose thatSulfurospirillumspp. produce molecular hydrogen with electrons derived from pyruvate oxidation by pyruvate:ferredoxin oxidoreductase and reduced ferredoxin. This hypothesis is supported by comparative proteome data, in which both PFOR and ferredoxin as well as hydrogenase 4 are up-regulated. A co-culture experiment withS. multivoransandMethanococcus voltaecultivated with lactate as sole substrate shows a syntrophic interaction between both organisms, since the former cannot grow fermentatively on lactate alone and the latter relies on hydrogen as electron donor. This opens up new perspectives on microbial communities, since Epsilonproteobacteria could play a yet unrecognized role as hydrogen producers in anoxic microbial communities.
Visualizing genome synteny with xmatchview
Authors: Warren René L.
Published: December 2017

In genomics research, the visual representation of DNA sequences is of prime importance. When displayed with additional information, or tracks, showing the position of annotated genes, alignments of sequence of interest, etc., these displays facilitate our understanding of genome and gene structure, and become powerful tools to assess the relationship between various sequence data. They can be used for troubleshooting sequence assemblies, in-depth sequence analysis, and eventually find their way in publications and oral presentations as they often translate complex and abundant data succinctly, with esthetically pleasing images. Here, I introduce xmatchview and xmatchview-conifer, two python applications for comparing genomes visually and assessing their synteny. Availability: https://github.com/warrenlr/xmatchview
Does force-field adaptation induce after-effects on space representation?
Authors: Michel Carine , Bonnetain Lucie , White Olivier
Published: December 2017

Prism adaptation is a well-known model to study sensorimotor adaptive processes. It has been shown that following prism exposure, after-effects are not only restricted to the sensorimotor level but extend as well into spatial cognition. The main purpose of the present study was to investigate in healthy individuals whether expansion to spatial cognition is restricted to adaptive processes peculiar to prism adaptation or whether it occurs as well following other forms of adaptive process such as adaptation to a novel dynamic environment during pointing movements. Representational after-effects were assessed by the perceptual line bisection task before and after adaptation to a leftward or a rightward force field. The main results showed that adaptation developed at sensorimotor level but did not produce after-effects in space representation. However appropriate analysis showed that the slower a participant de-adapt to a rightward dynamic perturbation, the stronger the influence on the perceptual midline judgment during the late phase of the bisection task. The discussion highlights the commonalities between prism and dynamic adaptation on the effects on space representation.
Cell-type specific parallel circuits in the bed nucleus of the stria terminalis and the central nucleus of the amygdala of the mouse
Authors: Ye Jiahao , Veinante Pierre
Published: December 2017

The central extended amygdala (EAc) is a forebrain macrosystem which has been widely implicated in fear, anxiety and pain. Its two key structures, the lateral bed nucleus of the stria terminalis (STL) and the central nucleus of amygdala (CeA), share similar mesoscale connectivity. However, it is not known whether they also share similar cell-specific neuronal circuits. We addressed this question using tract-tracing and immunofluorescence to reveal the connectivity of two neuronal populations expressing either protein kinase C delta (PKCδ) or somatostatin (SOM). PKCδ and SOM are expressed predominantly in the dorsal part of STL (STLD) and in the lateral/capsular parts of CeA (CeL/C). We found that, in both STLD and CeL/C, PKCδ+ cells are the main recipient of extra-EAc inputs from the external lateral part of the parabrachial nucleus (LPBE), while SOM+ cells are the sources of long-range projections to extra-EAc targets, including LPBE and periaqueductal gray. PKCδ+ cells can also integrate inputs from posterior basolateral nucleus of amygdala or insular cortex. Within EAc, PKCδ+, but not SOM+ neurons, serve as the major source of projections to the ventral part of STL and to the medial part of CeA. However, both cell types mediate interconnections between STLD and CeL/C. These results unveil the pivotal positions of PKCδ and SOM neurons in organizing parallel cell-specific neuronal circuits of CeA and STL, which further support the idea of EAc as a structural and functional macrostructure.
Aberrant cerebellar-default-mode functional connectivity underlying auditory verbal hallucinations in schizophrenia revealed by multi-voxel pattern analysis of resting-state functional connectivity MRI data
Authors: Itahashi Takashi , Mimura Masaru , Hasegawa Sayaka , Tani Masayuki , Kato Nobumasa , Hashimoto Ryu-ichiro
Published: December 2017

Past neuroimaging studies have reported that aberrant functional connectivity (FC) underlying auditory verbal hallucinations (AVHs) in schizophrenia is highly distributed over multiple functional networks. There is thus a need for exploratory approaches without limiting analysis to particular seed regions or functional networks, to identify FC alterations underlying AVH. We applied a multi-voxel pattern analysis (MVPA) of FC together with a series of post-hoc FC analyses to resting-state fMRI data acquired from 25 patients with schizophrenia and 25 matched healthy controls. First, the MVPA revealed multiple clusters exhibiting altered FC patterns in schizophrenia. Subsequent multiple linear regression analysis using scores of these clusters identified that FC alteration in the right cerebellum crus I was significantly associated with the severity of AVH. Furthermore, post-hoc FC analysis with the right crus I as a seed revealed significant FC alterations with regions distributed across multiple functional networks, including speech, default-mode, thalamus, and cerebellum. Subsequent linear regression analyses further demonstrated that, among these regions, only reduced FC in the left precuneus was significantly associated with the severity of AVH. Our unbiased exploratory analysis of FC data revealed a novel evidence for the crucial role of FC between cerebellar and default-mode networks in AVH. (198 words)
Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans
Authors: Lee Song-Hua , Omi Shizue , Thakur Nishant , Taffoni Clara , Belougne Jérôme , Engelmann Ilka , Ewbank Jonathan J. , Pujol Nathalie
Published: December 2017

When an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.
Late cortical tracking of ignored speech facilitates neural selectivity in acoustically challenging conditions
Authors: Fiedler Lorenz , Wöstmann Malte , Herbst Sophie K. , Obleser Jonas
Published: December 2017

Listening requires selective neural processing of the incoming sound mixture, which in humans is borne out by a surprisingly clean representation of attended-only speech in auditory cortex. How this neural selectivity is achieved even at negative signal-to-noise ratios (SNR) remains unclear. We show that, under such conditions, a late cortical representation (i.e., neural tracking) of the ignored acoustic signal is key to successful separation of attended and distracting talkers (i.e., neural selectivity). We recorded and modelled the electroencephalographic response of 18 participants who attended to one of two simultaneously presented stories, while the SNR between the two talkers varied dynamically. The neural tracking showed an increasing early-to-late attention-biased selectivity. Importantly, acoustically dominant ignored talkers were tracked neurally by late involvement of fronto-parietal regions, which contributed to enhanced neural selectivity. This neural selectivity by way of representing the ignored talker poses a mechanistic neural account of attention under real-life acoustic conditions.
DeepSimulator: a deep simulator for Nanopore sequencing
Authors: Li Yu , Han Renmin , Bi Chongwei , Li Mo , Wang Sheng , Gao Xin
Published: December 2017

Motivation

Oxford Nanopore sequencing is a rapidly developed sequencing technology in recent years. To keep pace with the explosion of the downstream data analytical tools, a versatile Nanopore sequencing simulator is needed to complement the experimental data as well as to benchmark those newly developed tools. However, all the currently available simulators are based on simple statistics of the produced reads, which have difficulty in capturing the complex nature of the Nanopore sequencing procedure, the main task of which is the generation of raw electrical current signals.

Results

Here we propose a deep learning based simulator, DeepSimulator, to mimic the entire pipeline of Nanopore sequencing. Starting from a given reference genome or assembled contigs, we simulate the electrical current signals by a context-dependent deep learning model, followed by a base-calling procedure to yield simulated reads. This workflow mimics the sequencing procedure more naturally. The thorough experiments performed across four species show that the signals generated by our context-dependent model are more similar to the experimentally obtained signals than the ones generated by the official context-independent pore model. In terms of the simulated reads, we provide a parameter interface to users so that they can obtain the reads with different accuracies ranging from 83% to 97%. The reads generated by the default parameter have almost the same properties as the real data. Two case studies demonstrate the application of DeepSimulator to benefit the development of tools in de novo assembly and in low coverage SNP detection.

Availability

The software can be accessed freely at: https://github.com/lykaust15/deep_simulator.
Hepatic NF-kB-inducing Kinase (NIK) Suppresses Liver Regeneration in Chronic Liver Disease
Authors: Xiong Yi , Torsoni Adriana Souza , Wu Feihua , Shen Hong , Liu Yan , Canet Mark J , Shah M. Yatrik , Omary M. Bishr , Liu Yong , Rui Liangyou
Published: December 2017

Hepatocyte replication maintains liver homeostasis and integrity. It is impaired in chronic liver disease, promoting disease progression. Herein, we have identified NF-kB-inducing kinase (NIK) as an unrecognized suppressor of hepatocyte replication. Hepatic NIK was aberrantly activated in chronic liver disease. Hepatocyte-specific deletion of NIK or its downstream mediator IKKα substantially accelerated hepatocyte proliferation and liver regeneration following partial hepatectomy. Mechanistically, NIK and IKKα suppressed the mitogenic JAK2/STAT3 pathway, thereby inhibiting hepatocyte cell cycle progression. Remarkably, inactivation of hepatic NIK largely reversed suppression of the hepatic JAK2/STAT3 pathway, hepatocyte replication, and liver regeneration induced by either chronic liver injury or metabolic stress. Our data suggest that hepatic NIK acts as a rheostat for liver regeneration to restrain liver overgrowth. Pathologic activation of hepatic NIK blocks hepatocyte replication, likely contributing to liver disease progression.
OmicsNet: Integration of Multi-Omics Data using Path Analysis in Multilayer Networks
Authors: Akhmedov Murodzhon , Arribas Alberto , Montemanni Roberto , Bertoni Francesco , Kwee Ivo
Published: December 2017

Integrative analysis of heterogeneous omics data is essential to obtain a comprehensive overview of otherwise fragmented information and to better understand dysregulated biological pathways leading to a specific condition. One of the major challenges in systems biology is to develop computational methods for proper integration of multi-omics datasets. We propose OmicsNet that uses a multilayer network for the integration and analysis of multi-omics data of heterogeneous types. Each layer of the multilayer network represents a certain data type: input layers correspond to genotype features and nodes in the output layer correspond to phenotypes, while intermediate layers may represent genesets or biological concepts to facilitate functional interpretation of the data. OmicsNet then calculates the highest coefficient paths in multilayer network from each genomic feature to the phenotype by computing an integrated score along the paths. These paths may indicate the most plausible signalling cascade caused by perturbed genotype features leading to a particular phenotype response. With example applications, we illustrate the potential power of OmicsNet in the functional analysis, biomarker discovery and drug response prediction in personalized medicine using multi-omics data.
The bovine alveolar macrophage DNA methylome is resilient to infection withMycobacterium bovis
Authors: O’Doherty Alan Mark , Rue-Albrecht Kevin , Magee David Andrew , Ahting Simone , Irwin Rachelle Elizabeth , Hall Thomas Johnathan , Browne John Arthur , Nalpas Nicolas Claude , Walsh Colum Patrick , Gordon Stephen Vincent , Wojewodzic Marcin Wlodzimierz , MacHugh David Evan
Published: December 2017

DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due toMycobacterium bovis(M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect ofM. bovisinfection on the bAM DNA methylome. The methylomes of bAM infected withM. boviswere compared to those of non-infected bAM 24 hours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33–66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM.
State-Transition Analysis of Time-Sequential Gene Expression Identifies Critical Points That Predict Leukemia Development
Authors: Rockne Russell C. , Branciamore Sergio , Qi Jing , Frankhouser David , O’Meally Denis , Hua Wei-Kai , Cook Guerry J. , Carnahan Emily , Zhang Lianjun , Marom Ayelet , Wu Herman , Maestrini Davide , Wu Xiwei , Yuan Yate-Ching , Liu Zheng , Wang Leo D. , Forman Stephen J. , Carlesso Nadia , Kuo Ya-Huei , Marcucci Guido
Published: December 2017

Temporal dynamics of gene expression are informative of changes associated with disease development and evolution. Given the complexity of high-dimensional temporal datasets, an analytical framework guided by a robust theory is needed to interpret time-sequential changes and to predict system dynamics. Herein, we use acute myeloid leukemia as a proof-of-principle to model gene expression dynamics in a transcriptome state-space constructed based on time-sequential RNA-sequencing data. We describe the construction of a state-transition model to identify state-transition critical points which accurately predicts leukemia development. We show an analytical approach based on state-transition critical points identified step-wise transcriptomic perturbations driving leukemia progression. Furthermore, the gene(s) trajectory and geometry of the transcriptome state-space provides biologically-relevant gene expression signals that are not synchronized in time, and allows quantification of gene(s) contribution to leukemia development. Therefore, our state-transition model can synthesize information, identify critical points to guide interpretation of transcriptome trajectories and predict disease development.

Graphical Abstract

In brief

The theory of state-transition is applied to acute myeloid leukemia (AML) to model transcriptome dynamics and trajectories in a state-space, and is used to identify critical points corresponding to critical transcriptomic perturbations that predict leukemia development.

Highlights

Leukemia transcriptome dynamics are modeled as movement in transcriptome state-space

State-transition model and critical points accurately predicts leukemia development

Critical point-based approach identifies step-wise transcriptome events in leukemia

State-based geometric analysis provides quantification of leukemogenic contribution
The PTPRT pseudo-phosphatase domain is a denitrase
Authors: Zhao Yiqing , Zhao Shuliang , Hao Yujun , Wang Benlian , Zhang Peng , Feng Xiujing , Chen Yicheng , Song Jing , Mieyal John , Markowitz Sanford , Ewing Rob M. , Conlon Ronald A. , Miyagi Masaru , Wang Zhenghe
Published: December 2017

Protein tyrosine nitration occurs under both physiological and pathological conditions1. However, enzymes that remove this protein modification have not yet been identified. Here we report that the pseudo-phosphatase domain of protein tyrosine receptor T (PTPRT) is a denitrase that removes nitro-groups from tyrosine residues in paxillin. PTPRT normally functions as a tumor suppressor and is frequently mutated in a variety of human cancers including colorectal cancer2,3. We demonstrate that some of the tumor-derived mutations located in the pseudophosphatase domain impair the denitrase activity. Moreover, PTPRT mutant mice that inactivate the denitrase activity are susceptible to carcinogen-induced colon tumor formation. This study uncovers a novel enzymatic activity that is involved in tumor suppression.
Handling Multiplicity in Neuroimaging through Bayesian Lenses with Multilevel Modeling
Authors: Chen Gang , Xiao Yaqiong , Taylor Paul A. , Rajendra Justin K. , Riggins Tracy , Geng Fengji , Redcay Elizabeth , Cox Robert W.
Published: December 2017

Here we address the current issues of inefficiency and over-penalization in the massively univariate approach followed by the correction for multiple testing, and propose a more efficient model that pools and shares information among brain regions. Using Bayesian multilevel (BML) modeling, we control two types of error that are more relevant than the conventional false positive rate (FPR): incorrect sign (type S) and incorrect magnitude (type M). BML also aims to achieve two goals: 1) improving modeling efficiency by having one integrative model and thereby dissolving the multiple testing issue, and 2) turning the focus of conventional null hypothesis significant testing (NHST) on FPR into quality control by calibrating type S errors while maintaining a reasonable level of inference efficiency The performance and validity of this approach are demonstrated through an application at the region of interest (ROI) level, with all the regions on an equal footing: unlike the current approaches under NHST, small regions are not disadvantaged simply because of their physical size. In addition, compared to the massively univariate approach, BML may simultaneously achieve increased spatial specificity and inference efficiency, and promote results reporting in totality and transparency. The benefits of BML are illustrated in performance and quality checking using an experimental dataset. The methodology also avoids the current practice of sharp and arbitrary thresholding in thep-value funnel to which the multidimensional data are reduced. The BML approach with its auxiliary tools is available as part of the AFNI suite for general use.
Case report of Schöpf–Schulz–Passarge syndrome resulting from a missense mutation, p.Arg104Cys, in WNT10A
Authors: Hsu Tzu‐Chien , Lee Julia Yu‐Yun , Hsu Mark Ming‐Long , Chao Sheau‐Chiou
Published: December 2017

Schöpf–Schulz–Passarge syndrome (SSPS) is a rare ectodermal dysplasia characterized by cysts of the eyelids, hypodontia, hypotrichosis, palmoplantar keratosis and onychodystrophy, and it is not common in Asia according to the published work. This autosomal recessive disorder was believed to result from mutations in the WNT10A gene. We report a 54‐year‐old Taiwanese man with SSPS resulted from a homozygous mutation (p.Arg104Cys) in WNT10A. This mutation has not been reported in odonto‐onycho‐dermal dysplasia but was demonstrated to link with dental abnormalities. This report implies the significance of WNT10A gene mutation in ectodermal dysplasia and highlights the clinical features of SSPS.
Ecological context and the probability of mistakes underlie speed choice
Authors: Wheatley Rebecca , Niehaus Amanda C. , Fisher Diana O. , Wilson Robbie S.
Published: December 2017

Movement is fundamental to the ecology of animals, and an animal's choice of movement speed determines the duration, energetic costs, and probability of success of any given activity. It is often assumed that animals should use maximum speeds when escaping from predators, but an increasing number of studies find animals rarely move as fast as they can in nature because faster speeds come with a greater chance of mistakes. Mathematical modelling suggests that, when escaping predators, prey animals should optimise speeds to simultaneously outrun their pursuer and minimise their probability of slipping. This can be particularly important when running along narrow structures like branches. When foraging, however, animals should avoid moving at high speeds, which are often energetically costly and decrease the ability to detect food or predators.

In this study, we examined how trade‐offs between speed and probability of slipping influenced the speed choice of wild antechinus (Antechinus mysticus) during escaping and foraging behaviours. We also examined how this trade‐off affected foraging behaviour.

Antechinus ran significantly faster when escaping (1.207 ± 0.033 m/s) than foraging (0.145 ± 0.002 m/s), and slipped 37% more often during escapes. However, foraging antechinus still slipped frequently on narrow branches, despite running an order of magnitude more slowly than they did on wide branches. Furthermore, antechinus slipped at lower speeds when foraging than they did when escaping, suggesting that avoiding mistakes is less highly prioritized when foraging.

Antechinus visited the feeding station accessed by a wide branch more frequently (and ate more while there) compared with feeding stations accessed by narrow branches, even when those branches were 33% or 67% shorter. This suggests that foraging decisions may be based on potential limitations to speed and the probability of slipping over distance to cover.

Though activities such as running can be fundamental to animals’ fitness, a general framework to understand how animals select speeds in nature is still being developed. We test the assumption that animals choose running speeds to minimise their motor mistakes, and demonstrate the cost of mistakes is likely to be different across ecological and behavioural contexts.

A plain language summary is available for this article.
Anti‐angiogenesis effect of β‐D‐mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model
Authors: Rastegari‐Pouyani Mohsen , Mostafaie Ali , Mansouri Kamran , Mortazavi‐Jahromi Seyed Shahabeddin , Mohammadi‐Motlagh Hamid‐Reza , Mirshafiey Abbas
Published: December 2017

Angiogenesis is a process through which new capillaries are formed from pre‐existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The β‐D‐mannuronic acid (M2000) is a novel non‐steroidal anti‐inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti‐angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti‐proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen‐cytodex model and the chick chorioallantoic membrane (CAM) assay were then used to evaluate the anti‐angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 μg/mL) had no cytotoxic effect on human umbilical vein endothelial cells (HUVECs). It was also illustrated that M2000 had little or no anti‐proliferative effect on HUVECs. In addition, the anti‐angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose‐dependent in the in vivo status. This study showed that M2000 could be considered as an anti‐angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti‐inflammatory effects may partly be attributable to its anti‐angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis‐related disorders.
Are the Greens ‘Neither Left nor Right but Out in Front’? What the Carbon Pollution Reduction Scheme Debate Reveals About Ideological Divisions Between Labor and the Greens
Authors: Edwards Lindy
Published: December 2017

In 2009, the Rudd Labor Government proposed a Carbon Pollution Reduction Scheme (CPRS) but was unable to secure support from the Australian Greens. This paper uses this case study to examine ideological divisions that may hamper policy making within Australia's left in the future. It finds the Greens saw the issue through a classic left schema that constructed the environmental crisis as having been created by the powerful exploiting the vulnerable. In contrast, Labor saw the issue through a liberal schema that constructed the crisis as a product of a morally neutral market failure. These different framings led to very different views on the appropriateness of the polluting industries’ compensation package. It concludes that co‐operation between the parties in the future is likely to centre on issues they both view through the left schema.
Incentives, Resources and Combinations of Innovation Radicalness and Innovation Speed
Authors: Behrens Judith , Patzelt Holger
Published: December 2017

Although scholars have independently explored the antecedents of innovation radicalness and innovation speed, this study's focus on combinations of radicalness and speed offers a number of new insights. Drawing on a comparative case study approach of ten innovation departments of large organizations, the authors’ findings provide evidence that intrinsic rewards trigger innovation radicalness, but the simultaneous presence of extrinsic rewards diminishes innovation speed. Further, the authors show that the availability of high levels of non‐financial resources increases innovation radicalness, but the additional provision of high levels of financial resources leads to a slower process of developing these radical innovations to market. The analysis also uncovers the mechanisms by which extrinsic rewards and financial resources slow down the development of radical innovations. The authors discuss the implications of these findings for the literature on innovation management and managerial practice.
Trust in Scandinavia: Findings from Moving Borders between Denmark and Germany
Authors: Andersen Rasmus Fonnesbaek
Published: December 2017

Scandinavian societies express the world's highest levels of trust in surveys and display high levels of social capital more generally. Scholars and policy makers disagree on whether this reflects high economic equality brought about by inclusive, universalist welfare states after the Second World War or historical legacies of political stability and relative social harmony. This article utilizes a geographic regression discontinuity (GRD) natural experiment from history of moving borders between Denmark and Germany to examine the effect of belonging to a Scandinavian state on trust and cooperative behavior. Results from historical Danish rule prior to 1864 in North Germany and German rule in South Denmark from 1864 to 1920 suggest that institutional differences influenced early mass political behavior, but not social behavior. However, such early regime impacts petered out quickly. Today, there is little to no discernable difference in trust attributable to Danish state heritage in North Germany or South Denmark. This suggests that sizable differences in social trust between Germany and Denmark are instead attributable to post‐1920 factors.
New insights into diet breadth of polyphagous and oligophagous aphids on two Arabidopsis ecotypes
Authors: Wattier Christopher , Turbant Amélie , Sargos‐Vallade Lisa , Pelloux Jérôme , Rustérucci Christine , Cherqui Anas
Published: December 2017

We investigated whether plant ecotype might affect aphid performance and behavior. The probing behaviors of the polyphagous aphid Myzus persicae and the oligophagous aphid Brevicoryne brassicae on two ecotypes of Arabidopsis thaliana, WS and Col‐0 were recorded using the direct current electrical penetration graph method (DC‐EPG). Myzus persicae displayed a significant preference for the WS ecotype but was not greatly disturbed on Col‐0, while B. brassicae discriminated between the two A. thaliana ecotypes, feeding less on WS than on Col‐0. A Principal Component Analysis of aphid probing behavior data recorded on Col‐0 and WS ecotypes showed that the one of M. persicae was positively correlated with the phloem ingestion phases while the one of B. brassicae was more related to nonfeeding phase. The survival of the aphid species was followed during early larval stages on the two ecotypes and a significantly higher mortality was observed of B. brassicae neonates compared to M. persicae, both reared on WS. Moreover, transcriptomic analysis of noninfested plant leaves from both ecotypes was monitored and underlined constitutive differences between Col‐0 and WS gene expression that might explain the different aphid behaviors. Among a unigene set comprising 39 042 sequences for A. thaliana, 6% were differently expressed affecting, for example, the secondary metabolites and cell wall pathways: two third upregulated in WS and one third upregulated in Col‐0. Thus, the “ecotype” variable should be taken into account when setting up a plant–insect experimental research.
Seed vigour contributes to yield improvement in dry direct‐seeded rainfed lowland rice
Authors: Yamane K. , Garcia R. , Imayoshi K. , Mabesa‐Telosa R.C. , Banayo N.P.M.C. , Vergara G. , Yamauchi A. , Sta. Cruz P. , Kato Y.
Published: December 2017

Dry direct‐seeded rice (DSR) cultivation is widely spreading in tropical Asia, but drought and nutrient deficiency stresses often cause crop failure in rainfed lowlands. The objective of this study was to dissect the physio‐morphological characteristics associated with crop establishment and early vigour of DSR under drought and P deficiency conditions in the Philippines. It was found that new drought‐resistant cultivars bred for DSR (Rc348 and Rc192) had faster germination and sprout growth than popular irrigated rice cultivars (Rc222 and Rc10) under soil water deficit due to rapid moisture acquisition by the germinating seeds from drying soils. There was a significant correlation between seed moisture content and the reduction in seed dry weight, and between reduction in seed dry weight and shoot elongation under both control and drought stress treatments at the germination stage. At the seedling stage, the root growth of Rc348 under drought tended to be more vigorous with its higher root‐to‐shoot ratio compared to Rc222 and Rc10. The seedling vigour of Rc348 under P deficiency was also greater than that of Rc222 due to its greater root growth and P uptake. The yields of Rc348 and Rc192 grown under rainfed condition at the target drought‐prone site where a dry spell of 13 days occurred during crop establishment were higher (4.0–4.1 t ha−1) than the yield of Rc10 (3.0 t ha−1). These results suggest that quick germination and seedling vigour with quick root anchorage and great nutrient uptake capacity, even with limitations of soil moisture and nutrients, would be important traits for DSR in rainfed lowlands.
Managing opioid overdose in pregnancy with take‐home naloxone
Authors: Blandthorn Julie , Bowman Ellen , Leung Laura , Bonomo Yvonne , Dietze Paul
Published: December 2017

Programs have recently been established in Australia and internationally to allow wider access to naloxone to people at risk of opioid overdose yet there are no guidelines relating to the administration of naloxone to pregnant women, particularly regarding dose requirements and resuscitative measures peculiar to pregnancy. This paper provides practical guidelines to health workers in relation to any complications that may arise during opioid overdose response (including the administration of naloxone) for pregnant women and the follow up required ensuring best possible outcomes for mother and baby.
POST‐PRIVATIZATION OWNERSHIP AND FIRM PERFORMANCE: A LARGE META‐ANALYSIS OF THE TRANSITION LITERATURE
Authors: IWASAKI Ichiro , MIZOBATA Satoshi
Published: December 2017

This paper aims to perform a large‐scale meta‐analysis of the relationship between post‐privatization ownership and firm performance in Central and Eastern Europe and the former Soviet Union. Baseline estimation of a meta‐regression model that employs a total of 2,894 estimates drawn from 121 previous studies indicated the superior impact of foreign ownership on firm performance in comparison with state and domestic private entities. Furthermore, the estimation of an extended meta‐regression model that explicitly controls for the idiosyncrasies of transition economies and privatization policies strongly suggested that differences between countries in location, privatization method, and speed of policy implementation strongly influence the link between post‐privatization ownership structure and firm performance. We also found that these factors not only cause a remarkable gap between countries in terms of ex post improvement in firm performance but also significantly affect the interrelationship between foreign investors, domestic outsider owners, and firm managers, and the relative superiority of various domestic outsiders. Conclusive evidence of the harm caused to ex post firm performance by voucher privatization is one of the most noteworthy empirical findings in this paper.
Oseltamivir and indomethacin reduce the oxidative stress in brain and stomach of infected rats
Authors: Guzmán David Calderón , Herrera Maribel Ortiz , Brizuela Norma Osnaya , Mejía Gerardo Barragán , García Ernestina Hernández , Olguín Hugo Juárez , Ruíz Norma Labra , Peraza Armando Valenzuela
Published: December 2017

The aim of this study was to determine the effect of oseltamivir and indomethacin on lipid peroxidation (LP), GABA levels, and ATPase activity in brain and stomach of normal and infected rats (IR), as novel inflammation model. Female Sprague Dawley rats grouped five each, either in the absence or presence of a live culture of Salmonella typhimurium (S. typh), were treated as follows: group 1 (control), PBS buffer; group 2, oseltamivir (100 mg/kg); group 3, indomethacin (67 μg/rat); group 4, oseltamivir (100 mg/kg) + indomethacin (67 μg/rat). All drugs were given intraperitoneally for 5 days. IR received the same treatments and the brain and stomach of the rats were removed in order to measure levels of GABA, LP, and total ATPase, using validated methods. Levels of GABA increased in stomach and cortex of IR with oseltamivir, but decreased in striatum and cerebellum/medulla oblongata of IR with indomethacin. LP decreased in the three brain regions of IR with oseltamivir. ATPase increased in stomach of IR and non‐IR with oseltamivir and in striatum and cerebellum/medulla oblongata of IR with indomethacin. Results suggest that the effect of free radicals produced in an infection and inflammatory condition caused by S. typh could be less toxic by a combination of oseltamivir and indomethacin.
Motivated or Demotivated to Be Creative: The Role of Self‐Regulatory Focus in Transformational and Transactional Leadership Processes
Authors: Kark Ronit , Van Dijk Dina , Vashdi Dana Rachel
Published: December 2017

Numerous studies have recognised the importance of transformational leadership style for encouraging employees’ creativity. Self‐regulation studies have highlighted the influence of a promotion focus on employees’ creative behaviours. Yet both leadership and self‐regulation theories have paid less attention to the role transactional leadership style and situational prevention regulatory focus may play in affecting employees’ creativity. In this article we present a theoretical model which examines transformational and transactional leadership styles and both promotion and prevention situational self‐regulatory focus (SRF). The model suggests that while transformational leadership promotes creativity, at least partially by enhancing follower's situational promotion SRF, transactional leadership style (transactional active) is aligned with followers’ prevention situational SRF, which is associated with leaders’ hindering of followers’ creativity. Findings from two studies, an experimental study (N = 189) and a field study (N = 343 employees and 75 managers), support this model, showing that the relationship between different types of leadership and creativity are more complex than previously regarded. The theoretical and practical implications are discussed.
Editorial: there is trouble ahead, but just how much? The troubling reality of America's excesses and NAFLD
Authors: Brennan P. N. , Dillon J. F.
Published: December 2017

Linked Content

This article is linked to Wong et al paper. To view this article please visit https://doi.org/10.1111/apt.14327.
Editorial: rifaximin—a kick in the gut for spontaneous bacterial peritonitis?
Authors: Woodhouse C. , Shawcross D. L.
Published: December 2017

Linked Content

This article is linked to Goel et al and Goel and Nguyen papers. To view these articles visit https://doi.org/10.1111/apt.14361 and https://doi.org/10.1111/apt.14450.
Editorial: the influence of genetic factors in mediating the effects of tobacco smoke in IBD
Authors: Adams A. , Kalla R. , Satsangi J.
Published: December 2017

Linked Content

This article is linked to Lang et al papers. To view these articles visit https://doi.org/10.1111/apt.14378 and https://doi.org/10.1111/apt.14447.
Editorial: the influence of genetic factors in mediating the effects of tobacco smoke in IBD—Authors’ reply
Authors: Lang B. M. , Beerenwinkel N. , Misselwitz B.
Published: December 2017

Linked Content

This article is linked to Adams et al and Lang et al papers. To view these articles visit https://doi.org/10.1111/apt.14334 and https://doi.org/10.1111/apt.14378.
Editorial: rifaximin—a kick in the gut for spontaneous bacterial peritonitis? Authors’ reply
Authors: Goel A. , Nguyen M. H.
Published: December 2017

Linked Content

This article is linked to Goel et al and Woodhouse and Shawcross papers. To view these articles visit https://doi.org/10.1111/apt.14361 and https://doi.org/10.1111/apt.14406.
HLA‐DQA1‐HLA‐DRB1 polymorphism is a major predictor of azathioprine‐induced pancreatitis in patients with inflammatory bowel disease
Authors: Wilson A. , Jansen L. E. , Rose R. V. , Gregor J. C. , Ponich T. , Chande N. , Khanna R. , Yan B. , Jairath V. , Khanna N. , Sey M. , Beaton M. , McIntosh K. , Teft W. A. , Kim R. B.
Published: December 2017

Background

Azathioprine (AZA)‐induced pancreatitis is an unpredictable and dose‐independent adverse event affecting 2%‐7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at‐risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine‐induced pancreatitis.

Aim

To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles.

Methods

A retrospective cohort study evaluated 373 AZA‐exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA‐DQA1*02:01‐HLA‐DRB1*07:01 haplotype and were sub‐divided based on the presence (n = 13) or absence (n = 360) of an AZA‐induced pancreatitis diagnosis. The risk of AZA‐induced pancreatitis was assessed based on rs2647087 genotype.

Results

The risk of pancreatitis during AZA‐therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02‐36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80‐145.26, P = 0.0001) for homozygous variant (C/C) patients.

Conclusions

The class II HLA region (at rs2647087) is an important marker of AZA‐induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD.
G protein‐coupled receptor gpr34l mutation affects thrombocyte function in zebrafish
Authors: Kim Seongcheol , Alsrhani Abdullah , Zafreen Lala , Khandekar Gauri , Marlow Florence L , Abrams Elliott W. , Mullins Mary C. , Jagadeeswaran Pudur
Published: December 2017

Haemostasis is a defence mechanism that has evolved to protect organisms from losing their circulating fluid. We have previously introduced zebrafish as a model to study the genetics of haemostasis to identify novel genes that play a role in haemostasis. Here, we identify a zebrafish mutant that showed prolonged time to occlusion (TTO) in the laser injury venous thrombosis assay. By linkage analysis and fine mapping, we found a mutation in the orphan G protein‐coupled receptor 34 like gene (gpr34l) causing a change of Val to Glu in the third external loop of Gpr34l. We have shown that injection of zebrafish gpr34l RNA rescues the prolonged TTO defect. The thrombocytes from the mutant showed elevated levels of cAMP that supports the defective thrombocyte function. We also have demonstrated that knockdown of this gene by intravenous Vivo‐Morpholino injections yielded a phenotype similar to the gpr34l mutation. These results suggest that the lack of functional Gpr34l leads to increased cAMP levels that result in defective thrombocyte aggregation.