bluuebunny/crossref_metadata_2025 huggingface dataset:
Autocratic time horizons and the growth effect of foreign direct investment
Authors: Bak Daehee , Moon Chungshik
Published: May 2019

The positive influence of foreign direct investment (FDI) on host countries' economic growth has been widely debated. Given the mixed empirical evidence, scholars have sought to find the economic preconditions under which FDI spillovers are likely to occur and facilitate economic growth in the host countries. Those preconditions are not exogenously dictated but largely shaped by governments' policy preferences. Particularly in autocracies, an autocrat's policy preferences are the driving force that determines whether a host country is likely to be equipped with growth-friendly institutions and policies. We argue that such economic institutions and policies are dependent on the time horizons of autocrats in power. Our empirical analysis covering 64 autocratic countries from 1970 to 2005 supports our main argument that FDI has a positive effect on growth when autocratic time horizons are sufficiently long, and positive FDI spillovers mainly occur through the protection of property right institutions.
Resistance of some rice varieties to the African striped borer, Chilo zacconius (Bleszynski)
Authors: Ukwungwu M. N. , Odebiyi J. A.
Published: May 2019

Sixty selected rice varieties were tested for resistance to damage by the African striped borer, Chilo zacconius. Artificial infestation with first instar larvae in screenhouse showed that Lac 23 (white), IR 2035-120-3, 1R 4625-132-1-2, Colombia 1 and N 21-1 had significantly low “dead hearts” and larval survival. Damage was also low when these varieties were exposed to adults in the screenhouse and in the field. Both local and exotic varieties possessed resistance. Antibiosis conferred resistance to the borer in the varieties screened.
A miniaturized dual band EBG unit cell for UWB antennas with high selective notching
Authors: Abdalla Mahmoud A. , Al-Mohamadi Abdullah A. , Mohamed Ibrahim S.
Published: May 2019

A high selective dual band and miniaturized electromagnetic band gap (EBG) unit cell is presented in this paper. The analysis and characterization of the new cell are explained. The modified compact EBG unit cell is based on cutting two inverted U-shaped slots inside the typical mushroom-like EBG. The modified EBG has a 70% size reduction. The dual-band functionality of the structure is confirmed by applying it in a dual-notch ultra-wideband antenna (3.1–10.6 GHz), and the notch frequencies are 5.2 and 5.8 GHz. The dual-band functionality has advantages of a highly selective bandpass between them. The antenna can suppress interference frequencies in less than 100 MHz bandwidth without affecting the antenna performance in the whole bandwidth. Presented results are addressed in terms of circuit modeling, 3D full-wave simulations, and measurements.
Petition-and-Response and Liminal Petitioning in Comparative/Historical Perspective
Authors: Zaret David
Published: May 2019

Before its deployment as a practice by insurgent social movements for mobilizing public opinion in the long nineteenth century, petitioning was a ubiquitous, relatively uniform practice with no connection to popular insurgency. It was nearly the inverse, though just as prominent, phenomenon: an instrument of state as opposed to an instrument of protest, occurring wherever rulership relied on administrative techniques for generating and deploying its authority. Humble subjects sought benevolent deployments of power in pursuit of goals that were within and not about the rules of the game. This mode of petitioning is aptly described as petition-and-response, a term of art from classical scholarship that is applicable to diverse patrimonial states across Eurasia with diverse ideological systems. The transition to modern petitioning as a repertoire for contentious politics was an extended, uneven process. It was facilitated initially by the unquestioned legitimacy of petitionary etiquette with regard to form and rhetoric, as opposed to explicit invocation of novel ideas about natural rights. Liminal petitioning had contradictory elements of deference to and defiance of power relations that diminished perceptions of novelty in novel activities that mobilized and invoked popular opinion on contentious political issues.
Beckenboden der Frau: Anatomie und normale Funktion
Authors: Betschart Cornelia , Singer Adrian , Scheiner David
Published: May 2019

Zusammenfassung. Das komplexe Zusammenspiel der anatomischen Strukturen am Beckenboden hat in der Evolution zur Kontinenz von Blase und Darm, dem sexuellen Erleben und der Reproduktion geführt. Diese Fähigkeiten haben alle eine wichtige individuelle und auch übergeordnete Rolle, dank derer erst soziale Interaktionen möglich werden. Um die Funktionen besser zu verstehen, sind anatomische zugrundeliegende Konzepte essentiell. Was in früheren Jahrhunderten durch Leichendissektionen an Wissen gewonnen wurde, wird heutzutage durch moderne Bildgebung und Bildverarbeitung erweitert. Im folgenden Artikel wollen wir den Leserinnen und Lesern eine Übersicht der anatomisch wichtigen Strukturen am Beckenboden geben.
Deszensus genitalis der Frau
Authors: Huemer Hansjörg
Published: May 2019

Zusammenfassung. Behandlungswürdige Erkrankungen des Beckenbodens, insbesondere eine Senkung der Vagina oder des Uterus betreffen in etwa jede zehnte Frau während ihres Lebens. Eine Indikation für eine Behandlung ist dann gegeben, wenn Symptome auftreten, die für eine Senkung typisch sind. Dies kann einerseits lediglich ein Senkungsgefühl bzw. Fremdkörpergefühl sein, andererseits auch Beschwerden im Bereich der benachbarten Organe im Sinne einer gestörten Blasen- oder Stuhlentleerung. Ebenso kann die Sexualität dadurch beeinträchtigt sein. Im Hinblick auf eine Prophylaxe ist es wichtig die Risikofaktoren zu kennen und wenn möglich zu beeinflussen. Die Therapiemöglichkeiten haben sich in den letzten Jahren sowohl im Bereich der konservativen Behandlung, noch viel mehr jedoch im Bereich der Operationen verbreitert, sodass wir heute in der Lage sind, die jeweils individuell beste Therapie den Bedürfnissen der Patientin anpassen zu können.
Improved Simulations of The Inner Magnetosphere During High Geomagnetic Activity With the RAM‐SCB Model
Authors: Engel Miles A. , Morley Steven K. , Henderson Michael G. , Jordanova Vania K. , Woodroffe Jesse R. , Mahfuz Rehana
Published: May 2019

Simulating times of high geomagnetic activity are an important part of the continuing efforts to understand space weather and its impacts on humanity. Recent improvements to the Ring‐current Atmosphere interactions Model with Self‐Consistent magnetic field (RAM‐SCB) have been undertaken, with the purpose of expanding the accuracy and robustness of the model during these highly active times. The improvements include a number of changes to the functionality of both the RAM model and the self‐consistent magnetic field calculation. In addition, the models have been modernized and rewritten in an effort to make them more user friendly and understandable. The effect of these changes is shown by simulating the day of 17 March 2013, which saw Sym‐H drop below −100 nT and included a magnetosphere push‐in within geosynchronous orbit. The comparison between the previous model configuration and this new configuration is investigated by calculating a series of metrics for the relation between the observed and modeled Sym‐H, as well as the >10‐keV electron flux measured by the HOPE and MAGEIS instruments aboard RBSP‐B and the simulated electron flux. These metrics show that the improvements to the model have increased the accuracy of the model for the given simulation.
Wavenumber Analysis of EMIC Waves
Authors: Chen Lunjin , Zhu Hui , Zhang Xiaojia
Published: May 2019

It has been highly controversial as to whether and how efficient electromagnetic ion cyclotron (EMIC) waves can scatter sub–megaelectronvolt (MeV) to multi–megaelectron volt electrons into the atmospheric loss cone. The capability of EMIC wave scattering essentially depends on the wavenumber spectra, instead of readily available frequency spectra. We present a method to obtain the EMIC wavenumbers directly from the wave electromagnetic field measurements, from which we further evaluate the characteristics of electron minimum resonant energy and electron scattering rate due to EMIC waves. Based on the analysis of EMIC waves identified from 5.5 years of Van Allen Probes field measurement, we find that only a small fraction of H+ band wave events can resonate with electrons down to MeV, while none of He+ band waves at the maximum wave power can. The electron scattering rate increases with increasing levels of geomagnetic activities. The scattering rate for H+ band is sufficient to cause significant precipitation of electrons for a broad energy range (including MeV electrons), especially during times with high geomagnetic activity.
Alfvén Ion Cyclotron Waves in Sheath Regions Driven by Interplanetary Coronal Mass Ejections
Authors: Ala‐Lahti Matti , Kilpua Emilia K. J. , Souček Jan , Pulkkinen Tuija I. , Dimmock Andrew P.
Published: May 2019

We report on a statistical analysis of the occurrence and properties of Alfvén ion cyclotron (AIC) waves in sheath regions driven by interplanetary coronal mass ejections (ICMEs). We have developed an automated algorithm to identify AIC wave events from magnetic field data and apply it to investigate 91 ICME sheath regions recorded by the Wind spacecraft. Our analysis focuses on waves generated by the ion cyclotron instability. AIC waves are observed to be frequent structures in ICME‐driven sheaths, and their occurrence is the highest in the vicinity of the shock. Together with previous studies, our results imply that the shock compression has a crucial role in generating wave activity in ICME sheaths. AIC waves tend to have their frequency below the ion cyclotron frequency, and, in general, occur in plasma that is stable with respect to the ion cyclotron instability and has lower ion β‖ than mirror modes. The results suggest that the ion beta anisotropy β⊥/β‖>1 appearing in ICME sheaths is regulated by both ion cyclotron and mirror instabilities.
CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia
Authors: Pan Jing , Niu Qing , Deng Biping , Liu Shuangyou , Wu Tong , Gao Zhiyong , Liu Zhaoli , Zhang Yue , Qu Xiaomin , Zhang Yanlei , Liu Shaohui , Ling Zhuojun , Lin Yuehui , Zhao Yongqiang , Song Yanzhi , Tan Xiyou , Zhang Yan , Li Zhihui , Yin Zhichao , Chen Bingzhen , Yu Xinjian , Yan Ju , Zheng Qinlong , Zhou Xuan , Gao Jin , Chang Alex H. , Feng Xiaoming , Tong Chunrong
Published: May 2019

Despite worldwide promising clinical outcome of CD19 CAR-T therapy, relapse after this therapy is associated with poor prognosis and has become an urgent problem to be solved. We conducted a CD22 CAR T-cell therapy in 34 relapsed or refractory (r/r) B-ALL pediatric and adult patients who failed from previous CD19 CAR T-cell therapy. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 24 of 30 patients (80%) that could be evaluated on day 30 after infusion, which accounted for 70.5% of all 34 enrolled patients. Most patients only experienced mild cytokine-release syndrome and neurotoxicity. Seven CR patients received no further treatment, and 3 of them remained in remission at 6, 6.6, and 14 months after infusion. Eleven CR patients were promptly bridged to transplantation, and 8 of them remained in remission at 4.6 to 13.3 months after transplantation, resulted in 1-year leukemia-free survival rate of 71.6% (95% CI, 44.2–99.0). CD22 antigen loss or mutation was not observed to be associated with relapsed patients. Our study demonstrated that our CD22 CAR T-cells was highly effective in inducing remission in r/r B-ALL patients, and also provided a precious window for subsequent transplantation to achieve durable remission.
Patterns of inter- and intrasubspecific homologous recombination inform eco-evolutionary dynamics of Xylella fastidiosa
Authors: Potnis Neha , Kandel Prem P , Merfa Marcus V , Retchless Adam C , Parker Jennifer K , Stenger Drake C , Almeida Rodrigo P P , Bergsma-Vlami Maria , Westenberg Marcel , Cobine Paul A , De La Fuente Leonardo
Published: May 2019

High rates of homologous recombination (HR) in the bacterial plant pathogen Xylella fastidiosa have been previously detected. This study aimed to determine the extent and explore the ecological significance of HR in the genomes of recombinants experimentally generated by natural transformation and wild-type isolates. Both sets of strains displayed widespread HR and similar average size of recombined fragments consisting of random events (2–10 kb) of inter- and intrasubspecific recombination. A significantly higher proportion and greater lengths (>10 kb, maximum 31.5 kb) of recombined fragments were observed in subsp. morus and in strains isolated in Europe from intercepted coffee plants shipped from the Americas. Such highly recombinant strains pose a serious risk of emergence of novel variants, as genetically distinct and formerly geographically isolated genotypes are brought in close proximity by global trade. Recently recombined regions in wild-type strains included genes involved in regulation and signaling, host colonization, nutrient acquisition, and host evasion, all fundamental traits for X. fastidiosa ecology. Identification of four recombinant loci shared between wild-type and experimentally generated recombinants suggests potential hotspots of recombination in this naturally competent pathogen. These findings provide insights into evolutionary forces possibly affecting the adaptive potential to colonize the host environments of X. fastidiosa.
Uncultured Nitrospina-like species are major nitrite oxidizing bacteria in oxygen minimum zones
Authors: Sun Xin , Kop Linnea F M , Lau Maggie C Y , Frank Jeroen , Jayakumar Amal , Lücker Sebastian , Ward Bess B
Published: May 2019

Oxygen minimum zones (OMZs) are marine regions where O2 is undetectable at intermediate depths. Within OMZs, the oxygen-depleted zone (ODZ) induces anaerobic microbial processes that lead to fixed nitrogen loss via denitrification and anammox. Surprisingly, nitrite oxidation is also detected in ODZs, although all known marine nitrite oxidizers (mainly Nitrospina) are aerobes. We used metagenomic binning to construct metagenome-assembled genomes (MAGs) of nitrite oxidizers from OMZs. These MAGs represent two novel Nitrospina-like species, both of which differed from all known Nitrospina species, including cultured species and published MAGs. Relative abundances of different Nitrospina genotypes in OMZ and non-OMZ seawaters were estimated by mapping metagenomic reads to newly constructed MAGs and published high-quality genomes of members from the Nitrospinae phylum. The two novel species were present in all major OMZs and were more abundant inside ODZs, which is consistent with the detection of higher nitrite oxidation rates in ODZs than in oxic seawaters and suggests novel adaptations to anoxic environments. The detection of a large number of unclassified nitrite oxidoreductase genes in the dataset implies that the phylogenetic diversity of nitrite oxidizers is greater than previously thought.
Regulation of locomotor speed and selection of active sets of neurons by V1 neurons
Authors: Kimura Yukiko , Higashijima Shin-ichi
Published: May 2019

During fast movements in vertebrates, slow motor units are thought to be deactivated due to the mechanical demands of muscle contraction, but the associated neuronal mechanisms for this are unknown. Here, we perform functional analyses of spinal V1 neurons by selectively killing them in larval zebrafish, revealing two functions of V1 neurons. The first is the long-proposed role of V1 neurons: they play an important role in shortening the cycle period during swimming by providing in-phase inhibition. The second is that V1 neurons play an important role in the selection of active sets of neurons. We show that strong inhibitory inputs coming from V1 neurons play a crucial role in suppressing the activities of slow-type V2a and motor neurons, and, consequently, of slow muscles during fast swimming. Our results thus highlight the critical role of spinal inhibitory neurons for silencing slow-component neurons during fast movements.
The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy
Authors: Salvarani Nicolò , Crasto Silvia , Miragoli Michele , Bertero Alessandro , Paulis Marianna , Kunderfranco Paolo , Serio Simone , Forni Alberto , Lucarelli Carla , Dal Ferro Matteo , Larcher Veronica , Sinagra Gianfranco , Vezzoni Paolo , Murry Charles E. , Faggian Giuseppe , Condorelli Gianluigi , Di Pasquale Elisa
Published: May 2019

Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders. Here, we employ induced pluripotent stem cells (iPSCs) generated from human cells carrying heterozygous K219T mutation on LMNA to develop a disease model. Cardiomyocytes differentiated from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium current and diminished conduction velocity. Moreover, they have significantly downregulated Nav1.5 channel expression and increased binding of Lamin A/C to the promoter of SCN5A, the channel’s gene. Coherently, binding of the Polycomb Repressive Complex 2 (PRC2) protein SUZ12 and deposition of the repressive histone mark H3K27me3 are increased at SCN5A. CRISPR/Cas9-mediated correction of the mutation re-establishes sodium current density and SCN5A expression. Thus, K219T-LMNA cooperates with PRC2 in downregulating SCN5A, leading to decreased sodium current density and slower conduction velocity. This mechanism may underlie the conduction abnormalities associated with LMNA-cardiomyopathy.
Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps
Authors: Ailloud Florent , Didelot Xavier , Woltemate Sabrina , Pfaffinger Gudrun , Overmann Jörg , Bader Ruth Christiane , Schulz Christian , Malfertheiner Peter , Suerbaum Sebastian
Published: May 2019

The human pathogenHelicobacter pyloridisplays extensive genetic diversity. WhileH. pyloriis known to evolve during infection, population dynamics inside the gastric environment have not been extensively investigated. Here we obtained gastric biopsies from multiple stomach regions of 16 H. pylori-infected adults, and analyze the genomes of 10 H. pyloriisolates from each biopsy. Phylogenetic analyses suggest location-specific evolution and bacterial migration between gastric regions. Migration is significantly more frequent between the corpus and the fundus than with the antrum, suggesting that physiological differences between antral and oxyntic mucosa contribute to spatial partitioning ofH. pyloripopulations. Associations betweenH. pylorigene polymorphisms and stomach niches suggest that chemotaxis, regulatory functions and outer membrane proteins contribute to specific adaptation to the antral and oxyntic mucosa. Moreover, we show that antibiotics can induce severe population bottlenecks and likely play a role in shaping the population structure ofH. pylori.
Anchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis
Authors: Vogt Edgar-John , Tokuhiro Keizo , Guo Min , Dale Ryan , Yang Guanghui , Shin Seung-Wook , Movilla Maria Jimenez , Shroff Hari , Dean Jurrien
Published: May 2019

Following fertilization, cortical granules exocytose ovastacin, a metalloendopeptidase that cleaves ZP2 in the zona pellucida surrounding mouse eggs to prevent additional sperm binding. Using high- and super-resolution imaging with ovastacinmCherry as a fluorescent marker, we characterize cortical granule dynamics at single granule resolution in transgenic mouse eggs. Newly-developed imaging protocols provide an unprecedented view of vesicular dynamics near the plasma membrane in mouse eggs. We discover that cortical granule anchoring in the cortex is dependent on maternal MATER and document that myosin IIA is required for biphasic trafficking to the plasma membrane. We observe local clearance of cortical actin during exocytosis and determine that pharmacologic or genetic disruption of trafficking to the plasma membrane impairs secretion of cortical granules and results in polyspermy. Thus, the regulation of cortical granule dynamics at the cortex-plasma membrane interface is critical for exocytosis and the post-fertilization block to sperm binding that ensures monospermic fertilization.
Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation
Authors: Lempp Florian A. , Schlund Franziska , Rieble Lisa , Nussbaum Lea , Link Corinna , Zhang Zhenfeng , Ni Yi , Urban Stephan
Published: May 2019

Hepatitis delta virus (HDV) depends on the helper function of hepatitis B virus (HBV), which provides the envelope proteins for progeny virus secretion. Current infection-competent cell culture models do not support assembly and secretion of HDV. By stably transducing HepG2 cells with genes encoding the NTCP-receptor and the HBV envelope proteins we produce a cell line (HepNB2.7) that allows continuous secretion of infectious progeny HDV following primary infection. Evaluation of antiviral drugs shows that the entry inhibitor Myrcludex B (IC50: 1.4 nM) and interferon-α (IC50: 28 IU/ml, but max. 60–80% inhibition) interfere with primary infection. Lonafarnib inhibits virus secretion (IC50: 36 nM) but leads to a substantial intracellular accumulation of large hepatitis delta antigen and replicative intermediates, accompanied by the induction of innate immune responses. This work provides a cell line that supports the complete HDV replication cycle and presents a convenient tool for antiviral drug evaluation.
iSuRe-Cre is a genetic tool to reliably induce and report Cre-dependent genetic modifications
Authors: Fernández-Chacón Macarena , Casquero-García Verónica , Luo Wen , Francesca Lunella Federica , Ferreira Rocha Susana , Del Olmo-Cabrera Sergio , Benedito Rui
Published: May 2019

Most biomedical research aimed at understanding gene function uses the Cre-Lox system, which consists of the Cre recombinase-dependent deletion of genes containing LoxP sites. This system enables conditional genetic modifications because the expression and activity of the recombinase Cre/CreERT2 can be regulated in space by tissue-specific promoters and in time by the ligand tamoxifen. Since the precise Cre-Lox recombination event is invisible, methods were developed to report Cre activity and are widely used. However, numerous studies have shown that expression of a given Cre activity reporter cannot be assumed to indicate deletion of other LoxP-flanked genes of interest. Here, we report the generation of an inducible dual reporter-Cre mouse allele, iSuRe-Cre. By significantly increasing Cre activity in reporter-expressing cells, iSuRe-Cre provides certainty that these cells have completely recombined floxed alleles. This genetic tool increases the ease, efficiency, and reliability of conditional mutagenesis and gene function analysis.
A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages
Authors: Feng Yanxian , Mu Ruoyu , Wang Zhenzhen , Xing Panfei , Zhang Junfeng , Dong Lei , Wang Chunming
Published: May 2019

Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice.
Author Correction: Functional eubacteria species along with trans-domain gut inhabitants favour dysgenic diversity in oxalate stone disease
Authors: Suryavanshi Mangesh V. , Bhute Shrikant S. , Gune Rahul P. , Shouche Yogesh S.
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Bacterial and fungal gut communities of Agrilus mali at different developmental stages and fed different diets
Authors: Zhang Zhengqing , Jiao Shuo , Li Xiaohui , Li Menglou
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: High-Sensitivity cardiac Troponins in Cardio-Healthy Subjects: A Cardiovascular Magnetic Resonance Imaging Study
Authors: Aw Tar-Choon , Huang Wei-ting , Le Thu-Thao , Pua Chee-Jian , Ang Briana , Phua Soon-Kieng , Yeo Khung-Keong , Cook Stuart A. , Chin Calvin W. L.
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Pyrophosphate inhibits gluconeogenesis by restricting UDP-glucose formation in vivo
Authors: Ferjani Ali , Kawade Kensuke , Asaoka Mariko , Oikawa Akira , Okada Takashi , Mochizuki Atsushi , Maeshima Masayoshi , Hirai Masami Yokota , Saito Kazuki , Tsukaya Hirokazu
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: DNA demethylation is associated with malignant progression of lower-grade gliomas
Authors: Nomura Masashi , Saito Kuniaki , Aihara Koki , Nagae Genta , Yamamoto Shogo , Tatsuno Kenji , Ueda Hiroki , Fukuda Shiro , Umeda Takayoshi , Tanaka Shota , Takayanagi Shunsaku , Otani Ryohei , Nejo Takahide , Hana Taijun , Takahashi Satoshi , Kitagawa Yosuke , Omata Mayu , Higuchi Fumi , Nakamura Taishi , Muragaki Yoshihiro , Narita Yoshitaka , Nagane Motoo , Nishikawa Ryo , Ueki Keisuke , Saito Nobuhito , Aburatani Hiroyuki , Mukasa Akitake
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A Feature based Reconstruction Model for Fluorescence Microscopy Image Denoising
Authors: Maji Suman Kumar , Yahia Hussein
Published: May 2019

The advent of Fluorescence Microscopy over the last few years have dramatically improved the problem of visualization and tracking of specific cellular objects for biological inference. But like any other imaging system, fluorescence microscopy has its own limitations. The resultant images suffer from the effect of noise due to both signal dependent and signal independent factors, thereby limiting the possibility of biological inferencing. Denoising is a class of image processing algorithms that aim to remove noise from acquired images and has gained wide attention in the field of fluorescence microscopy image restoration. In this paper, we propose an image denoising algorithm based on the concept of feature extraction through multifractal decomposition and then estimate a noise free image from the gradients restricted to these features. Experimental results over simulated and real fluorescence microscopy data prove the merit of the proposed approach, both visually and quantitatively.
The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices
Authors: Kunschmann Tom , Puder Stefanie , Fischer Tony , Steffen Anika , Rottner Klemens , Mierke Claudia Tanja
Published: May 2019

Membrane ruffling and lamellipodia formation promote the motility of adherent cells in two-dimensional motility assays by mechano-sensing of the microenvironment and initiation of focal adhesions towards their surroundings. Lamellipodium formation is stimulated by small Rho GTPases of the Rac subfamily, since genetic removal of these GTPases abolishes lamellipodium assembly. The relevance of lamellipodial or invadopodial structures for facilitating cellular mechanics and 3D cell motility is still unclear. Here, we hypothesized that Rac1 affects cell mechanics and facilitates 3D invasion. Thus, we explored whether fibroblasts that are genetically deficient for Rac1 (lacking Rac2 and Rac3) harbor altered mechanical properties, such as cellular deformability, intercellular adhesion forces and force exertion, and exhibit alterations in 3D motility. Rac1 knockout and control cells were analyzed for changes in deformability by applying an external force using an optical stretcher. Five Rac1 knockout cell lines were pronouncedly more deformable than Rac1 control cells upon stress application. Using AFM, we found that cell-cell adhesion forces are increased in Rac1 knockout compared to Rac1-expressing fibroblasts. Since mechanical deformability, cell-cell adhesion strength and 3D motility may be functionally connected, we investigated whether increased deformability of Rac1 knockout cells correlates with changes in 3D motility. All five Rac1 knockout clones displayed much lower 3D motility than Rac1-expressing controls. Moreover, force exertion was reduced in Rac1 knockout cells, as assessed by 3D fiber displacement analysis. Interference with cellular stiffness through blocking of actin polymerization by Latrunculin A could not further reduce invasion of Rac1 knockout cells. In contrast, Rac1-expressing controls treated with Latrunculin A were again more deformable and less invasive, suggesting actin polymerization is a major determinant of observed Rac1-dependent effects. Together, we propose that regulation of 3D motility by Rac1 partly involves cellular mechanics such as deformability and exertion of forces.
Improving medication adherence in adult kidney transplantation (IMAKT): A pilot randomised controlled trial
Authors: Low Jac Kee , Manias Elizabeth , Crawford Kimberley , Walker Rowan , Mulley William R. , Toussaint Nigel D. , Dooley Michael , Kennedy Elaine , Smith Catherine L. , Nalder Michelle , Yip Doris , Williams Allison
Published: May 2019

Resources to support long-term medication adherence in kidney transplantation are limited. This study aimed to determine the efficacy of an intervention designed for kidney transplant recipients to enhance medication adherence. A single-blind, multi-site, 12-month pilot randomised controlled trial was conducted at all five public hospitals providing adult kidney transplantation in Victoria, Australia. Participants were recruited at 4 to 6 weeks post-transplantation. Thirty-five participants were randomly assigned to a 3-month intervention, involving a face-to-face meeting (a medication review and a consumer-centred video) and health coaching every two weeks. Thirty-six were randomised to receive usual care. All participants were followed for nine months post-intervention. There were no differences in adherence between groups measured by Medication Event Monitoring System (MEMS), however, it was underutilised by 42% of participants. Based on the self-reported Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©) score, the percentage of adherent participants decreased significantly between baseline and 3 to 12 months in the control group (p-values < 0.001) whilst the percentage of adherent participants in the intervention group remained constant over time. No group differences were detected in other outcomes. Due to the complex medication regimen, developing and testing a medication adherence intervention is difficult in kidney transplantation.
Enhanced remyelination during late pregnancy: involvement of the GABAergic system
Authors: Kalakh Samah , Mouihate Abdeslam
Published: May 2019

Pregnant women with MS experience fewer relapses, especially during the third trimester. In this study, we explore the cellular and molecular events that bring about the protective effect of late pregnancy on the course of de/remyelination in rats. Using cellular, molecular, and ultrastructural methods, we explored remyelination in response to a focal demyelination in the corpus callosum of late pregnant, virgin, and postpartum rats. We further explored the role of GABAAreceptor (GABAAR) in the promyelinating effect observed during late pregnancy. Remyelination in response to a gliotoxin-induced demyelination in the corpus callosum was enhanced in late pregnant rats when compared to that seen in virgin and postpartum rats. This pregnancy-associated promyelinating effect was lost when either the GABAAR was blocked or when 5α-reductase, the rate limiting enzyme for the endogenous GABAAR activator allopregnanolone, was inhibited. Taken together, these data suggest that the pregnancy-associated pro-myelination operates, at least in part, through a GABAergic activated system.
Development of a novel multiphysical approach for the characterization of mechanical properties of musculotendinous tissues
Authors: Kammoun Malek , Ternifi Redouane , Dupres Vincent , Pouletaut Philippe , Même Sandra , Même William , Szeremeta Frederic , Landoulsi Jessem , Constans Jean-Marc , Lafont Frank , Subramaniam Malayannan , Hawse John R. , Bensamoun Sabine F.
Published: May 2019

At present, there is a lack of well-validated protocols that allow for the analysis of the mechanical properties of muscle and tendon tissues. Further, there are no reports regarding characterization of mouse skeletal muscle and tendon mechanical properties in vivo using elastography thereby limiting the ability to monitor changes in these tissues during disease progression or response to therapy. Therefore, we sought to develop novel protocols for the characterization of mechanical properties in musculotendinous tissues using atomic force microscopy (AFM) and ultrasound elastography. Given that TIEG1 knockout (KO) mice exhibit well characterized defects in the mechanical properties of skeletal muscle and tendon tissue, we have chosen to use this model system in the present study. Using TIEG1 knockout and wild-type mice, we have devised an AFM protocol that does not rely on the use of glue or chemical agents for muscle and tendon fiber immobilization during acquisition of transversal cartographies of elasticity and topography. Additionally, since AFM cannot be employed on live animals, we have also developed an ultrasound elastography protocol using a new linear transducer, SLH20-6 (resolution: 38 µm, footprint: 2.38 cm), to characterize the musculotendinous system in vivo. This protocol allows for the identification of changes in muscle and tendon elasticities. Such innovative technological approaches have no equivalent to date, promise to accelerate our understanding of musculotendinous mechanical properties and have numerous research and clinical applications.
High fidelity fibre-based physiological sensing deep in tissue
Authors: Choudhary Tushar R. , Tanner Michael G. , Megia-Fernandez Alicia , Harrington Kerrianne , Wood Harry A. , Marshall Adam , Zhu Patricia , Chankeshwara Sunay V. , Choudhury Debaditya , Monro Graham , Ucuncu Muhammed , Yu Fei , Duncan Rory R. , Thomson Robert R. , Dhaliwal Kevin , Bradley Mark
Published: May 2019

Physiological sensing deep in tissue remains a clinical challenge. Here a flexible miniaturised sensing optrode providing a platform to perform minimally invasive in vivo in situ measurements is reported. Silica microspheres covalently coupled with a high density of ratiometrically configured fluorophores were deposited into etched pits on the distal end of a 150 µm diameter multicore optical fibre. With this platform, photonic measurements of pH and oxygen concentration with high precision in the distal alveolar space of the lung are reported. We demonstrated the phenomenon that high-density deposition of carboxyfluorescein covalently coupled to silica microspheres shows an inverse shift in fluorescence in response to varying pH. This platform delivered fast and accurate measurements (±0.02 pH units and ±0.6 mg/L of oxygen), near instantaneous response time and a flexible architecture for addition of multiple sensors.
Influences of age, mental workload, and flight experience on cognitive performance and prefrontal activity in private pilots: a fNIRS study
Authors: Causse Mickaël , Chua Zarrin K. , Rémy Florence
Published: May 2019

The effects of aging on cognitive performance must be better understood, especially to protect older individuals who are engaged in risky activities (e.g. aviation). Current literature on executive functions suggests that brain compensatory mechanisms may counter cognitive deterioration due to aging, at least up to certain task load levels. The present study assesses this hypothesis in private pilots engaged in two executive tasks from the standardized CANTAB battery, namely Spatial Working Memory (SWM) and  One Touch Stockings of Cambridge (OTS). Sixty-one pilots from three age groups (young, middle-aged, older) performed these two tasks from low to very high difficulty levels, beyond those reported in previous aging studies. A fNIRS headband measured changes in oxyhemoglobin (HbO2) in the prefrontal cortex. Results confirmed an overall effect of the difficulty level in the three age groups, with a decline in task performance and an increase in prefrontal HbO2 signal. Performance of older relative to younger pilots was impaired in both tasks, with the greatest impairment observed for the highest-load Spatial Working Memory task. Consistent with this behavioral deficit in older pilots, a plateau of prefrontal activity was observed at this highest-load level, suggesting that a ceiling in neural resources was reached. When behavioral performance was either equivalent between age groups or only slightly impaired in the older group, there were not any age-related differences in prefrontal activity. Finally, older pilots with extensive flying experience tend to show better preserved spatial working memory performance when compared to mildly-experienced of the same age group. The present findings are discussed in the frames of HAROLD and CRUNCH theoretical models of cognitive and neural aging, evoking the possibility that piloting expertise may contribute to preserve executive functions throughout adulthood.
A Simplified, Graded, Electrodiagnostic Criterion for Guillain-Barré Syndrome That Incorporates Sensory Nerve Conduction Studies
Authors: Umapathi Thirugnanam , Lim Christen Sheng Jie , Ng Brandon Chin Jie , Goh Eunice Jin Hui , Ohnmar O.
Published: May 2019

Traditional electrodiagnostic (EDX) criteria for Guillain-Barré Syndrome (GBS), e.g. those delineated by Ho et al. and Hadden et al., rely on motor nerve conduction studies (NCS), and focus on differentiating GBS subtypes instead of the accurate diagnosis of GBS. Sensory studies, including the sural-sparing pattern, are not routinely used in GBS EDX. We studied the utility of a simplified criterion that utilizes sensory NCS. Motor and sensory NCS abnormalities were defined by comparing against age and height adjusted norms derived from 245 controls. We considered the sural-sparing pattern a positive diagnostic feature. We analyzed 109 prospectively validated GBS patients and graded them as “Definite”, “Probable” and “Possible” based on the number of motor and sensory abnormalities detected. Using proposed EDX criteria, 35.8%, 43.1%, 11.9% of all GBS patients were considered “Definite”, “Probable” or “Possible” respectively; whereas traditional EDX criteria only diagnosed 49.5% of cases. 27.5%, 35.3% and 21.6% of patients with the Miller-Fisher Syndrome (MFS) subtype of GBS were considered “Definite”, “Probable” or “Possible” respectively. In comparison, traditional criteria only detected 15.7% of cases. Our proposed EDX criterion, that includes sensory NCS, improves and grades the diagnostic certainty of GBS, especially MFS.
Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma
Authors: Kuriakose Matthew , Younger Daniel , Ravula Arun Reddy , Alay Eren , Rama Rao Kakulavarapu V. , Chandra Namas
Published: May 2019

Blast-induced traumatic brain injury (bTBI) has been recognized as the common mode of neurotrauma amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from our laboratory have identified enhanced blood-brain barrier (BBB) permeability as a significant, sub-acute (four hours post-blast) pathological change in bTBI. We also found that NADPH oxidase (NOX)-mediated oxidative stress occurs at the same time post-blast when the BBB permeability changes. We therefore hypothesized that oxidative stress is a major causative factor in the BBB breakdown in the sub-acute stages. This work therefore examined the role of NOX1 and its downstream effects on BBB permeability in the frontal cortex (a region previously shown to be the most vulnerable) immediately and four hours post-blast exposure. Rats were injured by primary blast waves in a compressed gas-driven shock tube at 180 kPa and the BBB integrity was assessed by extravasation of Evans blue and changes in tight junction proteins (TJPs) as well as translocation of macromolecules from blood to brain and vice versa. NOX1 abundance was also assessed in neurovascular endothelial cells. Blast injury resulted in increased extravasation and reduced levels of TJPs in tissues consistent with our previous observations. NOX1 levels were significantly increased in endothelial cells followed by increased superoxide production within 4 hours of blast. Blast injury also increased the levels/activation of matrix metalloproteinase 3 and 9. To test the role of oxidative stress, rats were administered apocynin, which is known to inhibit the assembly of NOX subunits and arrests its function. We found apocynin completely inhibited dye extravasation as well as restored TJP levels to that of controls and reduced matrix metalloproteinase activation in the sub-acute stages following blast. Together these data strongly suggest that NOX-mediated oxidative stress contributes to enhanced BBB permeability in bTBI through a pathway involving increased matrix metalloproteinase activation.
Predation risk is a function of alternative prey availability rather than predator abundance in a tropical savanna woodland ecosystem
Authors: Nordberg Eric J. , Schwarzkopf Lin
Published: May 2019

Typically, factors influencing predation risk are viewed only from the perspective of predators or prey populations but few studies have examined predation risk in the context of a food web. We tested two competing hypotheses regarding predation: (1) predation risk is dependent on predator density; and (2) predation risk is dependent on the availability of alternative prey sources. We use an empirical, multi-level, tropical food web (birds–lizards–invertebrates) and a mensurative experiment (seasonal fluctuations in abundance and artificial lizards to estimate predation risk) to test these hypotheses. Birds were responsible for the majority of attacks on artificial lizards and were more abundant in the wet season. Artificial lizards were attacked more frequently in the dry than the wet season despite a greater abundance of birds in the wet season. Lizard and invertebrate (alternative prey) abundances showed opposing trends; lizards were more abundant in the dry while invertebrates were more abundant in the wet season. Predatory birds attacked fewer lizards when invertebrate prey abundance was highest, and switched to lizard prey when invertebrate abundance reduced, and lizard abundance was greatest. Our study suggests predation risk is not predator density-dependent, but rather dependent on the abundance of invertebrate prey, supporting the alternative prey hypothesis.
The risk factors of glycemic control, blood pressure control, lipid control in Chinese patients with newly diagnosed type 2 diabetes _ A nationwide prospective cohort study
Authors: Cai Xiaoling , Hu Dayi , Pan Changyu , Li Guangwei , Lu Juming , Ji Qiuhe , Su Benli , Tian Haoming , Qu Shen , Weng Jianping , Zhang Danyi , Xu Jie , Ji Linong
Published: May 2019

Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered atwww.clinicaltrials.gov(NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.
Interaction effect of oxytocin receptor (OXTR) rs53576 genotype and maternal postpartum depression on child behavioural problems
Authors: Choi Damee , Tsuchiya Kenji J. , Takei Nori
Published: May 2019

Previous studies have reported interaction effects of oxytocin receptor genotype (rs53576) and environmental factors on mental health in youth. However, the findings are mixed, especially regarding the type of allele (i.e., A vs. G), and it remains unanswered whether such an interaction presents at an early stage of development. Thus, using a unique longitudinal birth cohort sample in Japan (n = 568), we examined whether there was an effect of the interaction between the OXTR rs53576 genotype and maternal postpartum depression, as an environmental risk, on behavioural problems in children. Child behavioural problems (internalising and externalising problems) were ascertained using the Strengths and Difficulties Questionnaire when children were 6 years old. Maternal postpartum depression was measured using the Edinburgh Postnatal Depression Scale when children were at 2 months and 10 months of age. The results revealed a significant effect in the interaction between OXTR rs53576 genotype and maternal postpartum depression on externalising problems in children with AA genotype (β = 0.136, 95% CI 0.032 to 0.240), but not in those with GG/GA genotype. This indicates that an interaction of vulnerable genotypes (i.e., A allele of OXTR rs53576) with an environmental burden (i.e. maternal postpartum depression) may be one of the potential elements that predisposes the infant to developing behavioural problems early in life. Hence, special attention needs to be paid to children exposed to environmental risks such as maternal postpartum depression, to facilitate the provision of appropriate care.