bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering Role of Wnt Signalling in Cardiac Mesoderm and Cardiomyocyte Differentiation from Human iPSCs: Four-dimensional control of Wnt pathway for hiPSC-CMs differentiation
Authors: Zhao Meng , Tang Yawen , Zhou Yang , Zhang Jianyi 
Published: December 2019

AbstractDifferentiation of cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) is critically dependent upon the regulation of the Wnt signaling pathway. The mechanisms remain unclear with regard to the dose and timing of each differentiation inducer, and the interaction of the inducers that regulate the Wnt in mesendoderm specification to cardiac mesoderm. Consequently, it remains far from optimal in differentiation efficiency and consistency from hiPSC lines to CMs. Here, we have carefully deciphered the role of Wnt signaling pathway manipulation on mesoderm specification in a dosage and time dependent manner. To examine the hypothesis of that fate specification of hiPSC-CMs differentiation is dictated by temporal and spatial factors that regulate Wnt, we evaluate hiPSC-CM differentiation with: (1) two-phase modulation of Wnt, (2) dosage variant of GSK3β inhibitors, (3) treatment with insulin, and (4) 3-dimentional suspension culture environment on iPSC-CM differentiation. The results highlight the importance of mesendoderm specification to cardiac mesoderm, which needs precisely regulation of Wnt in a dosage dependent and temporal on/off manner. This temporal regulation dictates the final efficiency and purity of derived cardiomyocytes. After the initial activation of Wnt signaling pathway to generate mesendoderm, the maintenance of Wnt signaling at an appropriate dose is critical to direct the cell fate into cardiac mesoderm. Otherwise, lower Wnt signals lead to definitive endoderm and higher Wnt signals induce presomitic mesoderm differentiation. The precisely specification of cardiac mesoderm results in not only greater than 90% of cTnT+ cardiomyocytes but also high cardiomyocytes yield under both monolayer and suspension culture conditions. Thus, the current findings provide critical insights to decipher the temporal mechanism of Wnt activation in regulation of hiPSC-CMs differentiation, and more importantly provide the guidelines for the consistent and high-yield and high-quality hiPSC-CMs production in cardiovascular research.
Anderson localisation in steady states of microcavity polaritons
Authors: Sturges Thomas J. , Anderson Mitchell D. , Buraczewski Adam , Navadeh-Toupchi Morteza , Adiyatullin Albert F. , Jabeen Fauzia , Oberli Daniel Y. , Portella-Oberli Marcia T. , Stobińska Magdalena 
Published: December 2019

AbstractWe present an experimental signature of the Anderson localisation of microcavity polaritons, and provide a systematic study of the dependence on disorder strength. We reveal a controllable degree of localisation, as characterised by the inverse-participation ratio, by tuning the positional disorder of arrays of interacting mesas. This constitutes the realisation of disorder-induced localisation in a driven-dissipative system. In addition to being an ideal candidate for investigating localisation in this regime, microcavity polaritons hold promise for low-power, ultra-small devices and their localisation could be used as a resource in quantum memory and quantum information processing.
Methane hydrate emergence from Lake Baikal: direct observations, modelling, and hydrate footprints in seasonal ice cover
Authors: Granin N. G. , Aslamov I. A. , Kozlov V. V. , Makarov M. M. , Kirillin G. , McGinnis D. F. , Kucher K. M. , Blinov V. V. , Ivanov V. G. , Mizandrontsev I. B. , Zhdanov A. A. , Anikin A. S. , Granin M. N. , Gnatovsky R. Yu. 
Published: December 2019

AbstractThis paper provides a novel report of methane hydrates rising from bottom sediments to the surface of Lake Baikal, validated by photo and video records. The ascent of hydrates in the water column was confirmed by hydroacoustic data showing rising objects with velocities significantly exceeding the typical speeds (18–25 cm s−1) of gas bubbles. Mathematical modelling along with velocity and depth estimates of the presumed methane hydrates coincided with values observed from echograms. Modelling results also showed that a methane hydrate fragment with initial radius of 2.5 cm or greater could reach the surface of Lake Baikal given summer water column temperature conditions. Results further show that while methane bubbles released from the deep sedimentary reservoir would dissolve in the Lake Baikal water column, transport in hydrate form is not only viable but may represent a previously overlooked source of surface methane with subsequent emissions to the atmosphere. Methane hydrates captured within the ice cover may also cause the formation of unique ice structures and morphologies observed around Lake Baikal. Sampling of these ice structures detected methane content that exceeded concentrations measured in surrounding ice and from the atmosphere demonstrating a link with the methane transport processes described here.
Schizophyllum commune induces IL-17-mediated neutrophilic airway inflammation in OVA-induced asthma model mice
Authors: Hanashiro Jun , Muraosa Yasunori , Toyotome Takahito , Hirose Koichi , Watanabe Akira , Kamei Katsuhiko 
Published: December 2019

AbstractSchizophyllum communeis a ubiquitous basidiomycetous fungus typically found across the world, which has been detected in indoor and outdoor air. Some studies indicated that sensitization toS. communeis correlated with asthma severity in patients. Patients with chronic severe or acute fatal asthma have neutrophil-dominant airway inflammation. We hypothesized thatS. communecan exacerbate asthma. To test this hypothesis, we evaluated the direct immunomodulatory activities ofS. communein allergic airway inflammation induced by non-fungal sensitization. Ovalbumin (OVA)-induced asthma model mice were generated using wild-type (WT) andIl-17a−/−Il-17f−/−mice that were intratracheally exposed toS. commune, then immune responses in the lungs were assessed after 24 h. Intratracheal administration ofS. communein OVA-induced asthma model mice enhanced neutrophilic airway inflammation, increased the mRNA expression ofCXCL1andCXCL2in the lungs, and provoked IL-17A, and IL-17F production in BAL fluid. In addition, neutrophilic airway inflammation was significantly inhibited inIl-17a−/−Il-17f−/−mice compared with those found in WT mice. We demonstrated thatS. communeinduces neutrophilic airway inflammation in OVA-induced asthma model mice, and IL-17A and IL-17F had central roles in this activity. AsS. communeinhabits the general environment, including indoor and outdoor air, our results suggested thatS. communeis a causative agent of asthma exacerbation. This study has provided clues regarding the mechanisms behind fungi and asthma exacerbation.
Impact of Grafting, Salinity and Irrigation Water Composition on Eggplant Fruit Yield and Ion Relations
Authors: Semiz Gülüzar Duygu , Suarez Donald L. 
Published: December 2019

AbstractScarcity of fresh water in arid and semi-arid regions means that we must use more saline waters for irrigation and develop tools to improve crop salt tolerance. The objectives of our study were to (1) Evaluate fruit production, salt tolerance and ion composition of eggplant cv Angela, both nongrafted and when grafted on tomato cv Maxifort rootstock and (2) Evaluate eggplant specific toxicity effect of Cl−and Na+ions under saline conditions. We salinized the irrigation water with either a Na+-Ca2+- Cl−composition typical of coastal Mediterranean ground waters as well as a mixed Na+-Ca2+-SO42−Cl−type water, a composition more typical of interior continental basin ground. For each water type we evaluated 5 different salinity (osmotic) levels of –0.003 (control), –0.15, –0.30, –0.45 and –0.60 MPa. There were no statistically significant differences in the fruit yield relative to the water type, indicating that Cl−ion toxicity is not a major factor in eggplant yield associated with salinity. This conclusion was confirmed by the determination that leaf Cl content was not correlated with relative yield. The electrical conductivity of the saturation extract (ECe) at which yield is predicted to be reduced by 50% was 4.6 dS m−1for the grafted plants vs. 1.33 dS m−1for the nongrafted plants. The relative yield was very well correlated to leaf Na concentrations regardless of grafting status, indicating that Na is the toxic ion responsible for eggplant yield loss under saline conditions. The increased salt tolerance of cv Angela eggplant when grafted onto tomato Maxifort rootstock is attributed to a reduced Na uptake and increased Ca and K uptake with Maxifort rootstock.
Simultaneous detection and comprehensive analysis of HPV and microbiome status of a cervical liquid-based cytology sample using Nanopore MinION sequencing
Authors: Quan Lili , Dong Ruyi , Yang Wenjuan , Chen Lanyou , Lang Jidong , Liu Jia , Song Yu , Ma Shuiqing , Yang Jialiang , Wang Weiwei , Meng Bo , Tian Geng 
Published: December 2019

AbstractHuman papillomavirus (HPV) is a major pathogen that causes cervical cancer and many other related diseases. HPV infection related cervical microbiome could be an induce factor of cervical cancer. However, it is uncommon to find a single test on the market that can simultaneously provide information on both HPV and the microbiome. Herein, a novel method was developed in this study to simultaneously detect HPV infection and microbiota composition promptly and accurately. It provides a new and simple way to detect vaginal pathogen situation and also provide valuable information for clinical diagnose. This approach combined multiplex PCR, which targeted both HPV16 E6E7 and full-length 16S rRNA, and Nanopore sequencing to generate enough information to understand the vagina condition of patients. One HPV positive liquid-based cytology (LBC) sample was sequenced and analyzed. After comparing with Illumina sequencing, the results from Nanopore showed a similar microbiome composition. An instant sequencing evaluation showed that 15 min sequencing is enough to identify the top 10 most abundant bacteria. Moreover, two HPV integration sites were identified and verified by Sanger sequencing. This approach has many potential applications in pathogen detection and can potentially aid in providing a more rapid clinical diagnosis.
pKa of opioid ligands as a discriminating factor for side effects
Authors: Del Vecchio Giovanna , Labuz Dominika , Temp Julia , Seitz Viola , Kloner Michael , Negrete Roger , Rodriguez-Gaztelumendi Antonio , Weber Marcus , Machelska Halina , Stein Christoph 
Published: December 2019

AbstractThe non-selective activation of central and peripheral opioid receptors is a major shortcoming of currently available opioids. Targeting peripheral opioid receptors is a promising strategy to preclude side effects. Recently, we showed that fentanyl-derived μ-opioid receptor (MOR) agonists with reduced acid dissociation constants (pKa) due to introducing single fluorine atoms produced injury-restricted antinociception in rat models of inflammatory, postoperative and neuropathic pain. Here, we report that a new double-fluorinated compound (FF6) and fentanyl show similar pKa, MOR affinity and [35S]-GTPγS binding at low and physiological pH values. In vivo, FF6 produced antinociception in injured and non-injured tissue, and induced sedation and constipation. The comparison of several fentanyl derivatives revealed a correlation between pKa values and pH-dependent MOR activation, antinociception and side effects. An opioid ligand’s pKa value may be used as discriminating factor to design safer analgesics.
Age-related sensory decline mediates the Sound-Induced Flash Illusion: Evidence for reliability weighting models of multisensory perception
Authors: Hirst Rebecca J. , Setti Annalisa , Kenny Rose A. , Newell Fiona N. 
Published: December 2019

AbstractPerception of our world is proposed to arise from combining multiple sensory inputs according to their relative reliability. We tested multisensory processes in a large sample of 2920 older adults to assess whether sensory ability mediates age-related changes in perception. Participants completed a test of audio-visual integration, the Sound Induced Flash Illusion (SIFI), alongside measures of visual (acuity, contrast sensitivity, self-reported vision and visual temporal discrimination (VTD)) and auditory (self-reported hearing and auditory temporal discrimination (ATD)) function. Structural equation modelling showed that SIFI susceptibility increased with age. This was mediated by visual acuity and self-reported hearing: better scores on these measures predicted reduced and stronger SIFI susceptibility, respectively. Unexpectedly, VTD improved with age and predicted increased SIFI susceptibility. Importantly, the relationship between age and SIFI susceptibility remained significant, even when considering mediators. A second model showed that, with age, visual ‘gain’ (the benefit of congruent auditory information on visual judgements) was predicted by ATD: better ATD predicted stronger visual gain. However, neither age nor SIFI susceptibility were directly associated with visual gain. Our findings illustrate, in the largest sample of older adults to date, how multisensory perception is influenced, but not fully accounted for, by age-related changes in unisensory abilities.
X-ray-based virtual slicing of TB-infected lungs
Authors: Ortega-Gil Ana , Vaquero Juan José , Gonzalez-Arjona Mario , Rullas Joaquín , Muñoz-Barrutia Arrate 
Published: December 2019

AbstractHollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray–based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.
Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions
Authors: Schneider Augusto , Wood Hillary N. , Geden Sandra , Greene Catherine J. , Yates Robin M. , Masternak Michal M. , Rohde Kyle H. 
Published: December 2019

AbstractMacrophages are an important component of the innate immune response. Priming and activation of macrophages is stimulated by cytokines (i.e IFNγ). However, growth hormone (GH) can also stimulate macrophage activation. Based on these observations, the goal of this work was to 1) to compare the transcriptome profile of macrophages activatedin vitrowith GH and IFNγ, and 2) to assess the impact of GH on key macrophage functional properties like reactive oxygen species (ROS) production and phagosomal proteolysis. To assess the global transcriptional and functional impact of GH on macrophage programming, bone marrow derived macrophages were treated with GH or IFNγ. Our data strongly support a potential link between GH, which wanes with age, and impaired macrophage function. The notable overlap of GH with IFNγ-induced pathways involved in innate immune sensing of pathogens and antimicrobial responses argue for an important role for GH in macrophage priming and maturation. By using functional assays that report on biochemical activities within the lumen of phagosomes, we have also shown that GH alters physiologically relevant processes such as ROS production and proteolysis. These changes could have far reaching impacts on antimicrobial capacity, signaling, and antigen presentation.
A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease
Authors: Li Fei , Duan Jialin , Zhao Meina , Huang Shaojie , Mu Fei , Su Jing , Liu Kedi , Pan Yang , Lu Xinming , Li Jing , Wei Peifeng , Xi Miaomiao , Wen Aidong 
Published: December 2019

AbstractSalvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.
How Responsiveness From a Communication Partner Affects Story Retell in Aphasia: Quantitative and Qualitative Findings
Authors: Harmon Tyson G. , Jacks Adam , Haley Katarina L. , Bailliard Antoine 
Published: December 2019

Purpose
Because people with aphasia (PWA) frequently interact with partners who are unresponsive to their communicative attempts, we investigated how partner responsiveness affects quantitative measures of spoken language and subjective reactions during story retell.

Method
A quantitative study and a qualitative study were conducted. In Study 1, participants with aphasia and controls retold short stories to a communication partner who indicated interest through supportive backchannel responses (responsive) and another who indicated disinterest through unsupportive backchannel responses (unresponsive). Story retell accuracy, delivery speed, and ratings of psychological stress were measured and compared. In Study 2, participants completed semistructured interviews about their story retell experience, which were recorded, transcribed, and coded using qualitative analysis software.

Results
Quantitative results revealed increased psychological stress and decreased delivery speed across all participant groups during the unresponsive partner condition. Effects on delivery speed were more consistent for controls than participants with aphasia. Qualitative results revealed that participants with aphasia were more attuned to unresponsive partner behaviors than controls and reported stronger and more frequent emotional reactions. Partner responsiveness also affected how PWA perceived and coped with the communication experience.

Conclusions
Combined quantitative and qualitative findings suggest that, while unresponsive communication partners may not have robust effects on spoken language, they elicit strong emotional reactions from PWA and affect their communication experience. These findings support the need for communication partner training and suggest that training PWA on emotion regulation or relaxation techniques may help assuage their anxiety during socially challenging everyday communication and increase social participation.

Supplemental Material

https://doi.org/10.23641/asha.11368028
The nature of the NGC 2546: Not one but two open clusters
Authors: Alejo A. D. , González J. F. , Veramendi M. E. 
Published: December 2019

Context.As part of a broader project on the role of binary stars in clusters, we present a spectroscopic study of the open cluster NGC 2546, which is a large cluster lacking previous spectroscopic analysis.Aims.We report the finding of two open clusters in the region of NGC 2546. For the two star groups, we determine radial velocity, parallax, proper motion, reddening, distance modulus, and age, using our spectroscopic observations and available photometric and astrometric data, mainly from the secondGaiadata release (Gaia-DR2). We also determine the orbit of four spectroscopic binaries in these open clusters.Methods.From mid-resolution spectroscopic observations for 28 stars in the NGC 2546 region, we determined radial velocities and evaluate velocity variability. To analyze double-lined spectroscopic binaries, we used a spectral separation technique and fit the spectroscopic orbits using a least-squares code. The presence of two stellar groups is suggested by the radial velocity distribution and confirmed by available photometric and astrometric data. We applied a multi-criteria analysis to determine cluster membership, and obtained kinematic and physical parameters of the clusters.Results.NGC 2546 is actually two clusters, NGC 2546A and NGC 2546B, which are not physically related to each other. NGC 2546A has an age of about 180 Myr and a distance of 950 pc. It has a half-number radius of 8 pc and contains about 480 members brighter thanG = 18 mag. NGC 2546B is a very young cluster (<10 Myr) located at a distance of 1450 pc. It is a small cluster with 80 members and a half-number radius of 1.6 pc. Stars less massive than 2.5M⊙in this cluster would be pre-main-sequence objects. We detected four spectroscopic binaries and determined their orbits. The two binaries of NGC 2546A contain chemically peculiar components: HD 68693 is composed of two mercury-manganese stars and HD 68624 has a Bp silicon secondary. Among the most massive objects of NGC 2546B, there are two binary stars: HD 68572, withP = 124.2 d, and CD -37 4344 withP = 10.4 d.