bluuebunny/crossref_metadata_2025 huggingface dataset:
Coethnicity and Corruption: Field Experimental Evidence from Public Officials in Malawi
Authors: Seim Brigitte , Robinson Amanda Lea
Published: April 2019

Corruption is widespread in many developing countries, though public officials’ discretion in the solicitation of bribes may expose some citizens to more corruption than others. We derive expectations about how shared ethnicity between government officials and citizens should influence the likelihood of bribe solicitation. We evaluate these expectations through a field experiment in which Malawian confederates seek electricity connections from real government offices – an interaction that is often accompanied by bribe solicitation. Our field experiment exogenously varied coethnicity between the official and the confederate. We find that coethnicity increases the likelihood of expediting an electricity connection, both with and without a bribe, which we interpret as evidence of parochial corruption.
Akuter ischämischer Hirnschlag – Update
Authors: Heldner Mirjam R. , Kaesmacher Johannes , Mordasini Pasquale , Fischer Urs
Published: April 2019

Zusammenfassung. Durch eine intravenöse Thrombolyse und / oder endovaskuläre Therapie können bei korrekter Patientenselektion trotz möglicher Gefahr von Blutungskomplikationen Langzeitbehinderungen beim akuten ischämischen Hirnschlag gesenkt werden. Die neusten Studien untersuchten intravenöse Thrombolyse mit rt-PA im > 4.5 Stunden-Zeitfenster und bei unklarem Symptombeginn, Tenecteplase als intravenöses Thrombolytikum mit und ohne endovaskuläre Therapie, endovaskuläre Therapie im > 6 – 24 Stunden-Zeitfenster und bei unklarem Symptombeginn sowie die Prognose in Abhängigkeit von Vollnarkose oder Sedierung während der endovaskulären Therapie.
Testing the Strain Theory of Suicide – The Moderating Role of Social Support
Authors: Lew Bob , Chistopolskaya Ksenia , Liu Yanzheng , Talib Mansor Abu , Mitina Olga , Zhang Jie
Published: April 2019

Abstract. Background: According to the strain theory of suicide, strains, resulting from conﬂicting and competing pressures in an individual's life, are hypothesized to precede suicide. But social support is an important factor that can mitigate strains and lessen their input in suicidal behavior. Aims: This study was designed to assess the moderating role of social support in the relation between strain and suicidality. Methods: A sample of 1,051 employees were recruited in Beijing, the capital of China, through an online survey. Moderation analysis was performed using SPSS PROCESS Macro. Social support was measured with the Multidimensional Scale of Perceived Social Support, and strains were assessed with the Psychological Strains Scale. Results: Psychological strains are a good predictor of suicidality, and social support, a basic need for each human being, moderates and decreases the effects of psychological strains on suicidality. Limitations: The cross-sectional survey limited the extent to which conclusions about causal relationships can be drawn. Furthermore, the results may not be generalized to the whole of China because of its diversity. Conclusion: Social support has a tendency to mitigate the effects of psychological strains on suicidality.
High‐Resolution Mg/Ca Measurements of Foraminifer Shells Using Femtosecond LA‐ICP‐MS for Paleoclimate Proxy Development
Authors: Jochum K. P. , Jentzen A. , Schiebel R. , Stoll B. , Weis U. , Leitner J. , Repschläger J. , Nürnberg D. , Haug G. H.
Published: April 2019

Determination of Mg/Ca in foraminifer shells as a proxy of seawater temperature is of particular interest in paleoclimate reconstruction. Here we show that femtosecond–200 nm–laser ablation–inductively coupled plasma–mass spectrometry is a suitable technique to precisely and accurately determine Mg/Ca in the micrometer‐sized calcareous chambers of foraminifers. At low fluence (0.3–0.6 J/cm2) the double‐charged 44Ca++ and the single‐charged 25Mg+ ions are measured nearly simultaneously. Integrated single‐shot measurements using a pulse repetition rate of 1 Hz enable precise analyses at a depth resolution of about 50–100 nm/pulse corresponding to an ablated material of 0.3–0.6 ng calcite/pulse for a spot size of 55 μm. High‐resolution analyses can be performed until a depth of 10–20 μm and thus particularly suitable for thin‐shelled foraminifers. Reproducibility (relative standard deviation) is about 5% as approved by homogeneous reference materials. Calibration is performed with the microanalytical synthetic reference material MACS‐3. Magnesium and Ca data of different carbonate and silicate reference materials agree within uncertainties with reference values. The procedure has been successfully applied for detailed analyses of single chambers and shell‐depth profiles of live individuals and empty planktic and benthic foraminifer tests from different ocean basins.
Polarization Electric Field Inside Auroral Patches: Simultaneous Experiment of EISCAT Radars and KAIRA
Authors: Takahashi Toru , Virtanen Ilkka I. , Hosokawa Keisuke , Ogawa Yasunobu , Aikio Anita , Miyaoka Hiroshi , Kero Antti
Published: April 2019

The primary focus of this study was the motion of auroral patches and the polarization electric field generated therein observed on 9 November 2015 in an experiment using the European incoherent scatter (EISCAT) radars, Kilpisjärvi Atmospheric Imaging Receiver Array (KAIRA), and an all‐sky imager simultaneously. Based on the all‐sky imager data, the drift speed of the auroral patches corresponded to a southward electric field of 14.1( ± 3.7)–17.2( ± 4.5) mV/m. The convective electric field derived from the EISCAT radars and KAIRA observation was approximately 14.6 mV/m in the southward direction. This suggest that the spatial distribution of the auroral patches reflects the distribution of the cold plasma in the magnetosphere. The electron density and the height‐integrated Hall conductance between 80 and 120 km were enhanced by a factor of 2–4 inside the auroral patches. In this situation, a polarization electric field was generated therein. Enhanced ion velocities due to the polarization electric field was observed at up to 200‐km altitude; however, the absolute values of the ion velocities were approximately 40% of what was expected from the polarization electric field. A field‐aligned current (FAC) from 5 to 10 μA/m−2 in the edges of the auroral patches could explain the weakening of the polarization electric field. Since a FAC of that order of magnitude corresponded with that observed by the Swarm satellite, it was suggested that the polarization electric field was weakened by the FAC. Furthermore, the polarization electric field propagated upward from the dynamo region to at least 200 km.
AERONET Remotely Sensed Measurements and Retrievals of Biomass Burning Aerosol Optical Properties During the 2015 Indonesian Burning Season
Authors: Eck T. F. , Holben B. N. , Giles D. M. , Slutsker I. , Sinyuk A. , Schafer J. S. , Smirnov A. , Sorokin M. , Reid J. S. , Sayer A. M. , Hsu N. C. , Shi Y. R. , Levy R. C. , Lyapustin A. , Rahman Muhammad Arif , Liew Soo‐Chin , Salinas Cortijo Santo V. , Li Tan , Kalbermatter Daniel , Keong Kwoh Leong , Yuggotomo Muhammad Elifant , Aditya Fanni , Mohamad Maznorizan , Mahmud Mastura , Chong Tan Kok , Lim Hwee‐San , Choon Yeap Eng , Deranadyan Gumilang , Kusumaningtyas Sheila D. A. , Aldrian Edvin
Published: April 2019

An extreme biomass burning event occurred in Indonesia from September through October 2015 due to severe drought conditions, partially caused by a major El Niño event, thereby allowing for significant burning of peatland that had been previously drained. This event had the highest sustained aerosol optical depths (AODs) ever monitored by the global Aerosol Robotic Network (AERONET). The newly developed AERONET Version 3 algorithms retain high AOD at the longer wavelengths when associated with high Ångström exponents (AEs), which thereby allowed for measurements of AOD at 675 nm as high as approximately 7, the upper limit of Sun photometry. Measured AEs at the highest monitored AOD levels were subsequently utilized to estimate instantaneous values of AOD at 550 nm in the range of 11 to 13, well beyond the upper measurement limit. Additionally, retrievals of complex refractive indices, size distributions, and single scattering albedos (SSAs) were obtained at much higher AOD levels than possible from almucantar scans due to the ability to perform retrievals at smaller solar zenith angles with new hybrid sky radiance scans. For retrievals made at the highest AOD levels the fine‐mode volume median radii were ~0.25–0.30 micron, which are very large particles for biomass burning. Very high SSA values (~0.975 from 440 to 1,020 nm) are consistent with the domination by smoldering combustion of peat burning. Estimates of the percentage peat contribution to total biomass burning aerosol based on retrieved SSA and laboratory measured peat SSA were ~80–85%, in excellent agreement with independent estimates.
Using Ghost Fronts Within STEREO Heliospheric Imager Data to Infer the Evolution in Longitudinal Structure of a Coronal Mass Ejection
Authors: Scott C. J. , Owens M. J. , de Koning C. A. , Barnard L. A. , Jones S. R. , Wilkinson J.
Published: April 2019

Images of coronal mass ejections (CMEs) from the Heliospheric Imager instruments on board the Solar Terrestrial Relations Observatory (STEREO) spacecraft frequently contain rich structure. Here, we present analysis of the Earth‐directed CME launched on 12 December 2008 in which we interpret the revealed structure as projections of separate discrete sections of the physical boundary of the CME. By comparing the relative position of the outer and inner “ghost” fronts seen in the STEREO Heliospheric Imager 1 cameras with the positions of features determined from three CME models, we show that the two fronts seen in the images correspond to the expected position of the flank and nose of the CME where the background solar wind is uniform. In contrast, the flank of the CME observed expanding into a structured background solar wind results in the elongation between the two fronts being greater than expected. This is consistent with the CME flank distorting in the presence of a high‐speed solar wind stream. Further work is required to consolidate these results. The presence of a shock for this event was ruled out by consideration of the low CME speed and by studying in situ spacecraft data. The CME flank crossing the Thomson sphere was also ruled out as a cause of the ghost fronts. Ghost fronts could provide information about the longitudinal shape of the CME independent of geometric models. This technique could subsequently be used to improve space weather forecast models through techniques such as data assimilation.
Hypomethylation at non-CpG/CpG sites in the promoter of HIF-1α gene combined with enhanced H3K9Ac modification contribute to maintain higher HIF-1α expression in breast cancer
Authors: Li Chun , Xiong Wei , Liu Xiong , Xiao Wenjun , Guo Yuxian , Tan Junyu , Li Yaochen
Published: April 2019

HIF-1α has a broad impact on tumors, including enhanced utilization of glucose, tumor cell stemness, migration, metastasis and so on. In pilot study, we found that the expression of HIF-1α significantly increased in breast cancer cell lines and tissue samples with higher malignant behaviors and decreased in luminal subtype breast cancer cells and tissue samples. We analyzed and found there is one large CpG island in HIF-1α promoter around transcription start site, and the hypermethylation occurred at these CpGs and their surrounding non-CpGs sites. Epigenetic events driving tumorigenesis has been characterized. However, knowledge is lacking on the non-CpGs methylation of HIF-1α promoter in breast cancer cells. We validated that non-CpGs methylation can directly regulate HIF-1α expression by luciferase activity assay. We also found DNMT3a and Mecp2 play vital role in methylation at non-CpGs and CpGs sites. In addition, we noticed that H3K9ac modification could promote the transcription of HIF-1α in MDA-MB-231 cells by binding to the region contained hypomethylated non-CpG and CpG sites. Taken together, the hypomethylation status at non-CpG and CpG loci in HIF-1α promoter and H3K9ac modification together contribute to maintain higher HIF-1αactivity in invasive breast cancer cells when compared with the non-invasive breast cancer cells, which may establish a tissue-specific epigenetic modification pattern and point to the new directions for future understanding breast cancer therapy.
Decoupling tRNA promoter and processing activities enables specific Pol-II Cas9 guide RNA expression
Authors: Knapp David J. H. F. , Michaels Yale S. , Jamilly Max , Ferry Quentin R. V. , Barbosa Hector , Milne Thomas A. , Fulga Tudor A.
Published: April 2019

Spatial/temporal control of Cas9 guide RNA expression could considerably expand the utility of CRISPR-based technologies. Current approaches based on tRNA processing offer a promising strategy but suffer from high background. Here, to address this limitation, we present a screening platform which allows simultaneous measurements of the promoter strength, 5′, and 3′ processing efficiencies across a library of tRNA variants. This analysis reveals that the sequence determinants underlying these activities, while overlapping, are dissociable. Rational design based on the ensuing principles allowed us to engineer an improved tRNA scaffold that enables highly specific guide RNA production from a Pol-II promoter. When benchmarked against other reported systems this tRNA scaffold is superior to most alternatives, and is equivalent in function to an optimized version of the Csy4-based guide RNA release system. The results and methods described in this manuscript enable avenues of research both in genome engineering and basic tRNA biology.
Structural and biochemical evidence supporting poly ADP-ribosylation in the bacterium Deinococcus radiodurans
Authors: Cho Chao-Cheng , Chien Chia-Yu , Chiu Yi-Chih , Lin Meng-Hsuan , Hsu Chun-Hua
Published: April 2019

Poly-ADP-ribosylation, a post-translational modification involved in various cellular processes, is well characterized in eukaryotes but thought to be devoid in bacteria. Here, we solve crystal structures of ADP-ribose–bound poly(ADP-ribose)glycohydrolase from the radioresistant bacterium Deinococcus radiodurans (DrPARG), revealing a solvent-accessible 2’-hydroxy group of ADP-ribose, which suggests that DrPARG may possess endo-glycohydrolase activity toward poly-ADP-ribose (PAR). We confirm the existence of PAR in D. radiodurans and show that disruption of DrPARG expression causes accumulation of endogenous PAR and compromises recovery from UV radiation damage. Moreover, endogenous PAR levels in D. radiodurans are elevated after UV irradiation, indicating that PARylation may be involved in resistance to genotoxic stresses. These findings provide structural insights into a bacterial-type PARG and suggest the existence of a prokaryotic PARylation machinery that may be involved in stress responses.
The computational and neural substrates of moral strategies in social decision-making
Authors: van Baar Jeroen M. , Chang Luke J. , Sanfey Alan G.
Published: April 2019

Individuals employ different moral principles to guide their social decision-making, thus expressing a specific ‘moral strategy’. Which computations characterize different moral strategies, and how might they be instantiated in the brain? Here, we tackle these questions in the context of decisions about reciprocity using a modified Trust Game. We show that different participants spontaneously and consistently employ different moral strategies. By mapping an integrative computational model of reciprocity decisions onto brain activity using inter-subject representational similarity analysis of fMRI data, we find markedly different neural substrates for the strategies of ‘guilt aversion’ and ‘inequity aversion’, even under conditions where the two strategies produce the same choices. We also identify a new strategy, ‘moral opportunism’, in which participants adaptively switch between guilt and inequity aversion, with a corresponding switch observed in their neural activation patterns. These findings provide a valuable view into understanding how different individuals may utilize different moral principles.
Crizotinib-induced immunogenic cell death in non-small cell lung cancer
Authors: Liu Peng , Zhao Liwei , Pol Jonathan , Levesque Sarah , Petrazzuolo Adriana , Pfirschke Christina , Engblom Camilla , Rickelt Steffen , Yamazaki Takahiro , Iribarren Kristina , Senovilla Laura , Bezu Lucillia , Vacchelli Erika , Sica Valentina , Melis Andréa , Martin Tiffany , Xia Lin , Yang Heng , Li Qingqing , Chen Jinfeng , Durand Sylvère , Aprahamian Fanny , Lefevre Deborah , Broutin Sophie , Paci Angelo , Bongers Amaury , Minard-Colin Veronique , Tartour Eric , Zitvogel Laurence , Apetoh Lionel , Ma Yuting , Pittet Mikael J. , Kepp Oliver , Kroemer Guido
Published: April 2019

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.
Resolution of the ordinal phylogeny of mosses using targeted exons from organellar and nuclear genomes
Authors: Liu Yang , Johnson Matthew G. , Cox Cymon J. , Medina Rafael , Devos Nicolas , Vanderpoorten Alain , Hedenäs Lars , Bell Neil E. , Shevock James R. , Aguero Blanka , Quandt Dietmar , Wickett Norman J. , Shaw A. Jonathan , Goffinet Bernard
Published: April 2019

Mosses are a highly diverse lineage of land plants, whose diversification, spanning at least 400 million years, remains phylogenetically ambiguous due to the lack of fossils, massive early extinctions, late radiations, limited morphological variation, and conflicting signal among previously used markers. Here, we present phylogenetic reconstructions based on complete organellar exomes and a comparable set of nuclear genes for this major lineage of land plants. Our analysis of 142 species representing 29 of the 30 moss orders reveals that relative average rates of non-synonymous substitutions in nuclear versus plastid genes are much higher in mosses than in seed plants, consistent with the emerging concept of evolutionary dynamism in mosses. Our results highlight the evolutionary significance of taxa with reduced morphologies, shed light on the relative tempo and mechanisms underlying major cladogenic events, and suggest hypotheses for the relationships and delineation of moss orders.
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
Authors: Kranzler Henry R. , Zhou Hang , Kember Rachel L. , Vickers Smith Rachel , Justice Amy C. , Damrauer Scott , Tsao Philip S. , Klarin Derek , Baras Aris , Reid Jeffrey , Overton John , Rader Daniel J. , Cheng Zhongshan , Tate Janet P. , Becker William C. , Concato John , Xu Ke , Polimanti Renato , Zhao Hongyu , Gelernter Joel
Published: April 2019

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.
The lncRNA Neat1 promotes activation of inflammasomes in macrophages
Authors: Zhang Pengfei , Cao Limian , Zhou Rongbin , Yang Xiaolu , Wu Mian
Published: April 2019

The inflammasome has an essential function in innate immune, responding to a wide variety of stimuli. Here we show that the lncRNANeat1promotes the activation of several inflammasomes.Neat1associates with the NLRP3, NLRC4, and AIM2 inflammasomes in mouse macrophages to enhance their assembly and subsequent pro-caspase-1 processing.Neat1also stabilizes the mature caspase-1 to promote interleukin-1β production and pyroptosis. Upon stimulation with inflammasome-activating signals,Neat1, which normally resides in the paraspeckles, disassociates from these nuclear bodies and translocates to the cytoplasm to modulate inflammasome activation using above mechanism.Neat1is also up-regulated under hypoxic conditions in a HIF-2α-dependent manner, mediating the effect of hypoxia on inflammasomes. Moreover, in the mouse models of peritonitis and pneumonia,Neat1deficiency significantly reduces inflammatory responses. These results reveal a previously unrecognized role of lncRNAs in innate immunity, and suggest thatNeat1is a common mediator for inflammasome stimuli.
Cortex-wide neural interfacing via transparent polymer skulls
Authors: Ghanbari Leila , Carter Russell E. , Rynes Mathew L. , Dominguez Judith , Chen Gang , Naik Anant , Hu Jia , Sagar Md Abdul Kader , Haltom Lenora , Mossazghi Nahom , Gray Madelyn M. , West Sarah L. , Eliceiri Kevin W. , Ebner Timothy J. , Kodandaramaiah Suhasa B.
Published: April 2019

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We engineered ‘See-Shells’—digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>300 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. See-Shells allow calcium imaging from multiple, non-contiguous regions across the cortex. Perforated See-Shells enable introducing penetrating neural probes to perturb or record neural activity simultaneously with whole cortex imaging. See-Shells are constructed using common desktop fabrication tools, providing a powerful tool for investigating brain structure and function.
A high-quality apple genome assembly reveals the association of a retrotransposon and red fruit colour
Authors: Zhang Liyi , Hu Jiang , Han Xiaolei , Li Jingjing , Gao Yuan , Richards Christopher M. , Zhang Caixia , Tian Yi , Liu Guiming , Gul Hera , Wang Dajiang , Tian Yu , Yang Chuanxin , Meng Minghui , Yuan Gaopeng , Kang Guodong , Wu Yonglong , Wang Kun , Zhang Hengtao , Wang Depeng , Cong Peihua
Published: April 2019

A complete and accurate genome sequence provides a fundamental tool for functional genomics and DNA-informed breeding. Here, we assemble a high-quality genome (contig N50 of 6.99 Mb) of the apple anther-derived homozygous line HFTH1, including 22 telomere sequences, using a combination of PacBio single-molecule real-time (SMRT) sequencing, chromosome conformation capture (Hi-C) sequencing, and optical mapping. In comparison to the Golden Delicious reference genome, we identify 18,047 deletions, 12,101 insertions and 14 large inversions. We reveal that these extensive genomic variations are largely attributable to activity of transposable elements. Interestingly, we find that a long terminal repeat (LTR) retrotransposon insertion upstream of MdMYB1, a core transcriptional activator of anthocyanin biosynthesis, is associated with red-skinned phenotype. This finding provides insights into the molecular mechanisms underlying red fruit coloration, and highlights the utility of this high-quality genome assembly in deciphering agriculturally important trait in apple.
Transcriptomic Diversification of Granulosa Cells during Follicular Development in Chicken
Authors: Zhu Guoqiang , Fang Chao , Li Jing , Mo Chunheng , Wang Yajun , Li Juan
Published: April 2019

Granulosa cells play important roles in ovarian follicular development. To better understand the molecular mechanisms involved in this physiological process in chicken, high-throughput transcriptome analyses were performed to study the expression profiles of granulosa cells harvested from 6 mm white follicles, F5 follicles and F1 follicles. The analyses elucidated a clear tendency of granulosa cells in shifting its expression profile from proliferation to differentiation during follicular development. Transcripts down-regulated during this process were mainly associated with cell division, cell cycle and DNA replication while the up-regulated transcripts were related to ribosomal function, lipid metabolism and protein synthesis. Our study for the first time provides the complete gene expression profiles along follicular development supporting the active involvement of many genes characterized in cell signaling (AMH, Inhibins, Activins, BMPs) and transcription factors (SMAD3, SMAD5, ID1, ID2, ID3). Their temporal expression profiles support the notion of continual cross-talk between granulosa cells and its neighboring cells and shed light on the mechanisms behind avian follicular selection and pave the way to the better understanding of reproductive efficiency.
Analysis of the tendency for the electronic conductivity to change during alcoholic fermentation
Authors: Li Chongwei , Wang Yue , Sha Shuang , Yin He , Zhang Huilin , Wang Yongsheng , Zhao Bo , Song Fuqiang
Published: April 2019

The observation that the electronic conductivity begins to decease and then increases during alcoholic fermentation was first discovered in our work. To explain the tendency experiments were conducted to investigate the effect of the reducing sugar concentration, ethanol concentration, cell density, pH and ionic concentration. The results showed that the ionic concentration, reducing sugar concentration, cell concentration, pH and especially the ethanol concentration caused a change of the electronic conductivity. From 0 h to 60 h, the ethanol concentration had a significant negative correlation with the conductivity, which decreased with increasing ethanol concentration during fermentation. From 60 h to 68 h, when the ethanol concentration remained unchanged, the total ionic concentration had a significant positive correlation with the electronic conductivity, which increased with increasing ionic concentration (pH value decreases, cell autolysis). Thus, when the electronic conductivity reached its lowest point, the alcoholic content was the greatest. We concluded that it is feasible to directly reflect the change of the ethanol concentration using the change of the electronic conductivity by constructing a mathematical model. The results of this model could be applied for the completely on-line monitoring of the alcoholic fermentation process and for determining the end point of fermentation.
Calibrating the tree of vipers under the fossilized birth-death model
Authors: Šmíd Jiří , Tolley Krystal A.
Published: April 2019

Scaling evolutionary trees to time is essential for understanding the origins of clades. Recently developed methods allow including the entire fossil record known for the group of interest and eliminated the need for specifying prior distributions for node ages. Here we apply the fossilized birth-death (FBD) approach to reconstruct the diversification timeline of the viperines (subfamily Viperinae). Viperinae are an Old World snake subfamily comprising 102 species from 13 genera. The fossil record of vipers is fairly rich and well assignable to clades due to the unique vertebral and fang morphology. We use an unprecedented sampling of 83 modern species and 13 genetic markers in combination with 197 fossils representing 28 extinct taxa to reconstruct a time-calibrated phylogeny of the Viperinae. Our results suggest a late Eocene-early Oligocene origin with several diversification events following soon after the group’s establishment. The age estimates inferred with the FBD model correspond to those from previous studies that were based on node dating but FBD provides notably narrower credible intervals around the node ages. Viperines comprise two African and an Eurasian clade, but the ancestral origin of the subfamily is ambiguous. The most parsimonious scenarios require two transoceanic dispersals over the Tethys Sea during the Oligocene.
Author Correction: A randomized controlled trial of an ambulatory approach versus the hospital-based approach in managing suspected obstructive sleep apnea syndrome
Authors: Hui David S. , Ng Susanna S. , To Kin-Wang , Ko Fanny W. , Ngai Jenny , Chan Ken K. P. , Yip Wing-Ho , Chan Tat-On , Yiu Karen , Tam Wilson W. S.
Published: April 2019

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology
Authors: Vechetti Ivan J. , Wen Yuan , Chaillou Thomas , Murach Kevin A. , Alimov Alexander P. , Figueiredo Vandre C. , Dal-Pai-Silva Maeli , McCarthy John J.
Published: April 2019

We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to ~50% of WT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle.
MoNa – A Cost-Efficient, Portable System for the Nanoinjection of Living Cells
Authors: Simonis Matthias , Sandmeyer Alice , Greiner Johannes , Kaltschmidt Barbara , Huser Thomas , Hennig Simon
Published: April 2019

Injection techniques to deliver macromolecules to cells such as microinjection have been around for decades with applications ranging from probing whole organisms to the injection of fluorescent molecules into single cells. A similar technique that has raised recent interest is nanoinjection. The pipettes used here are much smaller and allow for the precise deposition of molecules into single cells via electrokinetics with minimal influence on the cells’ health. Unfortunately, the equipment utilized for nanoinjection originates from scanning ion conductance microscopy (SICM) and is therefore expensive and not portable, but usually fixed to a specific microscope setup. The level of precision that these systems achieve is much higher than what is needed for the more robust nanoinjection process. We present Mobile Nanoinjection (MoNa), a portable, cost-efficient and easy to build system for the injection of single cells. Sacrificing unnecessary sub-nanometer accuracy and low ion current noise levels, we were able to inject single living cells with high accuracy. We determined the noise of the MoNa system and investigated the injection conditions for 16 prominent fluorescent labels and fluorophores. Further, we performed proof of concepts by injection of ATTO655-Phalloidin and MitoTracker Deep Red to living human osteosarcoma (U2OS) cells and of living adult human inferior turbinate stem cells (ITSC’s) following neuronal differentiation with the MoNa system. We achieved significant cost reductions of the nanoinjection technology and gained full portability and compatibility to most optical microscopes.
Functional detection of botulinum neurotoxin serotypes A to F by monoclonal neoepitope-specific antibodies and suspension array technology
Authors: von Berg Laura , Stern Daniel , Pauly Diana , Mahrhold Stefan , Weisemann Jasmin , Jentsch Lisa , Hansbauer Eva-Maria , Müller Christian , Avondet Marc A. , Rummel Andreas , Dorner Martin B. , Dorner Brigitte G.
Published: April 2019

Botulinum neurotoxins (BoNTs) are the most potent toxins known and cause the life threatening disease botulism. Sensitive and broad detection is extremely challenging due to the toxins’ high potency and molecular heterogeneity with several serotypes and more than 40 subtypes. The toxicity of BoNT is mediated by enzymatic cleavage of different synaptic proteins involved in neurotransmitter release at serotype-specific cleavage sites. Hence, active BoNTs can be monitored and distinguished in vitro by detecting their substrate cleavage products. In this work, we developed a comprehensive panel of monoclonal neoepitope antibodies (Neo-mAbs) highly specific for the newly generated N- and/or C-termini of the substrate cleavage products of BoNT serotypes A to F. The Neo-mAbs were implemented in a set of three enzymatic assays for the simultaneous detection of two BoNT serotypes each by monitoring substrate cleavage on colour-coded magnetic Luminex-beads. For the first time, all relevant serotypes could be detected in parallel by a routine in vitro activity assay in spiked serum and food samples yielding excellent detection limits in the range of the mouse bioassay or better (0.3–80 pg/mL). Therefore, this work represents a major step towards the replacement of the mouse bioassay for botulism diagnostics.
Low genetic diversity and shallow population structure in the endangered vulture, Gyps coprotheres
Authors: Kleinhans Courtneë , Willows-Munro Sandi
Published: April 2019

Globally, vulture species are experiencing major population declines. The southern African Cape vulture (Gyps coprotheres) has undergone severe population collapse which has led to a listing of Endangered by the IUCN. Here, a comprehensive genetic survey ofG. coprotheresis conducted using microsatellite markers. Analyses revealed an overall reduction in heterozygosity compared to other vulture species that occur in South Africa (Gypaetus barbatus,Necrosyrtes monachus, andGyps africanus). Bayesian clustering analysis and principal coordinate analysis identified shallow, subtle population structuring across South Africa. This provides some support for regional natal philopatry in this species. Despite recent reductions in population size, a genetic bottleneck was not detected by the genetic data. TheG. coprotheres, however, did show a significant deficiency of overall heterozygosity. This, coupled with the elevated levels of inbreeding and reduced effective population size, suggests thatG. coprotheresis genetically depauperate. Given that genetic variation is considered a prerequisite for adaptation and population health, the low genetic diversity withinG. coprotherespopulations is of concern and has implications for the future management and conservation of this species.
Extracellular small non-coding RNA contaminants in fetal bovine serum and serum-free media
Authors: Mannerström Bettina , Paananen Riku O. , Abu-Shahba Ahmed G. , Moilanen Jukka , Seppänen-Kaijansinkko Riitta , Kaur Sippy
Published: April 2019

In the research field of extracellular vesicles (EVs), the use of fetal bovine serum (FBS) depleted of EVs for in vitro studies is advocated to eliminate the confounding effects of media derived EVs. EV-depleted FBS may either be prepared by ultracentrifugation or purchased commercially. Nevertheless, these preparations do not guarantee an RNA-free FBS for in vitro use. In this study we address the RNA contamination issue, of small non-coding (nc)RNA in vesicular or non-vesicular fractions of FBS, ultracentrifugation EV-depleted FBS, commercial EV-depleted FBS, and in our recently developed filtration based EV-depleted FBS. Commercially available serum- and xeno-free defined media were also screened for small ncRNA contamination. Our small ncRNA sequencing data showed that all EV-depleted media and commercially available defined media contained small ncRNA contaminants. Out of the different FBS preparations studied, our ultrafiltration-based method for EV depletion performed the best in depleting miRNAs. Certain miRNAs such miR-122 and miR-203a proved difficult to remove completely and were found in all media. Compared to miRNAs, other small ncRNA (snRNA, Y RNA, snoRNA, and piRNA) were difficult to eliminate from all the studied media. Additionally, our tested defined media contained miRNAs and other small ncRNAs, albeit at a much lower level than in serum preparations. Our study showed that no media is free of small ncRNA contaminants. Therefore, in order to screen for baseline RNA contamination in culturing media, RNA sequencing data should be carefully controlled by adding a media sample as a control. This should be a mandatory step before performing cell culture experiments in order to eliminate the confounding effects of media.
Implications of the strain irreversibility cliff on the fabrication of particle-accelerator magnets made of restacked-rod-process Nb3Sn wires
Authors: Cheggour Najib , Stauffer Theodore C. , Starch William , Goodrich Loren F. , Splett Jolene D.
Published: April 2019

The strain irreversibility cliff (SIC), marking the abrupt change of the intrinsic irreversible strain limit εirr,0 as a function of heat-treatment (HT) temperature θ in Nb3Sn superconducting wires made by the restacked-rod process (RRP®), is confirmed in various wire designs. It adds to the complexity of reconciling conflicting requirements on conductors for fabricating magnets. Those intended for the high-luminosity upgrade of the Large Hardon Collider (LHC) at the European Organization for Nuclear Research (CERN) facility require maintaining the residual resistivity ratio RRR of conductors above 150 to ensure stability of magnets against quenching. This benchmark may compromise the conductors’ mechanical integrity if their εirr,0 is within or at the bottom of SIC. In this coupled investigation of strain and RRR properties to fully assess the implications of SIC, we introduce an electro-mechanical stability criterion that takes into account both aspects. For standard-Sn billets, this requires a strikingly narrow HT temperature window that is impractical. On the other hand, reduced-Sn billets offer a significantly wider choice of θ, not only for ensuring that εirr,0 is located at the SIC plateau while RRR ≥ 150, but also for containing the strain-induced irreversible degradation of the conductor’s critical-current beyond εirr,0. This study suggests that HT of LHC magnets, made of reduced-Sn wires having a Nb/Sn ratio of 3.6 and 108/127 restacking architecture, be operated at θ in the range of 680 to 695 °C (when the dwell time is 48 hours).
Augmenting Bragg Reflection with Polymer-sustained Conical Helix
Authors: Joshi Vinay , Paterson Daniel A. , Storey John M. D. , Imrie Corrie T. , Chien Liang-Chy
Published: April 2019

There has been a recent surge of interest in smart materials and devices with stimuli-responsive properties for optical modulations. Cholesteric liquid crystals (CLCs) are a unique class of light-manipulating materials, and strongly interact with light and other electromagnetic (EM) waves. Because of their intricate helical structure, new properties of CLC have emerged revealing unique optical behavior that has resulted in rewriting Braggs’ law for how light interacts with soft materials. The aim of this work is to push the limits of spectral tuning with a new method of augmenting light-cholesteric interactions using a polymer-sustained conical helix (PSCH) structure. We experimentally explore the reversibility of reflective wavelength modulation and validate the mechanism enhanced by a polymer-sustained helicoidal structure via theoretical analyses. The conical helix structure of a CLC, formed by low-field-induced oblique orientation of cholesteric helices, is comprised of a chiral dopant, a conventional nematic, and bimesogenic and trimesogenic nematics. Polymerizing a small amount of a reactive mesogen in the CLC with an applied electric field produces a templated helical polymer network that enables three switched optical states, including light-scattering and transparent states as well as color reflection in response to an applied increasing or decreasing electric field. An electro-activated PSCH optical film covers a wide color space, which is appropriate for tunable color device applications. We envisage that this PSCH material will lead to new avenues for controlling EM waves in imaging and thermal control, smart windows and electronic papers.
A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora
Authors: Tandon Disha , Haque Mohammed Monzoorul , Gote Manoj , Jain Manish , Bhaduri Anirban , Dubey Ashok Kumar , Mande Sharmila S.
Published: April 2019

Fructo-oligosaccharides (FOS), a prebiotic supplement, is known for its Bifidogenic capabilities. However, aspects such as effect of variable quantities of FOS intake on gut microbiota, and temporal dynamics of gut microbiota (transitioning through basal, dosage, and follow-up phases) has not been studied in detail. This study investigated these aspects through a randomized, double-blind, placebo-controlled, dose-response relationship study. The study involved 80 participants being administered FOS at three dose levels (2.5, 5, and 10 g/day) or placebo (Maltodextrin 10 g/day) during dosage phase. Microbial DNA extracted from fecal samples collected at 9 intervening time-points was sequenced and analysed. Results indicate that FOS consumption increased the relative abundance of OTUs belonging to Bifidobacterium and Lactobacillus. Interestingly, higher FOS dosage appears to promote, in contrast to Maltodextrin, the selective proliferation of OTUs belonging to Lactobacillus. While consumption of prebiotics increased bacterial diversity, withdrawal led to its reduction. Apart from probiotic bacteria, a significant change was also observed in certain butyrate-producing microbes like Faecalibacterium, Ruminococcus and Oscillospira. The positive impact of FOS on butyrate-producing bacteria and FOS-mediated increased bacterial diversity reinforces the role of prebiotics in conferring beneficial functions to the host.
An innovation for microstructural modification and mechanical improvement of TiAl alloy via electric current application
Authors: Chen Zhanxing , Ding Hongsheng , Chen Ruirun , Guo Jingjie , Fu Hengzhi
Published: April 2019

In this article, microstructural evolution during the solidification of Ti-48Al-2Cr-2Nb with current density, as well as the formation mechanisms, are discussed, along with the impacts on microhardness and hot compression properties. The applied electric current promotes the solidification from the α primary phase to a largely β solidification in Ti-48Al-2Cr-2Nb. With an increase in supercooling, the solidification process have a tendency to change from an α-led primary phase to (α + β)-led primary phase. The primary dendrites, grain size, and lamellar spacing show a tendency to decrease first before increasing with increasing current density. Microhardness and high-temperature yield strength increase with a decrease in primary dendrite spacing, grain size, and lamellar spacing. Correlations between primary dendrite spacing, lamellar spacing, microhardness, yield strength, and current density are described by a fitting formula. An increase of α2 phase, due to the application of electric current, results in improved microhardness. The yield strength of Ti-48Al-2Cr-2Nb alloy increases linearly with microhardness. Yield stress increases with a decrease in microstructure parameters, in accordance with the Hall–Petch equation. The predominant modification mechanism with electric current application for TiAl solidification is the variation of supercooling and temperature gradients ahead of the mush zone due to Joule heating.
Azoreductase activity of dye-decolorizing bacteria isolated from the human gut microbiota
Authors: Zahran Sara A. , Ali-Tammam Marwa , Hashem Abdelgawad M. , Aziz Ramy K. , Ali Amal E.
Published: April 2019

The gut microbiota enriches the human gene pool and contributes to xenobiotic metabolism. Microbial azoreductases modulate the reduction of azo-bonds, activating produgs and azo polymer-coated dosage forms, or degrading food additives. Here, we aimed to screen the healthy human gut microbiota for food colorant-reducing activity and to characterize factors modulating it. Four representative isolates from screened fecal samples were identified as E. coli (AZO-Ec), E. faecalis (AZO-Ef), E. avium (AZO-Ev) and B. cereus (AZO-Bc). Both AZO-Ef and AZO-Ev decolorized amaranth aerobically and microaerophilically while AZO-Ec and AZO-Bc had higher aerobic reduction rates. The isolates varied in their activities against different dyes, and the azo-reduction activity mostly followed zero-order reaction kinetics, with a few exceptions. Additionally, the isolates had different pH dependence, e.g., AZO-Ec was not affected by pH variation while AZO-Bc exhibited variable degradation kinetics at different pH levels. Cell-free extracts showed NADH-dependent enzymatic activities 14–19 times higher than extracellular fractions. FMN did not affect the reducing activity of AZO-Ef cell-free extract, whereas AZO-Ec, AZO-Ev and AZO-Bc had significantly higher reduction rates in its presence (P values = 0.02, 0.0001 and 0.02, respectively). Using Degenerate primers allowed the amplification of azoreductase genes, whose sequences were 98–99% similar to genes encoding FMN-dependent-NADH azoreductases.