bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-omic meta-analysis identifies functional signatures of airway microbiome in chronic obstructive pulmonary disease
Authors: Wang Zhang , Yang Yuqiong , Yan Zhengzheng , Liu Haiyue , Chen Boxuan , Liang Zhenyu , Wang Fengyan , Miller Bruce E , Tal-Singer Ruth , Yi Xinzhu , Li Jintian , Stampfli Martin R , Zhou Hongwei , Brightling Christopher E , Brown James R , Wu Martin , Chen Rongchang , Shu Wensheng
Published: July 2020

The interaction between airway microbiome and host in chronic obstructive pulmonary disease (COPD) is poorly understood. Here we used a multi-omic meta-analysis approach to characterize the functional signature of airway microbiome in COPD. We retrieved all public COPD sputum microbiome datasets, totaling 1640 samples from 16S rRNA gene datasets and 26 samples from metagenomic datasets from across the world. We identified microbial taxonomic shifts using random effect meta-analysis and established a global classifier for COPD using 12 microbial genera. We inferred the metabolic potentials for the airway microbiome, established their molecular links to host targets, and explored their effects in a separate meta-analysis on 1340 public human airway transcriptome samples for COPD. 29.6% of differentially expressed human pathways were predicted to be targeted by microbiome metabolism. For inferred metabolite–host interactions, the flux of disease-modifying metabolites as predicted from host transcriptome was generally concordant with their predicted metabolic turnover in microbiome, suggesting a synergistic response between microbiome and host in COPD. The meta-analysis results were further validated by a pilot multi-omic study on 18 COPD patients and 10 controls, in which airway metagenome, metabolome, and host transcriptome were simultaneously characterized. 69.9% of the proposed “microbiome-metabolite–host” interaction links were validated in the independent multi-omic data. Butyrate, homocysteine, and palmitate were the microbial metabolites showing strongest interactions with COPD-associated host genes. Our meta-analysis uncovered functional properties of airway microbiome that interacted with COPD host gene signatures, and demonstrated the possibility of leveraging public multi-omic data to interrogate disease biology.
HIF-1α regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors
Authors: Xu Kangjing , He Zhongyuan , Chen Ming , Wang Nuofan , Zhang Diancai , Yang Li , Xu Zekuan , Xu Hao
Published: July 2020

The pentose phosphate pathway (PPP) plays a critical role in maintaining cellular redox homeostasis in tumor cells and macromolecule biosynthesis. Upregulation of the PPP has been shown in several types of tumor. However, how the PPP is regulated to confer selective growth advantages on drug resistant tumor cells is not well understood. Here we show a metabolic shift from tricarboxylic acid cycle (TCA) to PPP after a long period induction of Imatinib (IM). One of the rate-limiting enzymes of the PPP-phosphogluconate dehydrogenase (PGD), is dramatically upregulated in gastrointestinal stromal tumors (GISTs) and GIST cell lines resistant to Imatinib (IM) compared with sensitive controls. Functional studies revealed that the overexpression of PGD in resistant GIST cell lines promoted cell proliferation and suppressed cell apoptosis. Mechanistic analyses suggested that the protein level of hypoxia inducible factor-1α (HIF-1α) increased during long time stimulation of reactive oxygen species (ROS) produced by IM. Importantly, we further demonstrated that HIF-1α also had positive correlation with PGD, resulting in the change of metabolic pathway, and ultimately causing drug resistance in GIST. Our findings show that long term use of IM alters the metabolic phenotype of GIST through ROS and HIF-1α, and this may contribute to IM resistance. Our work offers preclinical proof of metabolic target as an effective strategy for the treatment of drug resistance in GIST.
Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs
Authors: Kumar Arvind , Basak Sandip , Rao Shanlin , Gicheru Yvonne , Mayer Megan L. , Sansom Mark S. P. , Chakrapani Sudha
Published: July 2020

Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structures have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unanswered. Here, we present Cryo-EM structures of the full-length GlyR protein complex reconstituted into lipid nanodiscs that are captured in the unliganded (closed), glycine-bound (open and desensitized), and allosteric modulator-bound conformations. A comparison of these states reveals global conformational changes underlying GlyR channel gating and modulation. The functional state assignments were validated by molecular dynamics simulations, and the observed permeation events are in agreement with the anion selectivity and conductance of GlyR. These studies provide the structural basis for gating, ion selectivity, and single-channel conductance properties of GlyR in a lipid environment.
The architecture and stabilisation of flagellotropic tailed bacteriophages
Authors: Hardy Joshua M. , Dunstan Rhys A. , Grinter Rhys , Belousoff Matthew J. , Wang Jiawei , Pickard Derek , Venugopal Hariprasad , Dougan Gordon , Lithgow Trevor , Coulibaly Fasséli
Published: July 2020

Flagellotropic bacteriophages engage flagella to reach the bacterial surface as an effective means to increase the capture radius for predation. Structural details of these viruses are of great interest given the substantial drag forces and torques they face when moving down the spinning flagellum. We show that the main capsid and auxiliary proteins form two nested chainmails that ensure the integrity of the bacteriophage head. Core stabilising structures are conserved in herpesviruses suggesting their ancestral origin. The structure of the tail also reveals a robust yet pliable assembly. Hexameric rings of the tail-tube protein are braced by the N-terminus and a β-hairpin loop, and interconnected along the tail by the splayed β-hairpins. By contrast, we show that the β-hairpin has an inhibitory role in the tail-tube precursor, preventing uncontrolled self-assembly. Dyads of acidic residues inside the tail-tube present regularly-spaced motifs well suited to DNA translocation into bacteria through the tail.
Directional translocation resistance of Zika xrRNA
Authors: Suma Antonio , Coronel Lucia , Bussi Giovanni , Micheletti Cristian
Published: July 2020

xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, $${5}^{\prime}$$

5

′

and $${3}^{\prime}$$

3

′

, are driven through a pore. Pulling the $${3}^{\prime}$$

3

′

end, as done by replicases, elicits a progressive unfolding; pulling the $${5}^{\prime}$$

5

′

end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the $${5}^{\prime}$$

5

′

end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials.
Coupling of 5S RNP rotation with maturation of functional centers during large ribosomal subunit assembly
Authors: Micic Jelena , Li Yu , Wu Shan , Wilson Daniel , Tutuncuoglu Beril , Gao Ning , Woolford John L.
Published: July 2020

The protein composition and structure of assembling 60S ribosomal subunits undergo numerous changes as pre-ribosomes transition from the nucleolus to the nucleoplasm. This includes stable anchoring of the Rpf2 subcomplex containing 5S rRNA, rpL5, rpL11, Rpf2 and Rrs1, which initially docks onto the flexible domain V of rRNA at earlier stages of assembly. In this work, we tested the function of the C-terminal domain (CTD) of Rpf2 during these anchoring steps, by truncating this extension and assaying effects on middle stages of subunit maturation. The rpf2Δ255-344 mutation affects proper folding of rRNA helices H68-70 during anchoring of the Rpf2 subcomplex. In addition, several assembly factors (AFs) are absent from pre-ribosomes or in altered conformations. Consequently, major remodeling events fail to occur: rotation of the 5S RNP, maturation of the peptidyl transferase center (PTC) and the nascent polypeptide exit tunnel (NPET), and export of assembling subunits to the cytoplasm.
Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry
Authors: Cao Feng , Liu Jackie J. , Zhou Susan , Cortez Miguel A. , Snead O. Carter , Han Jing , Jia Zhengping
Published: July 2020

Epilepsy and autism spectrum disorders (ASD) are two distinct brain disorders but have a high rate of co-occurrence, suggesting shared pathogenic mechanisms. Neuroligins are cell adhesion molecules important in synaptic function and ASD, but their role in epilepsy remains unknown. In this study, we show that Neuroligin 2 (NLG2) knockout mice exhibit abnormal spike and wave discharges (SWDs) and behavioral arrests characteristic of absence seizures. The anti-absence seizure drug ethosuximide blocks SWDs and rescues behavioral arrests and social memory impairment in the knockout mice. Restoring GABAergic transmission either by optogenetic activation of the thalamic reticular nucleus (nRT) presynaptic terminals or postsynaptic NLG2 expression in the thalamic neurons reduces the SWDs and behavioral arrests in the knockout mice. These results indicate that NLG2-mediated GABAergic transmission at the nRT-thalamic circuit represents a common mechanism underlying both epileptic seizures and ASD.
VoPo leverages cellular heterogeneity for predictive modeling of single-cell data
Authors: Stanley Natalie , Stelzer Ina A. , Tsai Amy S. , Fallahzadeh Ramin , Ganio Edward , Becker Martin , Phongpreecha Thanaphong , Nassar Huda , Ghaemi Sajjad , Maric Ivana , Culos Anthony , Chang Alan L. , Xenochristou Maria , Han Xiaoyuan , Espinosa Camilo , Rumer Kristen , Peterson Laura , Verdonk Franck , Gaudilliere Dyani , Tsai Eileen , Feyaerts Dorien , Einhaus Jakob , Ando Kazuo , Wong Ronald J. , Obermoser Gerlinde , Shaw Gary M. , Stevenson David K. , Angst Martin S. , Gaudilliere Brice , Aghaeepour Nima
Published: July 2020

High-throughput single-cell analysis technologies produce an abundance of data that is critical for profiling the heterogeneity of cellular systems. We introduce VoPo (https://github.com/stanleyn/VoPo), a machine learning algorithm for predictive modeling and comprehensive visualization of the heterogeneity captured in large single-cell datasets. In three mass cytometry datasets, with the largest measuring hundreds of millions of cells over hundreds of samples, VoPo defines phenotypically and functionally homogeneous cell populations. VoPo further outperforms state-of-the-art machine learning algorithms in classification tasks, and identified immune-correlates of clinically-relevant parameters.
Nano-topology optimization for materials design with atom-by-atom control
Authors: Chen Chun-Teh , Chrzan Daryl C. , Gu Grace X.
Published: July 2020

Atoms are the building blocks of matter that make up the world. To create new materials to meet some of civilization’s greatest needs, it is crucial to develop a technology to design materials on the atomic and molecular scales. However, there is currently no computational approach capable of designing materials atom-by-atom. In this study, we consider the possibility of direct manipulation of individual atoms to design materials at the nanoscale using a proposed method coined “Nano-Topology Optimization”. Here, we apply the proposed method to design nanostructured materials to maximize elastic properties. Results show that the performance of our optimized designs not only surpasses that of the gyroid and other triply periodic minimal surface structures, but also exceeds the theoretical maximum (Hashin–Shtrikman upper bound). The significance of the proposed method lies in a platform that allows computers to design novel materials atom-by-atom without the need of a predetermined design.
Author Correction: Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation
Authors: Zheng Jun , Fan Rong , Wu Huiqiong , Yao Honghui , Yan Yujie , Liu Jiamiao , Ran Lu , Sun Zhifang , Yi Lunzhao , Dang Li , Gan Pingping , Zheng Piao , Yang Tilong , Zhang Yi , Tang Tao , Wang Yang
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
One-step fabrication of carbonaceous adsorbent from corncob for enhancing adsorption capability of methylene blue removal
Authors: Wang Youming , Zhou Yulong , Jiang Guojing , Chen Peirong , Chen Zhen
Published: July 2020

A novel and simple method was described for preparation of carbonaceous adsorbent (CA) from corncob under phosphoric acid conditions. The method succeeded to introduce oxygen-containing groups onto the product surface through hydrothermal carbonization (HTC) at low temperature of 160 °C. Adsorption of methylene blue (MB) was studied systematically through the effect of pH, contact time and initial dye concentrations. The MB adsorption kinetics and isotherms experiments showed that Langmuir model and pseudo-second-order model could better describe the adsorption behavior, with a maximum adsorption capacity of MB was 140.25 mg/g. The high adsorption capacity could be ascribed to the presence of surface oxygen-containing functional groups and pore channels. In conclusion, it could be a potential adsorbent in the removal of methylene blue from wastewater.
Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells
Authors: White ElShaddai Z. , Pennant Nakea M. , Carter Jada R. , Hawsawi Ohuod , Odero-Marah Valerie , Hinton Cimona V.
Published: July 2020

Inadequate nutrient intake leads to oxidative stress disrupting homeostasis, activating signaling, and altering metabolism. Oxidative stress serves as a hallmark in developing prostate lesions, and an aggressive cancer phenotype activating mechanisms allowing cancer cells to adapt and survive. It is unclear how adaptation and survival are facilitated; however, literature across several organisms demonstrates that a reversible cellular growth arrest and the transcription factor, nuclear factor-kappaB (NF-κB), contribute to cancer cell survival and therapeutic resistance under oxidative stress. We examined adaptability and survival to oxidative stress following nutrient deprivation in three prostate cancer models displaying varying degrees of tumorigenicity. We observed that reducing serum (starved) induced reactive oxygen species which provided an early oxidative stress environment and allowed cells to confer adaptability to increased oxidative stress (H2O2). Measurement of cell viability demonstrated a low death profile in stressed cells (starved + H2O2), while cell proliferation was stagnant. Quantitative measurement of apoptosis showed no significant cell death in stressed cells suggesting an adaptive mechanism to tolerate oxidative stress. Stressed cells also presented a quiescent phenotype, correlating with NF-κB nuclear translocation, suggesting a mechanism of tolerance. Our data suggests that nutrient deprivation primes prostate cancer cells for adaptability to oxidative stress and/or a general survival mechanism to anti-tumorigenic agents.
Antibody drug separation using thermoresponsive anionic polymer brush modified beads with optimised electrostatic and hydrophobic interactions
Authors: Nagase Kenichi , Ishii Saki , Ikeda Koji , Yamada Sota , Ichikawa Daiju , Akimoto Aya Mizutani , Hattori Yutaka , Kanazawa Hideko
Published: July 2020

Antibody drugs play an important role in biopharmaceuticals, because of the specificity for target biomolecules and reduction of side effects. Thus, separation and analysis techniques for these antibody drugs have increased in importance. In the present study, we develop functional chromatography matrices for antibody drug separation and analysis. Three types of polymers, poly(N-isopropylacrylamide (NIPAAm)-co-2-acrylamido-2-methylpropanesulfonic acid (AMPS)-co-N-phenyl acrylamide (PhAAm)), P(NIPAAm-co-AMPS-co-n-butyl methacrylate (BMA)), and P(NIPAAm-co-AMPS-co-tert-butylacrylamide (tBAAm)), were modified on silica beads through atom transfer radical polymerisation. Rituximab elution profiles were observed using the prepared beads-packed column. Rituximab adsorption at high temperature and elution at low temperature from the column were observed, as a result of the temperature-modulated electrostatic and hydrophobic interactions. Using the column, rituximab purification from contaminants was performed simply by changing the temperature. Additionally, three types of antibody drugs were separated using the column through temperature-modulated hydrophobic and electrostatic interactions. These results demonstrate that the temperature-responsive column can be applied for the separation and analysis of biopharmaceuticals through a simple control of the column temperature.
The molecular basis of thioalcohol production in human body odour
Authors: Rudden Michelle , Herman Reyme , Rose Matthew , Bawdon Daniel , Cox Diana S. , Dodson Eleanor , Holden Matthew T. G. , Wilkinson Anthony J. , James A. Gordon , Thomas Gavin H.
Published: July 2020

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour. We demonstrated using phylogenetics, biochemistry and structural biology that this cysteine-thiol lyase (C-T lyase) is a PLP-dependent enzyme that moved horizontally into a unique monophyletic group of odour-forming staphylococci about 60 million years ago, and has subsequently tailored its enzymatic function to human-derived thioalcohol precursors. Significantly, transfer of this enzyme alone to non-odour producing staphylococci confers odour production, demonstrating that this C-T lyase is both necessary and sufficient for thioalcohol formation. The structure of the C-T lyase compared to that of other related enzymes reveals how the adaptation to thioalcohol precursors has evolved through changes in the binding site to create a constrained hydrophobic pocket that is selective for branched aliphatic thioalcohol ligands. The ancestral acquisition of this enzyme, and the subsequent evolution of the specificity for thioalcohol precursors implies that body odour production in humans is an ancient process.
The ‘Threat of Scream’ paradigm: a tool for studying sustained physiological and subjective anxiety
Authors: Beaurenaut Morgan , Tokarski Elliot , Dezecache Guillaume , Grèzes Julie
Published: July 2020

Progress in understanding the emergence of pathological anxiety depends on the availability of paradigms effective in inducing anxiety in a simple, consistent and sustained manner. The Threat-of-Shock paradigm has typically been used to elicit anxiety, but poses ethical issues when testing vulnerable populations. Moreover, it is not clear from past studies whether anxiety can be sustained in experiments of longer durations. Here, we present empirical support for an alternative approach, the ‘Threat-of-Scream’ paradigm, in which shocks are replaced by screams. In two studies, participants were repeatedly exposed to blocks in which they were at risk of hearing aversive screams at any time vs. blocks in which they were safe from screams. Contrary to previous ‘Threat-of-Scream’ studies, we ensured that our screams were neither harmful nor intolerable by presenting them at low intensity. We found higher subjective reports of anxiety, higher skin conductance levels, and a positive correlation between the two measures, in threat compared to safe blocks. These results were reproducible and we found no significant change over time. The unpredictable delivery of low intensity screams could become an essential part of a psychology toolkit, particularly when investigating the impact of anxiety in a diversity of cognitive functions and populations.
Three-dimensional super-resolution fluorescence imaging of DNA
Authors: Yardimci Sevim , Burnham Daniel R. , Terry Samantha Y. A. , Yardimci Hasan
Published: July 2020

Recent advances in fluorescence super-resolution microscopy are providing important insights into details of cellular structures. To acquire three dimensional (3D) super-resolution images of DNA, we combined binding activated localization microscopy (BALM) using fluorescent double-stranded DNA intercalators and optical astigmatism. We quantitatively establish the advantage of bis- over mono-intercalators before demonstrating the approach by visualizing single DNA molecules stretched between microspheres at various heights. Finally, the approach is applied to the more complex environment of intact and damaged metaphase chromosomes, unravelling their structural features.
Modulating electrophysiology of motor neural networks via optogenetic stimulation during neurogenesis and synaptogenesis
Authors: Pagan-Diaz Gelson J. , Drnevich Jenny , Ramos-Cruz Karla P. , Sam Richard , Sengupta Parijat , Bashir Rashid
Published: July 2020

Control of electrical activity in neural circuits through network training is a grand challenge for biomedicine and engineering applications. Past efforts have not considered evoking long-term changes in firing patterns of in-vitro networks by introducing training regimens with respect to stages of neural development. Here, we used Channelrhodopsin-2 (ChR2) transfected mouse embryonic stem cell (mESC) derived motor neurons to explore short and long-term programming of neural networks by using optical stimulation implemented during neurogenesis and synaptogenesis. Not only did we see a subsequent increase of neurite extensions and synaptophysin clustering, but by using electrophysiological recording with micro electrode arrays (MEA) we also observed changes in signal frequency spectra, increase of network synchrony, coordinated firing of actions potentials, and enhanced evoked response to stimulation during network formation. Our results demonstrate that optogenetic stimulation during neural differentiation can result in permanent changes that extended to the genetic expression of neurons as demonstrated by RNA Sequencing. To our knowledge, this is the first time that a correlation between training regimens during neurogenesis and synaptogenesis and the resulting plastic responses has been shown in-vitro and traced back to changes in gene expression. This work demonstrates new approaches for training of neural circuits whose electrical activity can be modulated and enhanced, which could lead to improvements in neurodegenerative disease research and engineering of in-vitro multi-cellular living systems.
Changes in the vaginal microbiota across a gradient of urbanization
Authors: Vargas-Robles Daniela , Morales Natalia , Rodríguez Iveth , Nieves Tahidid , Godoy-Vitorino Filipa , Alcaraz Luis David , Pérez María-Eglée , Ravel Jacques , Forney Larry J. , Domínguez-Bello María Gloria
Published: July 2020

The vaginal microbiota of healthy women typically has low diversity, which increases after perturbations. Among these, lifestyle associated with certain sexual and antimicrobial practices may be associated with higher diversity. To test this hypothesis, we characterized the vaginal microbiota in the cervicovaginal and introital sites in sexually active Amerindians (N = 82) spanning urbanization, and in urban mestizos (N = 29), in the Venezuelan Amazonas. HPV status was also considered. Sampling was performed in an urban gradient from remote villages to a town, and women were individually classified by the degree of urbanization (low, medium, and high). Amerindian cervicovaginal and introital microbiota diversity were not associated with major changes in urbanization or ethnicity. There was a non-significant trend of increased diversity with urbanization, with a few taxa found overrepresented in urban Amerindians (Brevibacterium linensandPeptoniphilus lacrimalis) or mestizos (Mobiluncus mulierisandPrevotella sp.). Among all women, cervicovaginal and introital samples clustered, respectively, in four and two community state types (CSTs), where most profiles were dominated byLactobacillus iners, Gardnerella vaginalisor were highly diverse profiles. HPV status did not associate with microbial diversity. In conclusion, no association was found between urban level and the vaginal microbiome in Amerindian women, and little difference was found between ethnicities.L. inersand high diversity profiles, associated with vaginal health outcomes, prevail in these populations.
A thrombolytic therapy using diagnostic ultrasound combined with RGDS-targeted microbubbles and urokinase in a rabbit model
Authors: Guan Lina , Wang Chunmei , Yan Xue , Liu Liyun , Li Yanhong , Mu Yuming
Published: July 2020

This study aimed to explore thrombolysis therapy based on ultrasound combined with urokinase and Arg–Gly–Asp sequence (RGDS)-targeted microbubbles by evaluating the histological changes in a thrombotic rabbit model. Forty-two New Zealand rabbits featuring platelet-rich thrombi in the femoral artery were randomized to (n = 6/group): ultrasound alone (US); urokinase alone (UK); ultrasound plus non-targeted microbubbles (US + M); ultrasound plus RGDS-targeted microbubbles (US + R); RGDS-targeted microbubbles plus urokinase (R + UK); ultrasound, non-targeted microbubbles and urokinase (US + M + UK); and ultrasound, RGDS-targeted microbubbles and urokinase (US + R + UK) groups. Diagnostic ultrasound was used transcutaneously over the thrombus for 30 min. We evaluated the thrombolytic effect based on ultrasound thrombi detection, blood flow, and histological observations. Among all study groups, complete recanalization was achieved in the US + R + UK group. Hematoxylin and eosin staining showed that the thrombi were completely dissolved. Scanning electron microscopy examination demonstrated that the fiber network structure of the thrombi was damaged. Transmission electron microscopy showed that the thrombus was decomposed into high electron-dense particles. Histology for von Willebrand factor and tissue factor were both negative in the US + R + UK group. This study revealed that a thrombolytic therapy consisting of diagnostic ultrasound together with RGDS-targeted and urokinase coupled microbubbles.
Combined LA-ICP-MS/LIBS: powerful analytical tools for the investigation of polymer alteration after treatment under corrosive conditions
Authors: Brunnbauer Lukas , Mayr Maximilian , Larisegger Silvia , Nelhiebel Michael , Pagnin Laura , Wiesinger Rita , Schreiner Manfred , Limbeck Andreas
Published: July 2020

Polymers are used in a variety of different areas, including applications in food packaging, automotive and the semiconductor industry. Information about degradation of these materials during application, but also uptake of pollutants from the surrounding environment is therefore of great interest. Conventional techniques used for polymer characterization such as FT-IR or Raman spectroscopy, but also thermo-analytical techniques offer insights into degradation processes but lack the possibility to detect uptake of inorganic species. Moreover, these techniques do not allow the measurement of depth profiles, thus information about degradation or pollutant uptake with sample depth is not accessible. In this work, we propose LA-ICP-MS and LIBS as powerful analytical tools for polymer characterization, overcoming the limitations of conventional analytical techniques used for polymer analysis. Applicability of the developed procedures is demonstrated by the analysis of artificially weathered polyimides and modern art materials, indicating that the degradation of the polymer but also the uptake of corrosive gases is not limited to the sample surface. Finally, a tandem LA-ICP-MS/LIBS approach is employed, which combines the advantages of both laser-based procedures, enabling the simultaneous analysis of polymer degradation and cadmium uptake of polystyrene after exposure to UV radiation and treatment with artificial sea water.
Borrelia burgdorferi spatiotemporal regulation of transcriptional regulator bosR and decorin binding protein during murine infection
Authors: Saputra Elizabeth P. , Trzeciakowski Jerome P. , Hyde Jenny A.
Published: July 2020

Lyme disease, caused by Borrelia burgdorferi, is an inflammatory multistage infection, consisting of localized, disseminated, and persistent disease stages, impacting several organ systems through poorly defined gene regulation mechanisms. The purpose of this study is to further characterize the spatiotemporal transcriptional regulation of B. burgdorferi during mammalian infection of borrelial oxidative stress regulator (bosR) and decorin binding protein (dbpBA) by utilizing bioluminescent B. burgdorferi reporter strains and in vivo imaging. Fluctuating borrelial load was also monitored and used for normalization to evaluate expression levels. bosR transcription is driven by two promoters, Pbb0648 and PbosR, and we focused on the native promoter. bosR expression is low relative to the robustly expressed dbpBA throughout infection. In distal tissues, bosR was the highest in the heart during in the first week whereas dbpBA was readily detectable at all time points with each tissue displaying a distinct expression pattern. This data suggests bosR may have a role in heart colonization and the induction of dbpBA indicates a RpoS independent transcriptional regulation occurring in the mammalian cycle of pathogenesis. These finding demonstrate that B. burgdorferi engages unknown genetic mechanisms to uniquely respond to mammalian tissue environments and/or changing host response over time.
SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells
Authors: Wyman Anne E. , Nguyen Trang T. T. , Karki Pratap , Tulapurkar Mohan E. , Zhang Chen-Ou , Kim Junghyun , Feng Theresa G. , Dabo Abdoulaye J. , Todd Nevins W. , Luzina Irina G. , Geraghty Patrick , Foronjy Robert F. , Hasday Jeffrey D. , Birukova Anna A. , Atamas Sergei P. , Birukov Konstantin G.
Published: July 2020

Acute lung injury (ALI), a common condition in critically ill patients, has limited treatments and high mortality. Aging is a risk factor for ALI. Sirtuins (SIRTs), central regulators of the aging process, decrease during normal aging and in aging-related diseases. We recently showed decreased SIRT7 expression in lung tissues and fibroblasts from patients with pulmonary fibrosis compared to controls. To gain insight into aging-related mechanisms in ALI, we investigated the effects of SIRT7 depletion on lipopolysaccharide (LPS)-induced inflammatory responses and endothelial barrier permeability in human primary pulmonary endothelial cells. Silencing SIRT7 in pulmonary artery or microvascular endothelial cells attenuated LPS-induced increases in ICAM1, VCAM1, IL8, and IL6 and induced endomesenchymal transition (EndoMT) with decreases in VE-Cadherin and PECAM1 and increases in collagen, alpha-smooth muscle actin, TGFβ receptor 1, and the transcription factor Snail. Loss of endothelial adhesion molecules was accompanied by increased F-actin stress fibers and increased endothelial barrier permeability. Together, these results show that an aging phenotype induced by SIRT7 deficiency promotes EndoMT with impaired inflammatory responses and dysfunction of the lung vascular barrier.
Estimating illegal fishing from enforcement officers
Authors: Donlan C. Josh , Wilcox Chris , Luque Gloria M. , Gelcich Stefan
Published: July 2020

While illegal, unreported, and unregulated (IUU) fishing is a premier issue facing ocean sustainability, characterizing it is challenging due to its clandestine nature. Current approaches can be resource intensive and sometimes controversial. Using Chile as an example, we present a structured process leveraging existing capacity, fisheries officers, that provides a monitoring tool to produce transparent and stand-alone estimates on the level, structure, and characteristics of illegal fishing. We provide a national illegal fishing baseline for Chile, estimating illegal activity for 20 fisheries, representing ~ 70% of annual national landings. For four fisheries, we also estimate the relative importance of illegal activities across sectors, stakeholders, and infrastructure. While providing new information, our results also confirm previous evidence on the general patterns of illegality. Our approach provides an opportunity for government agencies to formalize their institutional knowledge, while accounting for potential biases and reducing fragmentation of knowledge that can prevent effective enforcement. Estimating illegal activity directly from fisheries enforcement officers is complementary to existing approaches, providing a cost-effective, rapid, and rigorous method to measure, monitor, and inform solutions to reduce IUU fishing.
Genetic analysis reveals four interacting loci underlying awn trait diversity in barley (Hordeum vulgare)
Authors: Huang Biguang , Huang Daiqing , Hong Zonglie , Owie Swithin Omosuwa , Wu Weiren
Published: July 2020

Barley (Hordeum vulgare) awns contribute to grain yield, but the genetic basis of awn development remains largely unclear. Five barley lines differing in awn traits and row types were used to create four F2 populations. Genetic analyses revealed that four pairs of genes were involved in awn development: A/a (awnless/awned), B/b (awnless/awned), H/h (hooded/straight), and L/l (long/short). Of these four loci, A, H and L functioned on both central rows (CR) and lateral rows (LR) of the barley spikes, while B exhibited effect only on LR. A and B had duplicate effects on LR, and both showed dominant epistasis to loci H and L, whereas H was epistatic to L. Meanwhile, A and B were found to be genetically linked, with a row-type locus V located between them. The genetic distances of A-V and B-V were estimated to be 9.6 and 7.7 cM, respectively. Literature search suggested that A, H and V may correspond to the reported Lks1, Kap1 and Vrs1, respectively, whereas B is a novel gene specifically controlling awn development on LR, designated as Lsa1 for lateral spikelet awnless 1. The only barley homolog of wheat awn inhibitor gene B1, HORVU2Hr1G077570, is a potential candidate of Lsa1.
River flow prediction in data scarce regions: soil moisture integrated satellite rainfall products outperform rain gauge observations in West Africa
Authors: Brocca Luca , Massari Christian , Pellarin Thierry , Filippucci Paolo , Ciabatta Luca , Camici Stefania , Kerr Yann H. , Fernández-Prieto Diego
Published: July 2020

Satellite precipitation products have been largely improved in the recent years particularly with the launch of the global precipitation measurement (GPM) core satellite. Moreover, the development of techniques for exploiting the information provided by satellite soil moisture to complement/enhance precipitation products have improved the accuracy of accumulated rainfall estimates over land. Such satellite enhanced precipitation products, available with a short latency (< 1 day), represent an important and new source of information for river flow prediction and water resources management, particularly in developing countries in which ground observations are scarcely available and the access to such data is not always ensured. In this study, three recently developed rainfall products obtained from the integration of GPM rainfall and satellite soil moisture products have been used; namely GPM+SM2RAIN, PRISM-SMOS, and PRISM-SMAP. The prediction of observed daily river discharge at 10 basins located in Europe (4), West Africa (3) and South Africa (3) is carried out. For comparison, we have also considered three rainfall products based on: (1) GPM only, i.e., the Early Run version of the Integrated Multi-Satellite Retrievals for GPM (GPM-ER), (2) rain gauges, i.e., the Global Precipitation Climatology Centre, and (3) the latest European Centre for Medium-Range Weather Forecasts reanalysis, ERA5. Three different conceptual and lumped rainfall-runoff models are employed to obtain robust and reliable results over the 3-year data period 2015–2017. Results indicate that, particularly over scarcely gauged areas (West Africa), the integrated products outperform both ground- and reanalysis-based rainfall estimates. For all basins, the GPM+SM2RAIN product is performing the best among the short latency products with mean Kling–Gupta Efficiency (KGE) equal to 0.87, and significantly better than GPM-ER (mean KGE = 0.77). The integrated products are found to reproduce particularly well the high flows. These results highlight the strong need to disseminate such integrated satellite rainfall products for hydrological (and agricultural) applications in poorly gauged areas such as Africa and South America.
Applicability of care quality indicators for women with low-risk pregnancies planning hospital birth: a retrospective study of medical records
Authors: Ueda Kayo , Sado Toshiyuki , Takahashi Yoshimitsu , Igarashi Toshiko , Nakayama Takeo
Published: July 2020

Practices for planned birth among women with low-risk pregnancies vary by birth setting, medical professional, and organizational system. Appropriate monitoring is essential for quality improvement. Although sets of quality indicators have been developed, their applicability has not been tested. To improve the quality of childbirth care for low-risk mothers and infants in Japanese hospitals, we developed 35 quality indicators using existing clinical guidelines and quality indicators. We retrospectively analysed data for 347 women in Japan diagnosed with low-risk pregnancy in the second trimester, admitted between April 2015 and March 2016. We obtained scores for 35 quality indicators and evaluated their applicability, i.e., feasibility, improvement potential, and reliability (intra- and inter-rater reliability: kappa score, positive and negative agreement). The range of adherence to each indicator was 0–95.7%. We identified feasibility concerns for six indicators with over 25% missing data. Two indicators with over 90% adherence showed limited potential for improvement. Three indicators had poor kappa scores for intra-rater reliability, with positive/negative agreement scores 0.94/0.33, 0.33/0.95, and 0.00/0.97, respectively. Two indicators had poor kappa scores for inter-rater reliability, with positive/negative agreement scores 0.25/0.92 and 0.68/0.61, respectively. The findings indicated that these 35 care quality indicators for low-risk pregnant women may be applicable to real-world practice, with some caveats.
High diversity and variability of pipolins among a wide range of pathogenic Escherichia coli strains
Authors: Flament-Simon Saskia-Camille , de Toro María , Chuprikova Liubov , Blanco Miguel , Moreno-González Juan , Salas Margarita , Blanco Jorge , Redrejo-Rodríguez Modesto
Published: July 2020

Self-synthesizing transposons are integrative mobile genetic elements (MGEs) that encode their own B-family DNA polymerase (PolB). Discovered a few years ago, they are proposed as key players in the evolution of several groups of DNA viruses and virus–host interaction machinery. Pipolins are the most recent addition to the group, are integrated in the genomes of bacteria from diverse phyla and also present as circular plasmids in mitochondria. Remarkably, pipolins-encoded PolBs are proficient DNA polymerases endowed with DNA priming capacity, hence the name, primer-independent PolB (piPolB). We have now surveyed the presence of pipolins in a collection of 2,238 human and animal pathogenic Escherichia coli strains and found that, although detected in only 25 positive isolates (1.1%), they are present in E. coli strains from a wide variety of pathotypes, serotypes, phylogenetic groups and sequence types. Overall, the pangenome of strains carrying pipolins is highly diverse, despite the fact that a considerable number of strains belong to only three clonal complexes (CC10, CC23 and CC32). Comparative analysis with a set of 67 additional pipolin-harboring genomes from GenBank database spanning strains from diverse origin, further confirmed these results. The genetic structure of pipolins shows great flexibility and variability, with the piPolB gene and the attachment sites being the only common features. Most pipolins contain one or more recombinases that would be involved in excision/integration of the element in the same conserved tRNA gene. This mobilization mechanism might explain the apparent incompatibility of pipolins with other integrative MGEs such as integrons. In addition, analysis of cophylogeny between pipolins and pipolin-harboring strains showed a lack of congruence between several pipolins and their host strains, in agreement with horizontal transfer between hosts. Overall, these results indicate that pipolins can serve as a vehicle for genetic transfer among circulating E. coli and possibly also among other pathogenic bacteria.
Engineering a disulfide-gated switch in streptavidin enables reversible binding without sacrificing binding affinity
Authors: Marangoni Jesse M. , Wu Sau-Ching , Fogen Dawson , Wong Sui-Lam , Ng Kenneth K. S.
Published: July 2020

Although high affinity binding between streptavidin and biotin is widely exploited, the accompanying low rate of dissociation prevents its use in many applications where rapid ligand release is also required. To combine extremely tight and reversible binding, we have introduced disulfide bonds into opposite sides of a flexible loop critical for biotin binding, creating streptavidin muteins (M88 and M112) with novel disulfide-switchable binding properties. Crystal structures reveal how each disulfide exerts opposing effects on structure and function. Whereas the disulfide in M112 disrupts the closed conformation to increase koff, the disulfide in M88 stabilizes the closed conformation, decreasing koff 260-fold relative to streptavidin. The simple and efficient reduction of this disulfide increases koff 19,000-fold, thus creating a reversible redox-dependent switch with 70-fold faster dissociation kinetics than streptavidin. The facile control of disulfide formation in M88 will enable the development of many new applications requiring high affinity and reversible binding.
Gymnosperm glandular trichomes: expanded dimensions of the conifer terpenoid defense system
Authors: Celedon Jose M. , Whitehill Justin G. A. , Madilao Lufiani L. , Bohlmann Joerg
Published: July 2020

Glandular trichomes (GTs) are defensive structures that produce and accumulate specialized metabolites and protect plants against herbivores, pathogens, and abiotic stress. GTs have been extensively studied in angiosperms for their roles in defense and biosynthesis of high-value metabolites. In contrast, trichomes of gymnosperms have been described in fossilized samples, but have not been studied in living plants. Here, we describe the characterization of GTs on young stems of a hybrid white spruce. Metabolite and histological analysis of spruce GTs support a glandular function with accumulation of a diverse array of mono-, sesqui- and diterpenes including diterpene methylesters. Methylated diterpenes have previously been associated with insect resistance in white spruce. Headspeace analysis of spruce GTs showed a profile of volatiles dominated by monoterpenes and a highly diverse array of sesquiterpenes. Spruce GTs appear early during shoot growth, prior to the development of a lignified bark and prior to accumulation of terpenes in needles. Spruce GTs may provide an early, terpene-based chemical defense system at a developmental stage when young shoots are particularly vulnerable to foliage and shoot feeding insects, and before the resin duct system characteristic of conifers has fully developed.
Identifying critical nodes in temporal networks by network embedding
Authors: Yu En-Yu , Fu Yan , Chen Xiao , Xie Mei , Chen Duan-Bing
Published: July 2020

Critical nodes in temporal networks play more significant role than other nodes on the structure and function of networks. The research on identifying critical nodes in temporal networks has attracted much attention since the real-world systems can be illustrated more accurately by temporal networks than static networks. Considering the topological information of networks, the algorithm MLI based on network embedding and machine learning are proposed in this paper. we convert the critical node identification problem in temporal networks into regression problem by the algorithm. The effectiveness of proposed methods is evaluated by SIR model and compared with well-known existing metrics such as temporal versions of betweenness, closeness, k-shell, degree deviation and dynamics-sensitive centralities in one synthetic and five real temporal networks. Experimental results show that the proposed method outperform these well-known methods in identifying critical nodes under spreading dynamic.
Synthesis of thiophene-fused heptalenes by cycloaddition of azulenothiophenes with dimethyl acetylenedicarboxylate
Authors: Shoji Taku , Miura Kota , Ariga Yukino , Yamazaki Akari , Ito Shunji , Yasunami Masafumi
Published: July 2020

Heptalene has a fused structure of two cycloheptatrienes which is one of the non-aromatic bicyclic molecules with a 12π-electronic structure. We report herein the synthesis of thiophene-fused heptalene derivatives from the corresponding azulenothiophenes via cycloaddition reaction with dimethyl acetylenedicarboxylate. Their structure was clarified by single-crystal X-ray structural analysis. The electronic properties of the thiophene-fused heptalenes obtained by this study were characterized by UV/Vis and fluorescence spectroscopy measurements. The electrochemical features of these derivatives were also examined by voltammetry and spectroelectrochemical experiments.
Pulp regeneration with hemostatic matrices as a scaffold in an immature tooth minipig model
Authors: Jang Ji-Hyun , Moon Joung-Ho , Kim Sahng Gyoon , Kim Sun-Young
Published: July 2020

Control of blood clotting in root canal systems is one of the most critical and difficult concerns for regenerative endodontics therapy (RET). The purpose of this study was to investigate the effects of using gelatin- and fibrin-based hemostatic hydrogels as a scaffold on pulp regeneration in a minipig model. Cell viability of human dental pulp stem cells cultured three-dimensionally in gelatin-based and fibrin-based scaffolds was evaluated by MTT and live/dead assay. RET was performed on 24 immature premolars with an autologous blood clot (PC), gelatin-based and fibrin-based hemostatic matrices (GM and FM), or without the insertion of a scaffold (NC). The follow-up period was 12 weeks. Radiographic and histologic assessments for pulp regeneration were performed. Gelatin-based scaffolds exhibited significantly higher cell viability than fibrin-based scaffolds after 15 days (P < 0.05). The PC and GM groups showed favorable root development without inflammation and newly mineralized tissue deposited in the root canal system, while FM group presented inflammatory changes with the continuation of root development. The NC group exhibited internal root resorption with periapical lesions. The application of GM in RET led to favorable clinical outcomes of root development without inflammatory changes compared to conventional RET. Our results suggest that GM may serve as a viable regenerative scaffold for pulp regeneration.