bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression level of SOX2 at the blastocyst stage regulates the developmental capacity of bovine embryos up to day-13 of in vitro culture
Authors: Velásquez A.E. , Veraguas D. , Cabezas J. , Manríquez J. , Castro F.O. , Rodríguez-Alvarez L.L.
Published: October 2019

Quality of in vitro-produced embryos is influenced by changes in gene expression in response to adverse conditions. Gene markers for predicting ‘good embryos’ do not exist at present. We propose that the expression of pluripotency markers OCT4–SOX2–NANOG in D9 (day 9) bovine demi-embryos correlated with development at D13 (day 13). Day 8 in vitro-produced blastocysts were split in two cloned halves, one half (D9) was subjected to analysis of pluripotency markers and the other was kept in culture until D13 of development. Embryo development was scored and correlated with its own status at D9 and assigned to one of two categories: G1, arrested/dead; or G2, development up to D13. SOX2 and NANOG expression levels were significantly higher in embryos from G1 and there was also negative correlation between SOX2 and embryo survival to D13 (G3; r = −0.37; P = 0.03). We observed a significant reduction in the expression of the three studied genes from D9 to D13. Furthermore, there was a correlation between the expression of pluripotency markers at D9 and embryo diameter and the expression of trophoblastic markers at D13 (TP1–EOMES–FGF4–CDX2–TKDP1). Finally, the quotient between the relative expression of SOX2 and OCT4 in the D9 blastocysts from G1 and G2 showed that embryos that were considered as competent (G2) had a quotient close to one, while the other group had a quotient of 2.3 due to a higher expression of SOX2. These results might indicate that overexpression of SOX2 at the blastocyst stage had a negative effect on the control of embryonic developmental potential.
Improving Data Quality in Face-to-Face Survey Research
Authors: Logan Carolyn , Parás Pablo , Robbins Michael , Zechmeister Elizabeth J.
Published: October 2019

Data quality in survey research remains a paramount concern for those studying mass political behavior. Because surveys are conducted in increasingly diverse contexts around the world, ensuring that best practices are followed becomes ever more important to the field of political science. Bringing together insights from surveys conducted in more than 80 countries worldwide, this article highlights common challenges faced in survey research and outlines steps that researchers can take to improve the quality of survey data. Importantly, the article demonstrates that with the investment of the necessary time and resources, it is possible to carry out high-quality survey research even in challenging environments in which survey research is not well established.
An objective method of shape descriptor state establishment using elliptic Fourier analysis (EFA)
Authors: Gentallan Renerio P. , Altoveros Nestor C. , Borromeo Teresita H. , Endonela Leah E. , Hay Fiona R. , Lalusin Antonio G. , Reaño Consorcia E. , Yoshioka Yosuke
Published: October 2019

This research attempts to systematically establish shape descriptor states through elliptic Fourier analysis (EFA) using pili (Canarium ovatum Engl.) kernel as a model. Kernel images of 53 pili accessions from the National Plant Genetic Resources Laboratory (NPGRL), University of the Philippines Los Baños were acquired using VideometerLab 3. Shape features, such as roundness, compactness and elongation, were extracted from the images. Shapes outlines were characterized using elliptic Fourier coefficients calculated from SHAPE version 1.3 software. Principal component analysis and cluster analysis were used to elucidate clusters representing the shape descriptor states. The first principal component accounts for the variation in length to width ratio; whereas, the second and third principal components explain the variation in the location of the widest portion and the truncation of the apex and base of the kernel, respectively. Cluster analysis separated the different accessions into six distinct clusters at 0.04 Euclidian distance. Six descriptor states, narrowly elliptic, elliptic, widely elliptic, ovate, obovate and lance-ovate, were characterized from the shape outlines and visualized through R's shape on r package. The discrimination between clusters was validated through MANOVA and LDA with 95% correct classification. The Fourier coefficients were also able to represent the variation observed from the physical properties of shape. The method may be used in establishing shape descriptors of all plant parts of all crop species.
Die Seele berühren – Energiepsychologie in der Psychosomatik
Authors: Begré Stefan
Published: October 2019

Zusammenfassung. In diesem Artikel werden zwei Methoden zur Stressbewältigung aus dem boomenden Feld der Energiepsychologie vorgestellt. Trotz der ansehnlichen Publikationsdichte sind sie in den hausärztlichen und psychotherapeutischen Praxen und Institutionen immer noch wenig gängig. Die Rede ist vom «Shiatsu» und den «Techniken der Emotionalen Freiheit». Beide Verfahren bewegen sich an der Schnittstelle zwischen Körper und Geist. Beide Verfahren betonen die Achtsamkeit als wichtiges Behandlungsziel im Therapieprozess. Sie liegen damit im Trend östliche Denkweisen und Behandlungsansätze vermehrt in unsere westlich orientierte Medizin zu integrieren. Der Artikel gibt eine Übersicht über die Entstehungsgeschichte beider Methoden, mögliche Wirkmechanismen, ihre wissenschaftliche Evidenz und deren praktische Anwendungstechnik in der Psychosomatik.
Schematherapie bei psychosomatischen Störungen
Authors: Zens Christine
Published: October 2019

Zusammenfassung. Die Schematherapie (ST) ist als Weiterentwicklung der Kognitiven Verhaltenstherapie (KVT) als umfassendes Behandlungskonzept für Patienten mit tiefgreifenden chronischen Störungen entwickelt worden. Bei diesem integrativen psychotherapeutischen Ansatz werden kognitive, emotionsorientierte und behaviorale Interventionen und die Arbeit mit der therapeutischen Beziehung flexibel zu einem zielgerichteten und transparenten Vorgehen verbunden. Die Wirksamkeit der Schematherapie wurde dabei vor allem in Studien zur Behandlung verschiedener Persönlichkeitsstörungen belegt, positive Pilotstudien liegen auch bereits für verschiedene Achse-I-Störungen vor, z. B. Ess- oder Zwangsstörungen. Auch für Patienten mit chronischen psychosomatischen Beschwerden erscheint eine schematherapeutische Behandlung erfolgsversprechend. Dabei können die dem komplexen Bedingungsgefüge zugrunde liegenden Symptome, Verhaltensmuster und zentralen lebensgeschichtlichen Ereignisse mit Hilfe des Schemamodusmodells in einer dem Patienten gut zugänglichen Form konzeptualisiert und bearbeitet werden.
The Paradox of Leader-Member Exchange (LMX)	Differentiation
Authors: Xie Zhitao , Li Ning , Jiang Wan , Kirkman Bradley L.
Published: October 2019

Abstract. Drawing from the equity-equality paradigm and social interdependence theory, we examine cross-level effects of leader-member exchange (LMX) differentiation on both task performance and creativity using 461 team members and 98 team leaders in China. We demonstrate the paradoxical (i.e., positive and negative) effects of LMX differentiation in teams. Specifically, while LMX differentiation was positively, directly associated with task performance and creativity in more interdependent teams, it also had negative, indirect influences, through interactional justice climate, on these outcomes. Overall, in more interdependent teams, LMX differentiation had positive effects on employee performance-based outcomes, but in less interdependent teams, the effects were more negative. Our findings also provide practical implications for team governance.
Development of an I-Deals Motivation and Management	Measure
Authors: Bal P. Matthijs , Vossaert Lien
Published: October 2019

Abstract. This paper introduces three new dimensions to the idiosyncratic deals’ (i.e., i-deals) literature, and develops measures for these dimensions to broaden the scope of research on i-deals beyond i-deal timing and content. Based on four studies, the paper proposes and validates three new scales for measurement of i-deal motivation as well as management of i-deals. In Studies 1 and 2, the scales were developed and tested for their factor structure, reliability, and discriminant validity. Studies 3 and 4 provided further evidence for the psychometric properties of the new i-deals measures and examined antecedents and outcomes of i-deal motivation and management. The results suggest that the three scales can be used to reliably measure i-deal motivation and i-deal management.
Within-Subject Variability in Ingratiation as a Function of	Self-Esteem and Time
Authors: Schmitte Katharina , Schreurs Bert , Segers Mien , “Jim” Jawahar I. M.
Published: October 2019

Abstract. Adopting a within-person perspective, we theorize why ingratiation use directed toward an authority figure increases over time and for whom. We posit that as the appraisal event draws closer, the salience of achieving good evaluations increases, leading to an increasing use of ingratiation. We further propose that the increase will be stronger for individuals with low relative to high self-esteem. Participants were 349 students enrolled in a small-group, tutor-led management course. Data were collected in three bi-weekly waves and analyzed using random coefficient modeling. Results show that ingratiation use increased as time to the evaluation decreased, and low self-esteem students ingratiated more as time progressed. We conclude that ingratiation use varies as a function of contextual and inter-individual differences.
Optical vortices 30 years on: OAM manipulation from topological charge to multiple singularities
Authors: Shen Yijie , Wang Xuejiao , Xie Zhenwei , Min Changjun , Fu Xing , Liu Qiang , Gong Mali , Yuan Xiaocong
Published: October 2019

Thirty years ago, Coullet et al. proposed that a special optical field exists in laser cavities bearing some analogy with the superfluid vortex. Since then, optical vortices have been widely studied, inspired by the hydrodynamics sharing similar mathematics. Akin to a fluid vortex with a central flow singularity, an optical vortex beam has a phase singularity with a certain topological charge, giving rise to a hollow intensity distribution. Such a beam with helical phase fronts and orbital angular momentum reveals a subtle connection between macroscopic physical optics and microscopic quantum optics. These amazing properties provide a new understanding of a wide range of optical and physical phenomena, including twisting photons, spin–orbital interactions, Bose–Einstein condensates, etc., while the associated technologies for manipulating optical vortices have become increasingly tunable and flexible. Hitherto, owing to these salient properties and optical manipulation technologies, tunable vortex beams have engendered tremendous advanced applications such as optical tweezers, high-order quantum entanglement, and nonlinear optics. This article reviews the recent progress in tunable vortex technologies along with their advanced applications.
Autophagy in bone homeostasis and the onset of osteoporosis
Authors: Yin Xing , Zhou Chenchen , Li Jingtao , Liu Renkai , Shi Bing , Yuan Quan , Zou Shujuan
Published: October 2019

Autophagy is an evolutionarily conserved intracellular process, in which domestic cellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival, differentiation, and functioning of bone cells, including osteoblasts, osteocytes, and osteoclasts. Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases, including osteoporosis. This review aims to introduce the topic of autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role in the onset of osteoporosis and therapeutic potential.
Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes
Authors: Spyrou Maria A. , Keller Marcel , Tukhbatova Rezeda I. , Scheib Christiana L. , Nelson Elizabeth A. , Andrades Valtueña Aida , Neumann Gunnar U. , Walker Don , Alterauge Amelie , Carty Niamh , Cessford Craig , Fetz Hermann , Gourvennec Michaël , Hartle Robert , Henderson Michael , von Heyking Kristin , Inskip Sarah A. , Kacki Sacha , Key Felix M. , Knox Elizabeth L. , Later Christian , Maheshwari-Aplin Prishita , Peters Joris , Robb John E. , Schreiber Jürgen , Kivisild Toomas , Castex Dominique , Lösch Sandra , Harbeck Michaela , Herbig Alexander , Bos Kirsten I. , Krause Johannes
Published: October 2019

The second plague pandemic, caused byYersinia pestis, devastated Europe and the nearby regions between the 14thand 18thcenturies AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancientY. pestisgenomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of aY. pestislineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541–750 AD), suggesting a comparable evolutionary trajectory ofY. pestisduring both events.
Australian vegetated coastal ecosystems as global hotspots for climate change mitigation
Authors: Serrano Oscar , Lovelock Catherine E. , B. Atwood Trisha , Macreadie Peter I. , Canto Robert , Phinn Stuart , Arias-Ortiz Ariane , Bai Le , Baldock Jeff , Bedulli Camila , Carnell Paul , Connolly Rod M. , Donaldson Paul , Esteban Alba , Ewers Lewis Carolyn J. , Eyre Bradley D. , Hayes Matthew A. , Horwitz Pierre , Hutley Lindsay B. , Kavazos Christopher R. J. , Kelleway Jeffrey J. , Kendrick Gary A. , Kilminster Kieryn , Lafratta Anna , Lee Shing , Lavery Paul S. , Maher Damien T. , Marbà Núria , Masque Pere , Mateo Miguel A. , Mount Richard , Ralph Peter J. , Roelfsema Chris , Rozaimi Mohammad , Ruhon Radhiyah , Salinas Cristian , Samper-Villarreal Jimena , Sanderman Jonathan , J. Sanders Christian , Santos Isaac , Sharples Chris , Steven Andrew D. L. , Cannard Toni , Trevathan-Tackett Stacey M. , Duarte Carlos M.
Published: October 2019

Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO2 emission benefits of VCE conservation and restoration. Australia contributes 5–11% of the C stored in VCE globally (70–185 Tg C in aboveground biomass, and 1,055–1,540 Tg C in the upper 1 m of soils). Potential CO2 emissions from current VCE losses are estimated at 2.1–3.1 Tg CO2-e yr-1, increasing annual CO2 emissions from land use change in Australia by 12–21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions.
Bottom-up growth of homogeneous Moiré superlattices in bismuth oxychloride spiral nanosheets
Authors: Liu Lulu , Sun Yuanhui , Cui Xiaoqiang , Qi Kun , He Xin , Bao Qiaoliang , Ma Weiliang , Lu Jiong , Fang Hanyan , Zhang Peng , Zheng Lirong , Yu Liping , Singh David J. , Xiong Qihua , Zhang Lijun , Zheng Weitao
Published: October 2019

Moiré superlattices (MSLs) are modulated structures produced from homogeneous or heterogeneous 2D layers stacked with a twist angle and/or lattice mismatch. Expanding the range of available materials, methods for fabricating MSL, and realization of unique emergent properties are key challenges. Here we report a facile bottom-up synthesis of homogeneous MSL based on a wide-gap 2D semiconductor, BiOCl, using a one-pot solvothermal approach with robust reproducibility. Unlike previous MSLs usually prepared by directly stacking two monolayers, our BiOCl MSLs are realized in a scalable, direct way through chemical growth of spiral-type nanosheets driven by screw-dislocations. We find emergent properties including large band gap reduction (∼0.6 eV), two-fold increase in carrier lifetime, and strongly enhanced photocatalytic activity. First-principles calculations reveal that such unusual properties can be ascribed to the locally enhanced inter-layer coupling associated with the Moiré potential modulation. Our results demonstrate the promise of MSL materials for chemical and physical functions.
Hydrogen-bonded frameworks for molecular structure determination
Authors: Li Yuantao , Tang Sishuang , Yusov Anna , Rose James , Borrfors André Nyberg , Hu Chunhua T. , Ward Michael D.
Published: October 2019

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. We report herein an approach to molecular structure determination that relies on a versatile toolkit of guanidinium organosulfonate hydrogen-bonded host frameworks that form crystalline inclusion compounds with target molecules in a single-step crystallization, complementing the crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination.
Systematic identification of metabolites controlling gene expression in E. coli
Authors: Lempp Martin , Farke Niklas , Kuntz Michelle , Freibert Sven Andreas , Lill Roland , Link Hannes
Published: October 2019

Metabolism controls gene expression through allosteric interactions between metabolites and transcription factors. These interactions are usually measured with in vitro assays, but there are no methods to identify them at a genome-scale in vivo. Here we show that dynamic transcriptome and metabolome data identify metabolites that control transcription factors in E. coli. By switching an E. coli culture between starvation and growth, we induce strong metabolite concentration changes and gene expression changes. Using Network Component Analysis we calculate the activities of 209 transcriptional regulators and correlate them with metabolites. This approach captures, for instance, the in vivo kinetics of CRP regulation by cyclic-AMP. By testing correlations between all pairs of transcription factors and metabolites, we predict putative effectors of 71 transcription factors, and validate five interactions in vitro. These results show that combining transcriptomics and metabolomics generates hypotheses about metabolism-transcription interactions that drive transitions between physiological states.
Intrinsic magnetic topological insulator phases in the Sb doped MnBi2Te4 bulks and thin flakes
Authors: Chen Bo , Fei Fucong , Zhang Dongqin , Zhang Bo , Liu Wanling , Zhang Shuai , Wang Pengdong , Wei Boyuan , Zhang Yong , Zuo Zewen , Guo Jingwen , Liu Qianqian , Wang Zilu , Wu Xuchuan , Zong Junyu , Xie Xuedong , Chen Wang , Sun Zhe , Wang Shancai , Zhang Yi , Zhang Minhao , Wang Xuefeng , Song Fengqi , Zhang Haijun , Shen Dawei , Wang Baigeng
Published: October 2019

Magnetic topological insulators (MTIs) offer a combination of topologically nontrivial characteristics and magnetic order and show promise in terms of potentially interesting physical phenomena such as the quantum anomalous Hall (QAH) effect and topological axion insulating states. However, the understanding of their properties and potential applications have been limited due to a lack of suitable candidates for MTIs. Here, we grow two-dimensional single crystals of Mn(SbxBi(1-x))2Te4 bulk and exfoliate them into thin flakes in order to search for intrinsic MTIs. We perform angle-resolved photoemission spectroscopy, low-temperature transport measurements, and first-principles calculations to investigate the band structure, transport properties, and magnetism of this family of materials, as well as the evolution of their topological properties. We find that there exists an optimized MTI zone in the Mn(SbxBi(1-x))2Te4 phase diagram, which could possibly host a high-temperature QAH phase, offering a promising avenue for new device applications.
Rate-selected growth of ultrapure semiconducting carbon nanotube arrays
Authors: Zhu Zhenxing , Wei Nan , Cheng Weijun , Shen Boyuan , Sun Silei , Gao Jun , Wen Qian , Zhang Rufan , Xu Jun , Wang Yao , Wei Fei
Published: October 2019

Carbon nanotubes (CNTs) are promising candidates for smart electronic devices. However, it is challenging to mediate their bandgap or chirality from a vapor-liquid-solid growth process. Here, we demonstrate rate-selected semiconducting CNT arrays based on interlocking between the atomic assembly rate and bandgap of CNTs. Rate analysis confirms the Schulz-Flory distribution which leads to various decay rates as length increases in metallic and semiconducting CNTs. Quantitatively, a nearly ten-fold faster decay rate of metallic CNTs leads to a spontaneous purification of the predicted 99.9999% semiconducting CNTs at a length of 154 mm, and the longest CNT can be 650 mm through an optimized reactor. Transistors fabricated on them deliver a high current of 14 μA μm−1 with on/off ratio around 108 and mobility over 4000 cm2 V−1 s−1. Our rate-selected strategy offers more freedom to control the CNT purity in-situ and offers a robust methodology to synthesize perfectly assembled nanotubes over a long scale.
Non-motor correlates of wrist-worn wearable sensor use in Parkinson’s disease: an exploratory analysis
Authors: van Wamelen Daniel J. , Hota Shweta , Podlewska Aleksandra , Leta Valentina , Trivedi Dhaval , Rizos Alexandra , Parry Miriam , Chaudhuri K. Ray
Published: October 2019

Wearable sensors are becoming increasingly more available in Parkinson’s disease and are used to measure motor function. Whether non-motor symptoms (NMS) can also be measured with these wearable sensors remains unclear. We therefore performed a retrospective, exploratory, analysis of 108 patients with a diagnosis of idiopathic Parkinson’s disease enroled in the Non-motor Longitudinal International Study (UKCRN No. 10084) at King’s College Hospital, London, to determine the association between the range and nature of NMS and an accelerometer-based outcome measure of bradykinesia (BKS) and dyskinesia (DKS). NMS were assessed by the validated NMS Scale, and included, e.g., cognition, mood and sleep, and gastrointestinal, urinary and sexual problems. Multiple linear regression modelling was used to identify NMS associated with BKS and DKS. We found that BKS was associated with domains 6 (gastrointestinal tract; p = 0.006) and 8 (sexual function; p = 0.003) of the NMS scale. DKS was associated with domains 3 (mood/cognition; p = 0.016), 4 (perceptual problems; p = 0.025), 6 (gastrointestinal tract; p = 0.029) and 9 (miscellaneous, p = 0.003). In the separate domains, constipation was significantly associated with BKS. Delusions, dysphagia, hyposmia, weight change and hyperhidrosis were identified as significantly associated with DKS. None of the NMSS domains were associated with disease duration (p ≥ 0.08). In conclusion, measures of BKS and DKS were mainly associated with gastrointestinal problems, independent of disease duration, showing the potential for wearable devices to pick up on these symptoms. These exploratory results deserve further exploration, and more research on this topic in the form of comprehensive large-scale studies is needed.
Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice
Authors: Hayrabedyan Soren , Shainer Reut , Yekhtin Zhanna , Weiss Lola , Almogi-Hazan Osnat , Or Reuven , Farnsworth Charles L. , Newsome Scott , Todorova Krassimira , Paidas Michael J. , Brodie Chaya , Barnea Eytan R. , Mueller Martin
Published: October 2019

An autoimmune response against myelin protein is considered one of the key pathogenic processes that initiates multiple sclerosis (MS). The currently available MS disease modifying therapies have demonstrated to reduce the frequency of inflammatory attacks. However, they appear limited in preventing disease progression and neurodegeneration. Hence, novel therapeutic approaches targeting both inflammation and neuroregeneration are urgently needed. A new pregnancy derived synthetic peptide, synthetic PreImplantation Factor (sPIF), crosses the blood-brain barrier and prevents neuro-inflammation. We report that sPIF reduces paralysis and de-myelination of the brain in a clinically-relevant experimental autoimmune encephalomyelitis mice model. These effects, at least in part, are due to post-translational modifications, which involve cyclic AMP dependent protein kinase (PKA), calcium-dependent protein kinase (PKC), and immune regulation. In terms of potential MS treatment, sPIF was successfully tested in neurodegenerative animal models of perinatal brain injury and experimental autoimmune encephalitis. Importantly, sPIF received a FDA Fast Track Approval for first in human trial in autommuninty (completed).
A Rapid ATP Bioluminescence-based Test for Detecting Levofloxacin Resistance Starting from Positive Blood Culture Bottles
Authors: Matsui Atsushi , Niimi Hideki , Uchiho Yuichi , Kawabe Shunsuke , Noda Hideyuki , Kitajima Isao
Published: October 2019

Administering appropriate antimicrobial therapy as early as possible is important for rescuing bacteremic patients. Therefore, rapid antimicrobial susceptibility tests in positive blood culture specimens have been diligently sought. Adenosine triphosphate (ATP) bioluminescence-based methods have been used for rapid antimicrobial susceptibility tests. However, blood culture specimens have not been examined in many studies, possibly due to abundant intracellular ATP in blood corpuscles resulting in false-susceptible results. In this study, we developed a rapid ATP bioluminescence-based method for detecting antibiotic resistance starting from positive blood culture. To minimize background ATP originating from blood corpuscles, specimens were centrifuged and the supernatant diluted with broth, and an ATP-eliminating reagent was then added to the bacterial suspension at the beginning of incubation. This newly devised procedure reduced the background ATP by more than five orders of magnitude. In a pilot study using levofloxacin, no false-susceptible results were observed in 15 clinical specimens. Furthermore, the results indicated that the rapid method provided additional information about bacterial activities with high resolution, in contrast to the less-thorough findings with the conventional turbidity method. Therefore, our approach will contribute to the treatment of infectious diseases as a rapid antimicrobial susceptibility test.
Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle
Authors: Aung T. N. , Nourmohammadi S. , Qu Z. , Harata-Lee Y. , Cui J. , Shen H. Y. , Yool A. J. , Pukala T. , Du Hong , Kortschak R. D. , Wei W. , Adelson D. L.
Published: October 2019

We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.
CNN-based diagnosis models for canine ulcerative keratitis
Authors: Kim Joon Young , Lee Ha Eun , Choi Yeon Hyung , Lee Suk Jun , Jeon Jong Soo
Published: October 2019

The purpose of this methodological study was to develop a convolutional neural network (CNN), which is a recently developed deep-learning-based image recognition method, to determine corneal ulcer severity in dogs. The CNN model was trained with images for which corneal ulcer severity (normal, superficial, and deep) were previously classified by veterinary ophthalmologists’ diagnostic evaluations of corneal photographs from patients who visited the Veterinary Medical Teaching Hospital (VMTH) at Konkuk University and 3 different veterinary ophthalmology specialty hospitals in Korea. The original images (depicting normal corneas (36) and corneas with superficial (47) ulcers, deep (47) ulcers), flipped images (total 520), rotated images (total 520), and both flipped and rotated images (total 1,040) were labeled, learned and evaluated with GoogLeNet, ResNet, and VGGNet models, and the severity of each corneal ulcer image was determined. To accomplish this task, models based on TensorFlow, an open-source software library developed by Google, were used, and the labeled images were converted into TensorFlow record (TFRecord) format. The models were fine-tuned using a CNN model trained on the ImageNet dataset and then used to predict severity. Most of the models achieved accuracies of over 90% when classifying superficial and deep corneal ulcers, and ResNet and VGGNet achieved accuracies over 90% for classifying normal corneas, corneas with superficial ulcers, and corneas with deep ulcers. This study proposes a method to effectively determine corneal ulcer severity in dogs by using a CNN and concludes that multiple image classification models can be used in the veterinary field.
The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning
Authors: George Grace , Draycott Sally A. V. , Muir Ronan , Clifford Bethan , Elmes Matthew J. , Langley-Evans Simon C.
Published: October 2019

Exposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.
Antibacterial, angiogenic, and osteogenic activities of Ca, P, Co, F, and Sr compound doped titania coatings with different Sr content
Authors: Zhou Jianhong , Wang Xiaoli , Zhao Lingzhou
Published: October 2019

Titanium implants are often combined with microporous titania coatings simultaneously doped with various elements to enhance their antibacterial, angiogenic and osteogenic activities. To evaluate how Sr doping levels affect properties of titania coatings simultaneously doped with Ca, P, Co and F (TiCPCF coatings), we prepared coatings with Sr contents equal to 6, 11 and 18 wt% (TiCPCF-S6, TiCPCF-S11 and TiCPCF-S18, respectively) using micro-arc oxidation of titanium. Sr presence in TiCPCF coatings did not affect their phase compositions, microstructure, surface wettability, roughness, and adhesion to titanium. Antibacterial, angio- and osteo-genic activities of all the coatings were evaluated. Sr incorporation improved mesenchymal stem cell proliferation, osteogenic differentiation and implant osseointegration. TiCPCF-S11 showed the most optimum Sr content judging by its enhanced osteogenic activity. While Sr incorporation did not weaken angiogenic and antibacterial abilities of TiCPCF. Thus TiCPCF-S11 coating is a very strong candidate to be used as a next-generation bone implant material.
Antimicrobial peptide, cLF36, affects performance and intestinal morphology, microflora, junctional proteins, and immune cells in broilers challenged with E. coli
Authors: Daneshmand Ali , Kermanshahi Hassan , Sekhavati Mohammad Hadi , Javadmanesh Ali , Ahmadian Monireh
Published: October 2019

This study investigated the effects of an antimicrobial peptide (AMP), cLF36, on growth performance and the histophysiological changes of the intestine in E. coli-challenged broiler chickens. A total number of 360 day old male chicks were randomly assigned to 4 groups of 6 replicates as follows: T1) negative control diet based on corn-soybean meal without E. coli challenge and additives; T2) positive control diet based on corn-soybean meal and challenged with E. coli without any additives; T3) positive control diet challenged with E. coli and supplemented with 20 mg AMP (cLF36)/kg diet; T4) positive control diet challenged with E. coli and supplemented with 45 mg antibiotic (bacitracin methylene disalicylate)/kg diet. Results showed that T3 improved growth performance and the jejunal morphology of E. coli-challenged chickens similar to those of T4. While antibiotic non-selectively decreased the population of ileal bacteria, AMP increased the population of Lactobacillus spp. and decreased harmful bacteria in the ileum of E. coli-challenged chickens. Supplementing E. coli-challenged chickens with AMP improved the gene expression of immune cells and upregulated the expression of tight junction proteins compared to other challenged groups. In conclusion, although cLF36 beneficially affected growth performance and the intestinal morphology of E. coli-challenged chickens similar to those of the antibiotic group, this AMP drastically improved the intestinal microbiome, immune cells, and junctional proteins compared to other E. coli-challenged birds, and can be nominated as an alternative for growth promoter antibiotics.
A robust bacterial assay for high-throughput screening of human 4-hydroxyphenylpyruvate dioxygenase inhibitors
Authors: Neuckermans Jessie , Mertens Alan , De Win Dinja , Schwaneberg Ulrich , De Kock Joery
Published: October 2019

Hereditary tyrosinemia type 1 (HT1) and alkaptonuria (AKU) are inherited metabolic disorders caused by defective enzymes involved in tyrosine catabolism. Nitisinone, an ex-herbicide and member of the β-triketone family, is therapeutically applied to prevent accumulation of toxic metabolites in patients by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). Here, we developed a colorimetric bacterial whole-cell screening system that allows quantifying the inhibitory effects of human HPD inhibitors in a high-throughput and a robust fashion. The principle of our screening system is based on the degradation of tyrosine through 4-hydroxyphenylpyruvate into homogentisate by human HPD expressed in E. coli and subsequent production of a soluble melanin-like pigment. With the aim to optimise the assay, we tested different E. coli strains, expression and reaction temperatures, and time-points for supplementing the substrate. We found that in our assay the addition of prototypical β-triketone HPD inhibitors decreases pigment production in a dose-dependent manner with increasing inhibitor concentrations. In addition, plate uniformity, signal variability and spatial uniformity assessment showed that we have developed a robust high-throughput screening assay that is simple to use, cost-effective and enables identification and evaluation of novel therapeutic human HPD inhibitors for the treatment of tyrosine-related metabolic disorders.
Deciphering bacterial and fungal endophyte communities in leaves of two maple trees with green islands
Authors: Wemheuer Franziska , Wemheuer Bernd , Daniel Rolf , Vidal Stefan
Published: October 2019

Green islands (the re-greening of senescent leaf tissues) are particularly evident on leaves infected with fungal pathogens. To date, there is only a limited number of studies investigating foliar endophytic microorganisms in phytopathogen-infected leaves. Here, we analysed bacterial and fungal endophyte communities in leaves without green islands (control leaves; CL), within green island areas (GLA) and the surrounding yellow leaf areas (YLA) of leaves with green islands of Acer campestre and A. platanoides. GLA samples of A. campestre and A. platanoides were dominated by Sawadaea polyfida and S. bicornis, respectively, suggesting that these fungi might be responsible for the green islands. We detected a higher fungal richness and diversity in CL compared to GLA samples of A. campestre. Leaf status (CL, GLA, YLA) significantly altered the composition of fungal communities of A. campestre. This was related to differences in fungal community composition between YLA and GLA samples. Site was the main driver of bacterial communities, suggesting that bacterial and fungal endophytes are shaped by different factors. Overall, we observed Acer species-specific responses of endophyte communities towards the presence of green islands and/or leaf type, which might be attributed to several fungi and bacteria specifically associated with one Acer species.
Global areas of low human impact (‘Low Impact Areas’) and fragmentation of the natural world
Authors: Jacobson Andrew P. , Riggio Jason , M. Tait Alexander , E. M. Baillie Jonathan
Published: October 2019

Habitat loss and fragmentation due to human activities is the leading cause of the loss of biodiversity and ecosystem services. Protected areas are the primary response to this challenge and are the cornerstone of biodiversity conservation efforts. Roughly 15% of land is currently protected although there is momentum to dramatically raise protected area targets towards 50%. But, how much land remains in a natural state? We answer this critical question by using open-access, frequently updated data sets on terrestrial human impacts to create a new categorical map of global human influence (‘Low Impact Areas’) at a 1 km2resolution. We found that 56% of the terrestrial surface, minus permanent ice and snow, currently has low human impact. This suggests that increased protected area targets could be met in areas minimally impacted by people, although there is substantial variation across ecoregions and biomes. While habitat loss is well documented, habitat fragmentation and differences in fragmentation rates between biomes has received little attention. Low Impact Areas uniquely enabled us to calculate global fragmentation rates across biomes, and we compared these to an idealized globe with no human-caused fragmentation. The land in Low Impact Areas is heavily fragmented, compromised by reduced patch size and core area, and exposed to edge effects. Tropical dry forests and temperate grasslands are the world’s most impacted biomes. We demonstrate that when habitat fragmentation is considered in addition to habitat loss, the world’s species, ecosystems and associated services are in worse condition than previously reported.
Comparisons of lung and gluteus transcriptome profiles between yaks at different ages
Authors: Xin Jin-Wei , Chai Zhi-Xin , Zhang Cheng-Fu , Zhang Qiang , Zhu Yong , Cao Han-Wen , Ji Qiu-Mei , Zhong Jin-Cheng
Published: October 2019

The yak,Bos grunniens, is the only large mammal in the Qinghai-Tibet Plateau and has been bred to provide meat, milk, and transportation. Previous studies indicate that the immune system contributes to the yak’s adaptation to high-altitude environments. In order to further investigate changes in immune function during yak development, we compared the transcriptome profiles of gluteus and lung tissues among yaks at 6, 30, 60, and 90 months of age. Analyses of significantly differentially expressed genes (DEGs) in lung tissues revealed that immune function was more activated at 6-months and less activated at 90-months than in the 30 and 60-month-old animals. DEG exploration in gluteal tissues revealed that immune functions were more highly activated at both 6 and 90-months, compared with 30 and 60-months. Immune system activation in the muscle and lung tissues of 30-month-old yaks may increase their resistance to infections, while decreased may be due to aging. Furthermore, the higher immune activation status in the gluteal tissues in 90-month-old yaks could be due to muscle injury and subsequent regeneration, which is supported by the fact that 5 unigenes related with muscle injury and 3 related to muscle regeneration displayed greater expression levels at 90-months than at 30 and 60-months. Overall, the present study highlights the important role of the immune system in yak development, which will facilitate future investigations.
Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation
Authors: Ricobaraza Ana , Mora-Jimenez Lucia , Puerta Elena , Sanchez-Carpintero Rocio , Mingorance Ana , Artieda Julio , Nicolas Maria Jesus , Besne Guillermo , Bunuales Maria , Gonzalez-Aparicio Manuela , Sola-Sevilla Noemi , Valencia Miguel , Hernandez-Alcoceba Ruben
Published: October 2019

Dravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 °C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. 18F-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1aWT/A1783V mice. We conclude that the Scn1aWT/A1783V model is a robust research platform for the evaluation of new therapies against DS.
Loss of secretin results in systemic and pulmonary hypertension with cardiopulmonary pathologies in mice
Authors: Zaw Aung Moe , Sekar Revathi , Mak Sarah O. K. , Law Helen K. W. , Chow Billy K. C.
Published: October 2019

More than 1 billion people globally are suffering from hypertension, which is a long-term incurable medical condition that can further lead to dangerous complications and death if left untreated. In earlier studies, the brain-gut peptide secretin (SCT) was found to be able to control blood pressure by its cardiovascular and pulmonary effects. For example, serum SCT in patients with congestive heart failure was one-third of the normal level. These observations strongly suggest that SCT has a causal role in blood pressure control, and in this report, we used constitutive SCT knockout (SCT−/−) mice and control C57BL/6N mice to investigate differences in the morphology, function, underlying mechanisms and response to SCT treatment. We found that SCT−/− mice suffer from systemic and pulmonary hypertension with increased fibrosis in the lungs and heart. Small airway remodelling and pulmonary inflammation were also found in SCT−/− mice. Serum NO and VEGF levels were reduced and plasma aldosterone levels were increased in SCT−/− mice. Elevated cardiac aldosterone and decreased VEGF in the lungs were observed in the SCT−/− mice. More interestingly, SCT replacement in SCT−/− mice could prevent the development of heart and lung pathologies compared to the untreated group. Taken together, we comprehensively demonstrated the critical role of SCT in the cardiovascular and pulmonary systems and provide new insight into the potential role of SCT in the pathological development of cardiopulmonary and cardiovascular diseases.