bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of biosynthetic genes, specific SNP patterns and differences in transcript accumulation cause variation in hydroxynitrile glucoside content in barley cultivars
Authors: Ehlert Marcus , Jagd Lea Møller , Braumann Ilka , Dockter Christoph , Crocoll Christoph , Motawia Mohammed Saddik , Møller Birger Lindberg , Lyngkjær Michael Foged 
Published: April 2019

AbstractBarley (Hordeum vulgare L.) produces five leucine-derived hydroxynitrile glucosides, potentially involved in alleviating pathogen and environmental stresses. These compounds include the cyanogenic glucoside epiheterodendrin. The biosynthetic genes are clustered. Total hydroxynitrile glucoside contents were previously shown to vary from zero to more than 10,000 nmoles g−1 in different barley lines. To elucidate the cause of this variation, the biosynthetic genes from the high-level producer cv. Mentor, the medium-level producer cv. Pallas, and the zero-level producer cv. Emir were investigated. In cv. Emir, a major deletion in the genome spanning most of the hydroxynitrile glucoside biosynthetic gene cluster was identified and explains the complete absence of hydroxynitrile glucosides in this cultivar. The transcript levels of the biosynthetic genes were significantly higher in the high-level producer cv. Mentor compared to the medium-level producer cv. Pallas, indicating transcriptional regulation as a contributor to the variation in hydroxynitrile glucoside levels. A correlation between distinct single nucleotide polymorphism (SNP) patterns in the biosynthetic gene cluster and the hydroxynitrile glucoside levels in 227 barley lines was identified. It is remarkable that in spite of the demonstrated presence of a multitude of SNPs and differences in transcript levels, the ratio between the five hydroxynitrile glucosides is maintained across all the analysed barley lines. This implies the involvement of a stably assembled multienzyme complex.
Viscoelastic biomarker for differentiation of benign and malignant breast lesion in ultra- low frequency range
Authors: Nabavizadeh Alireza , Bayat Mahdi , Kumar Viksit , Gregory Adriana , Webb Jeremy , Alizad Azra , Fatemi Mostafa 
Published: April 2019

AbstractBenign and malignant tumors differ in the viscoelastic properties of their cellular microenvironments and in their spatiotemporal response to very low frequency stimuli. These differences can introduce a unique viscoelastic biomarker in differentiation of benign and malignant tumors. This biomarker may reduce the number of unnecessary biopsies in breast patients. Although different methods have been developed so far for this purpose, none of them have focused on in vivo and in situ assessment of local viscoelastic properties in the ultra-low (sub-Hertz) frequency range. Here we introduce a new, noninvasive model-free method called Loss Angle Mapping (LAM). We assessed the performance results on 156 breast patients. The method was further improved by detection of out-of-plane motion using motion compensation cross correlation method (MCCC). 45 patients met this MCCC criterion and were considered for data analysis. Among this population, we found 77.8% sensitivity and 96.3% specificity (p < 0.0001) in discriminating between benign and malignant tumors using logistic regression method regarding the pre known information about the BIRADS number and size. The accuracy and area under the ROC curve, AUC, was 88.9% and 0.94, respectively. This method opens new avenues to investigate the mechanobiology behavior of different tissues in a frequency range that has not yet been explored in any in vivo patient studies.
Metabolic resistance of the D-peptide RD2 developed for direct elimination of amyloid-β oligomers
Authors: Elfgen Anne , Hupert Michelle , Bochinsky Kevin , Tusche Markus , González de San Román Martin Estibaliz , Gering Ian , Sacchi Silvia , Pollegioni Loredano , Huesgen Pitter F. , Hartmann Rudolf , Santiago-Schübel Beatrix , Kutzsche Janine , Willbold Dieter 
Published: April 2019

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder leading to dementia. Aggregation of the amyloid-β peptide (Aβ) plays an important role in the disease, with Aβ oligomers representing the most toxic species. Previously, we have developed the Aβ oligomer eliminating therapeutic compound RD2 consisting solely of D-enantiomeric amino acid residues. RD2 has been described to have an oral bioavailability of more than 75% and to improve cognition in transgenic Alzheimer’s disease mouse models after oral administration. In the present study, we further examined the stability of RD2 in simulated gastrointestinal fluids, blood plasma and liver microsomes. In addition, we have examined whether RD2 is a substrate for the human D-amino acid oxidase (hDAAO). Furthermore, metabolite profiles of RD2 incubated in human, rodent and non-rodent liver microsomes were compared across species to search for human-specific metabolites that might possibly constitute a threat when applying the compound in humans. RD2 was remarkably resistant against metabolization in all investigated media and not converted by hDAAO. Moreover, RD2 did not influence the activity of any of the tested enzymes. In conclusion, the high stability and the absence of relevant human-specific metabolites support RD2 to be safe for oral administration in humans.
Clustering of integrin β cytoplasmic domains triggers nascent adhesion formation and reveals a protozoan origin of the integrin-talin interaction
Authors: Baade Timo , Paone Christoph , Baldrich Adrian , Hauck Christof R. 
Published: April 2019

AbstractIntegrins and integrin-dependent cell-matrix adhesions are essential for a number of physiological processes. Integrin function is tightly regulated via binding of cytoplasmic proteins to integrin intracellular domains. Yet, the complexity of cell-matrix adhesions in mammals, with more than 150 core adhesome proteins, complicates the analysis of integrin-associated protein complexes. Interestingly, the evolutionary origin of integrins dates back before the transition from unicellular life to complex multicellular animals. Though unicellular relatives of metazoa have a less complex adhesome, nothing is known about the initial steps of integrin activation and adhesion complex assembly in protozoa. Therefore, we developed a minimal, microscope-based system using chimeric integrins to investigate receptor-proximal events during focal adhesion assembly. Clustering of the human integrin β1 tail led to recruitment of talin, kindlin, and paxillin and mutation of the known talin binding site abolished recruitment of this protein. Proteins indirectly linked to integrins, such as vinculin, migfilin, p130CAS, or zyxin were not enriched around the integrin β1 tail. With the exception of integrin β4 and integrin β8, the cytoplasmic domains of all human integrin β subunits supported talin binding. Likewise, the cytoplasmic domains of integrin β subunits expressed by the protozoan Capsaspora owczarzaki readily recruited talin and this interaction was based on an evolutionary conserved NPXY/F amino acid motif. The results we present here validate the use of our novel microscopic assay to uncover details of integrin-based protein-protein interactions in a cellular context and suggest that talin binding to integrin β cytoplasmic tails is an ancient feature of integrin regulation.
High-Throughput, Time-Resolved Mechanical Phenotyping of Prostate Cancer Cells
Authors: Belotti Yuri , Tolomeo Serenella , Conneely Michael J. , Huang Tianjun , McKenna Stephen J. , Nabi Ghulam , McGloin David 
Published: April 2019

AbstractWorldwide, prostate cancer sits only behind lung cancer as the most commonly diagnosed form of the disease in men. Even the best diagnostic standards lack precision, presenting issues with false positives and unneeded surgical intervention for patients. This lack of clear cut early diagnostic tools is a significant problem. We present a microfluidic platform, the Time-Resolved Hydrodynamic Stretcher (TR-HS), which allows the investigation of the dynamic mechanical response of thousands of cells per second to a non-destructive stress. The TR-HS integrates high-speed imaging and computer vision to automatically detect and track single cells suspended in a fluid and enables cell classification based on their mechanical properties. We demonstrate the discrimination of healthy and cancerous prostate cell lines based on the whole-cell, time-resolved mechanical response to a hydrodynamic load. Additionally, we implement a finite element method (FEM) model to characterise the forces responsible for the cell deformation in our device. Finally, we report the classification of the two different cell groups based on their time-resolved roundness using a decision tree classifier. This approach introduces a modality for high-throughput assessments of cellular suspensions and may represent a viable application for the development of innovative diagnostic devices.
Crystalline orientation control of the platelet Nd2Fe14B phase to produce magnetic anisotropy via electromagnetic vibration processing
Authors: Li Mingjun , Tamura Takuya 
Published: April 2019

AbstractControlled crystalline orientation of the discontinuous phase in a composite enables the production of improved anisotropic properties, e.g., well-aligned Nd2Fe14B platelets by hot pressing and then soaking in a low-melting Nd-Cu eutectic melt to infiltrate to grain boundary. Alternatively, an anisotropic magnet can be fabricated by sintering Nd2Fe14B powder pre-aligned with a static magnetic field. In this study, we used a two-step electromagnetic vibration (EMV) technique to solidify the Nd70Cu30-30wt% Nd2Fe14B alloy, by which the magnetic Nd2Fe14B compound could be segmented into short laths and the easy magnetisation axes of these discontinuous platelets could be highly aligned, as revealed by electron backscatter diffraction (EBSD) patterns. Magnetic properties showed that the alloy exhibited strong anisotropy in its magnetism. Our present results opened a new avenue for the simple production of anisotropic Nd2Fe14B magnets via solidification without the powder metallurgy routine. Moreover, the technique is highly expected to be applied to other systems, e.g., graphene-reinforced metallic and/or polymer composites in which the alignment of graphene can maximise the anisotropy in the thermal or electrical properties of the composites.
Tubulin is actively exported from the nucleus through the Exportin1/CRM1 pathway
Authors: Schwarzerová K. , Bellinvia E. , Martinek J. , Sikorová L. , Dostál V. , Libusová L. , Bokvaj P. , Fischer L. , Schmit A. C. , Nick P. 
Published: April 2019

AbstractMicrotubules of all eukaryotic cells are formed by α- and β-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and β-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase.
A Tumor-Selective Monoclonal Antibody from Immunization with a Tumor-Associated Mucin Glycopeptide
Authors: Trabbic Kevin R. , Whalen Kaitlyn , Abarca-Heideman Karin , Xia Li , Temme J. Sebastian , Edmondson Elijah F. , Gildersleeve Jeffrey C. , Barchi Joseph J. 
Published: April 2019

AbstractWe have previously studied the generation of immune responses after vaccination with tumor-associated carbohydrate antigen (TACA)-containing glycopeptides from the tandem repeat (TR) sequence of MUC4, an aberrantly expressed mucin in pancreatic adenocarcinomas. A specific lead antigen from that study containing the Thomsen-Friedenreich TACA disaccharide facilitated the pursuit of a monoclonal antibody to this synthetic hapten. Initial evaluation of polyclonal antiserum resulting from immunization with a KLH conjugate of this glycopeptide into rabbits showed high titer antibodies by ELISA assays, and selective immunoreactivity with MUC4+ cells by western blot and flow cytometry techniques. Glycan microarray analysis showed an intriguing binding pattern where the antiserum showed near complete specificity for MUC4 TR glycopeptides and peptides, relative to all components on the array. Tissue staining also showed distinct tumor specificity to pancreatic tumor tissue in relation to normal pancreatic tissue, with a preference for more aggressive tumor foci. Based on this data, we produced a monoclonal antibody whose binding and reactivity profile was similar to that of the polyclonal serum, with the added benefit of being more specific for the N-terminal glycosylated peptide domain. This epitope represents a novel immunogen to potentially develop diagnostic antibodies or immunotherapies against various MUC4-positive cancers.
Tight N-observable uncertainty relations and their experimental demonstrations
Authors: Chen Zhi-Xin , Wang Hui , Li Jun-Li , Song Qiu-Cheng , Qiao Cong-Feng 
Published: April 2019

AbstractThe uncertainty relation, as one of the fundamental principles of quantum physics, captures the incompatibility of noncommuting observables in the preparation of quantum states. In this work, we derive two strong and universal uncertainty relations for N(N ≥ 2) observables with discrete and bounded spectra, one in multiplicative form and the other in additive form. To verify their validity, for illustration, we implement in the spin-1/2 system an experiment with single-photon measurement. The experimental results exhibit the validity and robustness of these uncertainty relations, and indicate the existence of stringent lower bounds.
A Comparison of Static and Dynamic Functional Connectivities for Identifying Subjects and Biological Sex Using Intrinsic Individual Brain Connectivity
Authors: Menon Sreevalsan S. , Krishnamurthy K. 
Published: April 2019

AbstractFunctional magnetic resonance imaging has revealed correlated activities in brain regions even in the absence of a task. Initial studies assumed this resting-state functional connectivity (FC) to be stationary in nature, but recent studies have modeled these activities as a dynamic network. Dynamic spatiotemporal models better model the brain activities, but are computationally more involved. A comparison of static and dynamic FCs was made to quantitatively study their efficacies in identifying intrinsic individual connectivity patterns using data from the Human Connectome Project. Results show that the intrinsic individual brain connectivity pattern can be used as a ‘fingerprint’ to distinguish among and identify subjects and is more accurately captured with partial correlation and assuming static FC. It was also seen that the intrinsic individual brain connectivity patterns were invariant over a few months. Additionally, biological sex identification was successfully performed using the intrinsic individual connectivity patterns, and group averages of male and female FC matrices. Edge consistency, edge variability and differential power measures were used to identify the major resting-state networks involved in identifying subjects and their sex.
Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells
Authors: Sekine Shin-ichiro , Kaneko Masayuki , Tanaka Masaki , Ninomiya Yuhei , Kurita Hisaka , Inden Masatoshi , Yamada Megumi , Hayashi Yuichi , Inuzuka Takashi , Mitsui Jun , Ishiura Hiroyuki , Iwata Atsushi , Fujigasaki Hiroto , Tamaki Hisamitsu , Tamaki Ryusei , Kito Shinsuke , Taguchi Yoshiharu , Tanaka Kortaro , Atsuta Naoki , Sobue Gen , Kondo Takayuki , Inoue Haruhisa , Tsuji Shoji , Hozumi Isao 
Published: April 2019

AbstractCausative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457−1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457−1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future.
Longitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils
Authors: Seiß Elena A. , Krone Anna , Formaglio Pauline , Goldmann Oliver , Engelmann Susanne , Schraven Burkhart , Medina Eva , Müller Andreas J. 
Published: April 2019

AbstractUpon the onset of inflammatory responses, bacterial pathogens are confronted with altered tissue microenvironments which can critically impact on their metabolic activity and growth. Changes in these parameters have however remained difficult to analyze over time, which would be critical to dissect the interplay between the host immune response and pathogen physiology. Here, we established an in vivo biosensor for measuring the growth rates of Staphylococcus aureus (S. aureus) on a single cell-level over days in an ongoing cutaneous infection. Using intravital 2-photon imaging and quantitative fluorescence microscopy, we show that upon neutrophil recruitment to the infection site and bacterial uptake, non-lethal dampening of S. aureus proliferation occurred. This inhibition was supported by NADPH oxidase activity. Therefore, reactive oxygen production contributes to pathogen containment within neutrophils not only by killing S. aureus, but also by restricting the growth rate of the bacterium.
Evolution of folate biosynthesis and metabolism across algae and land plant lineages
Authors: Gorelova V. , Bastien O. , De Clerck O. , Lespinats S. , Rébeillé F. , Van Der Straeten D. 
Published: April 2019

AbstractTetrahydrofolate and its derivatives, commonly known as folates, are essential for almost all living organisms. Besides acting as one-carbon donors and acceptors in reactions producing various important biomolecules such as nucleic and amino acids, as well as pantothenate, they also supply one-carbon units for methylation reactions. Plants along with bacteria, yeast and fungi synthesize folates de novo and therefore constitute a very important dietary source of folates for animals. All the major steps of folate biosynthesis and metabolism have been identified but only few have been genetically characterized in a handful of model plant species. The possible differences in the folate pathway between various plant and algal species have never been explored. In this study we present a comprehensive comparative study of folate biosynthesis and metabolism of all major land plant lineages as well as green and red algae. The study identifies new features of plant folate metabolism that might open new directions to folate research in plants.
Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy
Authors: Hong Xiaowei , Rzeczycki Phillip M. , Keswani Rahul K. , Murashov Mikhail D. , Fan Zhenzhen , Deng Cheri X. , Rosania Gus R. 
Published: April 2019

AbstractMacrophages are immune cells responsible for tissue debridement and fighting infection. Clofazimine, an FDA-approved antibiotic, accumulates and precipitates as rod-shaped, crystal-like drug inclusions within macrophage lysosomes. Drug treatment as well as pathophysiological states could induce changes in macrophage mechanical property which in turn impact their phenotype and function. Here we report the use of acoustic tweezing cytometry as a new approach for in situ mechanical phenotyping of macrophages and for targeted macrophage cytotripsy. Acoustic tweezing cytometry applies ultrasound pulses to exert controlled forces to individual cells via integrin-bound microbubbles, enabling a creep test for measuring cellular mechanical property or inducing irreversible changes to the cells. Our results revealed that macrophages with crystal-like drug inclusions became significantly softer with higher cell compliance, and behaved more elastic with faster creep and recovery time constants. On the contrary, phagocytosis of solid polyethylene microbeads or treatment with soluble clofazimine rendered macrophages stiffer. Most notably, application of ultrasound pulses of longer duration and higher amplitude in ATC actuated the integrin-bound microbubbles to mobilize the crystal-like drug inclusions inside macrophages, turning the rod-shaped drug inclusions into intracellular microblender that effectively destructed the cells. This phenomenon of acoustic mechanopharmaceutical cytotripsy may be exploited for ultrasound activated, macrophage-directed drug release and delivery.
Thermal transport across grain boundaries in polycrystalline silicene: A multiscale modeling
Authors: Khalkhali Maryam , Rajabpour Ali , Khoeini Farhad 
Published: April 2019

AbstractDuring the fabrication process of large scale silicene, through common chemical vapor deposition (CVD) technique, polycrystalline films are quite likely to be produced, and the existence of Kapitza thermal resistance along grain boundaries could result in substantial changes of their thermal properties. In the present study, the thermal transport along polycrystalline silicene was evaluated by performing a multiscale method. Non-equilibrium molecular dynamics simulations (NEMD) was carried out to assess the interfacial thermal resistance of various constructed grain boundaries in silicene. The effects of tensile strain and the mean temperature on the interfacial thermal resistance were also examined. In the following stage, the effective thermal conductivity of polycrystalline silicene was investigated considering the effects of grain size and tensile strain. Our results indicate that the average values of Kapitza conductance at grain boundaries at room temperature were estimated to be nearly 2.56 × 109 W/m2 K and 2.46 × 109 W/m2 K through utilizing Tersoff and Stillinger-Weber interatomic potentials respectively. Also, in spite of the mean temperature, whose increment does not change Kapitza resistance, the interfacial thermal resistance could be controlled by applying strain. Furthermore, it was found that by tuning the grain size of polycrystalline silicene, its thermal conductivity could be modulated up to one order of magnitude.