bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phrixotrix luciferase and 6′-aminoluciferins reveal a larger luciferin phenolate binding site and provide novel far-red combinations for bioimaging purposes
Authors: Bevilaqua V. R. , Matsuhashi T. , Oliveira G. , Oliveira P. S. L. , Hirano T. , Viviani V. R. 
Published: June 2019

AbstractHow the unique luciferase ofPhrixothrix hirtus(PxRE) railroad worm catalyzes the emission of red bioluminescence using the same luciferin of fireflies, remains a mystery. Although PxRE luciferase is a very attractive tool for bioanalysis and bioimaging in hemoglobin rich tissues, it displays lower quantum yield (15%) when compared to green emitting luciferases (>40%). To identify which parts of PxRE luciferin binding site (LBS) determine bioluminescence color, and to develop brighter and more red-shifted emitting luciferases, we compared the effects of site-directed mutagenesis and of larger 6′-substituted aminoluciferin analogues (6′-morpholino- and 6′-pyrrolidinyl-LH) on the bioluminescence properties of PxRE and green-yellow emitting beetle luciferases. The effects of mutations in the benzothiazolyl and thiazolyl parts of PxRE LBS on the KMand catalytic efficiencies, indicated their importance for luciferin binding and catalysis. However, the absence of effects on the bioluminescence spectrum indicated a less interactive LBS in PxRE during light emission. Mutations at the bottom of LBS of PxRE blue-shifted the spectra and increased catalytic efficiency, suggesting that lack of interactions of this part of LBS with excited oxyluciferin phenolate underlie red light emission. The much higher bioluminescence activity and red-shifted spectra of PxRE luciferase with 6′-morpholino- (634 nm) and 6′-pyrrolidinyl-luciferins (644 nm), when compared to other beetle luciferases, revealed a larger luciferin phenolate binding pocket. The size and orientation of the side-chains of L/I/H348 are critical for amino-analogues accommodation and modulate bioluminescence color, affecting the interactions and mobility of excited oxyluciferin phenolate. ThePxREluciferase and 6′-aminoluciferins provide potential far-red combinations for bioimaging applications.
Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
Authors: Biswas Sangita , Chung Seung Hyuk , Jiang Peng , Dehghan Samaneh , Deng Wenbin 
Published: June 2019

AbstractIn this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentiation in vitro and in vivo. During CNS development, Zfp488 is induced during the early stages of OL generation, and then again during terminal differentiation of OLs. Interestingly, the human ortholog Znf488, crucial for OL development in human, has been recently identified to function as a dorsoventral pattering regulator in the ventral spinal cord for the generation of P1, P2/pMN, and P2 neural progenitor domains. Forced expression of Zfp488 gene in human NSCs led to the robust generation of OLs and suppression of neuronal and astrocyte fate in vitro and in vivo. Zfp488 expressing NSC derived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and form myelin in Shiverer mice brain in vivo. After transplantation near a site of demyelination, Zfp488 expressing hNSCs migrated to the lesion and differentiated into premyelinating OLs. A certain fraction also homed in the subventricular zone (SVZ). Zfp488-ZsGreen1-hNSC derived OLs formed compact myelin in Shiverer mice brain seen under the electron microscope. Transplanted human neural stem cells (NSC) that have the potential to differentiate into functional oligodendrocytes in response to remyelinating signals can be a powerful therapeutic intervention for disorders where oligodendrocyte (OL) replacement is beneficial.
EEG Decoding Reveals the Strength and Temporal Dynamics of Goal-Relevant Representations
Authors: Hubbard Jason , Kikumoto Atsushi , Mayr Ulrich 
Published: June 2019

AbstractModels of action control assume that attentional control settings regulate the processing of lower-level stimulus/response representations. Yet, little is known about how exactly control and sensory/response representations relate to each other to produce goal-directed behavior. Addressing this question requires time-resolved information about the strength of the different, potentially overlapping representations, on a trial-by-trial basis. Using a cued task-switching paradigm, we show that information about relevant representations can be extracted through decoding analyses from the scalp electrophysiological signal (EEG) with high temporal resolution. Peaks in representational strength—indexed through decoding accuracy—proceeded from superficial task cues, to stimulus locations, to features/responses. In addition, attentional-set representations were prominent throughout almost the entire processing cascade. Trial-by-trial analyses provided detailed information about when and to what degree different representations predict performance, with attentional settings emerging as a strong and consistent predictor of within-individual and across-individual variability in performance. Also, the strength of attentional sets was related to target representations early in the post-stimulus period and to feature/response representations at a later period, suggesting control of successive, lower-level representations in a concurrent manner. These results demonstrate a powerful approach towards uncovering different stages of information processing and their relative importance for performance.
Interrogation of the infarcted and salvaged myocardium using multi-parametric mapping cardiovascular magnetic resonance in reperfused ST-segment elevation myocardial infarction patients
Authors: Hausenloy Derek J. , Lim Mei Xing , Chan Mervyn H. H. , Paradies Valeria , Francis Rohin , Kotecha Tushar , Knight Daniel S. , Fontana Marianna , Kellman Peter , Moon James C. , Bulluck Heerajnarain 
Published: June 2019

AbstractWe used multi-parametric cardiovascular magnetic resonance (CMR) mapping to interrogate the myocardium following ST-segment elevation myocardial infarction (STEMI). Forty-eight STEMI patients underwent CMR at 4 ± 2 days. One matching short-axis slice of native T1 map, T2 map, late gadolinium enhancement (LGE), and automated extracellular volume fraction (ECV) maps per patient were analyzed. Manual regions-of-interest were drawn within the infarcted, the salvaged and the remote myocardium. A subgroup analysis was performed in those without MVO and with ≤75% transmural extent of infarct. For the whole cohort, T1, T2 and ECV in both the infarcted and the salvaged myocardium were significantly higher than in the remote myocardium. T1 and T2 could not differentiate between the salvaged and the infarcted myocardium, but ECV was significantly higher in the latter. In the subgroup analysis of 15 patients, similar findings were observed for T1 and T2. However, there was only a trend towards ECVsalvage being higher than ECVremote. In the clinical setting, current native T1 and T2 methods with the specific voxel sizes at 1.5 T could not differentiate between the infarcted and salvaged myocardium, whereas ECV could differentiate between the two. ECV was also higher in the salvaged myocardium when compared to the remote myocardium.
The effect of cognitive training on the brain’s local connectivity organization in healthy older adults
Authors: Deng Lifu , Cheng Yan , Cao Xinyi , Feng Wei , Zhu Hong , Jiang Lijuan , Wu Wenyuan , Tong Shanbao , Sun Junfeng , Li Chunbo 
Published: June 2019

AbstractCognitive training has been shown effective in improving the cognitive function of older adults. While training related plasticity of the brain has been observed at different levels, it is still open to exploration whether local functional connectivity (FC) may be affected by training. Here, we examined the neuroimaging data from a previous randomized-controlled double-blinded behavioural study, in which healthy older adults participated in a 3-month cognitive training program. Resting-state fMRI was acquired at baseline and one year after training. The local FC in the brain was estimated using the regional homogeneity (ReHo), and the high ReHo clusters (HRCs) were extracted to quantify the level of local FC integration. Results showed that: (i) HRCs exhibited a power-law size distribution; (ii) local FC were less integrated in older participants than in younger participants; (iii) local FC in older participants of the training group became more integrated after training than the control group; (iv) the baseline local FC integration was positively correlated with educational level. These results indicated a training-related alteration in local FC.
Boiling Histotripsy-induced Partial Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Authors: Pahk Ki Joo , Shin Cheol-Hee , Bae In Yeong , Yang Yoosoo , Kim Sang-Heon , Pahk Kisoo , Kim Hyungmin , Oh Seung Ja 
Published: June 2019

AbstractBoiling histotripsy is a promising non-invasive High-Intensity Focused Ultrasound (HIFU) technique that employs HIFU mechanical effects to fractionate solid tumours without causing any significant thermal damage. It has been suggested that boiling histotripsy may induce a strong immune response due to the absence of denatured antigenic protein at the HIFU focus. The underlying immunological mechanisms of this technique are, however, poorly understood. In this study, we demonstrated the feasibility of using boiling histotripsy to mechanically fractionate human breast adenocarcinoma cells (MDA-MB-231) and the potential immunological effects induced by boiling histotripsy, for the first time. Our results showed that mechanical stresses produced by boiling histotripsy promote immunogenic cell death of cancer cells via TNF-induced necrosis signaling pathway. This immunogenic cell death significantly increases secretions of damage-associated molecular patterns (CRT, HSP70, HMGB-1), pro-inflammatory cytokines (IFN-γ, IL-1α, IL-1β, IL-18) and chemokines (IL-8) which are related to M1 macrophage activation. Furthermore, the levels of these signaling proteins increase with the degree of mechanical damage induced by boiling histotripsy. Together, the results presented can suggest that boiling histotripsy could be a potential therapeutic approach for not only mechanically destroying solid tumours (e.g., breast cancer) but also promoting immunogenic cell death via TNF-induced necrosis to trigger antitumour immunity.
Studies of the oligomerisation mechanism of a cystatin-based engineered protein scaffold
Authors: Zalar Matja , Indrakumar Sowmya , Levy Colin W. , Tunnicliffe Richard B. , Peters Günther H. J. , Golovanov Alexander P. 
Published: June 2019

AbstractEngineered protein scaffolds are an alternative to monoclonal antibodies in research and drug design due to their small size, ease of production, versatility, and specificity for chosen targets. One key consideration when engineering such proteins is retaining the original scaffold structure and stability upon insertion of target-binding loops. SQT is a stefin A derived scaffold protein that was used as a model to study possible problems associated with solution behaviour of such aptamers. We used an SQT variant with AU1 and Myc insertion peptides (SQT-1C) to study the effect of peptide insertions on protein structure and oligomerisation. The X-ray structure of monomeric SQT-1C revealed a cystatin-like fold. Furthermore, we show that SQT-1C readily forms dimers and tetramers in solution. NMR revealed that these oligomers are symmetrical, with inserted loops comprising the interaction interface. Two possible mechanisms of oligomerisation are compared using molecular dynamics simulations, with domain swap oligomerisation being thermodynamically favoured. We show that retained secondary structure upon peptide insertion is not indicative of unaltered 3D structure and solution behaviour. Therefore, additional methods should be employed to comprehensively assess the consequences of peptide insertions in all aptamers, particularly as uncharacterized oligomerisation may alter binding epitope presentation and affect functional efficiency.
Similar image search for histopathology: SMILY
Authors: Hegde Narayan , Hipp Jason D. , Liu Yun , Emmert-Buck Michael , Reif Emily , Smilkov Daniel , Terry Michael , Cai Carrie J. , Amin Mahul B. , Mermel Craig H. , Nelson Phil Q. , Peng Lily H. , Corrado Greg S. , Stumpe Martin C. 
Published: June 2019

AbstractThe increasing availability of large institutional and public histopathology image datasets is enabling the searching of these datasets for diagnosis, research, and education. Although these datasets typically have associated metadata such as diagnosis or clinical notes, even carefully curated datasets rarely contain annotations of the location of regions of interest on each image. As pathology images are extremely large (up to 100,000 pixels in each dimension), further laborious visual search of each image may be needed to find the feature of interest. In this paper, we introduce a deep-learning-based reverse image search tool for histopathology images: Similar Medical Images Like Yours (SMILY). We assessed SMILY’s ability to retrieve search results in two ways: using pathologist-provided annotations, and via prospective studies where pathologists evaluated the quality of SMILY search results. As a negative control in the second evaluation, pathologists were blinded to whether search results were retrieved by SMILY or randomly. In both types of assessments, SMILY was able to retrieve search results with similar histologic features, organ site, and prostate cancer Gleason grade compared with the original query. SMILY may be a useful general-purpose tool in the pathologist’s arsenal, to improve the efficiency of searching large archives of histopathology images, without the need to develop and implement specific tools for each application.
Apoptosis of cancer cells is triggered by selective crosslinking and inhibition of receptor tyrosine kinases
Authors: Wang Kaidi , Wang Xuan , Hou Yiying , Zhou Huihui , Mai Kangsen , He Gen 
Published: June 2019

AbstractReceptor tyrosine kinases (RTK) have been the most prevalent therapeutic targets in anti-cancer drug development. However, the emergence of drug resistance toward single target RTK inhibitors remains a major challenge to achieve long-term remissions. Development of alternative RTK inhibitory strategies that bypass drug resistance is much wanted. In the present study, we found that selected cell surface RTKs were inhibited and crosslinked into detergent resistant complexes by oligomeric but not monomeric concanavalin A (ConA). The inhibition of RTKs by ConA led to suppression of pro-survival pathways and induction of apoptosis in multiple cancer cell lines, while overexpression of constitutively activated protein kinase B (AKT) reversed the apoptotic effect. However, major cell stress sensing checkpoints were not influenced by ConA. To our knowledge, selective crosslinking and inhibition of cell surface receptors by ConA-like molecules might represent a previously unidentified mechanism that could be potentially exploited for therapeutic development.
Electronic band dispersion determination in azimuthally disordered transition-metal dichalcogenide monolayers
Authors: Park S. , Schultz T. , Han A. , Aljarb A. , Xu X. , Beyer P. , Opitz A. , Ovsyannikov R. , Li L.-J. , Meissner M. , Yamaguchi T. , Kera S. , Amsalem P. , Koch N. 
Published: June 2019

AbstractGenerally, the lack of long-range order in materials prevents from experimentally addressing their electronic band dispersion by angle-resolved photoelectron spectroscopy (ARPES), limiting such assessment to single crystalline samples. Here we demonstrate that the ARPES spectra of azimuthally disordered transition metal dichalcogenide (TMDC) monolayers with 2 H phase are dominated by their band dispersion along the two high symmetry directions Γ-K and Γ-M. We exemplify this by analyzing the ARPES spectra of four prototypical TMDCs within a mathematical framework, which allows to consistently explain the reported observations. A robust base for investigating TMDC monolayers significantly beyond single crystal samples is thus established.
High-fidelity amplified FISH for the detection and allelic discrimination of single mRNA molecules
Authors: Marras Salvatore A. E. , Bushkin Yuri , Tyagi Sanjay 
Published: June 2019

Significance
Although it is now possible to visualize single RNA molecules within cells by fluorescence in situ hybridization, the resulting signals are rather faint. Here we describe a method that produces amplified signals from single RNA molecules, while minimizing false-positive signals. Our probes enable detection of sparsely expressed mRNAs, and they are so specific that related mutant and wild-type mRNAs, differing from each other by as little as a single-nucleotide variation, yield distinct in situ signals in 2 distinguishable colors. This technology will aid studies of gene expression phenomena, such as allelic imbalance, and will be useful for the identification of mRNAs harboring somatic mutations in cancer cells, facilitating targeted therapy.
Rapid assembly and profiling of an anticoagulant sulfoprotein library
Authors: Watson Emma E. , Ripoll-Rozada Jorge , Lee Ashley C. , Wu Mike C. L. , Franck Charlotte , Pasch Tim , Premdjee Bhavesh , Sayers Jessica , Pinto Maria F. , Martins Pedro M. , Jackson Shaun P. , Pereira Pedro José Barbosa , Payne Richard J. 
Published: June 2019

Significance
Cardiovascular disease represents a significant health challenge, with towering economic and social costs resulting from the high levels of associated morbidity and mortality. For conditions resulting from undesired blood clotting, treatment options remain limited and are accompanied by significant side effects. Using a rapid chemical ligation platform, 34 homogeneously modified variants of tick anticoagulant proteins were generated. Access to this synthetic protein library enabled key structure–activity relationships to be elucidated and revealed unexpected differences in the mechanism of thrombin inhibition by this group of otherwise closely related molecules. The synthetic platform reported here provides a unique means to expedite the generation and identification of polypeptide and protein therapeutic leads for clotting-associated diseases.
Teaching English-Chinese textual translation strategies
Authors: Sun Kun 
Published: June 2019

AbstractThe topic-chain is a typical characteristic used to distinguish Chinese discourse from other languages, such as English. By studying how to make use of the topic-chain, one learns how to decipher English into natural and idiomatic Chinese translation. The idea of using topic-chains to explore English-Chinese (E-C) textual translation is relatively new to translation studies. As such, this paper provides a detailed account of cross-linguistic differences between English and Chinese, with regard to the topic-chain, as well as the differences between the topic-chain model and the approach of thematic progression theory. This study, based on contrastive analysis, constructs a model consisting of specific procedures that are simple and easy to use, thereby making English-Chinese textual translation a more manageable process. Use of topic-chain strategies will promote the efficiency and quality of E-C translation, and allow for Chinese translated text to be more idiomatic. This paper provides an overview of effective textual translation strategies that are useful both for translators and the field of translation studies as a whole. It addresses how to teach translation effectively to students, providing practical theory and practice for pedagogical instruction. Meanwhile, an experiment conducted provides the evidence that topic-chain for pedagogical instruction is significantly valid. The pedagogical design of these strategies emphasizes the training of students’ textual awareness and targets language-sensitive awareness. It is assumed that didactics can help students gain bilingual competence and strengthen their core transfer competence. This study, therefore, is significant not only in exploring the benefits and uses of textual translation studies, but has practical value when applied directly to translation learning and teaching.
Persistence and nonpersistence as complementary models of identical quantum particles
Authors: Goyal Philip 
Published: June 2019

Abstract
Classical mechanics is based on the notion that matter consists of persistent particles that can be reidentified (or tracked) across time. However, the mathematical symmetrization procedures (due to Dirac (1926 Proc. R. Soc. A 112 661) and Heisenberg (1926 Z. Phys.
38 411) and Feynman (1965 Quantum Mechanics and Path Integrals 1st edn (New York: McGraw-Hill))) used to describe identical particles within the quantum formalism are widely interpreted as implying that identical quantum particles are not persistent (so that the concept of ‘the same particle’ is not meaningful) or are persistent but not reidentifiable. However, it has not proved possible to rigorously reconcile these interpretations with the fact that identical particles are routinely assumed to be reidentifiable in particular circumstances—for example, a track in a bubble chamber is interpreted as a sequence of bubbles generated by one and the same particle (Mirman 1973 Il Nuovo Cimento
18B 110; de Muynck 1975 Int. J. Theor. Phys.
14 327; Dieks and Lubberdink 2011 Found. Phys.
41 1051; Jantzen 2011 Phil. Sci.
78 39). Moreover, these interpretations do not account for the mathematical form of the symmetrization procedures, leaving open theoretical possibilities other than bosonic and fermionic behavior, such as paraparticles (Messiah and Greenberg 1964 Phys. Rev.
136), which however do not appear to be realized in nature. Here we propose that the quantum mechanical behavior of identical particles is a manifestation of a novel kind of complementarity, a complementarity of persistence and nonpersistence. Accordingly, identical ‘particles’ are neither persistent nor nonpersistent; rather, these terms are to be understood as descriptors of different models of the same experimental data. We prove the viability of this viewpoint by showing how Feynman’s and Dirac’s symmetrization procedures arise through a synthesis of a quantum treatment of persistence and nonpersistence models of identical particle-like events, and by showing how reidentifiability emerges in a context-dependent manner. Finally, by drawing on a reconstruction of Feynman’s formulation of quantum theory (Goyal et al 2010 Phys. Rev. A 81 022109), we construct a precise parallel between the proposed persistence–nonpersistence complementary and Bohr’s wave–particle complementarity for individual particles, and detail their conceptual similarities and dissimilarities.