bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ng_ζ1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis
Authors: Rocker Andrea , Peschke Madeleine , Kittilä Tiia , Sakson Roman , Brieke Clara , Meinhart Anton 
Published: April 2018

AbstractBacterial toxin–antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin–antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.
TAK1 activation of alpha-TAT1 and microtubule hyperacetylation control AKT signaling and cell growth
Authors: Shah Nirav , Kumar Sanjay , Zaman Naveed , Pan Christopher C. , Bloodworth Jeffrey C. , Lei Wei , Streicher John M. , Hempel Nadine , Mythreye Karthikeyan , Lee Nam Y. 
Published: April 2018

AbstractAcetylation of microtubules (MT) confers mechanical stability necessary for numerous functions including cell cycle and intracellular transport. Although αTAT1 is a major MT acetyltransferase, how this enzyme is regulated remains much less clear. Here we report TGF-β-activated kinase 1 (TAK1) as a key activator of αTAT1. TAK1 directly interacts with and phosphorylates αTAT1 at Ser237 to critically enhance its catalytic activity, as mutating this site to alanine abrogates, whereas a phosphomimetic induces MT hyperacetylation across cell types. Using a custom phospho-αTAT1-Ser237 antibody, we screen various mouse tissues to discover that brain contains some of the highest TAK1-dependent αTAT1 activity, which, accordingly, is diminished rapidly upon intra-cerebral injection of a TAK1 inhibitor. Lastly, we show that TAK1 selectively inhibits AKT to suppress mitogenic and metabolism-related pathways through MT-based mechanisms in culture and in vivo. Collectively, our findings support a fundamental new role for TGF-β signaling in MT-related functions and disease.
Three-dimensional Cardiomyocytes Structure Revealed By Diffusion Tensor Imaging and Its Validation Using a Tissue-Clearing Technique
Authors: Lee Sang-Eun , Nguyen Christopher , Yoon Jongjin , Chang Hyuk-Jae , Kim Sekeun , Kim Chul Hoon , Li Debiao 
Published: April 2018

AbstractWe characterized the microstructural response of the myocardium to cardiovascular disease using diffusion tensor imaging (DTI) and performed histological validation by intact, un-sectioned, three-dimensional (3D) histology using a tissue-clearing technique. The approach was validated in normal (n = 7) and ischemic (n = 8) heart failure model mice. Whole heart fiber tracking using DTI in fixed ex-vivo mouse hearts was performed, and the hearts were processed with the tissue-clearing technique. Cardiomyocytes orientation was quantified on both DTI and 3D histology. Helix angle (HA) and global HA transmurality (HAT) were calculated, and the DTI findings were confirmed with 3D histology. Global HAT was significantly reduced in the ischemic group (DTI: 0.79 ± 0.13°/% transmural depth [TD] and 3D histology: 0.84 ± 0.26°/%TD) compared with controls (DTI: 1.31 ± 0.20°/%TD and 3D histology: 1.36 ± 0.27°/%TD, all p < 0.001). On direct comparison of DTI with 3D histology for the quantitative assessment of cardiomyocytes orientation, significant correlations were observed in both per-sample (R2 = 0.803) and per-segment analyses (R2 = 0.872). We demonstrated the capability and accuracy of DTI for mapping cardiomyocytes orientation by comparison with the intact 3D histology acquired by tissue-clearing technique. DTI is a promising tool for the noninvasive characterization of cardiomyocytes architecture.
Improved method for estimating adlayer thickness and bulk RI change for gold nanocrescent sensors
Authors: Abumazwed Ahmed , Kubo Wakana , Tanaka Takuo , Kirk Andrew G. 
Published: April 2018

AbstractThis paper presents a novel method employing the maximum likelihood estimation (MLE) technique alongside a nonlinear sensor response model to improve and extract more quantitative sensing results for localized surface plasmon resonance biosensors. The nonlinear response model treats the sensor response as a nonlinear function of the biomolecular adlayer thickness. This method makes use of the multiple resonance characteristic of nanocrescent structures in order to estimate the adlayer thickness and bulk refractive index (RI) change. Nanoimprint lithography is used here to fabricate the nanostructures. The finite element method (FEM) is used to model the nanocrescents and numerically validate the nonlinear-MLE method. Comparing to the established linear model, the proposed nonlinear-MLE method achieves 75% improvement in the limit of detection based on the estimated adlayer thickness and improves the bulk RI resolution by two orders of magnitude.
Mutations in VP1 and 5′-UTR affect enterovirus 71 virulence
Authors: Chang Ching-Kun , Wu Shang-Rung , Chen Ying-Chin , Lee Kuen-Jin , Chung Nai-Hsiang , Lu Yi-Ju , Yu Shu-Ling , Liu Chia-Chyi , Chow Yen-Hung 
Published: April 2018

AbstractEnterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD). The current EV71 propagating in Vero (EV-V) or sub-passaged in RD (EV-R) cells was used as a pathogen. Interestingly, EV-R exhibited differential virulence; challenging human scavenger receptor class B2-expressing (hSCARB2-Tg) mice with EV71 revealed that EV-V was more virulent than EV-R: 100% of mice that received lethal amounts of EV-V died, while all the mice that received EV-R survived. Severe pathogenesis correlated with viral burdens and proinflammatory cytokine levels were observed in EV-V-challenged mice, but controversy in EV-R-challenged mice. Consensus sequence analysis revealed EV-R rapidly acquired complete mutations at E145G and S241L and partial mutations at V146I of VP1, and acquired a T to C substitution at nucleotide 494 of the 5′-UTR. EV-R exhibited higher binding affinity for another EV71 receptor, human P-selectin glycoprotein ligand-1 (hPSGL-1), than EV-V. Both EV71s exhibited no significant difference in binding to hSCARB2. The molecular modelling indicate that these mutations might influence EV71 engagement with PSGL-1 and in vivo virulence.
Image Domain Gridding: a fast method for convolutional resampling of visibilities
Authors: van der Tol Sebastiaan , Veenboer Bram , Offringa André R. 
Published: April 2018

In radio astronomy obtaining a high dynamic range in synthesis imaging of wide fields requires a correction for time and direction-dependent effects. Applying direction-dependent correction can be done by either partitioning the image in facets and applying a direction-independent correction per facet, or by including the correction in the gridding kernel (AW-projection).
An advantage of AW-projection over faceting is that the effectively applied beam is a sinc interpolation of the sampled beam, where the correction applied in the faceting approach is a discontinuous piece wise constant beam. However, AW-projection quickly becomes prohibitively expensive when the corrections vary over short time scales. This occurs, for example, when ionospheric effects are included in the correction. The cost of the frequent recomputation of the oversampled convolution kernels then dominates the total cost of gridding.
Image domain gridding is a new approach that avoids the costly step of computing oversampled convolution kernels. Instead low-resolution images are made directly for small groups of visibilities which are then transformed and added to the large uv grid. The computations have a simple, highly parallel structure that maps very well onto massively parallel hardware such as graphical processing units (GPUs). Despite being more expensive in pure computation count, the throughput is comparable to classical W-projection. The accuracy is close to classical gridding with a continuous convolution kernel. Compared to gridding methods that use a sampled convolution function, the new method is more accurate. Hence, the new method is at least as fast and accurate as classical W-projection, while allowing for the correction for quickly varying direction-dependent effects.
Gefäßnotfälle im Notarztdienst – Teil 1: akute Extremitätenischämie und Gefäßverletzung
Authors: Beck Tino , Engelhardt Michael 
Published: April 2018

ZusammenfassungDer Beitrag stellt die diagnostischen sowie leitlinienkonforme therapeutische Sofortmaßnahmen bei Extremitätenischämie und Gefäßverletzungen vor und geht kurz auf die sich innerklinisch anschließende Therapie ein, um in der Praxis schneller eine Entscheidung treffen zu können, über welche gefäßchirurgischen und interventionellen Kompetenzen die aufnehmende Klinik verfügen muss.
Clinical Efficacy of Bone Reconstruction Surgery with Frozen Cortical Bone Allografts for Nonunion of Radial and Ulnar Fractures in Toy Breed Dogs
Authors: Nagahiro Yukari , Katori Daichi , Muroi Norihiro , Akagi Hiroyuki , Kanno Nobuo , Harada Yasuji , Yamaguchi Shinya , Hayashi Kei , Hara Yasushi , Munakata Shuntaro 
Published: April 2018

Objective To evaluate the effectiveness of frozen cortical bone allografts (FCBA) in the treatment of severe radial and ulnar atrophic nonunion fractures.
Animals Toy breed dogs with nonunion of radial and ulnar fractures (n = 15).
Methods Severe atrophic nonunion fractures were treated with FCBA (eight infected and seven non-infected fractures). Radiographs obtained immediately after surgery, and 1, 2, 3, 6 and 12 months later were evaluated and scored for the periosteal reaction at the bone regeneration sites, the healing process in the bone connection areas at both the proximal and distal sites, and the bone remodelling process within the allografts.
Results Improvements in the fracture-healing process and weight-bearing function were observed in all cases. Radiographic scores at the bone connection areas and within the allograft improved significantly over time (p < 0.05). There were not any significant differences in radiographic scores between the infected and non-infected groups.
Clinical Significance Bone reconstruction with FCBA is effective in the treatment of radial and ulnar nonunion fractures associated with large bone defects, regardless of the infection status of the surgical site.
Gothic fairy-tales and Deleuzian desire
Authors: Hirst Holly 
Published: April 2018

AbstractThis article seeks to address the ‘identity’ of the ‘gothic fairy-tale’ through an investigation of Rana Dasgupta’s Tokyo Cancelled (2005), a collection of globally oriented short stories that straddle the line between the gothic and the fairy-tale. The argument provides a close analysis of a number of the tales within Dasgupta’s collection to highlight the parity between the gothic and the fairy-tale at the level of both plot and character. Moving beyond the well-documented case of how a writer and critic such as Angela Carter exposes the latent horror of the fairy-tale, the argument seeks to explore the juncture of the gothic and the fairy-tale represented in Tokyo Cancelled and, in doing so, illustrate the ways in which fairy-tales and the gothic both depend upon certain configurations of desire while questioning the primacy of ‘horror’ and ‘terror’ to definitions of the gothic mode. While highlighting the similarities between fairy-tale and gothic forms, this article also posits the existence of ‘fairy-tale’ and ‘gothic’ sensibilities that are fundamentally different from one another, a difference that is founded ultimately upon the question of desire. Employing Gilles Deleuze and Felix Guattari’s concept of productive desire, a model that opposes that of ‘desire-as-fantasy’ and ‘desire-as-lack’, which are associated with the fairy-tale and explicitly rejected in Tokyo Cancelled, the article posits a particularly gothic conception of desire. This ‘gothic desire’ is central both to the gothic mode generally and to the ‘gothic fairy-tale’ more particularly. Rana Dasgupta’s work acts as an illustration of this conception of the ‘gothic fairy-tale,’ one which moves away from an emphasis on terror, horror, transgression and fear to focus instead on a widely differing creative project and a conception of desire as definitional to form.
Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide
Authors: Wang Hong-Xia , Song Ziyuan , Lao Yeh-Hsing , Xu Xin , Gong Jing , Cheng Du , Chakraborty Syandan , Park Ji Sun , Li Mingqiang , Huang Dantong , Yin Lichen , Cheng Jianjun , Leong Kam W. 
Published: April 2018

Significance
Delivery remains a significant challenge for robust implementation of CRISPR/Cas9. We report an efficient CRISPR/Cas9 delivery system comprising PEGylated nanoparticles based on the α-helical polypeptide PPABLG. Assisted by the high membrane-penetrating ability of the polypeptide, P-HNPs achieved efficient cellular internalization and endosomal escape. The CRISPR/Cas9 delivery system could reach 47.3% gene editing in cells, 35% gene deletion in vivo, and HeLa tumor growth suppression >71%, demonstrating an advantage over the existing conventional polycationic transfection reagents. Efficient also in knock-in and gene activation, the reported CRISPR/Cas9 delivery system serves to advance gene editing in vitro and in vivo.
Complex role of NK cells in regulation of oncolytic virus–bortezomib therapy
Authors: Kim Yangjin , Yoo Ji Young , Lee Tae Jin , Liu Joseph , Yu Jianhua , Caligiuri Michael A. , Kaur Balveen , Friedman Avner 
Published: April 2018

Significance
The present work considers the effect of NK cell treatment in a combination therapy with oncolytic virus (OV) and bortezomib. It demonstrates by cross-disciplinary analysis of a complex biological process that the standard strategies, wherein “more is better,” do not necessarily apply when multiple drugs of different classes and interactions are being used in the combination. While many combination clinical trials are being conducted with little forethought as to the interactions that may be expected between diverse agents, this work provides a basis for the generation of mathematical models and simulations that address the complexity of the interactions among the diverse agents and could play an important role in the future development of clinical trials.
Skin microbiota and allergic symptoms associate with exposure to environmental microbes
Authors: Lehtimäki Jenni , Sinkko Hanna , Hielm-Björkman Anna , Salmela Elina , Tiira Katriina , Laatikainen Tiina , Mäkeläinen Sanna , Kaukonen Maria , Uusitalo Liisa , Hanski Ilkka , Lohi Hannes , Ruokolainen Lasse 
Published: April 2018

SignificanceUrban, Westernized populations suffer extensively from noncommunicable diseases such as allergies. However, the overlapping effects of living environment and lifestyle are difficult to separate. Intriguingly, also our fellow animals, dogs, suffer from analogous diseases. Therefore, we suggest that pet dogs, sharing their environment and lifestyle with humans but having a comparatively simple life, provide a valuable model for understanding origins of noncommunicable diseases. We show that living environment and lifestyle concurrently, but still independently, shape both the skin microbiota and the risk of allergic disease in dogs. Urbanized lifestyle, featuring restricted animal contacts and small family size, is allergy promoting both in rural and urban dogs. Hence, both environment and lifestyle seem to influence the microbiota and, probably consequently, immune tolerance.
Quantifying ecological impacts of mass extinctions with network analysis of fossil communities
Authors: Muscente A. D. , Prabhu Anirudh , Zhong Hao , Eleish Ahmed , Meyer Michael B. , Fox Peter , Hazen Robert M. , Knoll Andrew H. 
Published: April 2018

Significance
The geologic record provides evidence of repeated diversification events and mass extinctions, which entailed benchmark changes in biodiversity and ecology. For insights into these events, we explore the fossil record of marine animal communities using a network-based approach to quantifying ecological change over time. The major radiations and mass extinctions of the Phanerozoic Eon resulted in the biggest ecological changes, as they involved the rise and decline of interrelated communities in relative dominance. Our analyses provide support for an ecological severity ranking of mass extinctions and illuminate the long-term consequences of the Ordovician radiation and Devonian mass depletion of biodiversity. Our work highlights the potential for irreversible ecosystem changes with species losses, both previously documented and predicted in the future.
Unexpected metabolic disorders induced by endocrine disruptors in
Xenopus tropicalis
provide new lead for understanding amphibian decline
Authors: Regnault Christophe , Usal Marie , Veyrenc Sylvie , Couturier Karine , Batandier Cécile , Bulteau Anne-Laure , Lejon David , Sapin Alexandre , Combourieu Bruno , Chetiveaux Maud , Le May Cédric , Lafond Thomas , Raveton Muriel , Reynaud Stéphane 
Published: April 2018

Significance
By performing a controlled exposure of an amphibian model to endocrine disruptors (EDs) at concentrations within the range of safe drinking water, we provide evidence of the role played by these widespread contaminants in amphibian population decline through metabolic disruption. In frogs exposed throughout their life cycle, this disruption induces a metabolic syndrome characteristic of a prediabetes state. Exposed animals produce progeny that metamorphose later, are smaller and lighter at the adult stage, and have reduced reproductive success. These transgenerational effects of EDs may impact overwintering survival, recruitment for reproduction, and fitness, each representing possible triggers of population decline.
COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer
Authors: Takayama Ken-ichi , Suzuki Takashi , Fujimura Tetsuya , Takahashi Satoru , Inoue Satoshi 
Published: April 2018

Significance
Activated androgen receptor signaling is a key driver to circumvent androgen-deprivation therapy in advanced prostate cancer. Cordon-bleu (COBL) has been identified as a specific player in morphogenesis by regulating actin networks in neurons. Here, we identify another COBL protein, COBL-like 1 (COBLL1), as an important factor that contributes to prostate cancer progression by stimulating androgen receptor signaling and modulating cell morphology. We show that COBLL1 is regulated by androgen and is highly up-regulated in treatment-resistant prostate cancer model cells, where COBLL1 mediates cell proliferation and migration, supporting a fundamental role for COBLL1 in prostate cancer. Our study shows the potential implications for therapeutic targeting of COBLL1 in advanced prostate cancer.
Trends in continental temperature and humidity directly linked to ocean warming
Authors: Byrne Michael P. , O’Gorman Paul A. 
Published: April 2018

Significance
Changes in surface temperature and humidity over land are important for climate-change impacts on humans and ecosystems. Here, we show how trends in land humidity and temperature in recent decades are linked to ocean warming. While changes in temperature and humidity have been different over land and ocean, these changes have combined to give equal changes in the moist static energy of the air over land and ocean, consistent with expectations from atmospheric dynamics. We show how this dynamical constraint, and an additional constraint based on moisture transport, may be used to predict land climate changes given the ocean warming. Land surfaces are complex to understand and model, yet our results show a remarkably simple behavior of the climate system that emerges at large scales.
Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer
Authors: Lee John K. , Bangayan Nathanael J. , Chai Timothy , Smith Bryan A. , Pariva Tiffany E. , Yun Sangwon , Vashisht Ajay , Zhang Qingfu , Park Jung Wook , Corey Eva , Huang Jiaoti , Graeber Thomas G. , Wohlschlegel James , Witte Owen N. 
Published: April 2018

SignificanceAdvanced prostate cancer is a deadly disease made up of multiple cancer subtypes that evolve during its natural history. Unfortunately, antibody- and cell-based therapies in development that target single tumor antigens found in conventional prostate cancer do not account for this heterogeneity. Here, we show that two major subtypes of advanced prostate cancer, prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC), exhibit distinct cell-surface expression profiles. Integrated analysis of gene expression and cell-surface protein expression of prostate cancer nominated multiple subtype-specific cell-surface antigens. We specifically characterize FXYD3 and CEACAM5 as targets for immune-based therapies in PrAd and NEPC and provide preliminary evidence of the antigen-specific cytotoxic activity of CEACAM5-directed chimeric antigen receptor T cells in NEPC.
Spatiotemporal encoding of search strategies by prefrontal neurons
Authors: Chiang Feng-Kuei , Wallis Joni D. 
Published: April 2018

Significance
Working memory is a capacity-limited system that is used by cognitive processes, such as planning, reasoning, and decision making, to temporarily store information for short periods of time. We often employ behavioral strategies to overcome the capacity limit, such as processing information in sequences, but how this is accomplished at the neural level is unknown. By recording the electrical activity of prefrontal neurons during working-memory tasks, we found that prefrontal neurons had spatiotemporal receptive fields, encoding both the spatial coordinates of behavioral targets and their organization within a sequence. Furthermore, the strength of this tuning could be dynamically modulated according to how much subjects relied on working memory or behavioral strategies.
A crowdsourcing approach to the description of regional variation in French object clitic clusters
Authors: Avanzi Mathieu , Stark Elisabeth 
Published: April 2018

AbstractOur contribution is dedicated to the empirical testing of alleged regional variants of object clitic clusters in modern French in France, Belgium and Switzerland. We provide some intriguing new insights into the regional distribution of non-standard variants and discuss one hypothesis on their nature and two hypotheses to explain their coming into being: language-contact (with Francoprovençal, Occitan and Oïl dialects, H1) and/or analogical leveling (H2), on the one hand, and their postsyntactic, rather than syntactic, nature, on the other (H3). Our main results reveal that the three non-standard variants where order in object clitic clusters is concerned are not regionally well-distributed, i.e. the observed distribution does not correspond to any cohesive area. In contrast, only one variant where the selection of the form (mevs.moi) is at issue seems to be regionally confined: it is found in French-speaking Switzerland, in Gascony, plus some rare attestations of it in the North of France. All in all, variation in object clitic clusters indicates a genuinely new geographical articulation of regional French that does not coincide with traditional dialectal areas.