bluuebunny/crossref_metadata_2025 huggingface dataset:
The Appraisal of Self-Care Agency Scale - Revised (ASA-R): Adaptation and Validation in a Sample of Spanish Older Adults
Authors: Alhambra-Borrás Tamara , Durá-Ferrandis Estrella , Garcés-Ferrer Jorge , Sánchez-García Javier
Published: October 2017

Self-care agency is an important determinant of healthy aging. The Appraisal of Self-care Agency Scale (ASA-R) (Sousa et al., 2010) is one of the main instrument to assess self-care capacity. The objectives of the study were: 1) to adapt and validate ASA-R scale for use in Spanish population; 2) to examine the dimensionality, validity and reliability; 3) and to establish the convergent validity of ASA-R using a self-reported health measure. The ASA-R Scale and the 12-item Short Form Health Survey (SF-12) were administered to 488 Spanish seniors aged 65 and over. Confirmatory Factor Analysis (CFA) was used to analyze the dimensionality, validity and reliability. Convergent validity was tested by correlating the ASA-R factors with the SF-12 subscales; correlations were significant (p < .005). CFA showed that the ASA-R Three Factor Model fit well to the data, showing satisfactory fit indices, with S-Bχ2 > 0.05 (0.436), RMSEA closer to 0 (0.006), SRMR < 0.08 (0.065), GFI and AGFI close to 1 (0.924 and 0.921), and CFI and NNFI > 0.95 (0.996 and 0.995). The results also demonstrated that ASA-R is a reliable and valid instrument. The ASA-R has demonstrated to be a reliable (CR indices > 0.7) and valid (AVE > 0.5) instrument in measuring self-care agency among Spanish older population.
Revolutionary Economic Reasoning in the Context of Revolution: The Origins and Fate of Bolshevik Economics
Authors: Mel΄nik Denis
Published: October 2017

By February 1917, the handful of future Bolshevik leaders of Russia were scattered all over the globe. Among the few things they had in common was a peculiar vision of the Russian economy and of global economic trends. That vision guided their revolutionary activity. Whether it was “correct” or not, they succeeded. With their grip on power secured, however, their economic reasoning had to confront new challenges, which eventually reshaped the original approach.
“Do It the Russian Way”: Narratives of the Russian Revolution in European History Textbooks
Authors: Fabrykant Marharyta
Published: October 2017

The article presents the results of narrative analysis of contemporary European history textbooks’ coverage of the 1917 Russian Revolution. The sample consists of 101 textbooks from 22 European states, published between 2000 and 2015 and currently in use in secondary and high schools. The results show that the Russian Revolution, unlike most other events in Russia's history, is narrated as a story not about Russianness, but about shared European historical experiences and social issues. The article discusses the implications of this way of narrating the Russian Revolution for the perceived logic of European history.
The Russian Revolution As a Tourist Attraction
Authors: Koenker Diane P.
Published: October 2017

Looking at Soviet guidebooks from the 1920s to the 1960s, this essay argues that 1905 and 1917 revolutionary places as “tourist attractions” were mostly tangential to the tourist experience, although one could argue that the entire USSR was a monument to the “revolution.” The revolution remained one destination of many possible tourist excursions, its memory one building block of many that made up the basis of Soviet citizenship. The revolution as tourist attraction did not celebrate 1917 as arupture, but rather a point of entry, the moment from which the many and not the few could share in a culture of world importance.
Design and fabrication of crack-junctions
Authors: Dubois Valentin , Niklaus Frank , Stemme Göran
Published: October 2017

Nanogap electrodes consist of pairs of electrically conducting tips that exhibit nanoscale gaps. They are building blocks for a variety of applications in quantum electronics, nanophotonics, plasmonics, nanopore sequencing, molecular electronics, and molecular sensing. Crack-junctions (CJs) constitute a new class of nanogap electrodes that are formed by controlled fracture of suspended bridge structures fabricated in an electrically conducting thin film under residual tensile stress. Key advantages of the CJ methodology over alternative technologies are that CJs can be fabricated with wafer-scale processes, and that the width of each individual nanogap can be precisely controlled in a range from <2 to >100 nm. While the realization of CJs has been demonstrated in initial experiments, the impact of the different design parameters on the resulting CJs has not yet been studied. Here we investigate the influence of design parameters such as the dimensions and shape of the notches, the length of the electrode-bridge and the design of the anchors, on the formation and propagation of cracks and on the resulting features of the CJs. We verify that the design criteria yields accurate prediction of crack formation in electrode-bridges featuring a beam width of 280 nm and beam lengths ranging from 1 to 1.8 μm. We further present design as well as experimental guidelines for the fabrication of CJs and propose an approach to initiate crack formation after release etching of the suspended electrode-bridge, thereby enabling the realization of CJs with pristine electrode surfaces.
Advances in diamond nanofabrication for ultrasensitive devices
Authors: Castelletto Stefania , Rosa Lorenzo , Blackledge Jonathan , Al Abri Mohammed Zaher , Boretti Albert
Published: October 2017

This paper reviews some of the major recent advances in single-crystal diamond nanofabrication and its impact in nano- and micro-mechanical, nanophotonics and optomechanical components. These constituents of integrated devices incorporating specific dopants in the material provide the capacity to enhance the sensitivity in detecting mass and forces as well as magnetic field down to quantum mechanical limits and will lead pioneering innovations in ultrasensitive sensing and precision measurements in the realm of the medical sciences, quantum sciences and related technologies.
A minimalist approach to stereoselective glycosylation with unprotected donors
Authors: Le Mai Hoang Kim , He Jing-xi , Báti Gábor , Chan-Park Mary B. , Liu Xue-Wei
Published: October 2017

Mechanistic study of carbohydrate interactions in biological systems calls for the chemical synthesis of these complex structures. Owing to the specific stereo-configuration at each anomeric linkage and diversity in branching, significant breakthroughs in recent years have focused on either stereoselective glycosylation methods or facile assembly of glycan chains. Here, we introduce the unification approach that offers both stereoselective glycosidic bond formation and removal of protection/deprotection steps required for further elongation. Using dialkylboryl triflate as an in situ masking reagent, a wide array of glycosyl donors carrying one to three unprotected hydroxyl groups reacts with various glycosyl acceptors to furnish the desired products with good control over regioselectivity and stereoselectivity. This approach demonstrates the feasibility of straightforward access to important structural scaffolds for complex glycoconjugate synthesis.
Mice in social conflict show rule-observance behavior enhancing long-term benefit
Authors: Choe Il-Hwan , Byun Junweon , Kim Ko Keun , Park Sol , Kim Isaac , Jeong Jaeseung , Shin Hee-Sup
Published: October 2017

Disorderly resolution of conflict is costly, whereas orderly resolution by consent rules enables quick settlement. However, it is unclear whether non-human animals can make and observe rules to resolve conflict without aggression. Here we report a new behavioral paradigm for mice: a modified two-armed maze that uses wireless electrical brain stimulation as reward. First, the mice were individually operant-trained to initiate and then receive the reward at the signaled arm. Next, two mice were coupled and had to cooperate to initiate reward but then to compete over reward allocation. Mice develop and observe a rule of reward zone allocation that increases the total amount of reward and reward equity between the pair. In the mutual rule-observance behavior, positive reciprocity and tolerance to the other’s violation are also observed. These findings suggest that rodents can learn to make and observe rules to resolve conflict, enhancing long-term benefit and payoff equity.
Adaptive artificial evolution of droplet protocells in a 3D-printed fluidic chemorobotic platform with configurable environments
Authors: Parrilla-Gutierrez Juan Manuel , Tsuda Soichiro , Grizou Jonathan , Taylor James , Henson Alon , Cronin Leroy
Published: October 2017

Evolution via natural selection is governed by the persistence and propagation of living things in an environment. The environment is important since it enabled life to emerge, and shapes evolution today. Although evolution has been widely studied in a variety of fields from biology to computer science, still little is known about the impact of environmental changes on an artificial chemical evolving system outside of computer simulations. Here we develop a fully automated 3D-printed chemorobotic fluidic system that is able to generate and select droplet protocells in real time while changing the surroundings where they undergo artificial evolution. The system is produced using rapid prototyping and explicitly introduces programmable environments as an experimental variable. Our results show that the environment not only acts as an active selector over the genotypes, but also enhances the capacity for individual genotypes to undergo adaptation in response to environmental pressures.
Colloidal zinc oxide-copper(I) oxide nanocatalysts for selective aqueous photocatalytic carbon dioxide conversion into methane
Authors: Bae Kyung-Lyul , Kim Jinmo , Lim Chan Kyu , Nam Ki Min , Song Hyunjoon
Published: October 2017

Developing catalytic systems with high efficiency and selectivity is a fundamental issue for photochemical carbon dioxide conversion. In particular, rigorous control of the structure and morphology of photocatalysts is decisive for catalytic performance. Here, we report the synthesis of zinc oxide-copper(I) oxide hybrid nanoparticles as colloidal forms bearing copper(I) oxide nanocubes bound to zinc oxide spherical cores. The zinc oxide-copper(I) oxide nanoparticles behave as photocatalysts for the direct conversion of carbon dioxide to methane in an aqueous medium, under ambient pressure and temperature. The catalysts produce methane with an activity of 1080 μmol gcat−1 h−1, a quantum yield of 1.5% and a selectivity for methane of >99%. The catalytic ability of the zinc oxide-copper(I) oxide hybrid catalyst is attributed to excellent band alignment of the zinc-oxide and copper(I) oxide domains, few surface defects which reduce defect-induced charge recombination and enhance electron transfer to the reagents, and a high-surface area colloidal morphology.
Water induced sediment levitation enhances downslope transport on Mars
Authors: Raack Jan , Conway Susan J. , Herny Clémence , Balme Matthew R. , Carpy Sabrina , Patel Manish R.
Published: October 2017

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought.
RETRACTED ARTICLE: Sulfur availability regulates plant growth via glucose-TOR signaling
Authors: Dong Yihan , Silbermann Marleen , Speiser Anna , Forieri Ilaria , Linster Eric , Poschet Gernot , Allboje Samami Arman , Wanatabe Mutsumi , Sticht Carsten , Teleman Aurelio A. , Deragon Jean-Marc , Saito Kazuki , Hell Rüdiger , Wirtz Markus
Published: October 2017

Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism. The downregulated TOR activity caused decreased translation, lowered meristematic activity, and elevated autophagy. Our results uncover a plant-specific adaptation of TOR function. In concert with GCN2, TOR allows photo-autotrophic eukaryotes to coordinate the fluxes of carbon, nitrogen, and sulfur for efficient cysteine biosynthesis under varying external nutrient supply.
Engineering a synthetic pathway for maleate in Escherichia coli
Authors: Noda Shuhei , Shirai Tomokazu , Mori Yutaro , Oyama Sachiko , Kondo Akihiko
Published: October 2017

Maleate is one of the most important dicarboxylic acids and is used to produce various polymer compounds and pharmaceuticals. Herein, microbial production of maleate is successfully achieved, to our knowledge for the first time, using genetically modified Escherichia coli. A synthetic pathway of maleate is constructed in E. coli by combining the polyketide biosynthesis pathway and benzene ring cleavage pathway. The metabolic engineering approach used to fine-tune the synthetic pathway drastically improves maleate production and demonstrates that one of the rate limiting steps exists in the conversion of chorismate to gentisate. In a batch culture of the optimised transformant, grown in a 1-L jar fermentor, the amount of produced maleate reaches 7.1 g L−1, and the yield is 0.221 mol mol−1. Our results suggest that the construction of synthetic pathways by combining a secondary metabolite pathway and the benzene ring cleavage pathway is a powerful tool for producing various valuable chemicals.
Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association
Authors: Patel Onisha , Griffin Michael D. W. , Panjikar Santosh , Dai Weiwen , Ma Xiuquan , Chan Howard , Zheng Celine , Kropp Ashleigh , Murphy James M. , Daly Roger J. , Lucet Isabelle S.
Published: October 2017

The mammalian pseudokinase SgK223, and its structurally related homologue SgK269, are oncogenic scaffolds that nucleate the assembly of specific signalling complexes and regulate tyrosine kinase signalling. Both SgK223 and SgK269 form homo- and hetero-oligomers, a mechanism that underpins a diversity of signalling outputs. However, mechanistic insights into SgK223 and SgK269 homo- and heterotypic association are lacking. Here we present the crystal structure of SgK223 pseudokinase domain and its adjacent N- and C-terminal helices. The structure reveals how the N- and C-regulatory helices engage in a novel fold to mediate the assembly of a high-affinity dimer. In addition, we identified regulatory interfaces on the pseudokinase domain required for the self-assembly of large open-ended oligomers. This study highlights the diversity in how the kinase fold mediates non-catalytic functions and provides mechanistic insights into how the assembly of these two oncogenic scaffolds is achieved in order to regulate signalling output.
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models
Authors: Tyzack Giulia E. , Hall Claire E. , Sibley Christopher R. , Cymes Tomasz , Forostyak Serhiy , Carlino Giulia , Meyer Ione F. , Schiavo Giampietro , Zhang Su-Chun , Gibbons George M. , Newcombe Jia , Patani Rickie , Lakatos András
Published: October 2017

Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1–ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics
Authors: Akaike Takaaki , Ida Tomoaki , Wei Fan-Yan , Nishida Motohiro , Kumagai Yoshito , Alam Md. Morshedul , Ihara Hideshi , Sawa Tomohiro , Matsunaga Tetsuro , Kasamatsu Shingo , Nishimura Akiyuki , Morita Masanobu , Tomizawa Kazuhito , Nishimura Akira , Watanabe Satoshi , Inaba Kenji , Shima Hiroshi , Tanuma Nobuhiro , Jung Minkyung , Fujii Shigemoto , Watanabe Yasuo , Ohmuraya Masaki , Nagy Péter , Feelisch Martin , Fukuto Jon M. , Motohashi Hozumi
Published: October 2017

Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins inEscherichia coliand mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substratel-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.
Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs
Authors: Syed Mansoor , Das Pragnya , Pawar Aishwarya , Aghai Zubair H. , Kaskinen Anu , Zhuang Zhen W. , Ambalavanan Namasivayam , Pryhuber Gloria , Andersson Sture , Bhandari Vineet
Published: October 2017

Hyperoxia-induced acute lung injury (HALI) is a key contributor to the pathogenesis of bronchopulmonary dysplasia (BPD) in neonates, for which no specific preventive or therapeutic agent is available. Here we show that lung micro-RNA (miR)-34a levels are significantly increased in lungs of neonatal mice exposed to hyperoxia. Deletion or inhibition of miR-34a improves the pulmonary phenotype and BPD-associated pulmonary arterial hypertension (PAH) in BPD mouse models, which, conversely, is worsened by miR-34a overexpression. Administration of angiopoietin-1, which is one of the downstream targets of miR34a, is able to ameliorate the BPD pulmonary and PAH phenotypes. Using three independent cohorts of human samples, we show that miR-34a expression is increased in type 2 alveolar epithelial cells in neonates with respiratory distress syndrome and BPD. Our data suggest that pharmacologic miR-34a inhibition may be a therapeutic option to prevent or ameliorate HALI/BPD in neonates.
A community effort to protect genomic data sharing, collaboration and outsourcing
Authors: Wang Shuang , Jiang Xiaoqian , Tang Haixu , Wang Xiaofeng , Bu Diyue , Carey Knox , Dyke Stephanie OM , Fox Dov , Jiang Chao , Lauter Kristin , Malin Bradley , Sofia Heidi , Telenti Amalio , Wang Lei , Wang Wenhao , Ohno-Machado Lucila
Published: October 2017

The human genome can reveal sensitive information and is potentially re-identifiable, which raises privacy and security concerns about sharing such data on wide scales. In 2016, we organized the third Critical Assessment of Data Privacy and Protection competition as a community effort to bring together biomedical informaticists, computer privacy and security researchers, and scholars in ethical, legal, and social implications (ELSI) to assess the latest advances on privacy-preserving techniques for protecting human genomic data. Teams were asked to develop novel protection methods for emerging genome privacy challenges in three scenarios: Track (1) data sharing through the Beacon service of the Global Alliance for Genomics and Health. Track (2) collaborative discovery of similar genomes between two institutions; and Track (3) data outsourcing to public cloud services. The latter two tracks represent continuing themes from our 2015 competition, while the former was new and a response to a recently established vulnerability. The winning strategy for Track 1 mitigated the privacy risk by hiding approximately 11% of the variation in the database while permitting around 160,000 queries, a significant improvement over the baseline. The winning strategies in Tracks 2 and 3 showed significant progress over the previous competition by achieving multiple orders of magnitude performance improvement in terms of computational runtime and memory requirements. The outcomes suggest that applying highly optimized privacy-preserving and secure computation techniques to safeguard genomic data sharing and analysis is useful. However, the results also indicate that further efforts are needed to refine these techniques into practical solutions.
Prediction of Indian Summer-Monsoon Onset Variability: A Season in Advance
Authors: Pradhan Maheswar , Rao A. Suryachandra , Srivastava Ankur , Dakate Ashish , Salunke Kiran , Shameera K. S.
Published: October 2017

Monsoon onset is an inherent transient phenomenon of Indian Summer Monsoon and it was never envisaged that this transience can be predicted at long lead times. Though onset is precipitous, its variability exhibits strong teleconnections with large scale forcing such as ENSO and IOD and hence may be predictable. Despite of the tremendous skill achieved by the state-of-the-art models in predicting such large scale processes, the prediction of monsoon onset variability by the models is still limited to just 2–3 weeks in advance. Using an objective definition of onset in a global coupled ocean-atmosphere model, it is shown that the skillful prediction of onset variability is feasible under seasonal prediction framework. The better representations/simulations of not only the large scale processes but also the synoptic and intraseasonal features during the evolution of monsoon onset are the comprehensions behind skillful simulation of monsoon onset variability. The changes observed in convection, tropospheric circulation and moisture availability prior to and after the onset are evidenced in model simulations, which resulted in high hit rate of early/delay in monsoon onset in the high resolution model.
A proteome view of structural, functional, and taxonomic characteristics of major protein domain clusters
Authors: Sun Chia-Tsen , Chiang Austin W. T. , Hwang Ming-Jing
Published: October 2017

Proteome-scale bioinformatics research is increasingly conducted as the number of completely sequenced genomes increases, but analysis of protein domains (PDs) usually relies on similarity in their amino acid sequences and/or three-dimensional structures. Here, we present results from a bi-clustering analysis on presence/absence data for 6,580 unique PDs in 2,134 species with a sequenced genome, thus covering a complete set of proteins, for the three superkingdoms of life, Bacteria, Archaea, and Eukarya. Our analysis revealed eight distinctive PD clusters, which, following an analysis of enrichment of Gene Ontology functions and CATH classification of protein structures, were shown to exhibit structural and functional properties that are taxa-characteristic. For examples, the largest cluster is ubiquitous in all three superkingdoms, constituting a set of 1,472 persistent domains created early in evolution and retained in living organisms and characterized by basic cellular functions and ancient structural architectures, while an Archaea and Eukarya bi-superkingdom cluster suggests its PDs may have existed in the ancestor of the two superkingdoms, and others are single superkingdom- or taxa (e.g. Fungi)-specific. These results contribute to increase our appreciation of PD diversity and our knowledge of how PDs are used in species, yielding implications on species evolution.
Anatomical Study of the Neurovascular in Flexor Hallucis Longus Tendon Transfers
Authors: Mao Haijiao , Dong Wenwei , Shi Zengyuan , Yin Weigang , Xu Dachuan , Wapner Keith L.
Published: October 2017

The transfer of the flexor hallucis longus tendon or flexor digitorum longus tendon is frequently used for the treatment of posterior tibial tendon insufficiency or chronic Achilles tendinopathy. According to several anatomical studies, harvesting the flexor hallucis longus (FHL) tendon may cause nerve injury. Sixty-eight embalmed feet were dissected and anatomically classified to define the relationship between Henry’s knot and the plantar nerves. Two different configurations were identified. In Pattern 1, which was observed in 64 specimens (94.1%), the distance between the medial plantar nerve and Henry’s knot was 5.96 mm (range, 3.34 to 7.84, SD = 1.12). In Pattern 2, which was observed in 4 specimens (5.9%), there was no distance between the medial plantar nerve (MPN) and Henry’s knot. No statistically significant difference was observed according to gender or side (p > 0.05). A retraction was performed to harvest the FHL through the posteromedial hindfoot incision using a single minimally invasive technique, and the medial and lateral plantar nerve lesions were scrupulously assessed. In conclusion, medial and lateral plantar nerve injuries did not occur more frequently, even after performing a single minimally invasive incision to harvest the FHL tendon, due to the large distance between the FHL tendon and the medial and lateral plantar nerves.
Comparison of DGT with traditional methods for assessing cadmium bioavailability to Brassica chinensis in different soils
Authors: Dai Yunchao , Nasir Mubasher , Zhang Yulin , Wu Haiming , Guo Honghong , Lv Jialong
Published: October 2017

There is no universally accepted method for evaluating cadmium (Cd) bioavailability in soil. The diffusive gradient in thin films (DGT) technique is a promising tool, but there is considerable debate about its suitability. The ability of this technique to estimate Cd bioavailability in soils was compared with the abilities of other traditional chemical extraction techniques (soil solution, ethylene diamine tetraacetic acid (EDTA), acetic acid (HAc), calcium chloride (CaCl2), and pseudo-total Cd methods) based on a greenhouse experiment using pakchoi (Brassica chinensis) grown in 15 soils from different provinces of China. In addition, we assessed whether these methods were independent of the soil properties. Correlations between the plant and soil Cd concentrations measured with the traditional extraction techniques were dependent on the pH and organic carbon (OC) content, indicating that these methods are influenced by the soil properties. In contrast, the DGT measurements were independent of the soil properties and showed a higher correlation coefficient compared to that of the traditional techniques. Hence, the DGT technique is better and should be preferable for assessing Cd biological effectiveness in different soil types.
Emergence of early alterations in network oscillations and functional connectivity in a tau seeding mouse model of Alzheimer’s disease pathology
Authors: Ahnaou A. , Moechars D. , Raeymaekers L. , Biermans R. , Manyakov N. V. , Bottelbergs A. , Wintmolders C. , Van Kolen K. , Van De Casteele T. , Kemp J. A. , Drinkenburg W. H.
Published: October 2017

Synaptic dysfunction and disconnectivity are core deficits in Alzheimer’s disease (AD), preceding clear changes in histopathology and cognitive functioning. Here, the early and late effects of tau pathology induction on functional network connectivity were investigated in P301L mice. Multichannel EEG oscillations were used to compute (1) coherent activity between the prefrontal cortex (PFC) and hippocampus (HPC) CA1-CA3 networks; (2) phase-amplitude cross frequency coupling (PAC) between theta and gamma oscillations, which is instrumental in adequate cognitive functioning; (3) information processing as assessed by auditory evoked potentials and oscillations in the passive oddball mismatch negativity-like (MMN) paradigm. At the end, the density of tau aggregation and GABA parvalbumin (PV+) interneurons were quantified by immunohistochemistry. Early weakening of EEG theta oscillations and coherent activity were revealed between the PFC and HPC CA1 and drastic impairments in theta–gamma oscillations PAC from week 2 onwards, while PV+ interneurons count was not altered. Moreover, the tau pathology disrupted the MMN complex amplitude and evoked gamma oscillations to standard and deviant stimuli suggesting altered memory formation and recall. The induction of intracellular tau aggregation by tau seed injection results in early altered connectivity and strong theta–gamma oscillations uncoupling, which may be exploited as an early electrophysiological signature of dysfunctional neuronal networks.
Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells
Authors: Cerino Giulia , Gaudiello Emanuele , Muraro Manuele Giuseppe , Eckstein Friedrich , Martin Ivan , Scherberich Arnaud , Marsano Anna
Published: October 2017

In vitrorecapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promotedin vitrothe early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells uponin vivoectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as anangiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.
Small Molecule Accurate Recognition Technology (SMART) to Enhance Natural Products Research
Authors: Zhang Chen , Idelbayev Yerlan , Roberts Nicholas , Tao Yiwen , Nannapaneni Yashwanth , Duggan Brendan M. , Min Jie , Lin Eugene C. , Gerwick Erik C. , Cottrell Garrison W. , Gerwick William H.
Published: October 2017

Various algorithms comparing 2D NMR spectra have been explored for their ability to dereplicate natural products as well as determine molecular structures. However, spectroscopic artefacts, solvent effects, and the interactive effect of functional group(s) on chemical shifts combine to hinder their effectiveness. Here, we leveraged Non-Uniform Sampling (NUS) 2D NMR techniques and deep Convolutional Neural Networks (CNNs) to create a tool, SMART, that can assist in natural products discovery efforts. First, an NUS heteronuclear single quantum coherence (HSQC) NMR pulse sequence was adapted to a state-of-the-art nuclear magnetic resonance (NMR) instrument, and data reconstruction methods were optimized, and second, a deep CNN with contrastive loss was trained on a database containing over 2,054 HSQC spectra as the training set. To demonstrate the utility of SMART, several newly isolated compounds were automatically located with their known analogues in the embedded clustering space, thereby streamlining the discovery pipeline for new natural products.
Therapeutic efficacy of a combined sage and bitter apple phytopharmaceutical in chronic DSS-induced colitis
Authors: Hoffmann Maximilian , Schwertassek Ulla , Seydel Aleksandra , Weber Klaus , Hauschildt Sunna , Lehmann Jörg
Published: October 2017

Inflammatory bowel diseases are multifactorial disorders of the gastrointestinal tract with rising incidence worldwide. Current standard therapies are only partially effective and often show severe adverse effects. Thus, novel, more efficient and well-tolerated therapeutic options are urgently needed. We have studied the therapeutic potential of a phytopharmaceutical combining sage and bitter apple (SBA) in the mouse model of chronic dextran sulfate sodium (DSS) colitis. SBA represents a traditional medicine against diarrhea and was shown to exhibit anti-inflammatory effects in vitro. In the chronic DSS colitis model SBA treatment significantly reduced clinical symptoms in a dose-dependent manner. The positive therapeutic effect of SBA was characterized by a decreased histopathological score indicating tissue healing. Moreover, the number of neutrophils as well as the expression of the neutrophil-recruiting chemokine CXCL-1/KC in the colon tissue was significantly reduced, whereas the recruitment of macrophages was induced. Also, the expression of inflammatory markers was significantly suppressed, while the expression of the anti-inflammatory cytokine interleukin-10 was induced in colon tissue following treatment with SBA. Phytopharmaceuticals are increasingly recognized as potential therapeutics in IBD. Thus, based on the results from this study, SBA can be considered as an alternative or supplementary option for IBD therapy.
The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation
Authors: Chiu Joy E. , Thekkiniath Jose , Choi Jae-Yeon , Perrin Benjamin A. , Lawres Lauren , Plummer Mark , Virji Azan Z. , Abraham Amanah , Toh Justin Y. , Zandt Michael Van , Aly Ahmed S. I. , Voelker Dennis R. , Mamoun Choukri Ben
Published: October 2017

The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for survival ofPlasmodium falciparumwithin human erythrocytes. Accordingly, a PA analog α-PanAm showed potent activity against blood stage parasitesin vitro; however, its efficacyin vivoand its mode of action remain unknown. We developed a new synthesis route for α-PanAm and showed that the compound is highly effective against blood stages of drug-sensitive and -resistantP. falciparumstrains, inhibits development ofP. bergheiin hepatocytes, and at doses up to 100 mg/kg also inhibits blood stage development ofP. chabaudiin mice. We used yeast and its pantothenate kinase Cab1 as models to characterize mode of action of α-PanAm and found that α-PanAm inhibits yeast growth in a PA-dependent manner, and its potency increases dramatically in a yeast mutant with defective pantothenate kinase activity. Biochemical analyses using14C-PA as a substrate demonstrated that α-PanAm is a competitive inhibitor of Cab1. Interestingly, biochemical and mass spectrometry analyses also showed that the compound is phosphorylated by Cab1. Together, these data suggest that α-PanAm exerts its antimicrobial activity by direct competition with the natural substrate PA for phosphorylation by the pantothenate kinase.
Exopolysaccharides from Lactobacillus plantarum NCU116 induce c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in mouse intestinal epithelial cancer cells
Authors: Zhou Xingtao , Hong Tao , Yu Qiang , Nie Shaoping , Gong Deming , Xiong Tao , Xie Mingyong
Published: October 2017

Exopolysaccharides (EPS) from lactic acid bacteria (LAB) have been reported to play vital parts in the modulation of cell-cycle and apoptosis in cancer cells. However, the mechanisms by which EPS regulate the proliferation and apoptosis of cancer cells remain incompletely understood. We thus used different cancer cells to evaluate the anticancer ability and to investigate the underlying molecular mechanism of EPS from Lactobacillus plantarum NCU116 (EPS116). Our studies showed that EPS116 inhibited the proliferation of cancer cells in a cell type manner, and remarkably repressed the growth and survival of CT26 through induction of apoptosis. Moreover, EPS116 increased the expression of pro-apoptotic genes, including Fas, Fasl and c-Jun, induced the phosphorylation of c-Jun in CT26 cells. Furthermore, TLR2 (Toll like receptor 2) was upregulated by EPS116, and the CT26 cells with TLR2 knockdown were found to be insensitive to EPS116, suggesting that the anti-cancer activity of EPS116 may be TLR2-dependent. Taken together, the suppressive efficacy of EPS116 on the proliferation of CT26 cells may be mediated via TLR2 and the activation of c-Jun dependent Fas/Fasl-mediated apoptotic pathway. Our study has, for the first time, shown that EPS from LAB induced c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in CT26 cells.
Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity
Authors: Fourbon Yann , Guéguinou Maxime , Félix Romain , Constantin Bruno , Uguen Arnaud , Fromont Gaëlle , Lajoie Laurie , Magaud Christophe , Lecomte Thierry , Chamorey Emmanuel , Chatelier Aurélien , Mignen Olivier , Potier-Cartereau Marie , Chantôme Aurélie , Bois Patrick , Vandier Christophe
Published: October 2017

It is generally accepted that voltage-gated Ca2+ channels, CaV, regulate Ca2+ homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca2+ protein α1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting α1D reduced the migration and the basal cytosolic Ca2+ concentration of HCT116 colon cancer cell line and modified the cytosolic Ca2+ oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly, NCX1/3 regulated membrane potential of HCT116 cells only when α1D was silenced, and blocking NCX1/3 increased cytosolic Ca2+ concentration and cell migration. However, membrane depolarization did not induce an increase in intracellular Ca2+. Patch-clamp experiments clearly showed that the inward Ca2+ current was absent. Finally, flow cytometry and immunofluorescence studies showed that α1D protein was localized at the plasma membrane, in cytosol and cell nuclei. Altogether, we uncover a novel signaling pathway showing that α1D is involved in the regulation of Ca2+ homeostasis and cell migration by a mechanism independent of its plasma membrane canonical function but that involved plasma membrane Na+/Ca2+ exchanger.
Gap enhanced fluorescence as a road map for the detection of very weakly fluorescent emitters from visible to ultraviolet
Authors: McArthur Duncan , Papoff Francesco
Published: October 2017

We analyze the enhancement of the rates of both the emission and the far field radiation for dipoles placed in the gap between a metallic nanorod, or nanosphere, and a metallic substrate. For wavelengths between 150 nm and 650 nm, the response of the gapped nanostructures considered in this work is dominated by few principal modes of the nanoparticle, which include self-consistently the effect of the substrate. For wavelengths shorter than 370 nm, the far field radiative enhancements of aluminum nanostructures are significantly higher than those for gold or silver. With aluminum, bright mode resonances are tunable over tens or hundreds of nanometers by changing the size of the nanoparticle and have far field radiative enhancements of up to three orders of magnitude. These results provide a road map to label-free detection of many emitters too weakly fluorescent for present approaches.
Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies
Authors: Zwetsloot P. P. , Kouwenberg L. H. J. A. , Sena E. S. , Eding J. E. , den Ruijter H. M. , Sluijter J. P. G. , Pasterkamp G. , Doevendans P. A. , Hoefer I. E. , Chamuleau S. A. J. , van Hout G. P. J. , Jansen of Lorkeers S. J.
Published: October 2017

Large animal models are essential for the development of novel therapeutics for myocardial infarction. To optimize translation, we need to assess the effect of experimental design on disease outcome and model experimental design to resemble the clinical course of MI. The aim of this study is therefore to systematically investigate how experimental decisions affect outcome measurements in large animal MI models. We used control animal-data from two independent meta-analyses of large animal MI models. All variables of interest were pre-defined. We performed univariable and multivariable meta-regression to analyze whether these variables influenced infarct size and ejection fraction. Our analyses incorporated 246 relevant studies. Multivariable meta-regression revealed that infarct size and cardiac function were influenced independently by choice of species, sex, co-medication, occlusion type, occluded vessel, quantification method, ischemia duration and follow-up duration. We provide strong systematic evidence that commonly used endpoints significantly depend on study design and biological variation. This makes direct comparison of different study-results difficult and calls for standardized models. Researchers should take this into account when designing large animal studies to most closely mimic the clinical course of MI and enable translational success.
MMP proteolytic activity regulates cancer invasiveness by modulating integrins
Authors: Das Alakesh , Monteiro Melissa , Barai Amlan , Kumar Sandeep , Sen Shamik
Published: October 2017

Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.
Margination and stretching of von Willebrand factor in the blood stream enable adhesion
Authors: Rack Kathrin , Huck Volker , Hoore Masoud , Fedosov Dmitry A. , Schneider Stefan W. , Gompper Gerhard
Published: October 2017

The protein von Willebrand factor (VWF) is essential in primary hemostasis, as it mediates platelet adhesion to vessel walls. VWF retains its compact (globule-like) shape in equilibrium due to internal molecular associations, but is able to stretch when a high enough shear stress is applied. Even though the shear-flow sensitivity of VWF conformation is well accepted, the behavior of VWF under realistic blood flow conditions remains poorly understood. We perform mesoscopic numerical simulations together with microfluidic experiments in order to characterize VWF behavior in blood flow for a wide range of flow-rate and hematocrit conditions. In particular, our results demonstrate that the compact shape of VWF is important for its migration (or margination) toward vessel walls and that VWF stretches primarily in a near-wall region in blood flow making its adhesion possible. Our results show that VWF is a highly optimized protein in terms of its size and internal associations which are necessary to achieve its vital function. A better understanding of the relevant mechanisms for VWF behavior in microcirculation provides a further step toward the elucidation of the role of mutations in various VWF-related diseases.
WNT-activated bone grafts repair osteonecrotic lesions in aged animals
Authors: Salmon B. , Liu B. , Shen E. , Chen T. , Li J. , Gillette M. , Ransom R. C. , Ezran M. , Johnson C. A. , Castillo A. B. , Shen W. J. , Kraemer F. B. , Smith A. A. , Helms J. A.
Published: October 2017

The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.