bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micro-Crack Induced Buckypaper/PI Tape Hybrid Sensors with Enhanced and Tunable Piezo-Resistive Properties
Authors: Danish Mustafa , Luo Sida 
Published: November 2019

AbstractPiezoresistive properties play a vital role in the development of sensor for structural health monitoring (SHM) applications. Novel stable crack initiation method (SCIM) is established to improve the gauge factor (GF) with maximum achievable working strain region for PI tape enabled buckypaper hybrid sensors. Cracks are generated by applying strain rate-controlled tension force using dynamic mechanical analyzer (DMA). The sensor has been cycled in tension to characterize GF with crack opening. It is determined experimentally that GF increases with increasing crack opening and crack becomes unstable when opening increases above 8 µm. Tremendous improvement in GF has been observed which improved from single-digit to several hundreds. The highest GF obtained so far is ~255, showing 75 times improvement compared with the ones without the SCIM implementation. The crack initiation strain (CIS) is characterized by sonication and centrifugation time. It is determined experimentally that the maximum CIS of 3.5% can be achieved with sonication time of 40 min and increasing centrifuge time has an in-significantly dropping effect on CIS. Excellent stability/reproducibility has been proved/demonstrated on SCIM implemented sensors through a rigorous 12,500 tensile cycle test on DMA. The performance of sensor is practically demonstrated in tension and bending on glass fiber reinforced polymer (GFRP) structures.
Structural insights into heme binding to IL-36α proinflammatory cytokine
Authors: Wißbrock Amelie , Goradia Nishit B. , Kumar Amit , Paul George Ajay Abisheck , Kühl Toni , Bellstedt Peter , Ramachandran Ramadurai , Hoffmann Patrick , Galler Kerstin , Popp Jürgen , Neugebauer Ute , Hampel Kornelia , Zimmermann Bastian , Adam Susanne , Wiendl Maximilian , Krönke Gerhard , Hamza Iqbal , Heinemann Stefan H. , Frey Silke , Hueber Axel J. , Ohlenschläger Oliver , Imhof Diana 
Published: November 2019

AbstractCytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.
The Relationship between Trial-by-Trial Variability and Oscillations of Cortical Population Activity
Authors: Daniel Edan , Meindertsma Thomas , Arazi Ayelet , Donner Tobias H. , Dinstein Ilan 
Published: November 2019

AbstractNeural activity fluctuates over time, creating considerable variability across trials. This trial-by-trial neural variability is dramatically reduced (“quenched”) after the presentation of sensory stimuli. Likewise, the power of neural oscillations, primarily in the alpha-beta band, is also reduced after stimulus onset. Despite their similarity, these phenomena have so far been studied and discussed independently. We hypothesized that the two phenomena are tightly coupled in electrophysiological recordings of large cortical neural populations. To test this, we examined magnetoencephalography (MEG) recordings of healthy subjects viewing repeated presentations of a visual stimulus. The timing, amplitude, and spatial topography of variability-quenching and power-suppression were remarkably similar. Neural variability quenching was eliminated by excluding the alpha-beta band from the recordings, but not by excluding other frequency-bands. Moreover, individual magnitudes of alpha-beta band-power explained 86% of between-subject differences in variability quenching. An alternative mechanism that may generate variability quenching is increased phase alignment across trials. However, changes in inter-trial-phase-coherence (ITPC) exhibited distinct timing and no correlations with the magnitude of variability quenching in individual participants. These results reveal that neural variability quenching is tightly coupled with stimulus-induced changes in the power of alpha-beta band oscillations, associating two phenomena that have so far been studied in isolation.
Earthquake and typhoon trigger unprecedented transient shifts in shallow hydrothermal vents biogeochemistry
Authors: Lebrato Mario , Wang Yiming V. , Tseng Li-Chun , Achterberg Eric P. , Chen Xue-Gang , Molinero Juan-Carlos , Bremer Karen , Westernströer Ulrike , Söding Emanuel , Dahms Hans-Uwe , Küter Marie , Heinath Verena , Jöhnck Janika , Konstantinou Kostas I. , Yang Yiing J. , Hwang Jiang-Shiou , Garbe-Schönberg Dieter 
Published: November 2019

AbstractShallow hydrothermal vents are of pivotal relevance for ocean biogeochemical cycles, including seawater dissolved heavy metals and trace elements as well as the carbonate system balance. The Kueishan Tao (KST) stratovolcano off Taiwan is associated with numerous hydrothermal vents emitting warm sulfur-rich fluids at so-called White Vents (WV) and Yellow Vent (YV) that impact the surrounding seawater masses and habitats. The morphological and biogeochemical consequences caused by a M5.8 earthquake and a C5 typhoon (“Nepartak”) hitting KST (12th May, and 2nd–10th July, 2016) were studied within a 10-year time series (2009–2018) combining aerial drone imagery, technical diving, and hydrographic surveys. The catastrophic disturbances triggered landslides that reshaped the shoreline, burying the seabed and, as a consequence, native sulfur accretions that were abundant on the seafloor disappeared. A significant reduction in venting activity and fluid flow was observed at the high-temperature YV. Dissolved Inorganic Carbon (DIC) maxima in surrounding seawater reached 3000–5000 µmol kg−1, and Total Alkalinity (TA) drawdowns were below 1500–1000 µmol kg−1 lasting for one year. A strong decrease and, in some cases, depletion of dissolved elements (Cd, Ba, Tl, Pb, Fe, Cu, As) including Mg and Cl in seawater from shallow depths to the open ocean followed the disturbance, with a recovery of Mg and Cl to pre-disturbance concentrations in 2018. The WV and YV benthic megafauna exhibited mixed responses in their skeleton Mg:Ca and Sr:Ca ratios, not always following directions of seawater chemical changes. Over 70% of the organisms increased skeleton Mg:Ca ratio during rising DIC (higher CO2) despite decreasing seawater Mg:Ca ratios showing a high level of resilience. KST benthic organisms have historically co-existed with such events providing them ecological advantages under extreme conditions. The sudden and catastrophic changes observed at the KST site profoundly reshaped biogeochemical processes in shallow and offshore waters for one year, but they remained transient in nature, with a possible recovery of the system within two years.
CRISPR/Cas9-mediated editing of Δ5 and Δ6 desaturases impairs Δ8-desaturation and docosahexaenoic acid synthesis in Atlantic salmon (Salmo salar L.)
Authors: Datsomor Alex K. , Olsen Rolf E. , Zic Nikola , Madaro Angelico , Bones Atle M. , Edvardsen Rolf B. , Wargelius Anna , Winge Per 
Published: November 2019

AbstractThe in vivo functions of Atlantic salmon fatty acyl desaturases (fads2), Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2 in long chain polyunsaturated fatty acid (LC-PUFA) synthesis in salmon and fish in general remains to be elucidated. Here, we investigate in vivo functions and in vivo functional redundancy of salmon fads2 using two CRISPR-mediated partial knockout salmon, Δ6abc/5Mt with mutations in Δ6fads2-a, Δ6fads2-b, Δ6fads2-c and Δ5fads2, and Δ6bcMt with mutations in Δ6fads2-b and Δ6fads2-c. F0 fish displaying high degree of gene editing (50–100%) were fed low LC-PUFA and high LC-PUFA diets, the former containing reduced levels of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids but higher content of linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acids, and the latter containing high levels of 20:5n-3 and 22:6n-3 but reduced compositions of 18:2n-6 and 18:3n-3. The Δ6abc/5Mt showed reduced 22:6n-3 levels and accumulated Δ6-desaturation substrates (18:2n-6, 18:3n-3) and Δ5-desaturation substrate (20:4n-3), demonstrating impaired 22:6n-3 synthesis compared to wildtypes (WT). Δ6bcMt showed no effect on Δ6-desaturation compared to WT, suggesting Δ6 Fads2-a as having the predominant Δ6-desaturation activity in salmon, at least in the tissues analyzed. Both Δ6abc/5Mt and Δ6bcMt demonstrated significant accumulation of Δ8-desaturation substrates (20:2n-6, 20:3n-3) when fed low LC-PUFA diet. Additionally, Δ6abc/5Mt demonstrated significant upregulation of the lipogenic transcription regulator, sterol regulatory element binding protein-1 (srebp-1) in liver and pyloric caeca under reduced dietary LC-PUFA. Our data suggest a combined effect of endogenous LC-PUFA synthesis and dietary LC-PUFA levels on srebp-1 expression which ultimately affects LC-PUFA synthesis in salmon. Our data also suggest Δ8-desaturation activities for salmon Δ6 Fads2 enzymes.
Exploring the limitations of biophysical propensity scales coupled with machine learning for protein sequence analysis
Authors: Raimondi Daniele , Orlando Gabriele , Vranken Wim F. , Moreau Yves 
Published: November 2019

AbstractMachine learning (ML) is ubiquitous in bioinformatics, due to its versatility. One of the most crucial aspects to consider while training a ML model is to carefully select the optimal feature encoding for the problem at hand. Biophysical propensity scales are widely adopted in structural bioinformatics because they describe amino acids properties that are intuitively relevant for many structural and functional aspects of proteins, and are thus commonly used as input features for ML methods. In this paper we reproduce three classical structural bioinformatics prediction tasks to investigate the main assumptions about the use of propensity scales as input features for ML methods. We investigate their usefulness with different randomization experiments and we show that their effectiveness varies among the ML methods used and the tasks. We show that while linear methods are more dependent on the feature encoding, the specific biophysical meaning of the features is less relevant for non-linear methods. Moreover, we show that even among linear ML methods, the simpler one-hot encoding can surprisingly outperform the “biologically meaningful” scales. We also show that feature selection performed with non-linear ML methods may not be able to distinguish between randomized and “real” propensity scales by properly prioritizing to the latter. Finally, we show that learning problem-specific embeddings could be a simple, assumptions-free and optimal way to perform feature learning/engineering for structural bioinformatics tasks.
Steroid hormones in hair reveal sexual maturity and competition in wild house mice (Mus musculus domesticus)
Authors: Carlitz Esther H. D. , Runge Jan-Niklas , König Barbara , Winkler Lennart , Kirschbaum Clemens , Gao Wei , Lindholm Anna K. 
Published: November 2019

AbstractEndocrine data from wild populations provide important insight into social systems. However, obtaining samples for traditional methods involves capture and restraint of animals, and/or pain, which can influence the animal’s stress level, and thereby undesirable release of hormones. Here, we measured corticosterone, testosterone and progesterone in the hair of 482 wild-derived house mice that experienced sexual competition while living under semi-natural conditions. We tested whether sex, age, weight and indicators of sexual maturity, reproduction and social conflicts predict hormone concentrations measured in hair (sampling at endpoint). We show that body weight, sex and age significantly predict cumulative testosterone and progesterone levels, allowing the differentiation between subadults and adults in both sexes. Corticosterone was only slightly elevated in older males compared to older females and increased with the level of visible injuries or scars. Testosterone in males positively correlated with body weight, age, testes size, and sperm number. Progesterone in females significantly increased with age, body weight, and the number of embryos implanted throughout life, but not with the number of litters when controlled for age and weight. Our results highlight the biological validity of hair steroid measurements and provide important insight into reproductive competition in wild house mice.
Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms
Authors: Basso Virginia , Tran Dat Q. , Schaal Justin B. , Tran Patti , Eriguchi Yoshihiro , Ngole Diana , Cabebe Anthony E. , Park A. young , Beringer Paul M. , Ouellette André J. , Selsted Michael E. 
Published: November 2019

AbstractInvasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.
Influence of the foveal curvature on myopic macular complications
Authors: Park Un Chul , Ma Dae Joong , Ghim Woon Hyung , Yu Hyeong Gon 
Published: November 2019

AbstractIn this cross-sectional study, we investigated whether a foveal curvature affects the development of two major myopic macular complications, myopic traction maculopathy (MTM) and myopic choroidal neovascularization (mCNV). In high myopic eyes (axial length ≥ 26.5 mm, refractive error ≤ −6 diopters) with posterior staphyloma, three different parameters of foveal curvature (staphyloma height, coefficient a, and curvature index) calculated based on the retinal pigment epithelium hyperreflective line in spectral domain optical coherence tomography image were compared among the MTM (72 eyes), mCNV (58 eyes), and control (69 eyes) group. The three curvature parameters showed a significant correlation with each other (all P’s < 0.001). The axial length, refractive error, and staphyloma types were comparable among the groups, but the means of all three curvature parameters were significantly greater in the MTM group compared to the mCNV and control groups (all P’s < 0.001). Furthermore, the curvature parameters had a significant correlation with myopic severity in the MTM group, but not in the other groups. These results suggest that a steeper change of foveal curvature plays a role in the development of MTM but not mCNV in high myopes.
Effects of global change factors and living roots on root litter decomposition in a Qinghai-Tibet alpine meadow
Authors: Shu Meng , Zhao Qingzhou , Li Zhen , Zhang Lin , Wang Peng , Hu Shuijin 
Published: November 2019

AbstractRoots account for a major part of plant biomass in Tibetan alpine meadows. Understanding root decomposition with global change is key to predict carbon (C) and nutrient dynamics on the Qinghai-Tibet Plateau. Yet, few experiments have carefully examined root decomposition as influenced by global change. We conducted a field study to investigate the effects of nitrogen (N) addition, air warming, precipitation change, and the presence/absence of living roots on root decomposition in a Tibetan alpine meadow. Our results showed that N addition increased the mass and C remaining, and induced N accumulation in the litter. Increased precipitation significantly amplified the positive effect of N addition on litter mass remaining. The presence of alive roots in the litterbags decreased root litter C remaining but significantly increased N and phosphorus remaining of the litter. However, we did not find any significant effects of air warming on the litter decomposition. In the Qinghai-Tibet Plateau, N deposition is predicted to increase and precipitation regime is predicted to change. Our results suggest that the interaction between increased N and precipitation may reduce root decomposition in the Qinghai-Tibet Plateau in the future, and that the large stock of living roots exert a dominant impact on nutrient dynamics of root decomposition in the Tibetan alpine systems.
A common mechanism allows selective targeting of GluN2B subunit-containing N-methyl-D-aspartate receptors
Authors: Schreiber Julian A. , Schepmann Dirk , Frehland Bastian , Thum Simone , Datunashvili Maia , Budde Thomas , Hollmann Michael , Strutz-Seebohm Nathalie , Wünsch Bernhard , Seebohm Guiscard 
Published: November 2019

AbstractN-methyl-D-aspartate receptors (NMDARs), especially GluN2B-containing NMDARs, are associated with neurodegenerative diseases like Parkinson, Alzheimer and Huntington based on their high Ca2+ conductivity. Overactivation leads to high intracellular Ca2+ concentrations and cell death rendering GluN2B-selective inhibitors as promising drug candidates. Ifenprodil represents the first highly potent prototypical, subtype-selective inhibitor of GluN2B-containing NMDARs. However, activity of ifenprodil on serotonergic, adrenergic and sigma receptors limits its therapeutic use. Structural reorganization of the ifenprodil scaffold to obtain 3-benzazepines retained inhibitory GluN2B activity but decreased the affinity at the mentioned non-NMDARs. While scaffold optimization improves the selectivity, the molecular inhibitory mechanism of these compounds is still not known. Here, we show a common inhibitory mechanism of ifenprodil and the related 3-benzazepines by mutational modifications of the receptor binding site, chemical modifications of the 3-benzazepine scaffold and subsequent in silico simulation of the inhibitory mechanism.
Alpha-synuclein is strategically positioned for afferent modulation of midbrain dopamine neurons and is essential for cocaine preference
Authors: Trubetckaia Olga , Lane Ariana E. , Qian Liping , Zhou Ping , Lane Diane A. 
Published: November 2019

AbstractAlpha-synuclein (α-syn) is an abundant neuroprotein elevated in cocaine addicts, linked to drug craving, and recruited to axon terminals undergoing glutamatergic plasticity - a proposed mechanism for substance abuse. However, little is known about normal α-syn function or how it contributes to substance abuse. We show that α-syn is critical for preference of hedonic stimuli and the cognitive flexibility needed to change behavioral strategies, functions that are altered with substance abuse. Electron microscopic analysis reveals changes in α-syn targeting of ventral tegmental area axon terminals that is dependent upon the duration of cocaine exposure. The dynamic changes in presynaptic α-syn position it to control neurotransmission and fine-tune the complex afferent inputs to dopamine neurons, potentially altering functional dopamine output. Cocaine also increases postsynaptic α-syn where it is needed for normal ALIX function, multivesicular body formation, and cocaine-induced exosome release indicating potentially similar α-syn actions for vesicle release pre- and post-synaptically.
Cajanonic acid A regulates the ratio of Th17/Treg via inhibition of expression of IL-6 and TGF-β in insulin-resistant HepG2 cells
Authors: Gong Yanfeng , Liu Huanbing , Tao Liming 
Published: November 2019

Abstract
Background: The objectives of the present study are to investigate whether cajanonic acid A (CAA) can reduce insulin resistance (IR) in HepG2 cells and to gain a preliminary understanding of the mechanisms underlying this effect.
Methods: Following induction of IR in HepG2 cells, we tested the regulatory effect of CAA on glucose consumption and evaluated hepatocyte production of IL-6, TGF-β, and key molecules in the insulin transduction pathway. A transwell co-culturing system was used to assess the effect of CAA on IR in HepG2 cells during the differentiation of CD4+ T cells by calculating the ratio of (Th17)/regulatory T cell (Treg). We evaluated the effect of CAA on the expression of IL-17RC cells and HepG2 cell apoptosis by immunofluorescence and flow cytometry assay.
Results: CAA improved dexamethasone-induced reduction in glucose consumption in HepG2 cells, inhibited hepatocyte production of IL-6 and TGF-β, increased the expression of IL-17RC cell, and increased cellular apoptosis in insulin-resistant HepG2 cells. When co-cultured with CD4+ T cells, insulin-resistant HepG2 cells induced a decrease in the ratio of Th17/Treg, but CAA dampened the effect. Application of IL-6 and TGF-β, together with CAA, reversed the effect of CAA on insulin-resistant HepG2 cells. Overexpression of IL17R, however, counteracted the effect of IL-6 neutralizing antibody within the culture system.
Conclusion: CAA can regulate the ratio of Th17/Treg by mediating the expression of IL-6 and TGF-β in insulin-resistant HepG2 cells.