bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental arginine controls multinuclear giant cell metabolism and formation
Authors: Brunner Julia S. , Vulliard Loan , Hofmann Melanie , Kieler Markus , Lercher Alexander , Vogel Andrea , Russier Marion , Brüggenthies Johanna B. , Kerndl Martina , Saferding Victoria , Niederreiter Birgit , Junza Alexandra , Frauenstein Annika , Scholtysek Carina , Mikami Yohei , Klavins Kristaps , Krönke Gerhard , Bergthaler Andreas , O’Shea John J. , Weichhart Thomas , Meissner Felix , Smolen Josef S. , Cheng Paul , Yanes Oscar , Menche Jörg , Murray Peter J. , Sharif Omar , Blüml Stephan , Schabbauer Gernot 
Published: January 2020

AbstractMultinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Β ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling.
No detectable Weddell Sea Antarctic Bottom Water export during the Last and Penultimate Glacial Maximum
Authors: Huang Huang , Gutjahr Marcus , Eisenhauer Anton , Kuhn Gerhard 
Published: January 2020

AbstractWeddell Sea-derived Antarctic Bottom Water (AABW) is one of the most important deep water masses in the Southern Hemisphere occupying large portions of the deep Southern Ocean (SO) today. While substantial changes in SO-overturning circulation were previously suggested, the state of Weddell Sea AABW export during glacial climates remains poorly understood. Here we report seawater-derived Nd and Pb isotope records that provide evidence for the absence of Weddell Sea-derived AABW in the Atlantic sector of the SO during the last two glacial maxima. Increasing delivery of Antarctic Pb to regions outside the Weddell Sea traced SO frontal displacements during both glacial terminations. The export of Weddell Sea-derived AABW resumed late during glacial terminations, coinciding with the last major atmospheric CO2 rise in the transition to the Holocene and the Eemian. Our new records lend strong support for a previously inferred AABW overturning stagnation event during the peak Eemian interglacial.
Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors
Authors: Wang Jue Xiang , Irvine Mark W. , Burnell Erica S. , Sapkota Kiran , Thatcher Robert J. , Li Minjun , Simorowski Noriko , Volianskis Arturas , Collingridge Graham L. , Monaghan Daniel T. , Jane David E. , Furukawa Hiro 
Published: January 2020

AbstractN-Methyl-D-aspartate receptors (NMDARs) play critical roles in the central nervous system. Their heterotetrameric composition generates subtypes with distinct functional properties and spatio-temporal distribution in the brain, raising the possibility for subtype-specific targeting by pharmacological means for treatment of neurological diseases. While specific compounds for GluN2A and GluN2B-containing NMDARs are well established, those that target GluN2C and GluN2D are currently underdeveloped with low potency and uncharacterized binding modes. Here, using electrophysiology and X-ray crystallography, we show that UBP791 ((2S*,3R*)-1-(7-(2-carboxyethyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) inhibits GluN2C/2D with 40-fold selectivity over GluN2A-containing receptors, and that a methionine and a lysine residue in the ligand binding pocket (GluN2D-Met763/Lys766, GluN2C-Met736/Lys739) are the critical molecular elements for the subtype-specific binding. These findings led to development of UBP1700 ((2S*,3R*)-1-(7-(2-carboxyvinyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) which shows over 50-fold GluN2C/2D-selectivity over GluN2A with potencies in the low nanomolar range. Our study shows that the l-glutamate binding site can be targeted for GluN2C/2D-specific inhibition.
Optimizing motor decision-making through competition with opponents
Authors: Ota Keiji , Tanae Mamoru , Ishii Kotaro , Takiyama Ken 
Published: January 2020

AbstractAlthough optimal decision-making is essential for sports performance and fine motor control, it has been repeatedly confirmed that humans show a strong risk-seeking bias, selecting a risky strategy over an optimal solution. Despite such evidence, the ideal method to promote optimal decision-making remains unclear. Here, we propose that interactions with other people can influence motor decision-making and improve risk-seeking bias. We developed a competitive reaching game (a variant of the “chicken game”) in which aiming for greater rewards increased the risk of no reward and subjects competed for the total reward with their opponent. The game resembles situations in sports, such as a penalty kick in soccer, service in tennis, the strike zone in baseball, or take-off in ski jumping. In five different experiments, we demonstrated that, at the beginning of the competitive game, the subjects robustly switched their risk-seeking strategy to a risk-averse strategy. Following the reversal of the strategy, the subjects achieved optimal decision-making when competing with risk-averse opponents. This optimality was achieved by a non-linear influence of an opponent’s decisions on a subject’s decisions. These results suggest that interactions with others can alter human motor decision strategies and that competition with a risk-averse opponent is key for optimizing motor decision-making.
Controlling for Participants’ Viewing Distance in Large-Scale, Psychophysical Online Experiments Using a Virtual Chinrest
Authors: Li Qisheng , Joo Sung Jun , Yeatman Jason D. , Reinecke Katharina 
Published: January 2020

AbstractWhile online experiments have shown tremendous potential to study larger and more diverse participant samples than is possible in the lab, the uncontrolled online environment has prohibited many types of psychophysical studies due to difficulties controlling the viewing distance and stimulus size. We introduce the Virtual Chinrest, a method that measures a participant’s viewing distance in the web browser by detecting a participant’s blind spot location. This makes it possible to automatically adjust stimulus configurations based on an individual’s viewing distance. We validated the Virtual Chinrest in two laboratory studies in which we varied the viewing distance and display size, showing that our method estimates participants’ viewing distance with an average error of 3.25 cm. We additionally show that by using the Virtual Chinrest we can reliably replicate measures of visual crowding, which depends on a precise calculation of visual angle, in an uncontrolled online environment. An online experiment with 1153 participants further replicated the findings of prior laboratory work, demonstrating how visual crowding increases with eccentricity and extending this finding by showing that young children, older adults and people with dyslexia all exhibit increased visual crowding, compared to adults without dyslexia. Our method provides a promising pathway to web-based psychophysical research requiring controlled stimulus geometry.
Wetting characteristics of Colocasia esculenta (Taro) leaf and a bioinspired surface thereof
Authors: Kumar Manish , Bhardwaj Rajneesh 
Published: January 2020

AbstractWe investigate wetting and water repellency characteristics of Colocasia esculenta (taro) leaf and an engineered surface, bioinspired by the morphology of the surface of the leaf. Scanning electron microscopic images of the leaf surface reveal a two-tier honeycomb-like microstructures, as compared to previously-reported two-tier micropillars on a Nelumbo nucifera (lotus) leaf. We measured static, advancing, and receding angle on the taro leaf and these values are around 10% lesser than those for the lotus leaf. Using standard photolithography techniques, we manufactured bioinspired surfaces with hexagonal cavities of different sizes. The ratio of inner to the outer radius of the circumscribed circle to the hexagon (b/a) was varied. We found that the measured static contact angle on the bioinspired surface varies with b/a and this variation is consistent with a free-energy based model for a droplet in Cassie-Baxter state. The static contact angle on the bioinspired surface is closer to that for the leaf for b/a ≈ 1. However, the contact angle hysteresis is much larger on these surfaces as compared to that on the leaf and the droplet sticks to the surfaces. We explain this behavior using a first-order model based on force balance on the contact line. Finally, the droplet impact dynamics was recorded on the leaf and different bioinspired surfaces. The droplets bounce on the leaf beyond a critical Weber number (We ~ 1.1), exhibiting remarkable water-repellency characteristics. However, the droplet sticks to the bioinspired surfaces in all cases of We. At larger We, we recorded droplet breakup on the surface with larger b/a and droplet assumes full or partial Wenzel state. The breakup is found to be a function of We and b/a and the measured angles in full Wenzel state are closer to the predictions of the free-energy based model. The sticky bioinspired surfaces are potentially useful in applications such as water-harvesting.
Optimized microwave assisted extraction (MAE) of alkaloids and polyphenols from Berberis roots using multiple-component analysis
Authors: Belwal Tarun , Pandey Aseesh , Bhatt Indra D. , Rawal Ranbeer S. 
Published: January 2020

AbstractBerberis, one of the major sources of berberine and polyphenols, is widely accepted genus for its medicinal properties. The inclusion of these phytochemicals in different health formulations has widened its scope in pharmaceuticals and nutraceuticals. In the present study, multi-component analysis (MCA) has been used to extract these nutraceutical compounds fromBerberis jaeschkeanaroots under microwave-assisted extraction (MAE) conditions. To determine the optimum extraction condition, different factors, including, microwave power, sample to solvent ratio, irradiation time, solvent pH and solvent concentration were tested under 42 experiments. The MCA includes, Plackett-Burmen and Central Composite Design and analyzes model fitness, regression coefficient (β), analysis of variance (ANOVA) and 3D response curve. The results showed significant model fitness and involvement of linear, quadratic and interactive effect of different factors. Under optimized MAE condition, [i.e. 1 g of sample extracted through 70 mL of a solution (100% methanol pH 2.0), provided microwave power of 598 W for 2 min of irradiation time], the berberine and palmatine contents were recorded as 46.38 mg g−1and 20.54 mg g−1respectively. Under optimized condition, the yield of alkaloids were found closer to the models’ predicted value. Similarly, total phenolic content and antioxidant activities were also found closer to the models’ predicted value. To test the suitability of the optimized MAE condition for other species i.e.,Berberis asiatica, extraction of alkaloids and polyphenolics was conducted and recorded higher yield to the previous records. Moreover, under optimum extraction condition, six and seven polyphenolic compounds fromB. jaeschkeanaandB. asiaticawere quantified respectively. The proposed MAE optimization design using MCA contributes towards faster and greener extraction of alkaloids and polyphenolics with higher yield. Moreover these greener approaches could sustainably utilize species during extract preparation and harnessing its nutraceutical and pharmaceutical potential. This study design could also be replicated on other valuable species or compounds for effective extraction of nutraceutical components and sustainable utilization of natural products.
Regulation and Maturation of the Shewanella oneidensis Sulfite Reductase SirA
Authors: Brockman Kenneth L. , Shirodkar Sheetal , Croft Trevor J. , Banerjee Rini , Saffarini Daad A. 
Published: January 2020

AbstractShewanella oneidensis, a metal reducer and facultative anaerobe, expresses a large number of c-type cytochromes, many of which function as anaerobic reductases. All of these proteins contain the typical heme-binding motif CXXCH and require the Ccm proteins for maturation. Two c-type cytochrome reductases also possess atypical heme-binding sites, the NrfA nitrite reductase (CXXCK) and the SirA sulfite reductase (CX12NKGCH). S. oneidensis MR-1 encodes two cytochrome c synthetases (CcmF and SirE) and two apocytochrome c chaperones (CcmI and SirG). SirE located in the sir gene cluster is required for the maturation of SirA, but not NrfA. Here we show that maturation of SirA requires the combined function of the two apocytochrome c chaperones CcmI and SirG. Loss of either protein resulted in decreased sulfite reductase. Furthermore, SirA was not detected in a mutant that lacked both chaperones, perhaps due to misfolding or instability. These results suggest that CcmI interacts with SirEFG during SirA maturation, and with CcmF during maturation of NrfA. Additionally, we show that CRP regulates expression of sirA via the newly identified transcriptional regulatory protein, SirR.
Prediction of suitable brewing cuppages of Dahongpao tea based on chemical composition, liquor colour and sensory quality in different brewing
Authors: Zhang Sifeng , Yang Yiqing , Cheng Xiaofang , Thangaraj Kuberan , Arkorful Emmanuel , Chen Xuan , Li Xinghui 
Published: January 2020

AbstractOolong tea is famous for its characteristic of durably brewing. To explore suitable brewing cuppages and the scientific methods to brew Oolong tea in multiple steeping process. Dahongpao tea (Zhengyan, Banyan and Zhouyan tea) is well known Oolong tea variety, brewed at 14 times and assessed its chemical composition, infusion colour and sensory quality in different brewing intervals. The results showed that Zhengyan tea (A3) had the best quality of steeping among the chosen tea. It could be brewed up to 10 cuppages with 80% sensory score. The chemical composition and tea infusion colour strength were higher in Zhengyan tea. Though, 70% caffeine leached within first three steeping. The Forest regression model revealed that the suitable brewing time ranges between 4 and 10 in the chosen Dahongpao tea variety. This study provides a scientific method and suitable steeping times for the drinking of different Dahongpao tea through dynamic analysis of quantity of chemical composition, infusion colour strength and sensory quality.
A Cellular Mechanism of Learning-Induced Enhancement of Synaptic Inhibition: PKC-Dependent Upregulation of KCC2 Activation
Authors: Kfir Adi , Awasthi Richa , Ghosh Sourav , Kundu Sankhanava , Paul Blesson , Lamprecht Raphael , Barkai Edi 
Published: January 2020

AbstractLong-term memory of complex olfactory learning is expressed by wide spread enhancement in excitatory and inhibitory synaptic transmission onto piriform cortex pyramidal neurons. A particularly interesting modification in synaptic inhibition is the hyperpolarization of the reversal potential of the fast post synaptic inhibitory potential (fIPSP). Here we study the mechanism underlying the maintenance of such a shift in the fIPSP. Blocking of the neuronal specific K+-Cl− co-transporter (KCC2) in neurons of trained rats significantly depolarized the averaged fIPSP reversal potential of the spontaneous miniature inhibitory post synaptic currents (mIPSCs), to the averaged pre-training level. A similar effect was obtained by blocking PKC, which was previously shown to upregulate KCC2. Accordingly, the level of PKC-dependent phosphorylation of KCC2, at the serine 940 site, was significantly increased after learning. In contrast, blocking two other key second messenger systems CaMKII and PKA, which have no phosphorylation sites on KCC2, had no effect on the fIPSP reversal potential. Importantly, the PKC inhibitor also reduced the averaged amplitude of the spontaneous miniature excitatory synaptic currents (mEPSCs) in neurons of trained rats only, to the pre-training level. We conclude that learning-induced hyper-polarization of the fIPSP reversal potential is mediated by PKC-dependent increase of KCC2 phosphorylation.
Screening of natural compounds that targets glutamate racemase of Mycobacterium tuberculosis reveals the anti-tubercular potential of flavonoids
Authors: Pawar Alka , Jha Prakash , Chopra Madhu , Chaudhry Uma , Saluja Daman 
Published: January 2020

AbstractTuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), a highly infectious disease accounting for nearly 1.5 million deaths every year and has been a major global concern. Moreover, resistance to anti-TB drugs is an arduous obstacle to effective prevention, TB care and management. Therefore, incessant attempts are being made to identify novel drug targets and newer anti-tubercular drugs to fight with this deadly pathogen. Increasing resistance, adverse effects and costly treatment by conventional therapeutic agents have been inclining the researchers to search for an alternative source of medicine. In this regard natural compounds have been exploited extensively for their therapeutic interventions targeting cellular machinery of MTB. Glutamate racemase (MurI) is an enzyme involved in peptidoglycan (PG) biosynthesis and has become an attractive target due to its moonlighting property. We screened various classes of natural compounds using computational approach for their binding to MTB-MurI. Shortlisted best docked compounds were evaluated for their functional, structural and anti-mycobacterial activity. The results showed that two flavonoids (naringenin and quercetin) exhibited best binding affinity with MTB-MurI and inhibited the racemization activity with induced structural perturbation. In addition, fluorescence and electron microscopy were employed to confirm the membrane and cell wall damages in mycobacterial cells on exposure to flavonoids. Together, these observations could provide impetus for further research in better understanding of anti-tubercular mechanisms of flavonoids and establishing them as lead molecules for TB treatment.
Post-20th century near-steady state of Batura Glacier: observational evidence of Karakoram Anomaly
Authors: Gao Haifeng , Zou Xiaojuan , Wu Jianfeng , Zhang Yinsheng , Deng Xiaoya , Hussain Saulat , Wazir Muhammad Atif , Zhu Guocai 
Published: January 2020

AbstractStable or marginal mass loss dominating in Karakoram has been reported widely through satellite and ground investigations. This work aimed to verify the variation in glacier mass by collecting ground-based data. By tracking profiles from the first survey by China–Pakistan Batura Glacier Investigation Group in 1974–1975, we revisited Batura Glacier and conducted an updated comparable measurement of the glacier surface elevation and ice thickness of this large valley glacier of Karakoram, in August 2017. Results of ground penetrating radar (GPR) measurement were used to improve the accuracy of an ice thickness distribution model (GlabTop2). The model calculation agreed reasonably with the measurement when the optimal basal shear stress (100 kPa for clean ice to 140 kPa for heavy debris cover) and shape factor (0.9) were used. We then used a glacier bed topographies map to calculate the ice flux. By subtracting the glacier surface topographies from the remote-sensing measurements, we observed a marginal thinning in Batura during 2000–2016, with a rate of variation in glacier surface elevation of −0.12 ± 0.27 m a−1. It indicated that the mass gain in the accumulation area nearly compensated the mass loss in the ablation area. In addition, both ground and satellite remote measurement reveal a steady rate of decrease in surface of the Batura tongue, implying an absence of significant variation during the past 40 years. Moreover, the mass conservation equation was applied to the Batura tongue, in combination with surface elevation variation and ice flux evolution. The tongue-averaged mass balance diminished by more than half from the 1970s to the 2010s. In summary, we inferred a near-steady state of Batura Glacier post 2000 based on the above-mentioned evidence of “Karakoram Anomaly”.
A Multi-Omics Interpretable Machine Learning Model Reveals Modes of Action of Small Molecules
Authors: Patel-Murray Natasha L. , Adam Miriam , Huynh Nhan , Wassie Brook T. , Milani Pamela , Fraenkel Ernest 
Published: January 2020

AbstractHigh-throughput screening and gene signature analyses frequently identify lead therapeutic compounds with unknown modes of action (MoAs), and the resulting uncertainties can lead to the failure of clinical trials. We developed an approach for uncovering MoAs through an interpretable machine learning model of transcriptomics, epigenomics, metabolomics, and proteomics. Examining compounds with beneficial effects in models of Huntington’s Disease, we found common MoAs for compounds with unrelated structures, connectivity scores, and binding targets. The approach also predicted highly divergent MoAs for two FDA-approved antihistamines. We experimentally validated these effects, demonstrating that one antihistamine activates autophagy, while the other targets bioenergetics. The use of multiple omics was essential, as some MoAs were virtually undetectable in specific assays. Our approach does not require reference compounds or large databases of experimental data in related systems and thus can be applied to the study of agents with uncharacterized MoAs and to rare or understudied diseases.
Delineation of cell death mechanisms induced by synergistic effects of statins and erlotinib in non-small cell lung cancer cell (NSCLC) lines
Authors: Otahal Alexander , Aydemir Duygu , Tomasich Erwin , Minichsdorfer Christoph 
Published: January 2020

AbstractHydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to overcome tyrosine kinase inhibitor (TKI) resistance in epithelial growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) cells in vivo and in vitro. However, little is known about the putative induction of non-apoptotic cell death pathways by statins. We investigated the effects of pitavastatin and fluvastatin alone or in combination with erlotinib in three NSCLC cell lines and examined the activation of different cell death pathways. We assessed apoptosis via fluorometric caspase assay and poly (ADP-ribose) polymerase 1 (PARP) cleavage. Furthermore, annexinV/propidium iodide (PI) flow cytometry was performed. Small molecule inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD), necrostatin 1 (Nec1), ferrostatin 1 (Fer1), Ac-Lys-Lys-Norleucinal (Calp1) were used to characterise cell death pathway(s) putatively (co-)activated by pitavastatin/erlotinib co-treatment. Synergism was calculated by additivity and isobolographic analyses. Pitavastatin and fluvastatin induced cell death in EGFR TKI resistant NSCLC cells lines A549, Calu6 and H1993 as shown by caspase 3 activation and PARP cleavage. Co-treatment of cells with pitavastatin and the EGFR TKI erlotinib resulted in synergistically enhanced cytotoxicity compared to pitavastatin monotherapy. Flow cytometry indicated the induction of alternative regulated cell death pathways. However, only co-treatment with mevalonic acid (Mev) or the pan-caspase inhibitor zVAD could restore cell viability. The results show that cytotoxicity mediated by statin/erlotinib co-treatment is synergistic and can overcome erlotinib resistance in K-ras mutated NSCLC and relies only on apoptosis.